[Chevychelov]

Аритмии
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Сердечно-сосудистая хирургия
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Врожденные пороки сердца
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Общая кардиология
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Сердечная недостаточность/трансплантация
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Интервенционная кардиология
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Неинвазивная кардиология
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Профилактика/сосуды
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Defibrillator Implantation Early After Myocardial Infarction
Steinbeck G, Andresen D, Seidl K, et al., on behalf of the IRIS Investigators.
N Engl J Med 2009;361:1427-1436.
Study Question: Do implantable cardioverter defibrillators (ICDs) improve survival when implanted in high-risk patients within 1 month of a myocardial infarction (MI)?
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Long-Term Results of Catheter-Based Treatment of Pulmonary Atresia and Intact Ventricular Septum
Marasini M, Gorrieri PF, Tuo G, et al.
Heart 2009;95:1520-1524.
Study Question: What are the outcomes of patients with pulmonary atresia with intact ventricular septum (PAIVS) after interventional perforation of the pulmonary valve?
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A Meta-Analysis of Remote Monitoring of Heart Failure Patients
Klersy C, De Silvestri A, Gabutti G, Regoli F, Auricchio A.
J Am Coll Cardiol 2009;54:1683-1694.
Study Question: What is the effect of remote patient monitoring (RPM) on the outcome of chronic heart failure (HF) patients?
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Hospitalizations After Heart Failure Diagnosis: A Community Perspective
Dunlay SM, Redfield MM, Weston SA, et al.
J Am Coll Cardiol 2009;54:1695-1702.
Study Question: What is the lifetime burden and risk factors for hospitalization after heart failure (HF) diagnosis in the community?
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Adherence to Antihypertensive Medications and Cardiovascular Morbidity Among Newly Diagnosed Hypertensive Patients
Mazzaglia G, Ambrosioni E, Alacqua M, et al.
Circulation 2009;120:1598-1605.
Study Question: What are the predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events?
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Neighborhood Resources for Physical Activity and Healthy Foods and Incidence of Type 2 Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis
Auchincloss AH, Diez Roux AV, Mujahid MS, et al.
Arch Intern Med 2009;169:1698-1704.
Study Question: Are neighborhood resources associated with incidence of type 2 diabetes mellitus (DM)?
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C-Reactive Protein as a Risk Factor for Coronary Heart Disease: A Systematic Review and Meta-Analyses for the U.S. Preventive Services Task Force
Buckley DI, Fu R, Freeman M, Rogers K, Helfand M.
Ann Intern Med 2009;151:483-495.
Study Question: C-reactive protein (CRP) may help to refine global risk assessment for coronary heart disease (CHD), particularly among persons who are at intermediate risk on the basis of traditional risk factors alone. Should CRP be incorporated into guidelines for CHD risk assessment?
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Emerging Risk Factors for Coronary Heart Disease: A Summary of Systematic Reviews Conducted for the U.S. Preventive Services Task Force
Helfand M, Buckley DI, Freeman M, et al.
Ann Intern Med 2009;151:496-507.
Study Question: Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. What is the evidence of value of new or emerging risk factors for improving global risk assessment for CHD?
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Myeloperoxidase, Subclinical Atherosclerosis, and Cardiovascular Disease Events
Wong ND, Gransar H, Narula J, et al.
JACC Cardiovasc Img 2009;2:1093-1099.
Study Question: Myeloperoxidase (MPO) is a leukocyte-derived enzyme-generating reactive oxidant species that has been shown to predict risk of cardiovascular disease (CVD) in selected populations. Does MPO predict future CVD events in asymptomatic adults, and does subclinical atherosclerosis affect this relation?
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Vardenafil Treatment for Patients With Pulmonary Arterial Hypertension: A Multicentre, Open-Label Study
Jing ZC, Jiang X, Wu BX, et al.
Heart 2009;95:1531-1536.
Study Question: What are the long-term effects of vardenafil, a phosphodiesterase-5 (PDE-5) inhibitor, in patients with pulmonary arterial hypertension (PAH)?
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[Chevychelov]

MitraClip for High Risk Patients
Hospital to Home - New Health Care Initiative
Pediatric IMPACT Registry
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Three-year efficacy of complex insulin regimens in Type 2 DM (N Engl J Med).
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Use of aldosterone antagonists in HF (JAMA).
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[Chevychelov]

Outcomes Following Endovascular vs Open Repair of Abdominal Aortic Aneurysm: A Randomized Trial
Lederle FA, Freischlag JA, Kyriakides TC, et al., for the Open Versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group.
JAMA 2009;302:1535-1542.
Open Versus Endovascular Repair (OVER)
Study Question: In the Veterans Affairs (VA) medical centers, what are the short-term (2-year) outcomes following open and endovascular (EVAR) abdominal aortic aneurysm (AAA) repair?
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Sex-Specific Trends in Midlife Coronary Heart Disease Risk and Prevalence
Towfighi A, Zheng L, Ovbiagele B.
Arch Intern Med 2009;169:1762-1766.
Study Question: What is the sex-specific midlife prevalence of myocardial infarction (MI) and risk of coronary heart disease (CHD)?
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Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients
The RENAL Replacement Therapy Study Investigators.
N Engl J Med 2009;361:1627-1638.
Study Question: What is the optimal intensity of renal-replacement therapy in patients with acute kidney injury who are critically ill?
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High Prevalence of Abnormal Nocturnal Oximetry in Patients With Hypertrophic Cardiomyopathy
Eleid MF, Konecny T, Orgban M, et al.
J Am Coll Cardiol 2009;54:1805-1809.
Study Question: What is the prevalence of nocturnal oxygen desaturation and obstructive sleep apnea (OSA) in a population of patients with hypertrophic cardiomyopathy (HCM)?
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Use of Aldosterone Antagonists in Heart Failure
Albert NM, Yancy CW, Liang L, et al.
JAMA 2009;302:1658-1665.
Study Question: How often are aldosterone antagonists prescribed based on heart failure (HF) management guideline criteria and investigator-defined appropriateness criteria, and what are the trends over time in patients hospitalized with HF?
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Effects of Liraglutide in the Treatment of Obesity: A Randomised, Double-Blind, Placebo-Controlled Study
Astrup A, Rössner S, Van Gaal L, et al., on behalf of the NN8022-1807 Study Group.
Lancet 2009;Oct 23:[Epub ahead of print].
Study Question: Liraglutide, a glucagon-like peptide-1 (GLP-1) administered subcutaneously once daily, is effective in diabetes and induces weight loss. What is the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes?
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Three-Year Efficacy of Complex Insulin Regimens in Type 2 Diabetes
Holman RR, Farmer AJ, Davies MJ, et al., for the 4-T Study Group.
N Engl J Med 2009;361:1736-1747.
Study Question: What is the relative value of specific insulin regimens superimposed on oral therapy in patients with type 2 diabetes mellitus?
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Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment: U.S. Preventive Services Task Force Recommendation Statement
U.S. Preventive Services Task Force.
Ann Intern Med 2009;151:474-482.
Study Question: Are nontraditional risk factors recommended in screening for coronary heart disease (CHD)?
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Reducing Psychosocial Stress: A Novel Mechanism of Improving Survival From Exercise Training
Milani RV, Lavie CJ.
Am J Med 2009;122:931-938.
Study Question: Does reducing psychosocial stress by exercise training improve survival among cardiac patients?
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Role of Lifestyle and Aging on the Longitudinal Change in Cardiorespiratory Fitness
Jackson AS, Sui X, Hebert JR, Church TS, Blair SN.
Arch Intern Med 2009;169:1781-1787.
Study Question: What is the impact of lifestyle and aging on longitudinal trends in cardiorespiratory fitness?
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[Chevychelov]

Pinnacle Network: Best Practices and Survival Tools
Perspectives on Comparative Effectiveness
Abnormal Oximetry and HCM
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Implantation of the Melody Transcatheter Pulmonary Valve in Patients With a Dysfunctional Right Ventricular Outflow Tract Conduit: Early Results From the U.S. Clinical Trial (J Am Coll Cardiol).
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Outcomes Following Endovascular vs Open Repair of Abdominal Aortic Aneurysm: A Randomized Trial (JAMA).
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Role of Lifestyle and Aging on the Longitudinal Change in Cardiorespiratory Fitness (Arch Intern Med).
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[Chevychelov]

N-Terminal Pro-B-Type Natriuretic Peptide Is a Major Predictor of the Development of Atrial Fibrillation. The Cardiovascular Health Study
Patton KK, Ellinor PT, Heckbert SR, et al.
Circulation 2009;120:1768-1774.
Study Question: Is N-terminal pro-B-type natriuretic peptide (NT-proBNP) a risk factor for atrial fibrillation (AF)?
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Aortic Valve Replacement: A Prospective Randomized Evaluation of Mechanical Versus Biological Valves in Patients Ages 55 to 70 Years
Stassano P, Di Tommaso L, Monaco M, et al.
J Am Coll Cardiol 2009;54:1862-1868.
Study Question: What are the long-term results after tissue versus mechanical aortic valve replacement (AVR) in patients ages 55-70 years?
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Pulmonary Embolism and Deep Venous Thrombosis in Trauma: Are They Related?
Velmahos GC, Spaniolas K, Tabbara M, et al.
Arch Surg 2009;144:928-932.
Study Question: In an academic, level 1 trauma center, what is the incidence in trauma patients undergoing computed tomography (CT) for pulmonary embolism (PE) and deep venous thrombosis (DVT)?
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Implantation of the Melody Transcatheter Pulmonary Valve in Patients With a Dysfunctional Right Ventricular Outflow Tract Conduit: Early Results From the U.S. Clinical Trial
Zahn EM, Hellenbrand WE, Lock JE, McElhinney DB.
J Am Coll Cardiol 2009;54:1722-1729.
Study Question: What is the safety, procedural success rate, and short-term effectiveness of the Melody transcatheter pulmonary valve in patients with dysfunctional right ventricular outflow tracts (RVOT)?
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Omega-3 Augmentation of Sertraline in Treatment of Depression in Patients With Coronary Heart Disease: A Randomized Controlled Trial
Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS.
JAMA 2009;302:1651-1657.
Study Question: Do omega-3 fatty acids augment sertraline in the treatment of depression in patients with coronary heart disease (CHD)?
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A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease
Pfeffer MA, Burdmann EA, Chen CY, et al., on behalf of the TREAT Investigators.
N Engl J Med 2009;Oct 30:[Epub ahead of print].
Study Question: What is the effect of darbepoetin alfa on clinical outcomes in patients with type 2 diabetes, chronic kidney disease, and anemia?
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2009 ACCF/AHA Focused Update on Perioperative Beta Blockade: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Fleischmann KE, Beckman JA, Buller CE, et al.
J Am Coll Cardiol 2009;54:2102-2128.
Perspective: The following are 10 points to remember about the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Focused Update on Perioperative Beta Blockade
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Association of Chronic Kidney Disease With the Spectrum of Ankle Brachial Index: The CHS (Cardiovascular Health Study)
Ix JH, Katz R, De Boer IH, et al.
J Am Coll Cardiol 2009;54:1176-1184.
Study Question: What is the association between chronic kidney disease (CKD) and ankle-brachial index (ABI)?
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Non-Cardiac Surgery and Antiplatelet Therapy Following Coronary Artery Stenting
Luckie M, Khattar RS, Fraser D.
Heart 2009;95:1303-1308.
Perspective: The following are 10 points to remember about this article
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Risks of Complications by Attending Physicians After Performing Nighttime Procedures
Rothschild JM, Keohane CA, Rogers S, et al.
JAMA 2009;302:1565-1572.
Study Question: Does being on call the night before impact the outcome of procedures performed by attending physicians?
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Bivalirudin in Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction (HORIZONS-AMI): 1-Year Results of a Randomised Controlled Trial
Mehran R, Lansky AJ, Witzenbichler B, et al., on behalf of the HORIZONS-AMI Trial Investigators.
Lancet 2009;374:1149-1159.
Study Question: What is the 1-year outcome of patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) who are treated with bivalirudin compared with those who are treated with glycoprotein IIb/IIIa inhibitors (GPIs)?
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[Chevychelov]

Early ICD Use After MI
Breaking News: ACC Responds to Final Medicare Rule
CRT Reduces CHF Events
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Long-term results after tissue vs. mechanical AVR (J Am Coll Cardiol).
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Use of ESAs in anemic patients with diabetes and CKD (TREAT).
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Just Published: 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade. Read the "10 Points to Remember" journal scan.
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Analyze This Image: Surface 12-Lead ECG From a 69-Year-Old Female With Idiopathic Nondilated Cardiomyopathy and Stable Heart Failure.
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New Case Study: A 39-Year-Old Woman Presents With Shortness of Breath and Palpitations for 2 Days.
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New Expert Opinion: Dr. Dominick J. Angiolillo on Pharmacogenetics in Cardiovascular Antithrombotic Therapy.
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New Conversations with Experts: Drs. Alan H. Gradman and Matthew R. Weir on Role of Anti-Renin Agents.
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[Chevychelov]

MADIT-CRT
Fighting for Patient Access
Niacin Decreases Carotid Disease
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Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension (J Am Coll Cardiol).
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Statin use and risk of gallstone disease followed by cholecystectomy (JAMA).
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Angioplasty and stenting for renal artery lesions (ASTRAL).
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Randomized on/off bypass trial (ROOBY).
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Cardiosource coverage of AHA Scientific Sessions 2009 begins Sunday, November 15th: Stay tuned for the latest news, including results from RE-LY, HEAAL, ARBITER 6-HALTS and more!
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New Case Study: A 61-Year-Old Patient With Hyperlipidemia Presents With Atypical Chest Pain.
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New Expert Opinion: Overcoming the Barriers to Stem Cell Therapy.
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[Chevychelov]

CHAMPION PCI and CHAMPION PLATFORM
Among patients undergoing PCI for a variety of indications in the CHAMPION PCI and CHAMPION PLATFORM trials, the use of intravenous cangrelor was not superior to clopidogrel 600 mg, either started before or after the procedure
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ACC Launches CV Practice Network
Cardiovascular practices face myriad challenges in today's health care environment — legislative and regulatory threats to payment, demands to demonstrate performance and justify clinical decisions, the emergence of reimbursement models based on efficiency or value, and the rise of new and untested business arrangements. To address these challenges, the ACC last month launched the PINNACLE Network™
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PLATO: Treatment with ticagrelor reduces CV death, MI, and stroke in STEMI patients.
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NCDR® Presents 14 Abstracts at AHA : The American Heart Association accepted 14 NCDR abstracts for presentation at the Annual Scientific Sessions.
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POPULAR: In patients undergoing elective PCI, several platelet function tests can help predict one-year thrombosis but not bleeding events.
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[Chevychelov]

AHA 2009 Meeting Coverage: Daily Wrap-up for Sunday
For more video coverage, visit the AHA 2009 channel
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ARBITER 6-HALTS
This trial showed that, among CHD patients on statin therapy, use of extended-release niacin caused a significant regression in carotid intima-media thickness. This agent was also superior to ezetimibe in reducing MACE and raising HDL cholesterol.
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New EHR Resource Available
Confused about what you should be looking for in an electronic health record (EHR) for your cardiology practice? The ACC recently published a new resource to assist cardiovascular practices in implementing an EHR.
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TREAT: Darbepoetin Alfa in Diabetic Patients With Chronic Kidney Disease Appears to Increase Stroke Risk
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MASS-DAC Registry: MI and Death Rate Similar for PCI at Centers Without Surgery On-Site, but Increased Revascularizations at One Year
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RE-LY: Dabigatran 150 mg is Superior to Warfarin in Reducing Stroke or Systemic Embolism in AF Patients
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PACE: In Patients With Normal Ventricular Function, RV Apical Pacing Results in Adverse LV Remodeling and Reduction in LVEF, Prevented by Biventricular Pacing
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Record-AF: Rhythm-Control Strategy is Preferred Therapeutic Option in Registry of Patients With Paroxysmal and Persistent AF
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[Chevychelov]

AHA 2009 Meeting Coverage: Daily Wrap-up Monday
For more video coverage, visit the AHA 2009 channel.
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HEAAL
Losartan 150 mg daily reduces all-cause mortality and HF admission in patients with HF, reduced LVEF, and intolerance to ACE inhibitors, compared with losartan 50 mg daily. Although beneficial, high-dose losartan results in more adverse events: hyperkalemia, hypotension, renal insufficiency, and angioedema.
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FAIR-HF: Treatment With Intravenous Iron in Patients With ron in Patients With CHF and Iron Deficiency Improves Symptoms, Functional Capacity, and Quality of Life
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Heart Mate II: Continuous-Flow LV Assist Devices in Patients With Advanced HF Significantly Reduces Stroke and Device Failure Compared With Pulsatile Devices
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Bypassing the Blues: Telephone-Delivered Collaborative Care for Treating Post-CABG Depression Results in Improved Health-Related Quality of Life, Physical Functioning, and Mood Symptoms
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CASCADE: After CABG, the Addition of Clopidogrel to Aspirin Does Not Significantly Reduce Vein Graft Intimal Hyperplasia or Improve Graft Patency
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OCTOPUS: After 7.5 Years, Off-Pump CABG Has Comparable Safety Profile as PCI, Lower Risk of Coronary Reinterventions, and Possibly Better Cognitive Performance
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POPE: Treatment With NSAIDs in Patients With Moderate to Large Postoperative Pericardial Effusion Does Not Reduce Pericardial Effusion
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[Chevychelov]

AHA 2009 Meeting Coverage: Daily Wrap-up Tuesday
For more video coverage, visit the AHA 2009 channel.
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ACCF, AHA Unveil Updated Guidelines for PCI
The ACCF, along with the AHA and the Society for Cardiovascular Angiography and Interventions, today is releasing a focused update that applies to two sets of Guidelines — the management of patients with STEMI and the management of patients undergoing PCI. Continue Reading. See also the "10 Points to Remember" journal scan and video interview with Dr. Kushner.
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BARI 2D: Quality of Life Results, Economic Outcomes, and 5-Year Results
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J-CHF: No Difference in Clinical Outcomes for 3 Doses of Carvedilol in Patients With Chronic Stable HF
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Predictors of Sudden Cardiac Death Change With Time After Myocardial Infarction: Results From the VALIANT Trial
Piccini JP, Zhang M, Pieper K, et al.
Eur Heart J 2009;Oct 23:[Epub ahead of print].
Study Question: Do risk factors for sudden cardiac death (SCD) change over time after myocardial infarction (MI)?
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Biventricular Pacing in Patients With Bradycardia and Normal Ejection Fraction
Yu CM, Chan JY, Zhang Q, et al.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: Does biventricular pacing prevent the deleterious effects of right ventricular (RV) apical pacing in patients with a normal ejection fraction (EF)?
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Revascularization Versus Medical Therapy for Renal-Artery Stenosis
The ASTRAL Investigators.
N Engl J Med 2009;361:1953-1962.
Study Question: What are the clinical benefits of percutaneous renal artery revascularization compared with modern, best medical therapy?
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Long-Term Prognostic Value of ST-Segment Resolution in Patients Treated With Fibrinolysis or Primary Percutaneous Coronary Intervention: Results From the DANAMI-2 (DANish trial in Acute Myocardial Infarction-2)
Sejersten M, Valeur N, Grande P, Nielsen TT, Clemmensen P, on behalf of the DANAMI-2 Investigators.
J Am Coll Cardiol 2009;54:1763-1769.
Study Question: What is the prognostic value of ST-segment resolution after primary percutaneous coronary intervention (pPCI) versus fibrinolysis?
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Statin Use and Risk of Gallstone Disease Followed by Cholecystectomy
Bodmer M, Brauchli YB, Krahenbuhl S, Jick SS, Meier CR.
JAMA 2009;302:2001-2007.
Study Question: What is the association between the use of statins, fibrates, or other lipid-lowering agents and the risk of incident gallstone disease followed by cholecystectomy?
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Simple Versus Complex Stenting Strategy for Coronary Artery Bifurcation Lesions in the Drug-Eluting Stent Era: A Meta-Analysis of Randomised Trials
Zhang F, Dong L, Ge J.
Heart 2009;95:1676-1681.
Study Question: What is the best strategy for interventional treatment of coronary bifurcation lesions in patients treated with drug-eluting stents (DES)?
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Long-Term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function
Brinkworth GD, Buckley JD, Noakes M, Clifton PM, Wilson CJ.
Arch Intern Med 2009;169:1873-1880.
Study Question: Is psychological function affected by a very low-carbohydrate diet used to promote weight loss?
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The Relative Efficacy and Safety of Clopidogrel in Women and Men: A Sex-Specific Collaborative Meta-Analysis
Berger JS, Bhatt DL, Cannon CP, et al.
J Am Coll Cardiol 2009;54:1935-1945.
Study Question: Are there gender-related differences in the efficacy and safety of clopidogrel?
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Major Lipids, Apolipoproteins, and Risk of Vascular Disease
The Emerging Risk Factors Collaboration.
JAMA 2009;302:1993-2000.
Study Question: What major lipids are most clearly associated with vascular disease?
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NCDR Highlights from AHA 2009
High LDL Levels in U.S. Population Drop Significantly
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Cardiosource has full coverage of AHA Scientific Sessions 2009, including results from:
ARBITER 6-HALTS: Extended-release niacin superior to ezetimibe as add-on to statin therapy
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HEAAL: High-dose losartan reduces all-cause mortality, HF hospitalization
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CHAMPION PCI and CHAMPION PLATFORM: Intravenous cangrelor not superior to clopidogrel for patients undergoing PCI
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RE-DEEM: Dabigatran With Dual-Antiplatelet Therapy after STEMI and NSTEMI Is Well Tolerated, With Relatively Low Bleeding
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ALLHAT: 10-Year Outcome Treatment Difference Shows Chlorthalidone Is Favored Over Amlodipine for Preventing HF
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CT-STAT: CT angiography triages at-risk chest-pain patients quicker and cheaper than standard stress testing
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Trends in High Levels of Low-Density Lipoprotein Cholesterol in the United States, 1999-2006
Study Question: Has there been a change in screening prevalence, use of cholesterol-lowering medication, and low-density lipoprotein cholesterol (LDL-C) levels in the United States between 1999 and 2006?
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Telephone-Delivered Collaborative Care for Treating Post-CABG Depression: A Randomized Controlled Trial
Study Question: What is the effectiveness of telephone-delivered collaborative care for post-coronary artery bypass grafting (CABG) depression versus usual physician care?
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A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease
Study Question: What are the prognostic implications of elevated troponin T levels in stable coronary disease patients?
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Braunwald's Heart Disease e-dition, Eighth Edition:

Text with Continually Updated Online Reference

By Peter Libby, MD, Robert O. Bonow, MD, Douglas P. Zipes, MD and Douglas L. Mann, MD, FACC

E-dition editor, Eugene Braunwald, MD
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Extended-Release Niacin or Ezetimibe and Carotid Intima-Media Thickness
Taylor AJ, Villines TC, Stanek EJ, et al.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: What is the effect of niacin or ezetimibe on common carotid intima-media thickness (CIMT) when added to statin therapy?
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Cardiovascular and Noncardiovascular Mortality Among Patients Starting Dialysis
de Jager DJ, Grootendorst DC, Jager KJ, et al.
JAMA 2009;302:1782-1789.
Study Question: Cardiovascular (CV) mortality is considered the main cause of death in patients receiving dialysis and is 10 to 20 times higher in such patients than in the general population. Is the high overall mortality in patients with end-stage renal disease (ESRD) starting dialysis a consequence of increased CV mortality risk only, or is non-CV mortality equally increased?
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Ferric Carboxymaltose in Patients With Heart Failure and Iron Deficiency
Anker SD, Colet JC, Filippatos G, et al., on behalf of the FAIR-HF Trial Investigators.
N Engl J Med 2009;Nov 17:[Epub ahead of print].
Study Question: Does treatment with intravenous iron (ferric carboxymaltose) improve symptoms in systolic HF and iron deficiency, either with or without anemia?
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Effects of High-Dose Versus Low-Dose Losartan on Clinical Outcomes in Patients With Heart Failure (HEAAL Study): A Randomized, Double-Blind Trial
Konstam MA, Neaton JD, Dickstein K, et al.
Lancet 2009;374:1840-8.
Study Question: How does high-dose losartan (an angiotensin-receptor blocker [ARB]) compare versus low-dose losartan on clinical outcomes in patients with heart failure (HF)?
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Advanced Heart Failure Treated With Continuous-Flow Left Ventricular Assist Device
Slaughter MS, Rogers JG, Milano CA, et al., on behalf of the HeartMate II Investigators.
N Engl J Med 2009;Nov 17:[Epub ahead of print].
Study Question: How does the newer HeartMate II left ventricular assist device (LVAD; a continuous-flow device) compare with the older more durable HeartMate XVE (a pulsatile-flow device)?
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Platelet Inhibition With Cangrelor in Patients Undergoing PCI
Harrington RA, Stone GW, McNulty S, et al., on behalf of CHAMPION PCI Investigators.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: What is the benefit of cangrelor, a reversible adenosine diphosphate (ADP) receptor antagonist, in patients undergoing percutaneous coronary intervention (PCI)?
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Intravenous Platelet Blockade With Cangrelor During PCI
Bhatt DL, Lincoff AM, Gibson CM, et al., on behalf of the CHAMPION PLATFORM Investigators.
N Engl J Med 2009;Nov 15:[Epub ahead of print].
Study Question: What is the benefit of cangrelor, a reversible adenosine diphosphate (ADP) receptor antagonist, in patients undergoing percutaneous coronary intervention (PCI)?
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Absolute Myocardial Blood Flow Determination Using Real-Time Myocardial Contrast Echocardiography During Adenosine Stress: Comparison With Single-Photon Emission Computed Tomography
Abdelmoneim SS, Dhoble A, Bernier M, et al.
Heart 2009;95:1662-1668.
Study Question: What is the feasibility and accuracy of real-time myocardial contrast echocardiography (MCE) to detect myocardial perfusion abnormalities using simultaneous technetium 99 m sestamibi single-photon emission computed tomography (SPECT) as a standard?
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A Selective Endothelin-Receptor Antagonist to Reduce Blood Pressure in Patients With Treatment-Resistant Hypertension: A Randomised, Double-Blind, Placebo-Controlled Trial
Weber MA, Black H, Bakris G, et al.
Lancet 2009;374:1423-1431.
Study Question: What is the blood pressure-lowering effect of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension?
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Choosing Your Fish - Mercury and BP

EVAR vs. Surgery for AAA

The French TAVI Registry
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National Efforts to Improve D2B Time (J Am Coll Cardiol).
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Prognostic implications of elevated troponin T levels in Stable CAD (NEJM).
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Cardiovascular Diseases and Risk of Hip Fracture
Sennerby U, Melhus H, Gedeborg R, et al.
JAMA 2009;302:1666-1673.
Study Question: Is there an association between cardiovascular disease (CVD) and risk of hip fracture, and if so, is this association due to genetic or lifestyle factors?
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A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease
Omland T, de Lemos JA, Sabatine MS, et al.
N Engl J Med 2009;Nov 25:[Epub ahead of print].
Study Question: What are the prognostic implications of elevated troponin T levels in stable coronary disease patients?
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C-Reactive Protein and the Risk of Stent Thrombosis and Cardiovascular Events After Drug-Eluting Stent Implantation
Park DW, Yun SC, Lee JY, et al.
Circulation 2009;120:1987-1995.
Study Question: What is the predictive usefulness of C-reactive protein (CRP) among patients treated with drug-eluting stents (DES)?
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Incidence and Predictors of Drug-Eluting Stent Fracture in Human Coronary Artery: A Pathologic Analysis
Nakazawa G, Finn AV, Vorpahl M, et al.
J Am Coll Cardiol 2009;54:1924-1931
Study Question: What is the incidence of, and what are the pathological correlates of coronary stent fracture at autopsy?
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Benefit of Facilitated Percutaneous Coronary Intervention in High-Risk ST-Segment Elevation Myocardial Infarction Patients Presenting to Nonpercutaneous Coronary Intervention Hospitals
Herrmann HC, Lu J, Brodie BR, et al., on behalf of the FINESSE Investigators.
JACC Cardiovasc Interv 2009;2:917-924.
Study Question: What is the benefit of facilitated percutaneous coronary intervention (PCI) in high-risk ST-segment elevation myocardial infarction (STEMI) patients presenting to non-PCI hospitals?
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Systematic Review: Sodium Bicarbonate Treatment Regimens for the Prevention of Contrast-Induced Nephropathy
Zoungas S, Ninomiya T, Huxley R, et al.
Ann Intern Med 2009;151:631-638.
Study Question: What is the benefit of using sodium bicarbonate-based hydration for prevention of contrast-induced nephropathy (CIN)?
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Non Fasting Lipid Assessment is OK
Patch Plus Lozenge Best for Smoking Cessation
Plaque and Acute Coronary Thrombosis
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PROVE IT-TIMI 22: Reduction in recurrent CV events with intensive vs. moderate lipid-lowering statin therapy after ACS (J Am Coll Cardiol).
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IDEAL: Total CV disease burden: intensive vs. moderate statin therapy (J Am Coll Cardiol).
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CABG vs. PCI in diabetic patients (CARDia)
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A Randomized Trial
Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L.
JAMA 2009;302:2222-2229.
Study Question: Does elimination of intravenous (IV) access and drug administration from advanced cardiac life support (ACLS) affect the outcome of cardiopulmonary resuscitation (CPR) in patients with out-of-hospital cardiac arrest (OHCA)?
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Triggering of Nocturnal Arrhythmias by Sleep-Disordered Breathing Events
Monahan K, Storfer-Isser A, Mehra R, et al.
J Am Coll Cardiol 2009;54:1797-1804.
Study Question: Does hypopnea or apnea during sleep trigger atrial fibrillation (AF) or nonsustained ventricular tachycardia (NSVT)?
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Survival Implication of Left Ventricular End-Systolic Diameter in Mitral Regurgitation due to Flail Leaflets: A Long-Term Follow-Up Multicenter Study
Tribouilloy C, Grigioni F, Avierinos JF, et al.
J Am Coll Cardiol 2009;54:1961-1968.
Study Question: Is there an association between left ventricular end-systolic diameter (LVESD) with survival after diagnosis in organic mitral regurgitation (MR) due to flail leaflet?
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Pooled Analysis of Rofecoxib Placebo-Controlled Clinical Trial Data: Lessons for Postmarket Pharmaceutical Safety Surveillance
Ross JS, Madigan D, Hill KP, Egilman DS, Wang Y, Krumholz HM.
Arch Intern Med 2009;169:1976-1985.
Study Question: When could the analysis of published and unpublished placebo-controlled trials have revealed cardiovascular risk associated with rofecoxib before its withdrawal?
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Intracoronary Optical Coherence Tomography: A Comprehensive Review: Clinical and Research Applications
Bezerra HG, Costa MA, Guagliumi G, Rollins AM, Simon DI.
JACC Cardiovasc Interv 2009;2:1035-1046.
Perspective: The following are 10 points to remember about intracoronary optical coherence tomography (OCT)
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Association of Hospital Primary Angioplasty Volume in ST-Segment Elevation Myocardial Infarction With Quality and Outcomes
Kumbhani DJ, Cannon CP, Fonarow GC, et al., on behalf of the Get With the Guidelines Steering Committee and Investigators.
JAMA 2009;302:2207-2213.
Study Question: What is the impact of hospital primary percutaneous coronary intervention (PCI) volume on outcomes and quality of care measures in patients presenting with ST-segment elevation myocardial infarction (STEMI)?
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National Efforts to Improve Door-to-Balloon Time: Results From the Door-to-Balloon Alliance
Bradley EH, Nallamothu BK, Herrin J, et al.
J Am Coll Cardiol 2009;54:2423-2429.
Study Question: What was the impact of the door-to-balloon (D2B) alliance on the time to reperfusion among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI)?
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Outcomes With Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein Graft Intervention: Results From the STENT (Strategic Transcatheter Evaluation of New Therapies) Group
Brodie BR, Wilson H, Stuckey T, et al., on behalf of the STENT Group.
JACC Cardiovasc Interv 2009;2:1105-1112.
Study Question: What are the outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients undergoing saphenous vein graft (SVG) intervention?
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Safety of Contrast Agent Use During Stress Echocardiography: A 4-Year Experience From a Single-Center Cohort Study of 26,774 Patients
Abdelmoneim SS, Bernier M, Scott CG, et al.
JACC Cardiovasc Imaging 2009;2:1048-1056.
Study Question: What is the short- and long-term safety of ultrasound contrast agents used during stress echocardiography (SE)?
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Effects of Liraglutide in the Treatment of Obesity: A Randomised, Double-Blind, Placebo-Controlled Study
Astrup A, Rössner S, Van Gaal L, et al., on behalf of the NN8022-1807 Study Group.
Lancet 2009;374:1606-1616.
Study Question: What is the effect of liraglutide, a glucagon-like peptide-1, on bodyweight and tolerability in obese individuals without type 2 diabetes?
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10-Year Follow-up of Diabetes Incidence and Weight Loss in the Diabetes Prevention Program Outcomes Study
Diabetes Prevention Program Research Group.
Lancet 2009;374:1677-1686.
Study Question: What is the persistence of the benefit seen from metformin and intensive lifestyle intervention in preventing diabetes in high-risk patients enrolled in the Diabetes Prevention Program (DPP) randomized clinical trial?
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Effects of High-Dose Modified-Release Nicotinic Acid on Atherosclerosis and Vascular Function: A Randomized, Placebo-Controlled, Magnetic Resonance Imaging Study
Lee JM, Robson MD, Yu LM, et al.
J Am Coll Cardiol 2009;54:1787-1794.
Study Question: What are the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function?
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Atorvastatin Reduces MI in PCI
Sibutramine & CV Risk
New-Onset HF Predicted by Gated SPECT
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Projected cancer risks from CT scans (Archives).
Study Question: What is the future cancer risk from current computed tomographic (CT) scan use in the United States?
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Relationship between coffee consumption and risk of type 2 diabetes (Archives).
Study Question: What is the relationship between coffee consumption and risk of type 2 diabetes mellitus?
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Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy (J Am Coll Cardiol).
Study Question: What gene mutation is associated with hypertrophic cardiomyopathy (HCM) in a large family with a heterogenous HCM phenotype?
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Американская Ассоциация Сердца выпустила список 10 основных достижений в исследованиях заболеваний сердца и инсульта за 2009 год. Отмечено, что достижения расположены в нем по названию соответствующей публикации, но тем не менее 2 первых места занимают имеющие большое общественное значение работы по профилактике
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Women Have a Lower Prevalence of Structural Heart Disease as a Precursor to Sudden Cardiac Arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study)
Chugh SS, Uy-Evanado A, Teodorescu C, et al.
J Am Coll Cardiol 2009;54:2006-2011.
Study Question: Are there gender-based differences in the clinical predictors of sudden cardiac arrest (SCA)?
Title: Women Have a Lower Prevalence of Structural Heart Disease as a Precursor to Sudden Cardiac Arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study)
Topic: Arrhythmias
Date Posted: 12/8/2009
Author(s): Chugh SS, Uy-Evanado A, Teodorescu C, et al.
Citation: J Am Coll Cardiol 2009;54:2006-2011.
Clinical Trial: No
Study Question: Are there gender-based differences in the clinical predictors of sudden cardiac arrest (SCA)?
Methods: The medical records of 1,568 adults with SCA were reviewed. Clinical predictors of SCA were compared between men (n = 1,012) and women (n = 556).
Results: The women (mean age 71 years) were significantly older than the men (mean age 65 years). In a multivariate analysis of multiple clinical variables, the predictors of SCA that were significantly less prevalent in women than men were prior documentation of coronary artery disease (odds ratio 0.34) and a left ventricular ejection fraction ≤35%.
Conclusions: Recognized structural heart disease prior to SCA is less prevalent in women than men.
Perspective: Prior studies have demonstrated that the implantation rate of implantable cardioverter-defibrillators (ICDs) is lower in women than men. The results of this study provide a possible explanation for the gender discrepancy in the ICD implantation rate. Because women are less likely to have recognized coronary artery disease or severe left ventricular dysfunction before SCA, they are less likely to meet the conventional criteria for ICD implantation. This emphasizes the need for identification of more accurate clinical predictors of SCA than simply prior myocardial infarction or a low ejection fraction. Fred Morady, M.D., F.A.C.C.
Source
Content provided by the American College of Cardiology Foundation

The RYR2-Encoded Ryanodine Receptor/Calcium Release Channel in Patients Diagnosed Previously With Either Catecholaminergic Polymorphic Ventricular Tachycardia or Genotype Negative, Exercise-Induced Long QT Syndrome: A Comprehensive Open Reading Frame Mutational Analysis
Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, et al.
J Am Coll Cardiol 2009;54:2065-2074.
Study Question: What is the prevalence of RYR2 mutations in subjects with exertional syncope and normal QT interval (previously classified as probable catecholaminergic polymorphic ventricular tachycardia [CPVT], possible CPVT, or atypical long QT syndrome)?
Title: The RYR2-Encoded Ryanodine Receptor/Calcium Release Channel in Patients Diagnosed Previously With Either Catecholaminergic Polymorphic Ventricular Tachycardia or Genotype Negative, Exercise-Induced Long QT Syndrome: A Comprehensive Open Reading Frame Mutational Analysis
Topic: Arrhythmias
Date Posted: 12/18/2009
Author(s): Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, et al.
Citation: J Am Coll Cardiol 2009;54:2065-2074.
Clinical Trial: No
Study Question: What is the prevalence of RYR2 mutations in subjects with exertional syncope and normal QT interval (previously classified as probable catecholaminergic polymorphic ventricular tachycardia [CPVT], possible CPVT, or atypical long QT syndrome)?
Methods: Mutational analysis of all RYR2 exons was performed using DNA sequencing on 155 unrelated patients (49% females, 96% Caucasian, age at diagnosis 20 ± 15 years, mean QTc 428 ± 29 ms), with either clinical diagnosis of CPVT (n = 110) or an initial diagnosis of exercise-induced long QT syndrome, but with QTc <480 ms and a subsequent negative long QT syndrome genetic test (n = 45).
Results: A total of 63 (34 novel) possible CPVT1-associated mutations, absent in 400 reference alleles, were detected in 73 unrelated patients (47%). Thirteen new mutation-containing exons were identified. Two-thirds of the CPVT1-positive patients had mutations that localized to 1 of 16 exons.
Conclusions: Possible CPVT1 mutations in RYR2 were identified in nearly one-half of this cohort; 45 of the 105 translated exons are now known to host possible mutations. Considering that approximately 65% of CPVT1-positive cases would be discovered by selective analysis of 16 exons, a tiered targeting strategy for CPVT genetic testing should be considered.
Perspective: CPVT is a malignant cardiac channelopathy that leads to mortality rates approaching 50% by age 35. CPVT is associated with gain of function mutations in RYR2, a large gene that codes for a protein involved in sarcoplasmic reticulum calcium release. However, mutation analysis of RYR2 in patients with CPVT has previously been limited without complete exon sequencing. The current study expanded this analysis to all exons in a cohort of unrelated subjects and control alleles, and found additional disease-associated mutations in 13 exons not typically sequenced. Validation of these findings (case-control) and proof of pathogenicity of these novel mutations will require additional study. Daniel T. Eitzman, M.D., F.A.C.C.
Source
Content provided by the American College of Cardiology Foundation

Genotype-Phenotype Aspects of Type 2 Long QT Syndrome
Shimizu W, Moss AJ, Wilde AA, et al.
J Am Coll Cardiol 2009;54:2052-2062.
Study Question: Does the type of KCNH2 mutation affect the clinical course of patients with type 2 long QT syndrome (LQTS)?
Title: Genotype-Phenotype Aspects of Type 2 Long QT Syndrome
Topic: Arrhythmias
Date Posted: 12/17/2009
Author(s): Shimizu W, Moss AJ, Wilde AA, et al.
Citation: J Am Coll Cardiol 2009;54:2052-2062.
Clinical Trial: No
Study Question: Does the type of KCNH2 mutation affect the clinical course of patients with type 2 long QT syndrome (LQTS)?
Methods: The subjects of this study were 858 patients with type 2 LQTS. The KCNH2 mutations were characterized and correlated with the time to first cardiac event (syncope, cardiac arrest, or sudden cardiac death).
Results: A total of 162 mutations of KCNH2 were identified in the 858 patients. A missense mutation, with a single amino acid substitution, had a prevalence of 62% and was the most common type of mutation. The mutation that was associated with the highest risk of a first cardiac event (hazard ratio 2.87) was a missense mutation in the transmembrane pore (S5-loop-S6). Therapy with a beta-blocker was associated with a 63% reduction in the risk of a first cardiac event, but only a 29% reduction in the risk of a lethal cardiac event.
Conclusions: In patients with type 2 LQTS, the highest risk of syncope, cardiac arrest, or sudden cardiac death is associated with a missense mutation in the transmembrane pore.
Perspective: The results suggest that genetic analysis may be useful in guiding the prophylactic therapy of asymptomatic patients with type 2 LQTS. An implantable cardioverter-defibrillator might be appropriate for patients with a high-risk mutation, whereas a beta-blocker could be used in patients with the low-risk mutations. Fred Morady, M.D., F.A.C.C.

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Title: Endovascular Stent-Grafts for the Treatment of Abdominal Aortic Aneurysms: NICE Technology Appraisal Guidance
Topic: Cardiovascular Surgery
Date Posted: 12/9/2009
Author(s): Hay N, McCracken F, Richardson J, George E, Barnett D.
Citation: Heart 2009;95:1798-800.
Clinical Trial: No
Perspective: The top 10 points to remember about the NICE guidance on the use of stent-grafts to treat abdominal aortic aneurysms (AAAs) are:

1. Endovascular aneurysm repair (EVAR) is recommended as a treatment option in patients with infrarenal AAAs for whom repair is considered appropriate.

2. Decisions as to whether to pursue EVAR or open AAA repair should be made jointly by the patient and his/her clinician.

3. Aneurysm size and morphology, patient age, life expectancy and fitness, and long- and short-term benefits and risks of the procedures should figure into the decision about which route of AAA repair is appropriate.

4. EVAR should only be performed in centers of excellence by clinical teams experienced in the management of patients with AAAs.

5. EVAR was not recommended for ruptured AAAs, except in the context of research.

6. EVAR has lower medium-term reduced rates of operative and aneurysm mortality.

7. EVAR, however, is not associated with a reduction in all-cause mortality long-term. In addition, EVAR is associated with increased rates of complications and reinterventions compared with open repair.

8. As most reports comparing open repair and EVAR use older devices, the appraisal committee suggested that the benefits of EVAR were likely greater than that seen in randomized control trials.

9. Assuming an endograft cost of 5000 pounds, the committee concluded that there was little or no difference in the initial procedure costs between EVAR and open repair.

10. In determining the fitness for surgery, which impacts cost-effectiveness, the group agreed that decisions over recommending EVAR versus open repair should be made on an individual basis, jointly between the patient and his/her clinician. Gilbert Upchurch, Jr., M.D.

Title: Mitral-Valve Repair for Mitral-Valve Prolapse
Topic: Cardiovascular Surgery
Date Posted: 12/9/2009
Author(s): Verma S, Mesana TG.
Citation: N Engl J Med 2009;361:2261-2269.
Clinical Trial: No
Perspective: This summary describes a case of a patient presenting with myxomatous degeneration of the mitral valve and severe mitral regurgitation (MR), and then discusses the clinical problem and the benefits and risks of mitral valve repair. Ten points to remember are:

1. ‘Mitral valve prolapse’ (myxomatous degeneration of the mitral valve) is the most common cause of MR in developed countries, with a prevalence of ~2.5%. There is a heterogeneous natural history of disease. In some patients, MR does not progress to severe, and life expectancy is normal; whereas in other patients (estimated at 5-10%), MR progresses to severe, with associated adverse outcomes.

2. The mitral valve apparatus is comprised of mitral leaflets, annulus, chordae tendinae, papillary muscles, and the associated left ventricular (LV) myocardium. The posterior mitral valve has three scallops. One terminology refers to the posterior scallops as P1, P2, and P3 (from anterolateral to posteromedial). MR can be caused by malcoaptation of myxomatous, prolapsing leaflets, potentially exacerbated by mitral annular dilation. (Although not discussed, MR also can be caused by partial flail of a leaflet, typically associated with rupture of one or more chordae.)

3. When present, chronic severe MR leads to volume overload of the LV, with LV dilation, hypertrophy, neurohumeral activation, and heart failure. Elevation of left atrial pressure leads to left atrial enlargement, atrial fibrillation, pulmonary venous congestion, and pulmonary hypertension.

4. There are no randomized trials comparing medical therapy with surgery for MR caused by mitral valve prolapse. However, some (but not all) observational studies suggest that survival is superior with early surgical intervention.

5. Mitral valve surgery can take the form of mitral valve replacement (with a mechanical or a tissue prosthesis) or mitral valve repair. There are no randomized trials comparing mitral valve repair and mitral valve replacement for MR caused by mitral valve prolapse. However, most (but not all) observational studies suggest that outcomes (including survival) are superior with mitral valve repair.

6. Surgical intervention generally is recommended for chronic severe MR and the presence of any symptoms, LV systolic dysfunction (in this review defined as an ejection fraction <60%, but based on American College of Cardiology [ACC]/American Heart Association [AHA] guidelines the threshold is ≤60%), significant LV enlargement (in this review defined as a systolic diameter >40 mm, but based on ACC/AHA guidelines the threshold is ≥40 mm), pulmonary arterial hypertension, or new atrial fibrillation. When surgery is indicated, current ACC/AHA and European Society of Cardiology (ESC) guidelines recommend preferential use of repair over replacement. If valve replacement is performed, subvalvular chordal attachments should be preserved.

7. There is debate regarding the use of ‘prophylactic’ mitral valve repair, used to treat chronic severe MR in an asymptomatic patient with none of the usual indications for surgery (see #6, above). ACC/AHA guidelines recommend prophylactic mitral valve repair if the likelihood of successful repair is >90%; the ESC guidelines recommend a more conservative approach.

8. Mitral valve repair is a specialized technique that should be carried out by an experienced repair surgeon. Individual and institutional experience is crucial; and high volumes are associated with both greater likelihood of valve repair rather than replacement, and lower procedural mortality.

9. Surgical valve repair can include resection of redundant or flail posterior segment(s); ‘sliding plasty’ to decrease posterior leaflet height; and chordal transposition, the use of artificial chordae, and edge-to-edge repair for anterior leaflet pathology.

10. Adverse outcomes associated with surgery include death, requirement for prolonged ventilatory support, renal insufficiency, stroke, thromboembolism, and late recurrence of MR sometimes requiring reoperation. David S. Bach, M.D., F.A.C.C.

Title: The Yield of Risk Stratification for Sudden Cardiac Death in Hypertrophic Cardiomyopathy Myosin-Binding Protein C Gene Mutation Carriers: Focus on Predictive Screening
Topic: Heart Failure/Transplant
Date Posted: 12/21/2009
Author(s): Christiaans I, Birnie E, van Langen IM, et al.
Citation: Eur Heart J 2009;Dec. 16:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the value of risk stratification with genetic screening and clinical evaluations in patients with MYBPC3 gene mutations?
Methods: Two hundred and thirty-five mutation carriers were evaluated for the presence of hypertrophic cardiomyopathy (HCM) and risk factors. A clinical diagnosis of HCM was made in 53 carriers (22.6%).
Results: Disease penetrance was variable for all types of MYBPC3 gene mutations, and women were affected less often than men (15% and 32%, respectively; p = 0.003). One risk factor was present in 87 carriers and 9 had two or more risk factors. Twenty-five carriers (11%) with one or more risk factors and manifest HCM could be at risk for sudden cardiac death (SCD).
Conclusions: At first evaluation, one-quarter of asymptomatic carriers were diagnosed with HCM. Risk factors for SCD were frequently present, and 11% of carriers could be at risk for SCD. The authors concluded that predictive genetic testing in HCM families and frequent cardiac evaluation for the presence of HCM and risk factors for SCD are justified until advanced age.
Perspective: Close clinical follow-up is indicated in relatives of patients with HCM. Knowledge of the mutation status may aid in follow-up if a likely causative mutation is identified. Most mutation carriers in the current study had the same Dutch founder mutation. However, because of the uncertainty of mutation causality in a diverse population and incomplete penetrance of mutation carriers, the added value of genetic testing remains unclear. Clinical outcomes data in HCM families managed with and without genetic screening would be necessary to address this question. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy: A Genome-Wide Analysis
Topic: Heart Failure/Transplant
Date Posted: 12/16/2009
Author(s): Chiu C, Bagnall RD, Ingles J, et al.
Citation: J Am Coll Cardiol 2009;Dec 16:[Epub ahead of print].
Clinical Trial: No
Study Question: What gene mutation is associated with hypertrophic cardiomyopathy (HCM) in a large family with a heterogenous HCM phenotype?
Methods: History, physical examination, electrocardiography, and two-dimensional echocardiography were performed, and blood was collected from family members (n = 23) for DNA analysis. The family was genotyped with markers from the 10-cM AB PRISM Human Linkage mapping set (Applied Biosystems, Foster City, CA), and 2-point linkage analysis was performed.
Results: Affected family members showed marked clinical diversity, ranging from asymptomatic individuals to those with syncope, heart failure, and premature sudden death. The disease locus for this family was mapped to chromosome 1q42.2-q43, near the marker D1S2850 (logarithm of odds ratio = 2.82, Ө = 0). A missense mutation, Ala119Thr, in the alpha-actinin-2 (ACTN2) gene was identified that segregated with disease in the family. An additional 297 HCM probands were screened for mutations in the ACTN2 gene using high-resolution melt analysis. Three causative ACTN2 mutations, Thr495Met, Glu583Ala, and Glu628Gly, were identified in an additional four families (total 1.7%) with HCM.
Conclusions: The authors concluded that this is the first genome-wide linkage analysis, which shows that mutations in ACTN2 cause HCM.
Perspective: ACTN2 is a multifunctional actin binding protein found in skeletal and cardiac muscle, where it is a major component of the Z-disc. A previous study using a candidate gene approach in a large HCM cohort identified ACTN2 mutations in 1.3% of the patients. By using a genome-wide approach, the current study confirms these previous findings, and provides stronger support for a causal relationship between ACTN2 mutations and HCM phenotypes. Additional confirmatory clinical studies as well as basic functional studies of these mutations to determine how they predispose to HCM will add important insight into the pathophysiology of this disease process. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction: Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial
Topic: Heart Failure/Transplant
Date Posted: 12/10/2009
Author(s): Daubert C, Gold MR, Abraham WT, et al., on behalf of the REVERSE Study Group.
Citation: J Am Coll Cardiol 2009;54:1837-1846.
Clinical Trial: No
Study Question: Is cardiac resynchronization therapy (CRT) of value in patients with asymptomatic or mildly symptomatic left ventricular dysfunction?
Methods: A CRT device was implanted in 262 patients (mean age 61 years) with an ejection fraction (EF) ≤40% (mean EF 28%), QRS ≥120 ms, and a New York Heart Association (NYHA) functional class of I-II. The patients were randomly assigned to CRT on (n = 180) or CRT off (n = 82), and followed for 24 months. The 1° endpoint was the heart failure (HF) clinical composite response. The criteria for a worsened HF composite response were death, hospitalization or crossover to alternate therapy because of worsened HF, or an increase in NYHA functional class.
Results: At 24 months of follow-up, a worsened HF composite response was significantly less prevalent in the CRT-on group (19%) than in the CRT-off group (34%). The left ventricular end-systolic volume index decreased to a significantly greater extent in the CRT-on group (27.5 ml/m2) than in the CRT-off group (2.7 ml/m2). A significantly smaller proportion of patients required hospitalization for HF in the CRT-on group (7.2%) than in the CRT-off group (17.1%).
Conclusions: CRT improves clinical outcomes and reverses remodeling in patients with asymptomatic or mildly symptomatic left ventricular function.
Perspective: The MADIT-CRT study recently demonstrated that CRT reduces the risk of HF events and reverses remodeling in patients with asymptomatic or mildly symptomatic left ventricular dysfunction. The present study provides further support for broadening the indications for CRT to include patients with a functional class of I-II. Fred Morady, M.D., F.A.C.C.

Title: Risk of Bleeding in Patients With Acute Myocardial Infarction Treated With Different Combinations of Aspirin, Clopidogrel, and Vitamin K Antagonists in Denmark: A Retrospective Analysis of Nationwide Registry Data
Topic: General Cardiology
Date Posted: 12/14/2009
Author(s): Sшrensen R, Hansen ML, Abildstrom SZ, et al.
Citation: Lancet 2009; 374:1967-1974.
Clinical Trial: No
Study Question: What is the long-term risk of bleeding among patients with myocardial infarction (MI) who are treated with aspirin, clopidogrel, or Coumadin or any combination of these agents?
Methods: The authors used nationwide registries from Denmark to identify patients ages 30 years or older who had been admitted to the hospital with first-time MI between 2000 and 2005. Prescription claims starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Patients could be in only one group at a time, although they could change groups as medications were started or stopped. Risk of hospital admission for bleeding, recurrent MI, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. Use of this model implies that patients were only deemed at risk for each exposure group while taking the corresponding antithrombotic drug(s).
Results: The total cohort was comprised of 40,812 patients. During a mean follow-up of 476 days, 1,852 (4.5%) patients required hospitalization for a nonfatal bleeding event. The annual incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. After adjusting for baseline differences, and using the aspirin group as a reference, adjusted hazard ratios for bleeding were 1.33 (95% confidence interval [CI], 1.11-1.59) for clopidogrel, 1.23 (95% CI, 0.94-1.61) for vitamin K antagonist, 1.47 (95% CI, 1.28-1.69) for aspirin plus clopidogrel, 1.84 (95% CI, 1.51-2.23) for aspirin plus vitamin K antagonist, 3.52 (95% CI, 2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (95% CI, 3.08-5.33) for triple therapy. Patients with nonfatal bleeding were at a higher risk of recurrent MI or death (37.9% vs. 18.4%; HR, 3.00; 95% CI, 2.75-3.27; p < 0.001) compared with patients without any bleeding events. Mean time from claiming a prescription of an antithrombotic treatment to occurrence of a bleeding event varied from 169 days for clopidogrel monotherapy to 275 days for monotherapy with a vitamin K antagonist. Most nonfatal bleeding events were gastrointestinal.
Conclusions: Risk of hospital admission for bleeding increased with the number of antithrombotic drugs used in patients with MI.
Perspective: This study adds to the evidence base guiding physicians contemplating use of Coumadin in patients with a recent MI. Both triple therapy and dual therapy with a vitamin K antagonist and clopidogrel was associated with extremely high risk of bleeding. Triple therapy or combination of Coumadin and clopidogrel should only be used after careful assessment of the risk–benefit ratio of the individual patient. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: C-Reactive Protein Concentration and Risk of Coronary Heart Disease, Stroke, and Mortality: An Individual Participant Meta-Analysis
Topic: Prevention/Vascular
Date Posted: 12/21/2009 8:00:00 PM
Author(s): The Emerging Risk Factors Collaboration.
Citation: Lancet 2009;Dec 22:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the association of C-reactive protein (CRP) concentration and risk of vascular and nonvascular outcomes, and is the relationship causal?
Methods: A collaborative study using meta-analysis was conducted between investigators of 54 prospective studies of cardiovascular risk factors who provided individual subject data regarding CRP and outcomes. The cohort included 160,309 people without a history of vascular disease (i.e., 1.31 million person-years at risk, 27,769 fatal or nonfatal disease outcomes). Within-study regression analyses were adjusted for within-person variation in risk factor levels. The primary outcome was coronary heart disease (CHD) (i.e. first-ever myocardial infarction or fatal CHD), with subsidiary analyses of stroke by subtype, death from vascular disease, and aggregate of nonvascular death.
Results: Loge CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischemic vascular disease and nonvascular mortality. Significant increases in risk ratios (RRs) were found for CHD per 1-standard deviation higher loge CRP concentration (threefold higher) RR 1.63 when initially adjusted for age and sex only, and RR 1.37 when adjusted further for conventional risk factors; 1.44 and 1.27 for ischemic stroke; 1.71 and 1.55 for vascular mortality; and 1.55 and 1.54 for nonvascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 for CHD; 1.32 for ischemic stroke; 1.34 for vascular mortality; and 1.34 for nonvascular mortality.
Conclusions: CRP concentration has continuous associations with the risk of CHD, ischemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. Associations with ischemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.
Perspective: There is debate about the clinical utility of CRP for risk assessment in cardiovascular disease as well as whether it is a causal relationship or simply a biomarker of risk. This study adds to the abundant literature supporting CRP as a risk marker for cardiovascular events and mortality. And the JUPITER trial provided clinical evidence that it may be useful to risk stratify persons with relatively normal lipid profiles for deciding statin therapy. CRP binds to low-density lipoprotein, and is found in atherosclerotic plaque, suggesting causality. However, this study showing attenuation of attributable risk when corrected for fibrinogen, and recent studies showing no relationship between genetic polymorphisms associated with a higher level of CRP and cardiovascular disease imply that CRP is a risk marker, but not a risk factor for cardiovascular events. And the important saga continues. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Association of Circulating Cholesteryl Ester Transfer Protein Activity With Incidence of Cardiovascular Disease in the Community
Topic: Prevention/Vascular
Date Posted: 12/16/2009
Author(s): Vasan RS, Pencina MJ, Robins SJ, et al.
Citation: Circulation 2009;120:2414-2420.
Clinical Trial: No
Study Question: What is the relationship between plasma cholesteryl ester transfer protein (CETP) activity and the incidence of cardiovascular disease (CVD)?
Methods: Plasma CETP activity was measured in 1978 Framingham Heart Study participants (mean age, 51 years; 54% women) who attended a routine examination from 1987 to 1990 and were free of CVD. On follow-up (mean, 15.1 years), 320 participants experienced a first CVD event (fatal or nonfatal coronary heart disease, cerebrovascular disease, peripheral vascular disease, or heart failure).
Results: In multivariable analyses adjusted for standard risk factors including high-density lipoprotein (HDL) cholesterol, plasma CETP activity was related inversely to the incidence of CVD events (hazard ratio [HR] for activity, at or above the median of 0.72; 95% confidence interval, 0.57-0.90; p = 0.004 [compared with below median]; HR per standard deviation increment, 0.86; 95% confidence interval, 0.76-0.97; p = 0.01). The inverse association of CETP activity with CVD incidence remained robust in time-dependent models updating standard risk factors every 4 years, and was maintained in analyses of incident “hard” CVD events (myocardial infarction, stroke, or heart failure).
Conclusions: In this prospective investigation of a community-based sample, lower plasma CETP activity was associated with greater CVD risk. These observations, if confirmed, challenge the concept that CETP inhibition may lower CVD risk.
Perspective: Although HDL levels are inversely related to the risk of CVD, pharmacologic strategies designed to raise HDL based on CETP inhibition have not produced beneficial vascular effects, and may even be harmful. Whether these adverse effects are due to off-target drug effects or to the mechanism of raising HDL is unclear and will be addressed in future clinical trials with other CETP inhibitors. Studies addressing relationships between genetic CETP abnormalities and circulating CETP concentrations with CVD have been controversial. The current study adds important prospective data to this controversial area and suggests CETP inhibitors will not have beneficial effects on CVD events, and may lead to harm. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Total Cardiovascular Disease Burden: Comparing Intensive With Moderate Statin Therapy: Insights From the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) Trial
Topic: Prevention/Vascular
Date Posted: 12/11/2009 9:00:00 AM
Author(s): Tikkanen MJ, Szarek M, Fayyad R, et al., on behalf of the IDEAL Investigators.
Citation: J Am Coll Cardiol 2009;54:2353-2357.
Clinical Trial: No
Study Question: What is the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event?
Methods: This was a post-hoc analysis of the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) trial, aimed to assess the comparative treatment efficacy of two statin regimens for the events beyond the first, using the broadest secondary endpoint (any cardiovascular disease [CVD]), consisting of the primary endpoint (coronary heart disease death, nonfatal myocardial infarction, and resuscitated cardiac arrest) plus the following: stroke, revascularization, hospitalization for unstable angina pectoris, hospitalization for congestive heart failure, and peripheral artery disease. The Wei, Lin, and Weissfeld method allows the analysis of repeated occurrence of events of the same type or of entirely different natures; it regards the recurrence times as multivariate event (failure) times, and models the marginal (individual) distribution for each event with the Cox proportional hazards model.
Results: In the IDEAL trial, compared with patients taking simvastatin 20-40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17% (p < 0.0001), of a second by 24% (p < 0.0001), of a third by 19% (p = 0.035), of a fourth by 24% (p = 0.058), and of a fifth by 28% (p = 0.117).
Conclusions: The authors concluded that intensive statin therapy continues to be more effective than standard statin therapy, even beyond the first event.
Perspective: This study explored the possibility that new information concerning treatment efficacy of intensive statin therapy compared with standard statin therapy could be gained by analysis of repeated occurrences (after the first event) of different types of CV events. The method allowed analysis of not only time to first CV event, but also time to second, third, fourth, and fifth events. The study results indicate that intensive statin therapy continued to be more effective than standard statin therapy even beyond the first event. This analysis provides new insights into the treatment of patients experiencing repeated occurrences of CVD and suggests that especially for such patients, intensive statin therapy is preferable to standard therapy. Debabrata Mukherjee, M.D., F.A.C.C.

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Time to Reperfusion and Myocardial Damage
ACC Takes Legal Action
CardioSmart Atlanta Healthfair at ACC.10
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Treatment of Aspirin-Resistant Patients With Omega-3 Fatty Acids Versus Aspirin Dose Escalation
Topic: Prevention/Vascular
Date Posted: 1/4/2010 5:00:00 PM
Author(s): Lev EI, Solodky A, Harelet N, et al.
Citation: J Am Coll Cardiol 2010;55:114-121.
Clinical Trial: No
Study Question: What is the effect of addition of omega-3 fatty acids or increase in aspirin dose on response to low-dose aspirin among patients who are aspirin-resistant?
Methods: Patients (n = 485) with stable coronary artery disease (CAD), taking low-dose aspirin (75-162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, CA). Further testing was performed by platelet aggregation. Aspirin resistance was defined by ≥2 of 3 criteria: VerifyNow score ≥550, 0.5 mg/ml arachidonic acid (AA)-induced aggregation ≥20%, and 10-µmol/L adenosine diphosphate (ADP)-induced aggregation ≥70%. Thirty patients (6.2%) were found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment, patients were re-tested.
Results: Both groups (n = 15 each) had similar clinical characteristics. After treatment, significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment.
Conclusions: The authors concluded that treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.
Perspective: This study suggests that either adding omega-3 fatty acids or increasing the aspirin dose can improve response to aspirin and reduce residual platelet reactivity in stable patients with CAD. Treatment with both regimens was associated with a reduction in aspirin-resistance rates. Furthermore, omega-3 fatty acid supplementation might have independent favorable effects in the secondary prevention of CAD and its complications. The investigators did not examine the clinical impact of their therapeutic interventions or whether routine monitoring of aspirin response has any impact on clinical outcomes. Further larger studies are required to assess hard clinical endpoints and evaluate whether the strategy tested in this pilot study has any clinical benefit in patients with cardiovascular disease found to be resistant to aspirin. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction (NORDISTEMI)
Trial Sponsor: Norwegian Health Authorities and AH Waage Foundation
Year Presented: 2009
Year Published 2009
Topic(s): General Cardiology, Interventional Cardiology
Summary Posted: 1/4/2010 5:00:00 PM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Supplemental Reviewer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Description
The goal of the trial was to evaluate immediate transfer for percutaneous coronary intervention (PCI) compared with conservative, ischemia-guided treatment among patients with ST-elevation myocardial infarction (STEMI) treated with thrombolysis with very long transfer times to PCI hospitals.
Hypothesis
Patients treated with thrombolytic therapy for STEMI with a very long transfer time to a PCI hospital would have a reduction in major adverse cardiac events (MACE) with immediate transfer for angiography and PCI, as compared to ischemia-guided treatment in local hospitals with transfer for rescue PCI, if needed.
Drugs/Procedures Used
Patients were treated with optimal medical therapy (tenecteplase [TNK], aspirin, enoxaparin, and clopidogrel) and were then randomized to immediate transfer for angiography/PCI (n = 134) or ischemia-guided treatment in local hospitals with transfer for rescue PCI if needed (n = 132). SPECT was performed at 3 months of follow-up.
Concomitant Medications
Aspirin (300 mg), TNK, enoxaparin (30 mg IV 1 mg/kg subcutaneously), clopidogrel (300 mg)
Principal Findings
Median time from symptom onset to TNK administration was 117 minutes in the invasive group and 126 minutes in the conservative group (p = 0.72). There was a slight excess of patients with treated hypertension in the conservative group (38% vs. 25%, p = 0.03), but other baseline characteristics were well balanced between treatment groups. Infarct location was anterior in 41% of patients.

Angiography was performed in 99% of the invasive group and 95% of the conservative group, with median time from TNK administration to arrival in the catheterization laboratory of 130 minutes and 5.5 days, respectively. PCI was performed in 89% of the invasive group and 71% of the conservative group, with a median time from TNK to PCI of 163 minutes and 3.0 days, respectively. The median transfer distance to the PCI center was 158 km among invasive patients. There were few complications associated with the transport: one death in the invasive group, ventricular fibrillation in 3% of the invasive group, and ventricular tachycardia in 1.5% of the conservative group. Stents were used in a higher proportion of the invasive group (86% vs. 68%). Radial access was used in 86% and glycoprotein IIb/IIIa inhibitors in 9%.

The primary endpoint of death, reinfarction, stroke, or new ischemia at 1 year did not differ between treatment groups (20.9% for invasive vs. 27.3% for conservative, p = 0.18). However, there was a significant reduction in the secondary endpoint of death, MI, or stroke at 12 months with the invasive strategy (6.0% vs. 15.9%, p = 0.01). Death was 2.2% versus 3.0%, reinfarction was 3.0% versus 9.1%, stroke was 2.2% versus 5.3%, and recurrent ischemia was 15.0% versus 15.2%, respectively for invasive versus conservative therapy.

At 30 days, the composite of death, reinfarction, stroke, or new ischemia was lower in the invasive group (10% vs. 21%, p = 0.03), but there was no difference in death, reinfarction, or stroke (4.5% vs. 9.8%, p = 0.14). Total bleeding events at 30 days were similar in both groups (13% for invasive group vs. 14% for conservative group, p = 0.68), as was GUSTO severe bleeding (1.5% vs. 2.3%), moderate bleeding (0% vs. 2.3%), and minor bleeding (10% vs. 9.8%).
Interpretation
Among TNK-treated patients with STEMI with very long transfer times to PCI hospitals, immediate transfer for PCI did not lead to a significant reduction in the primary composite endpoint of death, reinfarction, stroke, or new ischemia at 1 year compared with conservative, ischemia-guided treatment; however, a significant benefit was seen with the secondary endpoint of death, reinfarction, or stroke.

Previous studies such as DANAMI-2 have demonstrated that transfer of patients for primary PCI reduces the risk of death, reinfarction, or stroke compared with thrombolytic therapy. However, limited data are available for the comparison of immediate transfer for PCI compared with conservative ischemia-guided therapy in STEMI patients with very long transfer times who were previously treated with thrombolytic therapy. In the CARESS-in-AMI trial of STEMI patients treated with thrombolytic therapy, transfer for immediate PCI was associated with a reduction in the primary endpoint of death, reinfarction, or refractory ischemia at 30 days compared with conservative strategy, but transfer times (and presumably distances) were shorter than in NORDISTEMI, particularly in the conservative group.

There was a reduction in the secondary endpoint of death, reinfarction, stroke, or new ischemia at 30 days with immediate transfer in the present study, as well as a reduction in death, MI, or stroke at 12 months. Despite randomization to the conservative group, a large percentage of patients underwent PCI (71%), albeit in a delayed manner (median 3.0 days). The safety profile of the two strategies appeared similar, with no difference in bleeding by a variety of definitions. The low bleeding rates were probably attributable to the high use of radial access and low use of glycoprotein IIb/IIIa inhibitors.
Conditions
• Coronary heart disease
• Coronary heart disease / Acute MI
Therapies
• Early invasive and conservative strategies
Study Design
Randomized.
Patients Screened: 526
Patients Enrolled: 266
Mean Follow-Up: 12 months
Mean Patient Age: 60 years
% Female: 24

Primary Endpoints
Composite of death, reinfarction, stroke, or new ischemia by 12 months
Secondary Endpoints
Composite of death, reinfarction, or stroke by 12 months; bleeding complications within 30 days; transport complications; infarct size at 3 months (SPECT); quality of life at 12 months; total costs over 12 months
Patient Population
Age 18-75 years, symptoms of MI for <6 hours, ST-segment elevation ≥1 mm in two contiguous extremity leads or ≥2 mm in two contiguous precordial leads or new LBBB, expected time delay from first medical contact to PCI >90 minutes, receiving thrombolytic treatment with tenecteplase
Exclusions:
Standard contraindication for thrombolytic treatment, known serious renal failure (creatinine >250 mmol/L), cardiogenic shock, diseases with life expectancy <12 months
References: Bшhmer E, Hoffmann P, Abdelnoor M, Arnesen H, Halvorsen S. Efficacy and safety of immediate angioplasty versus ischemia-guided management after thrombolysis in acute myocardial infarction in areas with very long transfer distances: results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction). J Am Coll Cardiol 2010;55:102-10.

Presented by Dr. Sigrun Halvorsen at the European Society of Cardiology Congress, Barcelona, Spain, August 2009.

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Title: Recommendations for Interpretation of 12-Lead Electrocardiogram in the Athlete
Topic: Arrhythmias
Date Posted: 1/8/2010
Author(s): Corrado D, Pelliccia A, Heidlbuchel H, et al.
Citation: Eur Heart J 2009;Dec 22:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember from this position paper formulated by the European Society of Cardiology:

1. Electrocardiographic findings that are common and training-related and that do not require additional evaluation are sinus bradycardia, 1° atrioventricular block (AVB), incomplete right bundle branch block (BBB), early repolarization, and isolated voltage criteria for left ventricular hypertrophy (LVH).

2. Uncommon and training unrelated electrocardiographic findings that mandate further evaluation include T-wave inversion, ST-segment depression, pathological Q waves, atrial enlargement, a hemiblock, right ventricular hypertrophy, a BBB, or a Brugada-pattern of ST-segment elevation.

3. Training-related electrocardiographic findings are more common in men than women, athletes of African descent, and high-endurance athletes such as cyclists.

4. Sinus rates <30 bpm and sinus pauses >2 seconds are common in highly trained athletes, particularly during sleep.

5. A normal chronotropic response to exertion and the absence of bradycardia-related symptoms distinguishes training-related sinus bradycardia from sinus node dysfunction.

6. 1° AVB and Mobitz I 2° AVB are common, but Mobitz II 2° AVB or 3° AVB should not be assumed to be training-related and require evaluation.

7. Early repolarization in Caucasian athletes most commonly consists of upwardly concave ST-segments and tall and peaked T waves; in black athletes, there often is convex ST-segment elevation and negative T waves, mimicking a Brugada pattern.

8. In the presence of voltage criteria for LVH, pathological hypertrophy should be suspected if there is left atrial enlargement, left-axis deviation, repolarization abnormalities, or pathological Q waves.

9. T-wave inversion ≥2 mm in ≥2 adjacent leads should prompt evaluation for structural heart disease.

10. Electrophysiological testing for risk stratification with possible catheter ablation is appropriate in athletes with ventricular pre-excitation. Fred Morady, M.D., F.A.C.C.

Title: Improved Survival Among Patients With Eisenmenger Syndrome Receiving Advanced Therapy for Pulmonary Arterial Hypertension
Topic: Arrhythmias
Date Posted: 1/11/2010
Author(s): Dimopoulos K, Inuzuka R, Goletto S, et al.
Citation: Circulation 2010;121:20-25.
Clinical Trial: No
Study Question: Advanced therapy (AT) for pulmonary arterial hypertension (PAH) in the context of congenital heart disease improves pulmonary hemodynamics, functional class, and the 6-minute walk test. Has there been an effect of AT on survival in the Eisenmenger syndrome?
Methods: Data on all Eisenmenger patients attending a single center over the past decade were collected. Survival rates were compared between patients on and off AT with the use of a modified version of the Cox model, which treats modern AT as a time-varying covariate. Baseline differences were adjusted for the use of propensity scores.
Results: A total of 229 patients (ages 34.5 ± 12.6 years; 35.4% male) were included. The majority had complex anatomy, and 53.7% were in New York Heart Association (NYHA) class ≥III at baseline. Mean resting oxygen saturation was 84.3%. Sixty-eight patients (29.7%) either were on AT or had AT initiated during follow-up. During a median follow-up of 4.0 years, 52 patients died, only 2 of them while on AT. Patients on AT were at a significantly lower risk of death, both unadjusted and after adjustment for baseline clinical differences by propensity score regression adjustment (C statistic = 0.80; hazard ratio, 0.16; 95% confidence interval, 0.04-0.71; p = 0.015) and propensity score matching (hazard ratio, 0.10; 95% confidence interval, 0.01-0.78; p = 0.028). Despite being older and sicker, only 2 of the 68 patients who received AT for a median period of 2.4 years died, compared with 50 deaths in those not receiving AT.
Conclusions: Advanced treatment for PAH in a contemporary cohort of adults with Eisenmenger syndrome was associated with a lower risk of death. Survival benefits should be considered together with improved hemodynamics and functional class when decisions are made about treatment in this population.
Perspective: The prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors (advanced therapies) have each alone and in combination been effective at improving quality of life in PAH. A meta-analysis of randomized controlled trials of PH-specific therapies in various types of PAH recently showed a 43% reduction in overall mortality rate, but did not include the Eisenmenger syndrome. Placebo-controlled trials in congenital heart disease are limited, and placebo-controlled trials to assess the effects on mortality rate would be considered unethical. The survival advantage of those treated with advanced therapy in this single center as measured by the hazard ratio is over ninefold, despite the fact that patients receiving the novel drugs were more often NYHA class IV, older, and had more syncope. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Protective Effect of Periconceptional Folic Acid Supplements on the Risk of Congenital Heart Defects: A Registry-Based Case-Control Study in the Northern Netherlands
Topic: Congenital Heart Disease
Date Posted: 12/31/2009
Author(s): van Beynum IM, Kapusta L, Bakker MK, den Heijer M, Blom HJ, de Walle HE.
Citation: Eur Heart J 2009;Dec 1:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there a protective effect of periconceptional folic acid use on the risk of congenital heart disease (CHD)?
Methods: A case control study was performed using the EUROCAT–Northern Netherlands registry. All infants registered with CHD from 1996-2005 were included. Patients with CHD were categorized as having either: 1) an isolated single heart defect, 2) multiple heart defects, 3) heart defects associated with other congenital anomalies, or 4) a genetic anomaly with associated cardiac defect, such as in trisomy 21. Parents of registered infants completed questionnaires with items related to demographics, medications, vitamin intake, smoking habits, and alcohol consumption. Mothers were defined as using periconceptional folic acid if they took folic acid supplementation through the entire advised period of 4 weeks prior to conception and 8 weeks post-conception, or if they took folic acid following conception, regularly through the advised period. Others were categorized as nonusers, except when the use of folic acid was unknown or when a folic acid antagonist use was reported, which resulted in exclusion from the analysis. Analysis for potential confounders, including association of folic acid use with maternal age, maternal body mass index (BMI), smoking, ethyl alcohol (ETOH) use, year of birth, and maternal education level, was performed. Relative risk for CHD was calculated with odds ratios from logistic regression models.
Results: Complete data were available from the registry on 3,836 mothers, with 3,012 remaining after exclusion for maternal diabetes, reported use of folic acid antagonists, or presence of defects, which can be reduced with the use of folic acid (neural tube defects, oral clefts, hypospadias, and limb reduction anomalies). There were 611 cases with CHD, and 2,401 controls. The controls included infants with chromosomal or genetic aberrations or other congenital anomalies. There were no differences between cases and controls in maternal age, BMI, educational level, smoking, ETOH use, or year of birth. Adequate use of periconceptional folic acid was found in 56% of cases, and 61% of controls. Mothers who had periconceptional folic acid use were 18% less likely to deliver an infant with any type of CHD, and 38% less likely to deliver an infant with a septal defect. Subgroup analysis did not demonstrate a lower risk with the use of folic acid for conotruncal defects, atrioventricular septal defects, right-sided obstruction, or left-sided obstruction lesions. With adjustment for previously described potential confounders (maternal age, BMI, smoking, ETOH, educational level, and year of birth), the odds ratio was 0.82 (95% confidence interval, 0.68-0.997).
Conclusions: The use of periconceptional folic acid was found to reduce the risk of CHD compared to other nonfolic acid–related malformations. The overall risk reduction from this case control study was 18%, with 38% reduction in risk for septal defects.
Perspective: Reduction of risk for CHD with the use of folic acid has been debated in the literature. The investigators have demonstrated in this well-described study the risk reduction for CHD that is accompanied by the use of folic acid in the periconceptional period. Although a randomized trial on folic acid intake would provide a more certain answer to this research question, because folic acid is recommended during the periconceptional period to reduce other birth defects including neural tube defects, such a trial would be unethical. Case control trials are limited by the ability to adjust for potential confounders. In this study, van Bynum and colleagues did adjust for major confounders including the use of folic acid antagonists. The control group was a group of patients with anomalies thought unrelated to folic acid use. This is not a perfect substitute for the general population, but likely provides a more conservative estimate of the effect of folic acid. In conclusion, these data are supportive of a role of folic acid during the periconceptional period to reduce the risk of CHD by nearly 20%, with a 38% reduction in the rate of septal defects. The optimal dose and method of intake of folic acid through supplemented food, multivitamins, or an isolated folic acid supplement remains unclear. Caren S. Goldberg, M.D., F.A.C.C.

Title: Use of Genetics in the Clinical Evaluation of Cardiomyopathy
Topic: Heart Failure/Transplant
Date Posted: 12/29/2009
Author(s): Judge DP.
Citation: JAMA 2009;302:2471-2476.
Clinical Trial: No
Perspective: The following are 10 points to remember about use of genetics in the clinical evaluation of cardiomyopathy:

1. Dilated cardiomyopathy (DCM) occurs in approximately 1 in 2,500 persons in the United States, and at least 20-35% of these patients have an affected family member. Every patient presenting with DCM should have a family history taken, including information about CM, sudden cardiac death, and syndromic features over at least three generations. DCM in a single additional family member establishes the diagnosis of familial DCM, in the absence of other factors associated with CM such as severe hypertension, severe coronary artery disease, and excessive chronic ethyl alcohol use.

2. Since early treatment with angiotensin-converting enzyme (ACE) inhibitors has been shown to be beneficial in patients with left ventricular (LV) dysfunction, recognition of patients predisposed to DCM is clinically important. For example, a small study showed that incident CM was reduced in patients with Duchenne muscular dystrophy if they were treated with an ACE inhibitor prior to the onset of LV dysfunction.

3. Marked genetic heterogeneity complicates genetic testing for CM. Mutations in more than 35 genes have been associated with DCM, and genetic testing is clinically available for about half of these.

4. Mutations in the lamin A/C gene are found in 5-20% of patients with DCM, and may result in a worse prognosis. Ten percent of DCM patients have a mutation in a sarcomere gene.

5. Hypertrophic CM (HCM) occurs in about 1 in 500 persons in the United States, and is the most common cause of sudden death in young athletes. Most mutations identified are found in sarcomere genes. Sarcomere mutations can thus cause either HCM or DCM.

6. Fabry disease is an X-linked lysosomal storage disease due to deficiency of α-galactosidase A that may lead to LV hypertrophy, which is difficult to distinguish from HCM due to other mutations. Other features associated with Fabry disease include skin angiokeratomas, corneal clouding, neuropathy, anhidrosis, and renal failure. The Food and Drug Administration has approved recombinant enzyme treatment for this disease.

7. Familial amyloidosis may present with similar features to other forms of HCM, but with echocardiograms showing LV hypertrophy and electrocardiograms showing low voltage. Monoclonal light chains should be measured in the serum and urine in these cases, and a cardiac biopsy can confirm the diagnosis with appropriate staining. Familial cardiac amyloid is often due to mutations in the transthyretin gene, and may be associated with neuropathy and chronic diarrhea.

8. The development of genomic DNA sequencing chips will reduce the cost and increase the feasibility of genetic testing to become more widely applied in clinical practice; however, translating the information into clinical practice will be a major hurdle.

9. Genetic testing may provide the diagnostic gold standard for screening of relatives, thus allowing for more vigilant follow-up of those with positive testing. However, decisions not to undergo screening are based on issues such as: a) concern about establishing a pre-existing condition, b) potential negative impact on future insurance premiums and employment (although subjects should be protected by the Genetic Information Nondiscrimination Act [GINA]), and c) uncertainty regarding mutation pathogenicity.

10. Genetic counseling should be provided prior to genetic testing. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Novel Approaches for Preventing or Limiting Events (Naples) II Trial: Impact of a Single High Loading Dose of Atorvastatin on Periprocedural Myocardial Infarction
Topic: Interventional Cardiology
Date Posted: 1/7/2010
Author(s): Briguori C, Visconti G, Focaccio A, et al.
Citation: J Am Coll Cardiol 2009;54:2157-2163.
Clinical Trial: yes
Study Question: What is the effect of a single, high (80 mg) loading dose of atorvastatin on the rate of periprocedural myocardial infarction (MI)?
Methods: The day before the elective percutaneous coronary intervention (PCI), 668 statin-naive patients were randomly assigned to atorvastatin 80 mg (atorvastatin group; n = 338) or no statin treatment (control group; n = 330). Creatine kinase-myocardial isoenzyme (CK-MB) (upper limit of normal [ULN] 3.5 ng/ml) and cardiac troponin I (ULN 0.10 ng/ml) were assessed before and 6 and 12 hours after the intervention. Periprocedural MI was defined as a CK-MB elevation >3Ч ULN alone or associated with chest pain or ST-segment or T-wave abnormalities. The primary endpoint of the study was the rate of periprocedural MI, defined as a CK-MB elevation >3Ч ULN alone or associated with chest pain or ST-segment or T-wave abnormalities (new definition of MI), in the two study groups.
Results: The incidence of a periprocedural MI was 9.5% in the atorvastatin group and 15.8% in the control group (odds ratio, 0.56; 95% confidence interval, 0.35-0.89; p = 0.014). Median CK-MB peak after PCI was 2.10 ng/ml (interquartile range 1.00-12.50 ng/ml) in the atorvastatin group and 3.20 ng/ml (interquartile range 1.37-16.07 ng/ml) in the control group (p = 0.014). The incidence of cardiac troponin I elevation >3Ч ULN was 26.6% in the atorvastatin group and 39.1% in the control group (odds ratio, 0.56; 95% confidence interval, 0.40-0.78; p < 0.001).
Conclusions: The authors concluded that a single, high (80 mg) loading (within 24 hours) dose of atorvastatin reduces the incidence of periprocedural MI in elective PCI.
Perspective: This randomized study demonstrated that a single high (80 mg) loading dose of atorvastatin administered within 24 hours before stenting is effective in reducing the rate of periprocedural MI. This result confirms previous observations demonstrating that statins prevent MI after coronary stent implantation. However, in prior studies such as ARMYDA, statin administration was started several days before the procedure. The effectiveness of a single, high loading dose of a statin administered within 24 hours before stenting extends our knowledge of the cardioprotective effect of statin, obviating the need to postpone PCI in all statin-naive patients undergoing elective coronary procedures. The findings of this study need to be validated in a larger blinded study, but it makes clinical sense to administer a high dose of a potent statin prior to performing PCI. Debabrata Mukherjee, M.D., F.A.C.C.

Title: A Randomized Comparison of Transradial Versus Transfemoral Approach for Coronary Angiography and Angioplasty
Topic: Interventional Cardiology
Date Posted: 1/4/2010
Author(s): Brueck M, Bandorski D, Kramer W, Wieczorek M, Hцltgen R, Tillmanns H.
Citation: JACC Cardiovasc Interv 2009;2:1047-1054.
Clinical Trial: No
Study Question: What is the relative safety and feasibility of the transradial versus transfemoral approach for coronary angiography and intervention?
Methods: The authors randomized a total of 1,024 patients undergoing coronary catheterization to the transradial or transfemoral approach. Patients with an abnormal Allen's test, history of coronary artery bypass surgery, simultaneous right heart catheterization, chronic renal insufficiency, or known difficulties with the radial or femoral access were excluded.
Results: Successful catheterization was more common in the femoral (99.8% vs. 96.5%) compared with the radial group. Procedure time (median procedural duration 37.0 minutes vs. 40.2 minutes, p = 0.046) and radiation exposure (median dose area product 38.2 Gycm2 vs. 41.9 Gycm2, p = 0.034) were significantly lower in the transfemoral group compared with the transradial access group. There was no difference in the amount of contrast media use between the two groups. Vascular access site complications were higher in the transfemoral group (3.71% vs. 0.58%, p = 0.0008).
Conclusions: The use of radial access is associated with an increased procedural duration and radiation exposure, and a marked reduction in vascular complications.
Perspective: The reduction in groin complications and bleeding with the use of a radial approach has been highlighted in multiple studies. However, the increased radiation exposure to the patient and the operator is increasingly being recognized, and may translate into an increased late risk of malignancies. Better shielding strategies are needed to reduce this exposure so that the benefits of the radial approach can be obtained at minimal hazard to the patients or the operators. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Enoxaparin Versus Unfractionated Heparin in Elective Percutaneous Coronary Intervention: 1-Year Results From the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous Coronary Intervention Patients, An InternationaL randomized Evaluation) Trial
Topic: Interventional Cardiology
Date Posted: 1/5/2010
Author(s): Montalescot G, Gallo R, White HD, et al., on behalf of the STEEPLE Investigators.
Citation: JACC Cardiovasc Interv 2009;2:1083-1091.
Clinical Trial: yes
Study Question: What are the comparative long-term outcomes of patients who receive enoxaparin versus intravenous unfractionated heparin (UFH) for elective percutaneous coronary intervention (PCI)?
Methods: The authors reported the 1-year results of the STEEPLE trial. This trial randomized 3,528 patients undergoing elective PCI to receive either intravenous 0.50 mg/kg or 0.75 mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure for this analysis.
Results: One-year follow-up data were available for 2,636 patients. There was no difference in the risk of death from randomization to 1 year among patients treated with 0.50 mg/kg enoxaparin (2.3%), 0.75 mg/kg enoxaparin (2.2%), or UFH (1.9%). Independent predictors of 1-year mortality were nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio, 3.5; 95% CI, 1.7-7.3; p < 0.001), and major bleeding within 48 hours (hazard ratio, 3.0; 95% CI, 1.1-8.5; p = 0.04).
Conclusions: There was no difference in the long-term outcome of patients undergoing elective PCI who were treated with enoxaparin or UFH.
Perspective: This study provides two important messages. First, there is no difference in the 1-year outcome of patients undergoing PCI who are treated with UFH or enoxaparin, and either drug can be used based on physician and patient preference and cost. Second, both bleeding and ischemic events are associated with an increased risk of long-term mortality, and further efforts to improve outcome need to focus on a balanced reduction in ischemic and bleeding complications. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Role of the CHADS2 Score in the Evaluation of Thromboembolic Risk in Patients With Atrial Fibrillation Undergoing Transesophageal Echocardiography Before Pulmonary Vein Isolation
Topic: Noninvasive Cardiology
Date Posted: 1/5/2010
Author(s): Puwanant S, Varr BC, Shrestha K, et al.
Citation: J Am Coll Cardiol 2009;54:2032-2039.
Clinical Trial: No
Study Question: What is the role of the CHADS2 score in predicting left atrial (LA)/left atrial appendage (LAA) clot in patients scheduled for pulmonary vein isolation (PVI) for atrial fibrillation (AF)?
Methods: Transesophageal echocardiograms (TEEs) were performed prior to PVI in 1,058 AF patients and reviewed for presence of spontaneous echo contrast (SEC), sludge, or thrombus. A CHADS2 score was calculated for all patients who were subsequently followed for thromboembolic events after PVI.
Results: Patient age was 57 ± 11 years and 80% were male. CHADS2 scores of 0, 1, 2, 3, and ≥4 were present in 47%, 33%, 14%, 5%, and 1.3%. Paroxysmal AF was present in 81% and persistent or permanent AF in 9%. On TEE, SEC was noted in 374 (35%), sludge in 1.5%, and thrombus in 0.6%, with the remainder having no evidence of SEC, sludge, or thrombus. In the 498 patients with a CHADS2 score of 0, SEC was noted in 121 (24%) and sludge and thrombus was noted in none. For CHADS2 scores of 0, 1, 2, 3, and ≥4, SEC was noted in 24%, 33%, 59%, 74%, and 83%; sludge was noted in 0%, 2%, 4%, 9%, and 6%; thrombus in 0%, 1%, 2%, 0%, and 6% and a combination of sludge and thrombus in 0%, 2%, 5%, 9%, and 11%. LA emptying velocities (cm/s) for CHADS2 of 0 was 49 ± 20 and was 22 ± 15 in patients with CHADS2 score of 4-6. LAA sludge or thrombus was noted in eight patients with a CHADS2 score of 1, four of whom had left ventricular ejection fraction ≤35% and seven were in AF at the time of TEE. Sludge or thrombus was noted in 1% of patients with paroxysmal AF who were in normal sinus rhythm at the time of TEE compared to 2% and 5% for paroxysmal AF at the time of TEE or persistent AF. In the 3 months following PVI, 21 patients (1.8%) had an embolic event, only one of whom had LA/LAA thrombus/sludge at the time of TEE.
Conclusions: The prevalence of LA/LAA sludge and thrombus in patients undergoing AF ablation is low on screening TEE, but increases with increasingly higher CHADS2 score. The likelihood of thrombus/sludge in patients with CHADS2 score of 0 in sinus rhythm at the time of TEE who are adequately anticoagulated is negligible. TEE prior to PVI may be reserved for patients with CHADS2 score ≥1 or with persistent AF who are not adequately anticoagulated at the time of procedure.
Perspective: Over the past decade, LA ablative procedures for AF have dramatically increased in number. In many institutions, they consume substantial imaging resources, including a perceived need for routine preprocedure TEE to ensure absence of LA thrombus, which would be considered a contraindication to proceeding with the procedure. Most high-volume laboratories have anecdotally noted a remarkably low prevalence of thrombus in patients at clinically low risk of thrombus formation who are in sinus rhythm and adequately anticoagulated. This large study, from a highly experienced group, very nicely confirms that suspicion and hopefully may allow a more rational decision-making process with respect to preprocedure TEE. It should be emphasized that the patients reported here predominantly had paroxysmal AF and there are few enough patients with persistent AF that perhaps more caution would be advised in that setting. This study certainly suggests that patients with paroxysmal AF, in sinus rhythm at the time of evaluation, who have had adequate preprocedure anticoagulation have a negligible likelihood of pre-existing LA/LAA thrombus and that screening TEE is probably not needed. Screening should be reserved, even despite the overall low prevalence of LA thrombus, for those with a CHADS2 score ≥1 or persistent AF and/or inadequate preprocedure anticoagulation. Another critical finding was that the majority of post-procedural embolic events occurred in patients without pre-existing LA/LAA thrombus and are presumed to arise from thrombus developing either as a complication of the procedure or spontaneously in the LA/LAA as a result of less than ideal anticoagulation. An additional message of this study is obviously the need for scrupulous attention to adequate anticoagulation both pre- and post-procedure in these patients. William F. Armstrong, M.D., F.A.C.C.

Title: Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Topic: Prevention/Vascular
Date Posted: 12/29/2009
Author(s): Werner C, Fьrster T, Widmann T, et al.
Citation: Circulation 2009;120:2438-2447.
Clinical Trial: No
Study Question: Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. What are the effects of exercising on vascular telomere biology and endothelial apoptosis in mice, and what are the effects of long-term endurance training on telomere biology in humans?
Methods: C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise telomerase activity was evaluated in the thoracic aorta and in circulating mononuclear cells and compared with sedentary controls. Telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed and compared to untrained individuals.
Results: Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls including increased vascular expression of telomere repeat-binding factor, and reduced expression of vascular apoptosis regulators. Mice preconditioned by running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed endothelial stress resistance after physical activity. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls.
Conclusions: Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.
Perspective: Regular exercise training and better fitness are associated with many positive effects including blood pressure control, insulin sensitivity, less abdominal fat, better lipid profile, reduction in systemic inflammatory markers, and improved stress response and reduction in depression and anxiety. This study provides evidence for one of many potential molecular explanations for decreasing cardiovascular and overall mortality in fit men and women. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Cholesterol-Lowering Interventions and Stroke: Insights From a Meta-Analysis of Randomized Controlled Trials
Topic: Prevention/Vascular
Date Posted: 1/11/2010 5:00:00 PM
Author(s): De Caterina R, Scarano M, Marfisi RM, et al.
Citation: J Am Coll Cardiol 2010;55:198-211.
Clinical Trial: No
Study Question: Statins reduce the incidence of stroke. Is it related to cholesterol lowering or explained by alternative mechanisms?
Methods: A meta-analysis was performed of randomized trials of cholesterol-lowering treatments in cardiovascular disease reporting on stroke, involving 266,973 patients investigated and a cumulative 946,582 person-years of exposure. A meta-regression analysis was conducted regarding the extent of stroke reduction as a function of changes in total cholesterol.
Results: The odds ratio (OR) for the incidence of stroke in actively treated groups versus controls was 0.88 (95% confidence interval [CI], 0.83-0.94; p < 0.001). No treatment affected fatal strokes. Whereas statins decreased the risk of total stroke significantly (OR, 0.85; 95% CI, 0.78-0.92; p < 0.001), the benefit of nonstatin interventions was smaller and not statistically significant (diet OR, 0.92; fibrates OR, 0.98; other treatments OR, 0.81). They found a significant relationship between percent reduction of total (and low-density lipoprotein) cholesterol and percent reduction of total strokes (p = 0.0017), with each 1% reduction of total cholesterol predicting a 0.8% relative risk reduction of stroke. There was no significant association between stroke reduction and changes of high-density lipoprotein cholesterol levels, and inconsistent associations with reduction of triglycerides.
Conclusions: Among cholesterol-lowering treatments, statins are the most effective at decreasing the risk of total stroke, but their benefit is proportional to the percent reduction of total cholesterol and low-density lipoprotein cholesterol. No lipid-lowering intervention was associated with a reduction of fatal stroke.
Perspective: Observational studies have suggested that the relationship between strokes and lipids and lipoproteins in patients with strokes varies from coronary heart disease. This meta-analysis reports that the relationship between cholesterol and stroke reduction with statins is linear (1% reduction in total cholesterol predicts a 0.8% relative risk reduction of a stroke), with no evidence for pleiotropic effects. This is supported in a low-risk population without high-risk lipids. In the JUPITER trial, in which patients had a median total cholesterol of 186 mg/dl and a C-reactive protein >2 mg/dl, rosuvastatin 20 mg was associated with a 48% relative risk reduction for strokes. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Treatment of Aspirin-Resistant Patients With Omega-3 Fatty Acids Versus Aspirin Dose Escalation
Topic: Prevention/Vascular
Date Posted: 1/4/2010 5:00:00 PM
Author(s): Lev EI, Solodky A, Harelet N, et al.
Citation: J Am Coll Cardiol 2010;55:114-121.
Clinical Trial: No
Study Question: What is the effect of addition of omega-3 fatty acids or increase in aspirin dose on response to low-dose aspirin among patients who are aspirin-resistant?
Methods: Patients (n = 485) with stable coronary artery disease (CAD), taking low-dose aspirin (75-162 mg) for at least 1 week were screened for aspirin response with the VerifyNow Aspirin assay (Accumetrics, San Diego, CA). Further testing was performed by platelet aggregation. Aspirin resistance was defined by ≥2 of 3 criteria: VerifyNow score ≥550, 0.5 mg/ml arachidonic acid (AA)-induced aggregation ≥20%, and 10-µmol/L adenosine diphosphate (ADP)-induced aggregation ≥70%. Thirty patients (6.2%) were found to be aspirin resistant and randomized to receive either low-dose aspirin + omega-3 fatty acids (4 capsules daily) or aspirin 325 mg daily. After 30 days of treatment, patients were re-tested.
Results: Both groups (n = 15 each) had similar clinical characteristics. After treatment, significant reductions in AA- and ADP-induced aggregation and the VerifyNow score were observed in both groups. Plasma levels of thromboxane B2 were also reduced in both groups (56.8% reduction in the omega-3 fatty acids group, and 39.6% decrease in the aspirin group). Twelve patients (80%) who received omega-3 fatty acids and 11 (73%) who received aspirin 325 mg were no longer aspirin resistant after treatment.
Conclusions: The authors concluded that treatment of aspirin-resistant patients by adding omega-3 fatty acids or increasing the aspirin dose seems to improve response to aspirin and effectively reduces platelet reactivity.
Perspective: This study suggests that either adding omega-3 fatty acids or increasing the aspirin dose can improve response to aspirin and reduce residual platelet reactivity in stable patients with CAD. Treatment with both regimens was associated with a reduction in aspirin-resistance rates. Furthermore, omega-3 fatty acid supplementation might have independent favorable effects in the secondary prevention of CAD and its complications. The investigators did not examine the clinical impact of their therapeutic interventions or whether routine monitoring of aspirin response has any impact on clinical outcomes. Further larger studies are required to assess hard clinical endpoints and evaluate whether the strategy tested in this pilot study has any clinical benefit in patients with cardiovascular disease found to be resistant to aspirin. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Community-Based Interventions to Promote Blood Pressure Control in a Developing Country: A Cluster Randomized Trial
Topic: Prevention/Vascular
Date Posted: 12/31/2009
Author(s): Jafar TH, Hatcher J, Poulter N, et al., on behalf of the Hypertension Research Group.
Citation: Ann Intern Med 2009;151:593-601.
Clinical Trial: yes
Study Question: How effective are community-based interventions to control blood pressure in a developing country?
Methods: The authors reported the results of the Control Of Blood Pressure And Risk Attenuation-1 (COBRA-1) trial, a cluster randomized, 2 x 2 factorial, controlled trial of family-based home health education (HHE) using lay health workers and hypertension management training for general practitioners (GPs), conducted in Karachi, Pakistan. Subjects were over age 40 with known hypertension living in 12 randomly selected communities, with three clusters randomly assigned to each of the following groups: HHE alone, GP alone, HHE and GP combined, or no intervention. Outcome was reduction in systolic blood pressure from baseline to 2-year follow-up.
Results: Among 1,341 subjects, systolic blood pressure decrease was significantly greater in the HHE plus GP group (10.8 mm Hg; 95% confidence interval [CI], 8.9-12.8 mm Hg) compared with GP alone, HHE alone, or no intervention groups (5.8 mm Hg; 95% CI 3.9-7.7 mm Hg in each; p < 0.001), after adjusting for age, sex, and baseline blood pressure. The interaction between the main effect of GP training and HHE on the primary outcome was significant (p = 0.004 by intention-to-treat analysis; p = 0.0445 per protocol analysis).
Conclusions: The authors concluded that family-based HHE delivered by trained lay health workers, coupled with educating GPs about hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. The authors opined that both strategies in combination may be feasible for upscaling within the existing health systems of Indo-Asian countries.
Perspective: The authors demonstrated the efficacy of combining MD training with lay health education in improving blood pressure in a developing country. In some situations, it may be that overcoming barriers or lack of information is as important as selecting the best pharmaceutical agent. In addition to blood pressure lowering, the authors demonstrated that improvements in smoking, physical activity, and medication adherence were also associated with the combined use of HHE and GP training. It is interesting to note that the use of only HHE or GP training alone offered no benefit over no intervention. This suggests that, without the reinforcement of home intervention, improved training of GPs offers little improvement in blood pressure control. Although this study was done in a developing country where the challenges are different, this finding may have important lessons for improving health care in developed countries. James B. Froehlich, M.D., F.A.C.C.

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Anthracycline-Induced Cardiomyopathy
Mortality Same for Low vs High Volume PCI
Mummies Have Atherosclerosis
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Prevalence and Trends in Obesity Among US Adults, 1999-2008
Topic: Prevention/Vascular
Date Posted: 1/13/2010 11:00:00 AM
Author(s): Flegal KM, Carroll MD, Ogden CL, Curtin LR.
Citation: JAMA 2010;Jan 13:[Epub ahead of print].
Clinical Trial: No
Study Question: Has there been a change in the trend for increasing prevalence of obesity and overweight from 1999 through 2008?
Methods: The results are based on the analysis of height and weight measurements from 5,555 adult men and women ages 20 years or older obtained in 2007-2008 as part of the National Health and Nutrition Examination Survey (NHANES). Data from NHANES obtained in 2007-2008 were compared with results obtained from 1999 through 2006. Overweight was defined as a body mass index (BMI) of 25.0-29.9 kg/m2 and obesity was defined as a BMI of 30.0 kg/m2 or higher.
Results: In 2007-2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6-36.0%) overall, 32.2% among men, and 35.5% among women. The corresponding prevalence estimates for overweight and obesity combined were 68.0%, 72.3%, and 64.1%. Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007-2008 vs. 1999-2000, 1.12 [95% CI, 0.89-1.32]). For men, there was a significant linear trend (AOR for 2007-2008 vs. 1999-2000, 1.32 [95% CI, 1.12-1.58]); however, the three most recent data points did not differ significantly from each other.
Conclusions: The increase in the prevalence of obesity previously observed does not appear to be continuing at the same rate over the past 10 years, particularly for women and possibly for men.
Perspective: That the trend for increasing obesity appears to have stopped is not much of an accomplishment. Very few adults in the United States are unaware of the increased risk for cardiovascular disease, diabetes, and other disorders associated with obesity. The US population-based efforts to impact the prevalence of obesity from 1999-2008 by education have been impressive, but the results are disappointing. In 2007-2008, nearly 20% of men and women had a BMI >35 kg/m kg/m2, which underscores the need for novel and safe drugs for targeting weight loss. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Catheter Ablation of Stable Ventricular Tachycardia Before Defibrillator Implantation in Patients With Coronary Heart Disease (VTACH): A Multicentre Randomised Controlled Trial
Topic: Arrhythmias
Date Posted: 1/14/2010
Author(s): Kuck KH, Schaumann A, Eckardt L, et al., on behalf of the VTACH Study Group.
Citation: Lancet 2010;375:31-40.
Clinical Trial: yes
Study Question: What is the clinical value of prophylactic radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) before implantation of an implantable cardioverter/defibrillator (ICD)?
Methods: One hundred seven patients (mean age 66 years) with stable VT, prior myocardial infarction (MI), and an ejection fraction ≤50% (mean 34%) were randomly assigned to undergo RFCA plus ICD implantation (n = 52) or only ICD implantation (n = 55). Stored electrograms were analyzed to identify VT events during follow-up. Quality of life was measured at each clinic visit. The 1° endpoint was time to first episode of VT/ventricular fibrillation.
Results: Approximately 30% of patients in both groups received amiodarone during follow-up, and the mean follow-up duration was 22 months. The first episode of VT occurred at a median follow-up of 18.6 months in the ablation group, compared to only 5.9 months in the control group. Cardiac hospitalizations were significantly reduced in the ablation group compared to the control group (67% vs. 45%, respectively, at 24 months), but there were no significant differences in mortality or quality of life. The mean number of appropriate ICD shocks per patient per year was 0.6 in the ablation group and a significantly higher 3.4 in the control group.
Conclusions: RFCA of VT significantly reduces the incidence of VT during follow-up in post-MI patients treated with an ICD.
Perspective: In the OPTIC trial, amiodarone reduced ICD shocks by 73%. Instead of prophylactic RFCA of VT in all patients at the time of ICD implantation, one could make the case for treatment with amiodarone, with RFCA being reserved for patients who do not tolerate or who fail therapy with amiodarone. Fred Morady, M.D., F.A.C.C.

Title: Diabetic and Nondiabetic Patients With Left Main and/or 3-Vessel Coronary Artery Disease: Comparison of Outcomes With Cardiac Surgery and Paclitaxel-Eluting Stents
Topic: Cardiovascular Surgery
Date Posted: 1/15/2010
Author(s): Banning AP, Westaby S, Morice MC, et al.
Citation: J Am Coll Cardiol 2010;Jan 13:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the impact of diabetes on outcome of patients with complex three-vessel or left main coronary artery disease who are treated with coronary artery bypass grafting (CABG) or paclitaxel-eluting stents (PES)?
Methods: The authors reported the outcome of diabetic patients enrolled in the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) study. This study randomized 1,800 patients (452 with diabetes) to receive PES or CABG.
Results: Major adverse cardiac and cerebrovascular event rate at 1 year was higher among diabetic patients treated with PES compared with CABG (15.1 % vs. 11.8% ). There was no difference in the death/stroke/myocardial infarction rate with either revascularization strategy for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). Diabetic patients were at an increased risk of death after both CABG and PES. Mortality was higher after PES use (4.1% vs. 13.5%, p = 0.04) for diabetic patients with highly complex lesions (defined as a SYNTAX score ≥33). Compared with CABG, treatment with PES resulted in higher repeat revascularization for both nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001).
Conclusions: Diabetes is associated with worse outcome among patients undergoing PES-based revascularization for complex coronary artery disease.
Perspective: Diabetes is associated with a greater prevalence of coronary artery disease and diabetic patients have a worse outcome after coronary revascularization compared with nondiabetics. The pre-eminence of CABG over PCI for revascularization of diabetics in the angioplasty and bare-metal stent era was based on higher rates of target vessel revascularization with PCI. The results of this and other studies (i.e., CARDia) suggest that drug-eluting stents have not been able to completely bridge this gap, and CABG remains the revascularization strategy for diabetic patients with multivessel coronary artery disease. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Strength of Study Evidence Examined by the FDA in Premarket Approval of Cardiovascular Devices
Topic: General Cardiology
Date Posted: 1/15/2010
Author(s): Dhruva SS, Bero LA, Redberg RF.
Citation: JAMA 2009;302:2679-2685.
Clinical Trial: No
Study Question: What is the type and strength of evidence on which premarket approval (PMA)—the most stringent Food and Drug Administration (FDA) review process is based?
Methods: This was a systematic review of 123 summaries of safety and effectiveness data for 78 PMAs for high-risk cardiovascular devices that received PMA between January 2000 and December 2007. Examination of the methodological characteristics considered essential to minimize confounding and bias, as well as the primary endpoints of the 123 studies supporting the PMAs, was performed.
Results: Thirty-three of 123 studies (27%) used to support recent FDA approval of cardiovascular devices were randomized and 17 of 123 (14%) were blinded. Fifty-one of 78 PMAs (65%) were based on a single study. One hundred eleven of 213 primary endpoints (52%) were compared with controls and 34 of 111 controls (31%) were retrospective. One hundred eighty-seven of 213 primary endpoints (88%) were surrogate measures and 122 of 157 (78%) had a discrepancy between the number of patients enrolled in the study and the number analyzed.
Conclusions: The authors concluded that PMA of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias.
Perspective: This analysis suggests that the evidence presented for FDA-approved cardiovascular device PMAs came mostly from studies that were not blinded or randomized. The FDA approval process is an important determinant of health care spending, and spending on new devices increases when the FDA approves devices more quickly. Cost containment would likely occur if rigorous clinical effectiveness reviews were used for new drugs and technologies, and spending concentrated on devices shown to benefit patients definitively. This study further suggests that the FDA device approval process would benefit from rigorous research, using meaningful clinical outcomes and valid, active (not historical) controls in randomized, blinded studies (when possible) conducted in populations that reflect the US population. The emphasis of FDA in the future should be research that meets rigorous scientific standards for evidence of benefit and lack of harm to patients. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Familial Dilated Cardiomyopathy Caused by an Alpha-Tropomyosin Mutation: The Distinctive Natural History of Sarcomeric Dilated Cardiomyopathy
Topic: Heart Failure/Transplant
Date Posted: 1/18/2010 5:00:00 PM
Author(s): Lakdawala NK, Dellefave L, Redwood CS, et al.
Citation: J Am Coll Cardiol 2009;55:320-329.
Clinical Trial: No
Study Question: Are there sarcomere gene mutations responsible for dilated cardiomyopathy (DCM)?
Methods: Direct sequencing of six sarcomere genes was performed on 334 probands with DCM. A novel D230N missense mutation in the gene encoding alpha-tropomyosin (TPM1) was identified. Functional assessment was performed by the use of an in vitro reconstituted sarcomere complex to evaluate ATPase regulation and Ca2+ affinity as correlates of contractility.
Results: TPM1 D230N segregated with DCM in two large unrelated families. This mutation altered a conserved residue and was absent in >1,000 control chromosomes. In vitro studies demonstrated major inhibitory effects on sarcomere function with reduced Ca2+ sensitivity, maximum activation, and Ca2+ affinity compared with wild-type TPM1. Clinical manifestations ranged from decompensated heart failure or sudden death in those presenting early in life to asymptomatic left ventricular dysfunction in those diagnosed during adulthood.
Conclusions: Genetic segregation in two unrelated families and functional analyses demonstrate a pathogenic role for TPM1 mutations in DCM. In vitro results demonstrate contrasting effects of DCM and HCM mutations inTPM1, suggesting that specific functional consequences shape cardiac remodeling. Along with previous reports, data support a distinctive, age-dependent phenotype with sarcomere-associated DCM where presentation early in life is associated with severe, sometimes lethal disease.
Perspective: About one third of subjects with DCM have evidence of familial inheritance, most of whom show autosomal dominant transmission. Mutations in many genes have been linked to DCM, many of which are thought to affect myocyte force generation or energy production. While mutations in alpha-tropomysin are known to cause HCM, their role in DCM has been less conclusive. By showing segregation of TPM1 in two unrelated families, along with an in vitro phenotype, the current study provides very strong evidence for a causal role of TPM function in DCM. Interestingly, three of five infants with TPM1 showed marked recovery of left ventricular function. Additional studies aimed at determining mechanisms responsible for phenotypic heterogeneity and recovery potential of mutation carriers may lead to novel DCM screening and treatment strategies. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Cardio-Renal Syndromes: Report From the Consensus Conference of the Acute Dialysis Quality Initiative
Topic: Heart Failure/Transplant
Date Posted: 1/18/2010
Author(s): Ronco C, McCullough P, Anker SD, et al.
Citation: Eur Heart J 2009;Dec 25:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember about cardio-renal syndromes.

1. The Consensus Conference on Cardio-Renal Syndromes identified five subtypes that have different pathophysiology (refer to Figures 1-5 in J Am Coll Cardiol 2008;52:1527-39), prevention, and management strategies (refer to Table 1 in this article).

2. Type 1 or acute cardio-renal syndrome: acute worsening of heart function leading to kidney injury and/or dysfunction. About 27-40% of the patients with acute decompensated heart failure appear to develop acute kidney injury.

3 Type 2 or chronic cardio-renal syndrome: chronic abnormalities in heart function leading to kidney injury or dysfunction. This has been reported in 63% of patients hospitalized with congestive heart failure.

4. Type 3 or acute reno-cardiac syndrome: acute worsening of kidney function leading to heart injury and/or dysfunction. The effects on heart function are due to factors in addition to volume overload.

5. Type 4 or chronic reno-cardiac syndrome: chronic kidney disease leading to heart injury, disease, and/or dysfunction.

6. Type 5 or secondary cardio-renal syndrome: systemic conditions leading to injury and/or dysfunction of both heart and kidney (e.g., diabetes mellitus, sepsis, systemic lupus erythematosus, amyloidosis).

7. B-type natriuretic peptide (BNP) and NT-BNP may be elevated in cardio-renal syndrome types 1, 2, and 4.

8. Neutrophil gelatinase-associated lipocalin (NGAL) of urine and plasma and cystatin C are two biomarkers of renal injury that are most likely to be integrated in clinical practice and help with management of cardio-renal syndrome.

9. Bioimpedance vector analysis may contribute to better definition of the patient’s hydration status.

10. The presence of coronary artery disease should be excluded by stress echo or stress myocardial perfusion in types III, IV, and V and in types I and II cardio-renal syndrome when the primary disease is valvular, congenital, or myopathic to avoid contrast-induced renal damage. Ragavendra R. Baliga, M.B.B.S.

Title: Culprit Vessel Percutaneous Coronary Intervention Versus Multivessel and Staged Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Patients With Multivessel Disease
Topic: Interventional Cardiology
Date Posted: 1/18/2010 5:00:00 PM
Author(s): Hannan EL, Samadashvili Z, Walford G, et al.
Citation: JACC Cardiovasc Interv 2010;3:22-31.
Clinical Trial: No
Study Question: What is the best time to intervene on nonculprit vessels in patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease and undergo primary percutaneous coronary intervention (PCI)?
Methods: The authors assessed the outcome of STEMI patients with multivessel disease who underwent primary PCIs in New York between January 1, 2003, and June 30, 2006. Patients were categorized into those who underwent culprit vessel PCI only, those who underwent multivessel PCI during the index procedure, those undergoing nonculprit vessel PCI during the index admission, or those undergoing staged PCI to the nonculprit vessel within 60 days of the index admission. Propensity-matching was used to compare outcome within these subcategories.
Results: The study cohort was comprised of 4,024 patients of whom 3,521 patients (87.5%) underwent culprit vessel PCI only during the index procedure. Staged PCI during the index admission was performed in 259 patients, and 538 patients underwent staged PCI within 60 days of the index procedure. Among patients without hemodynamic compromise, those undergoing culprit vessel PCI during the index procedure had a lower in-hospital mortality than those undergoing multivessel PCI during the index procedure (0.9% vs. 2.4%, p = 0.04). There was no difference in long-term survival. There was no difference in outcome of those patients who underwent culprit vessel PCI only and those who underwent PCI to nonculprit vessel during the same hospitalization. Patients undergoing staged multivessel PCI within 60 days after the index procedure had a lower 12-month mortality rate than patients undergoing culprit vessel PCI only (1.3% vs. 3.3%, p = 0.04).
Conclusions: A strategy of culprit vessel PCI only at the time of STEMI is associated with the best outcome in patients with multivessel disease.
Perspective: Current American College of Cardiology/American Heart Association guidelines recommend culprit vessel PCI only in patients undergoing primary PCI (unless there is hemodynamic compromise). This study corroborates these findings, although the observational nature of the study and the fact that an overwhelming majority of patients were treated with culprit vessel PCI only, makes firm conclusions difficult. Since there are no data to the contrary, culprit vessel PCI only should remain the preferred revascularization strategy, and if there is an indication for PCI of a nonculprit vessel, such a procedure should be performed in a staged fashion. The optimal timing of such a staged procedure, however, remains unclear. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Diagnostic Accuracy of 320-Row Multidetector Computed Tomography Coronary Angiography in the Non-invasive Evaluation of Significant Coronary Artery Disease
Topic: Noninvasive Cardiology
Date Posted: 1/14/2010
Author(s): de Graaf FR, Schuijf JD, van Velzen J, et al.
Citation: Eur Heart J 2010;Jan 4:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the accuracy and feasibility of detecting obstructive coronary artery disease (CAD) with 320-row computed tomographic coronary angiography (CTA)?
Methods: CTA, using a new 320-row multidetector system and standard coronary arteriography, was performed in 64 patients with known or suspected CAD. CTA was analyzed on a per-segment, per-vessel, and per-patient basis. Usual selection criteria for CTA, including avoidance of atrial fibrillation, renal failure, and more, were employed. Beta-blockers were used when necessary to maintain heart rate <65 bpm. The 320-row CTA encompasses a 16 cm field of view, allowing imaging of the entire cardiac anatomy within a single heart beat.
Results: On a per-segment basis, 12 of 839 segments were deemed nondiagnostic. By standard coronary arteriography, 71 lesions ≥50% diameter stenosis were noted, 62 of which were detected with CTA. On a per-segment basis, the sensitivity, specificity, and positive and negative predictive values for detecting ≥50% coronary stenosis were 87%, 97%, 75%, and 99%. Data were nondiagnostic in 2 of 177 vessels containing 48 stenoses. Sensitivity, specificity, and positive and negative predictive values were 94%, 92%, 83%, and 97%. Data were analyzable in 60 of 64 patients resulting in sensitivity, specificity, and positive and negative predictive values of 100%, 88%, 92%, and 100%, respectively on a per-patient basis. On a per-segment basis, sensitivity, specificity, and positive and negative predictive values for detecting stenoses ≥70% were 96%, 99%, 74%, and 99.9%.
Conclusions: The study shows that 320-row CTA allows an accurate identification of obstructive CAD when compared to standard coronary arteriography.
Perspective: The 320-row multidetector scanner described here represents the latest generation of multidetector CTA. Multiple studies using the currently and commonly utilized 64-slice scanners have demonstrated excellent accuracy for detecting and excluding obstructive CAD in proximal coronary arteries, and CTA has been proposed as both a screening and prognostic tool in patients with known or suspected coronary disease. The potential advantages of a 320-row scanner are that it is capable of encompassing the entire length of the left ventricle in one heartbeat, thus reducing the likelihood of motion artifact. It also results in a reduced radiation and contrast dosage and less of a need for prolonged breath-holding. It is still dependent on a relative bradycardia, and an unstable rhythm such as atrial fibrillation or frequent premature ventricular contractions may interfere with gating. This relatively small study suggests that its overall accuracy with respect to sensitivity, specificity, and positive and negative predictive values are equivalent to that seen with the more well-established 64-slice scanner. When combined with what may be a more rapid throughput with less radiation and the ability to scan the entire heart in a single heartbeat, it may provide significant clinical and practical advantages in the future. William F. Armstrong, M.D., F.A.C.C.

Title: The Association Between Plaque Characterization by CT Angiography and Post-Procedural Myocardial Infarction in Patients With Elective Stent Implantation
Topic: Noninvasive Cardiology
Date Posted: 1/12/2010
Author(s): Uetani T, Amano T, Kunimura A, et al.
Citation: JACC Cardiovasc Imaging 2009;3:19-28.
Clinical Trial: No
Study Question: What is the association between volumetric characterization of target lesions by multidetector computed tomography (MDCT) angiography and the risk of postprocedural myocardial injury after elective stent implantation?
Methods: A total of 189 consecutive patients were enrolled; they underwent elective stent implantation after volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50 HU); 2) moderate-attenuation plaque (MAP) (50-150 HU); 3) lumen (151-500 HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque component in the target lesion was calculated using Color Code Plaque. Post-procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 hours after percutaneous coronary intervention were also evaluated.
Results: The volumes of LAP (87.9 ± 94.8 mm3 vs. 47.4 ± 43.7 mm3, p < 0.01) and MAP (111.6 ± 77.5 mm3 vs. 89.8 ± 67.1 mm3, p < 0.05) were larger in patients with post-procedural myocardial injury (defined as positive TnT) than in those with negative TnT. The volumes of LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume) correlated with biomarkers; the MAP fraction was inversely correlated with biomarkers. The volume of LAP was an independent predictor of positive TnT after adjusting for patient background, conventional intravascular ultrasound parameters, and procedural factors.
Conclusions: The authors concluded that post-procedural myocardial injury was associated with the volume and fraction of LAP, as detected by MDCT.
Perspective: This pilot study suggests a significant correlation between LAP volume within target lesions, as measured by MDCT, and post-procedural elevation of cardiac biomarker levels. The LAP volume was found to be an independent predictor of myocardial injury after elective stenting. Plaque evaluation by MDCT may, therefore, provide useful information to identify high-risk patients who are expected to have a better outcome with aggressive medical treatment or bypass surgery. However, evaluation of coronary plaque by MDCT involves significant exposure to radiation as well as use of iodinated contrast medium. Further evaluations with larger multicenter studies are indicated to validate the findings of this study and assess potential clinical utility/benefits. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Prevalence and Trends in Obesity Among US Adults, 1999-2008
Topic: Prevention/Vascular
Date Posted: 1/13/2010 11:00:00 AM
Author(s): Flegal KM, Carroll MD, Ogden CL, Curtin LR.
Citation: JAMA 2010;Jan 13:[Epub ahead of print].
Clinical Trial: No
Study Question: Has there been a change in the trend for increasing prevalence of obesity and overweight from 1999 through 2008?
Methods: The results are based on the analysis of height and weight measurements from 5,555 adult men and women ages 20 years or older obtained in 2007-2008 as part of the National Health and Nutrition Examination Survey (NHANES). Data from NHANES obtained in 2007-2008 were compared with results obtained from 1999 through 2006. Overweight was defined as a body mass index (BMI) of 25.0-29.9 kg/m2 and obesity was defined as a BMI of 30.0 kg/m2 or higher.
Results: In 2007-2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6-36.0%) overall, 32.2% among men, and 35.5% among women. The corresponding prevalence estimates for overweight and obesity combined were 68.0%, 72.3%, and 64.1%. Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007-2008 vs. 1999-2000, 1.12 [95% CI, 0.89-1.32]). For men, there was a significant linear trend (AOR for 2007-2008 vs. 1999-2000, 1.32 [95% CI, 1.12-1.58]); however, the three most recent data points did not differ significantly from each other.
Conclusions: The increase in the prevalence of obesity previously observed does not appear to be continuing at the same rate over the past 10 years, particularly for women and possibly for men.
Perspective: That the trend for increasing obesity appears to have stopped is not much of an accomplishment. Very few adults in the United States are unaware of the increased risk for cardiovascular disease, diabetes, and other disorders associated with obesity. The US population-based efforts to impact the prevalence of obesity from 1999-2008 by education have been impressive, but the results are disappointing. In 2007-2008, nearly 20% of men and women had a BMI >35 kg/m kg/m2, which underscores the need for novel and safe drugs for targeting weight loss. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Does Erectile Dysfunction Contribute to Cardiovascular Disease Risk Prediction Beyond the Framingham Risk Score?
Topic: Prevention/Vascular
Date Posted: 1/18/2010 5:00:00 PM
Author(s): Araujo AB, Hall SA, Ganz P, et al.
Citation: J Am Coll Cardiol 2009;55:350-356.
Clinical Trial: No
Study Question: Is erectile dysfunction (ED) predictive of cardiovascular disease (CVD) beyond traditional risk factors?
Methods: The Massachusetts Male Aging Study (MMAS) trial is a prospective, observational cohort study of aging, health, and endocrine and sexual function in a population-based random sample of men between ages 40 and 70 years. This study was conducted in 1,709 men (of 3,258 eligible men). The ED data were measured by self-report. Data on CVD were obtained from self-reports, the National Death Index, and medical records. CVD endpoints included myocardial infarction, atherosclerosis, stroke, coronary artery bypass graft surgery, and congestive heart failure. Subjects were followed for CVD for an average follow-up of 11.7 years. The association between ED and CVD was examined using the Cox proportional hazards regression model. The discriminatory capability of ED was examined using C statistics. The reclassification of CVD risk associated with ED was assessed using a method that quantifies net reclassification improvement.
Results: Of the prospective population, 1,057 men with complete risk factor data who were free of CVD and diabetes at baseline were included. Men with ED were older (mean 59 years vs. 54 years), had a higher prevalence of hypertension and smoking, slightly higher body mass index, lower total and high-density lipoprotein cholesterol, and higher Framingham risk score. Overall, 37% of men with ED were in the highest risk category for Framingham risk score, compared with 17% of men without ED. During follow-up, 261 (25%) new cases of CVD occurred, of which 61 were obtained by self-report only. Of the CVD events, 71 (27.2%) were fatal. Men without ED at baseline (n = 879) were followed for an average of 12.0 years and men with ED (n = 178) for 10.3 years. ED was associated with CVD incidence controlling for age (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.05-1.90), age and traditional CVD risk factors (HR, 1.41; 95% CI, 1.05-1.90), as well as age and Framingham risk score (HR, 1.40; 95% CI, 1.04-1.88). Despite these significant findings, ED did not significantly improve the prediction of CVD incidence beyond traditional risk factors. The data did not differ assuming none of those without verifiable CVD had an event.
Conclusions: Independent of established CVD risk factors, ED is significantly associated with increased CVD incidence. Nonetheless, ED does not improve the prediction of who will and will not develop CVD beyond that offered by traditional risk factors.
Perspective: The results are in conflict with most other observational studies. Considering the high socioeconomic status of a significant percent of participants, and the long-term follow-up, I suspect treatment of risk factors with statins and other drugs may have influenced the outcome. For clinical purposes, despite this report, I would still consider ED a marker of CV risk in low-risk middle-aged and older men. Melvyn Rubenfire, M.D., F.A.C.C.

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Cancer Risks From CT Scans
Dabigatran not Inferior to Warfarin
Cholesterol-Lowering Interventions and Stroke
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Use of Evidence-Based Therapies in Short-Term Outcomes of ST-Segment Elevation Myocardial Infarction and Non–ST-Segment Elevation Myocardial Infarction in Patients With Chronic Kidney Disease. A Report From the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network Registry
Topic: General Cardiology
Date Posted: 1/19/2010
Author(s): Fox CS, Muntner P, Chen AY, et al.
Citation: Circulation 2010;121:357-365.
Clinical Trial: No
Study Question: What is the association between chronic kidney disease (CKD) severity and short-term outcomes and the use of in-hospital evidence-based therapies among patients with ST-segment elevation myocardial infarction (STEMI) and non–STEMI (NSTEMI)?
Methods: The study sample was drawn from the Acute Coronary Treatment and Intervention Outcomes Network registry, a nationwide sample of STEMI (n = 19,029) and NSTEMI (n = 30,462) patients. Estimated glomerular filtration rate was calculated with the Modification of Diet in Renal Disease equation in relation to use of immediate (first 24 hours) therapies and early (first 48 hours) cardiac catheterization as well as in-hospital major bleeding events and death.
Results: Overall, 30.5% and 42.9% of patients with STEMI and NSTEMI, respectively, had CKD. Regardless of MI type, patients with progressively more severe CKD had higher rates of death. For STEMI, the odds ratio for stage 3a, 3b, 4, and 5 CKD compared with patients with no CKD was 2.49, 3.72, 4.82, and 7.97, respectively (Ptrend < 0.0001). For NSTEMI, the analogous odds ratios were 1.81, 2.41, 3.50, and 4.09 (P for trend < 0.0001). In addition, patients with progressively more severe CKD were less likely to receive immediate evidence-based therapies including aspirin, beta-blockers, or clopidogrel, were less likely to undergo any reperfusion (STEMI) or revascularization (NSTEMI), and had higher rates of bleeding.
Conclusions: The authors concluded that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates.
Perspective: Several studies over the past decade have highlighted the importance and undertreatment of CKD among patients with MI. Data from this contemporary cohort suggest that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates. Clinicians should be aware of the high likelihood of concomitant CKD and cardiovascular disease in patients presenting with MI to allow for appropriate treatment decisions and to adjust medication dosing. The underutilization of evidence-based therapies and procedures in the CKD population is an important health care quality issue and an opportunity to develop appropriate quality improvement initiatives to optimize care in these high-risk patients. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Second-Generation Everolimus-Eluting and Paclitaxel-Eluting Stents in Real-Life Practice (COMPARE)
Trial Sponsor: Abbott Vascular and Boston Scientific
Year Presented: 2009
Year Published 2010
Topic(s): Interventional Cardiology
Summary Posted: 1/18/2010
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Description
The current trial sought to compare outcomes between the everolimus-eluting stent (EES) (Xience V) and paclitaxel-eluting stent (PES) (Taxus Liberte) in a real-world situation.
Hypothesis
EES would be superior to PES in the treatment of coronary artery disease in unselected patients.
Drugs/Procedures Used
Patients meeting enrollment criteria were randomized to receive either EES or PES in a 1:1 fashion.
Concomitant Medications
Glycoprotein IIb/IIIa inhibitors (32%); aspirin 300 mg once, then 100 mg daily for life; clopidogrel 300 or 600 mg once, then 75 mg daily for 12 months.
Principal Findings
A total of 1,800 patients were randomized, 903 to PES and 897 to EES. Baseline characteristics were fairly similar between the two arms. About 25% of patients presented with acute myocardial infarction (MI), and 23% with non-ST-elevation MI. Multivessel disease was noted in 27% of the patients, and 18% were diabetic. Left main stenting was conducted in 2% of the patients. The mean stent length per lesion was 28 mm, and the mean number of lesions was 1.65 per patient.

The primary endpoint of major adverse cardiac events (MACE) at 1 year (all-cause mortality, nonfatal MI, and target vessel revascularization [TVR]) was significantly lower in the EES arm compared with PES (6.2% vs. 9.1%, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.95, p = 0.023). Similarly, the incidence of death, MI, and target lesion revascularization (TLR) at 1 year was significantly lower in the EES arm compared with PES (4.9% vs. 8.2%, HR 0.60, 95% CI 0.42-0.86, p = 0.005).

In addition, the incidence of nonfatal MI (2.8% vs. 5.4%, p = 0.007) and TVR (2.4% vs. 6.0%, p = 0.0001) was significantly lower in the EES arm. The incidence of stent thrombosis at 1 year was also significantly lower in the EES arm (0.7% vs. 2.6%, HR 0.26, 95% CI 0.11-0.64, p = 0.002). This was mainly due to a reduction in early stent thrombosis (p = 0.002), rather than late stent thrombosis (p = 0.25).
Interpretation
The results of this trial indicate that EES is superior to PES (Taxus Liberte) in the reduction in clinical endpoints including MACE, nonfatal MI, and stent thrombosis at 1 year, when utilized in a real-world situation. These results are similar to those of the recently presented SPIRIT IV trial. Earlier studies had demonstrated a greater reduction in late lumen loss with EES. The current trial demonstrates that low late lumen loss can be achieved with EES without a concomitant increase in stent thrombosis, as compared with PES.
Conditions
• Coronary heart disease
Therapies
• Stent/drug-eluting
Study Design
Randomized. Blinded. Parallel.
Patients Enrolled: 1,800
Mean Follow-Up: 1 year
% Female: 30

Primary Endpoints
All-cause mortality, nonfatal MI, and TVR at 1 year
Secondary Endpoints
Cardiac death, nonfatal MI, and ischemia-driven TLR at 1 year
All-cause mortality, nonfatal MI, and TVR at 3 and 5 years
Incidence of stent thrombosis at 1, 3, and 5 years
Patient Population
Patient is suitable candidate for PCI
Life expectancy >5 years
Exclusions:
No dual antiplatelet therapy for 1 year
Cardiogenic shock at presentation
Planned major surgery within 1 month
Participation in another trial
References: Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet 2010;375:201-9.

Presented by Dr. Pieter Smits at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2009), San Francisco, CA, September 23, 2009.

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Title: Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease (Efficacy and Safety of Varenicline)
Trial Sponsor: Pfizer
Year Published 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 1/14/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Description
The goal of the trial was to evaluate smoking cessation treatment with varenicline (Chantix), a partial α4β2 nicotinic acetylcholine receptor agonist, compared with placebo among patients with stable coronary disease.
Hypothesis
Varenicline would be more effective in smoking cessation.
Drugs/Procedures Used
In addition to smoking-cessation counseling, patients with stable coronary disease were randomized to varenicline 1 mg twice daily (n = 355) versus placebo (n = 359) for 12 weeks.
Principal Findings
Overall, 714 patients were randomized. There was no difference in baseline characteristics between the groups. In the varenicline group, the mean age was 57 years, 25% were women, body mass index was 27.5 kg/m2, mean duration of smoking was 40 years, mean number of cigarettes per day was 22.1, and the proportion of patients with previous serious attempts to quit smoking was 85.6%. Prior myocardial infarction was present in 45.9%, prior coronary revascularization in 46.2%, prior stroke in 4.5%, and peripheral arterial disease in 23.1%.

The continuous abstinence rate at 9-12 weeks was 47.0% for varenicline versus 13.9% for placebo (p < 0.0001). Abstinence diminished over time, although it was still better with varenicline. At 9-24 weeks, abstinence was 28.2% versus 9.5% (p < 0.001) and at 9-52 weeks, abstinence was 19.2% versus 7.2% (p < 0.001), respectively, for varenicline versus placebo.

All-cause mortality was 0.6% versus 1.4%, cardiovascular mortality was 0.3% versus 0.6%, and any cardiovascular event was 7.1% versus 5.7% (p = NS for all comparisons), respectively, for varenicline versus placebo. Study medication was stopped for an adverse event in 9.6% of the varenicline group versus 4.3% of the placebo group (p < 0.05). The most frequently reported adverse events were nausea (29.5% vs. 8.6%), vomiting (8.2% vs. 1.1%), insomnia (11.9% vs. 6.6%), abnormal dreams (7.9% vs. 1.7%), and constipation (6.5% vs. 2.0%), respectively, for varenicline versus placebo.
Interpretation
Among patients with stable coronary artery disease, the use of varenicline was effective at improving rates of smoking cessation compared with placebo. This was most evident from 9-12 weeks; however, it was also seen at 24-52 weeks. Cardiovascular outcomes were similar between the groups, although varenicline was associated with more gastrointestinal and sleep disturbances.

Varenicline has predominately been studied in otherwise healthy participants; therefore, the safety profile of this agent in individuals with documented coronary artery disease was unknown. Although not definitive, this trial documents that varenicline may be safe for use among individuals with stable coronary artery disease.
Conditions
• Coronary heart disease
• Prevention
Therapies
• Behavior Modification
Study Design
Randomized. Blinded. Parallel.
Patients Screened: 858
Patients Enrolled: 714
Mean Follow-Up: 52 weeks
Mean Patient Age: 57 years
% Female: 25

Primary Endpoints
Continuous abstinence rate for weeks 9-12
Patient Population
Patients 35-75 years of age who had smoked at least 10 cigarettes daily for the last year
Stable coronary artery disease diagnosed at least 2 months ago
Exclusions:
Cardiovascular procedure in the last 2 months
Any sign of cardiovascular instability
Uncontrolled hypertension
Significant cerebrovascular disease
Prior amputation from peripheral arterial disease
Severe congestive heart failure
Severe chronic obstructive pulmonary disease
Severe renal, hepatic, endocrine, or gastrointestinal disease
Cancer
Depression or treatment with antidepressants in the last month
Psychosis, panic, or bipolar disorder
Drug or alcohol dependence
Concurrent smoking cessation medication use including nicotine replacement therapy, bupropion, clonidine, or nortriptyline
References: Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation 2010;121:221-9.

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Title: A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease
Topic: General Cardiology
Date Posted: 1/19/2010
Author(s): Omland T, de Lemos JA, Sabatine MS, et al., on behalf of the Prevention of Events With Angiotensin Converting Enzyme Inhibition (PEACE) Trial Investigators.
Citation: N Engl J Med 2009;361:2538-2547.
Clinical Trial: No
Study Question: What are the prognostic implications of elevated troponin T levels in stable coronary artery disease (CAD) patients?
Methods: A new highly sensitive troponin T assay was used in 3,679 patients with stable CAD and preserved left ventricular function. Patients were followed for an average of 5.2 years for cardiovascular (CV) events.
Results: Concentrations of cardiac troponin T were at or above detection limit (0.001 μg/L) in 97.7% of patients (n = 3,593) and at or above the 99th percentile for apparently healthy subjects (0.0133 μg/L) in 11.1% of patients (n = 407). After adjustment for other prognostic indicators, there was a strong and graded increase in the cumulative incidence of CV death (hazard ratio [HR] per unit increase in natural log of troponin T level, 2.09; 95% confidence interval [CI], 1.60-2.74; p < 0.001) and of heart failure (HR, 2.20; 95% CI, 1.66-2.90; p < 0.001). Increased risk with higher troponin T levels was evident well below the limit of detection of conventional cardiac troponin T assays and below the 99th percentile of values in a healthy population. There was no association between troponin T levels, as measured with this assay, and incidence of myocardial infarction (MI) (HR, 1.16; 95% CI, 0.97-1.40; p = 0.11).
Conclusions: The authors concluded that after adjustment for other prognostic indicators, cardiac troponin T levels, as measured with a highly sensitive assay, were significantly associated with incidence of CV death and congestive heart failure, but not with MI in patients with stable CAD.
Perspective: Troponins T and I have become the ‘gold standard’ for the diagnosis of myocardial necrosis. However, low level elevations of cardiac troponins have been shown to be elevated in a small percentage of stable patients without evidence of acute coronary syndromes. These minor elevations are associated with adverse cardiac outcomes indicating that circulating levels of these contractile proteins may provide useful information beyond that gleaned in the setting of acute MI. With development of a highly sensitive troponin T assay, the authors of the current study have demonstrated that low troponin T levels may be useful in predicting some adverse CV outcomes, independent of conventional risk factors. Several questions are raised including the cellular source and mechanism of low level troponin generation, which may provide guidance to the appropriate management of these patients. The clinical utility of this sensitive screening assay will require additional studies. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Perioperative Practice: Time to Throttle Back
Topic: General Cardiology
Date Posted: 1/25/2010
Author(s): Chopra V, Flanders SA, Froehlich JB, Lau WC, Eagle KA.
Citation: Ann Intern Med 2010;152:47-51.
Clinical Trial: No
Perspective: This perspective discusses how the current practice of perioperative risk assessment often conflicts with trial-based evidence; and advocates that, by heeding existing evidence and by implementing the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, perioperaive costs can be reduced while outcomes are improved. The following are points to remember.

1. Screening stable patients for coronary artery disease (CAD) before noncardiac surgery does not improve perioperative outcomes.
Data suggesting benefit came from retrospective studies conducted almost exclusively in patients undergoing vascular surgery (and therefore predominantly at high risk).
In those retrospective trials, patients who underwent revascularization may have done so for indications other than upcoming surgery, again implying an independent assessment of high risk.

2. The preoperative identification of significant CAD does not necessarily lead to the identification of patients at increased perioperative cardiac risk.
Preoperative testing, whether noninvasive or invasive, screens for obstructive coronary lesions.
Data from autopsy studies reveal that fatal perioperative myocardial infarction frequently originated with a nonstenotic coronary lesion.
Increased perioperative risk often is associated with an angiographically low-grade lesion vulnerable to plaque rupture.

3. Preoperative coronary revascularization does not lower perioperative cardiac risk.
Among patients with stable CAD, coronary revascularization has no advantage over medical therapy in the prevention of myocardial infarction or death.
Among patients undergoing vascular surgery, randomized, prospective data demonstrate no advantage associated with revascularization compared to good medical therapy.
One relatively small study even demonstrated no clinical benefit associated with preoperative coronary revascularization among patients with high-risk coronary anatomy undergoing high-risk surgery.

4. Failure of a strategy to reduce risk using preoperative coronary revascularization might fail for several reasons.
The existing ‘gold standard’ for detecting CAD using coronary angiography is flawed.
Coronary artery biology appears to matter more than anatomy in defining risk.
Preoperative coronary revascularization is, as with any interventional procedure, associated with inherent risk.

5. The routine use in all patients of perioperative beta-adrenergic antagonists does not reduce perioperative adverse events.
Bradycardia and hypotension associated with indiscriminate beta-blocker use presumably add to adverse perioperative outcomes.
One large study found that perioperative beta-blocker therapy was beneficial only in patients at intermediate or higher risk.

6. Data support a strategy of beta-blocker therapy, titrated to hemodynamic variables, in high-risk patients with ischemic heart disease who are undergoing high-risk surgery.
These recommendations are reflected in the 2009 ACC/AHA Focused Update on Perioperative Beta-Blockers.

7. The implementation of an evidence-based doctrine of selective beta-blocker therapy among high-risk patients with ischemic heart disease undergoing high-risk surgery, selective preoperative functional testing only to identify those high-risk patients, and preoperative coronary revascularization only in very selected cases, is not necessarily the current standard of practice.
Factors affecting this might include legal concerns, pressure from surgeons, and provider bias caused by testing- and procedure-related income.

8. At the authors’ institution, two educational initiatives supporting the ACC/AHA perioperative guideline recommendations resulted in lower costs associated with preoperative risk assessment, but preserved or improved perioperative patient outcomes. David S. Bach, M.D., F.A.C.C.

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Title: Systematic Review: Prediction of Perioperative Cardiac Complications and Mortality by the Revised Cardiac Risk Index
Topic: General Cardiology
Date Posted: 1/25/2010
Author(s): Ford MK, Beattie WS, Wijeysundera DN.
Citation: Ann Intern Med 2010;152:26-35.
Clinical Trial: No
Study Question: What is the ability of the Revised Cardiac Risk Index (RCRI) to predict cardiac complications and death after noncardiac surgery?
Methods: MEDLINE, EMBASE, and ISI Web of Science (1966 to December 31, 2008) were searched for cohort studies that reported the association of the RCRI with major cardiac complications (cardiac death, myocardial infarction, and nonfatal cardiac arrest) or death (in-hospital or within 30 days of surgery). Two reviewers independently extracted study characteristics, documented outcome data, and evaluated study quality.
Results: Of 24 studies (including 792,740 patients), 18 studies reported cardiac complications; 6 of the 18 studies were prospective and had uniform outcome surveillance and blinded outcome adjudication. The RCRI discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery (area under the receiver-operating characteristic curve [AUC] 0.75 [95% confidence interval [CI], 0.72-0.79]), sensitivity 0.65 [CI, 0.46-0.81], specificity 0.76 [CI 0.58-0.88], positive likelihood ratio 2.78 [CI, 1.74-4.45], negative likelihood ratio 0.45 [CI, 0.31-0.67]). Prediction of cardiac events after vascular noncardiac surgery was less accurate (AUC 0.64 [CI, 0.61-0.66], sensitivity 0.70 [CI, 0.53-0.82], specificity 0.55 [CI, 0.45-0.66], positive likelihood ratio 1.56 [CI, 1.42-1.73], negative likelihood ratio 0.55 [CI, 0.40-0.76]). Six studies reported death, with a median AUC of 0.62 (range, 0.54-0.78). A pooled AUC for predicting death could not be calculated because of very high heterogeneity.
Conclusions: The authors concluded that RCRI discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery. However, it did not perform well at predicting cardiac events after vascular noncardiac surgery, or at predicting death.
Perspective: Perioperative adverse cardiac events complicating noncardiac surgery are responsible for significant morbidity and mortality. The RCRI is a multivariable index that uses readily available clinical information in an attempt to predict perioperative risk. (The model uses equally weighted components of coronary artery disease, heart failure, cerebrovascular disease, insulin-requiring diabetes mellitus, renal insufficiency [creatinine >2 mg/dl], and high-risk [suprainguinal vascular, intrathoracic, or intraperitoneal] surgery.) In its original, defining, single-institutional cohort of almost 3,000 patients over age 50 years who were undergoing major, elective noncardiac surgery; the model was shown to have good discriminatory power. However, the present study shows that the same index was more limited when tested in different patient populations in varying geographic locations. It is common that a study concludes that there is predictive power of a multivariate model because it correlates with the desired outcome in the population in which it was derived. Importantly, retrospective correlation, even among prospectively collected data, does not prove that a model will be predictive in other populations. The present study is an important reality check proving just that. David S. Bach, M.D., F.A.C.C.

Title: Use of Evidence-Based Therapies in Short-Term Outcomes of ST-Segment Elevation Myocardial Infarction and Non–ST-Segment Elevation Myocardial Infarction in Patients With Chronic Kidney Disease. A Report From the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network Registry
Topic: General Cardiology
Date Posted: 1/19/2010
Author(s): Fox CS, Muntner P, Chen AY, et al.
Citation: Circulation 2010;121:357-365.
Clinical Trial: No
Study Question: What is the association between chronic kidney disease (CKD) severity and short-term outcomes and the use of in-hospital evidence-based therapies among patients with ST-segment elevation myocardial infarction (STEMI) and non–STEMI (NSTEMI)?
Methods: The study sample was drawn from the Acute Coronary Treatment and Intervention Outcomes Network registry, a nationwide sample of STEMI (n = 19,029) and NSTEMI (n = 30,462) patients. Estimated glomerular filtration rate was calculated with the Modification of Diet in Renal Disease equation in relation to use of immediate (first 24 hours) therapies and early (first 48 hours) cardiac catheterization as well as in-hospital major bleeding events and death.
Results: Overall, 30.5% and 42.9% of patients with STEMI and NSTEMI, respectively, had CKD. Regardless of MI type, patients with progressively more severe CKD had higher rates of death. For STEMI, the odds ratio for stage 3a, 3b, 4, and 5 CKD compared with patients with no CKD was 2.49, 3.72, 4.82, and 7.97, respectively (Ptrend < 0.0001). For NSTEMI, the analogous odds ratios were 1.81, 2.41, 3.50, and 4.09 (P for trend < 0.0001). In addition, patients with progressively more severe CKD were less likely to receive immediate evidence-based therapies including aspirin, beta-blockers, or clopidogrel, were less likely to undergo any reperfusion (STEMI) or revascularization (NSTEMI), and had higher rates of bleeding.
Conclusions: The authors concluded that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates.
Perspective: Several studies over the past decade have highlighted the importance and undertreatment of CKD among patients with MI. Data from this contemporary cohort suggest that patients with CKD still receive fewer evidence-based therapies and have substantially higher mortality rates. Clinicians should be aware of the high likelihood of concomitant CKD and cardiovascular disease in patients presenting with MI to allow for appropriate treatment decisions and to adjust medication dosing. The underutilization of evidence-based therapies and procedures in the CKD population is an important health care quality issue and an opportunity to develop appropriate quality improvement initiatives to optimize care in these high-risk patients. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Dynamic Cardiovascular Risk Assessment in Elderly People: The Role of Repeated N-Terminal Pro–B-Type Natriuretic Peptide Testing
Topic: Heart Failure/Transplant
Date Posted: 1/25/2010 5:00:00 PM
Author(s): deFilippi CR, Christenson RH, Gottdiener JS, Kop WJ, Seliger SL.
Citation: J Am Coll Cardiol 2010;55:441-450.
Clinical Trial: No
Study Question: Does serial measurement of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people provide additional prognostic information to that from traditional risk factors?
Methods: The study cohort was comprised of 2,975 community-dwelling older adults free of heart failure (HF) in the longitudinal Cardiovascular Health Study. NT-proBNP was measured at baseline and 2-3 years later in the cohort. The risk of new-onset HF and mortality from cardiovascular causes was associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders.
Results: The study investigators found that NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR], 3.05; 95% confidence interval [CI], 2.46-3.78) and cardiovascular mortality (HR, 3.02; 95% CI, 2.36-3.86) compared with the lowest quintile (<47.5 pg/ml). Another important finding was that the inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among subjects with initially low NT-proBNP (<190 pg/ml), those who developed a >25% increase on follow-up to >190 pg/ml (21%) were at greater adjusted risk of HF (HR, 2.13; 95% CI, 1.68-2.71) and cardiovascular mortality (HR, 1.91; 95% CI, 1.43-2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25% increase (40%) were at higher risk of HF (HR, 2.06; 95% CI, 1.56-2.72) and cardiovascular mortality (HR, 1.88; 95% CI, 1.37-2.57), whereas those who developed a <25% decrease to ≤190 pg/ml (15%) were at lower risk of HF (HR, 0.58; 95% CI, 0.36-0.93) and cardiovascular mortality (HR, 0.57; 95% CI, 0.32-1.01) compared with those with unchanged high values.
Conclusions: The authors concluded that NT-proBNP levels independently predict HF and cardiovascular mortality in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk.
Perspective: This is an important study because it suggests NT-proBNP is an important long-term predictor of HF in the elderly and possibly an indicator of ‘subclinical’ heart failure. Another important take-away is that a level of 190 pg/ml may possibly be a cut-off point in patients without a ‘dry’ BNP (i.e., BNP at euvolemia). Further studies are required to validate these results. From a mechanistic perspective, I would be interested to know whether NT-proBNP level fluctuations reflect changes in left ventricular function such as E/E’ on tissue Doppler and other indicators of left ventricular diastolic function. Also, more data are needed to determine whether a single marker or a panel of biomarkers is superior in accurately predicting cardiovascular risk (Braunwald E. Heart Fail Clin 2009;4:xiii-xiv). Ragavendra R. Baliga, M.B.B.S.

Title: Supported High-Risk Percutaneous Coronary Intervention With the Impella 2.5 Device: The Europella Registry
Topic: Interventional Cardiology
Date Posted: 1/22/2010
Author(s): Sjauw KD, Konorza T, Erbel R, et al.
Citation: J Am Coll Cardiol 2009;54:2430-2434.
Clinical Trial: No
Study Question: What is the safety and feasibility of left ventricular (LV) support with the Impella 2.5 device during high-risk percutaneous coronary intervention (PCI)?
Methods: The Europella registry was comprised of patients from 10 tertiary PCI centers across Europe. It was designed to evaluate the safety and feasibility of all patients undergoing elective high-risk PCI with prophylactic mechanical cardiac support with the Impella 2.5. The Impella 2.5 (Abiomed, Inc.) is a novel catheter-mounted (9-F) micro-axial rotary blood pump (12-F), designed for short-term circulatory support. The registry was supported by Abiomed Europe GmbH. Safety and feasibility endpoints included incidence of 30-day adverse events and successful device function.
Results: Patients were older (62% were >70 years of age), 54% had an LV ejection fraction ≤30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (standard deviation 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively.
Conclusions: The authors concluded that this registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.
Perspective: The present study shows that periprocedural support with the Impella 2.5 for elective high-risk PCI is safe and feasible and extends prior observations from three smaller case series. It should be noted that all adverse events were based on clinical diagnoses assigned by the patient's physician. Overall, this multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI, but needs to be evaluated in prospective randomized clinical trials. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: ST Elevation on the Exercise ECG in Patients Presenting With Chest Pain and No Prior History of Myocardial Infarction
Topic: Noninvasive Cardiology
Date Posted: 1/20/2010
Author(s): Murphy JC, Scott PJ, Shannon HJ, et al.
Citation: Heart 2009;95:1792-1797.
Clinical Trial: No
Study Question: What is the etiology of ST-segment elevation (STE) noted during exercise stress testing (EST) in patients with chest pain, but without a prior history of myocardial infarction (MI)?
Methods: Stress testing with ECG monitoring was undertaken in 19,189 patients over an 8-year period. EST was performed with a standard Bruce protocol, and beta-blockers were held prior to testing. There was evidence of prior MI in 4,248, leaving 14,941 EST for evaluation. Within this cohort, 116 (0.78%) patients had STE during or after exercise. STE was defined as ≥1 mm STE 0.08 second after the J-point, occurring in two or more contiguous leads.
Results: All patients were Caucasian with an average age of 57 ± 11.1 years, and 79.3% were male. Mean exercise duration was 6 minutes (1.3-15) and mean maximum predicted heart rate achieved was 86.7% (61-115%). EST was terminated for chest pain in 56 and STE in 39. STE first occurred in stage 1 in 30%, in stage 2 in 30%, and was noted only in recovery in 24.1% of patients. Coronary arteriography was performed in 108 of the 116 patients, and coronary stenosis >70% was noted in all. Single-vessel disease was noted in 60 patients, 14 of whom had occluded or subtotally occluded arteries. Anterior STE was seen in 41 subjects, 40 of whom had severe disease in the left anterior descending coronary artery, and inferior STE was noted in 66, 63 of whom had either right or circumflex coronary disease. Only one subject had lateral STE.
Conclusions: STE on exercise treadmill testing is a rare but highly specific finding for severe coronary artery disease, and the location of STE predicts the anatomical location of the disease.
Perspective: STE on exercise electrocardiography has been noted for decades. It has been associated with a significant underlying wall motion abnormality and prior MI, and in some patient populations, has been hypothesized to relate to exercise-induced or post-exercise coronary vasospasm as well. In this exclusively Caucasian population, the incidence of STE during or after exercise was low, but the finding was highly specific for severe fixed obstructive coronary disease, with many patients having totally or subtotally occluded coronary arteries. The location of STE was 95% predictive of the anatomical disease location. Other studies with demographically different patient populations have suggested that STE may be more predictive of coronary vasospasm. Although rarely noted, STE on stress testing should probably prompt further assessment with coronary arteriography. William F. Armstrong, M.D., F.A.C.C.

Title: Statins, Fibrates, and Venous Thromboembolism: A Meta-Analysis
Topic: Prevention/Vascular
Date Posted: 1/20/2010
Author(s): Squizzato A, Galli M, Romualdi E, et al.
Citation: Eur Heart J 2009;Dec 22:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there an effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence?
Methods: MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics.
Results: Three randomized controlled trials (RCTs), three cohorts, and eight case-control studies were included in a systematic review, for a total of 863,805 patients. Statin use significantly reduced VTE risk (OR, 0.81; 95% CI, 0.66-0.99, random-effect model). There was a very high heterogeneity among the studies (I2 > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity (I2 = 0%).
Conclusions: This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase the risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted.
Perspective: Meta-analysis should be used primarily for hypothesis generating, but it is not likely that RCTs will be performed specifically to determine the impact of lipid therapies on incident VTE. I think the data are strong enough to use fibrates with care in persons with a history of VTE and who are at high risk, as well as to consider them a risk factor when assessing for clinical VTE. The antithrombotic effects of statins could be related to lipid effects on endothelial function, antiplatelet effects, and anti-inflammatory effects. The only posit for fibrates increasing VTE is an increase in homocysteine levels, a relatively weak explanation. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Prevalence of High Body Mass Index in US Children and Adolescents, 2007-2008
Topic: Prevention/Vascular
Date Posted: 1/22/2010
Author(s): Ogden CL, Carroll MD, Curtin MM, Flegal KM.
Citation: JAMA 2010;303:242-249.
Clinical Trial: No
Study Question: What is the prevalence of high body mass index (BMI) among children and adolescents in the United States?
Methods: Using data from the National Health and Nutrition Examination Survey, 2007-2008, BMI was estimated for 3,281 children (ages 2-19 years) and 719 infants and toddlers (ages birth to 2 years). Prevalence of high weight for recumbent length (≥95th percentile, based on Centers for Disease Control and Prevention growth charts) for infants and toddlers was calculated for five time periods from 1999 to 2008. Prevalence of high BMI was calculated for children (over the age of 2) and adolescents with high BMI defined as three groups: BMI ≥97th percentile, BMI ≥95th percentile, and BMI ≥85th percentile for age. Trends over time were examined by age, sex, and race/ethnicity.
Results: The prevalence of high BMI in 2007-2008 was 9.5% (95% confidence interval [CI], 7.3%-11.7%) for infants and toddlers. For children over the age of 2 and adolescents, the prevalence of those at or above the 97th percentile for BMI was 11.9% (95% CI, 9.8%-13.9%), 16.9% (95% CI, 14.1%-9.6%) for BMI ≥95th percentile, and 31.7% (95% CI, 29.2%-34.1%) for BMI ≥85th percentile. No significant trends over time were observed between 1999-2000 and 2007-2008, with the exception of boys, ages 6-19 years, with BMIs ≥97th percentile (odds ratio [OR], 1.52; 95% CI, 1.17-2.01) and for non-Hispanic white boys ages 6-19 years (OR, 1.87; 95% CI, 1.22-2.94).
Conclusions: The authors concluded that no significant linear trends were observed for high BMI over the past 11 years, with the exception of boys in the highest BMI category.
Perspective: These data suggest a leveling off of the prevalence of overweight and obese children in the United States. However, given the numbers of children with high BMI, aggressive prevention of obesity among US children is still warranted. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Two Self-Management Interventions to Improve Hypertension Control: A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 1/22/2010
Author(s): Bosworth HB, Olsen MK, Grubber JM, et al.
Citation: Ann Intern Med 2009;151:687-695.
Clinical Trial: yes
Study Question: What is the effectiveness of blood pressure (BP) self-management, or a tailored, nurse-administered health behavior intervention, or both, in the improvement of BP?
Methods: The authors reported the results of a 2 x 2 randomized trial, stratified by enrollment site and patient health literacy status, to either usual care, versus home BP monitoring thrice weekly, versus a tailored behavioral telephone intervention, versus behavioral intervention plus BP monitoring. Primary outcome was BP control at 6-month intervals over 24 months.
Results: Of 636 hypertensive patients, 475 (75%) completed the 24-month follow-up. The proportion of patients with controlled BP beyond that seen with usual care was 4.3% (95% confidence interval [CI], -4.5% to 12.9%) in the behavioral intervention group, 7.6% (95% CI, -1.9% to 17.0%) in the home BP monitoring group, and 11.0% (95% CI, 1.9% to 19.8%) in the combined intervention group. Relative to the usual care group, the change in systolic BP was 0.6 mm Hg (95% CI, -2.2 to 3.4 mm Hg) for the behavioral group, -0.6 mm Hg (95% CI, -3.6 to 2.3 mm Hg) for the BP monitoring group, and -3.9 mm Hg (95% CI, -6.9 to -0.9 mm Hg) for the combined intervention group. Similar findings occurred for diastolic BP.
Conclusions: The authors concluded that combined home BP monitoring and tailored behavioral telephone intervention improved BP control, both systolic and diastolic BP at 24 months, compared with usual care.
Perspective: This important study examines the relative effectiveness of simple home BP monitoring, versus continual behavioral 'coaching' regarding exercise, diet, weight, and other healthy lifestyle interventions. This study showed a trend toward improvement in BP with each intervention, but suggests that the only significant improvement came with using both home BP monitoring and the behavioral intervention. We know that home BP measurement is essential to accurately measuring BP (avoiding the very prevalent problem of white coat hypertension), as well as monitoring response to therapy. This study suggests that there are added benefits to combining behavioral intervention with this. Programs based on this type of intervention could have great health and cost benefits, if we could design a health care system with the capacity to efficiently provide this type of support. James B. Froehlich, M.D., F.A.C.C.

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INSTEAD – Type B Dissection
Omega-3 Fatty Acid Levels
The Future of Cardiology is in Atlanta
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: The Response of the QT Interval to the Brief Tachycardia Provoked by Standing: A Bedside Test for Diagnosing Long QT Syndrome
Topic: Arrhythmias
Date Posted: 1/27/2010 5:00:00 PM
Author(s): Viskin S, Postema PG, Bhuiyan ZA, et al.
Citation: J Am Coll Cardiol 2010;Jan 27:[Epub ahead of print].
Clinical Trial: No
Study Question: Is the response of the QT interval during an orthostatic increase in sinus rate useful for the diagnosis of long QT syndrome (LQTS)?
Methods: The QT interval was measured while supine and after standing in 68 patients with LQTS (mean age 32 years) and in 82 control subjects (mean age 35 years).
Results: The mean baseline corrected QT (QTc) was significantly longer in the LQTS group (465 ms) than in the control group (405 ms). After standing, the heart rate increased by a mean of 28 bpm in the control group and 26 bpm in the LQTS group. The mean QT interval during the maximum increase in sinus rate decreased by a mean of 21 ms in the control group and increased by a mean of 4 ms in the LQTS group. The mean QTc after standing increased to a significantly greater degree in the LQTS group (89 ms) than in the control group (50 ms).
Conclusions: An exaggerated increase in QTc during transient orthostatic acceleration of the sinus rate is helpful for identifying patients with LQTS.
Perspective: Prior studies have demonstrated impaired adaptation of the QTc to a gradual increase in sinus rate, such as during exercise. This study demonstrates that there also is impaired adaptation of the QTc to a brief and transient orthostatic increase in heart rate. The simple bedside maneuver of recording an electrocardiogram when an individual suddenly changes from the supine to upright position is most likely to be useful in patients suspected of having QTc who have only borderline prolongation of the baseline QTc. Fred Morady, M.D., F.A.C.C.

Title: ThermoCool AF (ThermoCool AF)
Trial Sponsor: Biosense Webster (makers of the NaviStar ThermoCool Irrigated Tip Catheter)
Year Published 2010
Topic(s): Arrhythmias
Summary Posted: 1/27/2010 4:00:00 PM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis

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Продолжение ThermoCool AF (ThermoCool AF)
Description
Numerous small studies have demonstrated the utility of catheter ablation with pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), as compared with antiarrhythmic drug therapy (ADT). ThermoCool AF is the largest trial to study this question in patients with symptomatic paroxysmal AF, who had not improved with at least one drug.
Hypothesis
Catheter ablation would be superior to ADT in patients with symptomatic AF.
Drugs/Procedures Used
Patients were randomized in a 2:1 fashion to either catheter ablation, or a previously unused antiarrhythmic drug (AAD) (Vaughn class I or III). In the catheter ablation group, PVI was performed using the NaviStar ThermoCool Irrigated Tip Catheter, and the Carto Navigation system. Additional ablation was left to the discretion of the investigator. In the ADT arm, a previously unused Food and Drug Administration approved medication for treating AF (dofetilide, flecainide, propafenone, sotalol, quinidine) at dosages recommended by the American College of Cardiology/American Heart Association/European Society of Cardiology was used. The choice of the drug was at the discretion of the investigator.
Concomitant Medications
Warfarin for 3 months
Principal Findings
A total of 167 patients were randomized, 106 to catheter ablation, and 61 to ADT. The trial was stopped after the first 150 patients were randomized, when interim analysis suggested a strong benefit with catheter ablation. Baseline characteristics were fairly similar between the two groups. The median duration of AF was about 5.7 years. Structural heart disease was present in about 11%, hypertension was present in about 49%, and cerebrovascular accident/transient ischemic attack was noted in 3% of the patients. The mean atrial diameter was about 4.2 cm. The majority of prior AAD failures were due to propafenone (50.3%). Others included sotalol (35.2%), flecainide (27.9%), amiodarone (7.9%), and dofetilide (2.4%). The mean number of class I/III drugs at baseline was 1.3. Most patients in the ADT arm received either flecainide (36%) or propafenone (41%).

Protocol-defined treatment failure was significantly lower in the catheter ablation arm compared with the ADT arm (66% vs. 16%, hazard ratio 0.30, 95% confidence interval 0.19-0.47, p < 0.001). Freedom from symptomatic (70% vs. 19%, p < 0.001) and any (63% vs. 17%, p < 0.001) recurrent atrial arrhythmia was also improved with catheter ablation. There was a high rate of cross-over from the ADT to catheter ablation arm (77%), at a mean of 3.9 months after the onset of the effectiveness evaluation period. Quality of life and symptom severity scores were significantly better in the catheter ablation arm, as compared with the ADT arm at 3 months.

The rate of major treatment-related adverse events at 30 days was similar between the catheter ablation and ADT arms (4.9% vs. 8.8, p = NS), including one pericardial effusion in the catheter ablation arm, and two life-threatening arrhythmias in the ADT arm.
Interpretation
The results of this multicenter trial indicate that catheter ablation with PVI is associated with significantly less treatment failure at 9 months, as compared with ADT, in patients with symptomatic AF, who have failed at least one AAD. There is also a significant reduction in recurrent atrial arrhythmias, a significant improvement in quality of life, without a significant difference in major treatment-related adverse events at 30 days. One limitation of this trial is that even though more than 5,000 patients were screened, only 167 were enrolled. This raises issues with generalizability of these findings. Additionally, all investigators in this trial had extensive experience with catheter ablation, which is a technically challenging procedure. Moreover, ablation practices are not standardized, and a variety of additional ablations besides PVI were frequently employed even in this trial. Hence, outcomes at less experienced centers are likely to be less impressive. Details of rate control between the two groups are also unavailable. Long-term outcomes and cost-effectiveness analyses are also necessary. However, this trial provides supportive evidence regarding the use of catheter ablation for symptomatic AF in patients who have failed at least one AAD.
Conditions
• Arrhythmias / Atrial fibrillation
Therapies
• Electrophysiologic study
Study Design
Randomized. Parallel.
Patients Screened: 5,545
Patients Enrolled: 167
NYHA Class (% I, II, II, IV): I (87%), II (13%)
Mean Follow-Up: 9 months (with a 3-month blanking period)
Mean Patient Age: 55.7 years
% Female: 34

Mean Ejection Fraction: 62.5%
Primary Endpoints
Freedom from protocol-defined treatment failure, which included documented symptomatic paroxysmal AF during the effectiveness evaluation period
Secondary Endpoints
Major treatment-related adverse events at 30 days
Patient Population
At least three symptomatic AF episodes within 6 months prior to randomization (≥1 episode verified by electrocardiography)
Lack of response to at least one AAD (class I, class III, or atrioventricular nodal blocker)
Exclusions:
AF >30 days in duration
Age <18 years
Ejection fraction <40%
Previous catheter ablation for AF
Documented left atrial thrombus
Amiodarone therapy in the preceding 6 months
New York Heart Association class III or IV symptoms
Myocardial infarction within past 2 months, or coronary artery bypass grafting within past 6 months
Thromboembolic event within the past 12 months
Severe pulmonary disease
Prior valvular cardiac surgical procedure
Presence of implantable cardioverter defibrillator
Contraindication to ADT or anticoagulation
Life expectancy <12 months
Left atrial size >5 cm in parasternal view
References: Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA 2010;303:333-40.

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Title: Best Bypass Surgery trial (BBS)
Trial Sponsor:
Danish Heart Foundation
Danish Medical Research Council
Copenhagen Hospital Corporations Medical Research Council
Rigshospitalet Research Council
Aase and Ejnar Danielsens Foundation
Gangsted Foundation
Danish Agency for Science, Technology, and Innovation

Year Published 2010
Topic(s): Cardiovascular Surgery, General Cardiology, Prevention/Vascular
Summary Posted: 1/27/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Research/Research Grants: Eisai; Research/Research Grants: Ethicon; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: The Medicines Company; Research/Research Grants: Bristol Myers Squibb; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Sanofi Aventis
Description
The goal of the trial was to evaluate coronary artery bypass graft surgery (CABG) performed off-pump versus on-pump in patients with coronary artery disease.
Hypothesis
Off-pump CABG would be associated with improved adverse outcomes in high-risk patients.
Drugs/Procedures Used
High-risk patients (EuroSCORE ≥5) with three-vessel coronary disease were randomized to off-pump CABG (n = 177) versus on-pump CABG (n = 164).
Concomitant Medications
Patients in the off-pump group were given 100 U/kg of unfractionated heparin to achieve an activated clotting time >200 seconds. Patients in the on-pump group were given 300 U/kg to achieve an activated clotting time >480 seconds, which was reversed with protamine sulfate at the end of the procedure.
Principal Findings
Overall, 341 patients were randomized. There was no difference in baseline characteristics between the groups. In the off-pump arm, the mean age was 76 years, 35% were women, body mass index was 26.3 kg/m2, 18% had diabetes, 11% had chronic obstructive pulmonary disease, 21% were current smokers, 51% had an ejection fraction >50%, and the mean EuroSCORE was 6.9. The predicted 30-day mortality was approximately 3%.

In the off-pump group, 4.5% of patients crossed over to on-pump CABG (mainly due to hemodynamic instability). In the on-pump group, 3.7% of patients crossed over to off-pump CABG (mainly due to severe aortic calcification). The mean number of grafts per patient was 3.22 in the off-pump group versus 3.34 in the on-pump group (p = 0.11), whereas the mean number of grafts to the lateral wall of the heart was 0.97 versus 1.14 (p = 0.01), respectively.

The 30-day composite primary outcome occurred in 15% of the off-pump group versus 18% of the on-pump group (p = 0.47). Death was 3.4% versus 6.7%, myocardial infarction was 5.1% versus 9.2%, stroke was 4.0% versus 3.7%, coronary re-intervention was 0.6% versus 1.8%, new-onset atrial fibrillation was 43% versus 44%, re-operation for bleeding was 5.1% versus 2.4%, and hemodialysis was 4.0% versus 4.9%, respectively for off-pump versus on-pump (p = NS, for all comparisons).
Interpretation
Among patients with three-vessel coronary artery disease and elevated clinical risk, the use of off-pump CABG is feasible. This method of revascularization is associated with similar short-term adverse events compared with on-pump CABG. While the mean number of grafts was similar between the groups, fewer grafts were placed to the lateral wall of the heart with off-pump CABG. This might affect long-term outcomes, which were shown to be worse with off-pump CABG in the larger ROOBY trial. The current trial was conducted at a single center and only reported outcomes to 30 days.
Conditions
• Coronary heart disease
• Coronary heart disease / Angina pectoris / Stable
Therapies
• CABG
Study Design
Randomized. Blinded. Parallel. Stratified.
Patients Screened: 2,578
Patients Enrolled: 341
NYHA Class (% I, II, II, IV): NYHA class III or IV: 29%
Mean Follow-Up: 30 days
Mean Patient Age: 76 years
% Female: 35

Mean Ejection Fraction: 51% with ejection fraction >50%
Primary Endpoints
Composite of all-cause mortality, acute myocardial infarction, resuscitated cardiac arrest, low cardiac output/cardiogenic shock, stroke, or coronary re-intervention at 30 days
Secondary Endpoints
Hyperdynamic shock
New-onset atrial fibrillation
Need for pacing more than 24 hours
Renal failure
Re-operation
Respiratory failure requiring re-intubation
Pneumonia
Length of stay in the intensive care unit and the hospital
Patient Population
Patients at least 54 years of age with EuroSCORE ≥5 and three-vessel coronary disease involving a marginal artery
Elective or subacute indication for surgery
Exclusions:
Previous heart surgery
Left ventricular ejection fraction <30%
Inability to provide informed consent
Unstable preoperative condition
References: Moller CH, Perko MJ, Lund JT, et al. No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery. The Best Bypass Surgery Trial. Circulation 2010;121:498-504.

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Title: Optimizing Hemodynamics in Heart Failure Patients by Systematic Screening of Left Ventricular Pacing Sites: The Lateral Left Ventricular Wall and the Coronary Sinus Are Rarely the Best Sites
Topic: Arrhythmias
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Derval N, Steendijk P, Gula LJ, et al.
Citation: J Am Coll Cardiol 2010;55:566-575.
Clinical Trial: No
Study Question: What is the optimal left ventricular (LV) pacing site for cardiac resynchronization therapy (CRT)?
Methods: Thirty-five patients (mean age 63 years) with a nonischemic cardiomyopathy (mean ejection fraction 28%) and left bundle branch block underwent hemodynamic measurements during dual-chamber (DDD) pacing from a lateral branch of the coronary sinus (CS) and at 10 prespecified endocardial LV sites. Hemodynamic results at pacing sites were expressed as a percentage variation from the hemodynamics during atrial pacing.
Results: There was a large range in the hemodynamic response to pacing at different sites within individual patients (+19% to +93%), and between different patients (-31% to +93%). None of the 11 pacing sites was consistently associated with the best hemodynamic response to pacing. DDD pacing at the best LV site yielded a better hemodynamic response (+31%) compared to CS pacing (+15%). The CS was the pacing site that yielded the best hemodynamic response in only 9% of patients.
Conclusions: The optimal LV site for CRT is unpredictable, must be identified on an individualized basis by testing, rarely is in the CS, and often is endocardial.
Perspective: The response rate to conventional CRT, with the LV lead in a branch of the CS, has been 60-80%. The results of this study suggest that the response rate to CRT can be improved by identifying the optimal pacing site on an individualized basis. Widespread adaptation of this approach into clinical practice may be hampered by the rigorous and lengthy testing protocol and by the potential problems associated with long-term endocardial LV pacing. Fred Morady, M.D., F.A.C.C.

Title: Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial
Topic: Arrhythmias
Date Posted: 1/28/2010
Author(s): Wilber DJ, Pappone C, Neuzil P, et al., on behalf of the ThermoCool AF Trial Investigators.
Citation: JAMA 2010;303:333-340.
Clinical Trial: yes
Study Question: Is radiofrequency catheter ablation (RFCA) more effective than antiarrhythmic drug therapy (ADT) in patients with paroxysmal atrial fibrillation (PAF)?
Methods: The subjects of this study were 159 patients (mean age 56 years) with symptomatic PAF who had failed to respond to treatment with ≥1 rhythm- or rate-control agent. The patients were randomized to RFCA (n = 103) with an irrigated-tip ablation catheter or ADT (n = 56) with flecainide, propafenone, dofetilide, sotalol, or quinidine. The ablation strategy was a minimum of wide-area pulmonary vein isolation, with additional ablation at the operator’s discretion. Redo RFCA was allowed during a 3-month blanking phase. Efficacy was assessed at clinic visits and with serial transtelephonic monitoring. The 1° endpoint was freedom from symptomatic AF during the 9 months after the blanking period.
Results: A redo ablation procedure was performed in 12.6% of patients in the RFCA group. The 1° endpoint was achieved significantly more often in the RFCA group (66%) than in the ADT group (16%). The rate of major adverse events was higher in the ADT group (8.8%) than in the RFCA group (4.9%).
Conclusions: RFCA is more effective than ADT for preventing PAF in patients who already have not responded to one antiarrhythmic drug.
Perspective: The results confirm that patients with AF who do not respond to one trial of ADT are unlikely to respond to subsequent ADTs, and support the current practice guidelines that consider catheter ablation of AF to be appropriate second-line therapy after failure of initial ADT. The modest efficacy of RFCA (66%) most likely reflects the difficulty in achieving permanent isolation of the pulmonary veins. Fred Morady, M.D., F.A.C.C.

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Title: Risk for Incident Atrial Fibrillation in Patients Who Receive Antihypertensive Drugs: A Nested Case-Control Study
Topic: Arrhythmias
Date Posted: 1/26/2010
Author(s): Schaer BA, Schneider C, Jick SS, Conen D, Osswald S, Meier CR.
Citation: Ann Intern Med 2010;152:78-84.
Clinical Trial: No
Study Question: Is the risk of developing atrial fibrillation (AF) affected by the type of medication used to treat hypertension?
Methods: The subjects of this retrospective study were selected from a primary-care database in the United Kingdom and all received monotherapy for hypertension. There were 4,661 patients who developed AF during follow-up and 18,642 matched control subjects who did not. Approximately 70% of patients in both groups were at least 70 years old. The class of drug used to treat the hypertension was analyzed in both groups.
Results: Compared to patients whose hypertension was treated with a calcium-channel blocker (CCB), recipients of an angiotension-converting enzyme inhibitor (ACEI) had a 25% lower risk of developing AF, recipients of an angiotension II-receptor blocker (ARB) had a 29% lower risk, and recipients of a beta-blocker had a 22% lower risk.
Conclusions: Treatment of hypertension with an ACEI, ARB, or beta-blocker reduces the risk of new-onset AF compared to CCBs.
Perspective: Several prior studies have demonstrated that ACEIs and ARBs reduce the risk of AF. Possible mechanisms include lowering of blood pressure, prevention or treatment of heart failure, and prevention of atrial fibrosis. CCBs lower the blood pressure, but do not prevent heart failure or atrial fibrosis. Therefore, the results of this study suggest that prevention of heart failure and/or atrial fibrosis explain the lower risk of AF when hypertension is treated with an ACEI, ARB, or beta-blockers. However, it should be noted that the study does not rule out the possibility of a proarrhythmic effect of CCBs compared to a neutral effect of ACEIs, ARBs, and beta-blockers on the risk of AF. Fred Morady, M.D., F.A.C.C.

Title: Aortic Elasticity and Size Are Associated With Aortic Regurgitation and Left Ventricular Dysfunction in Tetralogy of Fallot After Pulmonary Valve Replacement
Topic: Congenital Heart Disease
Date Posted: 1/26/2010
Author(s): Grotenhuis HB, Ottenkamp J, de Bruijn L, et al.
Citation: Heart 2009;95:1931-1936.
Clinical Trial: No
Study Question: What are the relationships between aortic elasticity, aortic valve competence, and biventricular function in patients with repaired tetralogy of Fallot (TOF) who have undergone pulmonary valve replacement?
Methods: A prospective case-controlled study was performed. Sixteen patients with TOF and 16 age- and gender-matched controls underwent cardiac magnetic resonance imaging for evaluation of aortic root dimensions, biventricular function, aortic elasticity, and quantification of aortic regurgitation.
Results: Aortic root dimensions at the sinuses of ******** were larger in the TOF patients (39.3 ± 5.4) compared with the controls (30.4 ± 3.1). Reduced aortic elasticity was also seen in the TOF group (pulse wave velocity in the aortic arch of 5.5 ± 1.2 m/s compared with 4.6 ± 0.9 m/s). TOF patients were also found to have increased aortic regurgitation (regurgitant fraction of 6% vs. 1%, p < 0.01) and decreased left ventricular ejection fraction (LVEF) (51% vs. 58%, p = 0.01), whereas right ventricular ejection fraction (RVEF) was preserved in both groups. The degree of aortic regurgitation fraction was associated with dilatation of the aortic root (r = 0.39-0.49, p < 0.05) and reduced aortic root distensibility (r = 0.44, p = 0.02). Reduced LVEF correlated with degree of aortic regurgitation and RVEF (r = 0.41, p = 0.02 and r = 0.49, p < 0.01, respectively).
Conclusions: Aortic root dilatation and reduced aortic elasticity are frequently seen in patients following repair of TOF and pulmonary valve replacement. Aortic wall pathology may contribute to LV dysfunction in this patient population.
Perspective: This paper studies the relationship between aortic root pathology and LV function in patients following TOF repair and subsequent pulmonary valve replacement. LV dysfunction has been well-documented in patients after TOF repair, and has often been attributed to intraventricular dependence, as well as perioperative insults with early bypass techniques. This study shows a relationship between relatively mild degrees of aortic insufficiency and root dilatation with LV dysfunction. Although the correlation coefficients are relatively weak, it appears that this was a consistent finding in a relatively small patient population. This study emphasizes the complexity of etiologies contributing to LV dysfunction in patients following repair of TOF. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Disease
Topic: General Cardiology
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Tachjian A, Maria V, Jahangir A, et al.
Citation: J Am Coll Cardiol 2010;55:515-525.
Clinical Trial: No
Study Question: How does the use of herbal supplements affect patients with cardiovascular disease?
Methods: This review was based on a search of PubMed and MEDLINE databases, for literature on herbal supplements published between 1966 and 2008. Search terms included cardiovascular agents, complementary therapies, herb–drug interactions, and cardiovascular disease interactions.
Results: Over 15 million children and adults in the United States consume herbal remedies or high-dose vitamins. Herbal remedies include plants or plant products. They compose a large majority of complementary alternative medicine therapies used with an estimated 30,000 dietary supplements sold in the United States. Herbs are considered food products and are not regulated as drugs. Lack of quality control has resulted in significant variation in herb supplements and inconsistent labeling of products. In one study, more than 40% of herbal products examined had incorrect labeling for amounts of ingredients listed. In addition, contamination of the supplement with heavy metals has been reported and pharmaceuticals have been found in herbal supplements. Since controlled trials are not available for most herbal remedies, an understanding of the efficacy of many of these therapies is not available. Reporting of adverse events related to herbal remedies is not mandatory; therefore, information on potential adverse effects is not well understood either.

Commonly used herbal supplements include St. John’s wort, motherwort, ginseng, ginkgo, grapefruit juice, saw palmetto, danshen, tetrandine and yohimbine, and licorice. St. John’s wort increases the hepatic cytochrome P450 system and thus can reduce levels of medications including cyclosporine. St. John’s wort may also reduce prothrombin time in patients talking warfarin. Motherwort can reduce platelet aggregation and increase risk of bleeding. Ginseng can affect blood pressure, causing both hypertension and hypotension. Ginkgo, when used in combination with antiplatelet agents, can increase bleeding time. Grapefruit juice can inhibit CYP3A4 enzyme and thus increase levels of calcium channel blockers, cyclosporine, and statins. Saw palmetto can increase bleeding risk among patients taking warfarin. Danshen reduces elimination of warfarin and may interfere with digoxin assays. Tetrandine is a vasoactive alkaloid, which can cause hepatotoxicity and renal toxicity. Yohimbine can increase blood pressure. Licorice is often used as an expectorant and can cause pseudoaldosteronism and hypokalemia.
Conclusions: The authors encourage physicians to ask patients about concomitant use of herbal therapies, in particular among patients who are taking cardiovascular medications with narrow therapeutic windows such as digoxin and warfarin. Increases in research, which provides controlled clinical evaluations of herbal therapies and improvements in regulation and oversight of such therapies, are warranted.
Perspective: This review outlines a number of concerns regarding the use of herbal therapies among patients taking cardiovascular medications. Improved education for both health care providers and patients, along with systematic evaluation of these therapies, will allow for safe and effective use of such therapies among patients with heart disease. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Death
Topic: General Cardiology
Date Posted: 1/29/2010
Author(s): Kramer MCA, Rittersma SZ, deWinter RJ, et al.
Citation: J Am Coll Cardiol 2010;55:122-132.
Clinical Trial: No
Study Question: What is the relationship of thrombus healing to underlying plaque morphology in sudden death?
Methods: All sudden death cases referred to the Examiner’s Office between 2005 and 2006 were reviewed. Of the 345 deaths reviewed, 181 died from coronary thrombi (129 ruptures and 52 erosions). A total of 111 cases with available demographic and pathologic data were included in this analysis. Sudden death was defined as natural deaths without extracardiac causes occurring within 6 hours after onset of anginal symptoms or last seen alive within 24 hours in a normal healthy state. Plaque ruptures (n = 65) were compared to plaque erosions (n = 50). Thrombus healing was classified as early (<1 day) or late stage. Late stage was further classified into lytic (1-3 days), infiltrating (4-7 days), or healing (>7 days). Morphology was examined including vessel dimensions, necrotic core size, and macrophage density.
Results: A total of 74 deaths were witnessed, of which 51 had typical cardiac symptoms, 8 had atypical symptoms, and 15 were asymptomatic. Sudden death victims with ruptures were older then those with erosions. Early thrombi were observed more often with plaque rupture. Late-stage thrombi comprised 69% of lesions (70/115). Women were more likely to have erosions than ruptures (26% vs. 11%, p = 0.06). Women were observed to have erosions with a greater prevalence of late-stage thrombi (44/50 or 88%), as compared to ruptures (35/65 or 54%). The internal elastic lamina area and percent stenosis were significantly smaller in erosions compared with ruptures, whereas plaque burden was higher. Less macrophage infiltration was observed in erosions compared to ruptures; however, no relationship was noted with thrombus organization. No association between healing and thrombus length or other parameters was observed.
Conclusions: The investigators concluded that many thrombi are late stage, organizing thrombi. Furthermore erosions, more often observed in younger age victims and women, were associated with late-stage thrombi.
Perspective: This study suggests the need to further characterize thrombi and examine outcomes such as sudden death in younger patients and women. Potentially, plaque erosions may warrant different management than plaque rupture; however, further study is needed to make such a determination. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Physical Activity Reduces Systemic Blood Pressure and Improves Early Markers of Atherosclerosis in Pre-Pubertal Obese Children
Topic: Noninvasive Cardiology
Date Posted: 1/26/2010
Author(s): Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR, Beghetti M.
Citation: J Am Coll Cardiol 2009;54:2396-2406.
Clinical Trial: yes
Study Question: Does physical activity improve systolic blood pressure and markers of atherosclerosis in pre-pubertal obese children?
Methods: This was a randomized controlled trial, which used an exercise intervention to improve cardiovascular markers in pre-pubertal obese children. Children were assigned to exercise or control groups, with 22 in each group. An additional 22 lean children were recruited as a comparison group. The exercise group performed 60 minutes of exercise three times per week during the 3-month intervention. After the initial 3 months, both the intervention and control groups performed exercise twice per week for a 2-month period. Clinical assessments were preformed at 3 and 6 months. Outcomes included change in office and 24-hour blood pressure, arterial intima-media thickness (IMT) and arterial stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body fat, cardiorespiratory fitness (maximal oxygen consumption [VO2max]), physical activity, and biological markers.
Results: At baseline, obese children had higher levels of blood pressure, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and C-reactive protein, and lower flow-mediated dilation, VO2max, physical activity, and high-density lipoprotein cholesterol compared to lean children. At 3 months, obese children in the exercise group had significant improvements in 24-hour systolic blood pressure, diastolic blood pressure, hypertension rate, office blood pressure, BMI z-scores, abdominal fat, and VO2max. At 6 months, changes in arterial stiffness and IMT were significant.
Conclusions: The authors concluded that regular exercise can reduce blood pressure, arterial stiffness, and abdominal fat, and can improve cardiorespiratory fitness and delay arterial wall remodeling among obese pre-pubertal children.
Perspective: This study demonstrates the importance of regular physical activity for the prevention of cardiovascular disease, starting at an early age. Clinicians should encourage families to incorporate regular physical activity for all members of a family, including young children. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: The Coronary Artery Calcium Score and Stress Myocardial Perfusion Imaging Provide Independent and Complementary Prediction of Cardiac Risk
Topic: Noninvasive Cardiology
Date Posted: 1/28/2010
Author(s): Chang SM, Nabi F, Xu J, et al.
Citation: J Am Coll Cardiol 2009;54:1872-1882.
Clinical Trial: No
Study Question: What are the relative prognostic implications and relationships between coronary artery calcium score (CACS) and single-photon emission computed tomography (SPECT) results?
Methods: CACS and stress SPECT were performed in 1,128 patients without known coronary disease who were subsequently followed for nonfatal myocardial infarction, cardiac death, revascularization, and all-cause mortality.
Results: Average patient age was 58.4 ± 9.8 years and 73% were male. Median follow-up was 6.9 years. Diabetes was present in 10% and hypertension in 52%. CACS was 0-10 in 24%, 11-100 in 21%, 101-400 in 28%, and >400 in 27% (four strata). SPECT was abnormal in 149 (13%), and 43 (4%) had a perfusion defect size (PDS) ≥15% and 34 (3%) had ischemic PDS ≥10%. Across the four strata of CAC scores, there was a statistically significant increase in age and male gender as well as number of cardiovascular risk factors. Similarly, patients with a normal versus abnormal SPECT tended to be younger and have a lower prevalence of risk factors. For the four strata of CACS, the frequency of abnormal SPECT was 1%, 2.3%, 9.8%, and 31%. Across the four strata of CACS, total cardiac events occurred in 0.7%, 0.97%, 1.3%, and 2.97% of subjects with a normal SPECT. Annualized cardiac event rates were 9.6% in patients with ≥15% stress PDS. Survival curves suggested separation of survival between patients with minimal and severe CACS 3 years after normal SPECT. Global chi-square analysis suggested an incremental value of CACS when added to SPECT and clinical results for predicting total cardiac events and all-cause mortality/nonfatal myocardial infarction.
Conclusions: CACS and SPECT are independent, complementary predictors of cardiac events. Patients with a normal SPECT but markedly abnormal CACS have a worse long-term outcome with respect to cardiovascular events.
Perspective: Both CACS and SPECT have been associated with an adverse prognosis. There has been substantial controversy with respect to the relative role of these two studies for screening and prognostic purposes. This study nicely demonstrates a complementary and additive role of calcium scoring in patients with a broad range of SPECT abnormalities. The major message of this study is that, even in the presence of a normal SPECT thallium, prognosis may be worse with markedly abnormal CACS. Importantly, for patients with abnormal CACS and normal thallium, the prognosis over the ensuing first 3 years was benign and only after 3 years did survival curves diverge, suggesting a warranty period of 3 years in patients with a normal SPECT thallium and a markedly abnormal CACS. This ‘warranty period’ is similar to that suggested previously even without the addition of CACS. This observation may not apply to high-risk patients, including diabetics. Based on this study, as well as the bulk of previously published data, incorporating CACS into clinical decision making appears to be a reasonable strategy and may allow identification of relatively higher-risk patients with initially normal perfusion studies who may warrant closer follow-up. William F. Armstrong, M.D., F.A.C.C.

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Title: Delayed Hyper-Enhancement Magnetic Resonance Imaging Provides Incremental Diagnostic and Prognostic Utility in Suspected Cardiac Amyloidosis
Topic: Noninvasive Cardiology
Date Posted: 1/28/2010
Author(s): Austin BA, Wilson Tang WH, Rodriguez ER, et al.
Citation: JACC Cardiovasc Imaging 2009;2:1369-1377.
Clinical Trial: No
Study Question: What is the diagnostic accuracy and prognostic value of delayed hyper-enhancement on cardiac magnetic resonance imaging (DHE-CMR) compared to standard electrocardiographic (ECG) and echocardiographic parameters in patients with suspected cardiac amyloid?
Methods: Routine ECG, echocardiography for Doppler diastolic parameters, and DHE-CMR were available in 47 patients with suspected cardiac amyloid, all of whom underwent either endomyocardial (n = 38) or extracardiac biopsy. Diastolic parameters included deceleration time, E/E' ratio, and diastolic grade. Cardiac amyloid was considered present if CMR revealed diffuse DHE of the subendocardium. The endpoint of all-cause mortality was tabulated.
Results: Average patient age was 62 years and 70% were male. Biopsy was positive for amyloid in 25 and negative in 22 patients. New York Heart Association class >II was present in 55% of biopsy-negative and 56% of biopsy-positive patients. Low voltage on the ECG (Carroll criteria) was noted in 55% of biopsy-negative and 60% of biopsy-positive patients. A speckled appearance on echocardiography was noted in no biopsy-negative patients and in four (16%) biopsy-positive patients. Ventricular septal thickness averaged 1.3 cm (1.1-1.6) in biopsy-negative and 1.7 cm (1.4-2) in biopsy-positive patients. A deceleration time ≤150 ms was noted in six biopsy-negative patients (27%) and eight (32%) biopsy-positive patients. Grade II or worse diastolic dysfunction was noted in nine biopsy-negative patients (41%) and 13 (50%) biopsy-positive patients. DHE-CMR was characteristic of cardiac amyloid in three biopsy-negative patients (14%) versus 19 (76%) biopsy-positive patients (p < 0.0001). Sensitivity, specificity, positive, and negative predictive values for low-voltage ECG were 76%, 48%, 54%, and 71%, and 35%, 62%, 43%, and 54% for deceleration time ≤150 ms. DHE-CMR had corresponding values of 88%, 90%, 88%, and 90%. Of the preceding parameters (plus others), only DHE-CMR was predictive of cardiac amyloid on multivariable analysis. At 1 year following biopsy, there were nine (19%) deaths in biopsy-positive patients, including seven who were DHE-CMR positive. On multivariable analysis, only DHE-CMR was predictive of mortality.
Conclusions: DHE-CMR is more accurate than echocardiographic or ECG parameters for diagnosing cardiac amyloid, and a positive DHE-CMR confers a worse 1-year prognosis than does advanced diastolic dysfunction on Doppler.
Perspective: Several previous studies have suggested a characteristic pattern on gadolinium-enhanced CMR to be diagnostic of cardiac amyloid. This study compares this finding to traditional ECG and echocardiographic parameters of abnormal diastolic function, and suggests that the accuracy of CMR exceeds these more traditional and widespread techniques. Previous studies have suggested that advanced diastolic dysfunction confers an adverse prognosis in patients with documented cardiac amyloid. It should be noted that virtually all studies evaluating echocardiographic and other parameters in cardiac amyloid are relatively limited in scope. This study suggests that a typical pattern of diffuse hyper-enhancement on CMR is not only more accurate for the diagnosis of cardiac amyloid, but has independent adverse prognostic implications. William F. Armstrong, M.D., F.A.C.C.

Title: Effects of the DASH Diet Alone and in Combination With Exercise and Weight Loss on Blood Pressure and Cardiovascular Biomarkers in Men and Women With High Blood Pressure: The ENCORE Study
Topic: Prevention/Vascular
Date Posted: 1/28/2010
Author(s): Blumenthal JA, Babyak MA, Hinderliter A, et al.
Citation: Arch Intern Med 2010;170:126-135.
Clinical Trial: No
Study Question: Does the DASH diet lower blood pressure and alter cardiovascular risk biomarkers among free-living adults?
Methods: This was a randomized controlled trial, which compared the DASH diet alone or in combination with a weight management program to usual diet controls. Participants were overweight or obese (body mass index 25-40 kg/m2) with prehypertension or stage one hypertension (130-149 mm Hg systolic blood pressure and/or 85-99 mm Hg diastolic blood pressure). Participants in the DASH diet alone or the usual diet groups consumed isocaloric meals with the goal of maintenance of their baseline weight. Those in the DASH plus weight management group consumed meals at a 500-caloric deficit. Exercise for this group consisted of three classes per week. The primary outcome of interest was clinic blood pressure and ambulatory blood pressure. Secondary outcomes included pulse wave velocity, flow-mediated dilation, baroreflex sensitivity, and left ventricular mass.
Results: Among the 144 participants, those randomized to the DASH diet plus weight management had the greatest reduction in clinic blood pressure (16.1/9.9 mm Hg), followed by the DASH diet alone (11.2/7.5 mm Hg), with the usual diet controls having the least change in blood pressure (3.4/3.8 mm Hg). Ambulatory blood pressure measures were similar. Greater improvements in pulse wave velocity, baroreflex sensitivity, and left ventricular mass were observed in participants randomized to the DASH diet and weight management, as compared to those randomized to the DASH diet alone.
Conclusions: The investigators concluded that for overweight or obese patients with prehypertension or stage one hypertension, the DASH diet with weight management resulted in significant reductions in blood pressure and improved vascular and autonomic tone.
Perspective: This study demonstrates the significance of combining dietary changes with increased physical activity. Incorporation of exercise to the DASH diet resulted in significant blood pressure reduction and improved vascular function. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart Disease
Topic: Prevention/Vascular
Date Posted: 1/29/2010
Author(s): Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA.
Citation: JAMA 2010;303:250-257.
Clinical Trial: No
Study Question: Is there a correlation between blood levels of omega-3 fatty acids and telomere length, a potential marker of biological age?
Methods: This was a prospective cohort study of 608 ambulatory outpatients with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years). Leukocyte telomere length was measured at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length.
Results: Individuals in the lowest quartile of DHA+EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; p < 0.001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted β coefficient x 10−3 = 0.06; 95% CI, 0.02-0.10) and after (adjusted β coefficient x 10−3 = 0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-standard deviation increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98).
Conclusions: Among a cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.
Perspective: High dietary intake of marine omega-3 fatty acids has previously been associated with reduced risk of death and cardiovascular disease. Many mechanisms for these beneficial effects have been proposed including antiplatelet, anti-arrhythmic, anti-inflammatory, and triglyceride-lowering effects. The current study raises a new potential mechanism of benefit from omega-3 fatty acids, reduced telomere shortening. During cell division, there is progressive loss of tandem repeat DNA sequences (telomeres) that form protective caps at the end of chromosomes. Eventually, this process leads to cell death. Genetic and environmental factors may influence telomere shortening, and short telomeres have been associated with cardiovascular disease and death. Factors that prevent telomere loss could lead to reduced disease burden and increased longevity. Additional studies are necessary to establish a causal relationship between omega-3 fatty acids and prevention of telomere shortening, as well as to uncover mechanisms by which this may occur. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Smoking Status and Long-Term Survival After First Acute Myocardial Infarction: A Population-Based Cohort Study
Topic: Prevention/Vascular
Date Posted: 1/29/2010
Author(s): Gerber Y, Rosen LJ, Goldbourt U, Benyamini Y, Drory Y, on behalf of the Israel Study Group on First Acute Myocardial Infarction.
Citation: J Am Coll Cardiol 2009;54:2382-2387.
Clinical Trial: No
Study Question: Is cigarette smoking reduction among persistent smokers associated with lower mortality?
Methods: Consecutive patients ≤65 years of age, discharged from eight hospitals in central Israel after first acute myocardial infarction (AMI) in 1992 to 1993, were followed through 2005. Extensive data, including self-reported smoking habits, were obtained at baseline and four times during follow-up. Cox proportional hazards regressions were used to assess the hazard ratios (HRs) for death associated with smoking categories modeled as time-dependent variables.
Results: At baseline, smokers were younger, more likely to be male, and had a lower prevalence of hypertension and diabetes than nonsmokers. Over a median follow-up of 13.2 years, 427 deaths occurred in 1,521 patients. The multivariable-adjusted hazard ratios for mortality were 0.57 (95% confidence interval [CI], 0.43-0.76) for never-smokers, 0.50 (95% CI, 0.36-0.68) for pre-AMI quitters, and 0.63 (95% CI, 0.48-0.82) for post-AMI quitters, compared with persistent smokers. Among persistent smokers, upon multivariable adjustment including pre-AMI intensity, each reduction of five cigarettes smoked daily after AMI was associated with an 18% decline in mortality risk (p < 0.001).
Conclusions: Smoking cessation either before or after AMI is associated with improved survival. Among persistent smokers, reducing intensity after AMI appears to be beneficial.
Perspective: The mechanisms leading to an increase in coronary events in smokers include that it promotes lipid oxidation, low high-density lipoprotein cholesterol, inflammation, thrombosis, oxidative stress, endothelial dysfunction, and coronary vasospasm. The type of coronary plaque and plaque rupture differ between smokers and nonsmokers. Despite the well known association of cigarette smoking and coronary events, the degree to which smoking cessation reduces very long-term mortality and the contribution of the degree of continuing abstinence or reduction over 10 years had not been studied. Further, the relationship between the value of total cessation and decreasing consumption was not known. The results provide very good evidence to enhance patient education in both primary and secondary prevention. Melvyn Rubenfire, M.D., F.A.C.C.

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Ablation Beats Drug Rx in PAF
Varenicline for Smokers with CAD
Ablate VT Before ICD Implant
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Endovascular Aortic Repair Versus Open Surgical Repair for Descending Thoracic Aortic Disease: A Systematic Review and Meta-Analysis of Comparative Studies
Topic: Cardiovascular Surgery
Date Posted: 2/3/2010 5:00:00 PM
Author(s): Cheng D, Martin J, Shennib H, et al.
Citation: J Am Coll Cardiol 2010;Feb 3:[Epub ahead of print].
Clinical Trial: No
Study Question: Does thoracic endovascular aortic repair (TEVAR) reduce death and morbidity compared with open surgical repair for descending thoracic aortic disease?
Methods: Data from 42 studies (four multicenter, 35 single center, and three registries) of TEVAR versus open repair of the descending aorta were examined by meta-analysis to determine mortality and morbidity rates for each approach. Meta-regression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Registry data were analyzed separately from comparative studies, as these data were thought to be too heterogeneous.
Results: The 42 nonrandomized studies included 5,888 patients. Patient characteristics were balanced, except that patients undergoing TEVAR tended to be older (p < 0.001). In comparative studies, all-cause mortality at 30 days (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.33-0.59) and paraplegia (OR, 0.42; 95% CI, 0.28-0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction (MI), aortic reintervention, and mortality at 2-3 years. Meta-regression to adjust for age imbalance, study design, and pathology did not materially change the results. Registry data suggested that overall perioperative complications were reduced. However, registry data did not demonstrate alterations in 30-day, 1-year, and 2- to 3-year mortality, or any of the single complications (stroke, acute MI, renal failure, ischemia to the gut or limb) examined.
Conclusions: This meta-analysis suggests that TEVAR reduces early mortality, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Moderate-term follow-up (2-3 years) failed to show a sustained survival benefit.
Perspective: I suspect anyone who performs or performed open and TEVAR for thoracic aortic aneurysms (TAAs) recognizes that short-term mortality and morbidity is lower in patients undergoing TEVAR. Importantly, of all the devastating complications associated with TAA repair, paraplegia risk is reduced almost 58%. The fact that no sustained benefit is obtained is likely due to one of two reasons: 1) the small collection of studies with moderate-term follow-up were underpowered to show a difference, or 2) the patients die from nonthoracic aortic disease (i.e., MIs). Even more so than endovascular repair of abdominal aortic aneurysms, TEVAR will completely dominate the landscape of repair over the next decade. Gilbert Upchurch, Jr., M.D.

Title: Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT)
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 2/1/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Description
The goal of the trial was to evaluate treatment with the weight loss agent sibutramine (Meridia) compared with placebo among overweight or obese individuals.
Hypothesis
Sibutramine would reduce cardiovascular events.
Drugs/Procedures Used
Obese patients were randomized to sibutramine versus placebo.
Principal Findings
Approximately 10,000 patients were randomized. Interim analysis revealed that the primary outcome of death, myocardial infarction, stroke, or resuscitated cardiac arrest occurred in 11.4% of the sibutramine group versus 10% of the placebo group.

Adverse events appeared to disproportionately occur in diabetics with cardiovascular disease. The primary outcome occurred in 6.5% versus 6.5% (p = 0.95) among diabetics without evident cardiovascular disease, 10.1% versus 8.3% (p = 0.15) among individuals with history of cardiovascular disease, and 13.9% versus 11.9% (p = 0.023) among diabetics with cardiovascular disease, respectively, for sibutramine versus placebo.
Interpretation
Interim analysis revealed that sibutramine may be associated with increased adverse cardiovascular events. Accordingly, new product labeling has been expanding to state that sibutramine should be avoided in individuals with a history of coronary artery disease, congestive heart failure, arrhythmia, peripheral arterial disease, uncontrolled hypertension, or stroke. The FDA is conducting an expedited safety review to determine if additional regulatory actions are needed.
Conditions
• Prevention
• Coronary heart disease
Therapies
• Medical
Study Design
Placebo controlled. Randomized. Parallel.
Primary Endpoints
Composite of death, myocardial infarction, stroke, or resuscitated cardiac arrest
Patient Population
Obese patients at least 55 years of age with:
Body mass index ≥30 kg/m2, or
Body mass index ≥27 kg/m2 with an additional cardiovascular risk factor (diabetes, high cholesterol, or hypertension)
References: U.S. Food and Drug Administration. Postmarket Drug Safety Information for Patients and Providers.

FDA: sibutramine now contraindicated in people with cardiovascular disease. CardioBrief, January 21, 2010.

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Title: Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia
Topic: General Cardiology
Date Posted: 2/5/2010
Author(s): Sanders AE, Wang C, Katz M, et al.
Citation: JAMA 2010;303:150-158.
Clinical Trial: No
Study Question: A single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine) in the cholesteryl ester transfer protein (CETP) gene has been associated with exceptional longevity and lower cardiovascular risk. Is it associated with less memory decline and dementia risk?
Methods: This is a prospective cohort study comprising 608 community-dwelling adults without dementia, ages 70 years or older, from the Einstein Aging Study with CETP genotype available. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) ε4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory, attention, and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or Alzheimer’s disease (AD) in similarly adjusted Cox proportional hazards models with age as the time scale. Primary outcome was memory decline and incident dementia.
Results: Fifteen participants with baseline dementia and 70 without follow-up were excluded, leaving 523 participants for the Cox analysis. Mean age was 78.2 (standard deviation [SD] 8.1) years, 61% were female, 69% white, 25.6% African-American, and 30% Ashkenazi Jewish. Valine allele frequency was 43.5% and did not differ by race. A total of 40 cases of incident dementia occurred during a mean follow-up of 4.3 [SD 3.1] years. Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline (difference in linear age slope, 0.22; 95% confidence interval [CI], 0.02-0.41; p = 0.03) and no significant differences on psychomotor speed. Valine homozygotes also had a lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; p = 0.02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; p = 0.04).
Conclusions: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.
Perspective: CETP V405 valine homozygosity is associated with lower CETP protein serum concentration and activity and corresponding increases in high-density lipoprotein (HDL) cholesterol levels and an increase in lipoprotein (HDL and low-density lipoprotein) particle size, each of which is associated with a decrease in cardiovascular event rates. The genotype was characterized as the ‘longevity gene’ in a New York community of Ashkenazi Jews who had an uncommon number of centenarians. Now we have evidence that living longer with this gene is associated with less cognitive loss per year. While the African-American participants had a similar incidence of CETP V405, there was not a protective effect from cognitive decline. The mechanism of decreasing dementia could be related to the vascular protective effect—not a bad thing to inherit from mom and dad. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Systematic Review of Guidelines on Cardiovascular Risk Assessment: Which Recommendations Should Clinicians Follow for a Cardiovascular Health Check?
Topic: General Cardiology
Date Posted: 2/3/2010
Author(s): Ferket BS, Colkesen EB, Visser JJ, et al.
Citation: Arch Intern Med 2010;170:27-40.
Clinical Trial: No
Study Question: Is there a reasonable correlation between the various guidelines on cardiovascular risk assessment to guide selection of screening interventions for a health check?
Methods: Guidelines in the English language published between January 1, 2003, and May 2, 2009, were retrieved using MEDLINE and CINAHL. This was supplemented by searching the National Guideline Clearinghouse, National Library for Health, Canadian Medical Association Infobase, and G-I-N International Guideline Library. The authors selected guidelines developed on behalf of professional organizations from Western countries, containing recommendations on cardiovascular risk assessment for the apparently healthy population. Twenty-seven guidelines met their criteria. One reviewer extracted information on conflicts of interest and recommendations.
Results: Sixteen of 27 guidelines reported conflicts of interest and 17 showed considerable rigor. These included recommendations on assessment of total cardiovascular risk (7 guidelines), dyslipidemia (2), hypertension (2), and dysglycemia (7). Recommendations on total cardiovascular risk and dyslipidemia included prediction models integrating multiple risk factors, whereas remaining recommendations were focused on single risk factors. No consensus was found on recommended target populations, treatment thresholds, and screening tests.
Conclusions: Differences among the guidelines imply important variation in allocation of preventive interventions. To make informed decisions, physicians should use only the recommendations from rigorously developed guidelines.
Perspective: The authors state: ‘Complete and unbiased information on benefits and harms is thus desirable. Transparency about how judgments have been made within guidelines allows physicians to make informed decisions on adopting recommendations.’ While a noble effort, the reality is that national guidelines are rarely followed, but are invaluable for providing health care systems, payers, and individual physicians with information from which to make an informed decision on standards for their patient cohorts and individual patients. That the guidelines differ significantly despite that each was developed by experts in their field and sponsored by national organizations or governments is not surprising. The reasons for the differences are not subtle. Some focus on societal costs, some include only evidenced-based data, some combine evidence and ‘expert opinion,’ and some focus on optimizing risk assessment and treatment for the individual rather than a population. Melvyn Rubenfire, M.D., F.A.C.C.

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The Response of the QT Interval to the Brief Tachycardia Provoked by Standing: A Bedside Test for Diagnosing Long QT Syndrome
Viskin S, Postema PG, Bhuiyan ZA, et al.
J Am Coll Cardiol 2010;Jan 27:[Epub ahead of print].
Study Question: Is the response of the QT interval during an orthostatic increase in sinus rate useful for the diagnosis of long QT syndrome (LQTS)?

Title: Relation Between Kidney Function, Proteinuria, and Adverse Outcomes
Topic: General Cardiology
Date Posted: 2/4/2010
Author(s): Hemmelgarn BR, Manns BJ, Lloyd A, et al., on behalf of the Alberta Kidney Disease Network.
Citation: JAMA 2010;303:423-429.
Clinical Trial: No
Study Question: What is the association between reduced glomerular filtration rate (GFR), proteinuria, and adverse clinical outcome?
Methods: The participants were from a community-based cohort study comprised of 920,985 adults who had at least one outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure were the main outcome measures. The median follow-up period was 35 months (range 0-59 months).
Results: The investigators found that a majority of individuals (89.1%) had an estimated GFR (eGFR) of ≥60 ml/min/1.73 m2. Over a median follow-up of 35 months, 3% of the participants (n = 27,959) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than twofold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of ≥60 ml/min/1.73 m2, as compared with those with eGFR of 45-59.9 ml/min/1.73 m2 and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs. 2.9 [95% CI, 2.7-3.0] per 1,000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1,000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level.
Conclusions: The authors concluded that risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
Perspective: Proteinuria and eGFR are two ‘independent’ (i.e., they do not go hand in hand) indicators of renal disease, and this study suggests that when both are abnormal, poorer outcomes, including all-cause mortality, progression to kidney failure, and acute myocardial infarction, are more likely to occur. The CHARM study suggested that proteinuria (spot urinary albumin-to-creatinine ratio) is an important prognostic predictor in patients with heart failure (Lancet 2009;374:543-550). Clearly the next step is to prevent target-organ damage, particularly prevention and control of diabetes and hypertension. The MICRO-HOPE (Lancet 2000;355:253-259) study suggested that angiotensin-converting enzyme inhibitor therapy with ramipril in diabetics is associated with a lower incidence of nephropathy. Ragavendra R. Baliga, M.B.B.S.

Title: N-Terminal Pro–B-Type Natriuretic Peptide-Guided Treatment for Chronic Heart Failure: Results From the BATTLESCARRED (NT-proBNP–Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) Trial
Topic: Heart Failure/Transplant
Date Posted: 2/2/2010
Author(s): Lainchbury JG, Troughton RW, Strangman KM, et al.
Citation: J Am Coll Cardiol 2010;55:53-60.
Clinical Trial: yes
Study Question: What are the effects of N-terminal pro–B-type natriuretic peptide (NT-proBNP)-guided therapy on clinical outcomes in heart failure (HF)?
Methods: The study cohort included 364 HF patients admitted to a single hospital for HF. The investigators randomly allocated 1:1:1 (stratified by age) to therapy guided by NT-proBNP levels or by intensive clinical management, or according to usual care (UC). The therapeutic strategies were applied for 2 years, with a follow-up period of 3 years.
Results: The investigators found that 1-year mortality was less in both the NT-proBNP- (9.1%) and clinically-guided (9.1%) groups compared with UC (18.9%; p = 0.03). Three-year mortality was selectively reduced in patients ≤75 years of age receiving NT-proBNP–guided therapy (15.5%) compared with their peers receiving either clinically managed treatment (30.9%; p = 0.048) or UC (31.3%; p = 0.021).
Conclusions: The authors concluded that intensive management of HF improves 1-year mortality compared with UC. Compared with clinically guided treatment and UC, NT-proBNP–guided treatment selectively improves longer-term mortality in patients ≤75 years of age.
Perspective: This is an important study because it supports the findings from the STARS-BNP study, which showed that titrating BNP therapy to <100 pg/ml reduced the composite endpoint of mortality and hospitalization due to HF compared with guideline-directed therapy. Ragavendra R. Baliga, M.B.B.S.

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Title: A Double-Blind, Randomized Study on Prevention and Existence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment
Topic: Interventional Cardiology
Date Posted: 2/1/2010 5:00:00 PM
Author(s): Sibbing D, Stegherr J, Braun S, et al.
Citation: J Am Coll Cardiol 2010;55:558-565.
Clinical Trial: No
Study Question: What is the evidence that a platelet rebound exists, and can it be attenuated by clopidogrel tapering?
Methods: Patients (n = 69) receiving clopidogrel treatment due to prior drug-eluting stent placement and planning to stop clopidogrel were recruited in a double-blind, randomized trial. Patients were randomized to either receive a prespecified tapering regimen (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was assessed with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after randomization. The primary endpoint was the highest value of adenosine diphosphate–induced PA measured with LTA in the weeks after complete cessation of clopidogrel in both groups.
Results: The highest values of adenosine diphosphate–induced PA after complete cessation of clopidogrel were similar between both groups (p = 0.21 with LTA, and p = 0.55 with MEA).
Conclusions: The authors concluded that tapering of clopidogrel does not result in lower platelet aggregation values after clopidogrel withdrawal.
Perspective: The primary finding of the study is that a tapering of clopidogrel treatment, as compared with abrupt cessation of the drug, does not result in significantly lower platelet aggregation values in the time period after complete cessation of clopidogrel treatment. Overall, the course of platelet aggregation values after clopidogrel cessation does not support the existence of a rebound phenomenon of platelets after discontinuation of clopidogrel. The clinical safety and efficacy of abrupt versus tapered interruption of chronic clopidogrel therapy after DES implantation is being addressed in the ISAR-CAUTION trial, and will provide additional clinical insight on the optimal method to discontinue clopidogrel therapy. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Endothelial Function, Carotid-Femoral Stiffness, and Plasma Matrix Metalloproteinase-2 in Men With Bicuspid Aortic Valve and Dilated Aorta
Topic: Noninvasive Cardiology
Date Posted: 2/8/2010 5:00:00 PM
Author(s): Tzemos N, Lyseggen E, Silversides C, et al.
Citation: J Am Coll Cardiol 2010;55:660-668.
Clinical Trial: No
Study Question: What is the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV)?
Methods: Thirty-two men (median age 31 years [range 28-32 years]) with nonstenotic BAV were categorized into two subgroups according to proximal ascending aorta dimensions (nondilated ≤35 mm and dilated ≥40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia, and carotid–femoral pulse wave velocity were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively.
Results: Despite similar severity of aortic stenosis, and left ventricular mass and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4-6%] vs. 8% [IQR 7-9%] change, p = 0.001), higher carotid–femoral pulse wave velocity (9.3 cm/s [IQR 9-10 cm/s] vs. 7 cm/s [IQR 6.9-7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460-1,674] vs. 1,036 [IQR 962-1,167], p = 0.001) compared to men with BAV and nondilated aorta.
Conclusions: The authors concluded that young men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid–femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention.
Perspective: BAV is the most common congenital heart malformation, occurring in 1-2% of the population. In addition to valvular dysfunction, BAV is associated with dilatation of the aortic root, which can lead to aortic dissection and rupture. The reason for this association is not clear and does not appear to be related to the degree of valvular dysfunction. The current study demonstrates that systemic changes in vascular function and stiffness, along with evidence of increased metalloprotease activity, are present in subjects with BAV and root dilatation. Additional confirmatory studies in a broader population (including women and patients with more stenotic BAV), along with genome-wide analyses, may lead to identification of novel biomarkers and treatment strategies for patients with BAV. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Cardiovascular Magnetic Resonance in Patients With Myocardial Infarction: Current and Emerging Applications
Topic: Noninvasive Cardiology
Date Posted: 2/2/2010
Author(s): Kim HW, Farzaneh-Far A, Kim RJ.
Citation: J Am Coll Cardiol 2009;55:1-16.
Clinical Trial: No
Perspective: This is a state-of-the-art review of the role of cardiac magnetic resonance imaging (CMR) in patients with acute and chronic myocardial infarction (MI). Ten points to remember include:

1. MI is a leading cause of morbidity and mortality for which a broad range of ever-changing therapeutic and diagnostic options are available. Outcomes are directly related to MI size. Similarly, diagnostic tests for detection of MI are also dependent on a critical mass of involved myocardium for detection. Current recommendations suggest a combination of electrocardiographic, enzymatic, and imaging techniques including CMR, echocardiography, and radionuclide imaging to establish the diagnosis.

2. CMR is a multi-technique imaging modality dependent on both hardware and software for acquisition. Acquisition software can be modified with different pulse sequences to obtain different unique and nonoverlapping data. A comprehensive CMR exam will include multiple pulse sequences designed to define cardiac anatomy and blood flow and to detect thrombus, infarction, perfusion, etc. Many CMR artifacts are specific to the pulse sequence utilized and, as such, will not be present on all images.

3. Commonly used CMR techniques include cine imaging for cardiac function, determination of ventricular volumes, and left ventricular mass as well as valvular morphology. CMR determined chamber size and mass are highly accurate and reproducible.

4. Other CMR techniques include specific imaging for acute myocardial injury as well as perfusion imaging at stress and with rest.

5. Use of gadolinium contrast for delayed imaging is a highly specific marker of MI. Gadolinium is excluded from normal, active myocytes and is sequestered in the interstitium. As such, when detected late after injection, it is a marker of nonviable areas of myocardium, but is not necessarily specific for ischemic heart disease.

6. The specific pattern of late gadolinium enhancement may allow a more specific diagnosis. The effects of coronary occlusion, typically spread in a wavefront from the endocardium to the epicardium and a matching pattern of gadolinium hyperenhancement, may be specific for the effects of coronary occlusion. Other diseases, such as acute myocarditis, present with patchy or mid-myocardial enhancement.

7. The spatial resolution of delayed enhancement (DE)-CMR is exceptionally high and in the clinical setting allows detection of MI involving as little as 1 g of myocardium. In comparison, wall motion abnormalities detected with echocardiography or other techniques will be dependent on a threshold of subendocardial involvement, and SPECT imaging may require >10 g of myocardial involvement before an abnormality is reliably detected.

8. In addition to detecting both acute and chronic MI, CMR may be useful for detecting complications such as aneurysm formulation, right ventricular involvement, pericarditis, and left ventricular thrombus.

9. Using DE-CMR as a marker for MI, a substantial number of clinically and electrocardiographically silent MIs are detected. DE-CMR detects 2-3 times more clinically occult MIs than does an electrocardiogram.

10. Because of the high spatial resolution and reproducibility of CMR for detecting and quantifying MI, it may serve as an accurate endpoint for clinical trials in which reduction in myocardial size rather than mortality is a surrogate endpoint. It has implications for allowing reduced sample size to be used in clinical trials. William F. Armstrong, M.D., F.A.C.C.

Title: Ginkgo Biloba for Preventing Cognitive Decline in Older Adults: A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 2/5/2010
Author(s): Snitz BE, O’Meara ES, Carlson MC, et al., on behalf of the Ginkgo Evaluation of Memory (GEM) Study Investigators.
Citation: JAMA 2009;302:2663-2670.
Clinical Trial: yes
Study Question: Does the herbal product Ginkgo biloba have an effect on long-term cognitive functioning in older adults?
Methods: The Ginkgo Evaluation of Memory (GEM) study is a randomized, double-blind, placebo-controlled clinical trial of 3,069 community-dwelling participants ages 72-96 years, which was conducted in six academic medical centers in the United States between 2000 and 2008. Median follow-up was 6.1 years. Participants received either twice-daily dose of 120 mg extract of G. biloba (n = 1,545) or identical appearing placebo (n = 1,524). Primary outcome was the rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.
Results: Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory, attention, visuospatial abilities, language, and executive functions. For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups. There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment.
Conclusions: Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.
Perspective: Like the great majority of studies funded by the National Institutes of Health designed to test the value of vitamin and herbal supplements, this excellent study shows no value for ginkgo, which has been taken by at least one third of my older patients over the past 15 years. The cost of the studies has been substantial and seems to have done little to reduce the excessive use and marketing of supplements. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Optimizing Statin Treatment for Primary Prevention of Coronary Artery Disease
Topic: Prevention/Vascular
Date Posted: 2/4/2010
Author(s): Hayward RA, Krumholz HM, Zulman DM, Timble JW, Vijan S.
Citation: Ann Intern Med 2010;152:69-77.
Clinical Trial: No
Study Question: Would a tailored treatment approach compare favorably to a treat-to-target approach for primary prevention of coronary artery disease (CAD)?
Methods: A simulated model of population-level effects was used to compare treat-to-target and tailored treatment approaches to statin therapy. Data sources included statin trials from 1994 to 2009 and nationally representative CAD risk factor data. The target population was U.S. persons ages 30-75 years with no history of myocardial infarction. Tailored treatment was based on a person’s 5-year CAD risk (simvastatin, 40 mg, for 5-15% CAD risk; and atorvastatin, 40 mg, for CAD risk >15%) versus treat-to-target approaches that escalate statin dose per National Cholesterol Education Program (NCEP) III guidelines (including an intensive approach that advances treatment whenever intensification is optional by NCEP III criteria). Outcomes included lifetime effects of 5 years of treatment, as measured by quality-adjusted life-years (QALYs) from a societal and patient perspective.
Results: The standard NCEP III treat-to-target approach would recommend that 37.9 million U.S. persons should receive statins, of which 7.9 million should receive high dose–potency therapy. Compared with no treatment, the standard NCEP III approach was estimated to save 48 QALYs per 1,000 persons treated for 5 years, resulting in about 1.83 million total QALYs saved in the United States. Compared with the standard NCEP III approach, the intensive NCEP III approach treated 15 million more persons and saved 570,000 more QALYs over 5 years. The tailored strategy treated a similar number of persons, as did the intensive NCEP III approach, but saved 500,000 more QALYs and treated fewer persons with high-dose statins. No circumstances were found in which a treat-to-target approach was preferable to tailored treatment.
Conclusions: A tailored treatment strategy prevents more CAD events while treating fewer persons with high-dose statins than low-density lipoprotein cholesterol–based target approaches. Results were robust, even with assumptions favoring a treat-to-target approach.
Perspective: I suspect there are two patterns of statin use in the United States. One group of physicians and their patients underuse and underdose, and the other is aggressive, sometimes overtreating, but usually appropriate dosing in patients at high risk. Very few actually use the guidelines. The approach suggested by Rod Hayward may underestimate the value of a tailored but simple treatment strategy, which might be benefited by further risk stratification with a coronary calcium score in middle-aged and older men and women. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Fulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in Children
Topic: Heart Failure/Transplant
Date Posted: 2/10/2010 5:00:00 PM
Author(s): Bratincsak A, El-Said HG, Bradley JS, Shayan K, Grossfeld PD, Cannavino CR.
Citation: J Am Coll Cardiol 2010;Feb 10:[Epub ahead of print].
Clinical Trial: No
Study Question: Is fulminant myocarditis associated with pandemic H1N1 influenza A virus in children?
Perspective: Acute myocarditis is a well-described manifestation of numerous viral infections, and may present with a broad spectrum of symptoms and clinical features. Fulminant myocarditis is thought to be rarely associated with influenza A and may present with fatal arrhythmias, high grade atrioventricular block, and even cardiogenic shock. The true prevalence of influenza-associated fulminant myocarditis is not known because of the lack of comprehensive screening, with only a few cases reported in the literature. The four documented cases of myocarditis in the current study, and other prior reports, raise the concern that the novel H1N1 influenza A virus may be more commonly associated with a severe form of myocarditis than previously seen influenza strains. These observations warrant a high index of clinical suspicion for myocarditis in children with H1N1 influenza A infection. Early diagnosis and rapid intervention with circulatory support may decrease morbidity and mortality, with the potential for saving myocardium and lives. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Altitude and the Heart: Is Going High Safe for Your Cardiac Patient?
Topic: General Cardiology
Date Posted: 2/8/2010
Author(s): Higgins JP, Tuttle T, Higgins JA.
Citation: Am Heart J 2010;159:25-32.
Clinical Trial: No
Perspective: Ease of travel and an interest in high altitude recreation exposes patients to the acute physiologic effects of high altitude and lower oxygen availability. Acute exposure to high altitude is associated with significant alterations to the cardiovascular system, with acute hypoxia, increased myocardial work, increased epinephrine release, and increased pulmonary artery pressures. This review summarized the physiology and clinical evidence regarding acute altitude exposure on the cardiopulmonary system, and made practical recommendations for patients with cardiovascular disease. Points to remember are:

1. Environmental changes when moving from sea level to high altitude include reductions in atmospheric pressure, oxygen pressure, humidity, and temperature. Significant changes typically begin at about 2500 m (8200 ft). The effect on patients depends on the degree of hypoxia, change in elevation, rate of ascent, level of acclimatization, exercise intensity at altitude, age, and genetics.

2. Moderate altitude is defined as 1500-2500 m (4950-8250 ft). High altitude is defined as >2500 m (8250 ft).

3. The acute cardiopulmonary effects of altitude include:
Tissue hypoxia, as a result of the significant decrease in oxygen availability in inspired air. Pulmonary vascular resistance increases 50-300%.
Initial hyperventilation leads to respiratory alkalosis that transiently shifts leftward the oxygen-hemoglobin dissociation curve. (After a few hours, increased red cell production of 2,3-diphosphoglycerate shifts the curve back to the right.)
Heart rate increased at rest. There is only a minimal reduction in resting stroke volume, but a decrease in maximal heart rate response lowers peak cardiac output.
A reduction in plasma volume caused by increased respiratory, urinary, and cutaneous losses. The resulting increased hematocrit is responsible for higher oxygen-carrying capacity per unit blood volume, helping maintain resting stroke volume.
Parasympathetic nervous system deactivation, with predomination of sympathetic nervous responses.
Glycogenolysis stimulated by the increase in epinephrine, causing increased use of glucose at rest and with exercise, and increased blood lactate levels.

4. Coronary artery disease. The acute physiological changes associated with high altitude result in earlier onset of ischemia and symptomatic angina in patients with coronary artery disease, and at a lower pressure-rate product.

5. Heart failure. Increased sympathetic activity results in vasoconstriction and tachycardia, as well as release of inflammatory mediators. Increased sympathetic activity results in increased heart rate and systemic vascular resistance. Pulmonary vasoconstriction leads to pulmonary hypertension (exacerbated with exercise), probably the most significant factor in reducing cardiopulmonary performance at altitude in patients with heart failure.

6. High altitude pulmonary edema. High-altitude (noncardiogenic) pulmonary edema affects unacclimatized people with a genetic predisposition, typically within 4 days of arriving at altitude. Causes are probably multifactorial, including pulmonary vascoconstriction leading to increased intravascular pressure.
Slow ascent serves as a preventative measure. (For ascent >3050 m [10,000 ft], ascent should be ≤305 m [1000 ft] daily with a rest every 1000 m [3300 ft].)
If suspected, immediate descent and administration of supplemental oxygen is the treatment of choice.
Nifedipine (sustained release 20-30 mg orally q 6 to 12 h) can both prevent and treat high-altitude pulmonary edema.
Tadalafil 10 mg bid or sildenafil 50 mg q 8h can be used to prevent high-altitude pulmonary edema, but treatment doses have not been established.

7. Arrhythmia. Increased sympathetic activity associated with high altitude can increase the frequency and duration of supraventricular and ventricular arrhythmias with or without underlying heart disease.

8. Congenital heart disease. In simple uncomplicated congenital heart disease (including atrial septal defect, restrictive ventricular septal defects, and patent ductus arteriosus), arterial oxygen desaturation can occur at high altitude when the usual left-to-right shunting of blood reverses, owing to increased right-sided pressures.

9. Recommendations for all people. The following recommendations apply to all individuals who plan to ascend to high altitude and/or exercise at elevation:
Limit activity to a lower maximal level than at sea level.
Raise sleeping altitude gradually.
At least moderate physical conditioning at sea level is encouraged before exercise at altitude.
Alcohol consumption should be minimized, and hydration should be maintained.
If cardiac status is unknown, exercise testing can be considered prior to travel.

10. Recommendations for patients with cardiovascular disease. The following recommendations apply to individuals with known cardiovascular disease who plan to ascend to high altitude and/or exercise at elevation:
Patients with unstable cardiac disease (unstable angina, uncontrolled ventricular arrhythmias, decompensated heart failure) should not exercise at high altitude.
Patients with severe cardiac diseases (including severe angina, heart failure, or valve disease) should not ascend to high altitude. Patients should avoid traveling to high altitude for 14 days after an acute coronary event. Patients with stable heart disease should limit physical activity for the first few days after ascent. Patients should be advised that they could become symptomatic at lower workloads when at altitude. Patients with prior high-altitude pulmonary edema and known intracardiac shunt should be advised to avoid travel to high altitude. Patients with pacemakers can safely travel to high altitude with no impact on ventricular stimulation thresholds.
David S. Bach, M.D., F.A.C.C.

Importance of MOC
Prevention of Torsades de Pointes in Hospital Settings
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Title: Endovascular Aortic Repair Versus Open Surgical Repair for Descending Thoracic Aortic Disease: A Systematic Review and Meta-Analysis of Comparative Studies
Topic: Cardiovascular Surgery
Date Posted: 2/3/2010 5:00:00 PM
Author(s): Cheng D, Martin J, Shennib H, et al.
Citation: J Am Coll Cardiol 2010;Feb 3:[Epub ahead of print].
Clinical Trial: No
Study Question: Does thoracic endovascular aortic repair (TEVAR) reduce death and morbidity compared with open surgical repair for descending thoracic aortic disease?
Methods: Data from 42 studies (four multicenter, 35 single center, and three registries) of TEVAR versus open repair of the descending aorta were examined by meta-analysis to determine mortality and morbidity rates for each approach. Meta-regression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Registry data were analyzed separately from comparative studies, as these data were thought to be too heterogeneous.
Results: The 42 nonrandomized studies included 5,888 patients. Patient characteristics were balanced, except that patients undergoing TEVAR tended to be older (p < 0.001). In comparative studies, all-cause mortality at 30 days (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.33-0.59) and paraplegia (OR, 0.42; 95% CI, 0.28-0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction (MI), aortic reintervention, and mortality at 2-3 years. Meta-regression to adjust for age imbalance, study design, and pathology did not materially change the results. Registry data suggested that overall perioperative complications were reduced. However, registry data did not demonstrate alterations in 30-day, 1-year, and 2- to 3-year mortality, or any of the single complications (stroke, acute MI, renal failure, ischemia to the gut or limb) examined.
Conclusions: This meta-analysis suggests that TEVAR reduces early mortality, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Moderate-term follow-up (2-3 years) failed to show a sustained survival benefit.
Perspective: I suspect anyone who performs or performed open and TEVAR for thoracic aortic aneurysms (TAAs) recognizes that short-term mortality and morbidity is lower in patients undergoing TEVAR. Importantly, of all the devastating complications associated with TAA repair, paraplegia risk is reduced almost 58%. The fact that no sustained benefit is obtained is likely due to one of two reasons: 1) the small collection of studies with moderate-term follow-up were underpowered to show a difference, or 2) the patients die from nonthoracic aortic disease (i.e., MIs). Even more so than endovascular repair of abdominal aortic aneurysms, TEVAR will completely dominate the landscape of repair over the next decade. Gilbert Upchurch, Jr., M.D.

Title: Laparoscopic Adjustable Gastric Banding in Severely Obese Adolescents: A Randomized Trial
Topic: Congenital Heart Disease
Date Posted: 2/11/2010
Author(s): O’Brien PE, Sawyer SM, Laurie C, et al.
Citation: JAMA 2010;303:519-526.
Clinical Trial: yes
Study Question: Is gastric banding comparable to optimal lifestyle intervention for weight loss among severely obese adolescents?
Methods: This was a prospective randomized controlled trial of adolescents (ages 14-18 years) comparing supervised lifestyle intervention or gastric banding. All subjects were severely obese, with a body mass index (BMI) greater than 35 kg/m2. Follow-up continued for 2 years, with a main outcome of weight loss. Secondary outcomes included changes in metabolic syndrome, insulin resistance, quality of life, and adverse outcomes.
Results: A total of 24 of the 25 subjects who received gastric banding and 18 of the 25 subjects who received supervised lifestyle modification completed the study. More gastric banding patients lost >50% of excess weight (corrected for age), as compared to the lifestyle intervention patients (84% vs. 12%). Mean weight change in the gastric banding group was 34.6 kg of weight loss (95% confidence interval [CI], 30.2-39.0%), representing an excess weight loss of 78.8% (95% CI, 66.6-91.0%) or 12.7 BMI units (95% CI, 11.3-14.2). The mean weight loss in the lifestyle intervention group was 3.0 kg (95% CI, 2.1-8.1), representing an excess weight loss of 13.2% (95% CI, 2.6%-21.0%) or 1.3 BMI units (95% CI, 0.4-2.9). At the end of the 2-year follow-up, no subjects in the gastric banding group had the metabolic syndrome, compared to 4 of the 18 completers in the lifestyle group. Improved quality of life was also observed among subjects who underwent gastric banding; however, seven patients required revisional procedures during the follow-up period.
Conclusions: The investigators concluded that among severely obese adolescents, gastric banding was associated with significant long-term weight loss and improvement in metabolic syndrome criteria.
Perspective: This study suggests that gastric banding is a potential therapy for adolescents who require significant weight loss. Larger-scale studies are warranted, which includes data on adverse effects after such procedures. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Standards of Medical Care in Diabetes—2010
Topic: General Cardiology
Date Posted: 2/12/2010
Author(s): American Diabetes Association.
Citation: Diabetes Care 2010;33:S11-S61.
Clinical Trial: No
Perspective: The following are 10 points to remember about standards of medical care in diabetes:

1. Criteria for the diagnosis of diabetes now include glycated hemoglobin (HbA1C) ≥6.5%. The testing should be performed in a National Glycohemoglobin Standardization Program–certified lab. Other criteria include fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/L), 2-hour plasma glucose ≥200 mg/dl (11.1 mmol/L) during an oral glucose tolerance testing (OGTT) (protocol defined by World Health Organization), or if a patient has symptoms of hyperglycemia and a random plasma glucose of ≥200 mg/dl. (Note that conditions of abnormal red cell turnover reduce accuracy of HbA1C; then glucose criteria should be used.)

2. Categories of increased risk for development of diabetes include impaired FPG (100-125 mg/dl [5.6-6.9 mmol/L]) or impaired OGTT (140-199 mg/dl [7.8-11.0 mmol/L]). Such patients should have structured lifestyle interventions to improve diet and physical activity and promote weight loss if warranted.

3. Criteria for testing for diabetes in asymptomatic adults include body mass index (BMI) ≥25 kg/m2 and additional risk factors such as physical inactivity, first-degree relative with diabetes, member of a high-risk ethnic group (African-American, Latino, Native American, Asian American, Pacific Islander), women diagnosed with gestational diabetes or who delivered babies >9 lbs., medical history of hypertension or blood pressure ≥140/90 mm Hg, high-density lipoprotein cholesterol <35 mg/dl and/or triglycerides >250 mg/dl, women with polycystic ovarian syndrome, HbA1C ≥5.7 or impaired fasting glucose on prior testing, conditions associated with diabetes (severe obesity, acanthosis nigrans), or history of CVD. If no risk factors, then testing is recommended after the age of 45 years. If testing is normal, repeat testing at 3-year intervals is recommended, with more frequent testing for those at increased risk or with borderline prior test results.

4. Women with gestational diabetes mellitus should be screened for diabetes at 6-12 weeks postpartum. Women at risk for gestational diabetes include those with severe obesity, prior history of gestational diabetes, polycystic ovarian syndrome, or a strong family history of diabetes. Women with those risk factors should be screened for gestational diabetes at the first prenatal visit.

5. Prevention and delay of type 2 diabetes include weight loss with recommended moderate physical activity of 150 minutes/week or greater (50-70% of maximum heart rate). Lifestyle counseling should also include nutritional advice, follow-up counseling to support these behavioral changes, and yearly monitoring for development of diabetes.

6. Recommendations for glycemic control in nonpregnant adults with diabetes include an HbA1C <7.0%, preprandial plasma glucose between 70 and 130 mg/dl (3.9-7.2 mmol/L), and peak postprandial plasma glucose 180 mg/dl (<10.0 mmol/L). HbA1C is the primary target for glycemic control and should be tested at least two times per year or at least quarterly in patients who are not at goal or whose therapy has changed.

7. Dietary recommendations for adults with diabetes include saturated fat intake <7% of total calories, minimal intake of trans fats, monitoring intake of carbohydrates, and digestible carbohydrates of 130 g/day. Meal planning can assist patients with adhering to these recommendations. Routine supplementation with antioxidants such as vitamin E, vitamin C, or carotene is not recommended.

8. Bariatric surgery should be considered for adults with a BMI >35 kg/m2 and type 2 diabetes, especially if comorbidities exist, which limit lifestyle modifications and/or pharmacologic therapy. Long-term benefits and cost-effectiveness including risks of bariatric surgery should be studied further in large populations of diabetics.

9. Psychosocial assessment should be included in ongoing management of diabetes. Screening for depression or other psychological problems including eating disorders or cognitive impairment is recommended when self-management is poor.

10. Other processes of care include an annual influenza vaccination and pneumococcal vaccination, blood pressure control goal of <130/80 mm Hg, and statin therapy (regardless of lipid levels) for diabetes with CVD, or without CVD over the age of 40 and with one or more risk factors. Goal LDL is <100 mg/dl (<2.6 mmol/l; <70 mg/dl if history of CVD is an option). Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Jet Lag
Topic: General Cardiology
Date Posted: 2/12/2010
Author(s): Sack RL.
Citation: N Engl J Med 2010;362:440-447.
Clinical Trial: No
Perspective: The following are 10 points to remember about jet lag:

1. Jet lag is a sleep disorder that results from crossing time zones too rapidly for the circadian clock to keep pace. The latter is normally synchronized to the solar light-dark cycle and promotes alertness during the day and sleep at night. Jet lag is compounded by travel fatigue, dehydration, and prolonged immobility.

2. Symptoms of jet lag include insomnia and daytime sleepiness, as well as dysfunction of mood, and physical and cognitive performance.

3. Melatonin is a hormone secreted for about 10-12 hours at night and is synchronized to the light-dark cycle by the circadian clock.

4. For short trips, jet lag can be minimized by maintaining the home sleep-wake schedule if it is possible, or alternatively for 2 days prior to the flight, shift the sleep schedule by 1-2 hours toward the destination time zone.

5. Treatment for jet lag includes use of appropriate exposure to light, melatonin, or both; supplement as needed with medication to counteract insomnia or daytime sleepiness.

6. In a comparison with melatonin, zolpidem 10 mg was more effective at reducing symptoms of jet lag, but it is not ideal because of duration of action. Upon landing in the new time zone, melatonin 0.5-3 mg may be helpful to promote sleep when traveling west to east.

7. Hypnosedatives need to be used with caution, as they may be expected to further increase the elevated risk for deep vein thrombosis.

8. A short-acting sleeping pill during the flight is preferred, such as zaleplon 5-10 mg. Sedatives should not be combined with alcohol.

9. Prior to and during the trip, hydration will help as well as avoiding caffeine for several hours prior to sleep time. When traveling east to west, seek bright sunlight in the evening; for west to east, seek bright sun in the morning.

10. Increased consumption of caffeinated beverages may counteract daytime sleepiness. An alternative to increase alertness and reduce other symptoms of jet lag my be slow-release caffeine (300 mg). This strategy needs to be weighed against possible increase in insomnia. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Altitude and the Heart: Is Going High Safe for Your Cardiac Patient?
Topic: General Cardiology
Date Posted: 2/8/2010
Author(s): Higgins JP, Tuttle T, Higgins JA.
Citation: Am Heart J 2010;159:25-32.
Clinical Trial: No
Perspective: Ease of travel and an interest in high altitude recreation exposes patients to the acute physiologic effects of high altitude and lower oxygen availability. Acute exposure to high altitude is associated with significant alterations to the cardiovascular system, with acute hypoxia, increased myocardial work, increased epinephrine release, and increased pulmonary artery pressures. This review summarized the physiology and clinical evidence regarding acute altitude exposure on the cardiopulmonary system, and made practical recommendations for patients with cardiovascular disease. Points to remember are:

1. Environmental changes when moving from sea level to high altitude include reductions in atmospheric pressure, oxygen pressure, humidity, and temperature. Significant changes typically begin at about 2500 m (8200 ft). The effect on patients depends on the degree of hypoxia, change in elevation, rate of ascent, level of acclimatization, exercise intensity at altitude, age, and genetics.

2. Moderate altitude is defined as 1500-2500 m (4950-8250 ft). High altitude is defined as >2500 m (8250 ft).

3. The acute cardiopulmonary effects of altitude include:
Tissue hypoxia, as a result of the significant decrease in oxygen availability in inspired air. Pulmonary vascular resistance increases 50-300%.
Initial hyperventilation leads to respiratory alkalosis that transiently shifts leftward the oxygen-hemoglobin dissociation curve. (After a few hours, increased red cell production of 2,3-diphosphoglycerate shifts the curve back to the right.)
Heart rate increased at rest. There is only a minimal reduction in resting stroke volume, but a decrease in maximal heart rate response lowers peak cardiac output.
A reduction in plasma volume caused by increased respiratory, urinary, and cutaneous losses. The resulting increased hematocrit is responsible for higher oxygen-carrying capacity per unit blood volume, helping maintain resting stroke volume.
Parasympathetic nervous system deactivation, with predomination of sympathetic nervous responses.
Glycogenolysis stimulated by the increase in epinephrine, causing increased use of glucose at rest and with exercise, and increased blood lactate levels.

4. Coronary artery disease. The acute physiological changes associated with high altitude result in earlier onset of ischemia and symptomatic angina in patients with coronary artery disease, and at a lower pressure-rate product.

5. Heart failure. Increased sympathetic activity results in vasoconstriction and tachycardia, as well as release of inflammatory mediators. Increased sympathetic activity results in increased heart rate and systemic vascular resistance. Pulmonary vasoconstriction leads to pulmonary hypertension (exacerbated with exercise), probably the most significant factor in reducing cardiopulmonary performance at altitude in patients with heart failure.

6. High altitude pulmonary edema. High-altitude (noncardiogenic) pulmonary edema affects unacclimatized people with a genetic predisposition, typically within 4 days of arriving at altitude. Causes are probably multifactorial, including pulmonary vascoconstriction leading to increased intravascular pressure.
Slow ascent serves as a preventative measure. (For ascent >3050 m [10,000 ft], ascent should be ≤305 m [1000 ft] daily with a rest every 1000 m [3300 ft].)
If suspected, immediate descent and administration of supplemental oxygen is the treatment of choice.
Nifedipine (sustained release 20-30 mg orally q 6 to 12 h) can both prevent and treat high-altitude pulmonary edema.
Tadalafil 10 mg bid or sildenafil 50 mg q 8h can be used to prevent high-altitude pulmonary edema, but treatment doses have not been established.

7. Arrhythmia. Increased sympathetic activity associated with high altitude can increase the frequency and duration of supraventricular and ventricular arrhythmias with or without underlying heart disease.

8. Congenital heart disease. In simple uncomplicated congenital heart disease (including atrial septal defect, restrictive ventricular septal defects, and patent ductus arteriosus), arterial oxygen desaturation can occur at high altitude when the usual left-to-right shunting of blood reverses, owing to increased right-sided pressures.

9. Recommendations for all people. The following recommendations apply to all individuals who plan to ascend to high altitude and/or exercise at elevation:
Limit activity to a lower maximal level than at sea level.
Raise sleeping altitude gradually.
At least moderate physical conditioning at sea level is encouraged before exercise at altitude.
Alcohol consumption should be minimized, and hydration should be maintained.
If cardiac status is unknown, exercise testing can be considered prior to travel.

10. Recommendations for patients with cardiovascular disease. The following recommendations apply to individuals with known cardiovascular disease who plan to ascend to high altitude and/or exercise at elevation:
Patients with unstable cardiac disease (unstable angina, uncontrolled ventricular arrhythmias, decompensated heart failure) should not exercise at high altitude.
Patients with severe cardiac diseases (including severe angina, heart failure, or valve disease) should not ascend to high altitude. Patients should avoid traveling to high altitude for 14 days after an acute coronary event. Patients with stable heart disease should limit physical activity for the first few days after ascent. Patients should be advised that they could become symptomatic at lower workloads when at altitude. Patients with prior high-altitude pulmonary edema and known intracardiac shunt should be advised to avoid travel to high altitude. Patients with pacemakers can safely travel to high altitude with no impact on ventricular stimulation thresholds.
David S. Bach, M.D., F.A.C.C.

Title: N-Terminal Pro–B-Type Natriuretic Peptide–Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure: A 3-Arm, Prospective, Randomized Pilot Study
Topic: Heart Failure/Transplant
Date Posted: 2/12/2010
Author(s): Berger R, Moertl D, Peter S, et al.
Citation: J Am Coll Cardiol 2010;55:645-653.
Clinical Trial: No
Study Question: Does the addition of N-terminal pro–B-type natriuretic peptide (BNP)–guided, intensive patient management (BM) to multidisciplinary care (MC) improve outcome in patients following hospitalization due to heart failure (HF)?
Methods: Hospitalized HF patients were randomized to BM, MC, or usual care (UC). MC included at least two consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse. In addition, BM included intensified up-titration of medication by HF specialists in high-risk patients. The investigators utilized NT-proBNP to define the level of risk and to monitor wall stress. This monitoring also allowed for anticipation of cardiac decompensation and adjustment of medication in advance.
Results: The study cohort was comprised of 278 patients. After 12 months, the BM group had the highest proportion of anti-neurohormonal triple-therapy (difference between all groups). Accordingly, BM reduced days of HF hospitalization (488 days) compared with the hospitalization for the MC (1,254 days) and UC (1,588 days) groups (p < 0.0001; significant differences among all groups). Using Kaplan-Meier analysis, the first HF rehospitalization (28%) was lower in the BM versus MC groups (40%; p = 0.06) and the MC versus UC groups (61%; p < 0.01). Moreover, the combined endpoint of mortality or HF rehospitalization was lower in the BM (37%) than in the MC group (50%; p < 0.05) and in the MC than in the UC group (65%; p = 0.04). Mortality rate was similar between the BM (22%) and MC groups (22%), but was lower compared with the UC group (39%; vs. BM: p < 0.02; vs. MC: p < 0.02).
Conclusions: The study authors concluded that when compared with MC alone, additional BM improves clinical outcome in patients after HF hospitalization.
Perspective: The main advantages of evaluating BNP in HF are for risk stratification, predicting mortality, confirming the diagnosis, and monitoring therapy. The findings of this study support the results of the BATTLESCARRED trial (J Am Coll Cardiol 2010;55:53-60), STARS-BNP trial (J Am Coll Cardiol 2007;49:1733-9), and the STARBRITE study (Am Heart J 2005;150:893-8), that BNP-guided therapy is beneficial, unlike the TIME-CHF study (JAMA 2009;301:383-92). Larger multicenter trials are needed to resolve these disparate results. Ragavendra R. Baliga, M.B.B.S.

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Title: Fulminant Myocarditis Associated With Pandemic H1N1 Influenza A Virus in Children
Topic: Heart Failure/Transplant
Date Posted: 2/10/2010 5:00:00 PM
Author(s): Bratincsak A, El-Said HG, Bradley JS, Shayan K, Grossfeld PD, Cannavino CR.
Citation: J Am Coll Cardiol 2010;Feb 10:[Epub ahead of print].
Clinical Trial: No
Study Question: Is fulminant myocarditis associated with pandemic H1N1 influenza A virus in children?
Perspective: Acute myocarditis is a well-described manifestation of numerous viral infections, and may present with a broad spectrum of symptoms and clinical features. Fulminant myocarditis is thought to be rarely associated with influenza A and may present with fatal arrhythmias, high grade atrioventricular block, and even cardiogenic shock. The true prevalence of influenza-associated fulminant myocarditis is not known because of the lack of comprehensive screening, with only a few cases reported in the literature. The four documented cases of myocarditis in the current study, and other prior reports, raise the concern that the novel H1N1 influenza A virus may be more commonly associated with a severe form of myocarditis than previously seen influenza strains. These observations warrant a high index of clinical suspicion for myocarditis in children with H1N1 influenza A infection. Early diagnosis and rapid intervention with circulatory support may decrease morbidity and mortality, with the potential for saving myocardium and lives. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Perioperative Management of Patients With Drug-Eluting Stents
Topic: Interventional Cardiology
Date Posted: 2/15/2010 5:00:00 PM
Author(s): Abualsaud AO, Eisenberg MJ.
Citation: JACC Cardiovasc Interv 2009;2:131-142.
Clinical Trial: No
Study Question: What is the best strategy for perioperative use of antiplatelet agents in patients with drug-eluting stents (DES) who need to undergo noncardiac surgery to avoid stent thrombosis?
Perspective: The following are 10 points to remember from this state-of-the-art paper about perioperative management of patients with DES:

1. DES are associated with a small, but significant increased risk of late and very late stent thrombosis compared with bare-metal stents.

2. Stent thrombosis is a platelet-mediated phenomenon that usually manifests as sudden death ST-segment elevation myocardial infarction, or malignant arrhythmias. It appears to be associated with a mortality ranging from 9-45%.

3. Premature cessation of dual antiplatelet therapy is the most important predictor of stent thrombosis. Current guidelines support continuation of dual antiplatelet therapy for 12 months after DES implantation.

4. The risk of perioperative stent thrombosis is increased in patients undergoing noncardiac surgery within 6 weeks of stent-based percutaneous coronary intervention (PCI).

5. In patients undergoing noncardiac surgery, continuation of aspirin is associated with a 1.5-fold increase in risk of bleeding while withdrawal of aspirin leads to an increase in cardiac, cerebral, and peripheral vascular events. Dual antiplatelet therapy is associated with an increased risk of bleeding complications.

6. All elective surgical procedures should be delayed by at least 6 months and ideally 12 months after DES placement.

7. Patients undergoing surgical procedures 12 months after PCI are at a lower risk of perioperative stent thrombosis compared with earlier surgery. However, if possible, dual antiplatelet therapy should be continued if bleeding risk is low. If the risk of perioperative bleeding is significantly high, then clopidogrel should be discontinued 5 days before surgery, and aspirin should be maintained. Clopidogrel should be restarted as soon as realistically feasible.

8. In patients with DES, when surgery cannot be delayed beyond a year after PCI and thienopyridine or dual antiplatelet therapy must be discontinued, intravenous small molecule glycoprotein IIb/IIIa inhibitors have been used as bridging therapy preoperatively, followed by early (usually immediately postop) resumption of dual antiplatelet therapy. The efficacy of this strategy has not been definitively proven. Use of heparin, low molecular weight heparin, Coumadin, or fondaparinux as bridge therapy for patients after discontinuing dual antiplatelet therapy is not advisable.

9. Primary PCI is the reperfusion therapy of choice in patients who develop perioperative myocardial infarction due to stent thrombosis.

10. The challenges associated with thienopyridine use could be overcome once ticagrelor is approved for clinical use. Its short half-life and its rapid onset of action would allow patients to discontinue ticagrelor only 1 day before surgery and resume it immediately after surgery, thereby potentially diminishing both the risk of perioperative bleeding and stent thrombosis. This hypothesis is also unproven at this point. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Impact of Femoral Vascular Closure Devices and Antithrombotic Therapy on Access Site Bleeding in Acute Coronary Syndromes: The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial
Topic: Interventional Cardiology
Date Posted: 2/9/2010
Author(s): Sanborn TA, Ebrahimi R, Manoukian SV, et al.
Citation: Circ Cardiovasc Interv 2010;3:57-62.
Clinical Trial: No
Study Question: What is the impact of vascular closure devices (VCDs) on access site bleeding in patients undergoing an early invasive approach for acute coronary syndromes (ACS) and coronary angiography using femoral arterial access?
Methods: The authors assessed the impact of VCD use on access site bleeding (ASB) among 11,621 patients undergoing femoral angiography in the ACUITY trial. The ACUITY trial randomized patients with ACS to receive heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus GPI, or bivalirudin monotherapy in an open-label fashion. Major ASB was defined as ASB requiring interventional or surgical correction, hematoma ≥5 cm at the access site, retroperitoneal bleeding, or hemoglobin drop ≥3 g/dl with ecchymosis or hematoma <5 cm, oozing blood, or prolonged bleeding (>30 minutes) at the access site.
Results: A VCD was used in 4,307 (37.1%) patients, and 7,314 (62.9%) had manual compression. The rate of ASB was lower in patients treated with VCD (2.5% vs. 3.3%, relative risk, 0.76; 95% confidence interval [CI], 0.61-0.94; p = 0.01). Rates of bleeding were lowest in patients treated with bivalirudin monotherapy and a VCD (0.7%). After adjusting for differences in baseline variables, both VCD use (odds ratio, 0.78; 95% CI, 0.61-0.99; p = 0.04) and bivalirudin monotherapy (odds ratio, 0.35; 95% CI, 0.25-0.49; p < 0.0001) were both independently associated with freedom from ASB.
Conclusions: Use of VCD was associated with a reduced rate of ASB in patients with ACS undergoing an early invasive approach.
Perspective: There are no large well-designed randomized trials supporting a reduction in bleeding events with VCDs. Prior meta-analyses suggest worse outcome with VCDs, whereas observational studies suggest better outcomes in patients treated with VCDs. It is not clear whether the findings of the current study reflect inability to adjust for confounding or are truly reflective of better outcomes with VCDs. The most effective strategy for reducing access site bleeding complications is radial access, and this strategy should be considered in all patients at risk for ASB. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Comparison of Ticagrelor With Clopidogrel in Patients With a Planned Invasive Strategy for Acute Coronary Syndromes (PLATO): A Randomised Double-Blind Study
Topic: Interventional Cardiology
Date Posted: 2/10/2010
Author(s): Cannon CP, Harrington RA, James S, et al., on behalf of the PLATelet inhibition and patient Outcomes (PLATO) Investigators.
Citation: Lancet 2010;375:283-293.
Clinical Trial: yes
Study Question: What is the relative efficacy and safety of ticagrelor compared with clopidogrel in patients undergoing an early invasive approach for acute coronary syndromes (ACS)?
Methods: The authors reported the outcome of 13,408 patients who were treated with a planned invasive strategy for an ACS and were enrolled in the PLATO trial. In this trial, patients were randomly assigned in a double dummy fashion to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were also treated with aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction (MI), or stroke.
Results: PCI was performed in 76.8% of the cohort and coronary artery bypass grafting in 5.8%. The primary composite endpoint at 1 year was less frequent in the ticagrelor group compared with the clopidogrel group (9.0% vs. 10.7%; hazard ratio, 0.84; 95% confidence interval, 0.75-0.94; p = 0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (11.6% vs. 11.5%, p = 0.8803) or GUSTO severe bleeding (3.2% vs. 2.9%, p = 0.3785). All-cause mortality was lower with ticagrelor (3.9% vs. 5.0%, p = 0.0103).
Conclusions: Ticagrelor seems to be preferable to clopidogrel for patients with ACS, for whom an early invasive strategy is planned.
Perspective: Ticagrelor is a reversible and direct-acting oral P2Y12- receptor antagonist with rapid onset and offset of action. It is a more potent platelet inhibitor compared with clopidogrel, and has demonstrated a reduction in ischemic events with no increase in bleeding over contemporary therapy. While the reduction in mortality may be a chance finding (there was no adjustment for multiple testing), the trends in both MI and death favor ticagrelor. This drug may displace the use of thienopyridines in patients with ACS. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Stent Graft Versus Balloon Angioplasty for Failing Dialysis-Access Grafts
Topic: Interventional Cardiology
Date Posted: 2/10/2010 5:00:00 PM
Author(s): Haskal ZV, Trerotola S, Dolmatch B, et al.
Citation: N Engl J Med 2010;362:494-503.
Clinical Trial: yes
Study Question: What is the benefit of using polytetrafluoroethylene (PTFE) stent graft compared with balloon angioplasty only for treating patients with venous anastomosis stenosis associated with hemodialysis grafts?
Methods: The authors randomized 190 patients who had venous anastomosis stenosis to undergo angioplasty only versus treatment with a PTFE stent graft. Primary endpoint was patency of the access site at 6 months.
Results: Randomization to stent graft was associated with better patency of the treatment site (51% vs. 23%, p < 0.001) and patency of the access circuit (38% vs. 20%, p = 0.008). Binary restenosis was much greater with angioplasty (78% vs. 28%, p < 0.001). The stent graft arm was more likely to be free of need for subsequent intervention at 6 months.
Conclusions: Stent grafting is superior to balloon angioplasty only for the treatment of venous anastomosis stenosis associated with hemodialysis grafts.
Perspective: Dialysis access using prosthetic grafts is inferior to autogenous arterio-venous fistulas due to the high incidence of graft failure. Venous anastomosis stenosis is a recalcitrant problem and is responsible for a large proportion of graft failures. Balloon angioplasty has been traditionally used for these lesions, although it has been plagued with a high restenosis rate. This trial has established stent grafts as the current standard of care for these lesions even though the recurrence rate with stent grafts still remains unacceptably high. Further research is needed to identify effective therapeutic strategies that can be used to further reduce restenosis in these lesions. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Physical Activity and Physiological Cardiac Remodelling in a Community Setting: The Multi-Ethnic Study of Atherosclerosis (MESA)
Topic: Noninvasive Cardiology
Date Posted: 2/9/2010
Author(s): Turkbey EB, Jorgensen NW, Johnson WC, et al.
Citation: Heart 2010;96:42-48.
Clinical Trial: No
Study Question: Is there an association between physical activity and left ventricular (LV) structure and function in the general population in a community setting?
Methods: Subjects included 4,992 multiethnic participants (age 45-84 years; 52% women) free of clinically apparent cardiovascular disease enrolled in a cross-sectional population-based study of subclinical atherosclerosis (The Multi-Ethnic Study of Atherosclerosis [MESA]). LV mass, volumes, and function were assessed by cardiac magnetic resonance imaging. Physical activity, defined as intentional exercise and total moderate and vigorous physical activity, was assessed by a standard semi-quantitative questionnaire.
Results: LV mass and end-diastolic volume were positively associated with physical activity (1.4 g/m2 [women] and 3.1 g/m2 [men] greater LV mass in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p = 0.05 and p < 0.001, respectively). Relationships were nonlinear, with stronger positive associations at lower levels of physical activity (test for nonlinearity; p = 0.02 and p = 0.03, respectively). Cardiac output and ejection fraction were unchanged with increased physical activity levels. Resting heart rate was lower in women and men with higher physical activity levels (22.6 bpm lower resting heart rate in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p < 0.001).
Conclusions: In a community-based population free of clinically apparent cardiovascular disease, higher physical activity levels were associated with proportionally greater LV mass and end-diastolic volume and lower resting heart rate.
Perspective: Predominantly studied in high-performance athletes, the ‘athlete’s heart’ has adapted to intense physical training with increased LV end-diastolic diameter, increased myocardial mass, and decreased resting heart rate. This study reveals that, among active individuals not trained as elite athletes, higher levels of physical activity are associated with cardiac changes similar to those seen with more intense training. It is important to note that increased LV mass, associated with increased cardiovascular risk among patients with hypertension, appears benign (or even beneficial) when it is acquired with physical activity. The known inverse relationship between moderate to vigorous physical activity and risk for premature death and other cardiovascular diseases occurs despite what is shown in this study. An increased LV mass, in other scenarios, would raise concern. David S. Bach, M.D., F.A.C.C.

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Title: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy
Topic: Noninvasive Cardiology
Date Posted: 2/15/2010
Author(s): Oyenuga O, Hara H, Tanaka H, et al.
Citation: JACC Cardiovasc Imaging 2009;2:1190-8.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy

Study Question: Does echocardiographic dyssynchrony assist in the selection of patients with borderline QRS duration for cardiac resynchronization therapy (CRT)?
Methods: Of 221 consecutive heart failure patients with a left ventricular ejection fraction (LVEF) ≤35% referred for CRT, 135 patients had increased QRS duration (>130 ms; 168 ± 26 ms) and 86 had a borderline increase in QRS duration (100-130 ms; 115 ± 8 ms). Dyssynchrony was assessed using interventricular mechanical delay, tissue Doppler imaging longitudinal velocity opposing wall delay, and speckle tracking radial strain for septal to posterior wall delay. Response to CRT was defined as ≥15% increase in EF, and reverse remodeling as ≥10% decrease in end-systolic volume.
Results: There were 201 patients with baseline quantitative echocardiographic data available, and 187 with follow-up data available 8 ± 5 months after CRT. A smaller proportion of borderline QRS duration patients (53%) were EF responders compared with 75% with widened QRS (p < 0.05). Interventricular mechanical delay ≥40 ms and opposing wall delay ≥65 ms were predictive of EF response in the wide QRS interval group, but not the borderline QRS duration group. However, speckle tracking radial dyssynchrony ≥130 ms was predictive of EF response in both wide QRS patients (88% sensitivity, 74% specificity) and borderline QRS patients (79% sensitivity, 82% specificity), and was associated with reverse remodeling with reduction in LV end-systolic volume (p < 0.0005).
Conclusions: Radial dyssynchrony by speckle tracking strain was associated with both EF and reverse remodeling responses to CRT in patients with borderline QRS duration, and has the potential to assist with patient selection.
Perspective: Among symptomatic patients with LV systolic dysfunction, CRT is associated with benefit in both symptoms and survival. However, as many as 30% of patients treated are ‘nonresponders,’ showing no demonstrable improvement after CRT. Current selection criteria for CRT include the presence of symptomatic heart failure, LV systolic dysfunction, and QRS prolongation. Although echocardiography has clear utility in the evaluation of LV mechanical dyssynchrony, it is not currently recommended for purposes of patient selection for CRT. Further, although a variety of measures of dyssynchrony can be examined on echocardiography, there is no consensus as to whether any one method has greater utility in predicting response to CRT. In this study, fewer patients with borderline QRS were responders than were patients with more prolonged QRS duration; however, echocardiographic assessment of radial dyssynchrony by speckle tracking had predictive power in determining response to CRT among patients with borderline QRS prolongation. Although echocardiography may not be needed for patient selection among those with QRS duration >130 ms, these data suggest that it could play a useful role among patients with heart failure, LVEF ≤35%, and borderline QRS prolongation. David S. Bach, M.D., F.A.C.C.

Title: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy
Topic: Noninvasive Cardiology
Date Posted: 2/15/2010
Author(s): Oyenuga O, Hara H, Tanaka H, et al.
Citation: JACC Cardiovasc Imaging 2009;2:1190-8.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy

Study Question: Does echocardiographic dyssynchrony assist in the selection of patients with borderline QRS duration for cardiac resynchronization therapy (CRT)?
Methods: Of 221 consecutive heart failure patients with a left ventricular ejection fraction (LVEF) ≤35% referred for CRT, 135 patients had increased QRS duration (>130 ms; 168 ± 26 ms) and 86 had a borderline increase in QRS duration (100-130 ms; 115 ± 8 ms). Dyssynchrony was assessed using interventricular mechanical delay, tissue Doppler imaging longitudinal velocity opposing wall delay, and speckle tracking radial strain for septal to posterior wall delay. Response to CRT was defined as ≥15% increase in EF, and reverse remodeling as ≥10% decrease in end-systolic volume.
Results: There were 201 patients with baseline quantitative echocardiographic data available, and 187 with follow-up data available 8 ± 5 months after CRT. A smaller proportion of borderline QRS duration patients (53%) were EF responders compared with 75% with widened QRS (p < 0.05). Interventricular mechanical delay ≥40 ms and opposing wall delay ≥65 ms were predictive of EF response in the wide QRS interval group, but not the borderline QRS duration group. However, speckle tracking radial dyssynchrony ≥130 ms was predictive of EF response in both wide QRS patients (88% sensitivity, 74% specificity) and borderline QRS patients (79% sensitivity, 82% specificity), and was associated with reverse remodeling with reduction in LV end-systolic volume (p < 0.0005).
Conclusions: Radial dyssynchrony by speckle tracking strain was associated with both EF and reverse remodeling responses to CRT in patients with borderline QRS duration, and has the potential to assist with patient selection.
Perspective: Among symptomatic patients with LV systolic dysfunction, CRT is associated with benefit in both symptoms and survival. However, as many as 30% of patients treated are ‘nonresponders,’ showing no demonstrable improvement after CRT. Current selection criteria for CRT include the presence of symptomatic heart failure, LV systolic dysfunction, and QRS prolongation. Although echocardiography has clear utility in the evaluation of LV mechanical dyssynchrony, it is not currently recommended for purposes of patient selection for CRT. Further, although a variety of measures of dyssynchrony can be examined on echocardiography, there is no consensus as to whether any one method has greater utility in predicting response to CRT. In this study, fewer patients with borderline QRS were responders than were patients with more prolonged QRS duration; however, echocardiographic assessment of radial dyssynchrony by speckle tracking had predictive power in determining response to CRT among patients with borderline QRS prolongation. Although echocardiography may not be needed for patient selection among those with QRS duration >130 ms, these data suggest that it could play a useful role among patients with heart failure, LVEF ≤35%, and borderline QRS prolongation. David S. Bach, M.D., F.A.C.C.

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TV Time Increases CV Mortality
Culprit or Multivessel PCI in STEMI?
FDA Approves Rosuvastatin for High CRP
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

[Chevychelov]

Title: Statins and Risk of Incident Diabetes: A Collaborative Meta-Analysis of Randomised Statin Trials
Topic: General Cardiology
Date Posted: 2/17/2010
Author(s): Sattar N, Preiss D, Murray HM, et al.
Citation: Lancet 2010;Feb 17:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there a relationship between statin use and development of diabetes?
Methods: The authors conducted a MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials search, from 1994–2009, for randomized controlled endpoint trials of statins. Trials included had more than 1,000 patients, with identical follow-up in every group, and duration of more than 1 year. Trials were excluded if they involved organ transplant or hemodialysis. The I2 statistic was used to measure heterogeneity between trials, and calculated risk estimates for incident diabetes were performed with a random-effect meta-analysis.
Results: Thirteen statin trials with 91,140 participants were identified, of whom 4,278 (2,226 assigned statins and 2,052 assigned control therapy) developed diabetes (defined as a fasting blood sugar >126 mg/dl) during a mean 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17), with little heterogeneity (I2 = 11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body mass index nor change in low-density lipoprotein cholesterol (LDL-C) accounted for residual variation in risk. Treatment of 255 (95% CI, 150-852) patients with statins for 4 years resulted in one extra case of diabetes.
Conclusions: Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events.
Perspective: The findings are of interest, but should have no impact on clinical practice. The lay literature has waved a flag of concern about statins inducing diabetes. But the modest 9% increase in diabetes is more than balanced by the benefits of statins in diabetics and nondiabetics alike. In the Cholesterol Treatment Trialists’ meta-analysis, for every 38.7 mg/dl reduction in LDL-C with statins, there was a 5.4 reduction in major coronary events per 255 patients treated for 4 years. As yet, there is no clear biologic or genetic explanation for the findings. In the PROVE-IT TIMI-22 trial, there was a slight increase in diabetes attributable to 80 mg of atorvastatin compared to 40 mg of pravastatin. Whether this is related to statin dosing or achieved LDL-C levels is not clear, but in the present meta-analysis, there was no difference between water-soluble and fat-soluble statins. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Association Between a Literature-Based Genetic Risk Score and Cardiovascular Events in Women
Topic: Prevention/Vascular
Date Posted: 2/17/2010
Author(s): Paynter NP, Chasman DI, Pare G, et al.
Citation: JAMA 2010;303:631-637.
Clinical Trial: No
Study Question: What is the ability of a literature-based genetic risk score to predict cardiovascular disease (CVD)?
Methods: Data from the Women’s Genome Health Study, a prospective cohort study of 19,313 women, were used for the present analysis. Women were followed for a median of 12.3 years. Genetic risk scores were created using the National Human Genome Research Institute's catalog of genome-wide association study results published between 2005 and 2009. The outcomes of interest included myocardial infarction (MI), stroke, arterial revascularization, and cardiovascular death.
Results: A total of 101 single nucleotide polymorphisms reported to be associated with CVD or at least one intermediate CVD phenotype (at a published p value of <107) were identified and risk alleles were added to create a genetic risk score. A total of 777 CVD events occurred during follow-up, including 199 MIs, 203 strokes, 63 CVD deaths, and 312 revascularization events. After adjustment for age, the genetic risk score was associated with CVD events (hazard ratio [HR], 1.02 per risk allele; 95% confidence interval [CI], 1.00-1.03). The corresponding absolute CVD risk was 3% over 10 years in the lowest tertile of genetic risk and 3.7% over 10 years in the highest tertile of genetic risk. After further adjustment for traditional risk factors, the genetic risk score did not improve discrimination or reclassification in risk score. The genetic risk score was not associated with CVD risk (HR, 1.00 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults-adjusted/allele; 95% CI, 0.99-1.01). Family history remained significantly associated with CVD risk.
Conclusions: The authors concluded that after adjustment for traditional risk factors, a genetic risk score was not significantly associated with incidence of CVD.
Perspective: This is an important study, which advances our understanding regarding the potential use of genetics in CVD risk. Given these results, continued use of traditional risk factors including the prevention of risk factors such as hypertension, hypercholesterolemia, diabetes, and obesity are the foundations of CVD practice. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Perioperative Management of Patients With Drug-Eluting Stents
Topic: Interventional Cardiology
Date Posted: 2/15/2010 5:00:00 PM
Author(s): Abualsaud AO, Eisenberg MJ.
Citation: JACC Cardiovasc Interv 2009;2:131-142.
Clinical Trial: No
Study Question: What is the best strategy for perioperative use of antiplatelet agents in patients with drug-eluting stents (DES) who need to undergo noncardiac surgery to avoid stent thrombosis?
Perspective: The following are 10 points to remember from this state-of-the-art paper about perioperative management of patients with DES:

1. DES are associated with a small, but significant increased risk of late and very late stent thrombosis compared with bare-metal stents.

2. Stent thrombosis is a platelet-mediated phenomenon that usually manifests as sudden death ST-segment elevation myocardial infarction, or malignant arrhythmias. It appears to be associated with a mortality ranging from 9-45%.

3. Premature cessation of dual antiplatelet therapy is the most important predictor of stent thrombosis. Current guidelines support continuation of dual antiplatelet therapy for 12 months after DES implantation.

4. The risk of perioperative stent thrombosis is increased in patients undergoing noncardiac surgery within 6 weeks of stent-based percutaneous coronary intervention (PCI).

5. In patients undergoing noncardiac surgery, continuation of aspirin is associated with a 1.5-fold increase in risk of bleeding while withdrawal of aspirin leads to an increase in cardiac, cerebral, and peripheral vascular events. Dual antiplatelet therapy is associated with an increased risk of bleeding complications.

6. All elective surgical procedures should be delayed by at least 6 months and ideally 12 months after DES placement.

7. Patients undergoing surgical procedures 12 months after PCI are at a lower risk of perioperative stent thrombosis compared with earlier surgery. However, if possible, dual antiplatelet therapy should be continued if bleeding risk is low. If the risk of perioperative bleeding is significantly high, then clopidogrel should be discontinued 5 days before surgery, and aspirin should be maintained. Clopidogrel should be restarted as soon as realistically feasible.

8. In patients with DES, when surgery cannot be delayed beyond a year after PCI and thienopyridine or dual antiplatelet therapy must be discontinued, intravenous small molecule glycoprotein IIb/IIIa inhibitors have been used as bridging therapy preoperatively, followed by early (usually immediately postop) resumption of dual antiplatelet therapy. The efficacy of this strategy has not been definitively proven. Use of heparin, low molecular weight heparin, Coumadin, or fondaparinux as bridge therapy for patients after discontinuing dual antiplatelet therapy is not advisable.

9. Primary PCI is the reperfusion therapy of choice in patients who develop perioperative myocardial infarction due to stent thrombosis.

10. The challenges associated with thienopyridine use could be overcome once ticagrelor is approved for clinical use. Its short half-life and its rapid onset of action would allow patients to discontinue ticagrelor only 1 day before surgery and resume it immediately after surgery, thereby potentially diminishing both the risk of perioperative bleeding and stent thrombosis. This hypothesis is also unproven at this point. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Intracardiac and Extracardiac Markers of Inflammation During Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 2/22/2010
Author(s): Marcus GM, Smith LM, Ordovas K, et al.
Citation: Heart Rhythm 2010;7:149-154.
Clinical Trial: No
Study Question: Does atrial fibrillation (AF) result in sequestration of inflammatory mediators in the left atrium (LA)?
Methods: C-reactive protein (CRP) and interleukin-6 (IL-6) levels were measured in blood samples drawn from 167 patients with AF and 207 control subjects with no history of AF. Venous samples were obtained in all subjects, and in 46 patients undergoing catheter ablation of AF, blood samples also were obtained from the LA, coronary sinus (CS), and femoral artery. LA volume was measured by computed tomography.
Results: The presence of AF at the time of blood sampling was associated with higher CRP and IL-6 levels (odds ratio, 1.7-1.8), independent of the type of AF and LA volume. Among the 46 patients who underwent blood sampling at multiple sites, the CRP level was higher in the LA than in the CS in the patients who were in AF, but were lower in the LA than in the CS in the patients who were in sinus rhythm at the time of sampling.
Conclusions: An ongoing episode of AF is independently associated with higher levels of inflammatory markers. Measurements of the relative levels of CRP and IL-6 in the LA and CS suggest that inflammatory mediators are sequestered in the LA during AF.
Perspective: Several studies have indicated that inflammatory markers such as CRP are associated with AF. For example, higher CRP levels pre-cardioversion are predictive of an early recurrence of AF post-cardioversion. A plausible explanation for this is that inflammation in the LA promotes atrial remodeling. The results of this interesting study suggest that AF itself results in higher levels of inflammatory cytokines in the LA, providing a potential mechanism by which ‘AF begets AF.’ Fred Morady, M.D., F.A.C.C.

Title: Nonsteroidal Anti-Inflammatory Drug Treatment for Postoperative Pericardial Effusion: A Multicenter Randomized, Double-Blind Trial
Topic: Cardiovascular Surgery
Date Posted: 2/22/2010
Author(s): Meurin P, Tabet JY, Thabut G, et al.
Citation: Ann Intern Med 2010;152:137-143.
Clinical Trial: yes
Study Question: Is the nonsteroidal anti-inflammatory drug (NSAID) diclofenac effective in reducing postoperative pericardial effusion volume after cardiac surgery?
Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted at five postoperative cardiac rehabilitation centers. A total of 196 patients with moderate to large pericardial effusion (grade 2, 3, or 4 on a scale of 0 to 4; measured by echocardiography) persistent more than 7 days after cardiac surgery were randomly assigned treatment with either diclofenac 50 mg or placebo twice daily for 14 days. Endpoints were change in effusion grade after 14 days of treatment and frequency of late cardiac tamponade.
Results: The initial mean pericardial effusion grade was 2.6 ± 0.7 in the placebo group and 2.8 ± 0.8 in the diclofenac group. The two groups showed similar mean decreases from baseline after treatment (-1.1 ± 1.2 grades for the placebo group vs. -1.4 ± 1.2) for the diclofenac group. The mean difference between groups was -0.28 grade (95% confidence interval, -0.63 to 0.06 grade, p = 0.105). There were 11 cases of late cardiac tamponade in the placebo group and nine in the diclofenac group (p = 0.64). Differences persisted after adjustment for grade of pericardial effusion at baseline, treatment site, and type of surgery.
Conclusions: In patients with pericardial effusion after cardiac surgery, the NSAID diclofenac neither reduced the size of postoperative pericardial effusions nor prevented late cardiac tamponade.
Perspective: Although not supported by data, NSAIDs might be used to treat postoperative pericardial effusion; rationale is based on the belief that their anti-inflammatory properties would result in a decrease, or cessation of increase, in effusion size, thereby avoiding cardiac tamponade. These data, although limited by relative small sample size that could have led to failure to detect a small benefit, refute the efficacy of the NSAID diclofenac (at a dose of 60 mg BID) for the treatment of postoperative pericardial effusion. In light of potential adverse effects associated with NSAID use (including renal insufficiency, volume retention exacerbating heart failure, and upper gastrointestinal disease), supporting data should be provided before the routine use of NSAIDs in this scenario. David S. Bach, M.D., F.A.C.C.

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Title: When Children With Kawasaki Disease Grow Up: Myocardial and Vascular Complications in Adulthood
Topic: Congenital Heart Disease
Date Posted: 2/19/2010
Author(s): Gordon JB, Kahn AM, Burns JC.
Citation: J Am Coll Cardiol 2009;54:1911-1920.
Clinical Trial: No
Perspective: The following are 10 points to remember from this state-of-the-art paper.

1. The cause of Kawasaki disease (KD) is unknown. The self-limited nature of illness, seasonality, and nationwide epidemics suggest an infectious trigger. Some element of genetic susceptibility is suspected.

2. Symptoms of KD include high fever for at least 4 days, rash, conjunctival infection, erythema of the lips and oropharynx, edema of the hands and feet, and palmar erythema.

3. Up to 25% of patients with untreated KD will develop coronary artery aneurysms. Aneurysm of systemic arteries can also occur.

4. Prompt treatment (within 10 days of onset of fever) will decrease incidence of aneurysms from 25-35%. The long-term coronary outcomes of children treated with intravenous immunoglobulin who do not develop aneurysms are unknown.

5. In young adults with coronary symptoms of unclear etiology, presence of proximal coronary aneurysms with or without calcification followed by normal distal coronary segments should prompt questioning about antecedent KD.

6. Impaired coronary flow reserve has been shown in patients with previous KD with no known coronary involvement, resolved coronary dilatation, and known coronary artery aneurysms.

7. A complete understanding of long-term outcomes of patients with KD will require a prospective registry.

8. Calcification at the site of previous coronary aneurysms can be helpful diagnostically and can be seen on chest radiography.

9. Tests which could be considered for adults with a previous history of KD and known coronary involvement include lipid screening, electrocardiogram, echocardiogram, functional studies such as stress echocardiograms, or nuclear studies.

10. For patients with persistent giant (≥8 mm) aneurysms, anticoagulation with warfarin for a goal international normalized ratio of 2.0-2.5 should be considered. Timothy B. Cotts, M.D., F.A.C.C.

Title: Association Between 9p21 Genomic Markers and Heart Disease: A Meta-Analysis
Topic: General Cardiology
Date Posted: 2/17/2010
Author(s): Palomaki GE, Melillo S, Bradley LA.
Citation: JAMA 2010;303:648-656.
Clinical Trial: No
Study Question: How strong is the association between genetic variation on chromosome 9p21 and coronary heart disease?
Methods: English-language articles that tested for 9p21 single-nucleotide polymorphisms (SNPs) with coronary heart/artery disease or myocardial infarction as primary outcomes were included. Included articles also provided race, number of participants, and data to compute an odds ratio (OR). Two independent reviewers performed data extraction, and 22 articles were included.
Results: Forty-seven data sets from the 22 articles were analyzed, including 35,872 cases and 95,837 controls. The summary OR for heart disease among individuals with two versus one at-risk allele was 1.25 (95% confidence interval [CI], 1.21-1.29). Age at disease diagnosis was a significant covariate, with ORs of 1.35 (95% CI, 1.30-1.40) for age 55 years or younger, and 1.21 (95% CI, 1.16-1.25) for age 75 years or younger. For a 65-year-old man, the 10-year heart disease risk for two versus one at-risk allele would be 13.2% versus 11%. For a 40-year-old woman, the 10-year heart disease risk for two versus one at-risk allele would be 2.4% versus 2.0%. Nearly identical results were found when comparing one versus zero at-risk alleles. Three studies showed net reclassification indexes ranging from −0.1% to 4.8%.
Conclusions: A statistically significant association between 9p21 SNPs and heart disease was found that varied by age at disease onset, but the magnitude of the association was small.
Perspective: Several studies have shown that SNPs in an intergenic region of 9p21 are associated with coronary artery disease. The magnitude of this association and the clinical utility of this genetic marker for risk stratification are controversial. The current meta-analysis casts doubt on use of these SNPs for practical management of patients, as this information is unlikely to affect treatment decisions. However, there is still much to be learned about the biological mechanisms underlying this association, which may lead to novel treatment strategies in the future. Daniel T. Eitzman, M.D., F.A.C.C.

[Chevychelov]

Title: Statins and Risk of Incident Diabetes: A Collaborative Meta-Analysis of Randomised Statin Trials
Topic: General Cardiology
Date Posted: 2/17/2010
Author(s): Sattar N, Preiss D, Murray HM, et al.
Citation: Lancet 2010;Feb 17:[Epub ahead of print].
Clinical Trial: No
Study Question: Is there a relationship between statin use and development of diabetes?
Methods: The authors conducted a MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials search, from 1994–2009, for randomized controlled endpoint trials of statins. Trials included had more than 1,000 patients, with identical follow-up in every group, and duration of more than 1 year. Trials were excluded if they involved organ transplant or hemodialysis. The I2 statistic was used to measure heterogeneity between trials, and calculated risk estimates for incident diabetes were performed with a random-effect meta-analysis.
Results: Thirteen statin trials with 91,140 participants were identified, of whom 4,278 (2,226 assigned statins and 2,052 assigned control therapy) developed diabetes (defined as a fasting blood sugar >126 mg/dl) during a mean 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17), with little heterogeneity (I2 = 11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body mass index nor change in low-density lipoprotein cholesterol (LDL-C) accounted for residual variation in risk. Treatment of 255 (95% CI, 150-852) patients with statins for 4 years resulted in one extra case of diabetes.
Conclusions: Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events.
Perspective: The findings are of interest, but should have no impact on clinical practice. The lay literature has waved a flag of concern about statins inducing diabetes. But the modest 9% increase in diabetes is more than balanced by the benefits of statins in diabetics and nondiabetics alike. In the Cholesterol Treatment Trialists’ meta-analysis, for every 38.7 mg/dl reduction in LDL-C with statins, there was a 5.4 reduction in major coronary events per 255 patients treated for 4 years. As yet, there is no clear biologic or genetic explanation for the findings. In the PROVE-IT TIMI-22 trial, there was a slight increase in diabetes attributable to 80 mg of atorvastatin compared to 40 mg of pravastatin. Whether this is related to statin dosing or achieved LDL-C levels is not clear, but in the present meta-analysis, there was no difference between water-soluble and fat-soluble statins. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage
Topic: General Cardiology
Date Posted: 2/17/2010 5:00:00 PM
Author(s): Slichter SJ, Kaufman RM, Assmann SF, et al.
Citation: N Engl J Med 2010;362:600-613.
Clinical Trial: yes
Study Question: What is the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia?
Methods: The investigators randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantations or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1 x 1011, 2.2 x 1011, or 4.4 x 1011, platelets per square meter of body-surface area, respectively) when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary endpoint was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria).
Results: In the 1,272 patients who received at least one platelet transfusion, the primary endpoint was observed in the 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were nonsignificant). The incidences of higher grades of bleeding and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25 x 1011) than in the medium-dose group (11.25 x 1011) or the high-dose group (19.63 x 1011; p = 0.002 for low vs. medium, p < 0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; p < 0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (p < 0.001).
Conclusions: The authors concluded that at doses between 1.1 x 1011 and 4.4 x 1011 platelets per square meter, the number of platelets in the prophylactic transfusion has no effect on the incidence of bleeding.
Perspective: The current study evaluated the effect of different platelet dosages on hemostasis and transfusion endpoints and suggests that the dose per prophylactic platelet transfusion (at doses between 1.1 x 1011 and 4.4 x 1011 platelets per square meter) does not significantly affect bleeding in patients with hypoproliferative thrombocytopenia. The median platelet increment after transfusion was higher after larger doses, as expected. Overall, the data suggest that when prophylactic transfusions are administered after a trigger threshold dose of 10,000 platelets/cubic millimeter is reached, dose has no effect on bleeding. A strategy of low-dose transfusion may therefore significantly reduce the quantity of transfused platelets, preserving scarce blood components. However, this may increase the total number of platelet transfusions. Additional studies to determine optimal dose and frequency of platelet transfusions in hypoproliferative thrombocytopenia are indicated. Debabrata Mukherjee, M.D., F.A.C.C

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Title: Serum Soluble ST2: A Potential Novel Mediator in Left Ventricular and Infarct Remodeling After Acute Myocardial Infarction
Topic: General Cardiology
Date Posted: 2/22/2010
Author(s): Weir RA, Miller AM, Murphy GE, et al.
Citation: J Am Coll Cardiol 2010;55:243-250.
Clinical Trial: No
Study Question: What is the relationship between serum concentrations of the soluble interleukin-1 receptor family member ST2 (sST2) and changes in left ventricular (LV) function after acute myocardial infarction (AMI)?
Methods: sST2 levels were measured in 100 patients (mean age 58.9 ± 12.0 years), admitted with AMI and resultant LV systolic dysfunction, at baseline, and 12 and 24 weeks. Patients underwent cardiac magnetic resonance imaging and measurement of N-terminal pro-brain natriuretic peptide, norepinephrine, and aldosterone at each time point.
Results: Median sST2 decreased from 263.3 pg/ml at baseline to 140.0 pg/ml at 24 weeks (p < 0.001). Serum sST2 correlated significantly with LVEF at baseline (r = -0.30, p = 0.002) and 24 weeks (r = -0.23, p = 0.026); change in sST2 correlated with change in LV end-diastolic volume index (r = -0.24, p = 0.023). Level of sST2 was positively associated with infarct volume index at baseline (r = 0.26, p = 0.005) and 24 weeks (r = 0.22, p = 0.037), and with change in infarct volume index (r = -0.28, p = 0.001). Level of sST2 correlated significantly with norepinephrine and aldosterone, but not with N-terminal pro-brain natriuretic peptide.
Conclusions: The authors concluded that measurement of sST2 early after AMI assists in the prediction of medium-term LV functional recovery.
Perspective: A soluble form of ST2 is found in the circulation that lacks intracellular and transmembrane domains. Thus, sST2 may act as a decoy receptor that interferes with cellular signaling via its ligand, IL-33. Preclinical studies indicate that IL-33 signaling may mediate cardioprotective effects. The current study demonstrates an intriguing association between levels of this potential inhibitor of IL-33/ST2 signaling with LV function and neurohormonal activation following AMI. sST2 may therefore serve as a potential useful biomarker in AMI patients. Additional studies are necessary to confirm these observations, as well as to explore the pathophysiological role of sST2 in LV remodeling and renin-angiotensin-aldosterone system activation. Daniel T. Eitzman, M.D., F.A.C.C

Title: Efficacy and Safety of Immediate Angioplasty Versus Ischemia-Guided Management After Thrombolysis in Acute Myocardial Infarction in Areas With Very Long Transfer Distances: Results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction)
Topic: Interventional Cardiology
Date Posted: 2/18/2010
Author(s): Bшhmer E, Hoffmann P, Abdelnoor M, Arnesen H, Halvorsen S.
Citation: J Am Coll Cardiol 2010;55:102-10.
Clinical Trial: yes
Study Question: What is the benefit of immediate transfer for percutaneous coronary intervention (PCI) (compared with an ischemia-guided approach) after thrombolysis in patients with very long transfer distances to PCI?
Methods: The authors randomized 266 patients treated with fibrinolytics for ST-elevation myocardial infarction (STEMI) with more than 90-minute transfer delays to PCI to immediate transfer for PCI or to management in the local hospitals, with early transfer if indicated for rescue or clinical deterioration. All patients were treated with tenecteplase, aspirin, enoxaparin, and clopidogrel. The primary outcome was a composite of death, reinfarction, stroke, or new ischemia at 1 year.
Results: Coronary angiography was performed in almost all patients (99% in the early invasive arm and 95% in the conservative arm), although the average delay to angiography was 5.5 days in the conservative arm. In the conservative arm, 27% (36) of patients were referred for rescue PCI. Overall, 89% of patients in the early invasive arm and 71% in the conservative arm underwent PCI. The primary endpoint occurred in 28 patients (21%) in the early invasive group compared with 36 (27%) in the conservative group (hazard ratio, 0.72; p = 0.19). The incidence of 30-day reinfarction (1.5% vs. 5.3%) and recurrent ischemia (6.0% vs. 12.1%) was nonsignificantly lower in the early invasive arm. The composite of death, reinfarction, or stroke at 12 months was significantly reduced in the early invasive compared with the conservative group (6% vs. 16%; hazard ratio, 0.36; p = 0.01). There was no significant difference in bleeding or infarct size.
Conclusions: A strategy of immediate transfer for PCI of patients with STEMI, treated with thrombolysis and clopidogrel in areas with long transfer distances did not improve the primary outcome significantly, but reduced the rate of death, reinfarction, or stroke at 12 months.
Perspective: This trial assessed the role for an early invasive approach in patients when rapid PCI or rapid transfer for primary PCI is not feasible. Although this trial did not meet its primary endpoint, the trends in ischemic events are similar to those seen in the larger TRANSFER-AMI trial (Cantor WJ, et al., N Engl J Med 200925;360:2705-18), supporting a strategy of early transfer for PCI after thrombolysis in patients with STEMI. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Second-Generation Everolimus-Eluting and Paclitaxel-Eluting Stents in Real-Life Practice (COMPARE): A Randomised Trial
Topic: Interventional Cardiology
Date Posted: 2/19/2010
Author(s): Kedhi E, Joesoef KS, McFadden E, et al.
Citation: Lancet 2010;375:201-209.
Clinical Trial: yes
Study Question: What is the safety and efficacy of the second-generation everolimus-eluting stent (EES) and paclitaxel-eluting stents (PES) in real-life practice?
Methods: The authors randomized 1,800 consecutive patients (ages 18-85 years) undergoing percutaneous coronary intervention (PCI) at their center to treatment with EES or PES in a single-blind fashion. The primary endpoint was a composite of all-cause mortality, myocardial infarction, and target vessel revascularization within 12 months.
Results: The primary endpoint occurred less frequently with the EES compared with the PES (6% vs. 9%, p = 0.02). This difference was driven by a lower risk of stent thrombosis (0.7% vs. 3%, p = 0.002), myocardial infarction (3% vs. 5%, p = 0.007), and target vessel revascularization (2% vs. 6%; p = 0.0001). There was no difference in all-cause mortality (2% vs. 2%) or cardiac mortality (1% vs. 1%).
Conclusions: The authors concluded that the EES was superior to PES in patients undergoing contemporary PCI.
Perspective: The results of this study corroborate those of the recently presented SPIRIT IV trial, suggesting that the EES is a superior stent to PES. Interestingly, there was no difference in outcome with the two stents in diabetic patients in the two trials. However, neither trial was powered specifically for this subset, and in the absence of a trial specifically evaluating outcomes in diabetic patients, EES should be preferentially used over PES in both diabetic and nondiabetic patients undergoing PCI. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: A Randomized Trial of a Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss
Topic: Prevention/Vascular
Date Posted: 2/16/2010
Author(s): Yancy WS Jr, Westman EC, McDuffie JR, et al.
Citation: Arch Intern Med 2010;170:136-145.
Clinical Trial: yes
Study Question: What is the relative value of two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), for weight loss and metabolic parameters?
Methods: Overweight or obese outpatients (n = 146) from Department of Veterans Affairs primary care clinics in North Carolina, were randomized to either LCKD instruction (initially, <20 g of carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus LFD instruction (<30% energy from fat, 500-1000 kcal/day deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters.
Results: The mean age was 52 years, and mean body mass index was 39.3 kg/m2; 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Baseline kcal/day energy intake and g/day of carbohydrates (carb), total fat, and type of fat were similar between groups. At 48 weeks, the reduction in total energy intake was similar (25%); the LCKD group had an average carb intake of 62 g/day and total fat 107 g/day compared to the O + LFD with 186 g/day of carbs and 57 g/day of total fat. The group assigned a LFD (defined as <30% of calories) averaged about 25% fat. The majority of weight loss for both interventions occurred in the first 12-24, weeks with maximum weight loss achieved at 24-36 weeks. Weight loss was similar for the LCKD (mean change, -9.5%) and the O + LFD (-8.5%) (p = 0.60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs. 1.5 mm Hg) and diastolic (-4.5 vs. 0.4 mm Hg) blood pressures (p < 0.001 for both comparisons). High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups. Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A1c levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant.
Conclusions: In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters, and was more effective for lowering blood pressure.
Perspective: The results in the high-fat LCKD are more impressive than usual because in most other studies, patients do not have the ability to tolerate the fat-induced ketosis and resume a higher carb intake and reduce the fat intake. This was not the case in this study lasting a year, which is also longer than most. As in other studies, this one demonstrated that weight loss is greater in those who attend more group sessions, which implies that these were effective, and that the patients were highly motivated. While the high-fat and low-carb diet is clearly helpful for weight reduction, studies are necessary to determine whether it improves cardiovascular and other outcomes without inducing unintended consequences. Until such studies are available, the Mediterranean diet with a 500-1000 kcal/day deficit seems to be the safest and most effective for long-term weight control and metabolic health. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Association Between a Literature-Based Genetic Risk Score and Cardiovascular Events in Women
Topic: Prevention/Vascular
Date Posted: 2/17/2010
Author(s): Paynter NP, Chasman DI, Pare G, et al.
Citation: JAMA 2010;303:631-637.
Clinical Trial: No
Study Question: What is the ability of a literature-based genetic risk score to predict cardiovascular disease (CVD)?
Methods: Data from the Women’s Genome Health Study, a prospective cohort study of 19,313 women, were used for the present analysis. Women were followed for a median of 12.3 years. Genetic risk scores were created using the National Human Genome Research Institute's catalog of genome-wide association study results published between 2005 and 2009. The outcomes of interest included myocardial infarction (MI), stroke, arterial revascularization, and cardiovascular death.
Results: A total of 101 single nucleotide polymorphisms reported to be associated with CVD or at least one intermediate CVD phenotype (at a published p value of <107) were identified and risk alleles were added to create a genetic risk score. A total of 777 CVD events occurred during follow-up, including 199 MIs, 203 strokes, 63 CVD deaths, and 312 revascularization events. After adjustment for age, the genetic risk score was associated with CVD events (hazard ratio [HR], 1.02 per risk allele; 95% confidence interval [CI], 1.00-1.03). The corresponding absolute CVD risk was 3% over 10 years in the lowest tertile of genetic risk and 3.7% over 10 years in the highest tertile of genetic risk. After further adjustment for traditional risk factors, the genetic risk score did not improve discrimination or reclassification in risk score. The genetic risk score was not associated with CVD risk (HR, 1.00 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults-adjusted/allele; 95% CI, 0.99-1.01). Family history remained significantly associated with CVD risk.
Conclusions: The authors concluded that after adjustment for traditional risk factors, a genetic risk score was not significantly associated with incidence of CVD.
Perspective: This is an important study, which advances our understanding regarding the potential use of genetics in CVD risk. Given these results, continued use of traditional risk factors including the prevention of risk factors such as hypertension, hypercholesterolemia, diabetes, and obesity are the foundations of CVD practice. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Effectiveness of Extended-Duration Transdermal Nicotine Therapy: A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 2/22/2010
Author(s): Schnoll RA, Patterson F, Wileyto EP, et al.
Citation: Ann Intern Med 2010;152:144-151.
Clinical Trial: yes
Study Question: Does extended nicotine therapy improve abstinence from tobacco?
Methods: This was a randomized controlled trial, which compared extended-duration nicotine replacement (24 weeks), standard-duration nicotine replacement (8 weeks), and placebo (16 weeks) for abstinence from tobacco. Participants were blinded to assignment. Subjects were eligible if they sought treatment for smoking from October 2004 to March 2008, were age 18-65 years, smoked 10 or more cigarettes per day for the past year or more, and had no comorbid conditions such as heart attack or stroke within the prior 6 months. Women who were pregnant or lactating, and people with a history of drug or alcohol abuse were excluded, as were those who were under current treatment for nicotine addiction. Abstinence from tobacco was confirmed by carbon monoxide levels at weeks 24 and 52. Secondary outcome measures included quitting characteristics such as lapses, relapse, and recover events.
Results: A total of 568 adult smokers were included. At 24 weeks, subjects randomized to extended-duration nicotine replacement had higher rates of point-prevalence abstinence compared to standard-duration therapy (31.6% vs. 20.3%; odds ratio [OR], 1.81; 95% confidence interval [CI], 1.23-2.66). Similar patterns were noted for prolonged abstinences (41.5% vs. 26.9%; OR, 1.97; 95% CI, 1.38-2.82) and continuous abstinence (19.2% vs. 12.6%; OR, 1.64; 95% CI, 1.04-2.60). Extended-duration therapy also reduced risk for lapse (OR, 0.77; 95% CI, 0.63-0.95) and improved chances for recovery after a lapse (OR, 1.47; 95% CI, 1.17-1.84). At 52 weeks, extended-duration therapy was associated with higher quit rates for prolonged abstinence. Time to relapse was longer among those randomized to extended-duration therapy compared to those on standard-duration therapy.
Conclusions: The investigators concluded that extended-duration nicotine therapy increased continuous abstinence at 24 weeks, with lower lapses and increased recovery after a lapse.
Perspective: Further study is warranted regarding the use of extended duration of nicotine therapy for smokers, including research in other populations such as those with heart disease, prior to widespread acceptance of extended-duration therapy. However, these data suggest the potential benefit for nicotine replacement beyond 8 weeks in many smokers. Elizabeth A. Jackson, M.D., F.A.C.C.

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Cocaine Sudden Death in Europe
ICTUS: Five Year Outcomes
ACC Members Fight Fee Schedule Cuts
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Title: Vascular Inflammation in Obesity and Sleep Apnea
Topic: Prevention/Vascular
Date Posted: 2/24/2010
Author(s): Jelic S, Lederer DJ, Adams T.
Citation: Circulation 2010;121:1014-1021.
Clinical Trial: No
Study Question: Both obesity and obstructive sleep apnea (OSA) are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. Are the endothelial alterations that are attributed commonly to obesity in fact related to OSA?
Methods: Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, the expression of nuclear factor-ĸB and nitrotyrosine were quantified by immunofluorescence in freshly harvested venous endothelial cells. Basal endothelial nitric oxide (NO) production and activity were quantified by the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation.
Results: Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (n = 38) than in OSA-free subjects (n = 33) regardless of central adiposity. Expression of nuclear factor-ĸB was greater in obese OSA patients than in obese OSA-free subjects (p = 0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine and nuclear factor-ĸB significantly decreased in OSA patients who adhered to continuous positive airway pressure ≥4 hours daily.
Conclusions: Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients.
Perspective: This study adds to the body of evidence that OSA may contribute to coronary risk and cardiovascular events. A few of the cardiometabolic effects of OSA include hypertension, increase in high-sensitivity C-reactive protein, heightened sympathetic tone, reactive platelets, dysglycemia, insulin resistance, and increase in cortisol, leptin, and growth hormone. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Early and Late Outcome of Treated Patients Referred for Syncope to Emergency Department: the EGSYS 2 Follow-Up Study
Topic: Arrhythmias
Date Posted: 2/24/2010
Author(s): Andrea U, Attilio DR, Franco G, et al., on behalf of the Evaluation of Guidelines in Syncope Study 2 (EGSYS 2) Group.
Citation: Eur Heart J 2010;Feb 18:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the prognosis of patients with syncope?
Methods: This was a multicenter, prospective study of 380 patients (mean age 66 years) with syncope initially evaluated in an emergency department (ED). Therapy was at the discretion of the treating physician. The mean duration of follow-up was 20 months. The 1° endpoint was death from any cause or syncope recurrence.
Results: The most common causes of syncope were neurocardiogenic syncope in 64% of patients, orthostatic hypotension in 17%, cardiac syncope in 15%, and an arrhythmia in 11%. All-cause mortality was 9.2%. The strongest predictors of mortality were structural heart disease or an abnormal electrocardiogram (hazard ratio [HR], 5.6), hypertension (HR, 3.0), and trauma from syncope (HR, 2.24). Mortality in patients with cardiac syncope was significantly higher than in patients with other causes of syncope (37% vs. 7-11%). Syncope recurred in 16% of patients and the recurrence rate was unrelated to the etiology of syncope. The strongest predictors of recurrent syncope were palpitations before syncope (HR, 3.4), male gender (HR, 1.8), and absence of prodrome (HR, 0.4).
Conclusions: The risk of death during follow-up in patients with syncope is related to associated cardiac disease. Syncope recurrence is unrelated to the cause of syncope.
Perspective: A limitation of this study is that left ventricular ejection fraction was not included in the analysis and probably would have been a stronger predictor of mortality than simply the presence of structural heart disease. Fred Morady, M.D., F.A.C.C.

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Title: Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION: Distal Protection Study)
Trial Sponsor: N/A
Year Published 2008
Topic(s): Interventional Cardiology
Summary Posted: 2/22/2010 5:00:00 PM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Description
The goal of the trial was to evaluate distal embolic protection prior to percutaneous coronary intervention (PCI) compared with PCI without embolic protection in native vessels in patients with ST-elevation myocardial infarction (STEMI).
Hypothesis
Distal embolic protection prior to PCI would be more effective in improving myocardial perfusion than PCI without embolic protection.
Drugs/Procedures Used
Patients were randomized to distal embolic protection prior to PCI (n = 312) or PCI without embolic protection (n = 314). Patients also received a drug-eluting stent versus bare-metal stent by 2 x 2 factorial design (results presented separately).
Principal Findings
Patients were well matched with baseline characteristics. In the embolic protection group, 81% received the FilterWire device, 13% received the SpideRx device, and in the remaining patients, distal protection could not be achieved. Initial Thrombolysis In Myocardial Infarction (TIMI) 0 or 1 flow was present in 67% of the embolic protection group and 68% of the PCI alone group. Similarly, visible thrombus was present in 68% and 75%, respectively.

For the primary outcome, complete ST-segment resolution occurred in 76% of the embolic protection group and 72% of the PCI alone group (p = 0.29). There was no difference in the primary outcome among any subgroup tested. There was no difference in the maximum level of creatine-kinase (p = 0.99), troponin T (p = 0.87), or wall motion index (p = 0.35) between the groups. There was also no difference in 30-day major adverse cardiac events (5.4% vs. 3.2%, p = 0.17), respectively for embolic protection versus PCI alone.

At 15 months, definite stent thrombosis had occurred in 2.9% of the embolic protection group versus 0.3% of the PCI alone group (p = 0.02) and target lesion revascularization was 12.5% versus 7% (p = 0.02), respectively.
Interpretation
Among patients with STEMI, distal embolic protection prior to PCI did not reduce the incidence of complete ST-segment resolution, maximum level of cardiac enzymes, wall motion index, or major adverse cardiac events compared with PCI alone. In fact, there were increased adverse events late in follow-up.

This trial complements the earlier EMERALD trial, which failed to show that GuardWire balloon occlusion improves the myocardial circulation compared with standard PCI alone. These findings are in contradistinction to the recently published TAPAS trial, which revealed that thrombus aspiration by the Export catheter significantly improved myocardial reperfusion.
Conditions
• Coronary heart disease / Acute MI
• Coronary heart disease
Therapies
• Stent
• PTCA
Study Design
Randomized.
Patients Screened: 1,687
Patients Enrolled: 626
Mean Follow-Up: 15 months
Mean Patient Age: 62 years
% Female: 26%

Primary Endpoints
Rate of complete (>70%) ST-segment resolution 90 minutes after PCI detected by continuous ST-segment monitoring
Secondary Endpoints
Time to >70% ST-segment resolution, maximal cardiac biomarkers, wall motion index by echocardiography at discharge, and major adverse cardiac events
Other Design Considerations
At the time of enrollment, patients underwent a second randomization to a drug-eluting stent versus a bare-metal stent.
Patient Population
STEMI within 12 hours of symptom onset with total ST-elevation of 4 mm in contiguous leads, age at least 18 years, and occluded or severely stenosed coronary artery without excessive calcification or tortuosity
Exclusions:
Previous MI, left main infarct-related artery, history of gastrointestinal bleeding, pregnancy, renal failure, limited (<1 year) life expectancy, or linguistic problems
References: Kaltoft A, Kelbжk H, Klшvgaardet L, al. Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-Month Follow-Up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) Trial. J Am Coll Cardiol 2010;55:867-71.

Presented by Dr. Leif Thuesen at the i2 Summit/American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.

Kelbaek H, Terkelsen CJ, Helqvist S, et al. Randomized comparision of distal protection versus conventional treatment in primary percutaneous coronary intervention: The Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION) Trial. J Am Coll Cardiol 2008;51:899-905.

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Title: Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation
Topic: Interventional Cardiology
Date Posted: 2/23/2010 4:00:00 PM
Author(s): Breet NJ, van Werkum JW, Bouman HJ, et al.
Citation: JAMA 2010;303:754-762.
Clinical Trial: No
Study Question: Can platelet function tests performed at time of percutaneous coronary intervention (PCI) predict clinical outcome?
Methods: The authors prospectively studied 1,069 consecutive patients that underwent elective stent-based PCI at their institution between December 2005 and December 2007. All patients were on clopidogrel, and on-treatment platelet reactivity was measured in all patients using light transmittance aggregometry, VerifyNow P2Y12 assay, Plateletworks assay, IMPACT-R, and the platelet function analysis system (PFA-100). Cut-off values for high on-treatment platelet reactivity were established by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety endpoint included TIMI major and minor bleeding.
Results: One-year follow-up was available for 99.8% of the patients. Adherence to clopidogrel was 95% after 6 months and 82% at 1 year. Over 1-year follow-up, there were 18 deaths (1.7%), 6.0% had nonfatal acute myocardial infarction, 1.2% presented with definite stent thrombosis, and 1.3% had a nonfatal ischemic stroke. There were three possible stent thromboses (0.3%), and bleeding events occurred in 5.1% of the patients (TIMI-major 3.1%, TIMI-minor bleeding 2.2%).The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (11.7% vs. 6.0%; p < 0 .001 area under the curve [AUC], 0.63), VerifyNow (13.3% vs. 5.7%, p < 0.001, AUC 0.62), and Plateletworks (12.6% vs. 6.1%, p = 0.005, AUC 0.61). The other assays were not able to discriminate between those with or without ischemic events. None of the tests identified patients at risk for bleeding.
Conclusions: Assessment of platelet function using light transmittance aggregometry, VerifyNow, and Plateletworks was significantly but modestly associated with ischemic events at 1 year.
Perspective: Multiple studies have established an association between a lesser degree of platelet inhibition and the occurrence of atherothrombotic events. The field has been clouded by the use of multiple platelet function assays with little inter-assay correlation. This study, with its large population and nearly 100% follow-up, provides much needed clarity to the field. Only three assays demonstrated a significant albeit moderate association between ischemic outcomes and degree of platelet inhibition. Given the moderate strength of the association, it would be premature to use platelet function testing to guide routine clinical practice at present. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 3)
Trial Sponsor: Nycomed Pharma GmbH, Unterschleibheim, Germany, and Deutsches Herzzentrum, Munich, Germany
Year Presented: 2008
Year Published 2008
Topic(s): General Cardiology, Interventional Cardiology
Summary Posted: 2/22/2010
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Downloadable Slide Set: Bivalirudin Versus Unfractionated Heparin in Biomarker Negative Patients With Stable and U...
Summary Slide: ISAR-REACT 3 Trial
Related Trial: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2)
Related Trial: Intracoronary Stenting and Antithrombotic Regimen Rapid Early Action for Coronary Treatment (ISAR REACT)
Journal Scan: Bivalirudin Versus Unfractionated Heparin During Percutaneous Coronary Intervention

Description
The goal of this trial was to assess whether bivalirudin is superior to unfractionated heparin (UFH) in terms of ischemic and hemorrhagic endpoints in troponin-negative patients undergoing percutaneous coronary intervention (PCI), after pretreatment with clopidogrel.
Hypothesis
Bivalirudin would be superior to UFH as an adjunct anticoagulant in troponin-negative patients undergoing PCI.
Drugs/Procedures Used
Patients who were biomarker negative, and who were undergoing PCI for stable or unstable angina were randomized to receive either UFH (bolus of 140 U/kg, followed by placebo infusion) or bivalirudin (bolus of 0.75 mg/kg, followed by infusion of 1.75 mg/kg/hr) during the procedure, in addition to 600 mg of clopidogrel and ≥325 mg aspirin at least 2 hours prior to the procedure.
Concomitant Medications
All patients received aspirin 80-325 mg indefinitely. Clopidogrel was continued as 75-150 mg/day for ≤3 days, and then 75 mg/day for at least 1 month after balloon angioplasty or implantation of bare-metal stents and for at least 6 months after implantation of drug-eluting stents.
Principal Findings
A total of 4,570 patients were randomized, 2,289 to the bivalirudin arm, and 2,281 to the UFH arm. The baseline characteristics of the two arms were comparable. About 27.4% of the patients were diabetic. The majority of patients (81.7%) had stable angina; the rest had unstable angina. The baseline ejection fraction was 58%, and 80% had evidence of multivessel disease. The majority of stents (87.7%) were drug-eluting stents.

The primary endpoint, a composite rate of death, myocardial infarction (MI), urgent target vessel revascularization, or in-hospital major bleeding at 30 days, was similar between the two arms (8.3% vs. 8.7% for bivalirudin and UFH, respectively; relative risk [RR] 0.94, 95% confidence interval [CI] 0.77-1.15; p = 0.57). The incidence of death, MI, and urgent target vessel revascularization (TVR) was 0.1% and 0.2% (p = 0.7), 5.6% and 4.8% (p = 0.24), and 0.8% and 0.7% (p = 0.75), for bivalirudin and UFH, respectively. The secondary endpoint of death, MI, and urgent revascularization at 30 days was 5.9% in the bivalirudin arm and 5.0% in the UFH arm (RR 1.16, 95% CI 0.91-1.49; p = 0.23).

The incidence of major bleeding was significantly reduced by 33% with bivalirudin (3.1%) compared with UFH (4.6%) (RR 0.66, 95% CI 0.49-0.90; p = 0.008). Similarly, the incidence of minor bleeding was significantly reduced (p = 0.0001). The incidence of transfusions and thrombocytopenia was similar between the two groups at 30 days.

At 1 year, the incidence of the primary endpoint was similar between the bivalirudin and heparin arms (17.1% vs. 17.5%, p = 0.82). Other endpoints such as death (1.9% vs. 1.7%, p = 0.67), MI (6.0% vs. 5.3%, p = 0.32), TVR (11.2% vs. 12.5%, p = 0.18), and definite stent thrombosis (0.7% vs. 0.7%, p = 1.0) were also similar between the two arms.
Interpretation
Bivalirudin had outperformed UFH (without glycoprotein IIb/IIIa) in a few trials, but pretreatment with clopidogrel was not routinely accomplished in these trials. This randomized trial sought to define the optimal adjunct anticoagulation therapy for troponin-negative patients with stable and unstable angina undergoing PCI, who were pretreated with 600 mg of clopidogrel. The results of this trial indicate that bivalirudin is not superior to UFH in these patients in reducing the incidence of death, MI, or need for urgent revascularization, although the incidence of major and minor bleeding is significantly reduced at 30 days. No difference was noted in any of the ischemic endpoints up to 1 year of follow-up.

The dose of heparin used in this study (140 U/kg) is higher than the dose used in other recent PCI trials. Moreover, activated clotting time was not routinely monitored in these patients. It is unknown to what extent this may have affected the primary endpoint, especially bleeding.
Conditions
• Coronary heart disease
Therapies
• Antiplatelet agent / Clopidogrel
• Anticoagulant / Heparin
• Anticoagulant / Bivalirudin
Study Design
Randomized. Blinded. Parallel.
Patients Enrolled: 4,570
Mean Follow-Up: 1 year
Mean Patient Age: 67
% Female: 24

Mean Ejection Fraction: 58%
Primary Endpoints
Composite rate of death, MI (creatine kinase-myocardial band [CK-MB] >2x upper limit of normal [ULN]), urgent TVR within 30 days, or in-hospital major bleeding
Secondary Endpoints
Composite rate of death, MI (CK-MB >2x ULN), or urgent TVR
Patient Population
Biomarker-negative (troponin T <0.03 μg/L or CK-MB less than ULN) patients undergoing PCI
Received 600 mg of clopidogrel at least 2 hours prior to the procedure
Age >18 years
Exclusions:
Acute coronary syndromes with positive biomarkers or ST-elevation MI <48 hours
Cardiogenic shock
History of heparin-induced thrombocytopenia or other bleeding diatheses
Creatinine >3 mg/dl
References: Schulz S, Mehilli J, Ndrepepa G, et al., on behalf of the ISAR-REACT 3 Trial Investigators. Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial. Eur Heart J 2010;Feb 11:[Epub ahead of print].

Kastrati A, Neumann FJ, Mehilli J, et al., on behalf of the ISAR-REACT 3 Trial Investigators. Bivalirudin versus unfractionated heparin during percutaneous coronary intervention. N Engl J Med 2008;359:688-96.

A Randomized, Double-Blind, Active-Controlled, Multi-Center Trial (ISAR-REACT 3) of Bivalirudin Versus Unfractionated Heparin in Troponin-Negative Patients Undergoing Percutaneous Coronary Interventions After Pre-Treatment With 600 mg of Clopidogrel. Presented by Dr. Adnan Kastrati at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

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Title: Outcomes and Complications of Catheter Ablation for Atrial Fibrillation in Females
Topic: Arrhythmias
Date Posted: 2/23/2010
Author(s): Patel D, Mohanty P, Biase L, et al.
Citation: Heart Rhythm 2010;7:167-172.
Clinical Trial: No
Study Question: Are there gender-based differences in the results of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF)?
Methods: This was a retrospective analysis of 518 women and 2,747 men who underwent RFCA of AF with a 3.5-mm irrigated-tip ablation catheter. All patients underwent pulmonary vein antrum isolation, with superior vena cava isolation and ablation of fractionated atrial electrograms as clinically indicated. Daily event monitor recordings were obtained for the first 5 months post-ablation, and a 48-hour or 7-day Holter monitor was performed at 3- to 6-month intervals. Efficacy was defined as freedom from AF/atrial tachycardia in the absence of antiarrhythmic drug therapy after an 8-week blanking period.
Results: The women were significantly older than the men (mean age 59 vs. 56 years) and the interval from diagnosis to referral for RFCA was significantly longer in the women (6.5 vs. 4.8 years). At a mean of 24 months of follow-up, efficacy was significantly lower in the women (68.5% vs. 77.5%). In women, higher body mass index, persistent AF, and nonpulmonary vein triggers were independent predictors of failure. There were no significant differences in the rate of complications other than vascular complications, which were more common in women (2.7% vs. 1.0%).
Conclusions: The authors concluded that women are referred for ablation of AF less often and later than men, and the efficacy of RFCA of AF is lower in women than men.
Perspective: Women also appear to be under-referred for diagnostic cardiovascular testing, defibrillator implantation, and coronary artery bypass grafting. The reason for this gender discrepancy is unclear. The lower efficacy of RFCA in women may be related to greater atrial remodeling associated with the longer interval from diagnosis to ablation. Fred Morady, M.D., F.A.C.C.

Title: Characterization of Conduction Recovery After Pulmonary Vein Isolation Using the “Single Big Cryoballoon” Technique.
Topic: Arrhythmias
Date Posted: 2/26/2010
Author(s): Furnkranz A, Chun KR, Nuyens D, et al.
Citation: Heart Rhythm 2010;7:184-190.
Clinical Trial: No
Study Question: What is the pattern of pulmonary vein (PV) reconnection after PV isolation using a 28-mm cryoablation balloon?
Methods: Thirty-five of 71 patients with paroxysmal atrial fibrillation (AF) had recurrent AF after undergoing PV isolation using a cryoablation balloon. The subjects of this study were the 26/35 patients (mean age 59 years) who underwent a repeat ablation procedure. The PVs were mapped with a ring catheter to identify sites of PV reconnection, and PV isolation was performed by radiofrequency catheter ablation (RFCA).
Results: PV reconnection was found in all patients. One PV was reconnected in 15% of patients, two PVs in 31%, three PVs in 35%, and four PVs in 19%. Conduction gaps were identified most commonly at the inferior aspect of the right PVs and the anterior ridge between the left PVs and the left atrial appendage. All PVs were successfully re-isolated by RFCA. During a mean follow-up of 98 days, 69% of the 26 patients remained AF-free.
Conclusions: When a 28-mm cryoablation balloon is used to isolate the PVs, the most common sites of conduction recovery are the inferior ostial sites and the left atrial appendage-PV ridge.
Perspective: An advantage of cryoablation over RFCA for PV isolation is a much lower risk of PV stenosis and esophageal injury. However, reliable cryoablation requires continuous tissue contact between the balloon and antral or ostial tissue. This can be difficult to attain because of variable shapes and sizes of the PV ostia, particularly when only a 28-mm balloon is used. Published clinical experience suggests that more reliable PV isolation can be achieved when the balloon size is tailored to individual PVs. Fred Morady, M.D., F.A.C.C.

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Title: Circumferential Pulmonary Vein Isolation and Linear Left Atrial Ablation as a Single-Catheter Technique to Achieve Bidirectional Conduction Block: The Pace-and-Ablate Approach
Topic: Arrhythmias
Date Posted: 2/25/2010
Author(s): Eitel C, Hindricks G, Sommer P, et al.
Citation: Heart Rhythm 2010;7:157-164.
Clinical Trial: No
Study Question: Can conduction block in the atrium after radiofrequency catheter ablation (RFCA) be accurately assessed with a single catheter?
Methods: RFCA to achieve antral pulmonary vein isolation (PVI) in all patients and also block across posterior left atrial ablation lines in patients with persistent atrial fibrillation (AF) was performed in 147 patients (mean age 57 years) with AF. A single irrigated-tip ablation catheter was used for antral PVI and linear ablation. Global atrial capture during pacing at 10 volts from the ablation catheter along the ablation line was used to identify gaps where additional RFCA was necessary to attain complete exit block. PVI was then verified with a conventional ring catheter.
Results: Using the “pace-and-ablate” approach, complete PVI was achieved in 95% of patients and confirmed with a ring catheter in 94% of patients. Complete conduction block was achieved across 74% of the posterior left atrial ablation lines. There was freedom from AF in 84% of patients at 12 months.
Conclusions: Conduction block can be reliably achieved across circumferential and linear atrial ablation lines using a single ablation catheter that is used to confirm conduction block by the absence of atrial capture when pacing along the ablation line.
Perspective: Conventional PVI is performed using an ablation catheter and a ring catheter to monitor the pulmonary veins. The advantage of the 'pace-and-ablate' strategy used in this study is that only a single catheter is necessary in the left atrium. A disadvantage of this technique is that it does not identify the number or locations of the gaps in the ablation lines. Fred Morady, M.D., F.A.C.C.

Title: Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: Proposed Modification of the Task Force Criteria
Topic: Arrhythmias
Date Posted: 2/25/2010
Author(s): Marcus FI, McKenna WJ, Sherrill D, et al.
Citation: Circulation 2010;Feb 19:[Epub ahead of print].
Clinical Trial: No
Study Question: How can the sensitivity and specificity of the original Task Force criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) be improved?
Methods: One hundred eight patients with genetically confirmed ARVC/D were compared to normal subjects. Multiple parameters were analyzed and diagnostic criteria were selected based on receiver operating characteristic curves that identified optimal sensitivity and specificity.
Results: A definite diagnosis of ARVC/D is warranted in the presence of two major criteria, one major plus two minor criteria, or four minor criteria. The major criteria identified in this study were: 1) right ventricular (RV) akinesia, dyskinesia, or aneurysm by magnetic resonance imaging (MRI), echocardiography, or angiography; 2) fibrous replacement (>50%) of RV myocardium on biopsy; 3) T-wave inversion in V1-V3; 4) epsilon wave in V1-V3; 5) ventricular tachycardia (VT) with a left bundle branch block morphology and superior axis; 6) ARVC/D in a first-degree relative based on Task Force criteria or pathologic confirmation; and 7) the presence of an ARVC/D-related mutation. The minor criteria included (but were not limited to) an abnormal signal-averaged electrocardiogram, VT with a left bundle branch block morphology and inferior axis, and confirmed ARVC/D in a second-degree relative.
Conclusions: The updated Task Force criteria are likely to improve the accuracy with which ARVC/D is diagnosed based on structural, histological, electrocardiographic, arrhythmic, and genetic criteria.
Perspective: ARVC/D is characterized by fibrofatty replacement of the RV myocardium. In the past, thinning of the RV wall and fatty infiltration identified by MRI were felt to be reliable diagnostic criteria. However, normal subjects now are recognized as sometimes having fatty replacement without any fibrous component, and this has impaired the specificity of MRI. Fred Morady, M.D., F.A.C.C.

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Title: Early and Late Outcome of Treated Patients Referred for Syncope to Emergency Department: the EGSYS 2 Follow-Up Study
Topic: Arrhythmias
Date Posted: 2/24/2010
Author(s): Andrea U, Attilio DR, Franco G, et al., on behalf of the Evaluation of Guidelines in Syncope Study 2 (EGSYS 2) Group.
Citation: Eur Heart J 2010;Feb 18:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the prognosis of patients with syncope?
Methods: This was a multicenter, prospective study of 380 patients (mean age 66 years) with syncope initially evaluated in an emergency department (ED). Therapy was at the discretion of the treating physician. The mean duration of follow-up was 20 months. The 1° endpoint was death from any cause or syncope recurrence.
Results: The most common causes of syncope were neurocardiogenic syncope in 64% of patients, orthostatic hypotension in 17%, cardiac syncope in 15%, and an arrhythmia in 11%. All-cause mortality was 9.2%. The strongest predictors of mortality were structural heart disease or an abnormal electrocardiogram (hazard ratio [HR], 5.6), hypertension (HR, 3.0), and trauma from syncope (HR, 2.24). Mortality in patients with cardiac syncope was significantly higher than in patients with other causes of syncope (37% vs. 7-11%). Syncope recurred in 16% of patients and the recurrence rate was unrelated to the etiology of syncope. The strongest predictors of recurrent syncope were palpitations before syncope (HR, 3.4), male gender (HR, 1.8), and absence of prodrome (HR, 0.4).
Conclusions: The risk of death during follow-up in patients with syncope is related to associated cardiac disease. Syncope recurrence is unrelated to the cause of syncope.
Perspective: A limitation of this study is that left ventricular ejection fraction was not included in the analysis and probably would have been a stronger predictor of mortality than simply the presence of structural heart disease. Fred Morady, M.D., F.A.C.C.

Title: Structural Abnormalities of the Pulmonary Trunk in Tetralogy of Fallot and Potential Clinical Implications: A Morphological Study
Topic: Congenital Heart Disease
Date Posted: 3/1/2010
Author(s): Bйdard E, McCarthy KP, Dimopoulos K, Giannakoulas G, Gatzoulis MA, Ho SY.
Citation: J Am Coll Cardiol 2009;54:1883-1890.
Clinical Trial: No
Study Question: Are intrinsic histological abnormalities present from birth in the pulmonary trunk of patients with tetralogy of Fallot (TOF)?
Methods: A review of 39 formalin-fixed necropsy heart specimens of patients with TOF was performed, and compared with 17 normal control specimens. Histological specimens were studied with light microscopy using standard stains, and findings were graded according to severity.
Results: Of the 39 patients in the TOF group, 11 had undergone palliative surgeries while 10 had undergone complete repair at a median age of 8 years (range 2.5-18 years). Histological changes of grade 2 were common, including medionecrosis in 59%, fibrosis in 36%, cyst-like formation in 56%, and abnormal elastic tissue configuration in 56%. Patients with TOF were found to have higher total histology grading scores (median 6, range 1-9) than controls (median 1, range 1-9). Histological abnormalities were noted in all TOF populations, including infants (median 3.5, range 1-9), patients post-palliative surgery (median score 5, range 2-9), and patients post-complete repair (median score 7.5, range 4-9).
Conclusions: Significant histological abnormalities of the pulmonary trunk in hearts with TOF are present from birth, and are seen in patients prior to and after palliative surgery or complete repair.
Perspective: Previous research has demonstrated histological abnormalities in the aortic root of patients with TOF. This study demonstrates similar abnormalities in the pulmonary tract, and shows them to be present even in fetal life. Although further study will be required to determine the clinical significance of these findings, it is possible that these histological abnormalities might predispose patients to pulmonary regurgitation and/or right ventricular dysfunction. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Thiazolidinedione Drugs and Cardiovascular Risks: A Science Advisory From the American Heart Association and American College of Cardiology Foundation
Topic: General Cardiology
Date Posted: 2/23/2010
Author(s): Kaul S, Bolger AF, Herrington D, et al.
Citation: J Am Coll Cardiol2010;Feb 23:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember about this science advisory.

1. The thiazolidinedione class of drugs, ligands of the peroxisome-proliferator–activated receptor-γ, which is intricately involved in insulin signaling, were the first drugs developed that directly targeted insulin resistance.

2. Two thiazolidinediones are currently available in the United States, rosiglitazone (Avandia) and pioglitazone (Actos).

3. To date, there has been only one randomized clinical trial prospectively designed to assess the effect of rosiglitazone on cardiovascular outcomes, the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial.

4. The majority of evidence regarding the cardiovascular effects of rosiglitazone is derived from meta-analyses of randomized clinical trials that evaluated the effects of rosiglitazone on glycemic control.

5. An association between rosiglitazone and ischemic heart disease (IHD) outcomes has not yet been firmly established. Additional prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone.

6. However, sufficient evidence has emerged to raise concerns about a potential adverse effect of rosiglitazone. The Food and Drug Administration’s decision on November 14, 2007, to allow rosiglitazone to remain on the market with an additional boxed warning about the risk of IHD events further reflects these uncertainties.

7. The majority of published studies do not suggest an increased hazard for IHD events in pioglitazone-treated patients. Accordingly, there is no boxed warning on the risk of IHD for pioglitazone.

8. On the basis of all available evidence, thiazolidinediones should not be used with an expectation of benefit with respect to IHD events, and should be used with the understanding that they might increase the risk of heart failure.

9. More data are urgently needed to clarify the effects of all existing and future glucose-lowering agents, including thiazolidinediones, on IHD events.

10. The ongoing Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) study will test the cardiovascular effects of rosiglitazone or pioglitazone when used as part of standard of care compared to similar standard of care without rosiglitazone or pioglitazone in patients with type 2 diabetes who have a history of or are at risk for cardiovascular disease. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Survival as a Function of HbA1c in People With Type 2 Diabetes: A Retrospective Cohort Study
Topic: General Cardiology
Date Posted: 2/25/2010
Author(s): Currie CJ, Peters JR, Tynan A, et al.
Citation: Lancet 2010;375:481-489.
Clinical Trial: No
Study Question: What are survival rates as a function of glycated hemoglobin (HbA1c) in people with type 2 diabetes?
Methods: Two cohorts of patients ages 50 years and older with type 2 diabetes were generated from the United Kingdom General Practice Research Database from November 1986 to November 2008. Investigators identified 27,965 patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents, and 20,005 who had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity were identified as important confounding factors, and Cox survival models were adjusted for these factors accordingly.
Results: For combined cohorts, compared with the HbA1c decile with the lowest hazard (median HbA1c 7.5%, interquartile range [IQR], 7.5-7.6%), the adjusted hazard ratio (HR) of all-cause mortality in the lowest HbA1c decile (6.4%, 6.1-6.6) was 1.52 (95% confidence interval [CI], 1.32-1.76), and in the highest HbA1c decile (median 10.5%, IQR 10.1-11.2%) was 1.79 (95% CI, 1.56-2.06). Results showed a general U-shaped association, with the lowest HR at an HbA1c of about 7.5%. HR for all-cause mortality in people given insulin-based regimens (2,834 deaths) versus those given combination oral agents (2,035) was 1.49 (95% CI, 1.39-1.59).
Conclusions: The authors concluded that low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events.
Perspective: The study suggests that an HbA1c of ~7.5% is associated with lowest all-cause mortality and lowest progression to large-vessel disease events in type 2 diabetes. An increase or decrease from this mean HbA1c value appears to be associated with heightened risk of adverse outcomes. The study data also suggests that oral combination therapy in a wide HbA1c range is safe with respect to all-cause mortality and large-vessel events, but for insulin-based therapy, a narrower range might be desirable. Whether intensification of glucose control with insulin therapy alone further heightens risk of death in patients with diabetes needs additional study. It should be noted that in the ADVANCE study, intensive glycemic control significantly reduced the primary endpoint, which was a combination of microvascular events and major adverse cardiovascular events. For now, the totality of evidence supports the 2010 American Diabetes Association recommendations for the HbA1c goal for adults in general to be <7%. Additional prospective studies are needed to refine optimal HbA1c levels in patients with diabetes. Debabrata Mukherjee, M.D., F.A.C.C

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Title: Natural History and Expansive Clinical Profile of Stress (Tako-Tsubo) Cardiomyopathy
Topic: General Cardiology
Date Posted: 3/1/2010
Author(s): Sharkey SW, Windenburg DC, Lesser JR, et al.
Citation: J Am Coll Cardiol 2010;55:333-341.
Clinical Trial: No
Related Resources
JACC Article: Natural History and Expansive Clinical Profile of Stress (Tako-Tsubo) Cardiomyopathy

Study Question: What is the clinical profile and natural history of stress cardiomyopathy?
Methods: The authors prospectively followed 136 consecutive patients who presented with stress-induced cardiomyopathy to their institution. This is a report of their clinical profile and outcome. The average follow-up was 2.3 years.
Results: Almost all the patients were women (n = 130; 96%), with an average age of 68 years (range 32-94 years). Most of the cases (121 patients, 89%) were precipitated by intensely stressful emotional (n = 64) or physical (n = 57) events, including 22 associated with sympathomimetic drugs or medical/surgical procedures. No precipitating stressor was identified in 15 (11%) patients. Stress cardiomyopathy developed on a background of beta-blocker in 25 (18%) patients. Twenty-five patients (18%) were taking beta-blockers at the time of stress cardiomyopathy events. Cardiovascular magnetic resonance (CMR) imaging identified three distinct patterns of involvement with mid left ventricular and apex involvement being most common, with the remainder of patients presenting with only apical, or only mid left ventricular involvement. Right ventricular involvement occurred in approximately 25% of patients. Rapid recovery to normal systolic function was common, although it was delayed >2 months in a small number of patients (5%). Right and/or left ventricular thrombi were identified in five patients (predominantly by CMR imaging), including two with embolic events. Three patients (2%) died in-hospital. Among those surviving to hospital discharge, 17 patients died, with most deaths within the first year and related to a noncardiac cause. Recurrent stress-induced cardiomyopathy developed in 5% of the survivors.
Conclusions: Stress-induced cardiomyopathy is a heterogeneous disorder with a generally good cardiac prognosis.
Perspective: This is an interesting paper that adds to the growing body of data on this increasingly recognized albeit rare disorder. The study corroborates earlier series suggesting generally good cardiac outcome in these patients. A small number of patients will develop recurrence of symptoms, and it is unclear how to identify these patients and if beta-blockers are truly protective. Multicentric registries are needed to better define the outcome and best treatment for these patients. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Carotid Artery Stenting Compared With Endarterectomy in Patients With Symptomatic Carotid Stenosis (International Carotid Stenting Study): An Interim Analysis of a Randomised Controlled Trial
Topic: Interventional Cardiology
Date Posted: 3/1/2010
Author(s): International Carotid Stenting Study Investigators.
Citation: Lancet 2010;Feb 26:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: International Carotid Stenting Study (ICSS)
Trial: Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)

Study Question: What is the relative safety and efficacy of carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) in patients with symptomatic carotid artery stenosis?
Methods: The ICSS (International Carotid Stenting Study) investigators randomized 1,713 patients with a recently symptomatic carotid artery lesion to CEA (n = 858) or CAS (n = 855). The primary endpoint of the trial is 3-year rate of fatal or disabling stroke. This paper reported the results of the interim safety endpoint of stroke death or procedural myocardial infarction (MI) at 120 days.
Results: At 120 days after randomization, the rate of disabling stroke or death was similar between the two groups (4.0% with CAS vs. 3.2 % in the CEA arm, hazard ratio [HR], 1.28; confidence interval [CI], 0.77-2.11). The incidence of stroke, death, or procedural MI (8.5% vs. 5.2%, HR, 1.69; p = 0.006) was higher in patients randomized to CAS. Patients randomized to CAS had an exaggerated hazard of mortality (HR, 2.76; 1.16-6.56) or any stroke (HR, 1.92; 1.27-2.89). There were three fatal MIs in the CAS arm and four nonfatal MIs in the CEA arm. Two centers had unexpectedly high rates of major adverse events (five deaths or disabling strokes among 11 patients undergoing CAS and one fatal stroke among those undergoing CEA) and enrollment from those centers was stopped prematurely.
Conclusions: Compared with CEA, CAS is associated with a greater risk for procedural stroke in patients with symptomatic carotid stenosis.
Perspective: This study adds to the ongoing debate on the relative safety and efficacy of CAS and CEA. The totality of available evidence suggests similar long-term efficacy of CEA and CAS (Meier et al., BMJ 2010), whereas the risk of procedural non-disabling stroke appears to be higher with CAS. The outcome of this study is in contrast to that of the recently reported CREST trial, where there was no difference in the primary endpoint (death, stroke, and procedural MI), although the risk of non-disabling stroke was lower with CEA, whereas the risk of MI was lower with CAS. The results of these trials suggest that the optional revascularization strategy (CAS vs. CEA) should be based on the patient’s unique risk of procedural complications, operator experience, and patient and physician preference. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Comparison of Platelet Function Tests in Predicting Clinical Outcome in Patients Undergoing Coronary Stent Implantation
Topic: Interventional Cardiology
Date Posted: 2/23/2010 4:00:00 PM
Author(s): Breet NJ, van Werkum JW, Bouman HJ, et al.
Citation: JAMA 2010;303:754-762.
Clinical Trial: No
Study Question: Can platelet function tests performed at time of percutaneous coronary intervention (PCI) predict clinical outcome?
Methods: The authors prospectively studied 1,069 consecutive patients that underwent elective stent-based PCI at their institution between December 2005 and December 2007. All patients were on clopidogrel, and on-treatment platelet reactivity was measured in all patients using light transmittance aggregometry, VerifyNow P2Y12 assay, Plateletworks assay, IMPACT-R, and the platelet function analysis system (PFA-100). Cut-off values for high on-treatment platelet reactivity were established by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety endpoint included TIMI major and minor bleeding.
Results: One-year follow-up was available for 99.8% of the patients. Adherence to clopidogrel was 95% after 6 months and 82% at 1 year. Over 1-year follow-up, there were 18 deaths (1.7%), 6.0% had nonfatal acute myocardial infarction, 1.2% presented with definite stent thrombosis, and 1.3% had a nonfatal ischemic stroke. There were three possible stent thromboses (0.3%), and bleeding events occurred in 5.1% of the patients (TIMI-major 3.1%, TIMI-minor bleeding 2.2%).The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (11.7% vs. 6.0%; p < 0 .001 area under the curve [AUC], 0.63), VerifyNow (13.3% vs. 5.7%, p < 0.001, AUC 0.62), and Plateletworks (12.6% vs. 6.1%, p = 0.005, AUC 0.61). The other assays were not able to discriminate between those with or without ischemic events. None of the tests identified patients at risk for bleeding.
Conclusions: Assessment of platelet function using light transmittance aggregometry, VerifyNow, and Plateletworks was significantly but modestly associated with ischemic events at 1 year.
Perspective: Multiple studies have established an association between a lesser degree of platelet inhibition and the occurrence of atherothrombotic events. The field has been clouded by the use of multiple platelet function assays with little inter-assay correlation. This study, with its large population and nearly 100% follow-up, provides much needed clarity to the field. Only three assays demonstrated a significant albeit moderate association between ischemic outcomes and degree of platelet inhibition. Given the moderate strength of the association, it would be premature to use platelet function testing to guide routine clinical practice at present. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Vascular Inflammation in Obesity and Sleep Apnea
Topic: Prevention/Vascular
Date Posted: 2/24/2010
Author(s): Jelic S, Lederer DJ, Adams T.
Citation: Circulation 2010;121:1014-1021.
Clinical Trial: No
Study Question: Both obesity and obstructive sleep apnea (OSA) are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. Are the endothelial alterations that are attributed commonly to obesity in fact related to OSA?
Methods: Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, the expression of nuclear factor-ĸB and nitrotyrosine were quantified by immunofluorescence in freshly harvested venous endothelial cells. Basal endothelial nitric oxide (NO) production and activity were quantified by the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation.
Results: Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (n = 38) than in OSA-free subjects (n = 33) regardless of central adiposity. Expression of nuclear factor-ĸB was greater in obese OSA patients than in obese OSA-free subjects (p = 0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine and nuclear factor-ĸB significantly decreased in OSA patients who adhered to continuous positive airway pressure ≥4 hours daily.
Conclusions: Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients.
Perspective: This study adds to the body of evidence that OSA may contribute to coronary risk and cardiovascular events. A few of the cardiometabolic effects of OSA include hypertension, increase in high-sensitivity C-reactive protein, heightened sympathetic tone, reactive platelets, dysglycemia, insulin resistance, and increase in cortisol, leptin, and growth hormone. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Coronary Heart Disease in Postmenopausal Recipents of Estrogen Plus Progestin Therapy: Does the Increased Risk Ever Disappear? A Randomized Trial
Topic: Prevention/Vascular
Date Posted: 2/25/2010
Author(s): Toh S, Hernandez-Diaz S, Logan R, Rossouw JE, Hernan MA.
Citation: Ann Intern Med 2010;152:211-217.
Clinical Trial: No
Study Question: Does risk for coronary heart disease (CHD) associated with hormonal replacement decrease over time?
Methods: Data from the Women’s Health Initiative (WHI), a randomized double-blinded, placebo-controlled trial, were used for this analysis. A total of 16,608 postmenopausal women (from 40 clinical centers in the United States) were included. Baseline data were collected from 1993 to 1998. Women with an intact uterus were randomized to either conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. The primary outcome of interest was CHD events including acute myocardial infarction, silent myocardial infarction identified through serial electrocardiograms, or death due to CHD.
Results: Women randomized to continuous hormonal replacement were at increased CHD risk compared to the placebo group for the initial 2 years (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.55-3.62) and for the first 8 years (HR, 1.69; 95% CI, 0.98-2.98). Among women within 10 years of menopause, the risk was also increased for those receiving continuous hormone therapy for the first 2 years (HR, 1.29; 95% CI, 0.52-3.18), with nonsignificant differences observed for the first 8 years (HR, 0.64; 95% CI, 0.21-1.99). The survival curves for continuous use and placebo crossed at about the 6-year time point (95% CI, 2-10 years).
Conclusions: The authors concluded that no suggestion of decreased risk for CHD was observed over the first 2 years of estrogen plus progesterone use, including among women who were less than 10 years postmenopausal.
Perspective: These data support recommendations that hormonal replacement therapy with conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) is not recommended for modification of CHD risk. In terms of CHD risk, other forms of hormonal replacement have not been studied; therefore, whether these data are generalizable to all forms of hormone therapy is not clear. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults
Topic: Prevention/Vascular
Date Posted: 3/3/2010 5:00:00 PM
Author(s): Selvin E, Steffes MW, Zhu H, et al.
Citation: N Engl J Med 2010;362:800-811.
Clinical Trial: No
Study Question: Is the glycated hemoglobin in persons without diabetes predictive of cardiovascular outcomes?
Methods: The prognostic value of glycated hemoglobin and fasting glucose were assessed for their ability to identify adults at risk for diabetes or cardiovascular disease. Glycated hemoglobin (glycohemoglobin or HgA1c) was measured in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990–1992 period) of the Atherosclerosis Risk in Communities (ARIC) study.
Results: Fifty-eight percent were women, 77% were white, 32% had hypertension, and 22.7% had a family history of diabetes. Mean values for risk factors were as follows: age 57 years, fasting blood sugar (FBS) 105 mg/dl, glycated hemoglobin 5.5%, low-density lipoprotein cholesterol 133 mg/dl, high-density lipoprotein cholesterol 51 mg/dl, and body mass index 27.7 kg/m2. The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios for diagnosed diabetes were 0.52, 1.00 (reference), 1.86, 4.48, and 16.47, respectively. For coronary heart disease, the hazard ratios were 0.96, 1.00 (reference), 1.23, 1.78, and 1.95, respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose.
Conclusions: In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause, as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.
Perspective: Persons with a glycated hemoglobin ≥6.5% or FBS >126 mg/dl are characterized as diabetics. The former represent the average blood sugar over 2 to 3 months. A level greater than 5.5% is associated with an increase in risk for diabetes and coronary disease independent of other variables, and the relative risk for 0.5% increments is considerable. The authors concluded that a glycated hemoglobin exceeding 6% may be a useful marker to identify persons at risk for development of diabetes, and cardiovascular disease and death. Consideration should be given to replacing the FBS with glycated hemoglobin for risk stratification of adults with and without vascular disease. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Characteristics, Performance Measures, and In-Hospital Outcomes of the First One Million Stroke and Transient Ischemic Attack Admissions in Get With The Guidelines-Stroke
Topic: Prevention/Vascular
Date Posted: 2/26/2010
Author(s): Fonarow GC, Reeves MJ, Smith EE, et al.
Citation: Circ Cardiovasc Qual Outcomes 2010;Feb 22:[Epub ahead of print].
Clinical Trial: No
Study Question: What are the demographics, treatments received, quality of care, and early clinical outcomes of the first million patients entered into the Get With The Guidelines (GWTG-Stroke) program?
Methods: The authors reported their analysis of data from an ongoing voluntary, continuous registry and performance improvement initiative that collects patient-level data on subjects with transient ischemic attack (TIA), stroke, subarachnoid hemorrhage, ischemic stroke, and intracerebral hemorrhage. Collected data included patient characteristics, performance measures, and in-hospital outcomes. Seven performance measures based on the American Heart Association/American Stroke Association and Joint Commissions Primary Stroke Centers Certification criteria for quality of care for stroke patients were observed. The authors defined all-or-none as a measure of the proportion of patients who received all of the performance measure interventions for which they were eligible.
Results: The authors reported data on the first million eligible patients at 1,392 participating hospitals between 2003 and 2009. There were 601,599 (60.2%) ischemic strokes, 108,671 (10.9%) intracerebral hemorrhages, 34,945 (3.5%) subarachnoid hemorrhages, 26,977 (2.7%) strokes otherwise not classified, and 227,788 (22.8%) TIAs. In-hospital mortality was significantly higher for both subarachnoid and intracerebral hemorrhage (20.4% and 25.0%, respectively), than for patients suffering ischemic stroke (5.5%) or TIA (0.3%). From 2003 to 2009 there were significant improvements, almost doubling the percentage of patients who received all of the indicated interventions (44.0-84.3%; + 40.3%, p < 0.0001). The authors also reported temporal improvements in the length of stay and risk-adjusted in-hospital mortality rate.
Conclusions: The authors concluded that the GWTG-Stroke program represents an integrated stroke and TIA registry that supports national surveillance, innovative research, and sustained quality improvement efforts facilitating evidence-based stroke/TIA care.
Perspective: This report represents a milestone in observational registries for stroke care in the United States. It is gratifying to note that adherence to agreed-upon quality of care interventions have improved significantly over the decade. It is particularly interesting and also gratifying to note that the use of thrombolytic therapy within 2 hours of presentation increased from <30% in 2003 to >70% of eligible patients in 2009 (p < 0.0001). Although the authors observed a significant improvement in quality of care as well as outcomes, the observational nature of these data makes it impossible to infer a causal relationship. Other temporal trends and changes in care may have contributed to the improvement in outcomes. This study does, however, demonstrate the feasibility of prospectively collected data on a national scale, providing nationally representative information and benchmarks for both care and outcomes of patients with all types of stroke. The GWTG-Stroke program will provide an excellent opportunity to study changes in stroke care nationally going forward. James B. Froehlich, M.D., F.A.C.C.

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Title: Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)
Trial Sponsor: National Institute of Neurological Diseases and Stroke
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 2/27/2010
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Related Trial: Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S: 30-Day and 4-Year Results)
Related Trial: Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)
Related Trial: Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS)
Related Trial: Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE: 30-Day and 2-Year Results)
Related Trial: International Carotid Stenting Study (ICSS)
Journal Scan: Carotid Artery Stenting Compared With Endarterectomy in Patients With Symptomatic Carotid Stenosis (International Carotid Stenting Study): An Interim Analysis of a Randomised Controlled Trial

Description
Current literature indicates that carotid artery stenting (CAS) is not superior to carotid endarterectomy (CEA), with a potentially higher risk of complications. Accordingly, CAS is currently reserved for high-risk patients, who are not good candidates for surgery. However, there has been a significant improvement in CAS and CEA techniques over the past few years. Therefore, the CREST study sought to compare outcomes between CAS and CEA in a contemporary population.
Hypothesis
Carotid stenting would be as safe and effective as carotid surgery in patients at risk for stroke.
Drugs/Procedures Used
In patients undergoing CAS, stenting was undertaken using the Rx Acculink stent. Embolic protection was achieved using the Rx Accunet system. CEA was performed using standard techniques.
Concomitant Medications
All patients were optimally treated with aspirin, antihypertensives, and other medications for stroke.
Principal Findings
A total of 2,502 patients were randomized, of which 1,262 were randomized to CAS and 1,240 to CEA. Of the total, 1,326 were symptomatic, and the rest were asymptomatic. The majority of patients had risk factors for cardiovascular disease, including diabetes (30%), hypertension (85%), dyslipidemia (83%), current smokers (25%), and prior coronary artery bypass grafting (21%).

Preliminary findings indicate that the primary endpoint of death, myocardial infarction (MI), or stroke at 30 days plus ipsilateral stroke thereafter was similar between the two arms (7.2% vs. 6.8%, hazard ratio 1.11, 95% confidence interval 0.81-1.51, p = 0.51). The incidence of death, MI, or stroke at 30 days was similar between the two arms (5.2% vs. 4.5%, p = 0.38). Periprocedural strokes were higher in the CAS arm (4.1% vs. 2.3%, p = 0.01). However, the incidence of debilitating and major strokes was similar between the two arms (0.9% vs. 0.7%, p = 0.52). Minor strokes were more frequent in the CAS group (2.7% vs. 1.5%, p < 0.05). The incidence of MI was significantly lower in the CAS arm, as compared with the CEA arm (1.1% vs. 2.3%, p = 0.03). Cranial nerve palsies were also more common in the CEA arm (0.3% vs. 4.8%, p < 0.0001). Long-term follow-up suggested that the incidence of ipsilateral stroke after the periprocedural period (approximately 4 years of follow-up) was similar between the two arms (2.0% vs. 2.4%, p = 0.85).

Subgroup analyses suggested that there was no difference based on gender or prior stroke/transient ischemic attack (TIA) status. However, there seemed to be evidence of effect modification by age, such that patients ≤69 years did better with CAS, whereras those ≥70 years did better with CEA. Moreover, the younger the patient, the greater the benefit with CAS, and conversely, the older the patient, the greater the benefit with CEA.
Interpretation
The results of the CREST trial indicate that CAS is associated with similar 30-day outcomes, as compared with CEA in a contemporary population. The risk of minor strokes is higher with CAS, whereas the risk of MI is higher with CEA. Older patients derive more benefit from CEA, whereas younger patients derive more benefit from CAS.

These findings are very interesting. Final full publication of these results is eagerly awaited. Perhaps based on this study, the Centers for Medicare and Medicaid (CMS) will reconsider its current coverage decision regarding CAS.
Conditions
• Carotid stenosis
Therapies
• Stent
Study Design
Randomized. Parallel.
Patients Enrolled: 2,502
Mean Follow-Up: 4 years
Mean Patient Age: 69.1 years
% Female: 37

Primary Endpoints
Occurrence of any stroke, MI, or death during a 30-day periprocedural period
Ipsilateral stroke during follow-up of up to 4 years
Secondary Endpoints
Restenosis
Health-related quality of life
Patient Population
Age >18 years
Symptomatic patients with recent neurological events (TIA or non-disabling stroke) with an associated carotid stenosis ≥50% by angiography, ≥70% by ultrasound, or ≥70% by computed tomography angiography (CTA) or magnetic resonance angiography (MRA)
Asymptomatic patients with no recent (in the last 6 months) neurological events referable to the study with artery and carotid stenosis (patients with symptoms beyond 180 days are considered asymptomatic) ≥60% by angiography or ≥70% by ultrasound or ≥80% by CTA or MRA
Exclusions:
Conditions that: 1) interfere with the evaluation of endpoints, 2) are known to interfere with the completion of CEA or CAS, or 3) affect the likelihood of survival for the study period (4 years)
Chronic atrial fibrillation and/or anticoagulation or episodic atrial fibrillation within the last 6 months
References: Presented by Dr. Wayne M. Clark at the International Stroke Conference, San Antonio, TX, February 26, 2010.

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Title: International Carotid Stenting Study (ICSS)
Trial Sponsor: Medical Research Council, the Stroke Association, Sanofi-Synthйlabo, European Union
Year Presented: 2009
Year Published 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 2/28/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Related Trial: Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)
Related Trial: Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S: 30-Day and 4-Year Results)
Related Trial: Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE: 30-Day and 2-Year Results)
Journal Scan: Carotid Artery Stenting Compared With Endarterectomy in Patients With Symptomatic Carotid Stenosis (International Carotid Stenting Study): An Interim Analysis of a Randomised Controlled Trial

Description
The goal of the trial was to evaluate treatment with carotid artery stenting compared with carotid endarterectomy among patients with recently symptomatic carotid artery stenosis.
Hypothesis
Carotid artery stenting would be more effective at preventing major cerebrovascular accidents.
Drugs/Procedures Used
Patients with recently symptomatic carotid artery stenosis were randomized to carotid artery stenting (n = 855) versus carotid endarterectomy (n = 858). The use of an embolic protection device was encouraged, but not mandatory during stenting.
Concomitant Medications
Patients who received a carotid stent were pretreated with aspirin and clopidogrel, and for 30 days after the procedure.
Principal Findings
Overall, 1,713 patients were randomized. In the stent group, the mean age was 70 years, 30% were women, the degree of carotid stenosis was 70-99% in 89% of patients, 32% had a recent transient ischemic attack, and 46% had a recent ischemic hemispheric stroke. Carotid stenting was performed at experienced centers in 88% and carotid endarterectomy was performed at experienced centers in 89%.

At 4 months, the composite outcome of death, stroke, or procedural myocardial infarction occurred in 8.5% of the stent group versus 5.2% of the endarterectomy group (p = 0.006). Similarly, any stroke occurred in 7.7% versus 4.1% (p = 0.002), any stroke or death 8.5% versus 4.7% (p = 0.001), any stroke or procedural death 8.0% versus 4.2% (p = 0.001), disabling stroke or death 4.0% versus 3.2% (p = 0.34), and all-cause death 2.3% versus 0.8% (p = 0.017), respectively for stent versus endarterectomy.

In the stent group, most of the strokes within 4 months were ipsilateral and ischemic in etiology (non-disabling and lasting more than 7 days). Cranial nerve palsy occurred in 1 versus 34 (p < 0.0001), and severe hematoma occurred in 9 versus 28 (p = 0.0007), respectively.
Interpretation
Among patients with a recent transient ischemic attack or stroke attributable to significant carotid artery stenosis, the use of carotid stenting was not superior to endarterectomy. Carotid artery stenting was associated with an increased hazard of death, stroke, or myocardial infarction within 4 months. There was also an excess of: 1) any stroke, 2) any stroke or death, 3) any stroke or procedural death, and 4) all-cause death among patients who received a carotid stent. There were fewer cranial nerve palsies and hematomas in the stent group. In the stent group, most strokes were ipsilateral, ischemic in etiology, and non-disabling, although lasting for >7 days.

The investigators performed a meta-analysis on three trials that enrolled symptomatic patients with carotid stenosis (EVA-3S, SPACE, and ICSS) and documented increased hazard of death, stroke, or myocardial infarction at 30 days with carotid stenting (p = 0.0002).

The recently presented CREST trial, which enrolled asymptomatic and symptomatic patients with carotid artery stenosis, found a similar incidence of death, stroke, or myocardial infarction within 30 days; however, minor strokes were increased with stenting, and myocardial infarctions were increased with carotid endarterectomy.
Conditions
• Carotid stenosis
• Cerebrovascular disease
• Prevention
Therapies
• Stent
• Carotid endarterectomy
Study Design
Randomized. Blinded. Parallel. Stratified.
Patients Enrolled: 1,713
Mean Follow-Up: 3 years
Mean Patient Age: 70 years
% Female: 30%

Primary Endpoints
3-year composite of fatal or disabling stroke in any territory
Secondary Endpoints
4-month composite of death, stroke, or procedural myocardial infarction
Any stroke
Any stroke or death
Any stroke or procedural death
Disabling stroke or death
All-cause death
Patient Population
Patients at least 40 years of age
Carotid artery stenosis >50%
Symptoms attributable to the carotid artery stenosis within the preceding 12 months
Exclusions:
Major stroke without recovery of function
Previous carotid artery stenting or endarterectomy or any contraindication for either procedure
Planned coronary artery bypass grafting or other major surgery
References: International Carotid Stenting Study Investigators. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010;Feb 26:[Epub ahead of print].

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Title: Aspirin for Asymptomatic Atherosclerosis (AAA)
Trial Sponsor: British Heart Foundation, Chief Scientist Office of the Scottish Executive, and Bayer Healthcare
Year Presented: 2009
Year Published 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 3/2/2010 4:00:00 PM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.

Related Resources
Summary Slide: AAA Trial
Related Trial: Physicians' Health Study (Aspirin component) (Physicians' Health (Aspirin))
Related Trial: Women's Health Study: Low-Dose Aspirin in Primary Prevention

Description
The goal of the trial was to evaluate treatment with aspirin compared with placebo for primary prevention among patients with a low ankle brachial index (ABI).
Hypothesis
Use of low-dose aspirin would be associated with a reduction in the composite outcome of a fatal or nonfatal coronary event, stroke, or revascularization for primary prevention in patients with a low ABI.
Drugs/Procedures Used
Subjects (n = 28,980) free of cardiovascular disease underwent ABI screening (ratio of systolic pressure in the ankle to that in the arm). Patients with low ABI (≤0.95) were randomized in a double-blind manner to 100 mg enteric coated aspirin (n = 1,675) versus matching placebo (n = 1,675). The trial was powered to detect a 25% reduction in events with aspirin versus placebo.
Concomitant Medications
At baseline, in the aspirin group, diuretics were used in 15.5%, beta-blockers in 10.0%, nitrates/calcium channel blockers in 6.6%, angiotensin-converting inhibitors/angiotensin-receptor blockers in 6.3%, and lipid-lowering agents in 4.1%.
Principal Findings
The mean ABI at study entry was 0.86. Mean age was 62 years, and 72% were women.

There was no difference in the primary endpoint of fatal or nonfatal coronary event, stroke, or revascularization between the aspirin and placebo groups (10.8% vs. 10.5%, respectively, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.84-1.27, p = NS). Likewise, there was no difference between the aspirin and placebo groups in the secondary composite endpoint, which included the primary endpoint plus angina, intermittent claudication, and transient ischemic attack (HR 1.00, 95% CI 0.85-1.17, p = NS) or in the secondary endpoint of all-cause mortality (HR 0.95, 95% CI 0.77-1.16, p = NS). There was also no difference in nonfatal stroke (2.2% vs. 2.3%, p = NS) or nonfatal myocardial infarction (MI) (3.7% vs. 4.1%, p = NS). Major bleeding requiring hospital admission occurred in 2.0% of the aspirin group and 1.2% of the placebo group (HR 1.71, 95% CI 0.99-2.97).
Interpretation
Among patients with a low ABI but no known cardiovascular disease, treatment with enteric coated aspirin was not associated with a difference in the composite endpoint of a fatal or nonfatal coronary event, stroke, or revascularization at a mean follow-up of 8.2 years compared with placebo. Aspirin therapy was associated with an increase in major bleeding.

The efficacy of aspirin for secondary prevention following a cardiovascular event has been well established in several large-scale trials, as well as in a patient-level meta-analysis by the Antithrombotic Trialists' Collaboration. However, the effect of aspirin for primary prevention has not been studied as extensively and has shown mixed results in the trials that are available. Low-dose aspirin decreased the risk of first MI by 44% compared with placebo in the Physician's Health Study. In the Women’s Health Study, there was no significant difference in major cardiovascular events, but stroke was lower in women randomized to aspirin compared with placebo.

Healthy subjects with a low ABI have previously been shown to be at high risk for future vascular events independent of other clinical cardiovascular risk factors. Despite the higher risk for vascular events, aspirin had no impact on vascular events in the present study, but did increase major bleeding. The compliance was relatively low in the study (60%), which could have contributed to the null findings. In addition, a relatively large treatment effect (25% RRR) was needed to detect a difference and it is possible that the study was underpowered to detect a smaller difference.
Conditions
• Prevention/Primary
Therapies
• Antiplatelet agent / Aspirin
Study Design
Placebo controlled. Randomized. Blinded.
Patients Screened: 28,980
Patients Enrolled: 3,350
Mean Follow-Up: 8.2 years
Mean Patient Age: 62 years
% Female: 72

Primary Endpoints
Composite of initial fatal or nonfatal coronary event or stroke or revascularization
Secondary Endpoints
All initial vascular events defined as a composite of a primary endpoint event or angina, intermittent claudication, or transient ischemic attack
All-cause mortality
Patient Population
Men and women ages 50-80 years and free of cardiovascular disease were recruited from general practice registers in Lanarkshire, Glasgow, and Edinburgh in Scotland and had an ABI screening test.
Those with a low ABI (≤0.95) who were not already taking routine aspirin or warfarin and volunteered were included.
Exclusions:
Severe indigestion
History of MI, stroke, angina, or peripheral arterial disease
Chronic liver or kidney disease
Chemotherapy
Contraindications to treatment with aspirin
An abnormally high or low packed cell volume
References: Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010;303:841-8.

Presented by Dr. Gary Fowkes at the European Society of Cardiology Congress, Barcelona, Spain, August 2009.

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Title: Warfarin and Aspirin Use in Atrial Fibrillation Among Practicing Cardiologists (From the AFFECTS Registry)
Topic: Arrhythmias
Date Posted: 3/4/2010
Author(s): Kowey PR, Reiffel JA, Myerburg R, et al.
Citation: Am J Cardiol 2010;Feb 22:[Epub ahead of print].
Clinical Trial: No
Related Resources
Journal Scan: Practice Patterns Among United States Cardiologists for Managing Adults With Atrial Fibrillation (From the AFFECTS Registry)

Study Question: What is the pattern of anticoagulation use in patients with atrial fibrillation (AF) in contemporary practice?
Methods: This was an analysis of 1,461 patients (mean age 66 years) who had AF (paroxysmal in 80%) without structural heart disease and who were enrolled in a multicenter registry. Participating cardiologists were trained in the practice guidelines of the American College of Cardiology/American Heart Association/European Society of Cardiology. Follow-up data were gathered for 1 year after enrollment. The choice of therapy was at the treating physician’s discretion. The Congestive heart failure, Hypertension, Age, Diabetes, Stroke (CHADS2) score was determined by post-hoc record review. A CHADS2 score ≥2 was considered indicative of a high risk of stroke.
Results: A rhythm-control strategy was used in 64% of patients and a rate-control strategy in 36%. Overall, 83% of patients received either warfarin (64%) or aspirin (32%), with no significant difference between the rhythm-control and rate-control groups. Among the high-risk patients, warfarin was used in 66% of rhythm-control patients and 73% of rate-control patients. Among the low-risk patients (CHADS2 <2), warfarin was used in 49% of rhythm-control patients and 60% of rate-control patients. The combined rate of embolism and cerebral nervous system bleeding was 0.9%.
Conclusions: Anticoagulation use in patients with AF often is inconsistent with practice guidelines.
Perspective: Several studies have indicated that warfarin is underused in patients with AF. The registry data in this study demonstrate that this continues to be the case, with approximately 25-35% of high-risk patients not receiving warfarin despite the guidelines training provided to the treating physicians. The results emphasize the need for more effective dissemination and implementation of practice guidelines. Fred Morady, M.D., F.A.C.C.

Title: Practice Patterns Among United States Cardiologists for Managing Adults With Atrial Fibrillation (From the AFFECTS Registry)
Topic: Arrhythmias
Date Posted: 3/4/2010
Author(s): Reiffel JA, Kowey PR, Myerburg R, et al.
Citation: Am J Cardiol 2010;Feb 22:[Epub ahead of print].
Clinical Trial: No
Related Resources
Journal Scan: Warfarin and Aspirin Use in Atrial Fibrillation Among Practicing Cardiologists (From the AFFECTS Registry)

Study Question: How do community-based cardiologists treat atrial fibrillation (AF)?
Methods: This was an analysis of 1,461 patients (mean age 66 years) who had AF (paroxysmal in 80%, symptomatic in 77%) without structural heart disease and who were enrolled in a multicenter, prospective registry. Participating cardiologists were trained in the practice guidelines of the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC). Follow-up data were gathered for 1 year after enrollment. The choice of therapy was at the treating physician’s discretion.
Results: At baseline, a rhythm-control strategy was chosen for 64% of patients and a rate-control strategy for 36%. Rhythm control was attempted significantly more often for paroxysmal AF (67%) than for persistent AF (55%). A rhythm-control strategy also was selected more often for symptomatic than asymptomatic persistent AF (60% vs. 40%, respectively), but in a similar proportion of patients with symptomatic and asymptomatic paroxysmal AF (68% and 63%, respectively). The most common first-line rhythm-control drugs were sustained-release propafenone (43%) and sotalol (17%), and the most common second-line drugs were sustained-release propafenone (36%) and amiodarone (22%).
Conclusions: Community-based treatment of AF in patients without structural heart disease is fairly compliant with ACC/AHA/ESC practice guidelines.
Perspective: The ACC/AHA/ESC guidelines recommend that a rate-control strategy be used for patients with minimally symptomatic or asymptomatic AF. It is noteworthy that a large proportion of patients with asymptomatic AF nevertheless are treated with rhythm-control drugs in community practice. It appears that, despite current guidelines, many cardiologists have not abandoned the deep-rooted (and logical) belief that sinus rhythm is better than AF for many patients. Fred Morady, M.D., F.A.C.C.

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Title: Inadvertent Electrical Isolation of the Left Atrial Appendage During Catheter Ablation of Persistent Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 3/2/2010
Author(s): Chan CP, Wong WS, Pumprueg S, et al.
Citation: Heart Rhythm 2010;7:173-180.
Clinical Trial: No
Study Question: What are the mechanisms of inadvertent isolation of the left atrial appendage (LAA) during atrial fibrillation (AF) ablation?
Methods: This study consisted of 11 patients (ejection fraction 0.43 ± 0.18, left atrial diameter 51 ± 8 mm) with persistent AF who had LAA conduction block during a procedure for AF (n = 8) or atrial tachycardia (AT) (n = 3). LAA isolation was defined as the complete elimination or dissociation of LAA potentials.
Results: LAA conduction block occurred during ablation at the Bachmann bundle region in six patients, mitral isthmus in three, LAA base in two, and coronary sinus in one. The mean distance from the ablation site to the LAA base was 5.0 ± 1.9 cm. LAA isolation was transient in all six patients in whom LAA conduction was monitored and was permanent in the four patients in whom conduction was not monitored during energy delivery. The remaining patient was noted to have LAA isolation during a redo procedure before any ablation. Nine of (82%) the 11 patients have remained arrhythmia-free without antiarrhythmic drugs at mean follow-up of 6 ± 7 months, and all have continued taking warfarin.
Conclusions: The authors concluded that electrical isolation of the LAA may occur during ablation of persistent AF and AT, and is due to disruption of the Bachmann bundle and its leftward extension.
Perspective: The primary finding of this study is that inadvertent LAA isolation may occur in patients undergoing a catheter ablation procedure for persistent AF or postablation AT, even if the ablation site is far removed from the appendage. The mechanism most likely is due to injury to the leftward extension of the Bachmann bundle and its branches that surround the base of the LAA. Although LAA conduction slowing was observed within seconds of initiation of RF current, the results of this study should not necessarily imply that the appendage may be isolated with a single lesion. It is more likely that LAA conduction was severely impaired either by prior ablation or as a result of a myopathic process in those patients, such that further injury (related to ablation) to the existing intra-atrial routes readily resulted in LAA isolation. Overall, the study suggests that monitoring LAA conduction during the procedure would be important in preventing LAA isolation. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis: Use of Propensity Score and Instrumental Variable Methods to Adjust for Treatment-Selection Bias
Topic: Cardiovascular Surgery
Date Posted: 3/3/2010
Author(s): Lalani T, Cabell CH, Benjamin DK, et al.
Citation: Circulation 2010;121:1005-1013.
Clinical Trial: No
Study Question: Is there a beneficial role for early surgical intervention in patients with native valve infective endocarditis (IE)?
Methods: Using a prospective, multinational cohort of patients with definite native valve IE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure.
Results: Of the 1,552 patients with native valve IE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] vs. 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] –5.9%, p < 0.001). With a combined instrument, the instrumental-variable adjusted ARR in mortality associated with early surgery was –11.2% (p < 0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR –10.9% for quintiles 4 and 5, p = 0.002) and those with paravalvular complications (ARR –17.3%, p < 0.001), systemic embolization (ARR –12.9%, p = 0.002), S. aureus native valve IE (ARR –20.1%, p < 0.001), and stroke (ARR –13%, p = 0.02), but not those with valve perforation or congestive heart failure.
Conclusions: This retrospective propensity-matched study suggests that early surgery for native valve IE is associated with an in-hospital mortality benefit compared with medical therapy alone.
Perspective: Traditional treatment of IE is extended antimicrobial therapy; surgical intervention is reserved for either specific early indications (persistent fevers or bacteremia despite appropriate antibiotic therapy, recurrent embolic events despite appropriate antibiotic therapy, or hemodynamic compromise as a result of valve destruction), or for later sequelae of valve destruction. This study, and some similar studies presented at recent meetings, suggests a possible shift in thinking, with a stated conclusion that earlier surgery is better. However, caveats abound. First, early surgery in this study was defined only as surgery during the initial hospitalization––not as surgery as soon as endocarditis is diagnosed. Second, as always (and unlike prospective, randomized trials), propensity score matching controls only for identified variables. At my institution, and I suspect at most others, there still needs to be a reason to operate ‘early.’ This means that, despite propensity score matching, patients operated early probably were different from those who were operated late (but in ways that were not identified). After the dust has settled, a fair conclusion might turn out to be that surgery to repair the damage done from IE might best be done after initial treatment of infection, but before months have passed. In the meantime, a bit of caveat emptor seems in order: Out of concern for early re-infection, it is doubtful that elective surgery for native valve IE should be done before a healthy amount of antimicrobial therapy has been administered. David S. Bach, M.D., F.A.C.C.

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Title: Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia
Topic: Congenital Heart Disease
Date Posted: 3/8/2010 5:00:00 PM
Author(s): Avis HJ, Hutten BA, Gagne C, et al.
Citation: J Am Coll Cardiol 2010;55:1121-1126.
Clinical Trial: yes
Related Resources
JACC Article: Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia

Study Question: What is the safety and efficacy of rosuvastatin therapy for children with familial hypercholesterolemia?
Methods: A 12-week, double-blind, randomized, placebo-controlled trial was performed, followed by a 40-week open-label extension phase. A total of 177 children (mean age 14.5 years) were enrolled, and were randomized either to placebo or rosuvastatin 5, 10, or 20 mg daily.
Results: Low-density lipoprotein cholesterol (LDL-C) reduction with 5, 10, and 20 mg of rosuvastatin was 38%, 45%, and 50%, respectively, as compared with placebo. During the open-label phase, maximum dosing of 20 mg daily resulted in 40% of patients achieving the treatment goal LDL-C of <110 mg/dl. No impact on growth or development was seen.
Conclusions: In children with familial hypercholesterolemia, rosuvastatin 20 mg resulted in LDL-C reductions of 50%. A minority of patients achieved the LDL-C target of 110 mg/dl, consistent with the high baseline LDL-C in this patient population.
Perspective: Familial hypercholesterolemia is associated with early atherosclerosis and cardiovascular events. This study demonstrates efficacy of the high potency HMG-CoA reductase inhibitor rosuvastatin in reducing LDL-C levels in adolescents. Despite a 50% reduction in LDL-C, a minority of patients reached the goal LDL-C, in large part due to the high baseline LDL-C level of 228-239 mg/dl. Compliance was an issue in the open-label extension of this study, with 60% of patients maintaining ≥80% compliance with the study drug. This is reflective of the challenge of compliance with drug therapy in adolescents. The long-term safety of these agents in adolescents has not yet been reported. Timothy B. Cotts, M.D., F.A.C.C.

Title: Cardiovascular Manifestations of Fabry Disease: Relationships Between Left Ventricular Hypertrophy, Disease Severity, and α-galactosidase A Activity
Topic: Congenital Heart Disease
Date Posted: 3/2/2010
Author(s): Wu JC, Ho CY, Skali H, et al.
Citation: Eur Heart J 2010;Jan 7:[Epub ahead of print].
Clinical Trial: No
Study Question: In patients with Fabry disease, what are the relationships between disease severity, α-galactosidase A (α-gal) activity, and cardiac abnormalities?
Methods: A prospective analysis of patients undergoing screening for clinical trials of enzyme replacement therapy was performed. Baseline echocardiograms, electrocardiograms, exams, basic laboratory studies, and α-gal activity were analyzed.
Results: A total of 139 patients (92 males and 47 females) were studied. Cardiovascular symptoms were reported in 60.4% of patients, while 84.8% of patients showed concentric left ventricular hypertrophy (LVH). In females, log-corrected α-gal activity was inversely associated with LV mass index (r = -0.45, p < 0.040). The most LVH and cardiac symptoms were seen in males with low α-gal activity, although LVH was present in females less than 20 years old.
Conclusions: Concentric LVH was the prominent cardiac pathology in patients with Fabry disease, occurring even in young females.
Perspective: Fabry disease is a rare X-linked recessive lysosomal storage disorder associated with infiltrative and occlusive disease of the heart, kidney, and in the brain. This study documents cardiac involvement in patients under consideration for enrollment in enzyme replacement therapy studies. As one of the studies required moderate renal dysfunction for participation, this analysis may have selected patients with more advanced disease. As even relatively young patients were seen to have cardiac involvement, there may be a role for early enzyme replacement therapy to positively impact the natural history of cardiac involvement. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Anthracycline-Induced Cardiomyopathy: Clinical Relevance and Response to Pharmacologic Therapy
Topic: Heart Failure/Transplant
Date Posted: 3/2/2010
Author(s): Cardinale D, Colombo A, Lamantia G, et al.
Citation: J Am Coll Cardiol 2010;55:213-220.
Clinical Trial: No
Related Resources
JACC Article: Anthracycline-Induced Cardiomyopathy: Clinical Relevance and Response to Pharmacologic Therapy

Study Question: What is the clinical relevance of anthracycline-induced cardiomyopathy (AC-CMP) and its response to heart failure (HF) therapy?
Methods: The study cohort was comprised of 201 consecutive patients with a left ventricular ejection fraction (LVEF) <45% due to AC-CMP. Enalapril and, when possible, carvedilol were promptly initiated after detection of LV systolic dysfunction. LVEF was measured at enrollment, every month for the first 3 months, every 3 months during the first 2 following years, and every 6 months afterward (mean follow-up 36 ± 27 months). Patients were considered responders, partial responders, or nonresponders according to complete, partial, or no recovery in LVEF, respectively. They also evaluated major adverse cardiac events during follow-up.
Results: Forty-two percent of the patients (n = 85) were responders, 13% (n = 26) were partial responders, and 45% (n = 90) were nonresponders. The percentage of responders progressively decreased as the time from the end of chemotherapy to the start of HF treatment increased; no complete recovery of LVEF was observed after 6 months. Responders showed a lower rate of cumulative cardiac events than partial and nonresponders (5%, 31%, and 29%, respectively; p < 0.001).
Conclusions: The study investigators concluded that in cancer patients developing AC-CMP, LVEF recovery and cardiac event reduction may be achieved when cardiac dysfunction is detected early and a modern HF treatment is promptly initiated.
Perspective: This is an important study, which confirms that early initiation of therapy with angiotensin-converting enzyme inhibitors (Circulation 2006;114:2474-81) and beta-blockers (J Am Coll Cardiol 2006;48:2258-62) in AC-CMP is beneficial. Ragavendra R. Baliga, M.B.B.S.

Title: Triage After Hospitalization With Advanced Heart Failure: The ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) Risk Model and Discharge Score
Topic: Heart Failure/Transplant
Date Posted: 3/5/2010
Author(s): O’Connor CM, Hasselblad V, Mehta RH, et al.
Citation: J Am Coll Cardiol 2010;55:872-878.
Clinical Trial: No
Related Resources
JACC Article: Triage After Hospitalization With Advanced Heart Failure: The ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) Risk Model and Discharge Score

Study Question: What are the predictors of morbidity and mortality at hospital discharge?
Methods: The investigators used data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial to develop a predictive model, and internally validated their approach by the bootstrapping method. They used model coefficients to generate an additive risk score. They also used data from FIRST (Flolan International Randomized Survival Trial) to externally validate this model.
Results: This study found that among patients discharged with complete data (n = 423), the 6-month mortality and death and rehospitalization rates were 18.7% and 64%, respectively. Risk factors for mortality at discharge included B-type natriuretic peptide, per doubling (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.15-1.75), cardiopulmonary resuscitation or mechanical ventilation during hospitalization (HR, 2.54; 95% CI, 1.12-5.78), blood urea nitrogen, per 20-U increase (HR, 1.22; 95% CI, 0.96-1.55), serum sodium, per unit increase (HR, 0.93; 95% CI, 0.87-0.99), age >70 years (HR, 1.05; 95% CI, 0.51-2.17), daily loop diuretic, furosemide equivalents >240 mg (HR, 1.49; 95% CI, 0.68-3.26), lack of beta-blocker (HR, 1.28; 95% CI, 0.68-2.41), and 6-minute walk, per 100-foot increase (HR, 0.955; 95% CI, 0.99-1.00; c-index 0.76). A simplified discharge score discriminated mortality risk from 5% (score = 0) to 94% (score = 8). Bootstrap validation demonstrated good internal validation of the model (c-index, 0.78; 95% CI, 0.68-0.83).
Conclusions: The authors concluded that the ESCAPE study discharge risk model and score refine risk assessment after in-hospital therapy for advanced decompensated systolic heart failure, allowing clinicians to focus surveillance and triage for early life-saving interventions in this high-risk population.
Perspective: This is an important study because it identifies patients with risk ‘at the time of discharge.’ Further studies are needed to determine whether this score adds incremental value to currently used yardsticks such as the Heart Failure Survival Score developed by Aaronson et al., the MUSIC risk score (see Journal Scan), or the Seattle Heart Failure Model (Circulation 2006;113:1424-33). Overall, it is becoming increasingly clear that clinicians would be expected to calculate mortality risk for all heart failure patients at the time of hospital discharge to better manage their patients. Ragavendra R. Baliga, M.B.B.S.

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Title: A Randomized Comparison of the Endeavor Zotarolimus-Eluting Stent Versus the TAXUS Paclitaxel-Eluting Stent in de novo Native Coronary Lesions: 12-Month Outcomes From the ENDEAVOR IV Trial
Topic: Interventional Cardiology
Date Posted: 3/5/2010
Author(s): Leon MB, Mauri L, Popma JJ, et al., on behalf of the ENDEAVOR IV Investigators.
Citation: J Am Coll Cardiol 2009;55:543-54.
Clinical Trial: yes
Related Resources
JACC Article: A Randomized Comparison of the Endeavor Zotarolimus-Eluting Stent Versus the TAXUS Paclitaxel-Eluting Stent in De Novo Native Coronary Lesions: 12-Month Outcomes From the ENDEAVOR IV Trial
Trial: Randomized, Controlled Trial of the Medtronic Endeavor Drug-Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR IV)

Study Question: What is the relative safety and efficacy of the zotarolimus-eluting stent (ZES) versus the paclitaxel-eluting stent (PES)?
Methods: The authors reported the 1-year results of the ENDEAVOR IV trial. This trial randomized 1,548 patients undergoing percutaneous coronary intervention to PES or ZES. The primary endpoint of the trial was 9-month target vessel failure defined as cardiac death, myocardial infarction, or target vessel revascularization (TVR).
Results: ZES was noninferior to PES at 9 months, with a target vessel failure of 6.6% versus 7.1%, (p [noninferiority] < 0.001). Patients randomized to ZES had a lower risk of periprocedural myocardial infarctions (0.5% vs. 2.2%, p = 0.007). There was no difference in the incidence of cardiac death, myocardial infarction, TVR, or stent thrombosis. Binary angiographic restenosis was higher in patients treated with ZES (15.3% vs. 10.4%), but it did not translate into a difference in target lesion revascularization (4.5% vs. 3.2%) or TVR (6.2% vs. 6.8%).
Conclusions: Use of ZES is associated with a similar clinical outcome compared with PES.
Perspective: The long-term follow-up of this trial (Leon MB, et al., JACC Cardiovasc Interv 2009;2:1208-18), which interestingly was published before the 1 year data, clearly supports the clinical efficacy and safety of the ZES. More long-term data are needed to assess if the trend towards lower stent thrombosis with ZES seen in this trial will be maintained. While awaiting the results of the larger ongoing trials, these data provide an evidence context to support use of ZES in simple native coronary artery lesions. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Increased Rate of Stent Thrombosis and Target Lesion Revascularization After Filter Protection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: 15-Month Follow-Up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) Trial
Topic: Interventional Cardiology
Date Posted: 3/4/2010
Author(s): Kaltoft A, Kelbжk H, Klшvgaard L, et al.
Citation: J Am Coll Cardiol 2010;55:867-871.
Clinical Trial: No
Related Resources
JACC Article: Increased Rate of Stent Thrombosis and Target Lesion Revascularization After Filter Protection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: 15-Month Follow-Up of the DEDICATION Trial
Trial: Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION: Distal Protection Study)
Trial: Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION: Stent Study)

Study Question: What are the long-term effects of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI)?
Methods: The 626 STEMI patients were assigned to distal protection (DP) (n = 312) or conventional treatment (CT) (n = 314). Clinical follow-up was performed after 1, 6, and 15 months, and angiographic follow-up after 8 months. All target lesion revascularizations (TLRs) were clinically driven. They reported the prespecified endpoints of stent thrombosis according to the criteria of the Academic Research Consortium, TLR, and reinfarction after 15 months.
Results: The total number of stent thrombosis was 11 in the DP group and 4 in the CT group (p = 0.06). The rate of definite stent thrombosis was significantly increased in the DP group compared with the CT group, with 9 cases versus 1 (p = 0.01). Clinically driven TLRs (31 patients vs. 18 patients, p = 0.05) and clinically driven target vessel revascularizations (37 patients vs. 22 patients, p = 0.04) were more frequent in the DP group.
Conclusions: The authors concluded that in primary PCI for STEMI, the routine use of DP increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization.
Perspective: The current study found no benefit of distal filter protection during primary PCI for STEMI with respect to short-, intermediate-, or long-term angiographic or clinical endpoints. Furthermore, there was a significantly increased rate of adverse cardiac events within 15 months in the group of patients treated with routine distal protection. Together with the results of the EMERALD, PROMISE, and PREMIAR trials, the results of this study demonstrate that routine use of a filter wire cannot be advocated and should be avoided with primary PCI for STEMI. On the contrary, aspiration thrombectomy appears to be beneficial in patients undergoing primary PCI and should be routinely considered. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Recommendations for Cardiovascular Magnetic Resonance in Adults With Congenital Heart Disease From the Respective Working Groups of the European Society of Cardiology
Topic: Noninvasive Cardiology
Date Posted: 3/3/2010
Author(s): Kilner PJ, Geva T, Kaemmerer H, Trindade PT, Schwitter J, Webb GD.
Citation: Eur Heart J 2010;Jan 11:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember about these recommendations.

1. Cardiac magnetic resonance (CMR) in adult congenital heart disease (ACHD) should be performed by appropriately trained specialists who can participate in the performance of studies and optimize acquisition protocols to best answer the clinical question as related to the underlying cardiac anatomy.

2. Many ACHD patients benefit from a baseline CMR study to identify anatomic issues not previously noted and to establish a baseline for comparison in the future.

3. The interval for follow-up CMR should be determined by the anatomic lesion involved, and for the potential for change or progression with time.

4. CMR can be useful for identification of anomalies of the systemic or pulmonary venous return.

5. In adults with coarctation of the aorta, CMR allows for assessment for recurrence of coarctation or aneurysm formation at a previous repair site. It can also assistant in planning of repeat procedures including percutaneous stent placement or surgical intervention.

6. CMR is an important tool in the assessment of the ACHD patient with tetralogy of Fallot. CMR allows for measurement of biventricular size and function, quantification of pulmonary insufficiency, and evaluation of the branch pulmonary arteries.

7. CMR may be used to determine all sources of pulmonary blood flow in patients with major aortopulmonary collateral arteries (MAPCAS) to optimize a surgical or percutaneous approach to treatment.

8. In adults with transposition of the great arteries who have undergone atrial switch type of procedures (i.e., Mustard or Senning procedure), CMR can be useful for assessing right ventricular function, assessing for baffle stenosis, and quantifying tricuspid insufficiency.

9. In adults with congenitally corrected transposition of the great arteries, CMR can assess right ventricular function, identify coexisting lesions, and quantify tricuspid insufficiency.

10. CMR can be used in patients following the Fontan procedure to assess the cavo-pulmonary connection, branch pulmonary arteries, ventricular size and function, and ventricular outflow tract. If contrast is used, timing of the contrast injection as well as possibility of dilution by lower extremity venous return should be considered. Timothy B. Cotts, M.D., F.A.C.C.

Title: Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults
Topic: Prevention/Vascular
Date Posted: 3/3/2010 5:00:00 PM
Author(s): Selvin E, Steffes MW, Zhu H, et al.
Citation: N Engl J Med 2010;362:800-811.
Clinical Trial: No
Study Question: Is the glycated hemoglobin in persons without diabetes predictive of cardiovascular outcomes?
Methods: The prognostic value of glycated hemoglobin and fasting glucose were assessed for their ability to identify adults at risk for diabetes or cardiovascular disease. Glycated hemoglobin (glycohemoglobin or HgA1c) was measured in whole-blood samples from 11,092 black or white adults who did not have a history of diabetes or cardiovascular disease and who attended the second visit (occurring in the 1990–1992 period) of the Atherosclerosis Risk in Communities (ARIC) study.
Results: Fifty-eight percent were women, 77% were white, 32% had hypertension, and 22.7% had a family history of diabetes. Mean values for risk factors were as follows: age 57 years, fasting blood sugar (FBS) 105 mg/dl, glycated hemoglobin 5.5%, low-density lipoprotein cholesterol 133 mg/dl, high-density lipoprotein cholesterol 51 mg/dl, and body mass index 27.7 kg/m2. The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes. For glycated hemoglobin values of less than 5.0%, 5.0 to less than 5.5%, 5.5 to less than 6.0%, 6.0 to less than 6.5%, and 6.5% or greater, the multivariable-adjusted hazard ratios for diagnosed diabetes were 0.52, 1.00 (reference), 1.86, 4.48, and 16.47, respectively. For coronary heart disease, the hazard ratios were 0.96, 1.00 (reference), 1.23, 1.78, and 1.95, respectively. The hazard ratios for stroke were similar. In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve. All these associations remained significant after adjustment for the baseline fasting glucose level. The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant in models with adjustment for all covariates as well as glycated hemoglobin. For coronary heart disease, measures of risk discrimination showed significant improvement when glycated hemoglobin was added to models including fasting glucose.
Conclusions: In this community-based population of nondiabetic adults, glycated hemoglobin was similarly associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause, as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.
Perspective: Persons with a glycated hemoglobin ≥6.5% or FBS >126 mg/dl are characterized as diabetics. The former represent the average blood sugar over 2 to 3 months. A level greater than 5.5% is associated with an increase in risk for diabetes and coronary disease independent of other variables, and the relative risk for 0.5% increments is considerable. The authors concluded that a glycated hemoglobin exceeding 6% may be a useful marker to identify persons at risk for development of diabetes, and cardiovascular disease and death. Consideration should be given to replacing the FBS with glycated hemoglobin for risk stratification of adults with and without vascular disease. Melvyn Rubenfire, M.D., F.A.C.C.

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Red Yeast Rice or Statins?
H1N1 and Myocarditis
Prognosis of Cardiac CT
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Low Diagnostic Yield of Elective Coronary Angiography
Topic: Interventional Cardiology
Date Posted: 3/10/2010 4:00:00 PM
Author(s): Patel MR, Peterson ED, Dai D, et al.
Citation: N Engl J Med 2010;362:886-895.
Clinical Trial: No
Study Question: What is the diagnostic yield of coronary angiography among patients with coronary artery disease (CAD) in a contemporary national sample?
Methods: From January 2004 to April 2008, at 663 hospitals in the American College of Cardiology National Cardiovascular Data Registry, the authors identified patients without known CAD who were undergoing elective cardiac catheterization. The patients' demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive CAD, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery, or stenosis of 70% or more of the diameter of a major epicardial vessel.
Results: A total of 398,798 patients were included in the study. The median age was 61 years; 52.7% of the patients were men, 26% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization, 149,739 patients (37.6%) had obstructive CAD. No CAD (defined as <20% of stenosis in all vessels) was reported in 39.2% of patients. Independent predictors of obstructive CAD included male sex (odds ratio [OR], 2.70; 95% confidence interval [CI], 2.64-2.76); older age (OR per 5-year increment, 1.29; 95% CI, 1.28-1.30); presence of insulin-dependent diabetes (OR, 2.14; 95% CI, 2.07-2.21); and presence of dyslipidemia (OR, 1.62; 95% CI, 1.57-1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive CAD than those who did not undergo any testing (41.0% vs. 35.0%, p < 0.001; adjusted OR, 1.28; 95% CI, 1.19-1.37).
Conclusions: The authors concluded that in this study, only a minority of patients without known coronary disease who underwent elective cardiac catheterization had obstructive CAD.
Perspective: This analysis of a contemporary national sample of patients suggests that only a minority of patients undergoing coronary angiography have obstructive CAD. The assessment of coronary stenosis was made by the interpreting/performing physician and it is possible that more stringent assessment may further lower the fraction of patients with obstructive CAD. It should also be noted that this study addresses only overutilization and not underutilization of coronary angiography in appropriate patients. However, it is obvious from this study that the current strategies used to make decisions for proceeding to coronary angiography, including clinical assessment and noninvasive testing, need substantial modification and improvement to increase the diagnostic yield of coronary angiography and prevent over- or underutilization to improve overall quality of patient care. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Endovascular Valve Edge-to-Edge Repair Study II (EVEREST II)
Year Presented: 2010
Topic(s): Cardiovascular Surgery
Summary Posted: 3/14/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Description
The goal of the trial was to evaluate treatment with the percutaneous MitraClip device compared with surgical mitral valve repair/replacement among patients with severe mitral regurgitation.
Hypothesis
Percutaneous mitral valve repair would be noninferior in regards to effectiveness and superior in regards to safety.
Drugs/Procedures Used
Patients with severe mitral regurgitation (3 to 4+) were randomized to the percutaneous mitral valve clip (n = 184) versus surgical repair/replacement (n = 95).
Principal Findings
Overall, 279 patients were enrolled. In the mitral clip group, the mean age was 67 years, 63% were men, 34% had atrial fibrillation, the mean ejection fraction was 60%, 8% had diabetes, 73% had a degenerative mitral valve, and 27% had functional mitral regurgitation. The only baseline characteristic that was different between the groups was congestive heart failure, which was present in 91% of the clip group and 78% of the control group (p < 0.01).

In the per-protocol analysis, 41 patients in the clip group did not achieve procedural success and were not analyzed further. Major adverse events at 30 days occurred in 9.6% of the clip group versus 57% of the control group (p < 0.0001 for superiority). This outcome was driven by increased need for blood transfusion in the control group. Clinical success rate at 12 months was 72% versus 88% (p = 0.0012 for noninferiority), respectively.

In the intention-to-treat analysis, major adverse events at 30 days occurred in 15% of the clip group versus 48% of the control group (p < 0.0001 for superiority). Clinical success rate at 12 months was 67% versus 74% (p = 0.0005 for noninferiority), respectively.

In the per-protocol group, 82% achieved 2+ or less mitral regurgitation versus 97% in the control group. New York Heart Association (NYHA) class I or II at follow-up was 98% in the clip group versus 88% in the control group.
Interpretation
Among patients with severe mitral regurgitation, repair with a percutaneous mitral valve clip was feasible. This therapy demonstrated improved safety at 30 days compared with surgery, largely by reducing the need for blood transfusion. The mitral valve clip was also noninferior for effectiveness at 12 months.
Conditions
• Valvular heart disease
• Prevention
Study Design
Randomized. Parallel.
Patients Enrolled: 279
Mean Follow-Up: 12 months
Mean Patient Age: 67 years
% Female: 38%

Mean Ejection Fraction: 60%
Primary Endpoints
Primary effectiveness endpoint: Freedom from death, surgery for mitral valve dysfunction, and >2+ mitral regurgitation at 12 months
Primary safety endpoint: Death, myocardial infarction, re-operation for failed surgical repair/replacement, nonelective cardiovascular surgery for adverse events, stroke, renal failure, deep wound infection, ventilation for more than 48 hours, gastrointestinal complication requiring surgery, new-onset atrial fibrillatin, sepsis, and transfusion of ≥2 U blood
Secondary Endpoints
Quality of life
NYHA functional class
Patient Population
Patients with severe mitral regurgitation (3 to 4+) and candidate for mitral valve surgery
Symptomatic: left ventricular (LV) ejection fraction >25% and LV end-systolic dimension <56 mm
Asymptomatic (with one or more of the following): LV ejection fraction 25-60%, LV end-systolic dimension >39, or new-onset atrial fibrillation, or pulmonary hypertension
Exclusions:
Myocardial infarction within 12 weeks
Need for other cardiac surgery
Serum creatinine >2.5 mg/dl
Endocarditis
Rheumatic heart disease
Mitral valve anatomical exclusions: mitral valve area <4 cm2, leaflet flail width (>14 mm) and gap (>9 mm), or leaflet tethering/coaptation depth (>11 mm) and length (<2 mm)
References: Presented by Dr. Ted Feldman at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

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Title: Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial (ACCORD BP)
Trial Sponsor: National Heart, Lung, and Blood Institute
Year Presented: 2010
Year Published 2010
Topic(s): General Cardiology, Noninvasive Cardiology
Summary Posted: 3/14/2010 8:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: ACCORD BP
Related Trial: United Kingdom Prospective Diabetes Study (UKPDS)
Related Trial: Hypertension Optimal Treatment Study (HOT)

Description
The goal of the trial was to evaluate a target systolic blood pressure <120 mm Hg compared with <140 mm Hg among patients with type 2 diabetes.
Hypothesis
Intensive blood pressure lowering would be effective in preventing cardiovascular events.
Drugs/Procedures Used
Half of the patients within the initial ACCORD trial with type 2 diabetes were randomized to a goal systolic blood pressure <120 mm Hg (n = 2,362) versus <140 mm Hg (n = 2,371).

The other half of the patients within the initial ACCORD trial were randomized to fenofibrate plus statin therapy versus placebo plus statin therapy.
Principal Findings
Overall 4,733 patients were enrolled. The mean age was 62 years, 48% were women, previous cardiovascular event was present in 34%, mean systolic blood pressure was 139 mm Hg, and mean glycated hemoglobin (HbA1c) was 8.3%.

At 1 year, mean systolic blood pressure was 119 mm Hg in the intensive group versus 134 mm Hg in the standard group, and mean number of antihypertensives was 3.4 versus 2.1, respectively.

The annual rate of cardiovascular mortality, myocardial infarction, or stroke was 1.9% versus 2.1% (p = 0.20), all-cause mortality was 1.3% versus 1.2% (p = 0.55), nonfatal myocardial infarction was 1.1% versus 1.3% (p = 0.25), and stroke was 0.3% versus 0.5% (p = 0.01), respectively, for intensive versus standard blood pressure target.

Serious adverse events were 3.3% versus 1.3% (p < 0.001), hypokalemia was 2.1% versus 1.1% (p = 0.01), and elevated serum creatinine was 12.9% versus 8.4% (p < 0.001), respectively.
Interpretation
Among patients with type 2 diabetes at high risk for cardiovascular events, a goal systolic blood pressure <120 mm Hg was not superior to a goal <140 mm Hg. This intensive target did not reduce composite cardiovascular events; however, there was a small reduction in any stroke from 0.5% to 0.3%. In the intensive systolic blood pressure group, there were more serious adverse events, hypokalemia, and elevated serum creatinine.

These findings contrast with the UKPDS and HOT trials, which documented benefit from blood pressure reduction; however, the mean systolic blood pressure in the intensively treated groups in those trials was 144 mm Hg.
Conditions
• Diabetes mellitus
• Hypertension
Therapies
• Medical
Study Design
Randomized. Parallel.
Patients Enrolled: 4,733
Mean Follow-Up: 5 years
Mean Patient Age: 62 years
% Female: 48%

Primary Endpoints
First occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
Patient Population
Patients with type 2 diabetes with an HbA1c ≥7.5%
Age 40-79 years with clinical cardiovascular disease or age 55-79 years with subclinical cardiovascular disease or at least two additional cardiovascular risk factors
Systolic blood pressure 130-180 mm Hg on 0-1 antihypertensive medications, 130-170 mm Hg on two medications, or 130-160 mm Hg on three medications
Exclusions:
Creatinine >1.5 mg/dl
Marked proteinuria
References: The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;Mar 14:[Epub ahead of print].

Presented by Dr. William Cushman at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Action to Control Cardiovascular Risk in Diabetes Lipid Trial (ACCORD Lipid)
Trial Sponsor:
National Heart, Lung, and Blood Institute
Fenofibrate was donated by Abbott
Simvastatin was donated by Merck

Year Presented: 2010
Year Published 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 3/14/2010 8:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Related Trial: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT)
Journal Scan: Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus

Description
The goal of the trial was to evaluate treatment with fenofibrate compared with placebo among patients with type 2 diabetes treated with an open-label statin medication.
Hypothesis
The addition of fenofibrate to statin therapy would be effective in preventing cardiovascular events.
Drugs/Procedures Used
Half of the patients within the initial ACCORD trial with type 2 diabetes treated with a statin medication were randomized to fenofibrate 160 mg daily (n = 2,765) versus placebo (n = 2,753). The other half of the patients within the initial ACCORD trial were randomized to a systolic blood pressure goal <120 mm Hg versus <140 mm Hg.
Concomitant Medications
At baseline, the use of insulin was 33%, metformin was 62%, any sulfonylurea was 52%, any thiazolidinedione was 18%, angiotensin-converting enzyme inhibitor was 54%, angiotensin-receptor blocker was 15%, aspirin was 56%, statin was 60%, and any lipid-lowering agent was 65%.
Principal Findings
Overall, 5,518 patients were enrolled in the study. The mean age was 62 years, 31% were women, 37% had a previous cardiovascular event, mean systolic blood pressure was 134 mm Hg, and mean glycated hemoglobin (HbA1c) was 8.1.

In the fenofibrate group, low-density lipoprotein (LDL) cholesterol decreased from 100 to 81 mg/dl, high-density lipoprotein (HDL) cholesterol increased from 38 to 41.2 mg/dl, and triglycerides decreased from 189 to 147 mg/dl. In the placebo group, LDL cholesterol decreased from 101 to 80 mg/dl (p = 0.16 between groups), HDL cholesterol increased from 38 to 40.5 mg/dl (p = 0.01 between groups), and triglycerides decreased from 186 to 170 mg/dl (p < 0.001 between groups).

The primary outcome, rate of major fatal or nonfatal cardiovascular event was 2.2 events/year with fenofibrate versus 2.4 events/year with placebo (p = 0.32).

The primary outcome plus revascularization or hospitalization for congestive heart failure was 5.4 events/year versus 5.6 events/year (p = 0.30), major coronary event was 2.6 events/year versus 2.8 events/year (p = 0.26), and all-cause mortality was 1.5 events/year versus 1.6 events/year (p = 0.33), respectively, for fenofibrate versus control.

Study drug was discontinued because of a decrease in estimated glomerular filtration rate in 2.4% versus 1.1%, respectively. In subgroup analysis, men appeared to benefit, while women appeared to be harmed from fenofibrate therapy (p for interaction = 0.01). Also, a high triglyceride (>203)/low HDL (<35) profile appeared to benefit (p for interaction = 0.06).
Interpretation
Among diabetic patients at high risk for cardiovascular disease, the addition of fenofibrate to statin therapy was not superior to statin therapy alone. Fenofibrate was not able to reduce rates of cardiovascular disease. Although fenofibrate reduced triglyceride levels, although there was only a small difference in mean HDL cholesterol between groups, which could help to explain lack of benefit. This agent may still have a role among individuals with a high triglyceride/low HDL profile. The possible harm noted among women deserves further study. This study is in contrast to the benefit of gemfibrozil seen in the HHS and VA-HIT trials.
Conditions
• Diabetes mellitus
• Hypercholesterolemia / Hyperlipidemia
Therapies
• Lipid-lowering agent
• Medical
Study Design
Placebo controlled. Randomized. Blinded. Parallel.
Patients Enrolled: 5,518
Mean Follow-Up: 4.7 years
Mean Patient Age: 62 years
% Female: 31%

Primary Endpoints
First occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
Secondary Endpoints
Combination of the primary outcome plus revascularization or hospitalization for heart failure
Combination of a fatal coronary event, nonfatal myocardial infarction, or unstable angina
Nonfatal myocardial infarction
Fatal or nonfatal stroke
Nonfatal stroke
All-cause death
Cardiovascular death
Hospitalization or death due to heart failure
Patient Population
Patients with type 2 diabetes with an HbA1c ≥7.5%
Age 40-79 years with clinical cardiovascular disease or age 55-79 years with subclinical cardiovascular disease or at least two additional cardiovascular risk factors
LDL cholesterol level between 60 and 180 mg/dl, HDL cholesterol <55 mg/dl for women and blacks or <50 mg/dl for all others, and triglycerides <750 mg/dl not on lipid therapy or <400 mg/dl on lipid therapy
References: The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;Mar 14:[Epub ahead of print].

Presented by Dr. Henry Ginsberg at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR)
Trial Sponsor: Novartis Pharma
Year Presented: 2010
Year Published 2010
Topic(s): General Cardiology, Prevention/Vascular
Summary Posted: 3/14/2010 8:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: NAVIGATOR

Description
The goal of the trial was to evaluate treatment with nateglinide (a short-acting insulin secretagogue), valsartan, or both among patients with impaired glucose tolerance.
Hypothesis
Nateglinide and valsartan would be more effective in preventing type 2 diabetes and cardiovascular events.
Drugs/Procedures Used
Patients with impaired glucose tolerance were randomized in a factorial manner to nateglinide (n = 4,645) versus placebo (n = 4,661) and to valsartan (n = 4,631) versus placebo (n = 4,675).

Valsartan was started at 80 mg daily and increased to 160 mg daily after 2 weeks. Nateglinide was started at 30 mg three times daily and increased to 60 mg three times daily after 2 weeks.

All patients underwent clinic and telephone-based lifestyle intervention aimed at reducing weight, limiting saturated fats, and increasing physical activity.
Concomitant Medications
At baseline, the use of any antihypertensive drug was 73%, lipid-lowering drug was 39%, and aspirin or another antiplatelet drug was 37%.
Principal Findings
Overall, 9,306 patients were randomized. There was no difference in baseline characteristics between the groups. In the valsartan group, the mean age was 64 years, mean weight was 84 kg, mean systolic blood pressure was 139 mm Hg, history of heart disease was present in 25% of patients, mean low-density lipoprotein (LDL) cholesterol was 177 mg/dl, and mean high-density lipoprotein (HDL) cholesterol was 50 mg/dl.

Considering the effect of valsartan: At a mean follow-up of 5 years, incident diabetes occurred in 33% of the valsartan group versus 37% of the placebo group (p < 0.001). The extended cardiovascular outcome occurred in 15% versus 15% (p = NS) and the core cardiovascular outcome occurred in 8.1% versus 8.1% (p = NS), respectively, for valsartan versus placebo. Hypotension-related adverse events occurred in 42% versus 36% (p < 0.001) and study drug discontinuation occurred in 12% versus 11% (p = NS), respectively.

Considering the effect of nateglinide: At a mean follow-up of 5 years, incident diabetes occurred in 36% of the nateglinide group versus 34% of the placebo group (p = 0.05). The extended cardiovascular outcome occurred in 14% versus 15% (p = NS) and the core cardiovascular outcome occurred in 7.9% versus 8.3% (p = NS), respectively, for nateglinide versus placebo. Hypoglycemia occurred in 20% versus 11% (p < 0.001) and study drug discontinuation occurred in 11% versus 10% (p = 0.23), respectively.
Interpretation
Among patients with impaired glucose tolerance and cardiovascular disease or cardiovascular risk factors, valsartan was effective at reducing incident diabetes. Despite this benefit, valsartan did not reduce long-term adverse cardiovascular events. Nateglinide reduced neither incident diabetes, nor adverse cardiovascular events. In fact, diabetes was marginally increased in the nateglinide group.

It is unknown why these agents were unable to reduce adverse cardiovascular events; however, patients also underwent lifestyle modification, which may have diminished any treatment effect. Also, blood pressure was fairly well-controlled, and the use of other risk-reducing therapies was good. Valsartan may have implications for the treatment of hypertension since thiazide agents and beta-blockers have been associated with the development of diabetes.
Conditions
• Diabetes mellitus
Therapies
• Angiotensin-receptor blocker / Valsartan
• Medical
Study Design
Placebo controlled. Randomized. Blinded. Parallel. Stratified.
Patients Screened: 43,502
Patients Enrolled: 9,306
Mean Follow-Up: 5 years
Mean Patient Age: 64 years
% Female: 50

Primary Endpoints
Onset of type 2 diabetes
Extended cardiovascular outcome: composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and hospitalization for heart failure or unstable angina
Core cardiovascular outcome: composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure
Patient Population
Patients with impaired glucose tolerance, fasting glucose level between 95 and 125 mg/dl
At least 50 years of age with known cardiovascular disease,
Or at least 55 years of age with at least one risk factor for cardiovascular disease
Exclusions:
Any laboratory abnormality or condition that could interfere with the assessment of drug efficacy and safety
Use of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker for hypertension
Use of an antidiabetic medication within the last 5 years
References: The NAVIGATOR Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;Mar 14:[Epub ahead of print].

The NAVIGATOR Study Group. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;Mar 14:[Epub ahead of print].

Presented by Dr. Robert Califf at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

ACC Cardio Career Guide: Get the latest information and advice you need to help you advance your career.
[Ссылки могут видеть только зарегистрированные и активированные пользователи]/16

[Chevychelov]

Title: Cryoballoon Ablation of Pulmonary Veins for Paroxysmal Atrial Fibrillation (STOP-AF)
Trial Sponsor: Medtronic Cryocath LP
Year Presented: 2010
Topic(s): Arrhythmias
Summary Posted: 3/15/2010 9:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: STOP-AF

Description
Although radiofrequency ablation (RFA) after pulmonary vein isolation (PVI) for atrial fibrillation (AF) has been shown to be associated with a reduction in symptomatic AF, especially paroxsymal AF, it often requires multiple lesions, and may be associated with complications. Further, antiarrhythmic drugs (AAD) can also be associated with significant morbidity and mortality. Accordingly, the investigators sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve PVI with a continuous cryolesion.
Hypothesis
Cryoballoon ablation would be safe and efficacious in the treatment of symptomatic AF.
Drugs/Procedures Used
Patients were randomized in a 2:1 fashion to either PVI with the cryoballoon, or treatment with a nonfailed AAD. Cryoballoons were available in two sizes, 23 mm and 28 mm. This is a double balloon, and is delivered by a steerable balloon through a 14F sheath. PVI was done without any ablation lines.
Principal Findings
A total of 245 patients were enrolled, 163 to the cryoballoon, and 82 to AAD. Baseline characteristics were fairly similar between the two arms. Most patients were highly symptomatic, with a mean of 23 symptomatic episodes in the 2 months prior to enrollment. About 22% of the patients had early permanent AF, whereas the rest had paroxysmal AF. In addition, 45% had a history of atrial flutter. Subjects had previously failed ≥1 AAD (36% flecainide, 47% propafenone, 29% sotalol). The mean CHADS2 score was 0.6, and mean left atrial diameter was 4.1 cm.

Balloon-only isolation of PVs was achieved in 90.8%, and the overall procedural success (≥3 PVs isolated) was achieved in 98.2% of the patients. The number of deliveries per PV ranged from 2.9 to 3.4. The mean duration of delivery ranged from 196 to 230 seconds, with a mean 62.8 minutes. The cryoballoon temperatures ranged from -49 to -54 degrees Celsius. About 40% of the patients also underwent cavo-tricuspid isthmus ablation. In addition, about 19% of the patients needed a repeat cryoablation procedure within the 90-day blanking period. There was also a high amount of cross-over from the AAD arm to the cryoballoon arm.

The incidence of the primary endpoint of treatment success was significantly better in the cryoablation arm, as compared with the AAD arm (69.9% vs. 7.3%, p < 0.001). A single ablation procedure was associated with success in 60.1% of the patients. In addition, 57.7% of patients in the cryoballoon arm were on no AADs at the end of follow-up, whereas 12.3% were still on one or more AADs. Of the 95% of patients in the cryoballoon arm who were on warfarin at baseline, only 24% were still on it at 12 months. Symptomatic AF was reduced from 100% at baseline to 19.6% in the cryoballoon arm. The incidence of new atrial flutter was higher in the AAD arm (3.7% vs. 15.9%).

The overall rate of procedural complications with cryoballoon ablation was 6.3%, which was lower than the projected rate of 14.8%. The incidence of combined AF events (disease and procedure related) was 3.1% vs. 8.5% in the cryoballoon and AAD arms, respectively (p < 0.001). The incidence of combined procedural events and major adverse AF events was similar between the two arms (6.1% vs. 8.5%, p = 0.60). Procedural complications with cryoballoon included PV stenosis (3.1% vs. 2.4%), and phrenic nerve palsy (13.5% vs. 7.3%). Of the 11.2% of patients who had phrenic nerve palsy post-procedure, only four (13.8%) had persistent phrenic nerve palsy at 12 months.
Interpretation
The results of the STOP-AF trial indicate that cryoballoon ablation is safe and efficacious in the treatment of symptomatic AF, as compared with AAD alone. A significant proportion of patients in the cryoballoon arm were free of AAD and warfarin use at the end of 12 months, as compared with baseline.

While these early results are interesting, they are tempered by a high incidence of procedural complications, especially phrenic nerve palsy with cryoballoon ablation. The mean number of applications per PV was about three, and it is likely that there is a steep learning curve associated with this procedure.

One potential limitation of this study was that about 45% of the patients had a history of atrial flutter, and a significant number of patients in the cryoballoon arm also underwent cavo-tricuspid isthmus ablation. Not surprisingly, new atrial flutter over the duration of follow-up was higher in the AAD arm, and would have contributed to the overall arrhythmia burden. Further studies will need to evaluate the efficacy of cryoballoon ablation versus conventional RFA with PVI.
Conditions
• Arrhythmias / Atrial fibrillation
Study Design
Randomized. Parallel.
Patients Enrolled: 245
NYHA Class (% I, II, II, IV): I (94%)
Mean Follow-Up: 12 months
Mean Patient Age: 56.6 years
% Female: 23

Mean Ejection Fraction: 60%
Primary Endpoints
Effectiveness:
Combined treatment failure (no detectable AF, no use of nonstudy drugs, no AF intervention)

Safety:
Major adverse AF events (composite of disease and treatment safety adverse events)
Composite of device and procedure-related adverse events
Patient Population
≥2 AF episodes in 2 months with ECG documentation of one
Treatment failure of ≥1 AAD
References: Presented by Dr. Douglas Packer at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Rate Control Efficacy in Permanent Atrial Fibrillation: A Comparison Between Lenient Versus Strict Rate Control II (RACE II)
Trial Sponsor: Netherlands Heart Foundation, and grants from AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Medtronic, Roche, and Sanofi Aventis.
Year Presented: 2010
Year Published 2010
Topic(s): Arrhythmias, General Cardiology
Summary Posted: 3/15/2010 8:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: RACE II
Related Trial: Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE)
Related Trial: Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)

Description
Although rate control has been shown to be associated with similar outcomes, as compared with rhythm control in patients with atrial fibrillation (AF), the optimal level of heart rate (HR) control/lowering is unclear. Current guidelines recommend strict rate control, although data to support this approach are lacking. Accordingly, the RACE II trial sought to investigate whether lenient rate control would be noninferior to strict rhythm control in patients with permanent AF.
Hypothesis
Lenient rate control would be noninferior to strict rate control in patients with permanent AF.
Drugs/Procedures Used
Patients were randomized to either a lenient rate control strategy (target resting HR <110 bpm), or strict control strategy (target resting HR <80 bpm, and <110 bpm with moderate exercise). HR control was achieved with the use of beta-blockers (45%), non-dihydropyridine calcium-channel blockers (6%) or digoxin (7.2%), or a combination of these. A small number of patients also received sotalol (5.0) and amiodarone (1.3%).
Concomitant Medications
Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (49.8%), statin (28.8%), vitamin K antagonist (98.7%), aspirin (1.6%)
Principal Findings
A total of 614 patients were randomized, 311 to lenient control, and 303 to strict control. Baseline characteristics were fairly similar between the two arms. The resting baseline HR was 96 bpm. The median duration of AF was 18 months, while the median duration of permanent AF was 3 months. About 20% had coexisting valvular heart disease. About 56.7% of these patients had symptomatic AF, and 1.8% had lone AF. The majority of patients had a CHADS2 score of 0 or 1 (60.7%), whereas 13.4% had a CHADS2 score >2.

The mean HR at the end of the dose-adjustment phase was 93 ± 9 bpm in the lenient control group, as compared with 76 ± 12 bpm in the strict control group (p < 0.001). Only nine patients in both groups were in normal sinus rhythm at the end of follow-up. Target HR was achieved in 97.7% of the patients in the lenient control arm, as compared with 67.0% in the strict control arm (p < 0.001). Only 1.9% of patients in the lenient control arm and 75.2% of patients in the strict control arm had resting HR <80 bpm. About 72.6% of patients in the strict control arm achieved an exercise HR of <110 bpm. About half of the patients in the strict control arm could not achieve target HR due to drug-related adverse events or was noted to be impossible to achieve with drugs.

The 3-year estimated cumulative incidence of the primary endpoint (cardiovascular [CV] death, hospitalization for heart failure and stroke, systemic embolism, major bleeding, arrhythmic events, and implantation of permanent pacemaker [PPM] or implantable cardioverter defibrillator [ICD]) was similar between the lenient and strict control arms (12.9% vs. 14.9%, hazard ratio 0.84, 90% confidence interval 0.58-1.21, p for noninferiority = 0.001). This was true for patients irrespective of CHADS2 score. Secondary outcomes, including CV death (2.9% vs. 3.9%), congestive heart failure (3.8% vs. 4.1%), bleeding (5.3% vs. 4.5%), syncope (1% vs. 1%), and PPM implantation (0.8% vs. 1.4%) were similar between the two arms. The incidence of stroke was significantly lower in the lenient control arm, as compared with the strict control arm (1.6% vs. 3.9%, p < 0.05).
Interpretation
The results of this trial indicate that a lenient rate control strategy, with a target resting HR <110 bpm is easier to achieve with beta-blockers, calcium-channel blockers, and/or digoxin, as compared with a strict control strategy, with a target resting HR <80 bpm, and an exercise HR <110 bpm. The former strategy is also noninferior for CV outcomes, and is associated with a reduction in the incidence of strokes.

Target HR was achieved in only 67% of the patients in the strict control arm. Hence, it is possible that if other means of achieving a lower HR were pursued, there may have been a difference in the strict control strategy. Furthermore, the majority of patients in this study were low risk (CHADS2 score 0-1). Although the investigators did not note a difference in patients with a higher CHADS2 score, few patients were available for this analysis. This also will need to be explored in further analyses.
Conditions
• Arrhythmias / Atrial fibrillation
Therapies
• Medical
Study Design
Randomized. Blinded. Parallel.
Patients Enrolled: 614
NYHA Class (% I, II, II, IV): I (65.1%), II (30.1%), III (4.7%)
Mean Follow-Up: 3 years
Mean Patient Age: 68 years
% Female: 34

Mean Ejection Fraction: 52%
Primary Endpoints
CV death, hospitalization for heart failure and stroke, systemic embolism, major bleeding, arrhythmic events, and implantation of PPM or ICD
Secondary Endpoints
CV death
Hospitalization for congestive heart failure and stroke
Systemic embolism
Major bleeding
Arrhythmic events
Implantation of PPM or ICD
All-cause mortality
Symptoms
Functional status
Patient Population
Permanent AF for up to 12 months
Age ≤80 years
Mean resting HR >80 bpm
Current use of anticoagulation (or aspirin alone, if deemed at low risk for thromboembolism)
Exclusions:
Paroxysmal AF
Known contraindications for either strict or lenient rate control (e.g., previous adverse effects on negative chronotropic drugs)
Unstable heart failure defined as New York Heart Association class IV heart failure or heart failure necessitating hospital admission <3 months before inclusion
Cardiac surgery <3 months
Any stroke
Current or foreseen pacemaker, ICD, and/or cardiac resynchronization therapy
Signs of sick sinus syndrome or AV conduction disturbances (i.e., symptomatic bradycardia or asystole >3 seconds or escape rate <40 bpm in awake symptom-free patients
Untreated hyperthyroidism or <3 months of euthyroidism
Inability to walk or bike
References: Van Gelder CI, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 2010;Mar 15:[Epub ahead of print].

Presented by Dr. Isabelle C. Van Gelder at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Duration of Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents (DES-LATE)
Trial Sponsor: Grants from the Cardiovascular Research Foundation (Korea), and a grant from the Korean Ministry of Health & Welfare as part of the Korea Health 21 Research & Development Project
Year Presented: 2010
Year Published 2010
Topic(s): General Cardiology, Interventional Cardiology
Summary Posted: 3/15/2010 11:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: DES-LATE
Related Trial: Comparison of Sirolimus and Paclitaxel-Eluting Stents Versus Zotarolimus-Eluting Stents in Real World Practice (ZEST — Presented at ACC.09/i2)

Description
Drug-eluting stents (DES) are associated with decreased restenosis and need for target lesion revascularization, as compared with bare-metal stents, in patients undergoing percutaneous coronary intervention (PCI). However, there is a higher risk of late stent thrombosis with DES, especially after clopidogrel is stopped.

Current guidelines mandate dual antiplatelet therapy (DAT) with aspirin and clopidogrel for at least 12 months after DES PCI, and it is sometimes continued as long as possible. The optimal long-term duration of DAT is thus unknown. DES-LATE is a composite of two separate clinical trials (REAL-LATE and ZEST-LATE), which were both designed to study the optimal duration of DAT following DES PCI.
Hypothesis
DAT with aspirin and clopidogrel would be superior to aspirin alone in patients who had undergone PCI at least 12 months earlier.
Drugs/Procedures Used
Patients in both trials received either clopidogrel 75 mg daily with low-dose aspirin (100-200 mg), or low-dose aspirin alone in an open-label fashion.
Concomitant Medications
Statins (79%), beta-blockers (66%), and angiotensin-converting enzyme inhibitors (46%)
Principal Findings
A total of 2,701 patients were randomized (1,625 in REAL-LATE and 1,076 in ZEST-LATE), of which 1,357 received DAT, whereas 1,344 received aspirin monotherapy. The two trials were merged due to slow enrollment. All patients were enrolled in South Korea. Baseline characteristics were fairly similar between the two arms. About 26% had diabetes, 3.5% had prior myocardial infarction (MI), and 12.5% had prior angioplasty. About 37.5% of patients underwent PCI for stable PCI, whereas the rest had acute coronary syndromes, including unstable angina (40.8%), ST-elevation MI (11%) and non-ST-elevation MI (10.7%). Multivessel disease was noted in about 48% of the patients, whereas the left anterior descending artery was revascularized in about 49% of the patients. The mean number of stents per lesion was 1.3, with a mean stented length of 31.4 mm. The majority of DES were sirolimus-eluting stents (SES; 57%); others included paclitaxel-eluting stents (PES; 24%), and zotarolimus-eluting stents (ZES; 19%).

The median time from index procedure to randomization was 12.8 months, and only 12% of patients were on DAT beyond 18 months prior to randomization. Although about 98.3% of the patients were still taking aspirin at the end of 2 years of follow-up, only 83% of patients in the DAT arm and 4.4% of the patients in the aspirin arm were taking clopidogrel at the end of 2 years of follow-up.

The incidence of the primary endpoint (MI or cardiovascular death) at 2 years was similar between the DAT and aspirin monotherapy arms (1.8% vs. 1.2%, hazard ratio 1.65, 95% confidence interval 0.80-3.36, p = 0.17). No difference was noted when the analysis was conducted separately for each trial. There was also no difference between the two arms in the incidence of all-cause mortality (1.6% vs. 1.4%, p = 0.24), MI (0.8% vs. 0.7%, p = 0.49), stroke (1.0% vs. 0.3%, p = 0.19), definite stent thrombosis (0.4% vs. 0.4%, p = 0.76), or need for repeat revascularization (3.1% vs. 2.4%, p = 0.22). The composite endpoint of MI, stroke, or all-cause mortality showed a trend towards being higher in the DAT arm compared with the aspirin arm at the end of 2 years (3.2% vs. 1.8%, p = 0.051); the rates at the end of 1 year were identical (1.1% vs. 1.1%, p=NS). TIMI major bleeding was similar between the two arms (0.2% vs. 0.1%, p = 0.35).
Interpretation
Although the risks of late stent thrombosis with DES, especially after cessation of DAT, are well known, the optimal duration of DAT following DES PCI is unknown. Data from observational studies have been conflicting, and no randomized trial has been conducted on this topic yet. This trial thus seeks to answer a very important question. In this trial, patients who had been on DAT for at least 12 months following DES PCI were randomized to continuing DAT for another 2 years, or stopping clopidogrel, and continuing aspirin only. The investigators found no difference in the incidence of any of the endpoints studied, including stent thrombosis. They did note a trend towards harm for the composite endpoint of death, MI, or stroke with DAT.

One limitation of this trial is that it represents the combination of two separate trials, which were merged due to slow enrollment. ZEST-LATE was a continuation of the ZEST trial, which compared ZES to SES, and had slightly different enrollment criteria as compared with REAL-LATE, which included a broader patient population. Thus, there may be some heterogeneity between the patients in the two trials. Further, despite the merger, the overall trial was still underpowered to detect differences in clinical outcomes between the two trials, since the event rates were <25% of anticipated. Moreover, the results of this trial suggest that continuation of DAT beyond 12-24 months after DES PCI is not associated with superior clinical outcomes, as compared with discontinuation of clopidogrel after this period.

Most patients in this trial received first-generation DES. It is thus unknown if these results will be applicable to second- and third-generation DES as well. Further, it is unclear whether the results of this trial can be applied to non-Asian populations. Individual variability in response to clopidogrel can be as high as 30% among different ethnic groups, and this has a bearing on ischemic and thrombotic outcomes. Future larger trials, confirming the above results in a more diverse patient population, are thus necessary.

Finally, it should be noted that patients who had experienced a major adverse cardiac event (MACE) or bleeding since implantation were excluded from this trial. The optimal duration of DAT in such patients, as well as high-risk patients, such as those with left main stents, is likely to be longer.
Conditions
• Coronary heart disease
Therapies
• Antiplatelet agent / Clopidogrel
• Antiplatelet agent / Aspirin
Study Design
Randomized. Parallel.
Patients Enrolled: 2,701
Mean Follow-Up: 19.2 months
Mean Patient Age: 62 years
% Female: 30

Mean Ejection Fraction: 59.5%
Primary Endpoints
Cardiovascular death or MI
Secondary Endpoints
All-cause mortality
Stroke
MI
Stent thrombosis
Repeat revascularization
Death, MI, or stroke
Cardiovascular death, MI, or stroke
TIMI major bleeding
Patient Population
DES implantation at least 12 months before enrollment
No MACE or major bleeding since stent implantation
On DAT at the time of enrollment
Exclusions:
Contraindication to antiplatelet therapy
Established indication for continuing clopidogrel, such as peripheral arterial disease
Life-expectancy <1 year
Anticipated noncompliance
Participation in another drug or coronary device study
References: Park SJ, Park DW, Kim YH, et al. Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 2010;Mar 15:[Epub ahead of print].

[Chevychelov]

Title: Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA Pilot Study)
Trial Sponsor: St. Jude Medical Foundation
Year Presented: 2010
Topic(s): Arrhythmias
Summary Posted: 3/15/2010 10:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: CABANA Pilot Study
Related Trial: ThermoCool AF

Description
The recently published ThermoCool AF study demonstrated the superiority of catheter ablation with pulmonary vein isolation (PVI) over antiarrhythmic drugs (AAD) in the management of patients with symptomatic atrial fibrillation (AF), who had failed at least one AAD. The CABANA pivotal trial tested the hypothesis that primary catheter ablation for the elimination of AF is superior to state-of-the-art drug therapy for reducing recurrent AF in high-risk patients.
Hypothesis
Catheter ablation would be superior to medical management in the treatment of recurrent AF in high-risk patients.
Drugs/Procedures Used
Catheter ablation was performed percutaneously, with isolation of all four pulmonary veins (PVI). Additional adjunctive linear or circumferential ablation was conducted as necessary. In the medical management arm, patients could be treated with rhythm (16%), rate control (13%), or both (71%).
Principal Findings
A total of 60 patients were randomized, in which 29 patients were randomized to catheter ablation, and 31 patients to medical management. Baseline characteristics were fairly similar between the two groups. About 80% had hypertension, 18% had diabetes, and 17% had underlying cardiomyopathies. About 35% had coronary artery disease, and 36% had class II or III heart failure. Paroxysmal AF was noted in 32%, and 68% had persistent or long-standing persistent AF. Prior antiarrhythmic drugs had been tried in 30%, with 25% having failed one AAD. About 23% of patients had a history of atrial flutter. About 39% of the patients had a CHADS2 score of ≥2.

The incidence of freedom from symptomatic AF after the blanking period was significantly higher in the catheter ablation arm, as compared with AAD (65% vs. 41%, hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.21-0.99, p = 0.03). However, the incidence of any AF, atrial flutter, or atrial tachycardia was similar between the two arms (66% vs. 72%, HR 0.69, 95% CI 0.37-1.32, p = 0.26). About 13% of patients crossed over from the AAD arm to the catheter ablation arm over the duration of follow-up, and 21% of patients in the catheter ablation arm needed at least one other ablation procedure.

Adverse events after catheter ablation included moderate PV stenosis in one patient; no cases of severe PV stenosis. In addition, two patients developed an AV fistula or a pseudoaneurysm, with no atrial esophageal fistulas.
Interpretation
The results of the CABANA pilot study indicate that catheter ablation is associated with a reduction in symptomatic AF in high-risk patients, as compared with AAD. In this small group of patients, there was no difference in the incidence of AF, atrial flutter, or atrial tachycardia between the two groups. Adverse event rates were low, including the incidence of PV stenosis.

The results of the CABANA pilot study will be used for designing the CABANA pivotal study.
Conditions
• Arrhythmias / Atrial fibrillation
Therapies
• Antiarrhythmic
Study Design
Randomized. Parallel.
Patients Enrolled: 60
NYHA Class (% I, II, II, IV): II or III (36%)
Mean Follow-Up: 12 months
Mean Patient Age: Median age: 61 years
% Female: 23

Mean Ejection Fraction: 55%
Primary Endpoints
AF recurrence
Secondary Endpoints
Complications with therapy
Change in left atrial volume and morphology
Recurrent hospitalization
Quality-of-life outcomes
Patient Population
• ≥2 paroxysmal AF episodes (≥1 hour) over 4 months or ≥1 persistent AF episode (>1 week)

• ≥65 years of age, or <65 years with ≥1 risk factor:
Hypertension
Diabetes
Heart failure
Prior cerebrovascular accident or transient ischemic attack
Left atrial size >5.0 cm (volume index ≥40 cc/m2)
Ejection fraction ≤35%

• Eligible for ablation and ≥2 rhythm control and/or ≥3 rate control drugs
References: Presented by Dr. Douglas Packer at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: A Randomized Clinical Trial of Three Doses of a Long-Acting Oral Direct Factor Xa Inhibitor Betrixaban in Patients With Atrial Fibrillation (EXPLORE-Xa)
Trial Sponsor: Portola Pharmaceuticals and Merck
Year Presented: 2010
Topic(s): Arrhythmias, Congenital Heart Disease, Prevention/Vascular
Summary Posted: 3/15/2010 10:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: EXPLORE-Xa

Description
The goal of the phase 2 trial was to evaluate treatment with three doses of the long-acting oral direct factor Xa inhibitor betrixaban compared with warfarin among patients with nonvalvular atrial fibrillation.
Hypothesis
Betrixaban would be superior in preventing significant bleeding events.
Drugs/Procedures Used
Patients with nonvalvular atrial fibrillation were randomized to one of three doses of betrixaban (40 mg, n = 127; 60 mg, n = 127; 80 mg, n = 127) versus warfarin, with goal international normalized ratio (INR) 2-3 (n = 127).
Principal Findings
Overall, 508 patients were randomized. The median age was 74 years, 54% had an estimated glomerular filtration rate >70 ml/min, mean CHADS2 score was 2.2, and 33% were women.

At 3 months, the number of major or clinically relevant nonmajor bleeds was one in the betrixaban 40 mg group, four in the betrixaban 60 mg group, five in the betrixaban 80 mg group, and four in the warfarin group. The number of strokes was 0, 1, 1, and 0 and the number of deaths was 1, 0, 0, 1, respectively, for the four groups.

Considering the extent of follow-up, the lowest hazard for the primary outcome was in the betrixaban 40 mg group, intermediate in the 60 mg and 80 mg groups, and highest in the warfarin group (p = 0.35, for betrixaban groups compared with warfarin).

Alanine aminotransferase (ALT) >2x ULN was 2.4% in the betrixaban groups and 2.4% in the warfarin group. Vomiting, nausea, and diarrhea were more common with betrixaban.
Interpretation
Among patients with atrial fibrillation, the three tested doses of betrixaban appeared to be well-tolerated. Bleeding seemed to be lowest with the betrixaban 40 mg group, compared with higher-dose betrixaban or warfarin. Larger clinical trials are warranted to determine the efficacy and safety of betrixaban.
Conditions
• Arrhythmias / Atrial fibrillation
Therapies
• Anticoagulant
• Medical
Study Design
Randomized. Blinded. Parallel.
Patients Screened: 561
Patients Enrolled: 508
Mean Follow-Up: 3-12 months
Mean Patient Age: 73 years
% Female: 33%

Primary Endpoints
Time to occurrence of major or clinically relevant nonmajor bleeding
Secondary Endpoints
Time to occurrence of any bleeding (major, clinically relevant nonmajor, and minimal)
Time to occurrence of death, stroke, myocardial infarction, or other systemic embolism
Patient Population
Patients with nonvalvular atrial fibrillation with at least one risk factor for stroke
Age at least 18 years of age
No uncontrolled hypertension
Aspirin ≤162 mg daily
INR ≤2.2 at randomization or unable to comply with INR monitoring
Exclusions:
Weight <40 kg
Hemodialysis withing the last year
Atrial fibrillation due to reversible cause
Mechanical prosthetic valve
Condition other than atrial fibrillation requiring anticoagulation
Systolic blood pressure >160 mm Hg
Active endocarditis
Scheduled major surgery or pulmonary vein isolation procedure
Stroke, systemic embolic event, or acute coronary syndrome within 30 days
Limited life expectancy
Thrombocytopenia
Elevated liver transaminases
History of long QT syndrome
Use of aspirin >162 mg daily
Use of verapamil
Use of an investigational drug or device within 30 days
Noncompliance with INR monitoring
Inability to provide informed consent
References: Presented by Dr. Michael Ezekowitz at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

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Title: Comparison of Zotarolimus-Eluting Stents and Sirolimus-Eluting Stents in Patients With Coronary Artery Disease (SORT OUT III)
Trial Sponsor: Cordis and Medtronic
Year Presented: 2008
Topic(s): Interventional Cardiology
Summary Posted: 3/15/2010 11:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Summary Slide: SORT-OUT III trial
Presentation Slides: SORT OUT III
Journal Scan: Efficacy and Safety of Zotarolimus-Eluting and Sirolimus-Eluting Coronary Stents in Routine Clinical Care (SORT OUT III): A Randomised Controlled Superiority Trial
Related Trial: Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II: Results Through 4 Years )
Related Trial: Randomized Controlled Trial of the Medtronic Endeavor Drug-Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR III: Results Through 3 Years)
Related Trial: Randomized, Controlled Trial of the Medtronic Endeavor Drug-Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR IV)
Related Trial: Comparison of Paclitaxel- and Sirolimus-Eluting Stents in Everyday Clinical Practice (SORT OUT II)

Description
Zotarolimus-eluting stents (ZES) are newer drug-eluting stents that have recently become available. The SORT OUT III study sought to compare the relative safety and efficacy of ZES with sirolimus-eluting stents (SES).
Hypothesis
ZES would be similar in efficacy and safety to SES.
Drugs/Procedures Used
Percutaneous coronary intervention (PCI) with ZES or SES in a 1:1 fashion
Concomitant Medications
Dual antiplatelet therapy for 12 months; lipid-lowering therapy (70%), glycoprotein IIb/IIIa inhibitors (17%)
Principal Findings
A total of 2,333 patients were randomized, 1,162 to ZES and 1,170 to SES. Baseline characteristics were fairly similar between the two groups. About 15% of the patients had diabetes. About one-half of the patients (52%) underwent PCI for stable angina, 38% for unstable coronary syndromes, and 7% for ST-elevation myocardial infarction (STEMI). Most patients (70%) had one-vessel disease. The mean number of stents per patient was 1.7, with a mean stent length of 18.0 mm.

The incidence of the composite endpoint at 9 months was significantly higher with ZES compared with SES (6% vs. 3%, hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.43-3.23, p = 0.0002). There was no difference between ZES and SES in the incidence of all-cause mortality at 9 months (2% vs. 2%, HR 1.40, 95% CI 0.76-2.56, p = 0.28). MI was significantly higher in the ZES arm compared with the SES arm (2% vs. <1%, HR 4.55, 95% CI 1.54-13.4, p = 0.006). Similarly, definite stent thrombosis was significantly higher in the ZES arm compared with the SES arm (1% vs. <1%, p = 0.05). The need for target lesion revascularization was also significantly higher with ZES compared with SES (4% vs. 1%, HR 4.25, 95% CI 2.26-7.97, p < 0.0001), with a significantly higher rate of in-stent restenosis (3% vs. 1%, HR 6.28, 95% CI 2.65-14.9, p < 0.0001).

At 18 months, there was still an increase in the incidence of the composite endpoint in the ZES arm compared with SES (10% vs. 5%, p < 0.0001), as well as mortality (4% vs. 3%, p = 0.035), MI (2% vs. 1%, p = 0.03), target lesion revascularization (6% vs. 2%, p < 0.0001), and in-stent restenosis (5% vs. 1%, p < 0.0001). The incidence of definite stent thrombosis was similar between the two arms (1% vs. 1%, p = 0.13).
Interpretation
The results of the SORT-OUT III trial indicate that the ZES are associated with a higher incidence of MI, target lesion revascularization, clinically significant restenosis, as well as definite stent thrombosis at 9 months, compared with SES. In addition, patients receiving ZES had a significantly higher mortality, as compared with patients receiving SES at 18 months. Both groups were on dual antiplatelet therapy for at least 12 months. In this trial, the investigators tried to include as diverse a population as possible, with no major exclusions, thus mirroring "real-world" practice as best as possible.

One limitation of this trial is that although they prospectively followed patients, outcomes data were obtained from national registries, rather than direct patient contact. Thus, although it is unlikely that there would be a differential bias with respect to outcomes, there could be an under-reporting or a lag in reporting of certain outcomes. In events with a low incidence rate, such as stent thrombosis, this might be an important consideration.
Conditions
• Coronary heart disease
Therapies
• Stent/drug-eluting
Study Design
Randomized. Parallel.
Patients Screened: 9,221
Patients Enrolled: 2,333
Mean Follow-Up: 18 months
Mean Patient Age: 64.3 years
% Female: 26

Mean Ejection Fraction: 51%
Primary Endpoints
Safety:
All-cause mortality
Cardiac mortality
MI
Definite stent thrombosis

Efficacy:
Clinically driven target lesion revascularization
Clinically significant re-stenosis (ISR)
Patient Population
Patients undergoing PCI for any indication
References: Rasmussen K, Maeng M, Kaltoft A, et al. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial. Lancet 2010;Mar 15:[Epub ahead of print].

Presented by Dr. Michael Maeng at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Presented by Dr. Jens Flensted Lassen at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2008), Washington, DC, October 2008.

[Chevychelov]

Official Title: The Impact of Remote Monitoring with Automatic Clinician Notifications on the Clinical Care of ICD and CRT-D Patients (CONNECT)
Event: ACC Annual Scientific Session 2010
Topic(s): Arrhythmias
Presenter: George H. Crossley, III
Writer(s): Xiushui Ren
Date Posted: 3/15/2010
Related Resources
Presentation Slides: CONNECT

Summary
Remote monitoring in patients with implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds) appears to improve patient care and reduce healthcare utilization.

Background
Because expanded indications for ICDs and CRT-D have resulted in a substantially increased number of device implants, clinicians have adjusted their practices to enable proper follow-up. Newer ICD and CRT-D devices provide remote monitoring capabilities that are designed to allow for more efficient follow-up and reduce healthcare utilization.

The Clinical evaluation Of remote NotificatioN to rEduCe Time to clinical decision (CONNECT) study is a randomized controlled trial to examine the clinical and health care utilization impact of wireless remote monitoring versus routine in-office care.

Study Design
The CONNECT study randomized 1997 patients implanted with a Medtronic wireless ICD or CRT-D to remote monitoring (n=1014) versus routine in-office care (n=983). Patients monitored remotely were given a wireless home monitor for transmitting device diagnostics to the clinician's office. Examples of key diagnostics include atrial tachycardia (AT) and atrial fibrillation (AF) daily burden, rapid ventricular response during AT/AF, and shocks delivered. Both groups had lead and device integrity (including lead impedance out of range, VF detection, low battery voltage, and excessive charge time) alerts on.

All patients were followed for 15 months post-implant. Patients in the remote monitoring arm had office visits at only one month and 15 months post-implant. Patients in the routine care arm had office visits at one, three, six, nine, 12, and 15 months post-implant.

The primary objective was to compare time to clinical decision between patients managed remotely and patients managed with routine in-office care. The key secondary objective was to assess the impact of remote monitoring and early notification on healthcare utilization.

Results and Conclusions
Baseline characteristics were similar between the two groups. The mean age was 65 years, and 71% were men. CRT-D comprised 35% of the total devices. The mean LV ejection fraction was 29%, and approximately 88% of the patients were NYHA class II and III.

At follow-up, there were a total of 317 events (172 in remote monitoring arm and 145 in routine in-office care) triggering clinical decisions. The majority of events were high AT/AF burden, fast V rate, and ICD shocks. The median time from event to clinical decision was significantly shorter for the remote monitoring arm (4.6 vs 22 days, p<0.001). The total yearly clinic visits per patient were 3.9 and 6.3 for remote monitoring and routine care groups, respectively. The length of stay per hospitalization for remote monitoring and routine care groups was 3.3 and 4.0 days, p=0.002, respectively.

Thus remote monitoring in patients with ICD and CRT-D resulted in a significant reduction in time from onset of events to clinical decisions in response to arrhythmias and device issues. In addition, remote monitoring seemed to reduce overall healthcare utilization including reduced number of clinic visits and short hospital stay. These data support the use of remote monitoring ICD and CRT-D.

Perspective
It is important to note that, the effect of remote monitoring on battery life and device cost is unclear.

[Chevychelov]

Title: 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine
Source: Developed in Collaboration With the American College of Emergency Physicians, Endorsed by the North American Society for Cardiovascular Imaging
Topic: Noninvasive Cardiology
Date Posted: 3/16/2010 8:00:00 AM
Author(s): Hiratzka LF, Bakris GL, Beckman JA, et al.
Citation: J Am Coll Cardiol 2010;Mar 16:[Epub ahead of print].
Clinical Trial: No
Related Resources
JACC Article: 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary
Guideline: Thoracic Aortic Disease: Guidelines for the Diagnosis and Management of Patients With

Perspective: The following are 12 points to remember about the 2010 thoracic aortic disease guidelines.

1. The goal of this guideline is to improve the health outcomes and quality of life for all patients with thoracic aortic disease. Thoracic aortic diseases are usually asymptomatic and not easily detectable until an acute and often catastrophic complication occurs.

2. Imaging of the thoracic aorta with computed tomographic imaging (CT), magnetic resonance imaging (MRI), or in some cases, echocardiographic examination is the only method to detect thoracic aortic diseases and determine risk for future complications. Measurements of aortic diameter should be taken at reproducible anatomic landmarks, perpendicular to the axis of blood flow, and reported in a clear and consistent format.

3. The identification and treatment of patients at risk for acute and catastrophic disease presentations (e.g., thoracic aortic dissection and thoracic aneurysm rupture) prior to such an occurrence are paramount to eliminating the high morbidity and mortality associated with acute presentations.

4. Aortic imaging is recommended at the time of diagnosis of Marfan syndrome or Loeys-Dietz syndrome to determine the aortic root and ascending aortic diameters, and 6 months thereafter to determine the rate of enlargement of the aorta. Annual imaging is recommended for patients with Marfan syndrome and if stability of the aortic diameter is documented. Loeys-Dietz patients should have yearly MRI from the cerebrovascular circulation to the pelvis.

5. Aortic imaging is recommended for first-degree relatives of patients with thoracic aortic aneurysm and/or dissection to identify those with asymptomatic disease.

6. Providers should routinely evaluate any patient presenting with complaints that may represent acute thoracic aortic dissection to establish a pretest risk of disease that can then be used to guide diagnostic decisions. This process should include specific questions about medical history, family history, and pain features, as well as a focused examination to identify findings that are associated with aortic dissection.

7. Urgent and definitive imaging of the aorta using transesophageal echocardiogram (TEE), CT scanning, or MRI is recommended to identify or exclude thoracic aortic dissection in patients at high risk for the disease by initial screening.

8. Initial management of thoracic aortic dissection should be directed at decreasing aortic wall stress by controlling heart rate and blood pressure with beta-blockers or nondihydropyridine calcium channel-blockers in those with contraindications to beta-blockers. If systolic blood pressures remain >120 mm Hg after adequate heart rate control has been obtained, then angiotensin-converting enzyme inhibitors and/or other vasodilators should be administered intravenously to further reduce blood pressure that maintains adequate end-organ perfusion.

9. Urgent surgical consultation should be obtained for all patients diagnosed with thoracic aortic dissection regardless of the anatomic location (ascending vs. descending) as soon as the diagnosis is made or highly suspected.

10. For patients with ascending thoracic aortic dissection, all aneurysmal aorta and the proximal extent of the dissection should be resected. A partially dissected aortic root may be repaired with aortic valve resuspension. Extensive dissection of the aortic root should be treated with aortic root replacement with a composite graft or with a valve sparing root.

11. Stringent control of hypertension, lipid profile optimization, smoking cessation, and other atherosclerosis risk-reduction measures should be instituted for patients with small aneurysms not requiring surgery, as well as for patients who are not considered surgical or stent graft candidates.

12. For patients with degenerative or traumatic aneurysms of the descending thoracic aorta exceeding 5.5 cm, saccular aneurysms, or postoperative pseudoaneurysms, endovascular stent grafting should be strongly considered when feasible. Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Paclitaxel-Eluting Stent Versus Conventional Stent in ST-Segment Elevation Myocardial Infarction (PASSION: 5-Year Follow-Up)
Year Presented: 2006
Year Published 2006
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.

Related Resources
Summary Slide: PASSION Trial
Presentation Slides: PASSION
Related Trial: Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated With Angioplasty (TYPHOON )
Related Trial: Helsinki Area Acute Myocardial Infarction Treatment Re-Evaluation - Should the Patients Get a Drug-Eluting or Normal Stent (HAAMU-STENT - Presented at TCT 2006)
Related Trial: MISSION (MISSION – Presented at AHA 2006)
Related Trial: Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION: Stent Study)
Guideline: ST-Elevation Myocardial Infarction: Guidelines for the Management of Patients with

Description
The goal of the trial was to evaluate treatment with paclitaxel-eluting stents compared with bare-metal stents among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).
Hypothesis
Paclitaxel-eluting stents would be superior at reducing the need for revascularization.
Drugs/Procedures Used
Patients undergoing primary PCI were randomized to paclitaxel-eluting Express2 stent (n = 309) or bare-metal stents (n = 310) with either the Express2 or Liberte platform. Use of the glycoprotein IIb/IIIa inhibitors abciximab or tirofiban was at the discretion of the treating physician. Patients did not undergo angiographic follow-up in this trial, but were followed for clinical events.
Concomitant Medications
Aspirin (80-100 mg) and clopidogrel (300 mg loading dose followed by 75 mg/d for 6 months)
Principal Findings
Mean time from symptom onset to angioplasty was 3 hours. Left anterior descending artery was the culprit in 50% of patients, and 45% of patients had multivessel disease. Procedural success was 95%. An average of 1.3 stents was used in both arms.

The primary endpoint of death, reinfarction, or target lesion revascularization (TLR) at 1 year did not differ between treatment groups (8.8% for paclitaxel-eluting stent group vs. 12.8% for bare-metal stent group, p = 0.12). Cardiac death or MI occurred in 5.5% of the paclitaxel-eluting stent group and 7.2% of the bare-metal stent group (p = 0.40). There was also no difference in TLR (5.3% vs. 7.8%, p = 0.23). There were three cases of stent thrombosis in each group.

At 5 years, cardiac death, MI, or TLR was 18.3% versus 22.0% (p = 0.24), cardiac death was 8.9% versus 11.5% (p = 0.28), MI was 6.5% versus 4.3% (p = 0.28), and TLR was 7.3% versus 10.5% (p = 0.16), respectively, for paclitaxel-eluting stents versus bare-metal stents. Cummulative definite stent thrombosis was 3.6% versus 1.7% (p = 0.20), definite or probable stent thrombosis was 3.9% versus 3.4% (p = 0.85), and possible stent thrombosis was 6.8% versus 6.7% (p = 0.93), respectively. Censoring events that occurred within 30 days, the cummulative 5-year incidence of definite stent thrombosis, was 2.9% versus 0.8% (p = 0.06), respectively.
Interpretation
Among patients undergoing primary PCI for STEMI, use of paclitaxel-eluting stents was not associated with a difference in the primary composite endpoint at 1 year compared with bare-metal stents.

Drug-eluting stents have been widely studied in the setting of elective PCI, but relatively little randomized data exist in the setting of STEMI. The present trial is the first large-scale randomized study with paclitaxel-eluting stents compared with bare-metal stents conducted exclusively in the STEMI population.

The TYPHOON trial demonstrated a reduction in target vessel revascularization with sirolimus-eluting stents over bare-metal stents in STEMI patients. However, there were several important differences between the trial in addition to the different drug-eluting stent used, including an angiographic follow-up in the TYPHOON trial, which may have increased the repeat revascularization rate. The TLR rate in the present study was very low in both arms.

At 5 years, cardiac death, MI, or TLR was similar between the groups; however, late stent thrombosis (between 30 days and 5 years) was increased with paclitaxel-eluting stents.
Conditions
• Coronary heart disease
• Coronary heart disease / Acute MI
Therapies
• Stent
• Stent/drug-eluting
Study Design
Randomized. Blinded.
Patients Enrolled: 619
Mean Follow-Up: 5 years
Mean Patient Age: 61 years
% Female: 24

Primary Endpoints
Composite of death, recurrent MI, or TLR (within 5 mm of stent edges) at 1 year
Secondary Endpoints
MACE at 5 years
Individual components of MACE
Stent thrombosis
Patient Population
STEMI with chest pain for >20 minutes and ST elevation in ≥2 contiguous leads;
Infarct-related artery with a de novo lesion suitable for stenting on diagnostic angiography
Exclusions:
Cardiogenic shock
Mechanical ventilation
Failed fibrinolysis
Expected mortality of <6 months
References: Presented by Dr. Maarten Vink at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Laarman GJ, Suttorp MJ, Dirksen MT, et al. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med 2006;355:1105-13.

Presented by Dr. Maurits T. Dirksen at the March 2006 i2 Annual Scientific Session, Atlanta, GA.

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Title: Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE)
Trial Sponsor: National Heart, Lung, and Blood Institute
Year Presented: 2010
Topic(s): General Cardiology, Heart Failure/Transplant
Summary Posted: 3/16/2010 8:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: DOSE

Description
Although intravenous (IV) diuretics are routinely used in clinical practice, the optimal dosage and route of administration are not well understood. In addition, observational studies have demonstrated worsening creatinine and clinical outcomes with higher dose of furosemide. Accordingly, the DOSE study sought to evaluate the safety and efficacy of different strategies for diuretic dosing in patients with acute decompensated heart failure (ADHF).
Hypothesis
The DOSE study sought to evaluate the safety and efficacy of two strategies for furosemide dosing in patients with ADHF: 1) route of administration (Q12 hour bolus vs. continuous infusion), and 2) dosing (low intensification to 1x oral dose vs. high intensification to 2.5x oral dose).
Drugs/Procedures Used
Patients were randomized in a 2x2 factorial design to either Q12 hour bolus versus continuous infusion, or low intensification to 1x oral dose versus high intensification to 2.5x oral dose of furosemide. About 48 hours after randomization, patients could be changed over to oral diuretics, continued on same strategy, or undergo a 50% increase in dose, as deemed appropriate.
Concomitant Medications
Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (64%), beta-blockers (83%), aldosterone antagonists (28%)
Principal Findings
A total of 308 patients were randomized in a 2x2 factorial fashion. The mean ejection fraction was 35 ± 18%, with a baseline furosemide dose of 131 mg/day. About 57% of the patients had ischemic cardiomyopathy, 53% had atrial fibrillation or atrial flutter, and 51% had diabetes. The mean systolic blood pressure was 119 mm Hg, with a mean heart rate of 78 bpm. Mean sodium was 138 mg/dl, and mean creatinine was 1.6 mg/dl. The mean N-terminal B-type natriuretic peptide (NT-proBNP) was 7439 pg/ml.

There was no difference between Q12 dosing and continuous infusion of furosemide on the visual analog scale (VAS) area under the curve (AUC) (4236 vs. 4373, p = 0.47). Change in creatinine was also similar (0.05 vs. 0.07 mg/dl, p = 0.45). Secondary endpoints such as net volume loss (4237 vs. 4249 ml, p = 0.89), % treatment failure (38% vs. 39%, p = 0.88), change in weight at 72 hours (-6.8 vs. 8.1 lbs, p = 0.20), dyspnea VAS AUC at 72 hours (4456 vs. 4699, p = 0.36), and length of stay (5 vs. 5 days, p = 0.97) were similar between the two arms. The incidence of a composite of death, rehospitalization, or emergency department visit was similar between the two arms (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.86-1.66, p = 0.3).

For the low and high intensification of furosemide dosing analysis, there was no difference on the VAS AUC (4171 vs. 4430, p = 0.06). Change in creatinine was also similar (0.04 vs. 0.08 mg/dl, p = 0.21). Secondary endpoints such as net volume loss (3575 vs. 4899 ml, p = 0.001), change in weight at 72 hours (-6.1 vs. 8.7 lbs, p = 0.011), and dyspnea VAS AUC at 72 hours (4478 vs. 4688, p = 0.04) were significantly worse in the low intensification arm, as compared with the high intensification arm, respectively.

Other outcomes such as length of stay (6 vs. 5 days, p = 0.55), and % treatment failure (37% vs. 40%, p = 0.56) were similar between the two arms. The % of patients with increase in creatinine of >0.3 mg/dl within 72 hours was lower in the low intensification arm (14% vs. 23%, p = 0.04). However, this was transient, since there was no overall change in creatinine or cystatin C between the two groups. There was also no difference between the two groups in serum creatinine over the 60 day follow-up period. The incidence of a composite of death, rehospitalization, or emergency department visit was similar between the two arms (HR 0.83, 95% CI 0.60-1.16, p = 0.28).
Interpretation
The results of the DOSE trial illustrate that there is no difference in global symptom relief, as assessed by the VAS AUC, or change in renal function, with a Q12 versus continuous infusion, or low versus high intensification of furosemide dosing. Further, continuous dosing was not associated with an improvement in any of the secondary outcomes assessed, including net diuresis, weight loss, or treatment failure. On the other hand, high intensification (2.5x oral dose) of furosemide was associated with a significant reduction in net diuresis, weight loss, and symptom relief, as compared with low intensification. Changes in creatinine noted in the high intensification arm are transient.

These results are important, and aim to address two important clinically relevant questions regarding the use of diuretics in patients with ADHF. One of the limitations is that the study protocol permitted change in congestive heart failure (CHF) medications 48 hours after randomization, based on clinical response. This could have biased the results towards the null. An analysis of outcomes at 48 hours may be helpful to address this issue. Also, these results are applicable to patients with chronic CHF, who did not require inotropes or intravenous vaspodilators, and who were on moderate to high doses of diuretic at baseline.
Conditions
• Heart failure
Therapies
• Diuretic
Study Design
Randomized. Parallel. Factorial.
Patients Enrolled: 308
Mean Follow-Up: 60 days
Mean Patient Age: Median age: 66 years
% Female: 27

Mean Ejection Fraction: 35
Primary Endpoints
Efficacy:
Patient Global Assessment by VAS over 72 hours using AUC
Safety:
Change in creatinine from baseline to 72 hours
Secondary Endpoints
Change in weight over 24, 48, 72, and 96 hours
Freedom from signs and symptoms of congestion at 72 hours
Bivariate vector of change in creatinine and weight at 72 hours
Dyspnea VAS AUC over 24, 48, and 72 hours
Change in serum creatinine at 24, 48, and 96 hours, day 7 (or discharge), and day 60
Change in cystatin C at 72 hours, day 7 (or discharge), and day 60
Persistent or worsening HF
Development of worsening renal function (increase in creatinine >0.3 mg/dl at any time during initial 72 hours)
Treatment failure (persistent HF, worsening renal failure, or death)
Index hospitalization length of stay
Death, rehospitalization, or emergency department visit within 60 days
Patient Population
≥18 years old
Prior clinical diagnosis of HF with daily home use of oral loop diuretic for at least 1 month
Daily oral dose of furosemide ≥80 mg and ≤240 mg (or equivalent)
Identified within 24 hours of hospital admission
HF defined by at least one symptom and one sign
Anticipated need for IV loop diuretics for at least 48 hours
Willingness to provide informed consent
Exclusions:
Received or planned IV vasoactive treatment (inotropes, vasodilators) or ultra-filtration therapy for HF
Systolic blood pressure <90 mm Hg
Serum creatinine >3.0 mg/dl at baseline or renal replacement therapy
BNP <250 ng/ml or NT-proBNP <1000 mg/ml (if measured for clinical purposes)
Acute coronary syndrome within 4 weeks
Anticipated need for coronary angiography or other procedures requiring IV contrast
References: Presented by Dr. G. Michael Felker at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

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Title: Comparison of AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting to Direct Stenting Alone in Patients With Acute Myocardial Infarction (JETSTENT)
Trial Sponsor: Medrad Interventional/Possis
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: JETSTENT
Related Trial: Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS)
Related Trial: AngioJet Rheolytic Thrombectomy In Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction (AiMI)

Description
The goal of the trial was to evaluate treatment with AngioJet rheolytic thrombectomy plus stenting compared with direct stenting alone among patients with acute myocardial infarction (MI).
Hypothesis
AngioJet rheolytic thrombectomy would be superior at improving myocardial perfusion and clinical outcomes.
Drugs/Procedures Used
Patients with ST-elevation MI (STEMI) were randomized to AngioJet rheolytic thrombectomy plus stenting (n = 256) versus direct stenting alone (n = 245).

Temporary pacemaker and balloon pre-dilatation were strongly discouraged.
Concomitant Medications
Routine abciximab in both groups
Principal Findings
Overall, 501 patients were enrolled. There was no difference in baseline characteristics between the groups. In the rheolytic thrombectomy group, the mean age was 63 years, 24% were women, 14% had diabetes, cardiogenic shock was present in 2.7%, time from symptoms to the emergency room was 125 minutes, time from the emergency room to percutaneous coronary intervention was 34 minutes, reference vessel diameter was 2.9 mm, and Thrombolysis in Myocardial Infarction (TIMI) flow 0/1 was 84%.

Procedural time was 60 minutes in the rheolytic thrombectomy group versus 46 minutes in the direct stenting group (p < 0.001), mean stents per patient were 1.3 versus 1.4 (p = 0.022), and mean stent length was 24 mm versus 26 mm (p = 0.050), respectively.

The primary outcome of at least 50% ST resolution was 86% with rheolytic thrombectomy versus 79% with direct stenting alone (p = 0.043). Infarct size was 12% versus 13% (p = 0.40), respectively.

Major adverse cardiac events (MACE) at 1 month was 3.1% versus 6.9% (p = 0.05), death 1.6% versus 2.9%, MI 0.8% versus 1.2%, target vessel revascularization (TVR) 0.8% versus 2.5%, and stroke 0 versus 0.4%, respectively.

MACE at 6 months was 12.0% versus 20.7% (p = 0.012), death 3.0% versus 4.9%, MI 0.8% versus 1.3%, TVR 7.7% versus 14.1%, and stroke 0.4% versus 0.4%, respectively.

TIMI major bleeding was 3.9% versus 1.6% (p = 0.12), need for pacing was 0.08% versus 0% (p = 0.17), and perforation was 0% versus 0.04% (p = 0.33).
Interpretation
Among patients with STEMI, the use of rheolytic thrombectomy was beneficial. This device improved myocardial reperfusion as well as 6-month MACE. Rheolytic thrombectomy increased procedural time; however, it did not appear to increase procedural complications such as need for pacing or vessel perforation. The thrombectomy group was also associated with slightly fewer stents per patient and shorter total stent length.

Importantly, there was no signal for increased strokes, which was a concern in the AiMI trial. Notable differences in the current trial are that pacing was not routinely employed and the use of lytics was excluded.

While this trial demonstrated benefit for rheolytic thrombectomy, the use of simpler aspiration thrombectomy catheters likely remains preferential. The Export catheter was beneficial in the TAPAS trial, and meta-analyses of aspiration thrombectomy devices have also demonstrated their benefit.
Conditions
• Coronary heart disease / Acute MI
• Coronary heart disease
Therapies
• Rheolytic Thrombectomy (AngioJet)
Study Design
Randomized. Parallel.
Patients Enrolled: 501
Mean Follow-Up: 6 months
Mean Patient Age: 63 years
% Female: 24%

Primary Endpoints
Early ST-segment resolution, defined as 50% ST resolution at 30 minutes
Final infarct size by scintigraphy at 1 month
TIMI flow, TIMI blush, and corrected TIMI frame count
Secondary Endpoints
Composite of death, MI, urgent TVR, and stroke at 1, 6, and 12 months
Composite of death and readmission for congestive heart failure at 12 months
Patient Population
Patients with STEMI within 12 hours of symptom onset
TIMI thrombus grade 3-5
Infarct artery vessel diameter ≥2.5 mm
Exclusions:
Lysis
Stroke within 30 days
Surgery within 6 weeks
Pre-stented infarct-related artery
References: Presented by Dr. David Antoniucci at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

[Chevychelov]

Title: Radial Artery Grafts Versus Saphenous Vein Grafts in Coronary Artery Bypass Surgery: VA Cooperative Study (VA CABG)
Trial Sponsor: VA Cooperative Studies Program
Year Presented: 2010
Topic(s): Cardiovascular Surgery, General Cardiology, Prevention/Vascular
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Related Resources
Presentation Slides: VA CABG
Related Trial: Radial Artery Patency Study (RAPS)

Description
The goal of the trial was to evaluate coronary artery bypass grafting (CABG) with radial artery grafts compared with saphenous vein grafts among patients with stable coronary artery disease (CAD).
Hypothesis
Radial artery CABG would be more effective at improving long-term graft patency.
Drugs/Procedures Used
All patients with stable CAD received a left internal mammary artery graft to the left anterior descending artery whenever possible. The best remaining recipient vessel was then randomized to a radial artery graft (n = 366) versus a saphenous vein graft (n = 367).
Principal Findings
Overall, 733 patients were randomized. Overall mortality was 2%, operative mortality was 0.7%, myocardial infarction was 1%, and stroke was 2%.

The primary endpoint, graft patency at 1 year, was 89% for radial artery grafts versus 89% for saphenous vein grafts (p = NS). Graft patency was also similar between the groups with the following anastomoses: left anterior descending (83% vs. 88%), circumflex (93% vs. 89%), and right coronary artery (86% vs. 88%).

High-grade disease (string sign) in the graft was observed in 8% versus 1% (p < 0.001), respectively. Endoscopic harvesting resulted in no difference in radial artery patency (100% vs. 89%, p = NS); however, it did lower saphenous vein graft patency (78% vs. 91%, p = 0.009).
Interpretation
Among patients undergoing elective CABG, the use of radial grafts was not superior to saphenous vein grafts. Angiographic graft patency was similar between the groups at 1 year. Endoscopic harvest of saphenous vein grafts appeared to lower patency.
Conditions
• Coronary heart disease
• Coronary heart disease / Saphenous vein grafts
• Prevention
• Coronary heart disease / Angina pectoris / Stable
Therapies
• CABG
Study Design
Randomized. Parallel.
Patients Enrolled: 733
Mean Follow-Up: 5 years
Primary Endpoints
One-year angiographic graft patency
Patient Population
Patients with stable CAD undergoing elective CABG
References: Presented by Dr. Steven Goldman at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

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Title: Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION: Stent Study)
Trial Sponsor: Supported by unrestricted grants from Cordis/Johnson & Johnson, Medtronic, Abbott, and Boston Scientific.
Year Presented: 2007
Year Published 2008
Topic(s): Interventional Cardiology
Summary Posted: 3/16/2010 11:00:00 AM
Writer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly

Related Resources
Summary Slide: DEDICATION STENT
Presentation Slides: DEDICATION Stent Study
Related Trial: Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction (DEDICATION: Distal Protection Study)
Related Trial: Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI — Presented at TCT 2009)
Journal Scan: Increased Rate of Stent Thrombosis and Target Lesion Revascularization After Filter Protection in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: 15-Month Follow-Up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) Trial
Related Trial: Paclitaxel-Eluting Stent Versus Conventional Stent in ST-Segment Elevation Myocardial Infarction (PASSION: 5-Year Follow-Up)
Related Trial: Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction (SESAMI)

Description
The goal of the trial was to evaluate use of a drug-eluting stent (DES) compared with a bare-metal stent (BMS) among patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).
Hypothesis
DES would be superior to BMS for AMI.
Drugs/Procedures Used
Patients undergoing primary PCI were randomized to the use of a DES (n = 313) or BMS (n = 313). Choice of DES was at the discretion of the investigator. Angiographic follow-up was performed at 8 months. Patients also received distal embolic protection versus PCI without embolic protection by 2 x 2 factorial design (results presented separately).
Concomitant Medications
Patients received 300-500 mg aspirin, 300-600 mg clopidogrel, and 10,000 U unfractionated heparin. A beta-blocker was administered if blood pressure and heart rate allowed. Patients were treated with a glycoprotein (GP) IIb/IIIa inhibitor in the catheterization laboratory.
Principal Findings
The infarct artery was the left anterior descending in 42% of patients, and 63% had single-vessel disease. GP IIb/IIIa inhibitors were used in 96% of cases. In the DES arm, the sirolimus-eluting stent was used in 47% of cases and the paclitaxel-eluting stent in 40%. Final Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow was present in 90% of patients at the end of the PCI.

At 8-month angiographic follow-up, in-stent late lumen loss was smaller in the DES group compared with the BMS group (0.09 mm vs. 0.69 mm, p < 0.001). Percent diameter stenosis was lower in the DES group (21.7% vs. 34.0%, p < 0.001), as was binary restenosis (4.8% vs. 16.6%, p < 0.001). Major adverse cardiac events (MACE) at 8 months were lower in the DES group compared with the BMS group (8.9% vs. 14.4%, p < 0.05), driven by a reduction in target lesion revascularization (TLR) (5.1% vs. 13.1%, p < 0.001). There was no difference in MI (1.6% vs. 2.6%, p = 0.42). Cardiac death trended higher in the DES group (4.2% vs. 1.6%, p = 0.09), as did overall mortality (5.1% vs. 2.6%, p = 0.14). There was no difference in stent thrombosis, with seven cases in the DES group versus eight cases in the BMS group (p = 0.72).

At 3 years, the incidence of MACE was significantly lower in the DES arm, as compared with the BMS arm (11.5% vs. 18.2%, p = 0.024). This was driven predominately by a reduction in the need for TLR (6.1% vs. 16.3%, p < 0.001). There was no difference in MI between the two arms (1.9% vs. 3.2%, p = 0.45). The trend towards an increase in all-cause mortality with DES noted at 8 months was still present at 3 years (10.5% vs. 6.4%, p = 0.08). However, there was a significant increase in cardiovascular mortality with DES at the end of 3 years (6.1% vs. 1.9%, p = 0.013). However, the incidence of stent thrombosis was similar between the two arms (p = 0.5).
Interpretation
Among patients undergoing primary PCI for AMI, use of a DES was associated with a reduction in late lumen loss at 8 months compared with use of a BMS, but cardiac mortality trended higher. At 3 years, there was a significant reduction in MACE, driven predominantly by a significant reduction in TLR in the DES arm, as compared with BMS. Of concern though, all-cause mortality at 3 years showed a trend towards being higher with DES, as compared with BMS, and cardiovascular mortality was significantly higher.

The reasons for the increase in cardiovascular mortality with DES noted in this trial are not clear. Although there was no difference in stent thrombosis between the two arms, the total duration of dual antiplatelet therapy was not reported.

These results are contrary to the 2-year results of the HORIZONS-STENT trial, which showed an improvement in TLR, but no difference in mortality between DES and BMS. These outcomes need to be studied in other long-term trials of patients with AMI receiving DES versus BMS.
Conditions
• Coronary heart disease
• Coronary heart disease / Acute MI
Therapies
• Stent
• Stent/drug-eluting
Study Design
Randomized. Parallel.
Patients Screened: 1,687
Patients Enrolled: 626
Mean Follow-Up: 3 years
Mean Patient Age: 62 years
% Female: 27

Mean Ejection Fraction: 48%
Primary Endpoints
Late lumen loss at 8 months
Secondary Endpoints
Cardiac events at 8 months
Patient Population
Acute onset typical chest pain within 12 hours
ST-elevation of >4 mm in contiguous leads
High-grade stenosis or occlusion of a native major coronary artery that can be crossed with a soft or intermediate tip guidewire
Possibility to perform distal protection of the infarct-related artery
Exclusions:
History of previous MI
Use of fibrinolytic agents for the index infarction
Left main stenosis
Heavy calcification of abdominal aorta or occlusive iliofemoral disease hampering access to the coronary ostias by the femoral route
Known renal failure
Other significant cardiac disease
Other severe disease with an expected survival <1 year
Known allergy to clopidogrel or contrast media
Gastrointestinal bleeding within 1 month
References: Presented by Dr. Peter Clemmensen at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Kelbaek H, Thuesen L, Helqvist S, et al., on behalf of the DEDICATION Investigators. Drug-eluting versus bare metal stents in patients with ST-segment-elevation myocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION) trial. Circulation 2008;118:1155-62.

Presented by Dr. Henning Kelbaek, at TCT 2007, Washington, DC

[Chevychelov]

Title: Surgical Treatments for Ischemic Heart Failure Hypothesis 2 (STICH)
Trial Sponsor: National Heart, Lung, and Blood Institute; and National Institutes of Health
Year Presented: 2009
Year Published 2009
Topic(s): Cardiovascular Surgery, Heart Failure/Transplant
Summary Posted: 3/16/2010 9:00:00 AM
Writer: Ms. Sabina A. Murphy
Author Disclosure: Consulting Fees: Eli Lilly
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Author Disclosure: Research/Research Grants: Astra Zeneca; Consultant Fees/Honoraria: Duke Clinical Research Institute; Research/Research Grants: Heartscape; Research/Research Grants: PLx Pharma; Research/Research Grants: Cogentus; Research/Research Grants: Sanofi Aventis; Data Safety Monitoring Board (Gov’t/Nonprofit): Duke Clinical Research Institute; Research/Research Grants: Bristol Myers Squibb; Research/Research Grants: Eisai; Research/Research Grants: Takeda; Research/Research Grants: The Medicines Company; Research/Research Grants: Ethicon
Supplemental Reviewer: Dharam J. Kumbhani, M.D., S.M.
Author Disclosure: This author has nothing to disclose.

Related Resources
Summary Slide: STICH Trial
Presentation Slides: STICH QOL
Presentation Slides: STICH
Related Trial: Coronary Artery Surgery Study (CASS)
Guideline: Heart Failure in Adults: 2009 Focused Update of the 2005 Guidelines for the Diagnosis and Management of
CVN: STICH Trial: CABG vs CABG + SVR

Description
The goal of the trial was to evaluate medical therapy versus surgical therapy for patients with obstructive coronary disease and congestive heart failure.
Hypothesis
Coronary artery bypass grafting (CABG) with surgical ventricular reconstruction (SVR) in patients with anterior-apical regional left ventricular (LV) dysfunction would be superior to CABG alone in reducing death and cardiac hospitalization, and improving quality of life.
Drugs/Procedures Used
Patients with coronary artery disease and anterior-apical regional LV dysfunction were randomized to CABG (n = 499) or CABG + SVR (n = 501).
Concomitant Medications
For the CABG and CABG + SVR groups: beta-blockers (85%, 87%), angiotensin-converting enzyme inhibitor (80%, 82%), digoxin (17%, 14%), diuretics (69%, 66%), aspirin (77%, 77%), and statins (79%, 75%)
Principal Findings
No significant differences in baseline clinical characteristics were present between groups. However, more arterial conduits were utilized in patients undergoing CABG alone. SVR added a median of 27 minutes of cardiopulmonary bypass time to the procedure. A greater reduction in LV end-systolic volume index (LVESVI) was observed in the SVR group (-19% vs. -6%, p < 0.001). However, there was no significant difference in the primary endpoint of death and cardiac hospitalization (58% vs. 59%, p = 0.90). There was no greater improvement in New York Heart Association heart failure classification or Canadian Cardiovascular Society angina classification with SVR in addition to CABG.

Quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and Center for Epidemiological Studies Depression Scale, was not significantly different between groups. In the US cohort, medical costs were greater with CABG + SVR than with CABG alone ($70,717 vs. $56,122, p = 0.004).

In a subgroup of 595 patients in whom LVESVI could be calculated, patients with a baseline LVESVI ≤90 ml/m2 had a significant reduction in mortality with CABG + SVR, as compared with CABG alone (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.35-1.00, p = 0.05). However, in patients with LVESVI >90 ml/m2, there was no difference between the two groups (HR 1.24, 95% CI 0.75-2.06, p = 0.41).
Interpretation
The STICH trial represents the first multicenter randomized trial of CABG + SVR in patients with coronary artery disease. Although SVR was demonstrated to reduce LVESV to a greater extent than CABG alone, this result did not translate into an improvement in cardiovascular morbidity or mortality in this study. Based on these results, routine SVR at the time of CABG should not be recommended at this time. Although there seemed to be a mortality benefit in patients with an LVESVI <90 ml/m2 (normal LVESVI ~25 ml/m2), this is exploratory, and needs to be confirmed in further studies.

The hypothesis 1 substudy of the STICH trial, comparing medical therapy alone with medical therapy + CABG, is ongoing.
Conditions
• Heart failure
• Heart failure / Ischemic
Therapies
• CABG
Study Design
Randomized.
Patients Enrolled: 1,000
NYHA Class (% I, II, II, IV): 49% class III or IV
Mean Follow-Up: 48 months
Mean Patient Age: 62 years
% Female: 15%

Mean Ejection Fraction: 28% (median)
Primary Endpoints
For the comparison of medical versus surgical therapy, the primary endpoint is long-term survival.
For the comparison of CABG plus surgical ventricular reconstruction versus CABG alone, the primary endpoint is long-term survival free of cardiac hospitalization.
Secondary Endpoints
Cost-effectiveness and quality of life for each treatment
Exercise capacity
30-day mortality
Cardiac hospitalization
Noncardiac hospitalization
Myocardial infarction
Stroke
Patient Population
Coronary artery disease amenable to CABG
LV ejection fraction ≤35%
Dominant anterior wall akinesia or dyskinesia
Exclusions:
Recent myocardial infarction
Need for aortic valve replacement
Planned percutaneous coronary intervention
Noncardiac disease resulting in a life expectancy <3 years
References: Presented by Dr. Robert E. Michler at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Surgical Treatment for Ischemic Heart Failure (STICH) Trial: CABG Versus CABG + SVR. Presented by Drs. Robert H. Jones and Daniel Mark at ACC.09/i2, Orlando, FL, March 2009.

Jones RH, Velazquez EJ, Michler RE, et al., on behalf of the STICH Hypothesis 2 Investigators. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J Med 2009;360:1705-17.

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Title: Lenient Versus Strict Rate Control in Patients With Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 3/15/2010
Author(s): Van Gelder CI, Groenveld HF, Crijns HJ, et al.
Citation: N Engl J Med 2010;Mar 15:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Rate Control Efficacy in Permanent Atrial Fibrillation: A Comparison Between Lenient Versus Strict Rate Control II (RACE II)

Study Question: Does strict heart rate (HR) control improve outcomes in patients with persistent atrial fibrillation (AF)?
Methods: In this multicenter study, 614 patients (mean age 68 years) with persistent AF were randomized to lenient HR control (n = 311, resting HR <110/minute) or strict HR control (n = 303, HR <80/minute at rest and <110/minute during moderate exercise) using beta-blockers, calcium-channel blockers, and/or digoxin. Follow-up was every 2 weeks until HR targets were reached and at 1, 2, and 3 years. The 1° endpoint was a composite of cardiovascular death, heart failure hospitalization, stroke, embolism, major hemorrhage, and major arrhythmic events.
Results: The HR targets were reached in 98% of patients in the lenient-control group and 67% of patients in the strict-control group, and the mean HRs after dose-adjustment were 93 bpm and 76 bpm in the two groups, respectively. There was no significant difference in the 3-year incidence of the 1° endpoint between the lenient-control (12.9%) and strict-control (14.9%) groups. A similar proportion of patients (approximately 46% in each group) had symptoms from AF at the end of the study.
Conclusions: Strict HR control does not improve outcomes or symptoms compared to lenient HR control in patients with persistent AF.
Perspective: The AFFIRM study used the same target HRs that were used in the strict-control group of this study, and the target HRs were achieved in >80% of patients. Yet in this study, adequate HR control was achieved in only 67% of patients in the strict-control group. Therefore, the study does not rule out the possibility that successful implementation of a strict-control strategy improves outcomes or symptoms compared to a lenient HR-control strategy. Fred Morady, M.D., F.A.C.C.

Title: Progression From Paroxysmal to Persistent Atrial Fibrillation: Clinical Correlates and Prognosis
Topic: Arrhythmias
Date Posted: 3/12/2010
Author(s): De Vos CB, Pisters R, Nieuwlaat R, et al.
Citation: J Am Coll Cardiol 2010;55:725-731.
Clinical Trial: No
Related Resources
JACC Article: Progression From Paroxysmal to Persistent Atrial Fibrillation: Clinical Correlates and Prognosis

Study Question: What are the predictors of arrhythmia progression in patients with paroxysmal atrial fibrillation (AF)?
Methods: The data in this study were gathered from 1,219 patients (mean age 64 years) with paroxysmal AF who were entered into the Euro Heart Survey on AF. Progression of paroxysmal to persistent AF was evaluated at 1 year of follow-up.
Results: Progression to persistent AF occurred in 15% of patients. The independent predictors of AF progression were history of heart failure (odds ratio [OR], 2.2), history of stroke/transient ischemic attack (OR, 2.0), age >75 years (OR, 1.6), chronic obstructive pulmonary disease (OR, 1.5), and hypertension (OR, 1.5). A scoring system (HATCH) was developed based on these five predictors. Approximately 50% of patients with a HATCH score of 6-7 had AF progression, compared with only 6% of patients with a HATCH score of 0.
Conclusions: Paroxysmal AF progresses to persistent AF at 1 year of follow-up in approximately 15% of patients. AF progression is associated with factors that predispose to atrial structural remodeling, including heart failure, hypertension, and age.
Perspective: It is noteworthy that treatment with rhythm-control drugs was not a negative predictor of AF progression. This suggests that a pharmacological rhythm-control strategy is unlikely to be effective in the face of factors that promote atrial structural remodeling. The efficacy of catheter ablation of paroxysmal AF in preventing AF progression in the presence of these factors remains to be well-defined. Fred Morady, M.D., F.A.C.C.

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Title: Lead Extraction in the Contemporary Setting: The LExICon Study. An Observational Retrospective Study of Consecutive Laser Lead Extractions
Topic: Arrhythmias
Date Posted: 3/9/2010
Author(s): Wazni O, Epstein LM, Carrillo RG, et al.
Citation: J Am Coll Cardiol 2010;55:579-586.
Clinical Trial: No
Related Resources
JACC Article: Lead Extraction in the Contemporary Setting: The LExICon Study. An Observational Retrospective Study of Consecutive Laser Lead Extractions

Study Question: How safe and effective is laser-assisted lead extraction (LALE)?
Methods: This was a multicenter, retrospective analysis of 1,449 consecutive patients (mean age 63 years) who underwent LALE of 1,684 pacemaker leads and 703 defibrillator leads in 2004-2007. Complete success was defined as removal of all lead material and partial success was defined as removal of all but <4 cm of the lead.
Results: The median lead age was 82 months. The two most common indications for extraction were infection (57%) and a nonfunctional lead (27%). LALE was completely successful in 96.5% and partially successful in 2.3% of patients. Predictors of procedure failure were a body mass index <25 kg/m2, lead age >10 years, and an extraction volume of <60 cases/4 years. A major adverse event (MAE) occurred in 4% of patients, and a MAE directly related to LALE (most commonly cardiac avulsion or vascular tear) occurred in 1.4%. In-hospital mortality was 1.9%, and mortality directly related to LALE was 0.3%. The predictors of in-hospital mortality were a history of pocket infection, endocarditis, diabetes, and renal insufficiency.
Conclusions: LALE has a high success rate and a low rate of MAEs. In-hospital mortality is largely a function of comorbidities.
Perspective: Prior to the advent of laser sheaths, the success rate of lead extraction using locking stylets and telescoping sheaths was approximately 65%. With the use of laser sheaths, studies published in 1999-2002 reported success rates of 90-94%. The present study indicates that technological refinements in the laser sheaths and additional operator experience have improved the success rate of LALE in contemporary practice to approximately 98%. Fred Morady, M.D., F.A.C.C.

Title: Percutaneous Pacemaker and Implantable Cardioverter-Defibrillator Lead Extraction in 100 Patients With Intracardiac Vegetations Defined by Transesophageal Echocardiogram
Topic: Arrhythmias
Date Posted: 3/9/2010
Author(s): Grammes JA, Schulze CM, Al-Bataineh M, et al.
Citation: J Am Coll Cardiol 2010;55:886-894.
Clinical Trial: No
Related Resources
JACC Article: Percutaneous Pacemaker and Implantable Cardioverter-Defibrillator Lead Extraction in 100 Patients With Intracardiac Vegetations Defined by Transesophageal Echocardiogram

Study Question: Can lead extraction be safely accomplished in patients with endocarditis and intracardiac vegetations?
Methods: This was a retrospective review of 100 patients (mean age 67 years) who underwent extraction of an infected lead and had an intracardiac vegetation by transesophageal echocardiography. The timing of reimplantation depended on resolution of the vegetations and blood culture sterility.
Results: The mean diameter of vegetations was 1.6 cm (range 0.2-4 cm). Two hundred leads with a mean implant duration of 51 months were extracted percutaneously and no patient required a surgical intervention. The most common pathogens were methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Embolization of a vegetation occurred in 2/100 patients (2%). A new pacemaker or implantable cardioverter defibrillator was implanted in 54% of patients a median of 7 days after extraction and none had a relapse of infection during a mean follow-up of 15 months. Long-term follow-up data were available in 71 patients. Among these patients, in-hospital mortality rate was 14% and late mortality was 13%. The most common cause of death was septicemia.
Conclusions: Standard techniques for percutaneous lead extraction are safe and effective in patients with intracardiac vegetations as large as 4 cm.
Perspective: Patients with an intracardiac vegetation often undergo thoracotomy and lead extraction under direct visualization to avoid septic embolization during percutaneous lead extraction. This study demonstrates that percutaneous lead extraction can be accomplished safely by a skilled operator even in the presence of intracardiac vegetations. However, operator experience is an important determinant of outcomes and should be taken into consideration when deciding on percutaneous versus surgical lead extraction. Fred Morady, M.D., F.A.C.C.

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Достижения по врожденным порокам сердца за прошлый год

Title: The Year in Congenital Heart Disease
Topic: Congenital Heart Disease
Date Posted: 3/9/2010
Author(s): Graham TP, Jr.
Citation: J Am Coll Cardiol 2010;55:147-155.
Clinical Trial: No
Related Resources
JACC Article: The Year in Congenital Heart Disease

Perspective: The following are 10 points to remember about the past year in congenital heart disease:

1. van den Berg et al. studied exercise performance, biventricular reserve, and N-terminal pro-B-type natriuretic peptide, and exercise performance in relation to right ventricular (RV) volume in patients following repair of tetralogy of Fallot (TOF) at less than 2 years of age. At mid-term follow-up, all parameters were well-preserved, and unrelated to RV volume (Int J Cardiol 2009;133:363-70).

2. Knauth et al. used cardiac magnetic resonance to predict clinical outcomes in patients with TOF, with a median time from clinical repair to evaluation of 21 years. Adverse outcomes, defined as death, sustained ventricular tachycardia (VT), and increase in New York Heart Association functional class to grade II or IV, occurred in 21% of patients. Severe RV dilation and right or left ventricular systolic dysfunction predicted major adverse events (Heart 2008;94:211-6).

3. In an additional study of pulmonary insufficiency after tetralogy repair, Harrild and colleagues compared patients with TOF and RV dilatation who had undergone pulmonary valve replacement, as compared with those who had not. No significant differences were seen in sudden death, VT, or a combined endpoint of sudden death/VT in patients who had undergone pulmonary valve replacement (Circulation 2009;119:445-51).

4. Shiraishi et al. studied the impact of the age at Fontan on exercise capacity, hemodynamics, and ventricular function in children with systemic left ventricles. VO2max, left ventricular ejection fraction, and cardiac index were all higher in patients undergoing Fontan at <3 years of age (Ann Thorac Surg 2009;87:555-61).

5. The Nationwide Inpatient Sample was used by Karamlou and colleagues to determine surgical practice patterns for adults with congenital heart disease. In-hospital mortality was lower (1.87%) for adults operated on by pediatric heart surgeons, as compared with 4.84% for those operated on by nonpediatric heart surgeons (Circulation 2008;118:2345-52).

6. Vida et al. studied the optimal timing of patent ductus arteriosus ligation in premature infants. Medical treatment was successful in 149 of 201 patients. More than two cycles of ibuprofen were associated with increased risk for bronchopulmonary dysplasia and acute renal failure (Ann Thorac Surg 2009;87:1509-16).

7. Bovй et al. investigated 93 children following the arterial switch procedure for D-transposition of the great arteries (D-TGA). At a mean follow-up of 5 years, aortic regurgitation >2+ developed in 10% of patients with D-TGA with intact ventricular septum and 23% of patients with D-TGA and ventricular septal defect (VSD). Freedom from re-intervention at 1, 5, and 10 years was 98%, 96%, and 96% for D-TGA/intact VSD and 65%, 63%, and 63% for D-TGA/VSD (Ann Thorac Surg 2008;85:823-30).

8. Because of a previous study implicating balloon atrial septostomy (BAS) as a cause of brain injury, Petit and colleagues reported on magnetic resonance imaging of patients prior to surgical repair of TGA. Of 26 patients, 14 underwent BAS. No strokes occurred, although 10 of 26 patients were found to have hypoxic brain injury in the form of periventricular leukomalacia. No association was seen between this finding and BAS. Infants with periventricular leukomalacia had lower preoperative oxygenation and longer time to surgery than infants without the finding (Circulation 2009;119:709-16).

9. Sharma et al. reported outcomes of children undergoing anatomic repairs for congenitally corrected TGA. A total of 31 patients underwent an atrial switch/Rastelli procedure with 17% early deaths and no late deaths. A total of 37 patients underwent a ‘double switch’ with 13.5% early mortality and 10.8% late mortality. An additional four patients required re-operations, four had left ventricular ejection fraction <40%, five had moderate aortic regurgitation, and five patients had symptomatic tricuspid insufficiency, one with tricuspid stenosis, and one with superior vena cava obstruction (J Thorac Cardiovasc Surg 2009;137:404-12).

10. Tabbutt et al. studied neurodevelopmental outcomes for 83 infants undergoing staged palliation for hypoplastic left heart syndrome at 1 year of age. The neuromuscular examination was abnormal or suspect in 65% of patients. The mean Mental Developmental Index score was 90, and 20 patients had scores <70. The mean Psychomotor Development Index was 74, with 42 patients having scores <70. In multivariate analysis, younger gestational age, presence of a genetic syndrome, and need for preoperative intubation had negative effects on neurodevelopmental outcomes. Operative factors, including duration of deep hypothermic circulatory arrest, were not shown to impact neurodevelopmental outcomes (Pediatrics 2008;121:476-83). Timothy B. Cotts, M.D., F.A.C.C.

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Title: Efficacy and Safety of Zotarolimus-Eluting and Sirolimus-Eluting Coronary Stents in Routine Clinical Care (SORT OUT III): A Randomised Controlled Superiority Trial
Topic: Interventional Cardiology
Date Posted: 3/15/2010
Author(s): Rasmussen K, Maeng M, Kaltoft A, et al., on behalf of the SORT OUT III Study Group.
Citation: Lancet 2010;Mar 15:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Comparison of Zotarolimus-Eluting Stents and Sirolimus-Eluting Stents in Patients With Coronary Artery Disease (SORT OUT III)

Study Question: What is the safety and efficacy of the zotarolimus-eluting stent (ZES) compared with the sirolimus-eluting stent (SES) in patients with coronary artery disease who are receiving routine clinical care?
Methods: The authors performed a single-blind superiority trial comparing SES to ZES in all adult patients with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention (PCI) at five high-volume centers in Denmark. Follow-up data were obtained from national administrative and health care registries. The primary endpoint was a composite of cardiac death, myocardial infarction, and target vessel revascularization events within 9 months. Intention-to-treat analyses were done at 9 and 18 months.
Results: The study randomized 1,162 patients to the ZES and 1,170 to a SES. The randomly allocated stent was implanted in 1,589 (98%) lesions allocated to the ZES and 1,569 (97%) lesions allocated to SES (p = 0.15). Six patients were lost to follow-up. All other patients were included in analyses at 30-day and 9-month follow-up. Eighteen-month follow-up was completed for 94% of the patients. At 9 months, patients treated with a ZES were more likely to have met the primary endpoint (6% vs. 3%; hazard ratio, 2.15; 95% confidence interval, 1.43-3.23; p = 0.0002). This difference was sustained at 18 months (10% vs. 5%; 2.19; 1.58-3.04; p < 0.0001). There was no difference in the all-cause mortality at 9 months (2% vs. 2%), whereas it was higher in the ZES patients at 18 months (4% vs. 3%; 1.03-2.50; p = 0.035).
Conclusions: The SES is superior to the ZES for patients undergoing PCI in routine clinical practice.
Perspective: Multiple studies have evaluated the relative efficacy and safety of a SES and a paclitaxel-eluting stent (PES), and most (but not all) of them suggest better outcomes with the SES. Data on comparative efficacy of the ZES and the everolimus-eluting stent (EES) are rather limited. The SPIRIT IV and COMPARE trials suggest that the EES is probably safer and more efficacious than the PES. The relative position of the ZES in the DES spectrum is harder to define. This trial suggests a lower rate of target lesion revascularization with SES that is not surprising since the SES has better anti-restenotic efficacy. The Endeavour III trial had demonstrated a late catch-up phenomenon with the SES, and longer-term follow-up of the SORT OUT III trial will be needed to establish the relative long-term safety and efficacy of ZES and SES. Hitinder S. Gurm, M.B.B.S., F.A.C.C

Title: Low Diagnostic Yield of Elective Coronary Angiography
Topic: Interventional Cardiology
Date Posted: 3/10/2010 4:00:00 PM
Author(s): Patel MR, Peterson ED, Dai D, et al.
Citation: N Engl J Med 2010;362:886-895.
Clinical Trial: No
Study Question: What is the diagnostic yield of coronary angiography among patients with coronary artery disease (CAD) in a contemporary national sample?
Methods: From January 2004 to April 2008, at 663 hospitals in the American College of Cardiology National Cardiovascular Data Registry, the authors identified patients without known CAD who were undergoing elective cardiac catheterization. The patients' demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive CAD, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery, or stenosis of 70% or more of the diameter of a major epicardial vessel.
Results: A total of 398,798 patients were included in the study. The median age was 61 years; 52.7% of the patients were men, 26% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization, 149,739 patients (37.6%) had obstructive CAD. No CAD (defined as <20% of stenosis in all vessels) was reported in 39.2% of patients. Independent predictors of obstructive CAD included male sex (odds ratio [OR], 2.70; 95% confidence interval [CI], 2.64-2.76); older age (OR per 5-year increment, 1.29; 95% CI, 1.28-1.30); presence of insulin-dependent diabetes (OR, 2.14; 95% CI, 2.07-2.21); and presence of dyslipidemia (OR, 1.62; 95% CI, 1.57-1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive CAD than those who did not undergo any testing (41.0% vs. 35.0%, p < 0.001; adjusted OR, 1.28; 95% CI, 1.19-1.37).
Conclusions: The authors concluded that in this study, only a minority of patients without known coronary disease who underwent elective cardiac catheterization had obstructive CAD.
Perspective: This analysis of a contemporary national sample of patients suggests that only a minority of patients undergoing coronary angiography have obstructive CAD. The assessment of coronary stenosis was made by the interpreting/performing physician and it is possible that more stringent assessment may further lower the fraction of patients with obstructive CAD. It should also be noted that this study addresses only overutilization and not underutilization of coronary angiography in appropriate patients. However, it is obvious from this study that the current strategies used to make decisions for proceeding to coronary angiography, including clinical assessment and noninvasive testing, need substantial modification and improvement to increase the diagnostic yield of coronary angiography and prevent over- or underutilization to improve overall quality of patient care. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Endovascular Stenting for Vertebral Artery Stenosis
Topic: Interventional Cardiology
Date Posted: 3/11/2010
Author(s): Jenkins JS, Patel SN, White CJ, et al.
Citation: J Am Coll Cardiol 2010;55:538-542.
Clinical Trial: No
Related Resources
JACC Article: Endovascular Stenting for Vertebral Artery Stenosis

Study Question: Is catheter-based therapy for symptomatic vertebral artery stenosis (VAS) safe and durable?
Methods: One-hundred five patients from 1995-2006 with symptomatic VAS (112 arteries, 71% male) underwent stent placement for extracranial (91%) and intracranial (9%), primarily in the V1 segment (83%). By angiography, 57 patients (54%) had bilateral VAS, 71 patients (68%) had concomitant carotid disease, and 43 patients (41%) had a prior stroke.
Results: A total of 133 stents were placed, which were primarily balloon-expandable bare metal (114). Procedural and clinical success was achieved in 105 (100%) and 95 (90.5%) patients, respectively. One-year follow-up was obtained in 87 (82.9%) patients, of which 69 patients (79.3%) remained symptom-free. Median follow-up was 29.1 months, with 74% of patients asymptomatic at last follow-up. At 1 year, 6 patients (5.7%) had died and 5 patients (5%) had a posterior circulation stroke.
Conclusions: The authors concluded that in “experienced hands,” stenting for symptomatic VAS has a very high procedural and clinical success rate, with few periprocedural complications, and is associated with durable symptom resolution in the majority of patients. They concluded that "endovascular stenting of vertebral artery atherosclerotic disease is safe and effective compared with surgical controls” (historical controls implied) “and should be considered first-line therapy for this disease.”
Perspective: Symptomatic VAS is a morbid and lethal disease, carrying a 5-year 30-35% risk of stroke and a 2-year mortality for medically managed patients of 30%. Despite this relative failure of medical therapy to prevent strokes in these patients, surgical revascularization is rarely performed, also due to the relatively high morbidity and mortality rates associated with surgery. Clearly, an endovascular option for the treatment of these patients is obviously attractive. While most of these stents were placed in the proximal vertebral artery, which has been reported to be less treacherous for stenting than the V2-V4 vertebral artery segments, the present report contains an order of magnitude of more patients than the next largest series. The authors of this large series document outstanding results, stenting a cohort of complex patients with vertebrobasilar disease. Let’s see if this approach becomes standard of care for this disease. Gilbert Upchurch, Jr., M.D.

Title: Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus
Topic: Prevention/Vascular
Date Posted: 3/14/2010
Author(s): The ACCORD Study Group.
Citation: N Engl J Med 2010;Mar 14:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Action to Control Cardiovascular Risk in Diabetes Lipid Trial (ACCORD Lipid)

Study Question: Does combination therapy with a statin plus a fibrate, as compared with statin monotherapy, reduce risk for cardiovascular disease (CVD) in patients with type 2 diabetes who are at high risk for CVD?
Methods: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was designed to examine the effects of intensive blood glucose control and either blood pressure or plasma lipid control on cardiovascular outcomes. The trial includes 10,251 diabetics from 77 sites in the United States and Canada. In the ACCORD Lipid study, 5,518 subjects were treated with open-label simvastatin (40 mg/day or less), with randomization of masked fenofibrate or placebo. All subjects had type 2 diabetes, defined as glycated hemoglobin (HgA1c) of 7.5% or greater and were at high risk for CVD (defined as evidence of clinical CVD [age 40-79 years] or two additional risk factors [age range 55-79 years]). Baseline lipid criteria included having a low-density lipoprotein cholesterol (LDL-C) between 60 and 180 mg/dl, high-density lipoprotein cholesterol (HDL-C) of 55 or less for women or blacks, 50 or less for all others, and triglycerides below 750 mg/dl not on lipid therapy (400 mg/dl if on lipid-lowering therapy). Fasting lipids were measured at 4, 8, and 12 weeks and annually thereafter. Secondary outcomes included the combination of the primary outcomes and revascularization or hospitalization for congestive heart failure. The primary outcomes of interest were first occurrence of nonfatal myocardial infarction, nonfatal stroke, or CVD death. Mean follow-up was 4.7 years.
Results: Subjects had a mean age of 62 years, 31% were female and 37% had a history of CVD. Use of statin therapy prior to enrollment was present in 66% of the study population. Mean LDL-C on treatment was 81.1 mg/dl in the fibrate group and 80.0 mg/dl in the placebo group. Mean HDL-C on treatment was 41.2 mg/dl in the fibrate group and 40.5 mg/dl in the placebo group. Annual rate of CVD events was 2.2% in the fenofibrate plus simvastatin groups and 2.4% in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79-1.08; p = 0.32). No significant differences between the two groups were observed for the secondary outcomes (HR, 0.94; 95% CI, 0.85-1.05; p = 0.30). Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (HR, 0.91; 95% CI, 0.75-1.10). In prespecified subgroup analysis, men appeared to have a benefit as opposed to women (p = 0.01 for interaction). In addition, the investigators observed a possible interaction according to the lipid subgroup, with a potential benefit for patients with both high triglycerides and low HDL-C levels at baseline (p = 0.057 for interaction).
Conclusions: The authors concluded that simvastatin plus fenofibrate did not reduce nonfatal myocardial infarction or stroke, and also did not reduce CVD mortality compared to simvastatin alone. Thus, these findings from ACCORD Lipid do not support the use of combination therapy (statin plus a fibrate) in high-risk patients with diabetes.
Perspective: This study provides data for clinicians treating diabetes who are at high risk for CVD, suggesting that therapy with statins should remain the core management strategy in prevention of CV events. However, the subgroup analysis warrants further evaluation; given the difference observed in benefits related to gender, statins without fibrate may be the treatment strategy of choice. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus
Topic: Prevention/Vascular
Date Posted: 3/14/2010
Author(s): The ACCORD Study Group.
Citation: N Engl J Med 2010;Mar 14:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Action to Control Cardiovascular Risk in Diabetes Blood Pressure Trial (ACCORD BP)

Study Question: Does lowering systolic blood pressure (SBP) to <120 mm Hg reduce risk for cardiovascular disease (CVD) in patients with type 2 diabetes?
Methods: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was designed to examine the effects of intensive blood glucose control and either blood pressure or plasma lipid control on cardiovascular outcomes. The trial includes 10,251 diabetics from 77 sites in the United States and Canada. In the ACCORD BP study, 4,733 subjects were randomized to intensive therapy for a goal SBP <120 mm Hg or standard therapy for a goal SBP of <140 mm Hg. All subjects had type 2 diabetes defined as glycated hemoglobin ≥7.5%, and were at high risk for CVD (defined as evidence of clinical CVD (age 40-79 years) or two additional risk factors (age range 55-79 years). Exclusion criteria included a body mass index >45, a serum creatinine of 1.5 mg/dl or greater, or protein excretion rate of <1.0 g. Baseline SPB had to be between 130 and 180 mm Hg on three or fewer antihypertensives. The primary outcomes of interest were nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary outcomes included the combination of the primary outcomes and revascularization or hospitalization for congestive heart failure. Mean follow-up was 4.7 years. Clinic visits were monthly for the first 4 months, then every 2 months thereafter.
Results: Mean age was 62 years for this study population, with 47.7% women and 37% having a history of CVD. After 1 year, the on-treatment SBP was 119.3 mm Hg in the intensive therapy group and 133.5 mm Hg in the standard therapy group. The annual rate of primary outcome events was 1.8% in the intensive therapy group and 2.09% in the standard therapy group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.73-1.06; p = 0.20). The annual rate of all-cause mortality was 1.28% for the intensive therapy group and 1.19% for the standard therapy group (HR, 1.07; 95% CI, 0.85-1.35; p = 0.55). The annual rate of stroke was 0.32% in the intensive therapy group and 0.53% in the standard therapy group (HR, 0.59; 95% CI, 0.39-0.89; p = 0.01). Reduced rates of nonfatal stroke were observed for the intensive therapy group (HR, 0.63; 95% CI, 0.41-0.96; p = 0.03). No significant differences were noted for major CVD events (fatal coronary events, nonfatal myocardial infarction, and unstable angina) (HR, 0.94; 95% CI, 0.79-1.12; p = 0.50) and fatal or nonfatal heart failure (HR, 0.94; 95% CI, 0.70-1.26; p = 0.67). Serious adverse events attributed to the antihypertensive treatment occurred in 3.3% of the intensive treatment group and 1.3% of the standard treatment group (p < 0.001).
Conclusions: The investigators concluded that among patients with type 2 diabetes who are at high risk for cardiovascular events, lowering SBP to <120 mm Hg did not reduce rates of fatal or nonfatal major cardiovascular events compared to a goal of SBP of <140 mm Hg.
Perspective: This landmark study adds to our understanding of management goals for high-risk diabetics and does not support aggressive lowering of SBP in high-risk diabetics. However, whether a blood pressure goal of <130 mm Hg provides significant benefit as compared to <140 mm Hg remains unanswered. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Effect of Valsartan/Nateglinide on the Incidence of Diabetes and Cardiovascular Events
Topic: Prevention/Vascular
Date Posted: 3/14/2010
Author(s): The NAVIGATOR Study Group.
Citation: N Engl J Med 2010;Mar 14:[Epub ahead of print], and N Engl J Med 2010;Mar 14:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR)

Study Question: Does use of short-acting insulin secretagogues and/or rennin-angiotensin-blockers reduce the risk of diabetes or cardiovascular (CV) events among patients with impaired glucose tolerance?
Methods: The NAVIGATOR study was designed as a 2 x 2 factorial, double-blind, randomized trial of patients with impaired glucose tolerance and either established CV disease (CVD) or risk factors for CVD. Patients were randomized to valsartan (up to 160 mg daily) or placebo and to nateglinide (up to 60 mg three times per day) or placebo and to valsartan (up to 160 mg/day) or placebo. Subjects also received lifestyle modification. Impaired fasting glucose tolerance was defined as a fasting plasma glucose concentration between 95 mg/dl and 125 mg/dl. Patients were excluded if they had taken antidiabetic medication within the prior 5 years. Participants were followed for a median of 5.0 years (median 6.5 years for vital status), with the primary outcomes being incident diabetes and CV events (CVD death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). The third primary outcome, extended composite CV outcomes, includes the core CV events (listed above) together with hospitalization for unstable angina or arterial revascularization.
Results: A total of 9,518 participants (mean age 63 years, 50% female) from 40 countries were enrolled in the study between January 2002 and January 2004. A total of 1,674 subjects developed diabetes during the follow-up period (36.0% in the nateglinide group and 33.9% in the placebo group). A total of 1,365 subjects experienced a CV event (14.2% in the nateglinide group and 15.2% in the placebo group). After adjustment for multiple comparisons, nateglinide did not significantly reduce cumulative incidence of diabetes, as compared with placebo (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.00-1.15; p = 0.05). CV outcomes also did not differ between subjects randomized to nateglinide or placebo (HR, 0.94; 95% CI, 0.82-1.09; p = 0.43 for core composite outcomes and HR, 0.93; 95% CI, 0.83-1.03; p = 0.16 for extended composite outcomes). Approximately 10% of the study population lost 5% of their baseline body weight, with those in the placebo group having a lower mean body weight compared to those in the nateglinide group. Mean waist circumference was also lower in the placebo group, as compared to the nateglinide group. Rates of adverse events did not differ in the two groups.

The cumulative incidence of diabetes was 33.1% in the valsartan group and 36.8% in the placebo group, with a significantly reduced risk for incidence of diabetes observed in the valsartan group (HR, 0.98; 95% CI, 0.80-0.92; p < 0.001). No difference was observed in extended CV outcomes (14.5% vs. 14.8%; HR, 0.96; 95% CI, 0.86-1.07; p = 0.43) or core CV outcomes (8.1% vs. 8.1%; HR, 0.99; CI, 0.86-1.14; p = 0.85).
Conclusions: The investigators concluded that among patients with impaired glucose tolerance and either established CVD or risk factors for CVD, nateglinide for 5 years did not reduce the incidence of diabetes or CV events. Use of valsartan for 5 years did not lead to reduction in the rate of CV events; however, a relative reduction (14%) was observed for incidence of diabetes.
Perspective: This large study of nateglinide and valsartan for prevention of diabetes and/or CVD was largely negative, with no benefit observed in reduction of CV outcomes for either drug, and a small benefit observed with valsartan in reduction of diabetes. In the face of prior studies, continued use of aggressive lifestyle modification, which has been shown to reduce these outcomes, as opposed to use of nateglinide and/or valsartan, is recommended. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Effects of β blockers and Calcium-Channel Blockers on Within-Individual Variability in Blood Pressure and Risk of Stroke
Topic: Prevention/Vascular
Date Posted: 3/12/2010
Author(s): Rothwell PM, Howard SC, Dolan E, et al.
Citation: Lancet Neurol 2010;Mar 12:[Epub ahead of print].
Clinical Trial: No
Related Resources
Journal Scan: Prognostic Significance of Visit-to-Visit Variability, Maximum Systolic Blood Pressure, and Episodic Hypertension

Study Question: What are the effects of beta-blockers and calcium-channel blockers on variability in blood pressure (BP), and do they explain the disparities in effect on stroke risk?
Methods: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19,257 patients with hypertension and other vascular risk factors, and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4,396 hypertensive patients ages 65-74 years. The investigators expressed visit-to-visit variability of BP during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean BP. For ASCOT-BPLA, they also studied within-visit variability and variability on 24-hour ambulatory blood pressure monitoring (ABPM).
Results: In ASCOT-BPLA, group systolic BP (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p < 0.0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p < 0.0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio, 0.78; 95% CI, 0.67-0.90) was partly attenuated by adjusting for mean SBP during follow-up (0.84, 0.72-0.98), but was abolished by also adjusting for within-individual SD of clinic SBP (0.99, 0.85-1.16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p < 0.0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p < 0.0001). Subsequent temporal trends in variability in BP during follow-up in the atenolol group correlated with trends in stroke risk.
Conclusions: The authors concluded that the opposite effects of calcium-channel blockers and beta-blockers on variability of BP account for the disparity in observed effects on risk of stroke.
Perspective: The current study suggests that patients with good control of mean BP, but a high residual variability in SBP had a five times higher risk of stroke than did those with low residual SBP variability in ASCOT-BPLA. Atenolol-based treatment and amlodipine-based treatment had opposite effects on within-individual variability in BP independent of their effects on mean BP. The reduced event rates in the amlodipine group, which could not be fully accounted for by changes in mean BP or in other risk factors, may possibly be explained by effects on visit-to-visit variability in SBP. These findings may have implications for the routine management of hypertension, particularly the choice of medication, since specific agents may have different effects on variability of BP leading to differences in clinical efficacy. Additional studies are indicated to assess treatment effects and clinical outcomes in relation to variability in BP. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Risk Score to Predict Serious Bleeding in Stable Outpatients With or at Risk of Atherothrombosis
Topic: Prevention/Vascular
Date Posted: 3/22/2010
Author(s): Ducrocq G, Wallace JS, Baron G, et al., on behalf of the REACH Investigators.
Citation: Eur Heart J 2010;Feb 24:[Epub ahead of print].
Clinical Trial: No
Study Question: What are the predictors of bleeding in outpatients with atherothrombosis?
Methods: The authors developed a risk model to predict major bleeding in 68,236 patients with or at risk of atherothrombosis enrolled in the REACH registry. The primary endpoint was serious bleeding (nonfatal hemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed and competing scores were compared on their discriminative ability. The final score was validated externally using the CHARISMA population.
Results: Serious bleeding occurred in 804 (1.42%, 95% confidence interval 1.32-1.52) patients between baseline and 2 years. A nine-item bleeding risk score was constructed based on age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, and hypercholesterolemia, and the score ranged from 0-23 points. Observed incidence of bleeding at 2 years was 0.46% in patients with a score of ≤6, 0.95% with a score of 7-8, 1.25% with a score of 9-10, and 2.76% with a score of 11 or greater. The score had moderate discrimination in the CHARISMA (c-statistic 0.64) and REACH population (c-statistics 0.68).
Conclusions: This score can help predict future risk of bleeding in patients with atherothrombosis.
Perspective: The issue of bleeding in patients with atherothrombosis is becoming more relevant since a large number of patients are being placed on prolonged (and even lifelong) antithrombotic and/or antiplatelet therapy. This problem is likely to be compounded in the near future as more potent antiplatelet and antithrombotic drugs are approved for clinical use. This risk score provides the first step towards quantifying bleeding risk in patients with atherothrombosis, and further studies are warranted to confirm if the use of this score can help improve patient outcome. Hitinder S. Gurm, M.B.B.S., F.A.C.C

Title: The Risk of Thromboembolism and Need for Oral Anticoagulation After Successful Atrial Fibrillation Ablation
Topic: Arrhythmias
Date Posted: 3/19/2010
Author(s): Thermistoclakis S, Corrado A, Marchlinski FE, et al.
Citation: J Am Coll Cardiol 2010;55:735-743.
Clinical Trial: No
Related Resources
JACC Article: The Risk of Thromboembolism and Need for Oral Anticoagulation After Successful Atrial Fibrillation Ablation

Study Question: Is it safe to discontinue oral anticoagulation therapy (OAT) after catheter ablation of atrial fibrillation (AF)?
Methods: This was a multicenter, retrospective analysis of 3,355 patients who underwent catheter ablation of AF and either were taken off OAT 3-6 months later (Off-OAT group, n = 2,692, mean age 57 years) because of a successful outcome or remained on OAT because of recurrent AF, pulmonary vein stenosis, or severe left atrial mechanical dysfunction (On-OAT group, n = 663, mean age 59 years). The CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke) score was calculated for every patient. The study endpoints were ischemic stroke and major hemorrhage.
Results: In the Off-OAT group, 125 patients had a history of stroke/transient ischemic attack, and 2.9% of patients restarted OAT because of recurrent AF a mean of 10 months after OAT discontinuation. During 28 months of follow-up, ischemic stroke occurred in 0.07% of Off-OAT patients and 0.45% of On-OAT patients. No patient with a CHADS2 score ≥2 had a stroke. The prevalence of major hemorrhage was significantly lower in the Off-OAT group (0.04%) than in the On-OAT group (2%).
Conclusions: OAT can be safely discontinued after successful catheter ablation of AF, even in high-risk patients with a history of stroke. Ongoing OAT after catheter ablation is associated with a >10-fold higher risk of major hemorrhage.
Perspective: Current guidelines recommend indefinite OAT after catheter ablation of AF in high-risk patients, even when AF appears to have been successfully eliminated. This study brings this recommendation into question. Before incorporating the results into clinical practice, it would be prudent to wait for confirmation in a randomized clinical trial. Fred Morady, M.D., F.A.C.C.

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Title: The ROSE (Risk Stratification of Syncope in the Emergency Department) Study
Topic: Arrhythmias
Date Posted: 3/19/2010
Author(s): Reed MJ, Newby DE, Coull AJ, Prescott RJ, Jacques KG, Gray AJ.
Citation: J Am Coll Cardiol 2010;55:713-721.
Clinical Trial: No
Related Resources
JACC Article: The ROSE (Risk Stratification of Syncope in the Emergency Department) Study

Study Question: How accurately does a clinical decision rule (CDR) based on clinical and biochemical markers predict outcomes in patients with syncope?
Methods: Data on multiple historical, examination, electrocardiographic, hematological, and biochemical variables including B-type natriuretic peptide (BNP) were gathered prospectively in 529 patients (mean age 64 years) who presented to an emergency department (ED) with syncope. An expert panel developed a Risk Stratification of Syncope in the Emergency Department (ROSE) CDR by reviewing the predictive value of these variables for the 1° endpoint, which was a combination of serious outcomes and mortality at 1 month of follow-up. The CDR then was validated in another cohort of 538 patients (mean age 62 years) with syncope.
Results: The ROSE CDR identified a patient with syncope as being at high risk and appropriate for hospital admission if any one of the following was present: BNP level ≥300 pg/ml, heart rate ≤50 bpm in the ED, fecal occult blood, anemia, chest pain with syncope, abnormal Q wave on the electrocardiogram, or oxygen saturation ≤94% on room air. The sensitivity and specificity of this CDR for a 1° endpoint were 92% and 74%, respectively. In the validation cohort, the sensitivity and specificity of the CDR for a 1° endpoint were 87% and 66%, respectively. The BNP was ≥300 pg/ml in 8/9 (89%) deaths.
Conclusions: The ROSE CDR has a high degree of accuracy for predicting death or a serious outcome in patients with syncope. Among the seven components of the CDR, a BNP ≥300 pg/ml has the highest sensitivity for all-cause mortality.
Perspective: Implementation of this CDR potentially could eliminate a large proportion of unnecessary hospitalizations in low-risk patients with syncope. Fred Morady, M.D., F.A.C.C.

Title: Differences in Patient Survival After Acute Myocardial Infarction by Hospital Capability of Performing Percutaneous Coronary Intervention: Implications for Regionalization
Topic: General Cardiology
Date Posted: 3/19/2010
Author(s): Chen J, Krumholz HM, Wang Y, et al.
Citation: Arch Intern Med 2010;170:433-439.
Clinical Trial: No
Study Question: Do patients with acute myocardial infarction (AMI) have better outcomes if admitted to hospitals with percutaneous coronary intervention (PCI) capability, and do these data support regionalization of MI care?
Methods: The authors evaluated Medicare claims data to assess outcome of patients hospitalized with AMI between January 1, 2004, and December 31, 2006. Hospital level data were evaluated to estimate 30-day risk-standardized mortality rates (RSMRs). The RSMRs for PCI and local non-PCI hospitals were compared within local health care regions defined by hospital referral regions (HRRs).
Results: Of a total 718,028 patients with MI, 72.8% (523,119) were admitted to 1,382 PCI hospitals, and 27.2% (194,909) patients were admitted to 2,491 non-PCI hospitals in 295 HRRs. The 30-day mortality was lower in the PCI hospitals (15.1% vs. 20.7%). The RSMRs were also lower in the PCI hospitals compared with non-PCI hospitals (mean, 16.1% vs. 16.9%; p < 0.001). There was considerable overlap in RSMRs between non-PCI and PCI hospitals within the same HRR. The RSMRs at the best-performing PCI hospital were lower than those at local non-PCI hospitals by 3% or more in 80 HRRs, whereas in 104 HRRs, the RSMRs at the best-performing PCI hospital were lower by 1.5% to 3.0%. Conversely, in 37 HRRs, the RSMRs at the best-performing PCI hospital were either similar to or higher than at local non-PCI hospitals.
Conclusions: Patients with MI have a better outcome when admitted to hospitals with PCI capability, but there is wide variation in outcome at PCI and non-PCI hospitals across different HRRs.
Perspective: This is a very elegantly designed study that evaluates potential regionalization of care for AMI. Although the outcome was in general better at PCI-capable hospitals, this was not universal, and a geographically tailored approach to regionalization would be required to ensure optimal outcome of patients with AMI. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Statins for the Primary Prevention of Cardiovascular Events in Women With Elevated High-Sensitivity C-Reactive Protein or Dyslipidemia: Results From the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and Meta-Analysis of Women From Primary Prevention Trials
Topic: Prevention/Vascular
Date Posted: 3/18/2010
Author(s): Mora S, Glynn RJ, Hsia J, MacFadyen JG, Genest J, Ridker PM.
Citation: Circulation 2010;121:1069-1077.
Clinical Trial: No
Related Resources
Trial: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)

Study Question: Is statin therapy effective for primary prevention of cardiovascular disease (CVD) in women?
Methods: Data from the JUPITER study were used for this analysis. A total of 6,801 women ≥60 years, and 11,001 men ≥50 years were included in the study. All participants had a C-reactive protein level ≥2 mg/L and a low-density lipoprotein cholesterol <130 mg/dl. Subjects were randomized to rosuvastatin or placebo and followed for a median of 1.9 years. In addition, a meta-analysis of randomized placebo-controlled trials using statins for primary prevention among women was performed to examine additional trials, including JUPITER. A total of 20,147 women, mean age 60-69 years, were included in the meta-analysis.
Results: Absolute CVD event rates, per 100 person-years in JUPITER, were 0.57 for women randomized to rosuvastatin and 1.04 for women randomized to placebo, and 0.88 for men randomized to rosuvastatin and 1.54 for men randomized to placebo. The relative risk (RR) reduction was 0.54 (95% confidence interval [CI], 0.37-0.80) for women and 0.58 (95% CI, 0.45-0.73) for men. Among women participants from JUPITER, there was a significant reduction in revascularization/unstable angina and nonsignificant reductions in secondary events such as myocardial infarction, stroke, and death. In the meta-analysis of 13,154 women, a significant reduction in primary CVD events was observed with statins (RR, 0.63; 95% CI, 0.49-0.82) and a nonsignificant reduction in total mortality (RR, 0.78; 95% CI, 0.53-1.15).
Conclusions: The authors concluded that data from the JUPITER trial suggest that statins reduce primary CVD events among women, with a relative risk similar to that observed in men. Further data from a meta-analysis supported this conclusion.
Perspective: These data support the use of statins in primary prevention of CVD events among women, particularly those ages ≥60. Identification of long-term risk in women will assist clinicians in identifying women who will receive the greatest primary risk reduction from statin therapy. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Duration of Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents
Topic: Interventional Cardiology
Date Posted: 3/17/2010
Author(s): Park SJ, Park DW, Kim YH, et al.
Citation: N Engl J Med 2010;Mar 15:[Epub ahead of print].
Clinical Trial: yes
Related Resources
Trial: Duration of Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents (DES-LATE)

Study Question: What are the potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents (DES)?
Methods: In two trials, the investigators randomly assigned a total of 2,701 patients who had received DES and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary endpoint was a composite of myocardial infarction (MI) or death from cardiac causes. Data from the two trials were merged for analysis.
Results: The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio [HR], 1.65; 95% confidence interval [CI], 0.80-3.36; p = 0.17). The individual risks of MI, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of MI, stroke, or death from any cause (HR, 1.73; 95% CI, 0.99-3.00; p = 0.051) and in the composite risk of MI, stroke, or death from cardiac causes (HR, 1.84; 95% CI, 0.99-3.45; p = 0.06).
Conclusions: The authors concluded that the use of dual antiplatelet therapy for a period longer than 12 months in patients who had received DES was not significantly more effective than aspirin monotherapy in reducing the rate of MI or death from cardiac causes.
Perspective: In the current study, extended use of dual antiplatelet therapy, for >12 months, was not more effective than aspirin monotherapy in reducing the risk of MI or death from cardiac causes among patients who had received DES. The rates of composite outcomes (MI, stroke, death) were in fact higher with clopidogrel plus aspirin than with aspirin alone, but this difference was not significant. However, it must be noted that the study had inadequate statistical power to allow for a definitive conclusion regarding the safety of clopidogrel discontinuation after 12 months. Additional studies addressing the use of dual antiplatelet therapy after implantation of DES are ongoing, and until such results are available, clinicians should recommend dual antiplatelet therapy for at least 12 months after implantation of DES, as supported by the American Heart Association/American College of Cardiology in a Science Advisory (J Am Coll Cardiol 2007;49:734-9), and the Food and Drug Administration. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Improved Survival Among Patients With Eisenmenger Syndrome Receiving Advanced Therapy for Pulmonary Arterial Hypertension
Topic: Congenital Heart Disease
Date Posted: 3/17/2010
Author(s): Dimopoulos K, Inuzuka R, Goletto S, et al.
Citation: Circulation 2010;121:20-25.
Clinical Trial: No
Study Question: What is the effect of advanced therapy (AT) (pulmonary vasodilators) on survival in patients with Eisenmenger syndrome?
Methods: A retrospective review was performed over a 10-year period at a single center. Survival rates were compared between patients on and off AT with use of a modified version of the Cox model, treating AT as a time-varying covariate.
Results: A total of 229 patients, mean age 34.5 ± 12.6 years, were studied. The majority had complex anatomy (atrioventricular septal defects, univentricular physiology, transposition of the great arteries, aortopulmonary window, common arterial trunk, and operated lesions), with 29.7% of patients having Down syndrome. Mean resting oxygen saturation was 84.3%. Sixty-eight patients (29.7%) were on AT at the beginning of the study period or started on AT at some point during the study period. The majority of patients on AT were on bosentan (73.5%), whereas some were on sildenafil (25%) and epoprostenol (1.5%). During a median follow-up of 4.0 years, 52 patients died, 2 of them while on AT. Patients on AT were at a significantly lower risk of death, both unadjusted and adjusted for baseline clinical differences by propensity score regression adjustment (C-statistic, 0.8; hazard ratio, 0.16; 95% confidence interval, 0.04-0.71; p = 0.015) and propensity score matching (hazard ratio, 0.10; 95% confidence interval, 0.01-0.78; p = 0.028).
Conclusions: Pulmonary vasodilator therapy for pulmonary arterial hypertension in adults with Eisenmenger syndrome was associated with a lower risk of death.
Perspective: This important study is the first large-scale study to demonstrate survival benefit from pulmonary vasodilators in adults with Eisenmenger physiology. Historically, clinicians have favored a minimally interventional approach towards patients with Eisenmenger physiology with a goal of not upsetting the fragile homeostasis often seen in this patient population. The randomized and controlled BREATHE-5 study of bosentan demonstrated improvement in exercise capacity and pulmonary hemodynamics without compromising systemic oxygen saturation (Circulation 2006;114:1807-10). There was no demonstrated mortality benefit over a short study period, and patients generally did not have complex disease. In the current study, a majority of patients had complex disease, and almost one-third had Down syndrome, which is reflective of the population seen at most centers. These results suggest that clinicians should rethink the minimalist strategy often employed in adults with Eisenmenger physiology. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Intensive Multifactorial Intervention for Stable Coronary Artery Disease: Optimal Medical Therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) Trial
Topic: Prevention/Vascular
Date Posted: 3/22/2010 5:00:00 PM
Author(s): Maron DJ, Boden WE, O’Rourke RA, et al.
Citation: J Am Coll Cardiol 2010;55:1348-1358.
Clinical Trial: No
Related Resources
JACC Article: Intensive Multifactorial Intervention for Stable Coronary Artery Disease: Optimal Medical Therapy in the COURAGE Trial
Trial: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE)

Study Question: What is the effect of the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial on coronary risk factors?
Methods: The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention (PCI) in patients with stable coronary disease. All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. The primary outcome of this analysis is change in coronary risk factors.
Results: A total of 2,287 patients were followed for an average of 4.6 years. There were no differences between groups (PCI or no-PCI at baseline) for the following: mean age was 62 years, 85% male, 86% white, 32% diabetic, 66% hypertensive, 23% current smokers, and 38% had a previous myocardial infarction. Mean baseline values were: low-density lipoprotein cholesterol (LDL-C) 101 mg/dl, high-density lipoprotein cholesterol 39 mg/dl, triglycerides 145 mg/dl, and body mass index 28.8 kg/m2. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked ≥150 minutes/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 ± 0.13 kg/m2 to 29.3 ± 0.23 kg/m2 (p < 0.001). Appropriate medication use increased from prerandomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; rennin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 ± 0.49 mm Hg to 123 ± 0.88 mm Hg. LDL-C decreased from a median of 101 ± 0.83 mg/dl to 72 ± 0.88 mg/dl.
Conclusions: Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols, and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease.
Perspective: Congratulations to the COURAGE nurse clinical case managers and investigators. The risk factor reduction in COURAGE far exceeds community practice. One of the messages from this analysis is that nurse case managers trained in changing behavior, nutrition, exercise, smoking cessation, and evidence-based drug therapies provide a standard of care that can exceed that of busy practitioners. Institutions and physicians should consider incorporating nurse case manager care for patients with coronary disease, possibly in consort with cardiac rehabilitation that includes several follow-up visits over the first year. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Alcohol Consumption and Cardiovascular Mortality Among U.S. Adults, 1987 to 2002
Topic: Prevention/Vascular
Date Posted: 3/22/2010 5:00:00 PM
Author(s): Mukamal KJ, Chen CM, Rao SR, Breslow RA.
Citation: J Am Coll Cardiol 2010;55:1328-1335.
Clinical Trial: No
Related Resources
JACC Article: Alcohol Consumption and Cardiovascular Mortality Among U.S. Adults, 1987 to 2002

Study Question: Is alcohol consumption associated with cardiovascular (CV) mortality?
Methods: Data from the National Health Interview Survey, an annual survey of US adults, were used for the analysis. Surveys from 1987 to 2002 were included. Alcohol consumption was examined by usual volume, frequency, and quantity. Information on binge drinking was also included. The outcome of interest was CV mortality, which was obtained through linkage to the National Death Index through 2002.
Results: A total of 245,207 US adults were included in this study, and 10,670 CV disease (CVD) deaths occurred over 1,987,439 person-years of follow-up. Light and moderate alcohol consumption was inversely associated with CV mortality. Compared to lifetime abstainers, a trend towards decreased CVD mortality was observed among lifetime infrequent drinkers (relative risk [RR], 0.95; 95% confidence interval [CI], 0.88-1.02), former drinkers (RR, 1.02; 95% CI, 0.94-1.11), and heavy drinkers (RR, 0.95; 95% CI, 0.82-1.10), whereas a significant decreased risk was observed for light drinkers (RR, 0.69; 95% CI, 0.59-0.82) and moderate drinkers (RR, 0.62; 95% CI, 0.50-0.77). These risks were similar in subgroups of age, sex, and baseline health status. No significant association was observed for CVD mortality and binge drinking. In looking at number of drinks per day, those who consumed three or more drinks per day had an increased risk of CVD mortality compared to those who consumed two drinks per day.
Conclusions: The authors concluded that light and moderate alcohol consumption was associated with reduced CVD mortality among a nationally representative sample of US adults, as compared with lifetime abstainers.
Perspective: These data support current recommendations that light (defined as current use of ≤3 drinks per week) to moderate (defined as >3 to 7 drinks per week for women and >3 to 14 drinks per week for men) alcohol consumption is not associated with increased CVD mortality. However, as the authors point out, this study is observational, and thus, confounding may influence these findings. Clinicians should continue to assess alcohol patterns among their patients, with recommendations tailored to the individual patient’s comorbidities, medication use, and preferences. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Percutaneous Mitral Valve Repair With the MitraClip System: Acute Results From a Real World Setting
Topic: Interventional Cardiology
Date Posted: 3/23/2010
Author(s): Tamburino C, Ussia GP, Maisano F, et al.
Citation: Eur Heart J 2010;Mar 18:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the short-term safety and efficacy of the percutaneous edge-to-edge repair approach for mitral regurgitation (MR) with the MitraClip system?
Methods: The authors reported their experience with the MitraClip system at two Italian hospitals. The primary efficacy endpoint was acute device success, defined as clip placement with reduction of MR to ≤2 +. The primary acute safety endpoint was 30-day freedom from major adverse events, defined as the composite of death, myocardial infarction, nonelective cardiac surgery for adverse events, renal failure, transfusion of more than 2 units of blood, ventilation for >48 hours, deep wound infection, septicemia, and new onset of atrial fibrillation.
Results: A total of 31 patients were treated between August 2008 and July 2009. The median age of the cohort was 71 years and 25 (81%) were men. The etiology of the MR was functional in 18 patients and degenerative disease in 13. A single clip was successfully implanted in 19 patients and two clips in 12 patients. The median device implantation time was 80 minutes, with procedure duration decreasing with increasing operator experience. At 30 days, there was one intraprocedural cardiac tamponade and one noncardiac death (from a gastrointestinal bleed), resulting in a primary safety endpoint of 93.6%. Acute device success was achieved in 96.8% of patients. There was a reduction in left ventricular diameters, diastolic left ventricular volume, diastolic annular septal–lateral dimension, and mitral valve area from baseline to 30 days.
Conclusions: Percutaneous MR repair using the MitraClip device can be accomplished with favorable short-term safety and efficacy.
Perspective: The results of this study support good short-term safety and efficacy of the MitraClip system. The results of the recently presented EVEREST II trial suggest a lower complication rate with MitraClip compared with open surgical repair and a noninferior clinical success at 1 year. While larger studies are required to assess the long-term safety and efficacy of this device, percutaneous mitral valve repair is likely to emerge as a viable option for many patients in the near future. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: 5-Year Clinical Outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) Trial: A Randomized Comparison of an Early Invasive Versus Selective Invasive Management in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome
Topic: Interventional Cardiology
Date Posted: 3/24/2010
Author(s): Damman P, Hirsch A, Windhausen F, Tijssen JG, de Winter RJ, on behalf of the ICTUS Investigators.
Citation: J Am Coll Cardiol 2010;55:858-864.
Clinical Trial: yes
Related Resources
JACC Article: 5-Year Clinical Outcomes in the ICTUS Trial: A Randomized Comparison of an Early Invasive Versus Selective Invasive Management in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome
Trial: Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS)

Study Question: What is the long-term outcome of patients with non–ST-elevation acute coronary syndromes (ACS) treated with an early invasive versus an ischemia-guided therapy?
Methods: The authors reported the 5-year outcome of patients enrolled in the Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) trial. This trial randomized 1,200 patients to an early invasive or selective invasive therapy. During the initial hospitalization, 76% of patients in the invasive arm and 40% of patients in the selective invasive therapy arm were revascularized.
Results: The 5-year revascularization rate was 81% in the invasive arm and 60% in the selective invasive arm. The cumulative rate of death or myocardial infarction was higher in the early invasive therapy arm (22.3% vs. 18.1%, hazard ratio, 1.29; 95% confidence interval, 1.00-1.66; p = 0.053). There was no difference in 5-year mortality (11.1% vs. 9.9%; p = 0.49). After risk stratification using the FRISC score, no benefit of an early invasive strategy was observed in reducing death or myocardial infarction in any of the risk groups.
Conclusions: There was no advantage of an early invasive therapy over selectively invasive therapy in patients with ACS.
Perspective: Current guidelines support an early invasive approach to treatment of patients with ACS. Prior studies had suggested better long-term survival with such an approach, but the results of the ICTUS trial suggest that either approach provides a similar outcome. This difference is largely due to the more liberal use of an invasive strategy in patients randomized to the selectively invasive arm such that over 54% of patients in this arm had undergone revascularization (54%) by 1 year. These results suggest that either an early invasive strategy or a selective (albeit liberally) invasive strategy can be used to treat patients with ACS based on patient and physician preference. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Parental Occurrence of Stroke and Risk of Stroke in Their Children: The Framingham Study
Topic: Prevention/Vascular
Date Posted: 3/23/2010
Author(s): Seshadri S, Beiser A, Pikula A, et al.
Citation: Circulation 2010;121:1304-1312.
Clinical Trial: No
Study Question: How does stroke in parents influence stroke risk in children?
Methods: Data from the Framingham Heart Study and offspring study were used for this analysis. Children with no history of stroke, who had parents with a history of stroke by the age of 65 years and who completed their first, third, fifth, and/or seventh study examination and were followed for up to 8 years after the baseline exam were included in the study population.
Results: A total of 3,443 offspring (53% female, mean age 48 ± 14 years) were included in the cohort. Over 77,534 person-years, a total of 106 parental strokes were documented, of which 74 were ischemic. Among the offspring, 128 strokes occurred, of which 106 were ischemic. In multivariate analysis, parental stroke was associated with an increased incidence of stroke in the offspring (hazard ratio [HR], 2.79; 95% confidence interval [CI], 1.68-4.66 for all stroke, and HR, 3.15; 95% CI, 1.69-5.88 for ischemic stroke) after adjustment for age, sex, and baseline stroke risk factors. This association was observed for both maternal and paternal stroke.
Conclusions: The authors concluded that occurrence of stroke in parents younger than 65 years is associated with increased risk of stroke in their children.
Perspective: These data suggest that parental stroke at an early age is an independent risk factor for stroke. Providers can easily obtain such information, which assists in the identification of patients who may be at increased risk for stroke. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Relationship Between Plasma Inflammatory Markers and Plaque Fibrous Cap Thickness Determined by Intravascular Optical Coherence Tomography
Topic: Interventional Cardiology
Date Posted: 3/23/2010
Author(s): Li QX, Fu QQ, Shi SW, et al.
Citation: Heart 2010;96:196-201.
Clinical Trial: No
Study Question: What is the relationship between human plaque fibrous cap thickness detected by intravascular optical coherence tomography (OCT) and the plasma levels of inflammatory factors in patients with coronary artery disease (CAD)?
Methods: The authors performed OCT in 46 patients with CAD (12 with acute myocardial infarction, 23 with unstable angina, and 11 patients with stable angina pectoris). Plasma levels of highly sensitive C-reactive protein (hs-CRP), interleukin (IL)-18, and tumor necrosis factor alpha (TNFα) were measured. Lesions with cap thickness less than 65 mcm were classified as thin cap fibroatheromas (TCFAs).
Results: There was an inverse correlation between the plasma levels of inflammatory markers and white blood cell (WBC) count and fibrous cap thickness (r = -0.775 for hs-CRP, r = -0.593 for IL-18, r = -0.60 for TNFα, and r = -0.356 for WBC count). Patients with TCFA had higher plasma levels of inflammatory factors as well as WBC counts than those with thicker fibrous caps. Receiver operator characteristic (ROC) curve analysis determined that an hs-CRP cut-off at 1.66 mg/L would detect TCFA with a sensitivity of 96% and a specificity of 90%, and was the strongest predictor of TCFA.
Conclusions: There is an inverse linear correlation between fibrous cap thickness and plasma levels of inflammatory markers.
Perspective: This is an interesting study that corroborates and extends earlier work (Raffel OC, et al., Arterioscler Thromb Vasc Biol 2007;27:1820-7). This study evaluated patients with different degrees of clinical instability, and it is not clear if the authors could adjust for the expected confounding. Patients with a greater degree of plaque instability are known to have elevation in inflammatory markers, and are also more likely to have TCFA; it would have been preferable to evaluate a more homogenous population. Further studies are warranted to better define peripheral markers of coronary instability. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Recent Declines in Hospitalizations for Acute Myocardial Infarction for Medicare Fee-for-Service Beneficiaries: Progress and Continuing Challenges
Topic: General Cardiology
Date Posted: 3/25/2010
Author(s): Chen J, Normand SL, Wang Y, Drye EE, Schreiner GC, Krumholz HM.
Citation: Circulation 2010;121:1322-1328.
Clinical Trial: No
Study Question: Have recent efforts to reduce cardiovascular risk had an effect on the rates of acute myocardial infarction (AMI) in the United States in elderly patients?
Methods: Medicare fee-for-service patients hospitalized in the United States with a principal discharge diagnosis of AMI were identified through the use of data from the Centers for Medicare and Medicaid Services from 2002 to 2007, a time period selected to reduce changes arising from the new definition of AMI. The Medicare beneficiary denominator file was used to determine the population at risk. AMI hospitalization rates were calculated annually per 100,000 beneficiary-years with Poisson regression analysis and stratified according to age, sex, and race.
Results: The annual AMI hospitalization rate in the fee-for-service Medicare population fell from 1,131 per 100,000 beneficiary-years in 2002 to 866 in 2007, a relative 23.4% decline. After adjustment for age, sex, and race, the AMI hospitalization rate declined by 5.8%/year. From 2002 to 2007, white men experienced a 24.4% decrease in AMI hospitalizations, whereas black men experienced a smaller decline (18.0%; p < 0.001 for interaction). Black women had a smaller decline in AMI hospitalization rate compared with white women (18.4% vs. 23.3%, respectively; p < 0.001 for interaction).
Conclusions: AMI hospitalization rates fell markedly in the Medicare fee-for-service population between 2002 and 2007. However, black men and women appeared to have had a slower rate of decline compared with their white counterparts.
Perspective: Whatever you are feeling about cost and value, a contemporary national database for major medical diagnosis and treatments should be one of the relatively simple tools of the new health care system. These data should be available upon request for clinical research regarding the effect and cost-effectiveness of diagnostic and treatment paradigms. I see no reason why the data cannot be very rapidly processed to test newer and competing strategies. This type of information will allow us to understand the differences in outcome that are attributable to variables, including gender and ethnicity, as in this study. Melvyn Rubenfire, M.D., F.A.C.C

Title: Cost-Effectiveness of Preparticipation Screening for Prevention of Sudden Cardiac Death in Young Athletes
Topic: Prevention/Vascular
Date Posted: 3/25/2010
Author(s): Wheeler MT, Heidenreich PA, Froelicher VF, Hlatky MA, Ashley EA.
Citation: Ann Intern Med 2010;152:276-286.
Clinical Trial: No
Study Question: What is the cost-effectiveness of electrocardiography (ECG) plus cardiovascular-focused history and physical examination compared with focused history and physical examination alone for preparticipation screening in young athletes?
Methods: A decision model was used to project the costs and survival rates for US male and female athletes participating in high school or college interscholastic sports. Assuming a single screening evaluation in each athlete, models of no screening, only focused history and physical examination, and focused history and physical examination plus ECG were compared. Rates of sudden cardiac death were extrapolated from an Italian study (Corrado D, et al., JAMA 2006;296:1593-1601).
Results: According to the authors’ model, addition of ECG to preparticipation screening saves 2.06 life-years per 1,000 athletes at an incremental total cost of $89 per athlete, and yields a cost-effectiveness ratio of $42,900 per life-year saved (95% confidence interval, $21,200 to $71,300 per life-year saved) compared with cardiovascular-focused history and physical examination alone. Compared with no screening, ECG plus cardiovascular-focused history and physical examination saves 2.6 life-years per 1,000 athletes screened and costs $199 per athlete, yielding a cost-effectiveness ratio of $76,100 per life-year saved ($62,400 to $130,000).
Conclusions: The authors concluded that screening young athletes with 12-lead ECG plus cardiovascular-focused history and physical examination may be cost-effective.
Perspective: No, no, no, no, no. This model—attempting to predict what might be, based on extrapolation of published data—used hotly contested data on sudden cardiac death rates in the Veneto region of Italy. Applied to the US population, the authors found, not surprisingly, that the conclusions drawn by the Italian authors would hold in the US, as well. However, there are very good reasons to believe that the Italian experience does not extrapolate to the US. The very high rate of sudden cardiac death in Italian athletes is due to arrhythmogenic right ventricular dysplasia, occurring at rates far higher than that seen in the US. Perhaps as a result, the rate of sudden cardiac death achieved with screening ECG in Italy now matches the low rates seen in the US without ECG screening. Rather than using the low rates of sudden cardiac death documented without ECG screening in the US, the authors appear to have essentially assured a ‘positive’ study by using data from different populations with different risks and different observed outcomes. David S. Bach, M.D., F.A.C.C.

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Title: Cardiovascular Screening in College Athletes With and Without Electrocardiography: A Cross-Sectional Study
Topic: Prevention/Vascular
Date Posted: 3/25/2010
Author(s): Baggish AL, Hutter AM Jr, Wang F, et al.
Citation: Ann Intern Med 2010;152:269-275.
Clinical Trial: No
Study Question: For purposes of screening college athletes before athletic participation, how do history and physical examination alone compare with a strategy including routine electrocardiography (ECG)?
Methods: Over a 3-year interval, 510 collegiate athletes at Harvard University (Cambridge, MA) who underwent preparticipation screening at the University Health Services were studied. Each participant underwent routine history, physical examination, ECG, and transthoracic echocardiography (TTE) to detect or exclude cardiac findings relevant to sports participation. TTE results were taken as the “gold standard” for disease presence. The performance of screening with history and physical examination only was compared with that of screening integrating history, examination, and ECG.
Results: Cardiac abnormalities relevant to sports participation risk were observed on TTE in 11 of 510 participants (prevalence, 2.2%; including mitral valve prolapse [n = 3], bicuspid aortic valve [n = 2], pulmonic stenosis [n = 1], left ventricular [LV] hypertrophy [n = 2], LV dilation [n = 2], and right ventricular dilation [n = 1]). Screening history and physical examination alone detected abnormalities in 5 of these 11 athletes (sensitivity 45.5%; 95% confidence interval [CI], 16.8-76.2% and specificity 94.4%; CI, 92.0-96.2%). ECG detected five additional participants with cardiac abnormalities (total 10 of 11 participants), with overall sensitivity of 90.9% (CI, 58.7-99.8%). However, including ECG reduced the specificity of screening to 82.7% (CI, 79.1-86.0%) and was associated with a false-positive rate of 16.9% (vs. 5.5% for screening with history and examination only). After further evaluation, athletic participation was restricted in three athletes (one each with TTE findings of pulmonic stenosis, LV hypertrophy, LV dilation).
Conclusions: Adding ECG to medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening in athletes. However, this strategy is associated with an increased rate of false-positive results when current ECG interpretation criteria are used.
Perspective: The debate continues as to whether US amateur athletes should undergo a mandatory screening ECG (as is the policy in Italy, and subsequently adopted by the European Union) in addition to only screening history and physical examination (as is the long-standing US policy). On the surface, this study appears to add weight to the argument for routine preparticipation ECG. However, caveats abound, many of which were discussed in an accompanying editorial (Maron BJ, Ann Intern Med 2010;152:324-6). In addition:
The population of student athletes at Harvard might be anticipated to be poorly reflective of all amateur athletes in the US. (In this study, only 10% of screened athletes were black.) Because nonpathologic ECG abnormalities are far more prevalent in black than in white athletes, it could be anticipated that such benign but abnormal ECGs likely were under-represented in this study, and would have served to further reduce the specificity of the ECG.
Low test specificity and the associated high rate of false-positives is a major issue with the routine use of preparticipation ECG. The best-case scenario is that more money is spent to do more tests to prove that everything was OK to begin with. The worse (and probably more realistic) outcome is that amateur athletes are denied the ability to participate—including many with no underlying cardiac disease, and others with disease, but no prohibitive risk. In a country plagued by obesity, diabetes, and their various sequelae, physical activity should be encouraged not just in principle but in practice. Setting a low threshold for exclusion from athletics only will serve to worsen our obesity epidemic.
The authors used as a ‘gold standard’ for disease any abnormality of an echocardiogram. But of the 11 athletes with an ‘abnormal’ TTE, athletic participation was limited in only three (one of whom had an abnormal physical examination). If our societal goal is to detect any cardiac disease in any child or young adult, then intended athletic participation is impertinent, and screening should be instituted universally. If our goal is to detect disease that might pose a risk to the athlete, then the denominator in this study should have been at most three, not 11 students.
David S. Bach, M.D., F.A.C.C.

Title: A Critical Decrease in Dominant Frequency and Clinical Outcome After Catheter Ablation of Persistent Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 3/24/2010
Author(s): Yoshida K, Chugh A, Good E, et al.
Citation: Heart Rhythm 2010;7:295-302.
Clinical Trial: No
Study Question: Is a critical decrease in the dominant frequency (DF) of persistent atrial fibrillation (AF) predictive of a clinical efficacy similar to that observed after termination of AF during radiofrequency ablation (RFA)?
Methods: Antral pulmonary vein isolation (APVI) followed by RFA of complex fractionated atrial electrograms (CFAEs) in the atria and coronary sinus was performed in 100 consecutive patients with persistent AF. The DF of AF in lead V1 and in the coronary sinus was determined by fast Fourier transform analysis at baseline and before termination of AF to identify a critical decrease in DF predictive of sinus rhythm after RFA. Multivariate logistic regression analysis was performed to identify the predictors of freedom from recurrent atrial arrhythmias after catheter ablation.
Results: A ≥11% decrease in DF had the highest accuracy in predicting freedom from atrial arrhythmias, with a sensitivity of 0.71 and a specificity of 0.82 (p < 0.001). At a mean follow-up of 14 ± 3 months after one ablation procedure, sinus rhythm was maintained off antiarrhythmic drugs in 8/35 (23%) and 20/26 (77%) patients with a <11% and ≥11% decrease in DF, respectively (p < 0.001). Sinus rhythm was maintained in 24/39 patients (62%) in whom RFA terminated AF. The duration of RFA and total procedure time were longer in patients with AF termination (95 ± 23 and 358 ± 87 minutes) than in patients with a <11% decrease in the DF (77 ± 16 and 293 ± 70 minutes) or ≥11% decrease in DF (80 ± 17 and 289 ± 73 minutes), respectively (p < 0.01). Among the variables of age, gender, left atrial diameter, duration of AF, left ventricular ejection fraction, duration of RFA, a ≥11% decrease in DF, and termination of AF, a ≥11% decrease in DF (odds ratio [OR], 9.89; 95% confidence interval [CI], 2.84-34.47) and termination during RFA (OR, 4.38; 95% CI, 1.50-12.80) were the only independent predictors of freedom from recurrent atrial arrhythmias.
Conclusions: The authors concluded that a decrease in the DF of AF by 11% in response to APVI and ablation of CFAEs was associated with a probability of maintaining sinus rhythm that was similar to that when RFA terminates AF.
Perspective: In this retrospective analysis of consecutive patients with persistent AF, patients who had a ≥11% decrease in the DF or termination of AF during ablation were more likely to remain in sinus rhythm than patients who remain in AF during RFA and have a lesser decrease in the DF. In fact, a reduction in the dominant frequency by 11% or more without termination of AF by catheter ablation was as predictive of a successful outcome as was termination of AF by RFA. The clinical utility of monitoring DF in real time to guide catheter ablation of AF requires further validation in prospective multicenter studies. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Prevalence of Diabetes Among Men and Women in China
Topic: Prevention/Vascular
Date Posted: 3/24/2010 5:00:00 PM
Author(s): Yang W, Lu J, Weng J, et al., on behalf of the China National Diabetes and Metabolic Disorders Study Group.
Citation: N Engl J Med 2010;362:1090-1101.
Clinical Trial: No
Study Question: What is the prevalence of diabetes among men and women residing in China?
Methods: A nationally representative sample of 46,239 adults, ages 20 years or older, from 14 provinces and municipalities in China, were included in this study. Subjects underwent glucose testing after an overnight fast, including fasting and 2-hour glucose measures, and oral glucose-tolerance testing. History of diabetes was based on self-report. World Health Organization diagnostic criteria were used to diagnose diabetes.
Results: The China National Diabetes and Metabolic Disorders study is a cross-sectional study conducted from June, 2007 through May, 2008. The age-standardized prevalence of diabetes was 9.7% (10.6% for men and 8.8% for women), and for prediabetes the prevalence was 15.5% (16.1% for men and 14.9% for women). This accounts for an estimated 92.4 million adults with diabetes and 148.2 million adults with prediabetes. The prevalence of diabetes increases with age from 3.2% among adults 20-39 years of age to 20.4% for adults 60 years or older. Prevalence of diabetes also increases with increasing weight, from 4.5% for those with a body mass index (BMI) less than 18.5, to 18.5% for those with a BMI of 30 or greater. Prevalence of diabetes was higher among urban dwellers, as compared to those residing in rural communities (11.4% vs. 8.2%). However, the prevalence of prediabetes was higher among rural residents. The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% for men and 10.9% vs. 2.2% for women). In multivariate models, factors associated with diabetes included male sex, older age, family history of diabetes, overweight or obesity, central obesity, increased heart rate, elevated systolic blood pressure, elevated serum triglycerides, and educational level below college.
Conclusions: The authors concluded that the observed prevalence of diabetes and prediabetes suggests a significant public health concern. Strategies for improving the diagnosis of prediabetes and diabetes and the prevention of diabetes are warranted.
Perspective: This cross-sectional study highlights a dramatic increase in diabetes over the past several decades. Given the increased prevalence in other countries, there is a clear need to globalize prevention efforts. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Risk of Fatal Arrhythmic Events in Long QT Syndrome Patients After Syncope
Topic: Arrhythmias
Date Posted: 3/17/2010
Author(s): Jons C, Moss AJ, Goldenberg I, et al.
Citation: J Am Coll Cardiol 2010;55:783-788.
Clinical Trial: No
Related Resources
JACC Article: Risk of Fatal Arrhythmic Events in Long QT Syndrome Patients After Syncope

Study Question: What factors are predictive of sudden cardiac death (SCD) after an episode of syncope in patients with the long QT syndrome (LQTS)?
Methods: The subjects of this study were 1,059 patients with LQTS and syncope who were entered into an international LQTS registry. Therapy with beta-blockers was at the discretion of the treating physician. Twenty percent of the patients had an implantable cardioverter defibrillator (ICD). The 1° endpoint was a severe arrhythmic event (SAE), defined as SCD, aborted cardiac arrest, or an appropriate ICD therapy.
Results: An SAE occurred in 210/1,059 patients. The strongest independent predictors of an SAE after an episode of syncope were ≥1 syncopal episodes on beta-blocker therapy (hazard ratio [HR], 3.6 compared to patients with one syncopal episode off beta-blocker therapy), >1 syncopal episode off beta-blocker therapy (HR, 2.0), and female gender with age 14-40 years (HR, 1.9). The strongest independent predictors of subsequent syncope after the start of beta-blocker therapy in patients with a previous syncope episode were male gender with age 0-13 years (HR, 3.2 compared to males with age 14-40 years), and female gender with age 0-13 years (HR, 3.0 compared to males with age 14-40 years).
Conclusions: In patients with LQTS, syncope during beta-blocker therapy is a strong predictor of an SAE and an appropriate indication for an ICD. Young children and women have the highest risk of recurrent syncope despite beta-blocker therapy after a syncopal episode.
Perspective: The factors that account for beta-blocker failure are unclear. The type of beta-blocker or the particular LQTS genotype was not predictive of SAEs in this study. It is possible that noncompliance or undertreatment played a role. Fred Morady, M.D., F.A.C.C.

Title: Thoracic Aortic Aneurysm: Clinically Pertinent Controversies and Uncertainties
Topic: Cardiovascular Surgery
Date Posted: 3/18/2010
Author(s): Elefteriades JA, Farkas EA.
Citation: J Am Coll Cardiol 2010;55:841-857.
Clinical Trial: No
Related Resources
JACC Article: Thoracic Aortic Aneurysm: Clinically Pertinent Controversies and Uncertainties

Perspective: The following are 10 points to remember from this state-of-the-art paper about thoracic aortic aneurysm.

1. This paper addresses clinical controversies and uncertainties regarding thoracic aortic aneurysm and its treatment.

2. The most recent data available from the Centers for Disease Control and Prevention indicate that aneurysm disease is the 18th most common cause of death in all individuals and the 15th most common in individuals older than age 65 years, accounting for 13,843 and 11,147 deaths in these two groups, respectively.

3. Estimating true aortic size is confounded by obliquity, asymmetry, and noncorresponding sites.

4. It is also important to remember that size is not the only important imaging criterion; shape matters as well, especially loss of the normal “waist” of the aorta at the sinotubular junction.

5. Although a virulent disease, thoracic aortic aneurysm is an indolent process. The thoracic aorta grows very slowly—at approximately 0.1 cm per year.

6. Symptomatic aneurysms should be resected regardless of size. It is important to intervene before the aorta reaches 6 cm in the ascending aorta and 7 cm in the descending aorta. Available data suggest that aneurysms in the ascending aorta need corrective surgery when the artery balloons to 5.5 cm.

7. A full spectrum of engineering calculations regarding the mechanical properties of the dilated aorta can be determined via measurement of six independent variables: aortic pressure in systole and diastole, aortic diameter in systole and diastole, and aortic wall thickness in systole and diastole, and may help optimize timing of surgery.

8. Recent evidence shows that many dissections are preceded by a specific severe exertional or emotional event. Findings that acute exertion and emotion often underlie the onset of acute aortic dissection constitute another reasonable rationale for beta-blocker therapy, with the intent of blunting pressure spikes.

9. Thoracic aortic aneurysm is multigenetic; consequently, no easy, comprehensive, full aortic genetic screen is currently generally available.

10. The decision to treat an aneurysm must be made with the same rigor for endovascular therapy as for open surgical therapy. The presence of a small thoracic aneurysm is not a valid indication for endovascular therapy just because stent therapy is available. Debabrata Mukherjee, M.D., F.A.C.C.

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Taper or Stop Clopidogrel?
VA Cooperative Study
MM-WES Study - Effect of Genotyping Warfarin Patients on utcomes
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: 5-Year Clinical Outcomes of the ARTS II (Arterial Revascularization Therapies Study II) of the Sirolimus-Eluting Stent in the Treatment of Patients With Multivessel De Novo Coronary Artery Lesions
Topic: Interventional Cardiology
Date Posted: 3/26/2010
Author(s): Serruys PW, Onuma Y, Garg S, et al., on behalf of the ARTS II Investigators.
Citation: J Am Coll Cardiol 2010;55:1093-1101.
Clinical Trial: yes
Related Resources
JACC Article: 5-Year Clinical Outcomes of the ARTS II (Arterial Revascularization Therapies Study II) of the Sirolimus-Eluting Stent in the Treatment of Patients With Multivessel De Novo Coronary Artery Lesions
Trial: Arterial Revascularization Therapies Study II: Sirolimus-Eluting Stent in the Treatment of Patients With Multivessel De Novo Coronary Artery Lesions (ARTS II: 5-Year Results)

Study Question: What are 5-year clinical outcomes, safety, and efficacy of sirolimus-eluting stents (SES) in the ARTS II (Arterial Revascularization Therapies Study II) compared with the outcomes of coronary artery bypass grafting (CABG) and bare-metal stenting (BMS) from the ARTS I trial?
Methods: The ARTS I study was a randomized trial of 1,205 patients with multivessel disease comparing CABG and BMS. The ARTS II study was a nonrandomized trial with the Cypher SES, applying the same inclusion and exclusion criteria, endpoints, and protocol definitions. The ARTS II trial enrolled 607 patients, with an attempt to enroll at least one-third of patients with three-vessel disease. The primary objective of ARTS II was to compare the safety and effectiveness of coronary stent implantation using the SES with the surgical arm of ARTS I.
Results: At 5 years, the death/stroke/myocardial infarction event-free survival rate was 87.1% in ARTS II SES, versus 86.0% (p = 0.1) and 81.9% (p = 0.007) in ARTS I CABG and BMS cohorts, respectively. The 5-year major adverse cardiac and cerebrovascular event (MACCE) rate in ARTS II (27.5%) was significantly higher than ARTS I CABG (21.1%, p = 0.02), and lower than in ARTS I BMS (41.5%, p < 0.001). The cumulative incidence of definite stent thrombosis was 3.8%. Thirty-two percent (56 of 176) of major adverse cardiac events (MACE) at 5 years were related to possible, probable, or definite stent thrombosis.
Conclusions: The authors concluded that at 5 years, SES had a safety record comparable to CABG and superior to BMS, and a MACCE rate that was higher than in patients treated with CABG, and lower than in those treated with BMS.
Perspective: The study reports that the 5-year composite safety endpoint of death, stroke, and myocardial infarction in the SES group was comparable to the CABG group, and lower than the BMS group. The MACCE rate in the SES group on the other hand was higher than the CABG group, which was mainly driven by a higher rate of repeat revascularization in the SES group; however, the MACCE rate of the SES group remained lower than that of the BMS group. Baseline SYNTAX score had a role in the prediction of 5-year MACCE events and suggests that patients with multivessel disease and a low SYNTAX score may be adequately treated with PCI, whereas those patients with high SYNTAX scores benefit from CABG. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Impact of Olmesartan on Progression of Coronary Atherosclerosis: A Serial Volumetric Intravascular Ultrasound Analysis From the OLIVUS (Impact of OLmesartan on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound) Trial
Topic: Prevention/Vascular
Date Posted: 3/26/2010
Author(s): Hirohata A, Yamamoto K, Miyoshi T, et al.
Citation: J Am Coll Cardiol 2010;55:976-982.
Clinical Trial: yes
Related Resources
JACC Article: Impact of Olmesartan on Progression of Coronary Atherosclerosis: A Serial Volumetric Intravascular Ultrasound Analysis From the OLIVUS Trial

Study Question: What is the effect of the angiotensin II receptor blocker, olmesartan, on the progression of coronary atherosclerosis?
Methods: A prospective, randomized, multicenter trial—Impact of OLmesartan on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound (OLIVUS)—was performed in 247 stable angina pectoris patients with native coronary artery disease (CAD). IVUS was performed at the time of percutaneous transluminal coronary angioplasty in nonculprit vessels (without angiographically significant lesions). Patients were randomly assigned to receive 10-40 mg of olmesartan or control drug, and were otherwise treated as per physician’s discretion. Serial IVUS examinations (baseline and 14-month follow-up) were performed to assess coronary atheroma volume. Volumetric IVUS analyses included lumen, plaque, vessel volume, percent atheroma volume (PAV), and percent change in total atheroma volume (TAV).
Results: Patient characteristics and blood pressure control were identical between the two groups. However, follow-up IVUS showed significantly decreased TAV and PAV in the olmesartan group (5.4% vs. 0.6 % for TAV and 3.1% vs. -0.7% for percent change in PAV, control vs. olmesartan, p < 0.05 for all).
Conclusions: Omesartan reduced the rate of coronary atheroma progression in patients with stable angina pectoris.
Perspective: Many preclinical studies have shown that blockade of the renin-angiotensin-aldosterone system (RAAS) leads to cardiovascular protection. However, studies looking at the effect of RAAS inhibition on clinical events in patients with CAD and preserved left ventricular function have been inconsistent. The reduction in atheroma progression observed in this study with olmesartan supports possible beneficial vascular effects of angiotensin II receptor inhibition on the background of modern medical therapy. Whether these IVUS changes translate into reduced coronary events will require further study. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Long-Term Pulmonary Regurgitation Following Balloon Valvuloplasty for Pulmonary Stenosis: Risk Factors and Relationship to Exercise Capacity and Ventricular Volume and Function
Topic: Congenital Heart Disease
Date Posted: 3/26/2010
Author(s): Harrild DM, Powell AJ, Trang TX, et al.
Citation: J Am Coll Cardiol 2010;55:1041-1047.
Clinical Trial: No
Related Resources
JACC Article: Long-Term Pulmonary Regurgitation Following Balloon Valvuloplasty for Pulmonary Stenosis: Risk Factors and Relationship to Exercise Capacity and Ventricular Volume and Function

Study Question: What are the predictors of pulmonary regurgitation (PR) following balloon valvuloplasty for pulmonary stenosis (PS), and what is the impact of PR on ventricular volume and function, and exercise tolerance?
Methods: Patients who had previously undergone balloon valvuloplasty for isolated valvar PS were recruited for this single-institution prospective study. Those with significant residual PS, additional congenital heart disease, or who had undergone cardiac surgery were excluded. Of 183 potentially eligible patients, 41 patients were enrolled and underwent cardiac magnetic resonance imaging (CMR) and exercise testing. Multiple parameters were analyzed for their impact on PR fraction, ventricular volume and function, and exercise function.
Results: Testing occurred a median of 13.1 years after balloon dilation. Median PR fraction was 10%; 34% had PR fraction >15%. Larger balloon-to-annulus ratio (p < 0.001) and younger age at procedure (p = 0.002) were correlated with higher PR fraction. Mean right ventricular (RV) end-diastolic volume z-score was 1.8 ± 1.9. PR fraction correlated closely with indexed RV end-diastolic volume (p < 0.001) and modestly with RV ejection fraction (p < 0.001). Peak VO2 (92% of predicted) and peak heart rate (96% of predicted) were mildly impaired. While no demographic or continuous CMR variable correlated with % of predicted peak VO2 or peak work, when PR fraction was dichotomized, peak VO2 was found to be lower in patients with PR fraction >15% (85% of predicted vs. 96% of predicted; p = 0.03).
Conclusions: Mild PR and RV dilation are common following balloon dilation for PS. Patients with larger PR fraction (>15%) have evidence of modestly impaired exercise capacity.
Perspective: Exercise capacity, as well as RV size and function, have been extensively studied in patients with pulmonary insufficiency in the setting of tetralogy of Fallot. This study assesses pulmonary insufficiency, exercise capacity, and RV status after balloon valvuloplasty for isolated PS. Overall, exercise capacity in this population is quite good, although patients with significant PR may have some exercise impairment. Additionally, a balloon-annulus ratio of >1.4 was associated with development of pulmonary insufficiency. The study is limited by a small sample size and relatively low (approximately 50%) enrollment rate, which may have introduced an enrollment bias. Timothy B. Cotts, M.D., F.A.C.C.

Title: Prognostic Importance of Atrial Fibrillation in Implantable Cardioverter-Defibrillator Patients
Topic: Arrhythmias
Date Posted: 3/26/2010
Author(s): Borleffs CJ, van Rees JB, van Welsenes GH, et al.
Citation: J Am Coll Cardiol 2010;55:879-885.
Clinical Trial: No
Related Resources
JACC Article: Prognostic Importance of Atrial Fibrillation in Implantable Cardioverter-Defibrillator Patients

Study Question: How does atrial fibrillation (AF) affect outcomes in patients with an implantable cardioverter defibrillator (ICD)?
Methods: This was a retrospective analysis of 913 patients (mean age 62 years, mean ejection fraction 32%) who received an ICD and were followed for a mean of approximately 30 months. The impact of AF on mortality and ICD therapies was analyzed.
Results: Seventy-three percent of patients had no AF, 9% had paroxysmal AF, 7% had persistent AF, and 11% had permanent AF. All-cause mortality at 3 years was significantly higher in the patients with permanent AF (32%) than in the patients with no AF (12%), paroxysmal AF (15%), or persistent AF (17%). The proportion of patients with an appropriate ICD therapy by 3 years of follow-up also was significantly higher in the permanent AF group (49%) than in the other three groups (26-29%). The 3-year rate of an inappropriate shock was lowest in the patients without AF (13%) and highest in the patients with permanent AF (32%).
Conclusions: Among ICD recipients, permanent AF is associated with a >2-fold increase in the risk of mortality and appropriate ICD therapies, and all types of AF are associated with a higher risk of inappropriate ICD shocks.
Perspective: The study does not provide any insight into the reasons why permanent AF is associated with higher mortality or a greater probability of ventricular tachycardia/fibrillation that triggers an appropriate ICD therapy. It may be that permanent AF simply is a marker of more severe myocardial disease. Another possible explanation is that the irregular ventricular rate during AF causes heterogeneous depolarization and repolarization, thereby promoting ventricular arrhythmias. Fred Morady, M.D., F.A.C.C.

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Title: Alcohol Consumption, Weight Gain, and Risk of Becoming Overweight in Middle-Aged and Older Women
Topic: Prevention/Vascular
Date Posted: 3/25/2010
Author(s): Wang L, Lee IM, Manson JE, Buring JE, Sesso HD.
Citation: Arch Intern Med 2010;170:453-461.
Clinical Trial: No
Study Question: Does regular alcohol consumption increase weight gain among middle-age and older women?
Methods: Data from the Women’s Health Study (WHS) were used for the present analysis. US women ages 38.9 years or older, with no cardiovascular disease, cancer, or diabetes at baseline, and who were normal weight (defined as a body mass index [BMI] of 18.5 to <25 at baseline) were included in this analysis. Women were asked how often they consumed alcoholic beverages. Body weight was reported at baseline and via eight annual follow-up questionnaires.
Results: A total of 19,200 women were included in the analysis. Over the 12.9 years of follow-up, 7,942 (41%) of these normal weight women became overweight or obese, of which 732 women (3.8%) became obese. An inverse relationship was observed between alcohol consumption at baseline and weight gain. After adjustment for age, baseline BMI, smoking status, nonalcoholic energy intake, physical activity level, and other lifestyle and dietary factors, the risk of becoming overweight or obese was 0.96 for women who consumed 0 to <5 g/day of alcohol, 0.86 for 5 to <15 g/day alcohol intake, 0.70 for 15 to <30 g/day alcohol intake, and 0.73 for 30 g/day or more alcohol intake (p for trend of < 0.001). The corresponding relative risks for becoming obese were 0.75, 0.43, 0.39, and 0.29 for these alcohol consumption categories, as compared to nondrinkers. These associations were similar for subgroups of age, smoking status, physical activity level, and baseline BMI.
Conclusions: The authors concluded that compared to nondrinkers, women who regularly consumed alcohol had a decreased risk of becoming overweight or obese over time.
Perspective: These data suggest that alcohol consumption is not associated with weight gain among middle-age and older women. However, these data do not suggest that alcohol intake can prevent weight gain. Careful evaluation of nutritional status in the context of individual patient’s goals and medical history is key to overall health. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: DNA Testing for Hypertrophic Cardiomyopathy: A Cost-Effectiveness Model
Topic: General Cardiology
Date Posted: 3/29/2010
Author(s): Wordsworth S, Leal J, Blair E, et al.
Citation: Eur Heart J 2010; Mar 18:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the most cost-effective way to screen family members for hypertrophic cardiomyopathy (HCM)?
Methods: This was an economic decision model comparing cascade screening by genetic, as opposed to clinical methods.
Results: The incremental cost per life-year saved was 14,397 euros for the cascade genetic compared with the cascade clinical approach. The costs for cascade molecular genetic testing were slightly higher than clinical testing in the short-term, but this was largely because the genetic approach is more effective and identifies more individuals at risk.
Conclusions: The authors concluded that the use of molecular genetic information in the diagnosis and management of HCM is a cost-effective approach to the primary prevention of sudden cardiac death (SCD) in these patients.
Perspective: The role of genetic screening in the management of patients with HCM is controversial. The cost of the testing, uncertainty surrounding the causality of some mutations identified, false negatives, and the practical impact on patient management are a few concerns. In this simulated analysis, the authors demonstrate the potential utility of a genetic screening approach for first degree relatives of an HCM proband. Although many assumptions are made, more patients at risk for sudden death could be identified with genetic screening, which would lead to a higher rate of implantable cardioverter defibrillator implants, and presumably reduced SCD. The argument for screening will become even stronger if therapies are identified that prevent or modify HCM development in mutation carriers. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Long-Term Effectiveness and Safety of Sirolimus Stent Implantation for Coronary In-Stent Restenosis: Results of the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry at 4 Years
Topic: Interventional Cardiology
Date Posted: 3/30/2010
Author(s): Liistro F, Fineschi M, Grotti S, et al.
Citation: J Am Coll Cardiol 2010;55:613-616.
Clinical Trial: No
Related Resources
JACC Article: Long-Term Effectiveness and Safety of Sirolimus Stent Implantation for Coronary In-Stent Restenosis: Results of the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry at 4 Years

Study Question: What is the long-term outcome of patients treated with a sirolimus-eluting stent (SES) for coronary in-stent restenosis?
Methods: The authors reported the 4-year results of the TRUE registry. This registry enrolled 244 patients undergoing SES implantation for bare-metal coronary stent restenosis at two Italian hospitals.
Results: The incidence of target lesion revascularization (TLR) at 9 months was 5%. At 4 years, all-cause mortality was 9.8% and cardiac mortality was 4.5%. Nonfatal myocardial infarction occurred in 3.2% and TLR in 11.1%. The cumulative event-free survival was 80%. Definite stent thrombosis occurred in five (2%) patients and possible stent thrombosis in another two (0.8%). Independent predictors of poor outcome were diabetes, renal dysfunction, and low ejection fraction.
Conclusions: SES for treatment of bare-metal stent restenosis is associated with reasonable long-term safety and efficacy.
Perspective: The incidence of clinically relevant bare-metal stent restenosis has dramatically declined due to wider use of drug-eluting stents. Drug-eluting stents have emerged as the dominant mode of therapy for bare-metal stent restenosis, although there have been concerns that this may be associated with a higher incidence of late stent thrombosis. This study adds to a growing evidence base supporting use of SES for this indication (Alfonso F, et al., J Am Coll Cardiol 2008;52:1621-7.). Further studies are warranted to confirm if other drug-eluting stents also provide similar safety and efficacy compared with SES. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Efficacy of High-Dose Atorvastatin Loading Before Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: The STATIN STEMI Trial
Topic: Interventional Cardiology
Date Posted: 3/30/2010
Author(s): Kim JS, Kim J, Choi D, et al., on behalf of the STATIN STEMI Investigators.
Citation: JACC Cardiovasc Interv 2010;3:332-9.
Clinical Trial: yes
Related Resources
JACC Cardiovasc Interv Article: Efficacy of High-Dose Atorvastatin Loading Before Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: The STATIN STEMI Trial
Trial: Efficacy of High-Dose Atorvastatin Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction (STATIN STEMI)

Study Question: What is the benefit of preprocedural high-dose statins in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI)?
Methods: The authors randomized 171 patients with STEMI to 80 mg atorvastatin (n = 86) or 10 mg atorvastatin (n = 85) arms for pretreatment before PCI. After PCI, both groups were treated with atorvastatin (10 mg). The primary endpoint was 30-day incidence of major adverse cardiac events (MACE) including death, nonfatal MI, and target vessel revascularization. Secondary endpoints included corrected Thrombolysis in Myocardial Infarction (TIMI) frame count, myocardial blush grade, and ST-segment resolution at 90 minutes after PCI.
Results: There was no difference in the primary endpoint, and MACE occurred in 5.9% versus 10.6% of patients in the 80 mg and 10 mg atorvastatin arms, respectively (p = 0.26). Corrected TIMI frame count was lower in the 80 mg atorvastatin arm (26.9 vs. 34.1, p = 0.01), and myocardial blush grade (2.2 vs. 1.9, p = 0.02) and ST-segment resolution (61.8 % vs. 50.6 %, p = 0.01) were better in the 80 mg atorvastatin arm.
Conclusions: High-dose atorvastatin pretreatment before PCI did not reduce MACE compared with low-dose atorvastatin, but was associated with an improvement in markers of myocardial perfusion after primary PCI.
Perspective: High-dose statins reduce reperfusion injury in animal models, and observational data suggest better outcome in patients with STEMI who are on chronic statin therapy. This trial failed to meet its primary endpoint, but it is unlikely that a reduction in hard events could be demonstrated in such a small trial. The improvement in markers of myocardial perfusion is encouraging, and further trials are needed to confirm these findings. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Nationwide Public-Access Defibrillation in Japan
Topic: Arrhythmias
Date Posted: 3/30/2010
Author(s): Kitamura T, Iwami T, Kawamura T, et al., on behalf of the Implementation Working Group for the All-Japan Utstein Registry of the Fire and Disaster Management Agency.
Citation: N Engl J Med 2010;362:994-1004.
Clinical Trial: No
Study Question: Do automatic external defibrillators (AEDs) improve survival in patients with out-of-hospital cardiac arrest (OHCA)?
Methods: The subjects of this study were 12,631 adults (mean age 64 years) with OHCA who were entered into a nationwide cardiac arrest registry in 2005-2007. During these 3 years, the number of public-access AEDs in Japan increased from 9,906 to 88,265. The 1° endpoint was survival at 1 month with minimal neurological impairment.
Results: The annual prevalence of bystander-initiated cardiopulmonary resuscitation (CPR) increased from 43.3% to 53.6% between 2005 and 2007, and the proportion of patients who received a shock from an AED increased from 1.2% to 6.2%. Survival at 1 month increased significantly from 10.6% in 2005 to 19.2% in 2007. Independent predictors of survival at 1 month included use of an AED (odds ratio [OR], 1.21) and time to first shock (OR, 0.91 per 1-minute increase).
Conclusions: An increase in public-access AEDs in Japan was associated with earlier defibrillation and an increase in survival at 1 month, with minimal neurological impairment in patients with OHCA.
Perspective: This is the first study to examine the potential impact of AEDs on outcomes after OHCA on a nationwide basis. Although the results are consistent with AEDs contributing to improved survival after OHCA, it is likely that other factors such as public education and an increase in bystander-initiated CPR also contributed. Fred Morady, M.D., F.A.C.C.

Title: Disparate Evolution of Right and Left Atrial Rate During Ablation of Long-Lasting Persistent Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 3/30/2010
Author(s): Hocini M, Nault I, Wright M, et al.
Citation: J Am Coll Cardiol 2010;55:1007-1016.
Clinical Trial: No
Related Resources
JACC Article: Disparate Evolution of Right and Left Atrial Rate During Ablation of Long-Lasting Persistent Atrial Fibrillation

Study Question: How are drivers in the right atrium (RA) recognized during radiofrequency catheter ablation (RFCA) of persistent atrial fibrillation (PsAF) in the left atrium (LA)?
Methods: RFCA in the LA was performed in 148 patients (mean age 58 years) with PsAF (mean duration 25 months). The AF cycle length (CL) in the LA appendage (LAA) and RA appendage (RAA) was monitored during RFCA. The endpoint of RFCA was termination of AF. RA ablation was performed if there was an RAA-LAA frequency gradient after RFCA in the LA.
Results: Sinus rhythm was restored by RFCA in 86% of patients. In 70% of patients, there was a left-right CL gradient and a parallel increase in LAA and RAA CLs during RFCA in the LA preceding AF termination. In 30% of patients, AF was not terminated by LA RFCA; in these patients, there was a right-left CL gradient and the RAA CL did not increase in parallel with the LAA CL. RFCA in the RA terminated AF in 55% of this group. Independent predictors of the need for RA RFCA included LAA CL ≤165 ms after LA RFCA and RAA CL ≤160 ms after LA RFCA. After a mean of 1.5 procedures/patient, 87% of patients were in sinus rhythm at a mean of 22 months of follow-up.
Conclusions: The failure of RAA CL to increase in parallel with the LAA CL during LA RFCA of PsAF identifies patients who require RA RFCA for termination of AF.
Perspective: The results suggest that the RA contains drivers of AF in approximately 20% of patients with PsAF. Fred Morady, M.D., F.A.C.C.

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Title: Usefulness of Exercise-Stress Echocardiography for Risk Stratification of True Asymptomatic Patients With Aortic Valve Stenosis
Topic: Noninvasive Cardiology
Date Posted: 3/29/2010
Author(s): Marйchaux S, Hachicha Z, Bellouin A, et al.
Citation: Eur Heart J 2010;Mar 21:[Epub ahead of print].
Clinical Trial: No
Study Question: Among asymptomatic patients with aortic stenosis (AS) with a normal response to exercise testing, does exercise stress echocardiography add incremental prognostic value to resting echocardiography?
Methods: A retrospective analysis was performed using data from 186 patients with at least moderate AS (valve area <1.5 cm2, indexed valve area <0.9 cm2/m2) and preserved left ventricular (LV) ejection fraction (≥50%) who underwent exercise stress echocardiography at one of four hospitals. Outcomes were cardiac death or aortic valve replacement (AVR) motivated by development of symptoms.
Results: There was an abnormal response to exercise in 51 (27%). Among the remaining 135 patients with a normal exercise test (53% with severe AS) at a mean follow-up of 20 ± 14 (median 19) months, a cardiac event occurred in 67 (AVR motivated by symptoms in 58, severe symptoms without AVR in four, symptoms awaiting AVR in one, cardiovascular death in three, and cardiac arrest followed by resuscitation and AVR in one). The variables independently associated with events were age ≥65 years (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.15-3.47; p = 0.01), diabetes (HR, 3.20; 95% CI, 1.33-6.87; p = 0.01), LV hypertrophy (HR, 1.96; 95% CI, 1.17-3.27; p = 0.01), resting mean gradient >35 mm Hg (HR, 3.60; 95% CI, 2.11-6.37; p < 0.0001), and exercise-induced increase in mean gradient >20 mm Hg (HR, 3.83; 95% CI, 2.16-6.67; p < 0.0001).
Conclusions: Exercise-induced increase in transvalvular gradient may be helpful to improve risk stratification in asymptomatic patients with AS and a normal exercise response. Exercise stress echocardiography may provide additional prognostic information over that obtained from standard exercise testing and resting echocardiography.
Perspective: Asymptomatic patients with severe AS traditionally are thought to have a low risk of adverse cardiac events, justifying a conservative philosophy of waiting for symptoms before considering AVR. However, it has become clear that not all asymptomatic patients are at the same low risk. Exercise testing (screening for the development of symptoms, hypotension, or complex ventricular arrhythmias) appears to offer incremental prognostic value. The present study suggests that an increase in AV gradient during exercise also might add incremental prognostic information. Notably, this study included roughly equal numbers of patients with moderate AS and with severe AS, and separate multivariate analyses revealed that an exercise-induced increase in gradient was strongly associated with risk in both categories. In addition, the authors observed that the increase in gradient during exercise did not correlate with resting gradient or any other resting echocardiographic variable. These findings serve to underscore some of the difficulties in determining the true hemodynamic impact of stenotic valve lesions, and the associated clinical challenges in treating patients with valvular heart disease. David S. Bach, M.D., F.A.C.C.

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Title: Physical Activity and Weight Gain Prevention
Topic: Prevention/Vascular
Date Posted: 3/31/2010
Author(s): Lee IM, Djousse L, Sesso HD, Wang L, Buring JE.
Citation: JAMA 2010;303:1173-1179.
Clinical Trial: No
Study Question: In 2008, federal guidelines recommended at least 150 minutes per week (7.5 metabolic equivalent [MET] hours per week) of moderate-intensity activity for “substantial health benefits.” What is the association of physical activity with long-term weight changes among women consuming a usual diet?
Methods: This prospective cohort study involved 34,079 healthy women participating in the Women’s Health Study from 1992-2007. At baseline and years 3, 6, 8, 10, 12, and 13, women reported their physical activity and body weight. Women were classified as expending <7.5, 7.5 to <21, and ≥21 MET hours per week of activity at each time. Repeated-measures regression prospectively examined physical activity and weight change over intervals averaging 3 years.
Results: At baseline, mean age was 54.2 years; about 50% of the women expended <7.5 MET hours per week; mean body mass index (BMI) was 26 kg/m2; 94% were white; and 40% were on hormone therapy. Mean (standard deviation) energy intake was similar between groups (~1725 [542] kcal/d). Women gained a mean of 2.6 kg throughout the study. A multivariate analysis comparing women expending ≥21 MET hours per week with those expending from 7.5 to <21 MET hours per week showed that the latter group gained a mean of 0.11 (0.04) kg (p = 0.003) over a mean interval of 3 years, and those expending <7.5 MET hours per week gained 0.12 (0.04) kg (p = 0.002). There was a significant interaction with BMI; an inverse dose-response relation between activity levels and weight gain among women with a BMI of <25 kg/m2 (p for trend < 0.001), but no relation among women with a BMI from 25-29.9 (p for trend = 0.56) or with a BMI of 30.0 kg/m2 or higher (p for trend = 0.50). A total of 4,540 women (13.3%) with a BMI lower than 25 kg/m2 at study start successfully maintained their weight by gaining <2.3 kg throughout. Their mean activity level over the study was 21.5 MET hours per week (~60 minutes a day of moderate-intensity activity).
Conclusions: Among women consuming a usual diet, physical activity was associated with less weight gain only among women whose BMI was lower than 25 kg/m2. Women successful in maintaining normal weight and gaining fewer than 2.3 kg over 13 years averaged approximately 60 minutes a day of moderate-intensity activity throughout the study.
Perspective: How many women 52 years of age would exercise 60 minutes a day in order to not gain more than 5 pounds over 13 years? One per 1,000? The authors had two posits, neither of which makes sense: 1) once overweight, it may be too late because physical activity is not associated with less weight gain; 2) sustaining high levels of physical activity (~60 minutes a day) is needed to successfully maintain normal BMI and prevent weight gain. While MET hours per week of activity is a reasonable way to estimate kcal/day of energy expenditure, over 95% of kcal of energy is expended at rest or during sleep. Weight gain in middle-aged men and women is highly related to increasing energy intake, which was not measured in these women. Adding the equivalent of one slice of bread per day (100 kcal) could on average result in ~10 pounds of weight gain in 1 year. The impact of supersizing and fast foods cannot be overcome by exercise. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Mipomersen, an Apolipoprotein B Synthesis Inhibitor, for Lowering of LDL Cholesterol Concentrations in Patients With Homozygous Familial Hypercholesterolaemia: A Randomised, Double-Blind, Placebo-Controlled Trial
Topic: Prevention/Vascular
Date Posted: 3/31/2010
Author(s): Raal FJ, Santos RD, Blom DJ, et al.
Citation: Lancet 2010;375:998-1006.
Clinical Trial: yes
Study Question: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder in which both low-density lipoprotein (LDL)-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. Is mipomersen, an anti-sense inhibitor of apolipoprotein (apo) B synthesis, as effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with HoFH?
Methods: A randomized, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics. Patients ages 12 years and older with clinical diagnosis or genetic confirmation of HoFH, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously or placebo weekly for 26 weeks. The primary endpoint was percentage change in LDL cholesterol concentration from baseline with analysis by intention to treat.
Results: Mean (standard deviation) age was 31 (12) years and seven were younger than 18 years old; 57% were women; 57% were true HoFH and 26% compound heterozygotes; 74% were on maximal statin dose + ezetimibe. Mean values for lipids were similar between groups: LDL cholesterol 425 mg/dl and apo B 270 mg/dl. Thirty-four patients were assigned to mipomersen and 17 to placebo. Forty-five patients completed the 26-week treatment period (28 mipomersen, 17 placebo). The mean percentage change in LDL-C was significantly greater with mipomersen (-24.7%, 95% confidence interval, -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p = 0.0003). The treatment effect of mipomersen on LDL cholesterol varied from -82% to +2% and with placebo varied from -30% to +40%. The most common adverse events were injection-site reactions (26 [76%] patients in the mipomersen group vs. four [24%] in the placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal.
Conclusions: Inhibition of apo B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous FH who are already receiving lipid-lowering drugs, including high-dose statins.
Perspective: The potential use of anti-sense oligonucleotides that inhibit protein synthesis by binding to mRNA is quite appealing for many conditions, particularly anti-apo B synthesis in FH where statins are limited in their ability to up-regulate LDL receptor activity. The 25% reduction in LDL cholesterol with mipomersen seems modest, but represents about a 100 mg/dl reduction. If mipomersen is safe, it has great potential in those refractory to statins, but more importantly those who are statin intolerant. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Loss of Pace Capture on the Ablation Line: A New Marker for Complete Radiofrequency Lesions to Achieve Pulmonary Vein Isolation
Topic: Arrhythmias
Date Posted: 4/2/2010
Author(s): Steven D, Reddy VY, Inada K, et al.
Citation: Heart Rhythm 2010;7:323-330.
Clinical Trial: No
Study Question: How useful is pacing on antral ablation lines for identifying target sites for pulmonary vein (PV) isolation?
Methods: Antral radiofrequency (RF) catheter ablation was performed in 30 patients (mean age 57 years) with paroxysmal atrial fibrillation. Ablation sites were tagged on an electroanatomical mapping system. A ring catheter was positioned in the PVs, but the operators were blinded to the electrogram recordings during ablation. Pacing was performed at 10 mA (2 ms pulse width) along the antral ablation line, and additional ablation was performed at sites of atrial capture until loss of capture was achieved along the entire ablation line. Bidirectional PV conduction block then was assessed with the ring catheter and by pacing within the PVs.
Results: Loss of capture along the entire antral ablation line was achieved for all pairs of ipsilateral PVs. Loss of pacing capture was associated with complete PV isolation by conventional criteria for 95% of ipsilateral PV pairs. Retrospective analysis of ring catheter recordings demonstrated that loss of capture along the antral ablation line required a mean of 10 additional RF applications beyond the point at which PV entrance block was achieved based on ring catheter electrograms.
Conclusions: Loss of pacing capture along antral ablation lines is a reliable indicator of PV isolation.
Perspective: The new technique described in this study has two advantages over existing endpoints for antral ablation to isolate the PVs: 1) only one catheter is required in the left atrium, and 2) loss of capture may be a more reliable indicator of complete conduction block than loss of PV potentials on a ring catheter. Fred Morady, M.D., F.A.C.C.

Title: Carotid Sinus Syndrome, Should We Pace? A Multicentre, Randomised Control Trial (Safepace 2)
Topic: Arrhythmias
Date Posted: 4/2/2010
Author(s): Ryan DJ, Nick S, Colette SM, Roseanne K.
Citation: Heart 2010;96:347-351.
Clinical Trial: yes
Study Question: Does pacing reduce falls in elderly patients with cardioinhibitory carotid sinus hypersensitivity (CICSH)?
Methods: The subjects of this study were 141 patients over the age of 65 years (mean age 78 years) who had a mean of approximately five falls in the prior year and ≥3 seconds of asystole during carotid sinus massage. They were randomly assigned to receive an implantable loop recorder (ILR, n = 71) or a dual-chamber pacemaker (n = 70). The 1° endpoint was the number of falls during 24 months of follow-up.
Results: The risk of falling during follow-up decreased by approximately 75% in both study groups. There was no significant difference in the number of falls during follow-up between the ILR and pacemaker groups. No episodes of asystole were recorded by the ILRs.
Conclusions: Pacing is of questionable value in elderly patients with falls and CICSH.
Perspective: The results dramatically demonstrate the nonspecific nature of a positive response to carotid sinus massage and also the placebo value of device implantation, even when the device is purely diagnostic. A prior single-center study (Safepace 1) reported that pacing did reduce the number of falling episodes in elderly patients with CICSH, but based on the results of this multicenter study, an ILR would seem more appropriate. Pacemaker implantation should be reserved for patients demonstrated to have symptomatic bradycardia or asystole. Fred Morady, M.D., F.A.C.C.

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Title: The Development of Heart Failure in Patients With Diabetes Mellitus and Pre-Clinical Diastolic Dysfunction: A Population-Based Study
Topic: Heart Failure/Transplant
Date Posted: 4/1/2010
Author(s): From AM, Scott CG, Chen HH.
Citation: J Am Coll Cardiol 2010;55:300-305.
Clinical Trial: No
Related Resources
JACC Article: The Development of Heart Failure in Patients with Diabetes Mellitus and Pre-Clinical Diastolic Dysfunction: A Population-Based Study

Study Question: What is the clinical outcome of diabetic patients with preclinical diastolic dysfunction (DD)?
Methods: Patients with diabetes mellitus (DM) who had evidence of DD, based on Doppler echocardiography [mitral valve inflow (E) to early annular velocity (e’); E/e’ >15], were identified from a database search. Data were collected retrospectively and tabulated for mortality, and development of congestive heart failure (CHF) and atrial fibrillation (AF). Patients with CHF predating the echocardiogram and those in whom CHF was diagnosed within 30 days of the echocardiogram were excluded from the analysis.
Results: A database search identified 12,014 subjects with DM, 2,770 of whom had Doppler assessment of DD. After excluding patients with valvular heart disease and a proximate diagnosis of CHF, 1,760 patients were included in the study, of whom 411 (23%) had E/e’ >15. Average follow-up was 2.9 ± 1.8 years. Patients with DD were older (67 ± 13 vs. 58 ± 14 years) and more often female (61% vs. 48%). Patients with DD had a higher prevalence of hypertension (91% vs. 84%), coronary artery disease (43% vs. 34%), larger left atrial volume (73 ± 25 vs. 60 ± 23 ml), and higher left ventricular mass index (107 ± 29 vs. 104 ± 23 g/m2) (all comparisons p < 0.001). For the population, E/e’ was 13 ± 6, and was 21 ± 6 in those with DD and 11 ± 3 in those without (p < 0.001). The probability of new CHF for patients with DD was 13.1% at 1 year and 36.9% at 5 years compared to 5.2% and 16.8% for those without DD (p < 0.001). The probability of death for diabetics with DD was 6.9% at 1 year and 30.8% at 5 years compared to 3.1% and 12.1% for those without DD (p < 0.001). At baseline, 1,450 patients were without a previous diagnosis of AF. AF subsequently developed in 6.8% of patients with DD at 1 year and 18.7% at 5 years compared to 2.1% and 8.8% for those without DD.
Conclusions: DD is present in 23% of patients with DM who did not have a proximate history of CHF, and is associated with a higher subsequent rate of CHF, higher mortality, and higher likelihood of AF.
Perspective: Previous studies have documented DD in patients with diabetes. This retrospective study demonstrates an association of DD with subsequent development of CHF, mortality, and AF. Multivariable analysis suggested that DD is an independent predictor of outcomes after adjusting for age, gender, hypertension, coronary disease, and other echocardiographic parameters, with a hazard ratio of 1.61. There are a number of limitations to this study including its retrospective nature and absence of data regarding the indication for the initial echocardiogram. Additionally, this was an overwhelmingly Caucasian population, and results may not be generalizable to the nonwhite population. Within the limits of retrospective study, patients with a previous diagnosis of CHF were excluded from the analysis; however, it is unclear what the indication of the echocardiogram was in a large number of presumably asymptomatic patients with diabetes. Additionally, the average E/e’ of 21 in the patients with DD suggests advanced DD with a high likelihood of markedly elevated left atrial pressures. The degree to which patients with a statistically high likelihood of markedly elevated left atrial pressures (>18 mm Hg) were truly asymptomatic requires further elucidation. This study would suggest that there is a substantial percentage of presumably asymptomatic patients (23%) with diabetes who have occult (or possibly impending) CHF. Whether aggressive approaches to hypertension and diabetes control would mitigate the development of subsequent AF, heart failure, and death would need to be prospectively evaluated. William F. Armstrong, M.D., F.A.C.C

Title: Risk and Fate of Cerebral Embolism After Transfemoral Aortic Valve Implantation: A Prospective Pilot Study With Diffusion-Weighted Magnetic Resonance Imaging
Topic: Cardiovascular Surgery
Date Posted: 4/1/2010
Author(s): Ghanem A, Mьller A, Nдhle CP, et al.
Citation: J Am Coll Cardiol 2010;55:1427-1432.
Clinical Trial: No
Related Resources
JACC Article: Risk and Fate of Cerebral Embolism After Transfemoral Aortic Valve Implantation: A Prospective Pilot Study With Diffusion-Weighted Magnetic Resonance Imaging

Study Question: What are the implications of silent and clinically apparent cerebral embolic events and neurological impairment after transfemoral aortic valve implantation (TAVI)?
Methods: Cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) was performed before, directly, and 3 months after TAVI with the current third-generation self-expanding CoreValve (Medtronic, Minneapolis, MN) prosthesis. At the timepoints of the serial MRI studies, focal neurological impairment was assessed according to the National Institutes of Health Stroke Scale (NIHSS), and serum concentration of neuron-specific enolase (NSE), a marker of the volume of brain tissue involved in an ischemic event, were determined. Association between frequency of embolic events and continuous variables was examined by Spearman's correlation.
Results: Thirty patients were enrolled; 22 completed the imaging protocol. Three patients (10%) had new neurological findings after TAVI, of whom only one (3.6%) had a permanent neurological impairment. Of the 22 TAVI patients with complete imaging data, 16 (72.7%) had 75 new cerebral lesions after TAVI presumed to be embolic. The NIHSS and NSE were not correlated with DW-MRI lesions.
Conclusions: The authors concluded that the incidence of clinically silent peri-interventional cerebral embolic lesions after TAVI is high.
Perspective: The current study suggests that the incidence of clinically silent peri-interventional cerebral embolic lesions after TAVI is high, but the incidence of persistent neurological impairment was quite low. The knowledge about silent TAVI-related cerebral embolism should highlight the importance of the careful management of peri-interventional anticoagulation in patients undergoing TAVI. Additional studies with longer-term clinical follow-up are indicated to understand the implications of the high rate of cerebral embolism with this procedure. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Identifying Patients at High Risk of a Cardiovascular Event in the Near Future: Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group
Topic: General Cardiology
Date Posted: 4/1/2010
Author(s): Eagle KA, Ginsburg GS, Musunuru K, et al.
Citation: Circulation 2010;121;1447-1454.
Clinical Trial: No
Perspective: Coronary artery disease is a complex process arising from the interplay of genetic variations, fluctuations in protein expression and activity, and environmental exposures. Thus, individuals with coronary artery disease may likely have differing manifestations of their disease despite having similar clinical phenotypes of atherosclerotic plaque and/or myocardial infarction. It is possible that future research on inflammation, endothelium, thrombosis, myocardium, environmental triggers, and psychosocial factors; imaging tests; and studies on genomics, proteomics, and gene expression will ultimately help unravel the complexity of coronary artery disease sufficiently to provide information on the risk of events for an individual patient. This in turn will help guide more precise and targeted therapies aimed at the particular individual. This working group recognized the need for comprehensive, integrative methods of analysis that will evaluate and assess the combined prognostic implications of these data to refine and fine-tune near-term risk assessment and ultimately guide optimal therapies for the individual patient. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Impact of Delay to Angioplasty in Patients With Acute Coronary Syndromes Undergoing Invasive Management: Analysis From the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial
Topic: Interventional Cardiology
Date Posted: 3/29/2010 5:00:00 PM
Author(s): Sorajja P, Gersh BJ, Cox DA, et al.
Citation: J Am Coll Cardiol 2010;55:1416-1424.
Clinical Trial: No
Related Resources
JACC Article: Impact of Delay to Angioplasty in Patients With Acute Coronary Syndromes Undergoing Invasive Management: Analysis From the ACUITY Trial
Trial: Acute Catheterization and Urgent Intervention Triage Strategy Trial (ACUITY )

Study Question: What is the impact of delay to angioplasty in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS)?
Methods: The authors assessed the impact of time to percutaneous coronary intervention (PCI) in patients enrolled in the ACUITY trials by categorizing them into those that underwent PCI <8 hours, 8-24 hours, and >24 hours after presentation.
Results: The study cohort was comprised of 7,749 patients who underwent PCI at a median of 19.5 hours after presentation. A total of 2,197 patients underwent PCI within 8 hours of presentation, 2,740 between 8-24 hours, and 2,812 underwent PCI >24 hours after presentation. PCI after >24 hours of presentation was associated with increased 30-day mortality (0.8%, 0.5%, and 1.7%), myocardial infarction (4.9%, 5.6%, and 8.0%), and composite of death, myocardial infarction, and unplanned revascularization (7.9%, 7.9%, and 10.4%). After adjusting for baseline differences, delay to PCI of >24 hours was a significant independent predictor of 30-day and 1-year mortality.
Conclusions: A delay from admission to PCI >24 hours in patients with NSTE-ACS was an independent predictor of early and late mortality and adverse ischemic outcomes.
Perspective: While an early invasive therapy is considered the preferred management strategy in patients with NSTE-ACS, how early is early enough is still debatable. Although this study suggests that the best outcome is seen in those who underwent PCI between 8-24 hours after admission, it is not clear if the difference in outcome was purely due to the delay to PCI or driven by factors that were responsible for the delay in PCI. The ABOARD study failed to detect a difference in outcome with immediate versus next day intervention (mean delay 21 hours), whereas the TIMACS trial suggested a benefit of early intervention (within 24 hours of presentation) in the highest risk patients. These data would suggest that it is probably best to time the intervention for the next working day in patients with NSTE-ACS. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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TAD Guidelines Address Catastrophic CV Disease
HF Patients Seem to Benefit from Clopidogrel
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Acute Myocardial Infarction Hospitalization in the United States, 1979 to 2005
Topic: General Cardiology
Date Posted: 4/5/2010
Author(s): Fang J, Alderman MH, Keenan NL, Ayala C.
Citation: Am J Med 2010;123:259-266.
Clinical Trial: No
Study Question: What are the trends in acute myocardial infarction (AMI) hospitalization rates for 27 years, from 1979 to 2005?
Methods: The investigators determined hospitalization rates for AMI by age and gender using data from the National Hospital Discharge Survey and US civilian population from 1979 to 2005, aggregated by 3-year groupings. They also assessed comorbid, complications, cardiac procedure use, and in-hospital case-fatality rates.
Results: Age-adjusted hospitalization rate for AMI identified by primary International Classification of Diseases code was 215 per 100,000 people in 1979-1981 and increased to 342 in 1985-1987. Thereafter, the rate stabilized for the next decade and then declined slowly after 1996 to 242 in 2003-2005. Trends were similar for men and women, although rates for men were almost twice that of women. Hospitalization rates increased substantially with age and were the highest among those ages 85 years or more. Although median hospital stay decreased from 12 to 4 days, intensity of hospital care increased, including use of coronary angioplasty, coronary bypass, and thrombolytics therapy. During the period, reported comorbidity from diabetes and hypertension increased. AMI complicated by heart failure increased, and cardiogenic shock decreased. Altogether, the in-hospital case-fatality rate declined.
Conclusions: The authors concluded that during the past quarter century, hospitalization for AMI increased until the mid-1990s, but has declined since then.
Perspective: This analysis suggests that during the past quarter century, hospitalization for AMI has only begun to decline more recently. At the same time, there has been a trend toward more intensive acute care and vastly expanded use of invasive procedures. The changes in AMI observed can be attributed to multiple factors, including change in incidence rates and reduction in risk of death before hospitalization, changing diagnostic criteria of MI, hospital treatment, and data-collection methods. The use of more sensitive biomarkers has probably contributed significantly to the increased diagnosis of MI in recent years. It is reassuring that in-hospital case-fatality rates have declined steadily, but we need to continue to be vigilant about providing optimal secondary preventative therapies to patients presenting with an MI. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Assessment of Radiofrequency Ablation Lesions by CMR Imaging After Ablation of Idiopathic Ventricular Arrhythmias
Topic: Noninvasive Cardiology
Date Posted: 4/5/2010
Author(s): Ilg K, Baman TS, Gupta SK, et al.
Citation: JACC Cardiovasc Imaging 2010;3:278-285.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Assessment of Radiofrequency Ablation Lesions by CMR Imaging After Ablation of Idiopathic Ventricular Arrhythmias

Study Question: How useful is cardiac magnetic resonance imaging (CMR) with delayed enhancement for assessing the lesions created by radiofrequency (RF) ablation of idiopathic ventricular tachycardia (VT) and premature ventricular complexes (PVCs)?
Methods: In a consecutive series of 35 patients (19 women, ages 48 ± 15 years, ejection fraction 0.56 ± 0.12) without structural heart disease who were referred for ablation of ventricular arrhythmias, CMR with delayed enhancement was performed before and after ablation. Ablation lesions were sought in the post-ablation CMR images. The endocardial area, depth, and volume of the lesions were measured. Lesion size was correlated with the type of ablation catheter used and the duration of RF energy delivered.
Results: In 25 of 35 patients (71%), ablation lesions were identified by delayed enhancement a mean of 22 ± 12 months after the initial ablation procedure. The mean lesion volume was 1.4 ± 1.4 cm3, with a mean endocardial area of 3.5 ± 3.0 cm2. The largest lesions (mean volume of 2.9 ± 2.1 cm3 with an endocardial area of 6.4 ± 3.4 cm2) were identified in patients in whom the arrhythmias originated in the papillary muscles. Ablation duration correlated with lesion size (r = 0.67, p < 0.001). There was no difference in lesion volume with irrigated versus nonirrigated ablation catheters (1.0 ± 0.73 vs. 2.0 ± 2.1 cm3, p = 0.09). Identification of ablation lesions in patients with a failed procedure identified the sites where ineffective RF energy lesions were created.
Conclusions: The authors concluded that RF ablation lesions can be detected long-term after an ablation procedure targeting ventricular arrhythmias in patients without previous infarction.
Perspective: This study suggests that ablation lesions that target idiopathic ventricular arrhythmias often result in scars that are apparent by CMR. A larger patient population is required to allow confirmation of the initial observations described in this study with regard to the lesion sizes created by different types of ablation catheters. In the future, real-time CMR guidance of VT ablation may provide the electrophysiologist with live information regarding the underlying scar substrate, and allow more precise treatment of lesions and optimal use of catheters. Such integration of CMR technology will also likely improve the safety and efficacy of VT ablation procedures. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Heart Failure Symptom Assessment and Management: Can Caregivers Serve as Proxy?
Topic: Heart Failure/Transplant
Date Posted: 4/5/2010
Author(s): Quinn C, Dunbar SB, Higgins M.
Citation: J Cardiovasc Nurs 2010;25:142-148.
Clinical Trial: No
Study Question: What is the degree of congruence between heart failure (HF) patients and their primary caregivers on symptom assessment and self-care management behaviors?
Methods: Seventy HF patients (primarily between 40 and 85 years of age) receiving home health care and their designated caregivers (CGs) were studied. Caregivers were predominately female (76%) and spouses (43%). Congruence in symptom assessment and management between HF patients and their designated CGs was measured in this descriptive cross-sectional study using the Heart Failure Symptom Survey and Self-care of Heart Failure Index.
Results: The Spearman correlation coefficient and concordance correlation coefficient were used to assess the degree of congruence on symptom evaluation scores from the Heart Failure Symptom Survey. Strongest correlations were seen on ratings of the HF patients’ symptoms of extremity edema, difficulty concentrating, and dizziness. Lower congruence (Spearman correlation <0.40) was found on feeling depressed, shortness of breath at night, and shortness of breath when lying down. Scores on the Self-care of Heart Failure Index self-care management and self-care confidence scales were not significantly different within the HF dyads.
Conclusions: The CG appears to be a reasonable substitute for patient responses in a community setting, based on moderate levels of correlations on most HF symptoms in this study. Symptoms for which there were higher levels of congruence include extremity edema, difficulty concentrating, and dizziness. Shortness of breath at night or while lying down, worsening cough, and bloated abdomen are more difficult for the CG to recognize.
Perspective: This is the first study to specifically examine congruence in symptom assessment with HF/CG dyads. Further studies are needed to explore the CG’s recognition of subtle symptoms of HF and how this affects HF patient outcomes. CG symptom assessment must include the subtle signs of HF that may not be easily recognized by another. Enhanced patient/CG education in this regard may be helpful in future symptom assessment. Suzanne Hughes, MSN, RN

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Title: Using Care Bundles to Reduce In-Hospital Mortality: Quantitative Survey
Topic: General Cardiology
Date Posted: 4/6/2010
Author(s): Robb E, Jarman B, Suntharalingam G, Higgens C, Tennant R, Elcock K.
Citation: BMJ 2010;340:c1234.
Clinical Trial: No
Study Question: What is the effect of care bundles targeted to the diagnoses responsible for the largest number of deaths on hospital inpatient mortality?
Methods: Eight care bundles of treatments known to be effective in reducing in-hospital mortality were used in the intervention year; adjusted mortality (from hospital episode statistics) was compared to the preceding year for the 13 diagnoses targeted by the intervention care bundles, 43 nontargeted diagnoses, and overall mortality for the 56 hospital standardized mortality ratio (HSMR) diagnoses covering 80% of hospital deaths. The institute defined a care bundle as “a collection of processes needed to effectively and safely care for patients undergoing particular treatments with inherent risks. Several interventions are ‘bundled’ together and, when combined, significantly improve patient care outcomes.” Change in adjusted mortality in targeted and nontargeted diagnostic groups and HSMR during the intervention year compared with the preceding year were the key measures of improvement.
Results: The standardized mortality ratio (SMR) of the targeted diagnoses and the HSMR both showed significant reductions, and the nontargeted diagnoses showed a slight reduction. Cumulative sum charts showed significant reductions of SMRs in 11 of the 13 diagnoses targeted in the year of the quality improvements, compared with the preceding year. The HSMR of the trust fell from 89.6 in 2006-7 to 71.1 in 2007-8 to become the lowest among acute trusts in England. Two hundred fifty-five fewer deaths occurred in the trust (174 of these in the targeted diagnoses) in 2007-8 for the HSMR diagnoses than if the 2006-7 HSMR had been applicable. From 2006-7 to 2007-8, there was a 5.7% increase in admissions, 7.9% increase in expected deaths, and 14.5% decrease in actual deaths.
Conclusions: The authors concluded that implementing care bundles can lead to reductions in death rates in the clinical diagnostic areas targeted and in the overall hospital mortality rate.
Perspective: The current study reports the results of implementing care bundles (guidelines for effective and safe patient care) targeted on reducing mortality in several diagnostic areas with a high numbers of deaths. Significant reductions in targeted disease and overall mortality were noted with these efforts. Prior initiatives in other countries using standardized orders and care protocols have also led to reduced mortality. The methods described in this study, of determining the main causes of death in a hospital and then using methods of treatment (care bundles) developed from evidence of their effectiveness to reduce mortality in the targeted diagnostic areas, could be applied to hospitals globally with improved outcomes. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Chocolate Consumption in Relation to Blood Pressure and Risk of Cardiovascular Disease in German Adults
Topic: Prevention/Vascular
Date Posted: 4/6/2010
Author(s): Buijsse B, Weikert C, Drogan D, Bergmann M, Boeing H.
Citation: Eur Heart J 2010;Mar 30:[Epub ahead of print].
Clinical Trial: No
Study Question: Does chocolate consumption decrease both blood pressure and incidence of cardiovascular disease (CVD)?
Methods: Data from the participants of the Postdam arm of the European Prospective Investigation into Cancer and Nutrition study were used for this analysis. Participants were from the general population of Postdam, Germany and its surroundings. Men and women took part in a baseline (1994-98) assessment, which included a food-frequency questionnaire, blood pressure measurement, anthropometric measures, sociodemographic factors, and lifestyle characteristics. Follow-up continued every 2-3 years (response rates ranged from 90-96%). Participants were excluded if a history of CVD was present at baseline. Additional exclusion criteria included use of antihypertensive medications (at baseline), missing information on blood pressure, diet, or the outcomes of interest (stroke and myocardial infarction [MI]). Cases of CVD (stroke and MI) were identified by self-report with verification through medical records.
Results: A total of 10,904 men (ages 40-65 years) and 16,644 women (ages 35-65 years) were included in the study. During the mean follow-up of 8 years, 166 cases of MI and 136 cases of stroke occurred. The top quartile of chocolate consumption included 8.1% of the cohort who consumed approximately 6 g/day more of chocolate compared to those in the bottom quartile. After controlling for age, sex, lifestyle factors, anthropometrics, diet, and prevalence of diabetes, chocolate consumption appeared protective for CVD (relative risk [RR], 0.61; 95% confidence interval [CI], 0.44-0.87). This relationship appeared stronger for stroke, with those in the top quartile for chocolate consumption having less risk (RR, 0.52; 95% CI, 0.30-0.89), as compared to those in the bottom quartile. For MI, the association was nonsignificant (RR, 0.73; 95% CI, 0.47-1.15). Mean systolic blood pressure was lower in the same group, 1.0 mm Hg (95% CI, -1.6 to -0.04 mm Hg) and mean diastolic was also lower, 0.9 mm Hg (95% CI, -1.13 to -0.5 mm Hg). Baseline blood pressure explained 12% of the lower risk.
Conclusions: The investigators concluded that chocolate consumption lowered blood pressure and risk of CVD, with a stronger association for stroke than for MI.
Perspective: This report adds to a growing body of literature related to chocolate and CVD health. Limitations of this particular study include the lack of information on the types of chocolate consumed such as dark chocolate. Further research related to specific components of chocolate would add to the information provided in this study. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: ACCF/ACR/AHA/ASNC/NASCI/SAIP/SCAI/SCCT 2010 Expert Consensus Document on Coronary Computed Tomographic Angiography: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents
Topic: Noninvasive Cardiology
Date Posted: 4/7/2010
Author(s): Mark DB, Berman DS, Budoff MJ, et al.
Citation: J Am Coll Cardiol 2010;Mar 1:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember about coronary computed tomographic angiography (CTA).

1. This document presents an expert consensus overview of the current and emerging clinical uses of coronary CTA in patients with suspected or known coronary artery disease.

2. Multidetector CT (MDCT) technology prior to 64-channel or “slice” systems should now be considered inadequate for cardiac imaging (except for studies limited to assessing coronary calcium).

3. As with any diagnostic technology, coronary CTA has technical limitations with which users should be familiar, and proper patient selection and preparation are important to maximize the diagnostic accuracy of the test.

4. Overall sensitivity and specificity of 64-channel coronary CTA compared with invasive coronary angiography on a per-patient basis are both high, and the number of indeterminate studies due to inability to image important coronary segments in the select cohorts represented is <5%.

5. In the context of the emergency department evaluation of patients with acute chest discomfort, currently available data suggest that coronary CTA may be useful in the evaluation of patients presenting with an acute coronary syndrome (ACS) who do not have either acute electrocardiogram changes or positive cardiac markers.

6. At heart rates between 55 and 65 bpm, current 64-channel CT provides sufficient cine frame rates to provide left ventricular function information with accuracy comparable to other noninvasive and invasive modalities.

7. The evaluation of stents by MDCT is significantly more difficult than the evaluation of coronary artery segments without stents, even using current generation 64-channel MDCT scanners. In clinical studies, stent size was an important determinant of the results, with 100% of ≥3.5 mm, 80% of 3 mm, and 33% of <3 mm stents being judged assessable.

8. To date, there are no published trials evaluating the impact of specific therapy on clinical outcome in asymptomatic subjects identified as having only noncalcified atheroma by coronary CTA.

9. Routine use of a “triple rule-out” CT scan for ACS, acute aortic syndrome, and pulmonary embolism should not be used as a substitute for a careful clinical evaluation, with targeted testing for the most likely causes of the patient’s symptoms.

10. The typical doses of radiation reported to be associated with coronary CTA exceed those reported for invasive coronary angiography. Close monitoring of radiation exposure administered to patients is necessary to weigh the benefits of this noninvasive test and potential future unintended consequences and costs. Debabrata Mukherjee, M.D., F.A.C.C., Christopher P. Cannon, M.D., F.A.C.C.

Title: Mortality in Adult Congenital Heart Disease
Topic: Congenital Heart Disease
Date Posted: 4/7/2010
Author(s): Verheugt CL, Uiterwaal CS, van der Velde ET, et al.
Citation: Eur Heart J 2010;Mar 5:[Epub ahead of print].
Clinical Trial: No
Study Question: What are the mortality rates, modes of death, and risk factors for mortality in adults with congenital heart disease?
Methods: The Dutch CONCOR (CONgenital CORvitia) national registry was used and linked to the national mortality registry. The goal of the CONCOR registry is to facilitate the study of outcomes of patients with congenital heart disease. Between November 2001 and December 2009, over 11,400 patients greater than age 18 have been recruited into the database.
Results: Of 6,933 adults with congenital heart disease, 197 (2.8%) died during a follow-up of 24,865 patient-years. Excess mortality was seen in patients with congenital heart disease, particularly in the young. Median age of death was 48.8 years, with 77% dying of cardiovascular causes. The most common causes of death included chronic heart failure (26%) and sudden death (19%). Predictors of mortality included age, severity of defect, number of interventions, and number of complications. Complications particularly associated with increased risk included endocarditis, supraventricular arrhythmias, ventricular arrhythmias, conduction disturbances, myocardial infarction, and pulmonary hypertension (hazard ratio range, 1.4-3.1; p < 0.05).
Conclusions: Mortality is increased in adults with congenital heart disease, with the majority of deaths due to cardiovascular causes. Mortality is increased by the presence of various known complications of congenital heart disease.
Perspective: Knowledge of the risk factors for and causes of mortality in adults with congenital heart disease is important to developing risk-reducing management strategies. The Dutch CONCOR database has become an important tool in assessing outcomes for adults with congenital heart disease. It is imperative that other countries follow suit. Recent health care legislation adopted in the United States includes provisions for the development of a national registry for patients with congenital heart disease. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Cognitive Deficits in Chronic Heart Failure
Topic: Heart Failure/Transplant
Date Posted: 4/7/2010
Author(s): Pressler SJ, Subramanian U, Kareken D, et al.
Citation: Nurs Res 2010;59:127-39.
Clinical Trial: No
Study Question: What are the types, frequency, and severity of cognitive deficits among patients with chronic heart failure (HF)? How are HF severity, age, and comorbidities related to these cognitive defects?
Methods: A sample of 414 participants completed the study (249 HF patients; 63 healthy and 102 medical participants). The HF patients completed measures of HF severity, comorbidity (multiple comorbidity, depressive symptoms), and neuropsychological functioning. Blood pressure and oxygen saturation were assessed at interview; clinical variables were abstracted from records. Participants in the comparison groups completed the same measures as the HF patients except those specific to HF.
Results: Compared with the healthy and medical participants, HF patients had poorer memory, psychomotor speed, and executive function. Significantly more HF patients (24%) had deficits in three or more domains. Higher (worse) HF severity was associated with more cognitive deficits; HF severity interacted with age to explain deficits in executive function. Surprisingly, men with HF had poorer memory, psychomotor speed, and visuospatial recall ability than women. Multiple comorbidity, hypertension, depressive symptoms, and medications were not associated with cognitive deficits in this sample.
Conclusions: HF results in losses of memory, psychomotor speed, and executive function in almost one fourth of patients. Patients with more severe HF are at risk for cognitive deficits. Older patients with more severe HF may have more problems in executive function, and men with HF may be at increased risk for cognitive deficits.
Perspective: The authors call for more studies designed to identify the mechanisms for the cognitive deficits observed in HF patients and to test innovative interventions to prevent cognitive decline. It is generally held that 25-50% of HF patients experience cognitive decline. HF patients and their families/caregivers are required to follow increasingly complex evidence-based regimens. This study and others raise issues around the impact of these cognitive deficits on self-care management and adherence to therapies. Suzanne Hughes, MSN, RN

Title: Quality of Care Among Obese Patients
Topic: General Cardiology
Date Posted: 4/6/2010 4:00:00 PM
Author(s): Chang VW, Asch DA, Werner RM.
Citation: JAMA 2010;303:1274-1281.
Clinical Trial: No
Study Question: What is the effect of patient weight status on common outpatient quality measures?
Methods: Eight different performance measures were examined in two national-level patient populations: 1) Medicare beneficiaries (n = 36,122) using data from the Medicare Beneficiary Survey (1994-2006); and 2) recipients of care from the Veterans Health Administration (VHA) (n = 33,550) using data from an ongoing performance-evaluation program (2003-2004). Performance measures among eligible patients for diabetes care (eye examination, glycated hemoglobin [HbA1c] testing, and lipid screening), pneumococcal vaccination, influenza vaccination, screening mammography, colorectal cancer screening, and cervical cancer screening were the main outcome measures. Measures were based on a combination of administrative claims, survey, and chart review data.
Results: The investigators found no evidence that obese or overweight patients were less likely to receive recommended care relative to normal-weight patients. Moreover, success rates were marginally higher for obese and/or overweight patients on several measures. The most notable differentials were observed for recommended diabetes care among Medicare beneficiaries: comparing obese versus normal-weight patients with diabetes, obese patients were more likely to receive recommended care on lipid screening (72% vs. 65%; odds ratio, 1.37; 95% confidence interval, 1.09-1.73) and HbA1c testing (74% vs. 62%; odds ratio, 1.73; 95% confidence interval, 1.41-2.11). All analyses were adjusted for sociodemographic factors, health status, clinical complexity, and visit frequency.
Conclusions: The authors concluded that among samples of patients from the Medicare and VHA populations, there was no evidence across eight performance measures that obese or overweight patients received inferior care when compared with normal-weight patients.
Perspective: Given that the majority of US adults are already overweight or obese, it is vitally important to ensure that these patients receive equitable and effective treatment. In the current study, the authors found no evidence in two large and important US patient populations that obese and overweight patients receive lower quality of care than normal-weight patients on common preventive services. Although underlying success rates for these performance measures were generally high across the board, they were nowhere near 100% and more work needs to be done to improve compliance with performance measures in both obese and nonobese patients. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Vitamins C and E to Prevent Complications of Pregnancy-Associated Hypertension
Topic: Prevention/Vascular
Date Posted: 4/7/2010 4:00:00 PM
Author(s): Roberts JM, Myatt L, Spong CY, et al., on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
Citation: N Engl J Med 2010;362:1282-1291.
Clinical Trial: yes
Study Question: Do antioxidant vitamins (C and E) reduce the risks of adverse events related to pregnancy-associated hypertension?
Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial of pregnant women conducted between July 2003 and February 2008. Subjects were randomized to vitamin C (1000 mg) and vitamin E (400 IU) or placebo between the 9th and 16th week of pregnancy. All women were nulliparous and at low risk for pre-eclampsia. Women were excluded if a prior pregnancy had lasted greater than 19 weeks 6 days, they had elevated blood pressure (135 and/or 85 mm Hg or higher), proteinuria, used antihypertensive medications, or were taking vitamin C or E supplements. The primary outcome of interest was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death.
Results: A total of 10,154 women were included in the study. Outcomes were available for 9,969 women. There were no significant differences between the two groups for the outcomes evaluated including the primary outcome (relative risk, 1.07; 95% confidence interval, 0.91-1.25). Similar rates of pre-eclampsia were also observed (relative risk, 1.07; 95% confidence interval, 0.93-1.24). Rates of adverse perinatal outcomes did not differ between the two groups. Among women randomized at less than 13 weeks compared to those randomized after 13 weeks, no differences were observed between the two groups.
Conclusions: The investigators concluded that supplementation with vitamins C and E, started in the 9th to 16th week of pregnancy, did not reduce the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension among a low-risk cohort of women.
Perspective: These findings do not support the use of vitamin C or E supplementation for the prevention of adverse events related to pregnancy-related hypertension. Many questions remain unanswered, particularly regarding dosing and timing of supplements. However, further understanding regarding the pathophysiology related to pregnancy-associated hypertension is warranted prior to further studies of antioxidant vitamins. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Outcomes With Concurrent Use of Clopidogrel and Proton-Pump Inhibitors: A Cohort Study
Topic: General Cardiology
Date Posted: 4/8/2010
Author(s): Ray WA, Murray KT, Griffin MR, et al.
Citation: Ann Intern Med 2010;152:337-345.
Clinical Trial: No
Study Question: What are the clinical outcomes (gastrointestinal bleeding and cardiovascular [CV] events) in patients treated with both clopidogrel and proton pump inhibitors (PPIs)?
Methods: This was a retrospective cohort study of 20,596 patients (including 7,593 concurrent users of clopidogrel and PPIs) hospitalized between 1999 and 2005 for myocardial infarction, coronary artery revascularization, or unstable angina pectoris. Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious CV disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other CV death).
Results: Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50; 95% confidence interval, 0.39-0.65). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7-36.9) hospitalizations for gastroduodenal bleeding per 1,000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious CV disease was 0.99 (CI, 0.82-1.19) for the entire cohort and 1.01 (CI, 0.76-1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization.
Conclusions: The authors concluded that in patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with a reduced incidence of hospitalizations for gastroduodenal bleeding without an increase in serious CV events.
Perspective: Patients with CV disease on clopidogrel are commonly also treated with PPIs. Because some PPIs have been shown to inhibit activity of the enzyme responsible for biotransformation of clopidogrel, CYP2C19, concern has been raised that PPI coadministration may reduce the effectiveness of clopidogrel, resulting in increased CV events. This is particularly relevant in patients following stent placement, where clopidogrel is effective in reducing stent thrombosis. While some studies have shown this interaction is clinically significant, recent data from TRITON-TIMI 38 found no increased CV risk associated with PPI use. The current study also supports the concept that the benefits of PPI use in patients at risk of gastrointestinal bleeding outweigh potential adverse CV risks in patients on clopidogrel. Data from additional trials will be helpful to clarify CV risk estimates associated with concomitant PPI and clopidogrel use. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Food Price and Diet and Health Outcomes: 20 Years of the CARDIA Study
Topic: Prevention/Vascular
Date Posted: 4/9/2010
Author(s): Duffey KJ, Gordon-Larsen P, Shikany JM, Guilkey D, Jacobs DR Jr, Popkin BM.
Citation: Arch Intern Med 2010;170:420-426.
Clinical Trial: No
Related Resources
Trial: Coronary Artery Risk Development in Young Adults (CARDIA)

Study Question: Is there a relationship between food prices and individual intake of “healthy” versus “unhealthy” choices, and are there potential health benefits?
Methods: A 20-year longitudinal study included 12,123 respondent days from 5,115 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Associations between food price, dietary intake, overall energy intake, weight, and homeostatic model assessment insulin resistance (HOMA-IR) scores were assessed using conditional log-log and linear regression models.
Results: The real price (inflated to 2006 US dollars) of soda and pizza decreased over time. The largest percentage decrease was for soda, falling from $2.71 to $1.42 (48% decrease; the price of whole milk increased). During periods with a 10% increase in the price of soda or pizza, there was a -7.12% or -11.5% change in energy from these foods, respectively. A $1.00 increase in soda price was also associated with lower daily energy intake (-124 kcal), lower weight (-1.05 kg), and lower HOMA-IR score (-0.42); similar trends were observed for pizza. A $1.00 increase in the price of both soda and pizza was associated with greater changes in total energy intake (-181.49 kcal), body weight (-1.65 kg), and HOMA-IR (-0.45).
Conclusions: Policies aimed at altering the price of soda or away-from-home pizza may be effective mechanisms to steer US adults toward a more healthful diet and help reduce long-term weight gain or insulin levels over time.
Perspective: This type of data likely influenced government policy regarding availability of soda and pizza in schools, and of course would encourage use of taxation to address the fattening of America. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Evaluation of Bromocriptine in the Treatment of Acute Severe Peripartum Cardiomyopathy: A Proof-of-Concept Pilot Study
Topic: Heart Failure/Transplant
Date Posted: 4/9/2010
Author(s): Sliwa K, Blauwet L, Tibazarwa K, et al.
Citation: Circulation 2010;121:1465-1473.
Clinical Trial: No
Study Question: Does bromocriptine have beneficial effects in acute severe peripartum cardiomyopathy (PPCM)?
Methods: The investigators conducted a prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n = 10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n = 10). There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the two study groups. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n = 21) was studied as a secondary endpoint. The investigators performed blinded clinical, hemodynamic, and echocardiographic assessments at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4-6 weeks after diagnosis in PPCM-Br patients.
Results: The investigators found that PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27-58%; p = 0.012) compared with PPCM-Std patients (27-36%) at 6 months. One patient in the PPCM-Br group died compared with four patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n = 1, 10%) experienced the composite endpoint of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction ≤35% at 6 months compared with the PPCM-Std patients (n = 8, 80%; p = 0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival.
Conclusions: The investigators concluded that addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive.
Perspective: Prolactin, mainly its 16-kDa angiostatic and proapoptotic form, has been shown to be an factor in PPCM pathophysiology (Cell 2007;128:589-600 ). In animal models, blockade of prolactin with the dopamine-2D agonist, bromocriptine, prevents the onset of PPCM. Earlier reports have also shown bromocriptine to be effective in women with PPCM (J Am Coll Cardiol 2007;50:2354-2355). The findings of this study represent one more piece of evidence suggesting that bromocriptine is beneficial in PPCM. However, the natural history of PPCM is variable, and therefore, double-blind randomized studies are now needed to confirm the efficacy of this therapy in PPCM, a potentially life-threatening condition. Ragavendra R. Baliga, M.B.B.S.

Title: Drugs vs. Ablation for the Treatment of Atrial Fibrillation: The Evidence Supporting Catheter Ablation
Topic: Arrhythmias
Date Posted: 4/9/2010
Author(s): Nault I, Miyazaki S, Forclaz A, et al.
Citation: Eur Heart J 2010;Mar 23:[Epub ahead of print].
Clinical Trial: No
Study Question: Is radiofrequency catheter ablation (RFCA) more effective than antiarrhythmic drug therapy (ADT) for suppressing atrial fibrillation (AF)?
Methods: A systematic literature search yielded eight studies and two review articles that compared ADT and RFCA in patients with AF. The results of these studies were analyzed.
Results: A total of 763 patients participated in seven studies that directly compared ADT (n = 383) with RFCA (n = 380). Freedom from atrial arrhythmias was significantly higher with RFCA (79%) than with ADT (32%). In the four studies that were limited to patients with paroxysmal AF, the efficacy was 81% with RFCA and 29% with ADT. Large-scale surveys reported that the mortality rate of RFCA of AF is 0.1% and that the most common severe complications are pericardial tamponade (1.2%), cerebral thromboembolism (1%), and symptomatic pulmonary vein stenosis (0.6%).
Conclusions: RFCA is more effective than ADT for restoring and maintaining long-term sinus rhythm.
Perspective: Because of considerable variability in ablation strategy and the intensity of monitoring for asymptomatic AF during follow-up, pooling the results of published studies on the efficacy of RFCA is of questionable value. Furthermore, most patients recruited into these studies already had failed to respond to ADT with ≥1 agent, creating a bias against ADT. Despite these flaws, it does seem likely that RFCA is more effective than ADT for preventing AF. But this does not necessarily imply that RFCA should be first-line therapy for AF. Even if the efficacy of ADT is only about 30%, why not try ADT first and reserve an invasive procedure for patients who are not satisfied with their response to drug therapy? Fred Morady, M.D., F.A.C.C.

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Title: Determinants of Functional Recovery After Myocardial Infarction of Patients Treated With Bone Marrow-Derived Stem Cells After Thrombolytic Therapy
Topic: General Cardiology
Date Posted: 4/9/2010
Author(s): Miettinen JA, Ylitalo K, Hedberg P, et al.
Citation: Heart 2010;96:362-367.
Clinical Trial: No
Study Question: What factors are associated with functional recovery after myocardial infarction in patients treated with bone marrow-derived stem cells (BMC) following coronary reperfusion therapy?
Methods: Seventy-eight patients with ST-elevation MI (STEMI) were randomly assigned to receive either intracoronary BMC (n = 39) or placebo (n = 39) into the infarct-related artery 2-6 days following coronary reperfusion therapy. Efficacy of the BMC treatment was assessed by measurement of the change of global left ventricular ejection fraction (LVEF) from baseline to 6 months after STEMI. Various predefined variables (e.g., the levels of certain natriuretic peptides and inflammatory cytokines) were also analyzed as determinants of improvement in LVEF.
Results: In the BMC group, the most powerful determinant of the change in LVEF was the baseline LVEF (r = -0.58, p < 0.001). Patients with baseline LVEF at or below the median (≤62.5%) experienced a more marked improvement in LVEF (+12.7 ± 2.5 %units, p < 0.001) than those above the median (-0.8 ± 6.3 %units, p = 0.10). Elevated N-terminal probrain natriuretic peptide (p < 0.001) and N-terminal proatrial natriuretic peptide (p = 0.052) levels were also associated with improvement in LVEF in the BMC group, but not in the placebo group.
Conclusions: The global LVEF recovers most significantly after intracoronary infusion of BMC in patients with the most severe impairment of LVEF on admission. The baseline levels of natriuretic peptides are associated with LVEF recovery after BMC treatment.
Perspective: The effects of cell-based therapies on recovery of LV function following acute MI have been modest at best. The current study indicates that subgroups of MI patients may be more likely to benefit than others; in particular, those with the most myocardial damage may be most likely to benefit from this type of therapy. However, the LVEFs in this study following MI were relatively preserved. Additional studies with larger sample sizes and larger infarcts are needed to further evaluate this therapy. Daniel T. Eitzman, M.D., F.A.C.C.

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ARIC Study: C-IMT, Plaque and Risk Stratification
The Future of Antiarrhythmic Agents
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Atrial Fibrillation Is Independently Associated With Senile, Vascular, and Alzheimer’s Dementia
Topic: Arrhythmias
Date Posted: 4/12/2010
Author(s): Bunch TJ, Weiss JP, Crandall BG, et al.
Citation: Heart Rhythm 2010;7:433-437.
Clinical Trial: No
Study Question: Is atrial fibrillation associated with dementia?
Methods: Data from the Intermountain Heart Collaborative Study were used for the present analysis. Dementia was categorized into four groups: vascular, senile, Alzheimer’s, and nonspecific. Patients with pre-existing dementia or atrial fibrillation were excluded. Atrial fibrillation status was determined by a search of the hospital discharge summaries and the electrocardiographic database for all Intermountain Healthcare hospitals.
Results: Of the 37,025 consecutive patients (mean age 60.6 ± 17.9 years) included in the study, 10,161 developed atrial fibrillation, and 1,535 developed dementia over the 5-year follow-up period. Patients with dementia were older and had higher rates of hypertension, coronary artery disease, renal failure, heart failure, and prior strokes. Atrial fibrillation was independently associated with all dementia types, with the highest risk observed among those <70 years of age. Among subjects with dementia, those who had atrial fibrillation were at increased risk for death (hazard ratio [HR], 1.38; p = 0.01 for vascular dementia, HR, 1.41; p = 0.001 for senile dementia, HR, 1.44; p < 0.0001 for Alzheimer’s dementia, and HR, 1.38; p < 0.0001 for nonspecific dementia).
Conclusions: The authors concluded that atrial fibrillation was independently associated with all types of dementia, and the highest risk of Alzheimer’s dementia was in the younger subjects. In addition, the presence of atrial fibrillation in patients with dementia identified those at increased risk of death.
Perspective: These findings are clinically relevant in that they may assist providers in identification of patients that may require closer monitoring and support. However, a central question remains unanswered: Would maintenance of sinus rhythm reduce incident dementia? Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Dietary Glycemic Load and Index and Risk of Coronary Heart Disease in a Large Italian Cohort: The EPICOR Study
Topic: Prevention/Vascular
Date Posted: 4/13/2010
Author(s): Sieri S, Krogh V, Berrino F, et al.
Citation: Arch Intern Med 2010;170:640-647.
Clinical Trial: No
Study Question: Is glycemic load associated with increased risk of coronary heart disease (CHD)?
Methods: Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study’s Italian cohort were used for the present study. Subjects were excluded if they had a prior history of cardiovascular disease or diabetes, or if data were missing on diet or lifestyle factors. The primary outcome of interest was CHD, defined as the occurrence of acute myocardial infarction, acute coronary syndrome, or coronary revascularization during follow-up.
Results: A total of 47,749 subjects (32,578) were followed over a median of 7.9 years. CHD events were experienced in 158 men and 305 women. Women in the highest quartile for carbohydrate intake had a significantly greater risk for CHD compared to those in the lowest quartile (relative risk [RR], 2.0; 95% confidence interval [CI], 1.16-3.43). No such association was observed in men. Increasing carbohydrate intake from high-glycemic index foods was also associated with increased risk for CHD in women (RR, 1.68; 95% CI, 1.02-2.75), which was not observed with low-glycemic index foods. A similar observation was noted for high glycemic load (RR, 2.24; 95% CI, 1.26-3.98) also among the women subjects, but not observed in men subjects.
Conclusions: The investigators concluded that among this cohort of Italian men and women, high dietary glycemic load (and index) and carbohydrate intake was associated with CHD risk in women, but not men.
Perspective: It is surprising that high glycemic load and carbohydrate intake is associated with increased CHD risk in women, but not men. Understanding factors that may explain this possible gender difference is warranted. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Enhanced Depression Care for Patients With Acute Coronary Syndrome and Persistent Depression Symptoms: Coronary Psychosocial Evaluation Studies Randomized Controlled Trial
Topic: General Cardiology
Date Posted: 4/13/2010
Author(s): Davidson KW, Rieckmann N, Clemow L, et al.
Citation: Arch Intern Med 2010;170:600-608.
Clinical Trial: yes
Study Question: Does an enhanced depression treatment for patients after acute coronary syndrome (ACS) improve depressive symptoms and reduce adverse cardiac events?
Methods: This was a randomized controlled trial conducted from January 2005 through February 2008 with ACS patients from five hospitals. A 3-month observation period prior to randomization was used to identify patients with persistent depressive symptoms. Following this observation phase, a 6-month trial was conducted. Patients were randomized to the intervention, which included patient preference for problem-solving therapy and/or pharmacotherapy, followed by a stepped-care approach. The control group received usual care and a third group of nondepressed patients was used as an observational group. The primary outcome of interest was patient satisfaction with depression care. Secondary outcomes included change in depressive symptoms (measured with Beck Depression Inventory), major adverse cardiac events, and death.
Results: A total of 237 patients were enrolled (80 in the intervention group, 77 in the control group, and 80 in the observation group). The number of patients who reported being satisfied with the depression care received was higher in the intervention group compared to those in the control group (odds ratio, 5.4; 95% confidence interval, 2.2-12.9). The Beck Depression Inventory Score decreased more in the intervention group (change, -5.7 vs. -1.9). At the end of the trial, three patients in the intervention group experienced adverse cardiac events, as did 10 patients in the usual care group and five in the nondepressed group.
Conclusions: The investigators concluded that an enhanced treatment for depression among patients with ACS was associated with greater satisfaction with care, reduced depressive symptoms, and a trend toward reduced cardiac events.
Perspective: Depressive symptoms are frequently experienced by patients after ACS. Finding effective interventions for depression can only help improve overall cardiac care. These findings suggest that this enhanced program may be effective for treatment of depression. Larger-scale studies are needed to confirm and extend these results. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Feasibility of FDG Imaging of the Coronary Arteries: Comparison Between Acute Coronary Syndrome and Stable Angina
Topic: Noninvasive Cardiology
Date Posted: 4/12/2010 5:00:00 PM
Author(s): Rogers IS, Nasir K, Figueroa AL, et al.
Citation: JACC Cardiovasc Imaging 2010;3:388-397.
Clinical Trial: No
Related Resources
JACC Cardiovasc Img Article: Feasibility of FDG Imaging of the Coronary Arteries: Comparison Between Acute Coronary Syndrome and Stable Angina

Study Question: Is the presence of fluorodeoxyglucose (FDG) uptake within the ascending aorta and left main coronary artery (LM), measured using positron emission tomography (PET) a measure of plaque inflammation?
Methods: Twenty-five patients (10 acute coronary syndrome [ACS] and 15 stable coronary artery disease (CAD; STABLE) underwent cardiac computed tomographic angiography and PET imaging with 18-FDG after invasive angiography. Images were co-registered, and FDG uptake was measured at locations of interest for calculation of target-to-background ratios (TBRs). Additionally, FDG uptake was measured at the site of the lesion deemed clinically responsible for the presenting syndrome (culprit) by virtue of locating the stent deployed to treat the syndrome.
Results: Mean age was 57.9 ± 9.8 years and 72% were male; 20% of the ACS and 68% of the STABLE group had a history of CAD. The FDG uptake was higher in the ACS versus the STABLE groups in the ascending aorta (median TBR 3.30 vs. 2.43, p = 0.02), as well as the LM (2.48 vs. 2.00, p = 0.03). The TBR was greater for culprit lesions associated with ACS than for lesions stented for stable coronary syndromes (2.61 vs. 1.74, p = 0.02). Furthermore, the TBR in the stented lesions (in ACS and STABLE groups) correlated with C-reactive protein (r = 0.58, p = 0.04).
Conclusions: In patients with recent ACS, FDG accumulation is increased both within the culprit lesion as well as in the ascending aorta and LM. This observation provides evidence of up-regulation of activity within atherosclerotic plaques in ACS and supports intensification of efforts to refine PET methods to image coronary plaque inflammation.
Perspective: FDG PET imaging provides a measure of glycolysis, which is increased in inflamed tissues including atherosclerotic plaques. The finding of increased uptake in the left main and aorta in persons with ACS is consistent with pathologic studies and clinical observations that the presence of one or more unstable plaques probably identifies the ‘vulnerable patient.’ Melvyn Rubenfire, M.D., F.A.C.C.

Title: Proximal Endovascular Occlusion for Carotid Artery Stenting: Results From a Prospective Registry of 1,300 Patients
Topic: Interventional Cardiology
Date Posted: 4/12/2010 5:00:00 PM
Author(s): Stabile E, Salemme L, Sorropago G, et al.
Citation: J Am Coll Cardiol 2010;55:1661-1667.
Clinical Trial: No
Related Resources
JACC Article: Proximal Endovascular Occlusion for Carotid Artery Stenting: Results From a Prospective Registry of 1,300 Patients

Study Question: What is the outcome of unselected patients undergoing carotid artery stenting (CAS) using proximal endovascular occlusion (PEO)?
Methods: The authors reported the outcome of 1,300 patients who underwent CAS at a single Italian center using PEO. An independent neurological assessment was performed before the procedure and at 1 hour, 24 hours, and 30 days after the procedure.
Results: PEO was achieved using the MOMA device. The procedure was successful in all but four patients (procedural success 99.7%). The in-hospital complication rate was low and included five deaths (0.38%), six major strokes (0.46%), and five minor strokes (0.38%). There was no acute myocardial infarction. By 30 days of follow-up, there were two additional deaths and one patient had a minor stroke. The overall 30-day stroke and death incidence was 1.38% (n = 19) and was higher in the symptomatic patients compared with asymptomatic patients (30-day stroke and death 3.04% vs. 0.82%; p < 0.01). There was no significant difference in outcome of those at high surgical risk compared with those at average surgical risk. Independent predictors of adverse events were symptomatic status, operator experience, and hypertension.
Conclusions: CAS performed using PEO is safe and effective in an unselected patient population.
Perspective: CAS provides a similar long-term efficacy compared with CEA, but multiple studies have demonstrated a higher rate of procedural stroke with CAS. This study had one of the lowest rates of stroke described with CAS, and it would be important to evaluate if similar results can be reproduced across multiple centers. This study provides strong support for using PEO in patients undergoing CAS. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Survival After Application of Automatic External Defibrillators Before Arrival of the Emergency Medical System: Evaluation in the Resuscitation Outcomes Consortium Population of 21 Million
Topic: Arrhythmias
Date Posted: 4/12/2010 5:00:00 PM
Author(s): Weisfeldt ML, Sitlani CM, Ornato JP, et al., on behalf of the ROC Investigators.
Citation: J Am Coll Cardiol 2010;55:1713-1720.
Clinical Trial: No
Related Resources
JACC Article: Survival After Application of Automatic External Defibrillators Before Arrival of the Emergency Medical System: Evaluation in the Resuscitation Outcomes Consortium Population of 21 Million

Study Question: Does bystander use of an automatic external defibrillator (AED) improve survival after out-of-hospital cardiac arrest (OHCA)?
Methods: The subjects of this study were 13,769 patients (median age 67 years) with OHCA who were entered into a registry during a 17-month period in 2005-2007. The relationship between AED use and survival to hospital discharge was analyzed.
Results: An AED was used before arrival of emergency medical system (EMS) personnel in 289/13,769 patients (2.1%). Survival in the overall group was 7%, compared to 24% when an AED was applied before EMS arrival and 38% when an AED shock was delivered before EMS arrival. By multivariate analysis that accounted for multiple potential confounding variables, the use of an AED before EMS arrival significantly increased the odds of survival by 80%.
Conclusions: The use of community-based AEDs in patients with OHCA improves survival.
Perspective: Prior observational studies on the value of community-based AEDs have reported conflicting results, with some studies reporting no impact on survival of patients with OHCA. However, a prospective, randomized, community-based study (the PAD trial) reported a 2-fold improvement in survival with the use of AEDs. The 1.8-fold survival benefit with AEDs in the present study confirms the results of the PAD trial in a larger population of patients. These results emphasize the importance of both early defibrillation and public education programs to improve survival after OHCA. Fred Morady, M.D., F.A.C.C.

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Title: Contemporary Mortality Risk Prediction for Percutaneous Coronary Intervention: Results From 588,398 Procedures in the National Cardiovascular Data Registry
Topic: Interventional Cardiology
Date Posted: 4/14/2010
Author(s): Peterson ED, Dai D, DeLong ER, et al.
Citation: J Am Coll Cardiol 2010;Mar 31:[Epub ahead of print].
Clinical Trial: No
Related Resources
JACC Article: Contemporary Mortality Risk Prediction for Percutaneous Coronary Intervention: Results From 588,398 Procedures in the National Cardiovascular Data Registry

Study Question: What are the factors that predict mortality risk following percutaneous coronary intervention (PCI)?
Methods: Data from 181,775 procedures performed from January 2004 to March 2006 were used to develop risk models based on preprocedural and/or angiographic factors using logistic regression. These models were independently evaluated in two validation cohorts: contemporary (n = 121,183, January 2004 to March 2006) and prospective (n = 285,440, March 2006 to March 2007). Model discrimination and calibration were assessed in the overall population, within the two validation samples, and among select subpopulations of both of these groups.
Results: Overall, PCI in-hospital mortality was 1.27%, ranging from 0.65% in elective PCI to 4.81% in ST-segment elevation myocardial infarction patients. Multiple preprocedural clinical factors were significantly associated with in-hospital mortality. Angiographic variables provided only modest incremental information to preprocedural risk assessments. The overall National Cardiovascular Data Registry (NCDR) model, as well as a simplified NCDR risk score (based on eight key preprocedure factors), had excellent discrimination (c-index: 0.93 and 0.91, respectively). Discrimination and calibration of both risk tools were retained among specific patient subgroups, in the validation samples, and when used to estimate 30-day mortality rates among Medicare patients.
Conclusions: The authors concluded that risks for early mortality following PCI can be accurately predicted in contemporary practice.
Perspective: The authors used data from the NCDR CathPCI Registry, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions, and developed and validated contemporary models for assessing periprocedural PCI mortality risk. Each of these appear to have excellent predictive accuracy throughout the full spectrum of patient risk, and important patient subgroups. It is possible that these models will have multiple future applications including bedside risk estimation, comparison of hospital performance, and risk adjustment. Independent validation in other large PCI databases would provide additional support for clinical use of this model. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Effect of Noninsulin Antidiabetic Drugs Added to Metformin Therapy on Glycemic Control, Weight Gain, and Hypoglycemia in Type 2 Diabetes
Topic: Prevention/Vascular
Date Posted: 4/13/2010 4:00:00 PM
Author(s): Phung OJ, Scholle JM, Talwar M, Coleman CI.
Citation: JAMA 2010;303:1410-1418.
Clinical Trial: No
Study Question: What is the relative efficacy, risk of weight gain, and hypoglycemia associated with noninsulin antidiabetic drugs in patients with type 2 diabetes mellitus (DM) not controlled by metformin alone?
Methods: A literature search was conducted via MEDLINE and Cochrane CENTRAL through January 2010, as well as a manual search of references for additional relevant studies. Study selection included randomized controlled trials (RCTs) with at least 3 months’ duration, evaluating noninsulin antidiabetic drugs added to metformin in patients experiencing an inadequate response to maximized and stable (≥4 weeks at ≥1500 mg or maximally tolerated dose) metformin therapy. Mixed-treatment comparison meta-analysis was used to calculate the weighted mean difference for changes from baseline in glycosylated hemoglobin (HbA1c) and body weight and relative risk (RR) of HbA1c goal attainment and hypoglycemia.
Results: Overall, 27 RCTs (n = 11,198) were included. Mean (range) trial duration was 32 (12-52) weeks. The different classes of drugs were associated with similar HbA1c reductions (range, 0.64%-0.97%) compared with placebo. Although use of thiazolidinediones, sulfonylureas, and glinides were associated with weight gain (range, 1.77-2.08 kg), glucagon-like peptide-1 analogs, α-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were associated with weight loss or no weight change. Sulfonylureas and glinides were associated with higher rates of hypoglycemia than with placebo (RR range, 4.57-7.50).
Conclusions: When added to maximal metformin therapy, all noninsulin antidiabetic drugs were associated with similar HbA1c reductions, but differed in their associations with weight gain and risk of hypoglycemia.
Perspective: Weight gain and hypoglycemia are clearly important unintended consequences of hypoglycemic agents. The relative value of combining metformin with first and second generation hypoglycemics compared to the third and fourth generation agents, which are associated with weight loss and less hypoglycemia, needs to be assessed in clinical trials. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Health Care Insurance, Financial Concerns in Accessing Care, and Delays to Hospital Presentation in Acute Myocardial Infarction
Topic: General Cardiology
Date Posted: 4/13/2010 4:00:00 PM
Author(s): Smolderen KG, Spertus JA, Nallamothu BK.
Citation: JAMA 2010;303:1392-1400.
Clinical Trial: No
Study Question: What is the association between lack of health insurance and financial concerns about accessing care among those with health insurance, and the time from symptom onset to hospital presentation (prehospital delays) during acute myocardial infarction (AMI)?
Methods: This was a multicenter, prospective study using a registry of 3,721 AMI patients enrolled between April 2005, and December 2008, at 24 US hospitals. Health insurance status was categorized as: insured without financial concerns, insured but have financial concerns about accessing care, and uninsured. Insurance information was determined from medical records, while financial concerns among those with health insurance were determined from structured interviews. The primary outcome measure was prehospital delay times (≤2 hours, >2-6 hours, or >6 hours), adjusted for demographic, clinical, and social and psychological factors using hierarchical ordinal regression models.
Results: Of 3,721 patients, 2,294 were insured without financial concerns (61.7%), 689 were insured but had financial concerns about accessing care (18.5%), and 738 were uninsured (19.8%). Uninsured and insured patients with financial concerns were more likely to delay seeking care during AMI and had prehospital delays of greater than 6 hours among 48.6% of uninsured patients and 44.6% of insured patients with financial concerns compared with only 39.3% of insured patients without financial concerns. Prehospital delays of less than 2 hours during AMI occurred among 36.6% of those insured without financial concerns compared with 33.5% of insured patients with financial concerns and 27.5% of uninsured patients (p < 0.001). After adjusting for potential confounders, prehospital delays were associated with insured patients with financial concerns (adjusted odds ratio, 1.21; 95% confidence interval, 1.05-1.41; p = 0.01) and with uninsured patients (adjusted odds ratio, 1.38; 95% confidence interval, 1.17-1.63; p < 0.001).
Conclusions: The authors concluded that lack of health insurance and financial concerns about accessing care among those with health insurance were each associated with delays in seeking emergency care for AMI.
Perspective: The authors found that uninsured patients and insured patients with financial concerns about accessing medical treatment were more likely to delay seeking emergency care for AMI, a common presentation of coronary artery disease. These findings underscore important consequences from inadequate or absent health care insurance coverage for the substantial number of individuals in the United States experiencing AMIs. Efforts to reduce prehospital delays for AMI and other emergency conditions may have only limited benefit unless US health care insurance coverage is extended and improved. If financial concern about the cost of care can be eliminated or ameliorated, patients are more likely to present in a timely manner. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Remote Ischemic Conditioning Before Hospital Admission, as a Complement to Angioplasty, and Effect on Myocardial Salvage in Patients With Acute Myocardial Infarction: A Randomised Trial
Topic: Interventional Cardiology
Date Posted: 4/15/2010
Author(s): Bшtker HE, Kharbanda R, Schmidt MR, et al.
Citation: Lancet 2010;375:727-734.
Clinical Trial: yes
Study Question: Does remote ischemic conditioning, done before primary percutaneous coronary intervention (PPCI), increase myocardial salvage?
Methods: A total of 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerized block randomization to receive PPCI with (n = 166 patients) versus without (n = 167) remote conditioning (intermittent arm ischemia through four cycles of 5-minute inflation and 5-minute deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to the hospital, and PPCI in the hospital. The primary endpoint was myocardial salvage index at 30 days after PPCI, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol.
Results: Eighty-two patients were excluded on arrival at the hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (interquartile range, 0.50-0.93; n = 73) in the remote conditioning group versus 0.55 (0.35-0.88, n = 69) in the control group, with median difference of 0.10 (95% confidence interval [CI], 0.01-0.22; p = 0.0333); mean salvage index was 0.69 (standard deviation, 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI, 0.01-0.21; p = 0.0333). Major adverse coronary events were death (n = 3 per group), reinfarction (n = 1 per group), and heart failure (n = 3 per group).
Conclusions: The authors concluded that remote ischemic conditioning before hospital admission increases myocardial salvage, and has a favorable safety profile.
Perspective: The current study shows that remote ischemic conditioning induced by intermittent upper-arm ischemia and done before PPCI, can attenuate reperfusion injury in patients with evolving myocardial infarction, thereby resulting in increased myocardial salvage. This protective effect seemed to be strongest in patients with totally occluded vessels and with infarcts in the left anterior descending artery, both of which were associated with almost double the area at risk. The effectiveness of remote conditioning after onset of target-organ ischemia could have implications for myocardial infarction and stroke treated with thrombolytics, but needs to be tested in large-scale clinical trials. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Association Between Admission Supine Systolic Blood Pressure and 1-Year Mortality in Patients Admitted to the Intensive Care Unit for Acute Chest Pain
Topic: Prevention/Vascular
Date Posted: 4/14/2010
Author(s): Stenestrand U, Wijkman M, Fredrikson M, Nystrom FH.
Citation: JAMA 2010;303:1167-1172.
Clinical Trial: No
Study Question: What is the relation between long-term mortality and admission blood pressure (BP) in patients admitted to the medical intensive care unit (ICU) for acute chest pain?
Methods: The authors evaluated the RIKS-HIA (Registry of Information and Knowledge About Swedish Heart Intensive Care Admissions) to analyze the association between long-term mortality and supine admission systolic BP in 119,151 patients who were treated at any Swedish ICU for the symptom of chest pain from 1997 through 2007. Patients were divided into quartiles of systolic BP Q1, <128 mm Hg; Q2, from 128 to 144 mm Hg; Q3, from 145 to 162 mm Hg; and Q4, ≥163 mm Hg. The main outcome measure was all-cause mortality.
Results: Mean follow-up was 2.47 years. The highest mortality was seen in the first quartile and the lowest in the fourth quartile. After adjusting for age, sex, smoking, diastolic BP, use of antihypertensive medication at admission and discharge, and use of lipid-lowering and antiplatelet medication at discharge, patients in the fourth quartile had the lowest 1-year mortality compared with quartile 2 (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.72-0.80), while the hazard was worse in quartile 1 (HR, 1.46; 95% CI, 1.39-1.52) and intermediate for Q3 (HR, 0.83; 95% CI, 0.79-0.87). The better prognosis in Q4 compared with Q2 was maintained in patients with a final diagnosis of angina or myocardial infarction (HR, 0.75; 95% CI, 0.71-0.80).
Conclusions: A higher systolic BP at admission in patients admitted to the ICU is associated with a better long-term survival.
Perspective: The association between a higher BP and better short-term outcome in patients with chest pain has been previously established (Khot, JAMA 2003). This study suggests that this association is valid for intermediate-term mortality. While high BP may be of prognostic importance in large hospitalized populations, its direct implication for patient care is somewhat unclear. Poorly controlled hypertension remains a major public health problem, and the results of this study should not distract from the need to ensure optimal BP control in all patients. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Bupropion and Cognitive Behavioral Therapy for Weight-Concerned Women Smokers
Topic: Prevention/Vascular
Date Posted: 4/14/2010
Author(s): Levine MD, Perkins KA, Kalarchian MA, et al.
Citation: Arch Intern Med 2010;170:543-550.
Clinical Trial: yes
Study Question: Does a combination of bupropion and cognitive behavioral therapy enhance abstinence among weight-concerned women smokers?
Methods: This was a randomized double-blind placebo-controlled trial of women smokers who reported concern regarding weight gain, conducted between September 1999 and October 2005. All subjects, women between the ages of 18 and 65 years, expressed an interest in quitting smoking, smoked 10 or more cigarettes per day, and reported concerns about weight again after smoking cessation. All women received smoking cessation counseling. Subjects were randomized to one of two adjunctive counseling components, one of which was cognitive behavioral therapy, which included a focus on weight. Women were also randomized to bupropion or placebo for 6 months. The primary outcomes of interest were rates and duration of biochemically verified prolonged abstinence. Additional outcomes included point-prevalent abstinence, post-cessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns.
Results: A total of 349 women (86% white) were included in the study. Women in the cognitive behavioral therapy for smoking-related weight concerns plus bupropion group experienced higher rates of abstinence and longer time to relapse compared to those in the standard behavioral therapy plus bupropion group (34% vs. 21%, p = 0.05). At 12 months, rates of sustained abstinence did not differ between the two groups. For women receiving standard behavior therapy, women randomized to bupropion versus placebo, no differences in abstinence rates were observed at either 6 or 12 months. There were no significant differences in abstinent women in weight gain or weight concerns between the groups. Women randomized to standard behavioral therapy plus bupropion had greater decreases in nicotine withdrawal and depressive symptoms compared to women receiving standard behavioral therapy plus placebo.
Conclusions: The investigators concluded that among weight concerned women smokers, bupropion together with cognitive behavioral therapy, which included a focus on weight, was effective at sustained abstinence and was not associated with changes in weight postsmoking cessation.
Perspective: This study highlights the use of behavioral programs which meet the concerns of smokers. For women who may have concerns regarding possible weight gain with smoking cessation, a behavioral program that addresses such concerns makes sense. Combining therapy with pharmacologic agents such as bupropion appears to increase the rates of sustained abstinence, although abstinence rates at 12 months are not optimal, suggesting that further research on different frequencies or duration of counseling is needed. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Myeloperoxidase and C-Reactive Protein Have Combined Utility for Long-Term Prediction of Cardiovascular Mortality After Coronary Angiography
Topic: Prevention/Vascular
Date Posted: 4/14/2010
Author(s): Heslop CL, Frohlich JJ, Hill JS.
Citation: J Am Coll Cardiol 2010;55:1102-1109.
Clinical Trial: No
Related Resources
JACC Article: Myeloperoxidase and C-Reactive Protein Have Combined Utility for Long-Term Prediction of Cardiovascular Mortality After Coronary Angiography

Study Question: Do plasma levels of oxidative stress biomarkers predict cardiovascular (CV) mortality after coronary angiography?
Methods: Myeloperoxidase (MPO), nitrotyrosine, oxidized low-density lipoprotein, and antioxidant capacity were measured in a prospective cohort of 885 selective coronary angiography patients followed up for >13 years for CV mortality.
Results: MPO independently predicted coronary artery disease, and top tertile MPO levels predicted a 2.4-fold risk of CV mortality (95% confidence interval [CI], 1.47-2.98), compared with patients with lowest tertile MPO levels. MPO also improved risk model discrimination and patient risk category classification. Elevations in multiple oxidative stress biomarkers predicted increased mortality risk; however, the strongest risk prediction was achieved by assessing MPO and C-reactive protein (CRP) together. Patients with either MPO or CRP elevated had 5.3-fold higher CV mortality risk (95% CI, 1.86-14.9), and patients with high levels of both MPO and CRP had a 4.3-fold risk compared with patients with only elevated markers (95% CI, 2.26-8.31). These results remained significant, with adjustment for CV risk factors and baseline disease burden.
Conclusions: The authors concluded that MPO accurately predicted CV mortality risk in coronary angiography patients. Considering MPO and CRP together may improve long-term risk assessment and coronary artery disease patient outcomes.
Perspective: Atherosclerosis is a systemic, complex disorder, involving numerous biological pathways. Although targeting cholesterol metabolism with statin therapy has proved highly beneficial to the population at risk for complications of atherosclerosis, there remains residual risk, and additional biomarkers for risk stratifying patients and guiding existing and future treatment strategies are needed. Combinations of biomarkers reflecting different pathways involved in atherogenesis/plaque rupture may be particularly useful for assessing risk as demonstrated in this study; however, additional studies will be needed to determine clinical usefulness. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: S38G Single-Nucleotide Polymorphism at the KCNE1 Locus Is Associated With Heart Failure
Topic: Heart Failure/Transplant
Date Posted: 4/15/2010
Author(s): Fatini C, Sticchi E, Marcucci R, et al.
Citation: Heart Rhythm 2010;7:363-367.
Clinical Trial: No
Study Question: What is the association of single-nucleotide polymorphism (SNP) S38G in KCNE1 with heart failure (HF)?
Methods: Investigators genotyped 197 out of 323 previously investigated patients, along with 352 healthy controls comparable for age and sex. This study was replicated in 186 HF patients and in 200 healthy subjects comparable for age and sex.
Results: A significant difference in genotype distribution and allele frequency between patients and controls was observed for the KCNE1 S38G SNP (p = 0.002 and p = 0.0008, respectively). The KCNE1 38G variant was associated with a significant predisposition to HF under a dominant (odds ratio [OR], 2.22 [1.23-3.28]; p = 0.008) and additive (OR, 2.13 [1.09-4.15]; p = 0.03) model, after adjustment for age, sex, and traditional cardiovascular risk factors. No difference in genotype distribution and allele frequency for the KCNE1 S38G SNP according to functional New York Heart Association class was found (p = 0.4 and p = 0.3, respectively). In the HF replication study, the KCNE1 38G allele frequency was significantly higher in comparison with that observed in the control population (38G = 0.59 vs. 0.49; p = 0.004). The 38G allele was associated with HF predisposition under the recessive (OR [95% confidence interval (CI)] 2.49 [1.45- 4.29]; p = 0.001) and additive models (OR [95% CI] 2.63 [1.29-5.35]; p = 0.008), after adjustment for traditional risk factors.
Conclusions: The KCNE1 S38G SNP is associated with predisposition to HF in two study populations.
Perspective: The S38G KCNE1 SNP may affect potassium current, leading to increased action potential duration. This SNP has been associated with predisposition to atrial fibrillation in some studies. The current study now suggests a possible association of this SNP with HF, presumably by affecting functional properties of ventricular myocytes, although the mechanism remains to be shown. Additional studies in larger populations with genome-wide data will be helpful to confirm this association. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Modeled Economic Evaluation of Alternative Strategies to Reduce Sudden Cardiac Death Among Children Treated for Attention Deficit/Hyperactivity Disorder
Topic: Congenital Heart Disease
Date Posted: 4/15/2010
Author(s): Denchev P, Kaltman JR, Schoenbaum M, Vitiello B.
Citation: Circulation 2010;121:1329-1337.
Clinical Trial: No
Study Question: What is the cost-effectiveness of pretreatment screening with electrocardiogram (ECG) for reducing sudden cardiac death (SCD) risk in children with attention deficit/hyperactivity disorder (ADHD)?
Methods: A state-transition Markov model was constructed with 10 annual cycles spanning 7-17 years of age. Three strategies were studied: 1) performing a history and physical with cardiology referral if abnormal; 2) performing a history and physical with ECG if history and physical is normal and subsequent cardiology referral if either is abnormal; or 3) performing a screening history and physical with ECG, and referral only if ECG is abnormal. Multiple assumptions were made, most importantly that stimulants increase the risk of SCD in patients with heart disease by 10%. In the model, children with SCD-associated cardiac abnormalities would be restricted from competitive athletic activities and would not receive stimulants.
Results: The incremental cost-effectiveness of strategy 2 (history and physical followed by ECG if abnormal) was $39,300 per life saved. The incremental cost-effectiveness of strategy 3 (referral only if screening ECG was abnormal) was $27,300 per life saved. The expected cost benefits of screening were due mostly because of restriction from athletics as opposed to SCD as a result of stimulant use.
Conclusions: Adding ECG screening to history and physical pretreatment screening for children with ADHD has borderline cost-effectiveness for preventing SCD, with improved cost-effectiveness with ECG screening alone.
Perspective: This interesting economic analysis is limited by the large number (no less than 10) of significant assumptions made in constructing the statistical model. The most important of these is the premise underlying the study, that stimulants do in fact confer additional risk on children with underlying congenital heart disease. The authors acknowledge that this has not yet been demonstrated in the literature. Interestingly, this study shows overlap with another controversial issue, which is ECG screening prior to sports participation. This practice is common in some parts of Europe, but is not part of preparticipation screening in the United States. Most of the cost benefit of screening in this study came from the expected restriction from sports for children found to have structural heart disease, as opposed to the avoidance of stimulants. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Attenuation of the Effect of the FTO rs9939609 Polymorphism on Total and Central Body Fat by Physical Activity in Adolescents: The HELENA Study
Topic: Prevention/Vascular
Date Posted: 4/16/2010
Author(s): Ruiz JR, Labayen I, Ortega FB, et al., on behalf of the HELENA Study Group.
Citation: Arch Pediatr Adolesc Med 2010;164:328-333.
Clinical Trial: No
Study Question: Does physical activity attenuate the effect of the FTO rs9939609 polymorphism on body fat in adolescents?
Methods: Data from the subjects enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study were used for the present analysis. A total of 3,865 adolescents were recruited into the study, of which 1,155 provided blood samples; 752 of these were tested for the FTO rs9939609 polymorphism and had data on physical activity. Physical activity was assessed through accelerometry worn for between 3 and 7 days for at least 8 hours. Weight, height, waist circumference, and triceps and subscapular skinfold thickness were measured.
Results: A total of 752 (413 girls) were included in the study. The A allele of the FTO rs9939609 polymorphism was significantly associated with high body mass index (BMI) (+0.42 per risk allele), higher body fat percentage (+1.03% per risk allele), and higher waist circumference (+0.85 cm per risk allele). Significant or borderline gene-physical activity interactions were observed for BMI (p = 0.02), body fat percentage (p = 0.06), and waist circumference (p = 0.10). The effect of the FTO rs9939609 polymorphism on body fat was lower among adolescents who met daily physical activity recommendations (defined as 60 minutes per day or more of moderate to vigorous physical activity) compared with those who did not meet these activity guidelines. Results were similar for boys and girls.
Conclusions: The investigators concluded that adolescents who met daily physical activity recommendations may significantly reduce the effect of the FTO rs9939609 polymorphism on obesity.
Perspective: These data support recommendations for daily physical activity among children and adolescents. Further research such as randomized controlled trials to study the association of physical activity and body fat in relation to the FTO rs9939609 polymorphism would add to these current findings. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Prospective Randomized Comparison Between the Conventional Electroanatomical System and Three-Dimensional Rotational Angiography During Catheter Ablation for Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 4/16/2010
Author(s): Knecht S, Wright M, Akrivakis S, et al.
Citation: Heart Rhythm 2010;7:459-465.
Clinical Trial: No
Study Question: Does three-dimensional rotational atriography (3DRA) affect the outcome of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) compared to electroanatomical mapping (EAM) systems?
Methods: Ninety-one patients (mean age 58 years) undergoing RFCA of AF (persistent in 63%) were randomly assigned to 3DRA (n = 47) or imaging with a Carto EAM system (n = 44). The RFCA strategy consisted of pulmonary vein isolation plus substrate modification as clinically indicated.
Results: There was no significant difference in the mean time required for 3DRA (14 minutes) versus creation of the Carto map (17 minutes). The mean procedure time was 224 minutes and did not differ significantly between the 3DRA and Carto groups. There was no significant difference in radiation exposure between the two groups. At a mean of 10 months of follow-up, 52% of patients were free of AF/flutter, with no significant difference between the two study groups.
Conclusions: 3DRA does not increase the amount of radiation exposure compared to an EAM system and does not affect the efficacy of RFCA of AF.
Perspective: In theory, a major advantage of 3DRA over EAM is that it provides an accurate, real-time reconstruction of the left atrium (LA) and pulmonary veins that is not operator dependent. Although EAM can be integrated with anatomically accurate computed tomography (CT) images of the LA, LA volume may have been different at the time of CT and CT exposes patients to more radiation than 3DRA. Disadvantages of 3DRA include its lack of advanced mapping functions and the need for a contrast agent. This study shows that either imaging modality can be used, depending on operator preference, without compromising clinical outcomes. Fred Morady, M.D., F.A.C.C.

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Title: Combined Use of Cryoablation and Focal Open-Irrigation Ablation for Treatment of Persistent Atrial Fibrillation: Results From a Pilot Study
Topic: Arrhythmias
Date Posted: 4/16/2010
Author(s): Mansour M, Forleo GB, Pappalardo A, et al.
Citation: Heart Rhythm 2010;7:452-458.
Clinical Trial: No
Study Question: How effective is the combination of cryoablation for pulmonary vein isolation (PVI) and radiofrequency ablation (RFA) for substrate modification in patients with persistent atrial fibrillation (AF)?
Methods: Twenty-two patients (mean age 57 years) with persistent AF underwent a three-step ablation procedure: PVI using a 23- or 28-mm cryoballoon; RFA of complex fractionated electrograms; and linear RFA along the roof, mitral isthmus, and septum. Recurrent AF during follow-up was defined as AF/flutter >30 seconds in duration after a 5-week blanking period.
Results: The median duration of cryoablation was 48 minutes and the median procedure time was 262 minutes. The efficacy of the cryoballoon for PVI was 92%. At a mean follow-up of 6 months, 86% of patients were free of recurrent AF. The only complication was transient right phrenic nerve paralysis in 9% of patients.
Conclusions: The combined use of cryoablation and RFA for persistent AF is feasible and has favorable short-term results.
Perspective: The major advantage of cryoablation over RFA is a much lower risk of esophageal injury and PV stenosis. Cryoballoons can achieve PVI with a small number of cryoenergy applications, but substrate modification and linear ablation with cryoenergy would require the use of a focal cryoablation catheter, which is not practical because of extremely long procedure times. The advantages of RFA are the relatively short application times and the ability to create drag lesions. This pilot study demonstrates that cryoablation and RFA can be combined to exploit the respective advantages of the two energy sources. Further studies are needed to compare the combined approach with conventional RFA and to establish long-term efficacy. Fred Morady, M.D., F.A.C.C.

ARMYDA-4 RELOAD Trial
New Videos on CV Imaging
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Title: Medication Adherence in Cardiovascular Disease
Topic: General Cardiology
Date Posted: 4/19/2010
Author(s): Baroletti S, Dell’Orfano H.
Citation: Circulation 2010;121:1455-1458.
Clinical Trial: No
Perspective: The following are 10 points to remember about medication adherence in cardiovascular disease.

1. Nonadherence to medications is common, with reports of >60% of cardiovascular patients being nonadherent. Less than 40% of cardiac patients report taking medications such as aspirin, beta-blockers, and statins.

2. The time period immediately after discharge is a high-risk time for nonadherence. Of patients who are adherent to medications, up to 50% of those patients will discontinue their antihypertensive medications in the 6-12 months after hospitalization. Only 40% of patients after acute coronary syndrome will continue statin therapy for 2 years (after hospitalization).

3. Primary nonadherence (not filling initial prescriptions) is associated with increased 1-year mortality after myocardial infarction (MI). Among patients who do not fill any prescriptions within 120 days of having an MI, there is an 80% increased odds of death compared to those who filled all prescriptions. Secondary nonadherence (inability to take medications correctly or refill prescriptions) is also associated with increased mortality and rehospitalization.

4. Factors related to nonadherence can be categorized into three groups: socioeconomic, communication-related, and motivational.

5. Socioeconomic factors relate to the patient’s ability to pay for medications due to lack of adequate health care coverage, unemployment, retirement, or indigence.

6. Communications-related factors that affect adherence include health illiteracy, inadequate communication including language and/or cultural barriers, substance or alcohol abuse, and mental illness.

7. Factors related to motivation can also impact adherence. Patients are less likely to adhere to a medication if there is no noticeable benefit. Unlike antibiotics or pain medications, cardiac medications such as antihypertensives, aspirin, or statins often do not make the patient feel better, thus can be perceived by the patient as not being necessary. A concern regarding adverse effects of medications may also decrease adherence for medication such as statins.

8. Potential solutions for nonadherence include intensive education by the medical team regarding the importance of cardiac medications, and should include details of the purpose of each specific medication prior to discharge. Management strategies can be tailored to the patient’s specific needs including use of generic formularies, once-per-day dosing, or combination medications. Social work involvement is recommended if health care coverage is a concern. Use of family and/or interpreter services may improve adherence if language or cultural barriers exist.

9. In the outpatient setting, follow-up 1-2 weeks after hospitalization to review medical management and assess for barriers to adherence can reduce nonadherence. Use of drug reminder charts and ongoing assessment of financial barriers, the patient’s perceptions for the use of medications, and involvement of patients in the medical decision making can also improve adherence.

10. Online information to address nonadherence includes resources for payment assistance and low-cost drugs ([Ссылки могут видеть только зарегистрированные и активированные пользователи] and [Ссылки могут видеть только зарегистрированные и активированные пользователи]); resources related to communication to improve adherence ([Ссылки могут видеть только зарегистрированные и активированные пользователи] and [Ссылки могут видеть только зарегистрированные и активированные пользователи]), and resources related to motivational factors and patient education ([Ссылки могут видеть только зарегистрированные и активированные пользователи] and [Ссылки могут видеть только зарегистрированные и активированные пользователи]). Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Fasting Plasma Glucose in Non-Diabetic Participants and the Risk for Incident Cardiovascular Events, Diabetes, and Mortality: Results From WOSCOPS 15-Year Follow-Up
Topic: Prevention/Vascular
Date Posted: 4/21/2010
Author(s): Preiss D, Welsh P, Murray HM, et al.
Citation: Eur Heart J 2010 Apr 15. [Epub ahead of print].
Clinical Trial: No
Related Resources
Trial: The West of Scotland Coronary Prevention Study (WOSCOPS)

Study Question: Is a fasting plasma glucose (FPG) in the nondiabetic range a risk factor for long-term risk of cardiovascular disease (CVD)?
Methods: A total of 6,447 men with hypercholesterolemia (4.5-6 mmol/L) participating in the West of Scotland Coronary Prevention Study (WOSCOPS) who had a FPG but no history of CVD or diabetes (FPG <7.0 mmol/L), were followed for CV events and mortality over 14.7 years of follow-up. Patients were randomized to pravastatin 40 mg daily or placebo and followed initially for an average of 4.9 years. The primary outcome of the follow-up extension study is the relationship between FPG and CVD defined as a composite of fatal and nonfatal CVD events including coronary heart disease (CHD), stroke, and CHD deaths. Comparison of time to first event was determined by Cox proportional hazards models with Q2 as referent because of the J-shaped relationship between FPG and CVD mortality (18 mg/dl glucose = 1 mmol/L glucose).
Results: Mean age was 55 years; 2,381 nonfatal/fatal CV events and 1,244 deaths occurred. Participants were divided into fifths of baseline FPG, Q1 (≤4.3 mmol/L) to Q5 (>5.1-6.9 mmol/L). Compared with Q2 (>4.3-4.6 mmol/L), men in Q5 had no elevated risk for CV events (hazard ratio [HR], 0.95 [0.83-1.08]), or all-cause mortality (HR, 0.96) in fully adjusted analyses despite a significant risk for incident diabetes (HR, 22.05 [10.75-45.22]). After further dividing Q5 into fifths, Q5a-e, individuals in Q5e (FPG 5.8-6.9 mmol/L) were also not at increased risk of CV events or other endpoints compared with Q2. All results were similar using Q1 as the referent.
Conclusions: Elevations in FPG in the nondiabetic range were not associated with long-term risk of CV events in middle-aged men in WOSCOPS. These data suggest that the current FPG cutoff for diagnosing diabetes also appropriately identifies western men at risk of CVD.
Perspective: That an elevated fasting glucose predicts the development of diabetes over 5 years, but not CV events over the following 10 years in WOSCOPS is a surprise, considering the findings in other populations. In stark conflict is the recent report from the Atherosclerotic Risk in Communities Study (Selvin E, et al. N Engl J Med 2010;362:800-11) in which a glycated hemoglobin >5.5% is associated with an increase in risk for diabetes and coronary disease independent of other variables, and the relative risk for each 0.5% increment in glycated hemoglobin is considerable. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Implantable Cardiac Device Procedures in Older Patients: Use and In-Hospital Outcomes
Topic: Heart Failure/Transplant
Date Posted: 4/21/2010
Author(s): Swindle JP, Rich MW, McCann P, Burroughs TE, Hauptman PJ.
Citation: Arch Intern Med 2010;170:631-637.
Clinical Trial: No
Study Question: What are the age-specific practices and outcomes among patients with heart failure undergoing implantable cardioverter defibrillator (ICD) implantation?
Methods: The cohort included patients older than 18 years with a diagnosis of heart failure who underwent implantation of an ICD or cardiac resynchronization therapy (CRT) between January 1, 2004, and December 31, 2005. Data included patient demographics, comorbidities, type of device, procedural complications, length of stay, total cost of hospitalization, and hospital characteristics. Multivariate stepwise logistic regression analysis was used to identify risk factors for in-hospital mortality. Age groups were chosen to directly evaluate mortality risk among patients 80 years or older relative to younger patients, as this cohort was excluded from randomized clinical trials or was markedly under-represented.
Results: The authors identified 26,887 patients who received an implantable device. The median age was 70.0 years (17.5% were ≥80 years), 72.6% were male, and 31.3% were of nonwhite race/ethnicity. Compared with younger patients, those 80 years or older were more likely to receive CRT alone. In-hospital mortality increased from 0.7% among patients younger than 80 years to 1.2% among those ages 80-85 years and 2.2% among those older than 85 years (p < 0.001). Independent predictors of in-hospital mortality included age 80 years or older, elevated comorbidity score, inotrope use, and procedure-related complications.
Conclusions: The authors concluded that advanced age is an independent predictor of in-hospital mortality following device implantation, suggesting that additional study is needed to define criteria for appropriate device use in older patients.
Perspective: The investigators found that despite the fact that most device trials have excluded patients 80 years or older, more than one-fifth of ICD and CRT devices are implanted in this age group. Furthermore, procedure-related complication rates and in-hospital mortality are elevated in patients with advanced age. It seems that additional studies are required to clarify the appropriateness of device implantation in older patients with heart failure, as well as the merits of less invasive options and/or medical therapies. For the present, physicians need to individualize therapy based on the medical issues and patient wishes, and meaningfully discuss the potential risks and benefits of the procedure with each patient. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Caloric Sweetener Consumption and Dyslipidemia Among US Adults
Topic: Prevention/Vascular
Date Posted: 4/20/2010 4:00:00 PM
Author(s): Welsh JA, Sharma A, Abramson JL, Vaccarino V, Gillespie C, Vos MB.
Citation: JAMA 2010;303:1490-1497.
Clinical Trial: No
Related Resources
For Patients: High-Sugar Diet Linked to Cholesterol

Study Question: How do added sugars affect lipids among adults?
Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 were used for the present analysis. Dietary intake was assessed through 24-hour recalls. US adults, ages 18 years or older, who participated in the NHANES 1999-2006 survey and provided fasting blood samples were included. Adults who were pregnant, had unreliable or missing dietary data, body mass index >65, were on lipid-lowering medications, or had known diabetes were excluded. Respondents were grouped by intake of added sugars (<5%, 5% to <10%, 10% to <17.5%, 17.5% to <25%, and ≥25% of total energy intake). Outcomes of interest included mean high-density lipoprotein (HDL) cholesterol, mean triglyceride, and mean low-density lipoprotein (LDL) cholesterol. Results were weighted to be representative of the US population.
Results: A total of 6,113 respondents were included in the analysis. As sugar consumption increased, respondents were more likely to be younger, non-Hispanic blacks and have low income. Number of cigarettes was also associated with increased sugar consumption. Added sugars comprised a mean of 15.3% of calories consumed. Total energy and percent total energy from carbohydrates increased as percent of total calories from added sugars increased. Intake of added sugars was inversely proportional to percent total calories from total, polyunsaturated, monounsaturated, and saturated fats. A similar pattern was noted for protein and fiber. Adjusted mean HDL levels were inversely proportional to added sugar consumptions, while mean triglyceride levels were positively related to sugar intake. A similar pattern for LDL cholesterol was observed for women, but not for men. For adults who consumed ≥10% of calories from added sugars, the odds of low HDL were 50% to >300% compared to the reference group of <5% of calories from added sugar.
Conclusions: The investigators concluded that there is a significant correlation between added sugars and lipid levels among US adults.
Perspective: These data suggest that health care providers should counsel patients to avoid significant intake of sweetened foods, as an important cardiovascular prevention measure. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Treatment and Risk in Heart Failure: Gaps in Evidence or Quality?
Topic: Heart Failure/Transplant
Date Posted: 4/20/2010
Author(s): Peterson PN, Rumsfeld JS, Liang L, et al., on behalf of the American Heart Association Get With The Guidelines-Heart Failure Program.
Citation: Circ Cardiovasc Qual Outcomes 2010;Apr 13:[Epub ahead of print].
Clinical Trial: No
Study Question: Does the paradoxical inverse relationship between risk and treatment of heart failure patients reflect larger gaps in care quality or higher rates of treatment contraindications in patients with higher risk?
Methods: The study cohort was comprised of 18,307 patients with left ventricular systolic dysfunction surviving hospitalization between January 2005 and June 2007 from 194 hospitals participating in the Get With The Guidelines (GWTG)–Heart Failure Program. Patients were categorized according to their estimated risk for in-hospital mortality using a validated risk score. The proportion of patients with documented contraindications to angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers and beta-blockers as well as the use of these medications among patients without contraindications at hospital discharge was determined across levels of risk.
Results: For each therapy, the proportion of patients with contraindications was significantly higher with increasing patient risk (p < 0.001 for each). However, even after excluding those with contraindications, the use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers and beta-blockers was significantly lower with increasing risk (p < 0.001 for each).
Conclusions: The use of evidence-based therapies is lower in patients with heart failure at higher risk of mortality both because of higher rates of contraindications to therapy and lower rates of use among eligible patients. Optimizing heart failure outcomes will require both the expansion of the evidence base for treating the highest-risk patients as well as the development of effective strategies to assure that eligible high-risk patients receive all appropriate therapies.
Perspective: The absolute benefits of an intervention are proportional to the patient’s underlying risk. These are sobering data, suggesting that we often fail to treat those at greatest risk––those who stand to benefit the most from treatment. Although contraindications were shown in this study to account for some failure of therapy among higher-risk patients, risk itself also appeared to be responsible for failure to utilize evidence-based therapies. Experience suggests that not all patients fit into checked boxes, and not all failures to treat are necessarily unjustified (even if the appropriate contraindication was not documented). However, this study should give pause, and serve to remind us that risk itself should be considered an indication, not a contraindication, to therapy. David S. Bach, M.D., F.A.C.C.

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Title: Evidence of Disparity in the Application of Quality Improvement Efforts for the Treatment of Acute Myocardial Infarction: The American College of Cardiology’s Guidelines Applied in Practice Initiative in Michigan
Topic: Heart Failure/Transplant
Date Posted: 4/20/2010
Author(s): Olomu AB, Grzybowski M, Ramanath VS, et al., on behalf of the American College of Cardiology Foundation Guidelines Applied in Practice Steering Committee.
Citation: Am Heart J 2010;159:377-384.
Clinical Trial: No
Study Question: Did the structured initiative for improving care of patients with acute myocardial infarction (Guidelines Applied in Practice [GAP]) lead to comparable care of white and nonwhite patients admitted to GAP hospitals in Michigan?
Methods: Medicare patients were comprised of two cohorts: 1) those admitted before GAP implementation (n = 1,368), and 2) those admitted after GAP implementation (n = 1,489). The main outcome measure was adherence to guideline-based medications and recommendations and use of the GAP discharge tool. Chi squared and Fisher exact tests were used to determine differences between white patients (n = 2,367) and nonwhite patients (n = 490).
Results: In-hospital GAP tool and aspirin use significantly improved for white and nonwhite patients. Beta-blocker use in-hospital improved significantly for nonwhite patients only (66% vs. 83.3%; p = 0.04). At discharge, nonwhite patients were 28% and 64% less likely than white patients to have had the GAP discharge tool used (p = 0.004) and receive smoking cessation counseling (p < 0.001), respectively. Among white patients, GAP improved discharge prescription rates for aspirin by 10.8% (p < 0.001) and beta-blockers by 7.0% (p = 0.047). Nonwhite patients’ aspirin prescriptions increased by 1.0% and beta-blocker prescriptions decreased by 6.0% (both P values were nonsignificant).
Conclusions: The GAP program led to significant increases in rates of evidence-based care in both white and nonwhite Medicare patients. However, nonwhite patients received less frequent use of the discharge tool and smoking cessation counseling. Policies designed to reduce racial disparities in health care must address disparity in the delivery of quality improvement programs.
Perspective: There was not adequate sample size to determine if the evidence for racial disparities, as found in the GAP program, occurred as a result of different levels of care by practitioners within the same institutions. As the authors suggest, it is highly likely that the findings represent decreased availability of resources to fully implement the GAP discharge tool in those hospitals serving a higher percentage of nonwhite patients, and the nonwhite patients are more likely to be cared for in lower quality performing hospitals. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Erectile Dysfunction Predicts Cardiovascular Events in High-Risk Patients Receiving Telmisartan, Ramipril, or Both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials
Topic: General Cardiology
Date Posted: 4/20/2010
Author(s): Bцhm M, Baumhдkel M, Teo K, et al., on behalf of the ONTARGET/TRANSCEND Erectile Dysfunction Substudy Investigators.
Citation: Circulation 2010;121:1439-1446.
Clinical Trial: No
Related Resources
Trial: ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET)
Trial: Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND)

Study Question: Is erectile dysfunction (ED) predictive of mortality and cardiovascular (CV) outcomes in high-risk men?
Methods: In a prespecified substudy, 1,549 patients underwent double-blind randomization, with 400 participants assigned to receive ramipril, 395 telmisartan, and 381 the combination thereof (ONTARGET), as well as 171 participants assigned to receive telmisartan and 202 placebo (TRANSCEND). ED was evaluated at baseline, at 2-year follow-up, and at the visit before closeout. The effect of baseline erectile function on the primary composite outcome (death due to CV causes, myocardial infarction [MI], stroke, or hospitalization for heart failure) and all-cause mortality was assessed with Cox regression analysis, stratifying by treatment allocation to account for combining the two studies and adjusting for age and clinical variables. Hazard ratios with 95% confidence intervals were used to examine the relationship of the severity of ED with subsequent clinical outcomes.
Results: Approximately 55% had ED and 45% had no ED or mild ED; mean blood pressure was 140/81 mm Hg; 40% of those with ED had diabetes compared to 26% in those with no/mild ED (p < 0.0001), and there were no differences between groups for ankle-brachial index or medications including beta-blockers (57.5%). All-cause deaths occurred in 11.3% of the patients who reported ED at baseline, but only in 5.6% of patients with no/mild ED at baseline (hazard ratio [HR], 2.04; p = 0.0002). ED was predictive of the composite primary outcome that occurred in 16.2% with ED compared to 10.3% with no/mild ED (HR, 1.62; p = 0.001), which was dominated by CV death (HR, 1.93; p = 0.016), and MI (HR, 2.02; p = 0.017). The study medications did not influence the course or development of ED.
Conclusions: ED is a potent predictor of all-cause death and the composite of CV death, MI, stroke, and heart failure in men with CV disease. Trial treatment did not significantly improve or worsen ED.
Perspective: ED was very common in this study. Interestingly, it did not vary with use of beta-blockers at baseline, and there was no impact of telmisartan or ramipril. ED was highly predictive of CV death and MI, but not stroke (regardless of adjustment for age and blood pressure) or heart failure when these variables were evaluated independently. Total mortality increased with increasing degrees of ED. While ED is associated with endothelial dysfunction and atherosclerosis, it is not clear as to why it would impact total mortality. Melvyn Rubenfire, M.D., F.A.C.C

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Title: Differences Between Beta-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial
Topic: Heart Failure/Transplant
Date Posted: 4/19/2010 5:00:00 PM
Author(s): Jabbour A, Macdonald PS, Keogh AM, et al.
Citation: J Am Coll Cardiol 2010;55:1780-1787.
Clinical Trial: yes
Study Question: What are the respiratory, hemodynamic, and clinical effects of switching between β1-selective and nonselective beta-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD)?
Methods: A randomized, open-label, triple-crossover trial involving 51 subjects receiving optimal therapy for CHF was conducted in two Australian teaching hospitals. Subjects were a mean age of 66 years (standard deviation [SD] 12 years) and had New York Heart Association (NYHA) functional class I (n = 6), II (n = 29), or III (n = 16); and left ventricular ejection fraction (mean of 37%, SD 10%); 35 had coexistent COPD. Subjects received each beta-blocker, dose-matched, for 6 weeks before resuming their original beta-blocker. Echocardiography, N-terminal prohormone brain natriuretic peptide (NT-BNP), central augmented pressure from pulse waveform analysis, respiratory function testing, 6-minute walk distance, and NYHA functional class were assessed at each visit.
Results: The investigators found that NT-BNP was significantly lower with carvedilol than with metoprolol or bisoprolol (mean: carvedilol 1001 [95% confidence interval (CI), 633-1367] ng/L; metoprolol 1371 [95% CI, 778-1964] ng/L; bisoprolol 1349 [95% CI, 782-1916] ng/L; p < 0.01), and returned to baseline level on recommencement of the initial beta-blocker. Central augmented pressure (a measure of pulsatile afterload) was lowest with carvedilol (carvedilol 9.9 [95% CI, 7.7-12.2] mm Hg; metoprolol 11.5 [95% CI, 9.3-13.8] mm Hg; bisoprolol 12.2 [95% CI, 9.6-14.7] mm Hg; p < 0.05). In subjects with COPD, forced expiratory volume in 1 second was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 [95% CI, 1.67-2.03] L/s; metoprolol 1.94 [95% CI, 1.73-2.14] L/s; bisoprolol 2.0 [1.79-2.22] L/s; p < 0.001). The NYHA functional class, 6-minute walk distance, and left ventricular ejection fraction did not change. The beta-blocker switches were well tolerated.
Conclusions: The authors concluded that switching between β1-selective beta-blockers and the nonselective beta-blocker carvedilol is well tolerated, but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from β1-selective beta-blockers to carvedilol causes short-term reduction of central augmented pressure and NT-BNP.
Perspective: Managing two conditions simultaneously involves trade-offs. Typically, HF specialists have chosen bisoprolol first-line in patients with clinically significant reactive airways disease such as asthma. In this study, carvedilol was associated with a 'better' hemodynamic response, as evidenced by lower NT-BNP and central aortic pressure, but associated with poorer forced expiratory volume in 1 second (FEV1) responses. However, the poorer FEV1 responses were not associated with worsening NYHA functional class or 6-minute walk test. Larger blinded randomized studies are needed to determine which beta-blocker has the best clinical outcome in CHF patients with COPD. Ragavendra R. Baliga, M.B.B.S.

Title: Combined Heart Failure Device Diagnostics Identify Patients at Higher Risk of Subsequent Heart Failure Hospitalizations: Results From PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) Study
Topic: Heart Failure/Transplant
Date Posted: 4/19/2010 5:00:00 PM
Author(s): Whellan DJ, Ousdigian KT, Al-Khatib SM, et al., on behalf of for the PARTNERS Study Investigators.
Citation: J Am Coll Cardiol 2010;55:1803-1810.
Clinical Trial: No
Related Resources
JACC Article: Combined Heart Failure Device Diagnostics Identify Patients at Higher Risk of Subsequent Heart Failure Hospitalizations: Results From PARTNERS HF Study

Study Question: What is the ability of combined heart failure (HF) device diagnostic information to predict clinical deterioration of HF in patients with systolic left ventricular dysfunction?
Methods: The investigators analyzed data from 694 cardiac resynchronization therapy (CRT) defibrillator patients from the PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) who were followed for 11.7 ± 2 months. The PARTNERS HF was a prospective, multicenter, observational study in patients receiving CRT implantable cardioverter-defibrillators. HF events were independently adjudicated. The investigators developed a combined HF device diagnostic algorithm on an independent data set. The algorithm was considered positive if a patient had two of the following abnormal criteria during a 1-month period: long atrial fibrillation duration, rapid ventricular rate during atrial fibrillation, high fluid index (≥60), low patient activity, abnormal autonomics (high night heart rate or low heart rate variability), or notable device therapy (low CRT pacing or implantable cardioverter-defibrillator shocks), or if they only had a very high (≥100) fluid index. The investigators used univariate and multivariable analyses to determine predictors of subsequent HF events within a month.
Results: The investigators found that 90 patients had 141 adjudicated HF hospitalizations with pulmonary congestion at least 60 days after implantation. Patients with a positive combined HF device diagnostics had a 5.5-fold increased risk of HF hospitalization with pulmonary signs or symptoms within the next month (hazard ratio, 5.5; 95% confidence interval, 3.4-8.8; p < 0.0001), and the risk remained high after adjusting for clinical variables (hazard ratio, 4.8; 95% confidence interval, 2.9-8.1; p < 0.0001).
Conclusions: The authors concluded that monthly review of HF device diagnostic data identifies patients at a higher risk of HF hospitalizations within the subsequent month.
Perspective: Although this was not a blinded study, this is an important study because it identifies patients most likely to have HF hospitalizations. The ability to predict hospitalizations will allow HF disease management programs to focus on highest risk patients to reduce hospitalizations and associated costs. A large blinded randomized study would be needed to validate the findings of this study, whether more frequent analysis of the data improves the ability to risk stratify, and how these findings compare with data obtained from other implantable hemodynamic device monitors (see Circulation 2010;121:1086-95). Ragavendra R. Baliga, M.B.B.S.

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Title: Lipid Re-screening: What Is the Best Measure and Interval?
Topic: Prevention/Vascular
Date Posted: 4/22/2010
Author(s): Takahashi O, Glasziou PP, Perera R, et al.
Citation: Heart 2010;96:448-452.
Clinical Trial: No
Study Question: What is the long-term true change variation (‘signal’) and short-term within-person variation (‘noise’) of the different lipid measures and the optimal interval for lipid re-screening?
Methods: A retrospective cohort study was conducted from 2005 to 2008 at a medical health check-up program in Tokyo. A total of 15,810 apparently healthy Japanese adults not taking cholesterol-lowering drugs at baseline underwent an annual measurement of fasting serum lipids. Measurement of the ratio of long-term true change variation (‘signal’) to the short-term within-person variation (‘noise’) was determined for individual lipid components and the ratio of total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) to HDL-C.
Results: At baseline, 53% were male; mean age was 49 years; body mass index (BMI) was 22.5 kg/m2 [standard deviation (SD) (3.2)]; mean TC level 5.3 mmol/L (0.9 mmol/L), triglycerides 1.1 (0.8); and mean ratio TC/HDL and LDL/HDL level at baseline were 3.5 (1.0) and 2.0 (0.8), respectively. Each had annual check-ups over 4 years. Short-term within-person variations of TC, LDL, HDL, TC/HDL, and LDL/HDL were 0.12 (coefficient of variation [CV] 6.4%), 0.08 (CV 9.4%), 0.02 (CV 8.0%) mmol2/L2, 0.08 (CV 7.9%), and 0.05 (CV 10.6%), respectively. The ratio of signal-to-noise at 3 years was largest for TC/HDL (1.6), followed by LDL/HDL (1.5), LDL (0.99), TC (0.8), and HDL (0.7), suggesting that cholesterol ratios are more sensitive re-screening measures.
Conclusions: The signal-to-noise ratios of standard single lipid measures (TC, LDL, and HDL) are weak over 3 years, and decisions based on these measures are potentially misleading. The ratios, TC/HDL and LDL/HDL, seem to be better measures for monitoring assessments. The lipid re-screening interval should be >3 years for those not taking cholesterol-lowering drugs.
Perspective: The results support the use of TC/HDL as the preferred lipid parameter for risk stratification, but are not generalizable. This Japanese cohort had a low BMI and low-risk lipid profile. The degree to which increasing BMI and triglycerides would alter the conclusion is not known, but may be considerable. The ratio of LDL to HDL needs to be obtained fasting, and in most cohort studies, has less ability than the TC/HDL to discriminate risk of cardiovascular events. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism: A Multicenter Prospective Study (PIOPED III)
Topic: Noninvasive Cardiology
Date Posted: 4/21/2010
Author(s): Stein PD, Chenevert TL, Fowler SE, et al., on behalf of the PIOPED III (Prospective Investigation of Pulmonary Embolism Diagnosis III) Investigators.
Citation: Ann Intern Med 2010;152:434-443.
Clinical Trial: No
Related Resources
Trial: Prospective Investigation of Pulmonary Embolism Diagnosis Study (PIOPED)

Study Question: What is the accuracy of gadolinium-enhanced magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism?
Methods: In a prospective, multicenter study performed between April 2006 and September 2008, 371 adult patients at seven hospitals evaluated for pulmonary embolism were studied. Independently read magnetic resonance imaging was compared with the reference standard for diagnosis. (The reference standard used various tests, including computed tomographic angiography and venography, ventilation–perfusion lung scan, venous ultrasonography, D-dimer assay, and clinical assessment.)
Results: Magnetic resonance angiography, averaged across centers, was technically inadequate in 92 of 371 (25%) patients; the proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 59 of 104 (57%) patients with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. Of note, a high proportion of patients with suspected embolism was not eligible or declined to participate.
Conclusions: The authors concluded that magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well, and only for patients for whom standard tests are contraindicated. In patients with technically adequate images, combined magnetic resonance pulmonary angiography and magnetic resonance venography have a higher sensitivity than does magnetic resonance pulmonary angiography alone, but it is more difficult to obtain technically adequate images with the two procedures.
Perspective: This is a realistic look at the application of a newer diagnostic imaging tool to a common clinical problem that has good (albeit imperfect) existing methods for diagnosis. The important strengths of magnetic resonance imaging were countered in this study by technically inadequate images in many patients who underwent the test, and by a substantial number of patients who––in this clinical setting––were ineligible for, or who declined to have the test. David S. Bach, M.D., F.A.C.C.

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Title: Clinical Relevance of Clopidogrel Unresponsiveness During Elective Coronary Stenting: Experience With the Point-of-Care Platelet Function Assay-100 C/ADP
Topic: Interventional Cardiology
Date Posted: 4/21/2010
Author(s): Moerenhout CM, Claeys MJ, Haine S, et al.
Citation: Am Heart J 2010;159:434-438.
Clinical Trial: No
Study Question: What is the clinical impact of unresponsiveness to clopidogrel in patients undergoing elective coronary artery stenting?
Methods: The authors evaluated the association between preprocedural platelet inhibition and postprocedural myonecrosis in 250 patients undergoing elective percutaneous coronary intervention (PCI). Platelet aggregation testing was performed at the time of the intervention using a point-of-care assay, the Platelet Function Assay (PFA-100C/ADP; Dade-Behring, Deerfield, IL). Nonresponse to clopidogrel was defined as a PFA closure time of <71 seconds under dual oral antiplatelet therapy. Postprocedural myonecrosis was defined as an elevation in creatine kinase-MB >1x the upper limit of normal 12-24 hours after intervention. The secondary endpoint was a composite endpoint of major adverse cardiac events (MACE) including death, myocardial infarction, and stent thrombosis at 6 months.
Results: Preprocedural PFA closure time was determined in 242 patients and ranged from 31 to 300 seconds, with a mean value of 147 seconds. Seventeen (7%) patients were nonresponders. Post-PCI myonecrosis occurred in 29 patients (12%) and was more common in nonresponders than in normal responders (29% vs. 11%, p = 0.04). This difference remained significant after adjusting for baseline differences. MACE at 6 months occurred in 13 patients and was comprised of one sudden death possibly related to stent thrombosis and 12 post-PCI myocardial infarctions. MACE was nonsignificantly more common in the nonresponder group (12% vs. 5%, respectively; p = 0.2).
Conclusions: The investigators concluded that unresponsiveness to clopidogrel as assessed by PFA-100C/ADP is an independent risk factor for thrombotic complications after coronary intervention.
Perspective: This small underpowered study suggests that patients who are poorly responsive to clopidogrel are more likely to have myonecrosis after elective PCI. While the study did not find a significant difference in postprocedural MI, this was probably related to the small study size. Larger studies are needed to confirm these findings and to assess the utility of using either prasugrel or larger doses of clopidogrel in patients who are nonresponders to clopidogrel. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes: Observations From the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary–Thrombolysis In Myocardial Infarction 36) Trial
Topic: General Cardiology
Date Posted: 4/23/2010
Author(s): Morrow DA, Scirica BM, Sabatine MS, et al.
Citation: J Am Coll Cardiol 2010;55:1189-1196.
Clinical Trial: No
Related Resources
JACC Article: B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes: Observations From the MERLIN–TIMI 36 Trial
Trial: Metabolic Efficiency With Ranolazine for Less Ischemia in NSTE-ACS (MERLIN-TIMI 36)

Study Question: What is the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS)?
Methods: The investigators measured plasma BNP in all available baseline samples (n = 4,543) among patients with non–ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST Elevation Acute Coronary–Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml.
Results: Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial endpoint (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP >80 pg/ml, ranolazine reduced the primary endpoint (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.66-0.94; p = 0.009). The effect of ranolazine in patients with BNP >80 pg/ml was directionally similar for recurrent ischemia (HR, 0.78; 95% CI, 0.62-0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR, 0.83; 95% CI, 0.66-1.05; p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05).
Conclusions: The authors concluded that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP.
Perspective: This study confirms prior observations that patients with ACS who have an elevated BNP concentration at baseline are at substantially higher risk of adverse outcomes, including cardiovascular death, heart failure, recurrent ischemic events, tachyarrhythmias, and reduced exercise capacity. In such high-risk patients, ranolazine had a significant benefit, with a reduction in the primary endpoint of cardiovascular death, myocardial infarction, or recurrent ischemia. This potential benefit of ranolazine needs to be prospectively evaluated. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Role of Cardiac Magnetic Resonance Imaging in the Detection of Cardiac Amyloidosis
Topic: Noninvasive Cardiology
Date Posted: 4/22/2010
Author(s): Syed IS, Glockner JF, Feng D, et al.
Citation: JACC Cardiovasc Imaging 2010;3:155-164.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Role of Cardiac Magnetic Resonance Imaging in the Detection of Cardiac Amyloidosis

Study Question: What is the role of cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) for identification of patients with cardiac amyloidosis (CA)?
Methods: LGE-CMR was performed in 120 patients with amyloidosis, 35 of whom had cardiac biopsy and the remaining 85 categorized as with or without CA by echocardiographic criteria (>12 mm mean wall thickness). LGE-CMR was characterized as global transmural, global subendocardial, patchy focal LGE, and suboptimal nulling.
Results: For the 35 patients with biopsy-proven CA, LGE was global in 29, suboptimal nulling in three, focal patchy in two and absent in only one patient. Left ventricular (LV) wall thickness by echo was >12 mm in 32 patients (91%). Cardiac histology revealed moderate to severe interstitial amyloid in 28, 25 (89%) of whom had global LGE. Three of five patients with ≤ mild interstitial amyloid had nonglobal LGE. In the 85 patients without cardiac biopsy, the echocardiogram suggested amyloid in 49, 42 of whom had LGE, including 18 with global transmural and eight with global subendocardial, 10 with suboptimal nulling, and a patchy pattern in six. Seven patients with echocardiographic wall thickness >12 mm had no LGE. Of the 36 patients without echo evidence of CA, 17 (47%) had LGE, which was global subendocardial in three, suboptimal nulling in six, and patchy in eight patients. LGE on CMR was associated with higher LV mass index and greater LV and right ventricular wall thickness, and a higher likelihood of low-voltage electrocardiogram.
Conclusions: LGE on CMR is common in patients with CA and appears related to the magnitude of interstitial amyloid deposition. Multiple patterns including global transmural and subendocardial as well as suboptimal myocardial nulling and focal patchy LGE are observed, and the presence and pattern of LGE is associated with morphological and clinical markers of prognosis.
Perspective: This is one of several fairly recent studies using LGE on CMR as a marker of cardiac amyloid in comparison with either cardiac histology or echocardiography findings. This study identifies several different LGE patterns, each of which was associated with CA on biopsy or echocardiography. Previous smaller studies have suggested a more specific pattern of global subendocardial involvement. It should be emphasized that the pattern detected may be technique dependent and that standardization of contrast administration, pulse sequencing, and timing of imaging for LGE may play a role in the overall detection rate of LGE. An important message from this study is that the pattern of amyloid correlated with the magnitude of interstitial infiltration on biopsy and also with a number of morphologic and biochemical markers of the presence and prognosis of patients with cardiac amyloid. In direct comparison to echocardiography, there clearly was a subset of patients in whom no echocardiographic wall thickening was detected yet LGE was present, suggesting a greater sensitivity of LGE-CMR for detecting early phases of cardiac amyloid than is available from echocardiographic wall thickness alone. Of note, more detailed parameters of myocardial deformation such as strain or detailed diastolic function parameters were not used in this study and may have allowed detection of more patients by echocardiography. Finally, it should be emphasized that all patients in this study had known amyloidosis and that the population was not heterogeneous, including patients with coronary disease, hypertensive vascular disease, or other forms of infiltrative cardiomyopathy, etc. William F. Armstrong, M.D., F.A.C.C.

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Title: Dronedarone for Atrial Fibrillation: Have We Expanded the Antiarrhythmic Armamentarium?
Topic: Arrhythmias
Date Posted: 4/22/2010
Author(s): Singh D, Cingolani E, Diamond GA, Kaul S.
Citation: J Am Coll Cardiol 2010;55:1569-1576.
Clinical Trial: No
Related Resources
JACC Article: Dronedarone for Atrial Fibrillation: Have We Expanded the Antiarrhythmic Armamentarium?

Conclusions: The following are 10 points to remember from this review of dronedarone:

1. Dronedarone was designed to eliminate the organ toxicity of amiodarone (its parent compound) without compromising efficacy.

2. Dronedarone is metabolized by CYP3A4, and the dosage of drugs that inhibit this cytochrome should be adjusted to avoid overexposure to dronedarone.

3. The half-life of dronedarone is 30 hours compared to approximately 2 months for amiodarone.

4. Dronedarone inhibits tubular secretion of creatinine and causes a 10-15% increase in serum creatinine without reducing the glomerular filtration rate.

5. The pooled results of four randomized trials demonstrate that dronedarone prevented a recurrence of atrial fibrillation (AF) in 57% of patients, compared to 46% with placebo.

6. In a randomized trial, dronedarone was 50% less effective than amiodarone for preventing AF and was not significantly better tolerated.

7. Dronedarone increases the risk of death in patients with severe or recently decompensated heart failure (HF).

8. In a clinical trial, dronedarone was associated with a 24% reduction in the risk of cardiovascular hospitalization and did not significantly affect mortality.

9. The main side effects of dronedarone are diarrhea, nausea, and rash, and there is no evidence that dronedarone causes proarrhythmia or endocrine, neurological, or pulmonary toxicity.

10. The available data support the limited use of dronedarone in patients without recently decompensated HF, mostly as a second-line agent as an alternative to amiodarone.
Perspective: It is clear that dronedarone is not what many had hoped for, namely ‘a safe amiodarone.’ Freedom from organ toxicity comes with the price of lower efficacy than amiodarone. This, along with the high cost ($9/day retail), may limit its use in clinical practice. Fred Morady, M.D., F.A.C.C.

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Title: Efficacy of Rosuvastatin Among Men and Women With Moderate Chronic Kidney Disease and Elevated High-Sensitivity C-Reactive Protein: A Secondary Analysis From the JUPITER (Justification for the Use of Statins in Prevention-an Intervention Trial Evaluating Rosuvastatin) Trial
Topic: Prevention/Vascular
Date Posted: 4/23/2010
Author(s): Ridker PM, MacFadyen J, Cressman M, Glynn RJ.
Citation: J Am Coll Cardiol 2010;55:1266-1273.
Clinical Trial: No
Related Resources
JACC Article: Efficacy of Rosuvastatin Among Men and Women With Moderate Chronic Kidney Disease and Elevated High-Sensitivity C-Reactive Protein: A Secondary Analysis From the JUPITER Trial
Trial: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)

Study Question: What is the efficacy of statin therapy in primary prevention among individuals with moderate chronic kidney disease (CKD)?
Methods: The authors performed a secondary analysis within JUPITER (Justification for the Use of Statins in Prevention–an Intervention Trial Evaluating Rosuvastatin) comparing cardiovascular and mortality outcomes among those with moderate CKD at study entry (n = 3,267) with those with baseline estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 (n = 14,528). JUPITER is the primary prevention trial of rosuvastatin 20 mg compared with placebo among men and women free of cardiovascular disease who had low-density lipoprotein cholesterol (LDL-C) <130 mg/dl and high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L.
Results: Study participants with moderate CKD were older (70 years vs. 65 years), more likely to be female, more likely to have a family history of premature atherothrombosis, and less likely to smoke. Among those with reduced eGFR, 3,253 had stage 3 impairment (eGFR between 30 and 59 ml/min/1.73 m2) and 14 had stage 4 impairment (eGFR between 15 and 29 ml/min/1.73 m2). Median follow-up was 1.9 years (maximum 5 years). Compared with an eGFR ≥60 ml/min/1.73 m2, JUPITER participants with moderate CKD had higher vascular event rates (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p = 0.0002). Among those with moderate CKD, rosuvastatin was associated with a 45% reduction in risk of myocardial infarction, stroke, hospital stay for unstable angina, arterial revascularization, or confirmed cardiovascular death (HR, 0.55; 95% CI, 0.38-0.82; p = 0.002) and a 44% reduction in all-cause mortality (HR, 0.56; 95% CI, 0.37-0.85; p = 0.005). Median LDL-C and hs-CRP reductions as well as side effect profiles associated with rosuvastatin were similar among those with and without CKD. Median eGFR at 12 months was marginally improved among those allocated to rosuvastatin, as compared with placebo.
Conclusions: Rosuvastatin reduces first cardiovascular events and all-cause mortality among men and women with LDL-C <130 mg/dl, elevated hs-CRP, and concomitant evidence of moderate CKD.
Perspective: The data on efficacy of statins for primary prevention in patients with CKD are mixed. This secondary analysis of JUPITER supports use of 20 mg of rosuvastatin even in those who are at relatively low risk based upon LDL-C if the hs-CRP is >2 mg/dl. It is important to consider that the results were achieved with rosuvastatin dosing that lowered the LDL-C by 52% and hs-CRP by 37%, which are considerably greater effects than achieved with standard statin dosing. Unfortunately, a creatinine >2 mg/dl was an exclusion criterion in JUPITER, so the relative benefit in patients with more severe CKD remains unclear. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Pre-Procedural Glucose Levels and the Risk for Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography
Topic: Interventional Cardiology
Date Posted: 4/23/2010
Author(s): Stolker JM, McCullough PA, Rao S, et al.
Citation: J Am Coll Cardiol 2010;55:1433-1440.
Clinical Trial: No
Related Resources
JACC Article: Pre-Procedural Glucose Levels and the Risk for Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography

Study Question: What is the relationship between hyperglycemia and risk of contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography for myocardial infarction (MI)?
Methods: The authors evaluated the association between preprocedural glucose level and CI-AKI in 6,358 patients with acute MIs undergoing coronary angiography. Patients were stratified into five preprocedural glucose groups: <110 mg/dl, 110 to <140 mg/dl, 140 to <170 mg/dl, 170 to <200 mg/dl, and ≥200 mg/dl. The primary outcome was CI-AKI and was defined as a rise in serum creatinine of ≥0.3 mg/dl absolute or ≥50% relative serum creatinine increase 48 hours after the procedure.
Results: There was no relationship between preprocedural glucose and CI-AKI in patients with known prior diabetes mellitus. There was a significant association between glucose and CI-AKI risk in patients without diabetes (CI-AKI rates across the five glucose groups from lowest to highest: 8.2%, 9.9%, 12.4%, 14.9%, and 24.3%; p < 0.001). The association between CI-AKI and preprocedural glucose in nondiabetics remained significant after adjusting for differences in baseline confounders (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.00-1.71 for glucose 110 to <140 mg/dl; OR 1.51, 95% CI 1.11-2.10 for glucose 140 to <170 mg/dl; OR 1.58, 95% CI 1.03-2.43 for glucose 170 to <200 mg/dl; and OR 2.14, 95% CI 1.46-3.14 for glucose >200 mg/dl.
Conclusions: Elevated preprocedural glucose is associated with greater risk for CI-AKI in nondiabetic patients who undergo coronary angiography for acute MI.
Perspective: New-onset renal dysfunction is common in patients undergoing primary percutaneous coronary intervention, although it is not certain if contrast media is the sole mediator of the so-called CI-AKI. This study found that hyperglycemia is a risk factor for this entity in nondiabetics, but not in diabetics. This suggests that hyperglycemia is likely a marker, but not a mediator of renal dysfunction in patients undergoing angiography for acute MI. It may be reasonable to consider measures to reduce the risk of renal dysfunction in hyperglycemic patients undergoing angiography (minimizing contrast volume and ensuring adequate prehydration). Hitinder S. Gurm, M.B.B.S., F.A.C.C

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Clinical Consequences of Intense Athletic Training
New Videos from JACC Interventions
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Title: Delays in Filling Clopidogrel Prescription After Hospital Discharge and Adverse Outcomes After Drug-Eluting Stent Implantation: Implications for Transitions of Care
Topic: General Cardiology
Date Posted: 4/26/2010
Author(s): Ho PM, Tsai TT, Maddox TM, et al.
Citation: Circ Cardiovasc Qual Outcomes 2010;Apr 20:[Epub ahead of print].
Clinical Trial: No
Study Question: How do delays in filling clopidogrel prescriptions impact on outcomes after drug-eluting stent (DES) placement?
Methods: Data from three large integrated health care systems, from January 1, 2004 to December 20, 2007, were reviewed as part of the present analysis. The study population comprised patients who were discharged after DES placement. Information regarding clopidogrel prescriptions was obtained from pharmacy dispensing data. The primary endpoint of interest was all-cause mortality or myocardial infarction (MI), ascertained through April 2008.
Results: A total of 7,402 patients were included in the cohort, of which 1,210 (16%) did not fill their clopidogrel prescription on the day of discharge. The median time delay was 3 days (interquartile range, 1-23 days). Compared to patients who filled their clopidogrel prescription on the day of discharge, patients with any delay had higher rates of the primary endpoint (death or MI) during follow-up (14.2% vs. 7.9%, p < 0.001). In multivariate analysis, patients who had delays in filling clopidogrel prescriptions had an increased risk for death or MI (hazard ratio, 1.53; 95% confidence interval, 1.25-1.87). Similar risks were observed when different time delay periods were examined from greater than 1-day delay to greater than 5-day delay. Adverse outcomes occurred most frequently in the first 30 days after discharge. Additional factors associated with delay included older age, prior MI, diabetes, renal failure, prior revascularization, cardiogenic shock, in-hospital bleeding, and clopidogrel use within 24 hours of admission.
Conclusions: The authors concluded that a substantial number of patients delay filling clopidogrel prescriptions after DES implantation and that this delay is associated with increased risk for adverse outcomes including death and MI.
Perspective: These data support the need for early follow-up after discharge from the hospital. Patients who are seen shortly after discharge are more likely to adhere to cardiac medications. It is concerning that many of the factors associated with delay in clopidogrel prescriptions are also associated with increased risk for in-stent thrombosis. It would be prudent to make sure that such patients have early follow-up with their health care providers or support staff. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Transcatheter Valve-in-Valve Implantation for Failed Bioprosthetic Heart Valves
Topic: Cardiovascular Surgery
Date Posted: 4/26/2010
Author(s): Webb JG, Wood DA, Ye J, et al.
Citation: Circulation 2010;121:1848-1857.
Clinical Trial: No
Study Question: What is the role of transcatheter heart valve implantation within a failed bioprosthesis?
Methods: The investigators performed valve-in-valve implantations in 24 high-risk patients. Surgical reasons for determination of high risk included ≥2 prior thoracotomies in seven, severe pulmonary hypertension in seven, complex congenital cardiac disease in six, severe double-valve disease in five, hepatic cirrhosis in two, severe coronary disease in two, malignancy in one, and carcinoid syndrome in one patient. In addition, a subjective impression of frailty was documented by surgeons in seven elderly patients. Failed valves were aortic (n = 10), mitral (n = 7), pulmonary (n = 6), or tricuspid (n = 1) bioprostheses.
Results: The study investigators reported that implantation was successful, with immediate restoration of satisfactory valve function in all but one patient. No patient had more than mild regurgitation after implantation. No patients died during the procedure. Thirty-day mortality was 4.2%. Mortality was related primarily to learning-curve issues early in this high-risk experience. At baseline, 88% of patients were in New York Heart Association functional class III or IV; at the last follow-up, 88% of patients were in class I or II. At a median follow-up of 135 days (interquartile range, 46-254 days) and a maximum follow-up of 1,045 days, 91.7% of patients remained alive, with satisfactory valve function.
Conclusions: The authors concluded that transcatheter valve-in-valve implantation is a reproducible option for the management of bioprosthetic valve failure. Aortic, pulmonary, mitral, and tricuspid tissue valves were amenable to this approach.
Perspective: This is an important report about the utility of transcatheter valve-in-valve implantation for a failed bioprosthetic valve. Although the sample size is small, the encouraging results suggest that this approach may ultimately become the procedure of choice in valve replacement given the low perioperative risk accompanying this procedure. Large multicenter studies are needed to determine whether indeed this technique can be widely utilized. Ragavendra R. Baliga, M.B.B.S.

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Title: Reproducibility of Proximal Isovelocity Surface Area, Vena Contracta, and Regurgitant Jet Area for Assessment of Mitral Regurgitation Severity
Topic: Noninvasive Cardiology
Date Posted: 4/26/2010
Author(s): Biner S, Rafique A, Rafii F, et al.
Citation: JACC Cardiovasc Imaging 2010;3:235-243.
Clinical Trial: No
Study Question: What is the interobserver variability of different Doppler parameters of mitral regurgitation (MR) severity?
Methods: Data from 16 patients with MR were interpreted by 18 echocardiographers from 11 institutions. All echocardiograms were acquired on a standardized platform by a single experienced research sonographer and each echocardiographer evaluated the identical images for vena contracta width (VCW), effective regurgitant orifice area by proximal isovelocity surface area method (PISA), and qualitative assessment of MR jet area in the left atrium. Results were dichotomized as representing severe or nonsevere MR.
Results: The etiology of MR was degenerative in eight and functional in eight, and the MR jet was eccentric in ten and central in six. The PISA contour was spherical in ten and nonspherical in six, and the MR orifice was clearly identifiable in seven patients. There was ≥30% variation in PISA radius and VCW over the cardiac cycle in 7 of 16. Severity of MR on the basis of jet area was considered interpretable in 273 of 288 (95%) instances, in 206 of 288 (72%) for VCW, and in 72% for PISA. By jet area, MR was severe in 62% of cases and in 36% and 41% using VCW and PISA (p < 0.001). Raw agreement and Kappa coefficients for severity determination based on jet area were 75 ± 16% and 0.32. Corresponding values for VCW were 75 ± 15% and 0.28, and for PISA were 78 ± 15% and 0.37. Substantial (≥80%) raw agreement among readers, was noted for 44% of jet area measurements, 44% of VCW, and 38% of PISA measurements. Univariate predictors of suboptimal raw agreement (<80%) for jet area were degenerative etiology of MR, and for VCW, eccentric rather than central jets and an identifiable MR orifice. For PISA, predictors of suboptimal agreement were an eccentric jet, degenerative etiology, and ≥30% systolic variation in PISA radius.
Conclusions: Separation of severe from nonsevere MR by jet area, VCW, and PISA measurements is associated with substantial interobserver variability. An identifiable regurgitant orifice and stable dimensions of a regurgitant jet over the course of systole are associated with higher reproducibility.
Perspective: This study provides critically important information regarding the reproducibility of clinical assessment of MR severity by Doppler echocardiography. Current guidelines suggest a multi-modality approach to determine MR severity, including the parameters measured in this study as well as an assessment of left atrial and left ventricular size and function. In this study, 18 echocardiographers with between 2 and 40 years of experience evaluated identical images for determination of jet area, VCW, and PISA radius, all of which are common clinically employed parameters for determination of MR severity. The authors noted a disturbing lack of agreement among experienced observers for separation of severe from nonsevere MR based on traditional criteria of an effective regurgitant orifice >40 mm2, grade 3-4 visually assessed MR, or VCW ≥7 mm. This significant variability could be tracked to a degenerative etiology in which jets are frequently eccentric, the vena contracta may not be circular, and the PISA contour may not be truly hemispherical and/or varies in diameter over the course of systole. A minor limitation to this study, which can be expected in clinical practice as well, was the lack of standardization with respect to precisely where in the cardiac cycle PISA radius should be measured (average diameter, minimum diameter, maximum diameter, etc.) and similar lack of standardization for VCW. While a technical limitation in study design, the manner in which these echocardiograms were analyzed faithfully reproduces clinical practice. This study should provide a cautionary tale to the analyzing echocardiographer as well as the physician utilizing the information, and drives home the point that assessment of MR severity must be based on analyzing the entire spectrum of available data and certainly not based on a single “quantifiable” variable alone. William F. Armstrong, M.D., F.A.C.C.

Title: A Phase II, Randomized, Double-Blind, Multicenter, Based on Standard Therapy, Placebo-Controlled Study of the Efficacy and Safety of Recombinant Human Neuregulin-1 in Patients With Chronic Heart Failure
Topic: Heart Failure/Transplant
Date Posted: 4/26/2010 5:00:00 PM
Author(s): Gao R, Zhang J, Cheng L, et al.
Citation: J Am Coll Cardiol 2010;55:1907-1914.
Clinical Trial: yes
Related Resources
JACC Article: A Phase II, Randomized, Double-Blind, Multicenter, Based on Standard Therapy, Placebo-Controlled Study of the Efficacy and Safety of Recombinant Human Neuregulin-1 in Patients With Chronic Heart Failure

Study Question: What is the effect of recombinant human neuregulin-1 (rhNRG-1) on left ventricular (LV) function and symptoms in patients with chronic heart failure (CHF)?
Methods: Forty-four CHF patients designated as New York Heart Association functional class II or III were enrolled in a double-blind, randomized manner and treated with a placebo or rhNRG-1 (0.3, 0.6, or 1.2 μg/kg/day) for 10 days, in addition to standard therapies. The follow-up period was 90 days; LV function and structure measured by magnetic resonance imaging were the primary endpoints.
Results: Although not statistically different from placebo, the LV ejection fraction (LVEF)% was significantly increased by 27.11 ± 31.12% (p = 0.009) at day 30 after rhNRG-1 treatment in the 0.6-μg/kg group, whereas it was only increased 5.83 ± 25.75% in the placebo group (p = 0.49). In addition, there were decreases in end-systolic volume (ESV) (-11.58 ± 12.74%, p = 0.002) and EDV (-5.64 ± 10.03%, p = 0.05) in the 0.6-μg/kg/day group at day 30; more importantly, both ESV and end-diastolic volume (EDV) levels continued to decrease at day 90 (-20.79 ± 17.03% and -14.03 ± 13.17%, respectively), accompanied by a sustained increase in LVEF%. This suggests that short-term treatment with rhNRG-1 results in a long-term reversal of remodeling. The effective dose was proven to be tolerable and safe for CHF patients.
Conclusions: The authors concluded that rhNRG-1 improved the cardiac function of CHF patients by increasing the LVEF% and affected remodeling by decreasing ESV and EDV compared with pretreatment.
Perspective: Neuregulin-1 is expressed in the myocardium and appears to play an important role in the functional and structural integrity of the heart. Preclinical studies have demonstrated that injection of NRG-1 into adult mice leads to cardiomyocyte proliferation and promotes myocardial regeneration after myocardial infarction. Although the etiology of myocardial dysfunction in the current clinical study is not clear, one of the rhNRG-1 dose regimens may have provided beneficial effects on contractile function in patients with CHF. There was no beneficial effect of treatment on symptoms and results were not statistically different compared to the placebo group. The possible benefits of drug treatment were not observed in the high-dose group where adverse events were also most common. Additional clinical studies are needed to confirm a potential beneficial effect of this treatment. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction
Topic: Noninvasive Cardiology
Date Posted: 4/27/2010
Author(s): Chow BJ, Wells GA, Chen L, et al.
Citation: J Am Coll Cardiol 2010;55:1017-1028.
Clinical Trial: No
Related Resources
JACC Article: Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction

Study Question: What are the relative prognostic implications of findings on 64-slice cardiac computed angiography (CTA) compared to traditional risk factor assessment?
Methods: CTA was performed on 2,076 patients who were followed for a mean of 16 ± 8 months. CTA was analyzed for left ventricular ejection fraction (LVEF) and the CTA coronary arteriogram was evaluated on a 17-segment model. Coronary stenoses were defined as absent, <50%, 50-69%, or ≥70%. Patients were categorized as having nocoronary artery disease (CAD), nonobstructive CAD, or obstructive CAD. A total plaque score (TPS) was calculated as the number of segments involved with atherosclerotic plaque. Clinical predictors included nature of symptoms, age, and presence of hypertension and diabetes, among other variables. Patients were followed for major adverse cardiac events (MACE) of nonfatal myocardial infarction and cardiac death.
Results: Average subject age was 58 ± 11.7 years and 52% were male. The average pretest likelihood for CAD was 33.4 ± 34.3%. Nonanginal chest pain was present in 28%, atypical angina in 14.5%, and typical angina in 15.7%, and 42% had no chest pain. On CTA, LVEF was 64.2 ± 10.5%. Normal coronary arteries were noted in 591 (28.5%), nonobstructive CAD in 866 (41.7%), obstructive CAD ≥50% in 619 (29.8%), and CAD ≥70% in 427 (20.6%). High-risk CAD was present in 97 (4.7%), MACE occurred in one subject without CAD, in seven (0.8%) with nonobstructive CAD, in 19 (3.6%) with nonhigh-risk obstructive CAD, and in four (4.1%) with high-risk obstructive CAD. Overall, MACE was noted in 0.2%, 0.8%, 1.6%, 5.3%, and 7.0% of patients without CAD, with nonobstructive CAD, and with one-, two-, and three-vessel CAD (≥50%). Cox models of clinical and CTA variables revealed a global chi-square of 24.97 for clinical variables, which increased to 43.81 with the addition of CAD variables and 54.48 with subsequent addition of LVEF (for both p ≤ 0.001). A similar incremental yield for event prediction was noted for all-cause mortality and nonfatal myocardial infarction, with the sequential addition of CAD variables, LVEF, and TPS.
Conclusions: CTA variables of coronary stenosis severity, LVEF, and TPS have prognostic value in patients presenting for CTA and incremental value over routine clinical predictors.
Perspective: Multiple studies have demonstrated the diagnostic accuracy of CTA for identifying and quantifying CAD as well as calculation of LVEF. This study evaluated a large population of patients followed for an average of <2 years, and demonstrates the incremental value of CTA parameters of CAD presence and overall severity as well as LVEF to standard clinical variables for prediction of events. A significant limitation of this study is the relatively low number of events (31 patients with cardiac death or nonfatal myocardial infarction) and a large number of patients (n = 243) who underwent revascularization procedures. Data regarding indication for revascularization were not provided. Multiple studies have previously demonstrated a link between outcomes and LVEF as well as between coronary disease severity and outcome. The relative role of an anatomical assessment by CTA compared to functional assessment by stress testing remains uncertain. It is not unreasonable to incorporate results of CTA into clinical decision making. William F. Armstrong, M.D., F.A.C.C.

Title: Clinical Features and Outcome of Hypertrophic Cardiomyopathy Associated With Triple Sarcomere Protein Gene Mutations
Topic: Heart Failure/Transplant
Date Posted: 4/27/2010
Author(s): Girolami F, Ho CY, Semsarian C, et al.
Citation: J Am Coll Cardiol 2010;55:1444-1453.
Clinical Trial: No
Related Resources
JACC Article: Clinical Features and Outcome of Hypertrophic Cardiomyopathy Associated With Triple Sarcomere Protein Gene Mutations

Study Question: What is the clinical profile associated with triple sarcomere gene mutations in hypertrophic cardiomyopathy (HCM)?
Methods: The study cohort was comprised of 488 unrelated index HCM patients. These patients underwent screening for myofilament gene mutations by direct deoxyribonucleic acid sequencing of eight genes, including myosin binding protein C (*MYBPC3*), beta-myosin heavy chain (*MYH7)*, regulatory and essential light chains (MYL2, MYL3), troponin-T (TNNT2), troponin-I (*TNNI3*), alphatropomyosin (TPM1), and actin (ACTC).
Results: The investigators found that of the 488 index patients, four (0.8%) harbored triple mutations, as follows: *MYH7-*R869H, *MYBPC3-*E258K, and *TNNI3-*A86fs in a 32-year-old woman; *MYH7-*R723C, *MYH7-*E1455X, and *MYBPC3-*E165D in a 46-year-old man; *MYH7-*R869H, *MYBPC3*-K1065fs, and *MYBPC3-*P371R in a 45-year-old woman; and *MYH7*-R1079Q, *MYBPC3-*Q969X, and *MYBPC3-*R668H in a 50-year-old woman. One had a history of resuscitated cardiac arrest, and three had significant risk factors for sudden cardiac death, prompting the insertion of an implantable cardioverter defibrillator in all, with appropriate shocks in two patients. Moreover, three of four patients had a severe phenotype with progression to end-stage HCM by the fourth decade, requiring cardiac transplantation (n = 1) or biventricular pacing (n = 2). The fourth patient, however, had clinically mild disease.
Conclusions: The authors concluded that hypertrophic cardiomyopathy caused by triple sarcomere gene mutations was rare, but conferred a remarkably increased risk of end-stage progression and ventricular arrhythmias, supporting an association between multiple sarcomere defects and adverse outcome.
Perspective: This study has two important messages. The first is that triple sarcomere mutations are associated with adverse outcome, and the second is that these mutations are rare. More data are needed to determine whether early identification of triple sarcomere mutations by routine testing of HCM patients is a cost-effective strategy in the risk-stratification of these patients. Ragavendra R. Baliga, M.B.B.S.

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Title: Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction
Topic: Interventional Cardiology
Date Posted: 4/27/2010
Author(s): Mewton N, Croisille P, Gahide G, et al.
Citation: J Am Coll Cardiol 2010;55:1200-1205.
Clinical Trial: No
Related Resources
JACC Article: Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction

Study Question: What is the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function 5 days and 6 months after myocardial infarction (MI)?
Methods: The authors randomly assigned 58 patients with acute ST-elevation MI to placebo versus 2.5 mg of cyclosporine immediately before undergoing percutaneous coronary intervention. This trial demonstrated a reduction in infarct size with cyclosporine. This paper reports the results of the magnetic resonance imaging (MRI) substudy.
Results: Twenty-eight patients underwent an MRI at 5 days and 6 months. The infarct size at 6 months was smaller in the cyclosporine group (29 ± 15 g vs. 38 ± 14 g, p = 0.04). There was a significant reduction of LV end-systolic volume (72 ± 20 ml vs. 91 ± 36 ml, p = 0.04 at 5 days and 67 ± 24 vs. 84 ± 29, p = 0.05 at 6 months) in the cyclosporine group. There was no significant difference between the two groups in global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months.
Conclusions: Cyclosporine used prior to reperfusion of acute MI persistently reduces infarct size and does not have a detrimental effect on LV remodeling.
Perspective: This interesting pilot study suggests that a single dose of cyclosporine may be particularly beneficial in reducing reperfusion injury and may prevent adverse remodeling in patients with ST-elevation MI. Larger studies are needed to confirm the findings of this study before this approach can be incorporated into clinical practice. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Coronary Artery Calcium Score and Risk Classification for Coronary Heart Disease Prediction
Topic: Prevention/Vascular
Date Posted: 4/27/2010 4:00:00 PM
Author(s): Polonsky TS, McClelland RL, Jorgensen NW, et al.
Citation: JAMA 2010;303:1610-1616.
Clinical Trial: No
Study Question: To what degree does adding the coronary artery calcium score (CACS) to traditional risk factors improve the prediction model for cardiovascular events?
Methods: CACS was measured by computed tomography in 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident coronary heart disease (CHD) were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. The net reclassification was used to demonstrate the improvement for predicting CHD events using model 2 versus model 1.
Results: Mean age was 62 years and 46% were men. At baseline, about 5% (mean age 75 years) were in the high-risk group and >60% (mean age 58 years) were in the low-risk group. During a median of 5.8 years of follow-up among a final cohort of 5,878 patients, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; p < 0.001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. The use of statins or presence of diabetes did not influence the results.
Conclusions: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.
Perspective: The intermediate-risk group achieved a substantially higher net reclassification than the overall cohort and, therefore, appears to benefit the most from a CACS-adjusted strategy. The 6% incident CHD in the high-risk subjects with a zero CACS, supports a recommendation that high-risk persons do not benefit from CACS and rather should be treated based on standard guidelines. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: The Impact of Transcatheter Atrial Septal Defect Closure in the Older Population: A Prospective Study
Topic: Congenital Heart Disease
Date Posted: 4/28/2010
Author(s): Khan AA, Tan JL, Li W, et al.
Citation: JACC Cardiovasc Interv 2010;3:276-281.
Clinical Trial: No
Related Resources
JACC Cardiovasc Interv Article: The Impact of Transcatheter Atrial Septal Defect Closure in the Older Population: A Prospective Study

Study Question: What is the safety and efficacy of transcatheter atrial septal defect (ASD) closure in an older population?
Methods: In this single-center, prospective clinical trial, consecutive patients ages >40 years with hemodynamically significant ASD (defined by right heart dilation and Qp:Qs ≥1.5 by echocardiogram) were enrolled. Study protocol included laboratory testing (atrial and brain natriuretic peptides), electrocardiogram, chest X-ray, transthoracic echocardiogram (ECHO), 6-minute walk test (6MWT), quality of life (QOL; assessed with short form 36, version 2), and assessment of New York Heart Association (NYHA) functional class, with all tests performed immediately prior to ASD closure and at 6 weeks and 1 year post-closure. Transcatheter ASD closure was performed with the Amplatzer septal occluder (AGA Medical) using balloon sizing or intraprocedural echocardiography.
Results: Twenty-three patients (57% female, mean 69 years) were enrolled and all underwent successful device implantation. Significant comorbidities included atrial fibrillation (21%), hypertension (30%), hypercholesterolemia (26%), ischemic heart disease (13%), and chronic renal failure (4%). At the time of device implantation, mean pulmonary artery (PA) pressure was 22 mm Hg, Qp:Qs was 2.2, and ASD size was 18 mm. Mean implanted device size was 24 mm (range 10-36 mm), with two patients requiring implantation of two devices for separate defects. New-onset atrial fibrillation in one patient was the only significant periprocedural complication reported. NYHA functional class improved in the majority of patients from predominately class II (70%) preclosure to predominately class I (78%) at 1-year follow-up (p < 0.0001). 6MWT distance improved from 400 m at baseline to 451 and 493 m at 6-week and 1-year follow-up, respectively (p = 0.001). QOL physical and mental health scores increased significantly at 1 year (p ≤ 0.007). One-year ECHO follow-up demonstrated significant reduction in right ventricular diastolic dimension and right atrial volume, and increase in left ventricular diastolic and systolic dimensions and ejection fraction (p ≤ 0.004).
Conclusions: Percutaneous ASD closure is feasible in an older population and results in functional and anatomic improvements at 1 year.
Perspective: This prospective study, although nonrandomized, demonstrates that transcatheter ASD device closure can be undertaken in an older population with minimal procedural adverse effects. Efficacy of ASD device closure (i.e., presence of residual atrial level shunt) is not reported. The study cohort is small (n = 23), generally healthy (only 13% had ischemic heart disease), and uncommonly encountered clinically (no subjects had significant pulmonary hypertension despite a mean ASD size of 18 mm, Qp:Qs of >2:1, and age of nearly 70 years), all factors that limit the generalizability of this study. Timothy B. Cotts, M.D., F.A.C.C., Bryan Goldstein, M.D.

Title: Primary Transcatheter Patent Foramen Ovale Closure Is Effective in Improving Migraine in Patients With High-Risk Anatomic and Functional Characteristics for Paradoxical Embolism
Topic: Congenital Heart Disease
Date Posted: 4/28/2010
Author(s): Rigatelli G, Dell’Avvocata F, Ronco F, et al.
Citation: JACC Cardiovasc Interv 2010;3:282-287.
Clinical Trial: yes
Related Resources
JACC Cardiovasc Interv Article: Primary Transcatheter Patent Foramen Ovale Closure Is Effective in Improving Migraine in Patients With High-Risk Anatomic and Functional Characteristics for Paradoxical Embolism

Study Question: What is the effectiveness of transcatheter patent foramen ovale (PFO) closure in improving migraine in a group of patients with high-risk anatomic and functional characteristics for paradoxical embolism?
Methods: In this single-center, nonrandomized, prospective trial, patients with medication-refractory migraine and PFO referred for consideration of transcatheter PFO closure were enrolled. The Migraine Disability Assessment Score (MIDAS) was administered to all patients for evaluation of migraine severity. Device closure of PFO was performed in patients meeting high-risk inclusion criteria, including: curtain shunt pattern of right-to-left (R-L) shunt on transcranial Doppler (TC-D) and transesophogeal echocardiography (TEE), refractory and disabling migraine (MIDAS class 3-4), PFO, R-L shunt during normal respiration, atrial septal aneurysm, coagulation abnormalities, and presence of eustachian valve. Transcatheter PFO closure was performed using devices from AGA Medical Corporation and St. Jude Medical Incorporated, based on specific intracardiac echocardiographic findings. Follow-up included TEE, TC-D, MIDAS, and clinical interviews.
Results: Eighty-six patients (79% female, mean 35 ± 6.7 years) were enrolled and 40 met criteria for transcatheter PFO closure. Patients ineligible for PFO closure received standard of care medical management. Transcatheter PFO closure was successful and performed without periprocedural complications in all 40 subjects. The Amplatzer PFO Occluder was used in eight patients, Amplatzer Cribriform Occluder in 14 patients, and Premere occlusion system in 18 patients. At a mean follow-up of 29.2 ± 14.8 months, mean MIDAS score had fallen from 35.8 ± 4.7 to 8.3 ± 7.8 (p < 0.03) in the PFO closure group, and from 22.6 ± 7.1 to 19.1 ± 8.2 (p = 0.06) in the medical management group. PFO closure without residual shunt was achieved in 95% of subjects. Of 32 subjects who reported migraine with aura at baseline, all subjects reported abolishment of aura at follow-up. New-onset atrial fibrillation developed in 5% of PFO closure patients during follow-up.
Conclusions: In a highly selected population of patients with medically-refractory migraines and PFO with certain proposed high-risk anatomic and functional features, transcatheter PFO closure resulted in a marked reduction in migraine severity and abolition of aura.
Perspective: The MIST (Migraine Intervention with Starflex Technology) study, a large, randomized, sham-controlled study, failed to demonstrate significant symptomatic improvement in patients with migraine undergoing PFO closure. The question remains as to whether a subset of selected patients with migraine might benefit from PFO closure. This nonrandomized, possibly nonconsecutive, series reported by Rigatelli et al. is unique in its selection of patients with high-risk characteristics (for R-L shunt and microembolism) for PFO closure. This kind of highly selected group (whether using the described characteristics or others) may represent a subset of migraineurs more likely to respond to transcatheter therapy. However, the absence of a sham-control group and randomization of consecutive subjects severely limit the generalization of these data. Timothy B. Cotts, M.D., F.A.C.C., Bryan Goldstein, M.D.

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Title: Gene-Expression Profiling for Rejection Surveillance After Cardiac Transplantation
Topic: Heart Failure/Transplant
Date Posted: 4/28/2010
Author(s): Pham MX, Teuteberg JJ, Kfoury AG, et al., on behalf of the IMAGE Study Group.
Citation: N Engl J Med 2010;Apr 22:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the utility of peripheral blood gene-expression profiling compared to endomyocardial biopsy for monitoring of rejection in patients following heart transplantation?
Methods: A total of 602 patients who had undergone cardiac transplantation 6 months to 5 years previously were randomly assigned to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. A noninferiority comparison of the two approaches was performed with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation.
Results: During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04%; 95% confidence interval, 0.67-1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; p = 0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, p < 0.001).
Conclusions: The authors concluded that among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies.
Perspective: Routine endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant; however, this is an invasive procedure associated with risks and patient discomfort. Previous studies have demonstrated that scores derived from analysis of the expression of 11 informative genes from peripheral blood mononuclear cells correlate well with histologic rejection, leading to a commercially available test (Allomap). This test may be useful in reducing the need for some endomyocardial biopsies, although the current study was not blinded and only 20% of eligible patients were enrolled due to patient or physician preferences. The applicability of this approach to the general transplant population will require further study with additional larger trials. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Carotid Intima-Media Thickness and Presence or Absence of Plaque Improves Prediction of Coronary Heart Disease: The ARIC (Atherosclerosis Risk In Communities) Study
Topic: Noninvasive Cardiology
Date Posted: 4/29/2010
Author(s): Nambi V, Chambless L, Folsom AR, et al.
Citation: J Am Coll Cardiol 2010;55:1600-1607.
Clinical Trial: No
Related Resources
JACC Article: Carotid Intima-Media Thickness and Presence or Absence of Plaque Improves Prediction of Coronary Heart Disease: The ARIC (Atherosclerosis Risk In Communities) Study
Trial: Atherosclerosis Risk in Communities (ARIC)

Study Question: Does carotid intima-media thickness (CIMT) and the presence of plaque improve coronary heart disease (CHD) risk prediction when used with traditional risk factors?
Methods: Data from the Atherosclerosis Risk in Communities (ARIC) study, of 15,792 subjects (between 45 and 64 years old) from four US communities were used for the present analysis. Risk factor prediction models were considered for the total cohort of men and women. Models included traditional risk factors only, or risk factors with CIMT. Additional models included traditional risk factors and the presence of carotid plaque, and the traditional risk factors with CIMT together with plaque. Models were compared using the receiver-operating characteristic curve (AUC). Cox proportional hazard models were used to estimate 10-year risk for CHD. Number of subjects reclassified was also determined for each of the models.
Results: Of the 13,145 subjects included (5,682 men and 7,463 women), there were 1,812 CHD events over a 15.1-year follow-up. Plaque was observed in 13.6% of those with a CIMT in the <25th percentile, in 26.6% of those with a CIMT in the 25th-75th percentile, and 65.3% of those with a CIMT in the >75th percentile. An estimated 23% of the subjects were reclassified when CIMT and plaque were added to the models. CIMT and plaque resulted in the greatest improvement in the AUC; increasing from 0.742 for traditional risk factors only to 0.755 when both CIMT and plaque were added to the model. These models (containing both CIMT and plaque) also had the best net reclassification index in the overall population. For women, adding plaque to the traditional risk factors model had a more pronounced effect on the AUC than did the addition of CIMT. In contrast, adding CIMT to the traditional risk factors model had a more pronounced effect on the AUC than did the addition of plaque for men.
Conclusions: The authors concluded that the addition of CIMT and plaque to traditional risk factors improved risk prediction for CHD events.
Perspective: Addition of characteristics to present risk prediction models is in part dependent on added accuracy in prediction. However, examining the cost-benefit is needed prior to wide-scale adoption of measures such as CIMT. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Lipoprotein-Associated Phospholipase A2 and Risk of Coronary Disease, Stroke, and Mortality: Collaborative Analysis of 32 Prospective Studies
Topic: Prevention/Vascular
Date Posted: 4/29/2010 8:00:00 PM
Author(s): The Lp-PLA2 Studies Collaboration.
Citation: Lancet 2010;375:1536-1544.
Clinical Trial: No
Study Question: What is the association between circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with risk of coronary heart disease (CHD), stroke, and mortality under different circumstances?
Methods: A meta-analysis was performed using individual records from 79,036 participants in 32 prospective studies (yielding 17,722 incident fatal or nonfatal outcomes during 475,000 person-years at risk). Within study regressions were used to calculate risk ratios (RRs) per 1 standard deviation (SD) higher value of Lp-PLA2 or other risk factor. The primary outcome was CHD.
Results: Mean age at entry of the 79,036 participants was 64 years (SD 10). Lp-PLA2 activity and mass were associated with each other (r = 0.51; 95% confidence interval, 0.47-0.56) and pro-atherogenic lipids. There were rough log-linear associations of Lp-PLA2 activity and mass with risk of CHD and vascular death. RRs, adjusted for conventional risk factors, were 1.10 with Lp-PLA2 activity and 1.11 with Lp-PLA2 mass for CHD; 1.08 and 1.14 for ischemic stroke; 1.16 and 1.13 for vascular mortality; and 1.10 and 1.0 for nonvascular mortality, respectively. RRs with Lp-PLA2 were similar in people with and without initial stable vascular disease, apart from vascular death with Lp-PLA2 mass. Adjusted RRs for CHD were 1.10 with non–high-density lipoprotein (HDL) cholesterol and 1.10 (1.00-1.21) with systolic blood pressure.
Conclusions: Lp-PLA2 activity and mass each show continuous associations with risk of CHD, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA2 mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids.
Perspective: The additive relative risk of cardiovascular events associated with Lp-PLA2, an inflammatory enzyme expressed in atherosclerotic plaques, is modest. It is presently being evaluated as a therapeutic target for vascular disease prevention. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Digital Assessment of Endothelial Function and Ischemic Heart Disease in Women
Topic: Prevention/Vascular
Date Posted: 4/30/2010
Author(s): Matsuzawa Y, Sugiyama S, Sugamura K, et al.
Citation: J Am Coll Cardiol 2010;55:1688-1696.
Clinical Trial: No
Related Resources
JACC Article: Digital Assessment of Endothelial Function and Ischemic Heart Disease in Women

Study Question: Does reactive hyperemia peripheral arterial tonometry predict ischemic heart disease in women?
Methods: The study population was comprised of postmenopausal women scheduled for cardiac catheterization as an evaluation of chest pain. Digital reactive hyperemia peripheral arterial tonometry was measured prior to catheterization. Nonobstructive coronary artery disease (CAD) was diagnosed by angiography, including measurement of coronary blood flow and cardiac lactate production during intracoronary acetylcholine provocation testing and cardiac scintigraphy with stress test.
Results: Of the 140 women in whom digital reactive hyperemia peripheral arterial tonometry was measured, 68 (49%) had obstructive CAD and 42 (30%) had nonobstructive CAD. Reactive hyperemia peripheral arterial tonometry indexes were attenuated in both women with obstructive and nonobstructive CAD. In multivariate models, only the digital reactive hyperemia peripheral arterial tonometry index was significantly associated with ischemic heart disease, including obstructive CAD and nonobstructive CAD (odds ratio, 0.51; 95% confidence interval, 0.38-0.68). Reactive hyperemia peripheral arterial tonometry was a significant predictor of ischemic heart disease when added to risk models (area under the curve 0.85).
Conclusions: The investigators concluded that digital reactive hyperemia peripheral arterial tonometry is attenuated in women with ischemic heart disease, including women with nonobstructive CAD. Reactive hyperemia peripheral arterial tonometry may be a useful tool for identification of high-risk women.
Perspective: Further research is warranted to determine if reactive hyperemia peripheral arterial tonometry may assist in the identification of women at greatest risk for CHD events and to understand management of patients with nonobstructive CAD, which can assist in both symptom improvement and reduction in risk of events. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Long-Term Clinical Consequences of Intense, Uninterrupted Endurance Training in Olympic Athletes
Topic: General Cardiology
Date Posted: 4/30/2010
Author(s): Pelliccia A, Kinoshita N, Pisicchio C, et al.
Citation: J Am Coll Cardiol 2010;55:1619-1625.
Clinical Trial: No
Related Resources
JACC Article: Long-Term Clinical Consequences of Intense, Uninterrupted Endurance Training in Olympic Athletes

Study Question: What is the incidence of cardiac events and/or left ventricular (LV) dysfunction in athletes exposed to strenuous and uninterrupted training for extended periods of time?
Methods: Clinical profile and cardiac dimensions and function were assessed in 114 Olympic athletes (78% male, mean age 22 ± 4 years) free of cardiovascular disease and participating in endurance disciplines, and who experienced particularly intensive and uninterrupted training for 2-5 consecutive Olympic games (total 344 Olympic events), over a 4- to 17-year period (mean 8.6 ± 3 years).
Results: Over the extended period of training and competition, no cardiac events or new diagnoses of cardiomyopathies occurred in the 114 Olympic athletes. Global LV systolic function was unchanged (ejection fraction 62 ± 5% to 63 ± 5%, p = NS), and wall motion abnormalities were absent. In addition, LV diastolic volumes (142 ± 26 ml to 144 ± 25 ml, p = 0.52) and LV mass index (109 ± 21 g/m2 to 110 ± 22 g/m2, p = 0.74) were unchanged, and LV filling patterns remained within normal limits; left atrial dimension showed a mild increase (37.8 ± 3.7 mm to 38.9 ± 3.2 mm, p < 0.001).
Conclusions: In young Olympic athletes, extreme and uninterrupted endurance training over long periods of time (up to 17 years) was not associated with deterioration in LV function, significant changes in LV morphology, or occurrence of cardiovascular symptoms or clinical events.
Perspective: Despite general recommendations for regular physical activity, the world of medicine has a somewhat schizophrenic relationship with athletics. Even though regular physical exercise is associated with a lower incidence of mortal and morbid cardiac events, there remains some trepidation about the safety of more intense athletic competition. These data confirm that athletes who maintain very intense training over an extended period do not suffer cardiac consequences as a result of their athletic conditioning. It seems reasonable to encourage physical activity in practice as well as in principle, now armed with additional data showing that even intense physical conditioning does not represent a cardiac risk. David S. Bach, M.D., F.A.C.C.

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Gene Expression Profiles Rejection in Transplants
Three Studies Look at CV
Risk Markers
[Ссылки могут видеть только зарегистрированные и активированные пользователи]

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Title: Effects of Polyunsaturated Omega-3 Fatty Acids on Responsiveness to Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention The OMEGA-PCI (OMEGA-3 Fatty Acids After PCI to Modify Responsiveness to Dual Antiplatelet Therapy) Study
Topic: Interventional Cardiology
Date Posted: 4/30/2010
Author(s): Gajos G, Rostoff P, Undas A, Piwowarska W.
Citation: J Am Coll Cardiol 2010;55:1671-1678.
Clinical Trial: yes
Related Resources
JACC Article: Effects of Polyunsaturated Omega-3 Fatty Acids on Responsiveness to Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention The OMEGA-PCI Study

Study Question: What is the effect of omega-3 polyunsaturated fatty acids (PUFAs) on platelet response to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI)?
Methods: This was an investigator-initiated, prospective, single-center, double-blind, placebo-controlled, randomized study. Patients receiving standard dual antiplatelet therapy (aspirin 75 mg/day and clopidogrel 600 mg loading dose followed by 75 mg/day) were randomly assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmission aggregometry (adenosine diphosphate and arachidonic acid [AA] were used as agonists) and assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein at baseline, 12 hours, 3-5 days, and 30 days after randomization.
Results: The P2Y12 reactivity index was significantly lower, by 22.2%, after 1 month of treatment with omega-3 PUFAs compared with placebo when used in addition to dual antiplatelet therapy (p = 0.020). Maximal platelet aggregation induced by 5 and 20 µmol/L adenosine diphosphate was lower by 13.3% (p = 0.026) and 9.8% (p = 0.029), respectively, after 1 month of treatment with omega-3 PUFAs compared with placebo. Platelet aggregation after AA stimulation was low and did not change significantly throughout the study.
Conclusions: The addition of omega-3 ethyl esters to the combination of aspirin and clopidogrel significantly potentiates platelet response to clopidogrel after PCI.
Perspective: The effectiveness of dual antiplatelet therapy with aspirin and clopidogrel towards reducing stent thrombosis and other ischemic events in patients at high vascular risk has stimulated further interest in refining this therapeutic strategy. Several factors have been shown to contribute to variation in platelet response to clopidogrel, including CYP polymorphisms and interactions with other drugs. Omega-3 PUFAs, at higher doses than the current study, have been previously shown to exert antiplatelet and antithrombotic effects. The current study demonstrates that omega-3 PUFAs are also effective in potentiating the antiplatelet effects of clopidogrel. It will be especially interesting to determine whether omega-3 PUFAs will be effective in reducing stent thrombosis when added to aspirin and clopidogrel, although this will require a much larger study. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy
Topic: Prevention/Vascular
Date Posted: 4/30/2010
Author(s): Akdim F, Stroes ES, Sijbrands EJ, et al.
Citation: J Am Coll Cardiol 2010;55:1611-1618.
Clinical Trial: No
Related Resources
JACC Article: Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy

Study Question: How effective is antisense inhibition of apolipoprotein (apo) B in reducing low-density lipoprotein (LDL) cholesterol when patients are already on statin therapy?
Methods: This was a randomized, placebo-controlled, dose-escalation Phase 2 study designed to evaluate the effects of mipomersen in hypercholesterolemic subjects taking stable statin therapy. Seventy-four subjects were enrolled sequentially into one of six dose cohorts at a 4:1 (active/placebo) ratio. Subjects received seven doses of 300-400 mg over 5 weeks in the first five cohorts and 15 doses of 200 mg over 13 weeks in the sixth cohort. Prespecified endpoints included percentage change from baseline in apo B and LDL cholesterol. Safety was assessed with laboratory test results and by the incidence and severity of adverse events.
Results: The apo B and LDL cholesterol were reduced by 19% to 54% and 21% to 52%, respectively, at doses of 100 mg/wk mipomersen and higher in the 5-week treatment cohorts. Efficacy seemed to increase upon treatment for 13 weeks at a dose of 200 mg/wk. Injection site reactions (mild to moderate erythema [90%]) and hepatic transaminase increases (17%) were the most common adverse events, leading to discontinuation in two subjects and one subject, respectively. In the 13-week treatment cohort, 5 of 10 subjects (50%) had elevations ≥3x the upper limit of normal, four of which persisted on two consecutive occasions.
Conclusions: The authors concluded that mipomersen might hold promise for treatment of patients not reaching target LDL cholesterol levels on stable statin therapy.
Perspective: Reduction of LDL with statin therapy has proven to be effective in reducing cardiovascular events. However, not all patients reach target LDL levels with statins, and additional LDL-lowering therapies may be beneficial for these patients. The current study demonstrates that targeting apo B with antisense therapy may be beneficial in further lowering LDL. Several issues need to be addressed in additional trials including: the effect of mipomersen on LDL in patients treated with higher-dose statins, the implications of transaminase elevations, and whether beneficial effects on atherosclerosis will be achieved with mipomersen. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Finding the Right Job in Clinical Practice or Academia: Advice for Young Clinicians and Investigators
Topic: General Cardiology
Date Posted: 5/3/2010
Author(s): Alpert JS.
Citation: Circulation 2010;121:1862-1865.
Clinical Trial: No
Perspective: The following are 10 points to remember about finding the right job in clinical practice or academia.

1. Before one starts a job search, it is essential to make the very personal decision concerning what type of job one is seeking (i.e., clinical investigation, basic science investigation, clinical practice, clinical practice combined with teaching, industry-related positions, hospital-based employment, and health care administration).

2. To base a career decision on geographic considerations may seem frivolous in this day and age of enhanced communications and travel, but that is to deny the primordial influence that climate, locale, customs, and mores have on our evolving maturation.

3. The kind of job setting that one seeks will determine to a large degree the environment in which you will work. For example, for those who would like to work as a clinician/investigator, it is more than likely that they will find a job in a university hospital or a large private referral hospital linked to a medical school.

4. The curriculum vitae (CV) should be carefully prepared and read by a knowledgeable writer.

5. There are many ways to find job openings (journals, training sites, faculty mentors, etc.). There are many physician placement services that find doctors for a variety of practices. The placement service charges the practice for this service; the trainee does not have to pay anything initially, but the practice may attempt to recoup its investment by placing the cost of the placement service in the newly hired physician’s overhead budget.

6. Once the applicant has been invited to come for an interview with a prospective practice, it is important to gain as much knowledge as possible about the practice, the partners, the environment, the hospitals used by the practice, the status of the financial health of the practice, and the level of happiness of the physicians and staff who work in this setting.

7. Applicants should be friendly, positive, honest, and engaging during the interview and try to give the impression that they would be an asset to the practice or institution that is interviewing them.

8. One should not typically accept the first offer made because it makes the other party to the negotiations feel either that they offered too much at the start or that you are easily convinced to accept anything they propose. It is usually a good idea to have an attorney review the contract and discuss its terms and conditions with you before signing it.

9. Candidates who are international medical graduates must pay attention to the visa requirements for the United States. The prospective employer should be willing to offer them an H-1B visa, and some underserved positions will enable them to get an H-1B visa more easily than others.

10. There is an organization that specializes in helping physicians with opportunities for those who want to devote part of their workday to family concerns such as child rearing ([Ссылки могут видеть только зарегистрированные и активированные пользователи]). Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Multimarker Prediction of Coronary Heart Disease Risk: The Women’s Health Initiative
Topic: Prevention/Vascular
Date Posted: 5/3/2010 5:00:00 PM
Author(s): Kim HC, Greenland P, Rossouw JE, et al.
Citation: J Am Coll Cardiol 2010;55:2080-2091.
Clinical Trial: No
Related Resources
JACC Article: Multimarker Prediction of Coronary Heart Disease Risk: The Women’s Health Initiative

Study Question: To what degree do biomarkers contribute to improved coronary heart disease (CHD) risk prediction in postmenopausal women compared with assessment using traditional risk factors (TRFs) only?
Methods: The Women’s Health Initiative Hormone Trials enrolled 27,347 postmenopausal women ages 50-79 years. Associations of TRFs and 18 biomarkers were assessed in a nested case-control study including 321 patients with CHD and 743 controls. Four prediction equations for 5-year CHD risk were compared: two Framingham risk score covariate models; a TRF model including statin treatment, hormone treatment, and cardiovascular disease history as well as the Framingham risk score covariates; and an additional biomarker model that also included the five significantly associated markers of the 18 tested (interleukin-6, D-dimer, coagulation factor VIII, von Willebrand factor, and homocysteine).
Results: The TRF model showed an improved C-statistic (0.729 vs. 0.699, p = 0.001) and net reclassification improvement (6.42%) compared with the Framingham risk score model. The additional biomarker model showed additional improvement in the C-statistic (0.751 vs. 0.729, p = 0.001) and net reclassification improvement (6.45%) compared with the TRF model. Predicted CHD risks on a continuous scale showed high agreement between the TRF and additional biomarker models (Spearman’s coefficient = 0.918). Among the 18 biomarkers measured, C-reactive protein (CRP) level did not significantly improve CHD prediction either alone or in combination with other biomarkers.
Conclusions: Moderate improvement in CHD risk prediction was found when an 18-biomarker panel was added to predictive models using TRFs in postmenopausal women.
Perspective: While very interesting, this case-control study of the value of biomarkers in predicting CHD events in women adds little for the clinician who would like to know whether the high-sensitivity CRP (hs-CRP) is useful for assessing CHD event risk. The TRF model, which found no value to hs-CRP, included use of statins, hormone treatment, and a history of cardiovascular disease (not defined in the manuscript but prevalence of 14% in the control and 27% in the cases) at baseline. Each was independently associated with increased risk for CHD, but is expected to reduce the incremental value of hs-CRP. Ridker and colleagues demonstrated that the hs-CRP can be used to help decide the value of statin therapy in relatively low-risk men and women (JUPITER study), and that it adds considerably to risk prediction in intermediate- and high-risk women (JAMA 2007;297:611-9). Using the Woman’s Health Study of 24,558 healthy US women followed for cardiovascular events for a median of 10.2 years, adding hs-CRP to TRFs, resulted in reclassification of 40-50% of intermediate-risk into higher- or lower-risk categories with improved accuracy compared to other models. The model that has received the most attention is the Reynold’s Risk Score, which is a simplified model limited to age, systolic blood pressure, glycated hemoglobin if diabetic, current smoking, total and high-density lipoprotein cholesterol, hs-CRP, and parental history of myocardial infarction before age 60 years. Melvyn Rubenfire, M.D., F.A.C.C.

Title: The Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide for Death and Cardiovascular Events in Healthy Normal and Stage A/B Heart Failure Subjects
Topic: Heart Failure/Transplant
Date Posted: 5/3/2010 5:00:00 PM
Author(s): McKie PM, Cataliotti A, Lahr BD, et al.
Citation: J Am Coll Cardiol 2010;55:2140-2147.
Clinical Trial: No
Related Resources
JACC Article: The Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide for Death and Cardiovascular Events in Healthy Normal and Stage A/B Heart Failure Subjects

Study Question: What is the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors for heart failure (HF), which we term healthy normal?
Methods: The investigators included a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent an echocardiogram and NT-proBNP measurement. They further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. They defined healthy normal as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. They followed the study participants for mortality, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively.
Results: The investigators found that NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of mortality, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities.
Conclusions: The investigators concluded that these findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects, and have important implications for NT-proBNP–based strategies for early detection and primary prevention of cardiovascular disease.
Perspective: The ability of any diagnostic test, including biomarkers, to enhance the quality and efficacy of clinical care depends on several factors, including pretest probability, sensitivity and specificity, cost, benefits, risks, patient preference, and alternatives (such as continued observation, or proceeding to another test or empirical treatment). An important assumption in the Bayesian model is that a test adds new additional information above and beyond what is already known (Heart Fail Clin 2009;5:463-70). The findings of these investigators suggest that NT-proBNP does not add further value in risk stratification of healthy normal subjects. Other studies have suggested that biomarkers are indeed useful in screening for preclinical disease (N Engl J Med 2004;350:655-63). Larger studies are required to determine the precise utility of biomarkers in healthy subjects. Ragavendra R. Baliga, M.B.B.S.

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Title: Heart Failure With Preserved Ejection Fraction in Outpatients With Unexplained Dyspnea: A Pressure-Volume Loop Analysis
Topic: Heart Failure/Transplant
Date Posted: 5/4/2010
Author(s): Penicka M, Bartunek J, Trakalova H, et al.
Citation: J Am Coll Cardiol 2010;55:1701-1710.
Clinical Trial: No
Related Resources
JACC Article: Heart Failure With Preserved Ejection Fraction in Outpatients With Unexplained Dyspnea: A Pressure-Volume Loop Analysis

Study Question: Is heart failure with preserved ejection fraction (HFPEF) present in outpatients with unexplained chronic dyspnea, and does it elucidate its underlying mechanisms in this population, using invasive pressure-volume loop analysis?
Methods: The study cohort, comprised of 30 patients (ages 67 ± 8.6 years, 27% males) with preserved left ventricular (LV) EF (≥50%) and unexplained chronic New York Heart Association functional class II-III dyspnea, underwent heart catheterization. Patients with significant coronary artery stenosis (≥50%) were excluded. Pressure-volume loops were assessed using a conductance catheter at rest, hand-grip exercise, leg lifting, and nitroprusside and dobutamine infusion.
Results: Sixty-six percent (n = 20) of patients showed LV end-diastolic pressure >16 mm Hg (normal LV systolic function), whereas the remaining 10 patients served as controls. Patients with HFPEF had significantly higher end-diastolic stiffness (0.205 ± 0.074 vs. 0.102 ± 0.017, p < 0.001) at rest, and their end-diastolic pressure-volume relationship showed a consistent upward and leftward shift during all hemodynamic interventions compared with controls. Regarding the underlying mechanism of HFPEF, 70% (n = 14) of patients had markedly increased end-diastolic stiffness, which was considered a sufficient single pathology to induce increased LV end-diastolic pressure. Twenty percent (n = 4) of patients showed a concomitant presence of moderately increased stiffness and severe LV dyssynchrony, and the remaining 10% (n = 2) of patients, with normal stiffness, showed significant exercise-induced mitral regurgitation at hand-grip exercise. According to the study investigators, if the invasive pressure measurements were absent, only 25% (n = 5) of the outpatients with HFPEF fulfilled the European Society of Cardiology definition of HFPEF.
Conclusions: The authors concluded that a significant proportion of stable outpatients with unexplained chronic dyspnea may have HFPEF. In this cohort, increased LV stiffness, dyssynchrony, and dynamic mitral regurgitation were the major mechanisms underlying development of HFPEF.
Perspective: This is an important study because it suggests that patients with unexplained dyspnea may benefit from a right heart catheterization to determine the pulmonary capillary wedge pressure (as a surrogate for LV end-diastolic pressure) to make a diagnosis of HF. It has always been argued that HF is a ‘clinical’ diagnosis, but as technology evolves, we may continue to detect new HF patients that were hitherto undetected. Ragavendra R. Baliga, M.B.B.S.

Title: Relationship Between Early Physician Follow-up and 30-Day Readmission Among Medicare Beneficiaries Hospitalized for Heart Failure
Topic: Heart Failure/Transplant
Date Posted: 5/4/2010 4:00:00 PM
Author(s): Hernandez AF, Greinger MA, Fonarow GC, et al.
Citation: JAMA 2010;303:1716-1722.
Clinical Trial: No
Study Question: What is the association between outpatient follow-up within 7 days after discharge from a heart failure (HF) hospitalization and readmission within 30 days?
Methods: The study cohort consisted of 30,136 patients from 225 hospitals. The study was an observational analysis of patients ages ≥65 years with HF and discharged to home from hospitals participating in the HF quality improvement program from January 1, 2003, through December 31, 2006. The main outcome measure was all-cause readmission within 30 days after discharge.
Results: Median length of stay was 4 days (interquartile range, 2-6) and 21.3% of patients were readmitted within 30 days. At the hospital level, the median percentage of patients who had early follow-up after discharge from the index hospitalization was 38.3% (interquartile range, 32.4-44.5%). Compared with patients whose index admission was in a hospital in the lowest quartile of early follow-up (30-day readmission rate, 23.3%), the rates of 30-day readmission were 20.5% among patients in the second quartile (risk adjusted hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.78-0.93), 20.5% among patients in the third quartile (risk-adjusted HR, 0.87; 95% CI, 0.78-0.96), and 20.9% among patients in the fourth quartile (risk-adjusted HR, 0.91; 95% CI, 0.83-1.00).
Conclusions: The authors concluded that patients who are discharged from hospitals that have higher early follow-up rates have a lower risk of 30-day readmission.
Perspective: From Ragavendra R. Baliga, M.B.B.S.: This is an important study because it confirms what HF physicians have always known about the importance of timely follow-up of patients after discharge from an index HF hospitalization. The data from this study are particularly helpful to hospitals trying to put together a strategy to reduce re-admission rates for hospitalizations. It has been argued that all HF patients who are admitted to a hospital be managed by a Heart Failure Response Team whose responsibilities include ensuring that patients are scheduled for early follow-up (Heart Fail Clin 2009;5:xi-xiv). It would be interesting to know whether early and regular follow-up of HF patients eventually also results not only in reduced hospitalizations, but also in improved long-term survival.

Expert Commentary From Alfred A. Bove, M.D.: Until now, early follow-up for HF patients after discharge had face validity only. This study confirms the importance of establishing coordinated systems of care in which patients are evaluated early after discharge.

The American College of Cardiology's national quality improvement initiative, Hospital to Home (H2H), identifies early follow-up as one of three core concepts for reducing hospital readmissions. Discharged patients should have a follow-up visit scheduled within 1 week of discharge, as well as the means of getting to that appointment.

Providing support during the transition from inpatient to outpatient status is essential. Hospitals participating in the H2H initiative have increased scheduled appointments by having office practices block appointment slots for discharged patients and by having prepurchased time available.

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Title: Pneumococcal Vaccination and Risk of Acute Myocardial Infarction and Stroke in Men
Topic: Prevention/Vascular
Date Posted: 5/4/2010 4:00:00 PM
Author(s): Tseng HF Slezak JM, Quinn VP, et al.
Citation: JAMA 2010;303:1699-1706.
Clinical Trial: No
Study Question: Multiple studies have shown that preventing influenza by vaccination reduces the risk of vascular events. What is the association between pneumococcal vaccination and risk of acute myocardial infarction (MI) and stroke among men?
Methods: A prospective cohort study was conducted in participants in the California Men’s Health Study (ages 45-69 years) recruited between January 2002 and December 2003, and followed up until December 31, 2007. Demographic and detailed lifestyle characteristics were collected from surveys. Vaccination records were obtained from the Kaiser Immunization Tracking System. Primary outcome was the incidence of acute MI and stroke during the follow-up period in men who had no previous events.
Results: Of the nearly 400,000 men, 63% were white, 14% Hispanic, 7% black, and 8.2% Asian. Hypertension, diabetes, heart failure, and peripheral vascular disease were lower in those unvaccinated. During follow-up, there were 1,211 first MIs in vaccinated person-years (10.73 per 1,000 person-years) compared with 1,494 first MI events in unvaccinated person-years (6.07 per 1,000 person-years). For stroke, there were 651 events in vaccinated person-years (5.30 per 1,000 person-years) compared with 483 events in unvaccinated person-years (1.90 per 1,000 person-years). With propensity score adjustment, there was no evidence for an association between pneumococcal vaccination and reduced risk of acute MI (adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.98-1.21) or stroke (adjusted HR, 1.14; 95% CI, 1.00-1.31). An inverse association was also not found in men of different age and risk groups.
Conclusions: Among a cohort of men ages 45 years or older, receipt of pneumococcal vaccine was not associated with subsequent reduced risk of acute MI and stroke.
Perspective: The relationship between inflammatory markers and acute and chronic inflammation and infections and development of acute coronary syndromes is well established. Guidelines recommend pneumococcal vaccine for men and women with cardiovascular disease, diabetics, and all persons over 65 years old. About one-third of participants in this cohort study were given vaccines. From available data, those who received the vaccine were higher risk, yet accrued no benefit. Should this study be used to change the present guidelines? Certainly not for patients with established coronary disease and strokes who were excluded from this study. As with so many other preventive measures, the results of this study should be considered hypothesis generating for a controlled trial, perhaps in middle-aged and elderly men who are at intermediate risk for coronary events and strokes. The impact of other preventive treatments such as aspirin and statins on the relative value of pneumococcal vaccine cannot be assessed with this study. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Blood-Pressure Reduction With LCZ696, A Novel Dual-Acting Inhibitor of the Angiotensin II Receptor and Neprilysin: A Randomized, Double-Blind, Placebo-Controlled, Active Comparator Study
Topic: Prevention/Vascular
Date Posted: 5/5/2010
Author(s): Ruilope LM, Dukat A, Bohm M, Lacourciere Y, Gong J, Lefkowitz MP.
Citation: Lancet 2010;375:1255-1266.
Clinical Trial: yes
Study Question: Does the added effect of neprilysin inhibition to angiotensin II blockade improve blood pressure control?
Methods: A total of 1,328 patients ages 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks’ treatment in one of eight groups: 100 mg (n = 156 patients), 200 mg (n = 169), or 400 mg (n = 172) LCZ696; 80 mg (n = 163), 160 mg (n = 166), or 320 mg (n = 164) valsartan; 200 mg AHU377 (n = 165); or placebo (n = 173). The primary endpoint was the mean difference across the three single-dose pair-wise comparisons of LCZ696 versus valsartan (100 mg vs. 80 mg, 200 mg vs. 160 mg, and 400 mg vs. 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat.
Results: The reduction in diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction, –2.17 mm Hg; 95% confidence interval [CI], –3.28 to –1.06; p < 0.0001). The reduction in diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (–2.97 mm Hg; 95% CI, –4.88 to –1.07; p = 0.0023) and for 400 mg LCZ696 versus 320 mg valsartan (–2.70 mm Hg; –4.61 to –0.80; p = 0.0055). LCZ696 was well tolerated and no cases of angioedema were reported.
Conclusions: The authors concluded that compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure.
Perspective: Neprilysin is an endopeptidase that may play a role in a variety of disease processes, including hypertension. A previous clinical study using an inhibitor of neprilysin alone did not demonstrate meaningful reductions in blood pressure, which may have been due to reduced neprilysin-dependent breakdown of angiotensin II. The current study thus demonstrates that in the setting of angiotensin II inhibition, additional reduction of blood pressure occurs with inhibition of neprilysin (although in this trial, monotherapy with a neprilysin inhibitor also reduced blood pressure slightly). In contrast to previous trials with the vasopeptidase inhibitor, omapatrilat, angioedema did not occur. Additional trials in a more diverse population are necessary to determine safety and also assess which patients are likely to benefit from this type of treatment. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Minimally Invasive Versus Conventional Mitral Valve Surgery: A Propensity-Matched Comparison
Topic: Cardiovascular Surgery
Date Posted: 5/5/2010
Author(s): Svensson LG, Atik FA, Cosgrove DM, et al.
Citation: J Thorac Cardiovasc Surg 2010;139:926-932.
Clinical Trial: No
Study Question: How do outcomes compare after minimally invasive mitral valve surgery versus conventional surgery with medial sternotomy?
Methods: From January 1995 to January 2004 at a single, very large institution, 2,124 patients underwent isolated mitral valve surgery through a minimally invasive approach, and 1,047 underwent isolated mitral valve surgery through a conventional sternotomy. A propensity score based on 42 factors was used to obtain 590 well-matched patient pairs (56% of cases).
Results: In-hospital mortality was similar for propensity-matched patients: 0.17% (1 of 590) for those undergoing minimally invasive surgery and 0.85% (5 of 590) for those undergoing conventional surgery (p = 0.2). Occurrences of stroke (p = 0.8), renal failure (p > 0.9), myocardial infarction (p = 0.7), and infection (p = 0.8) also were similar. However, 24-hour mediastinal drainage was less after minimally invasive surgery (median 250 vs. 350 ml, p < 0.0001), and fewer patients received transfusions (30% vs. 37%, p = 0.01). More patients undergoing minimally invasive surgery were extubated in the operating room (18% vs. 5.7%, p < 0.0001), and postoperative forced expiratory volume in 1 second was higher. Early after operation, pain scores were lower (p < 0.0001) after minimally invasive surgery.
Conclusions: Within that portion of the spectrum of mitral valve surgery in which propensity matching was possible, minimally invasive mitral valve surgery had cosmetic, blood product use, respiratory, and pain advantages over conventional surgery, and no measured detriments. Mortality and morbidity for robotic and percutaneous procedures should be compared with these minimally invasive outcomes.
Perspective: This study from The Cleveland Clinic used propensity matching to attempt to compensate for differences between patients operated on using conventional sternotomy versus various less invasive approaches. (Minimally invasive operations involved an 8-10 cm [3-4 inch] skin incision, variably right paramedian including division of the third and fourth costal cartilages, a ‘J’ incision from the sternal notch to the fourth intercostal space, or partial right lower sternotomy; but not right minithoracotomy or robotic procedures.) The findings, and the thoughtful inclusion of study limitations in the manuscript, speak for themselves. There should be little debate that the same operation performed using a small incision would be better than that using a large incision. The debate is whether the operation is the same, and how universally applicable are the operative results. Ultimately, the ability to perform mitral valve repair rather than replacement, and the adequacy of the repair, should be more important issues than the size of the scar or even measures of postoperative mediastinal drainage and forced expiratory volume. At this high-volume center, surgeons were able to perform similar (and good) operations using a smaller incision compared to conventional sternotomy. But patients, providers, and insurers should remember and embrace that it is the quality of the surgery, not the size of the scar, that should be of paramount importance. David S. Bach, M.D., F.A.C.C.

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Title: Everolimus-Eluting Versus Paclitaxel-Eluting Stents in Coronary Artery Disease
Topic: Interventional Cardiology
Date Posted: 5/5/2010 4:00:00 PM
Author(s): Stone GW, Rizvi A, Newman W, et al.
Citation: N Engl J Med 2010;362:1663-1674.
Clinical Trial: yes
Study Question: What is the comparative efficacy of everolimus-eluting versus paclitaxel-eluting stents?
Methods: The investigators randomly assigned 3,687 patients at 66 US sites to receive everolimus-eluting or paclitaxel-eluting stents without routine follow-up angiography. The primary endpoint was a 1-year composter rate of target lesion failure (defined as cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization).
Results: Everolimus-eluting stents were superior to paclitaxel-eluting stents with respect to the primary endpoint of target lesion failure (4.2% vs. 6.8%; relative risk, 0.62; 95% confidence interval, 0.46-0.82; p = 0.001). Everolimus-eluting stents were also superior with respect to the major secondary endpoint of the 1-year rate of ischemia-driven target lesion revascularization (p = 0.001) and were noninferior with respect to the major secondary endpoint of the 1-year composite rate of cardiac death target lesion myocardial infarction (p < 0.001 for noninferiority, p = 0.09 for superiority). The 1-year rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents than with paclitaxel-eluting stents (1.9% vs. 3.1%; p = 0.02 for myocardial infarction; 0.17% vs. 0.85%; p = 0.004 for stent thrombosis). Target lesion failure was consistently reduced with everolimus-eluting stents as compared with paclitaxel-eluting stents in 12 prespecified subgroups, except in the subgroup of patients with diabetes (6.4% vs. 6.9%, p = 0.80).
Conclusions: The authors concluded that everolimus-eluting as compared with paclitaxel-eluting stents, resulted in reduced rates of target vessel failure at 1 year.
Perspective: In this prospective, randomized trial, everolimus-eluting stents as compared with paclitaxel-eluting stents resulted in reduced 1-year rate of target lesion failure and ischemia-driven target lesion revascularization. The rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents. The study suggests that with drug-eluting stents, it is possible to achieve minimal late loss with improved clinical efficacy, but without sacrificing safety or any increase in stent thrombosis. The lack of superiority of everolimus-eluting stents among diabetics calls for additional research on newer drugs in this high-risk cohort. Additional studies comparing everolimus-eluting stents with sirolimus- and zotarolimus-eluting stents are also indicated to gauge comparative efficacy with other drug-eluting stents. Debabrata Mukherjee, M.D., F.A.C.C

Title: The Effect of Optimal Medical Therapy on 1-Year Mortality After Acute Myocardial Infarction
Topic: General Cardiology
Date Posted: 5/6/2010
Author(s): Bramlage P, Messer C, Bitterlich N, et al.
Citation: Heart 2010;96:604-609.
Clinical Trial: No
Study Question: Five drug classes have been shown to improve the prognosis of acute myocardial infarction (AMI) in clinical trials: aspirin, beta-blockers, statins, renin angiotensin system (RAS) blockers, and thienopyridines. Does combining these drugs (termed optimal medical therapy [OMT]) result in a reduction in mortality in the clinical practice setting?
Methods: The SAMI (Secondary prevention after Acute Myocardial Infarction) registry was conducted in 2003-2004 in 5,353 patients with an AMI in 79 hospitals in Germany with a cardiology unit or internal medicine department. The primary outcome was the odds ratio (OR) and 95% confidence interval (CI) for mortality from MI in relationship to OMT adjusted for patient risk at baseline.
Results: Mean age was 66.3 years in the OMT group and 70.5 years in the suboptimal group; the type of AMI was ST-elevation MI (STEMI) in 54% in each group; and significantly more in the OMT group were taking one or more of the five drugs on admission. About 63% of each group had a percutaneous transluminal coronary angioplasty and 5% a coronary artery bypass graft (CABG), and >60% were given thrombolytics within 1 hour. At hospital discharge, 89% received aspirin, 90% beta-blockers, 84% statins, 81% RAS blockers, 70% a thienopyridine, and 46.2% OMT. Patients receiving OMT were younger, more frequently male, had more risk factors including nicotine use, hypertension, dyslipidemia, and more often had a history of a CABG. Total mortality was reduced by 74% in patients receiving OMT (adjusted OR, 0.26; 95% CI, 0.18-0.38) versus patients receiving one or no drug. This was consistent in subgroups defined by STEMI/NSTEMI, diabetes, and gender. Mortality was also reduced in patients receiving 2-4 drugs (adjusted OR, 0.49; 95% CI, 0.35-0.68), diabetic patients being the only subgroup with no significant effect. Analyses on the relative importance of either component revealed that withdrawal of beta-blockers (adjusted OR, 0.63; 95% CI, 0.34-1.16) and/or a combination of aspirin/clopidogrel (adjusted OR, 0.59; 95% CI, 0.20-1.17) abolished the risk reduction conferred by OMT.
Conclusions: OMT over 1 year was associated with a significantly lower mortality of patients with AMI in clinical practice. However, OMT is provided to less than half of eligible patients, leaving room for substantial improvement.
Perspective: The percentage of patients discharged on one or more of the five classes of drugs shown to have benefit in patients with an AMI in this study is impressive, but less than 50% received OMT. Increased mortality when withdrawing aspirin/clopidogrel from OMT is not surprising. I am particularly impressed with the impact of withdrawing beta-blockers from OMT on 1-year mortality, considering the mean left ventricular ejection fraction of 56% and the frequency of coronary revascularization. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: The Temporal Variability of Dominant Frequency and Complex Fractionated Atrial Electrograms Constrains the Validity of Sequential Mapping in Human Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 5/6/2010
Author(s): Habel N, Znojkiewicz P, Thompson N, et al.
Citation: Heart Rhythm 2010;7:586-593.
Clinical Trial: No
Study Question: Are dominant frequency (DF) and complex fractionated atrial electrograms (CFAEs) temporally stable during atrial fibrillation (AF)?
Methods: A 64-electrode basket catheter was used to simultaneously record multiple left atrial electrograms for 5 minutes during AF in 18 patients (mean age 60 years) prior to catheter ablation. DF was determined by fast Fourier transformation for each 5-second interval in the 5-minute recordings. CFAEs were identified using commercially available software.
Results: The mean temporal coefficient of variability for DF was 22.7%. CFAEs also were temporally unstable, having a mean duration of 8.8 seconds at individual sites. Sequential DF maps identified only 7% of DF sites, and sequential CFAE maps identified 64% of CFAE sites.
Conclusions: DF and CFAE maps created by sequential point-by-point acquisition of electrograms are of limited value because of temporal instability in DF and CFAEs.
Perspective: Ideally, DF and CFAE maps would be generated by simultaneous multisite recordings, but this is not clinically practical. However, the clinical impact of temporal instability in DF is unclear, particularly since it is not even clear that DF mapping is useful for identifying target sites for catheter ablation of AF. CFAEs commonly are used in clinical practice to select ablation sites, and this study shows that short sampling times may fail to identify CFAEs that are intermittent. However, intermittent CFAEs may not be as specific for appropriate target sites as are persistent CFAEs, so the clinical impact of temporal instability of CFAEs also is unclear. Fred Morady, M.D., F.A.C.C.

Title: Verapamil Eliminates the Hierarchical Nature of Activation Frequencies From the Pulmonary Veins to the Atria During Paroxysmal Atrial Fibrillation
Topic: Arrhythmias
Date Posted: 5/6/2010
Author(s): Kushiyama Y, Osaka T, Yokoyama E, et al.
Citation: Heart Rhythm 2010;7:577-583.
Clinical Trial: No
Study Question: How does verapamil affect dominant frequency (DF) in the pulmonary veins (PVs) and atria during atrial fibrillation (AF)?
Methods: Fast Fourier transform analysis to identify the DF was performed on electrograms recorded at the right atrial free wall (RAFW), coronary sinus (CS), left atrial appendage (LAA), and PVs during AF in 43 patients (mean age 57 years) with paroxysmal AF. Electrograms were recorded before and after infusion of 0.1 mg/kg of verapamil.
Results: At baseline, the maximum DF in the PVs (6.9 Hz) was significantly higher than the DF at the RAFW (6.2 Hz), CS (5.7 Hz), and LAA (5.9 Hz). Verapamil significantly increased DF at the RAFW, CS, and LAA to 6.9, 6.6, and 7.2 Hz, respectively. The maximum DF in the PVs increased to 7.1 Hz. After verapamil infusion, there was no significant difference in DF between the atria and PVs.
Conclusions: The frequency gradient between the PVs and atria during an episode of paroxysmal AF is abolished by verapamil.
Perspective: A higher DF in the PVs than in the atria is consistent with the observation that the PV muscle sleeves often provide the drivers that maintain an episode of paroxysmal AF. Verapamil increases DF in the atria by shortening action potential duration. Elimination of the DF gradient by verapamil suggests that the drug could be proarrhythmic by creating new high-frequency sources of AF in the atria during paroxysmal AF. Nevertheless, no studies have demonstrated clinically significant proarrhythmia from the use of calcium channel blockers in patients with AF. Fred Morady, M.D., F.A.C.C.

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Multi-marker Prediction of CHD Risk
Biomarkers, DES, and Vaccines
[Ссылки могут видеть только зарегистрированные и активированные пользователи]


Title: Relationships Between Emerging Measures of Heart Failure Processes of Care and Clinical Outcomes
Topic: Heart Failure/Transplant
Date Posted: 5/7/2010
Author(s): Hernandez AF, Hammill BG, Peterson ED, et al.
Citation: Am Heart J 2010;159:406-413.
Clinical Trial: No
Study Question: What is the relationship between emerging measures of heart failure processes of care and clinical outcomes?
Methods: The investigators used data for 20,441 Medicare beneficiaries in the OPTIMIZE-HF trial from March 2003 through December 2004, which they linked to Medicare claims data. They examined associations between hospital-level processes of care and patient outcomes. Performance measures included any beta-blocker for patients with left ventricular systolic dysfunction (LVSD); evidence-based beta-blocker for patients with LVSD; warfarin for patients with atrial fibrillation; aldosterone antagonist for patients with LVSD; implantable cardioverter defibrillator for patients with ejection fraction ≤35%; and referral to disease management. Outcome measures were unadjusted and adjusted associations of each process measure with 60-day and 1-year mortality and cardiovascular readmission at the hospital level.
Results: The investigators found that adjusted hazard ratios for 1-year mortality with a 10% increase in hospital-level adherence were 0.94 for any beta-blocker (95% confidence interval [CI], 0.90-0.98; p = 0.004), 0.95 for evidence-based beta-blocker (95% CI, 0.92-0.98; p = 0.004), 0.97 for warfarin (95% CI, 0.92-1.03; p = 0.33), 0.94 for aldosterone antagonists (95% CI, 0.91-0.98; p = 0.006), 0.92 for implantable cardioverter defibrillator (95% CI, 0.87-0.98; p = 0.007), and 1.01 for referral to disease management (95% CI, 0.99-1.03; p = 0.21).
Conclusions: The authors concluded that several evidence-based processes of care are associated with improved outcomes, can discriminate hospital-level quality of care, and could be considered as clinical performance measures.
Perspective: This study suggests that including all the key indicators of quality makes a substantial impact on medication compliance and consequently morbidity and mortality. Currently, ‘core-measures’ include only ACE inhibitor usage in heart failure, but this study suggests that including all the other therapies including beta-blocker and aldosterone antagonist utilization in the ‘core-measures’ should considerably improve the quality of care. Ragavendra R. Baliga, M.B.B.S.

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Title: Rosuvastatin for Primary Prevention in Older Persons With Elevated C-Reactive Protein and Low to Average Low-Density Lipoprotein Cholesterol Levels: Exploratory Analysis of a Randomized Trial
Topic: Prevention/Vascular
Date Posted: 5/7/2010
Author(s): Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM.
Citation: Ann Intern Med 2010;152:488-496.
Clinical Trial: No
Related Resources
Trial: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)

Study Question: Randomized data on statins for primary prevention in older persons are limited, and the relative hazard of cardiovascular disease associated with an elevated cholesterol level weakens with advancing age. What is the efficacy and safety of rosuvastatin in persons 70 years or older?
Methods: A secondary analysis was conducted in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), a randomized, double-blind, placebo-controlled trial in which the 17,802 participants were randomly assigned with low-density lipoprotein (LDL) cholesterol levels less than 130 mg/dl and high-sensitivity C-reactive protein (CRP) levels of 2.0 mg/L or more without cardiovascular disease. Participants were randomly assigned to receive 20 mg of rosuvastatin daily or placebo. The primary endpoint was the occurrence of a first cardiovascular event (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes).
Results: In the 70 years or older group, the median age was 74 years (interquartile 72-77, range 70-97 years). Compared to those 50-69 years old, a higher percentage of older participants were women or had hypertension, and lower percentages were obese or smoked cigarettes, relative to younger participants. A total of 5,695 (32%) of trial participants were 70 years or older and accrued 49% (n = 194) of the 393 confirmed primary endpoints. The rates of the primary endpoint in this age group were 1.22 and 1.99 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio, 0.61; 95% confidence interval [CI], 0.46-0.82; p < 0.001). Corresponding rates of all-cause mortality in this age group were 1.63 and 2.04 (hazard ratio, 0.80; CI, 0.62-1.04; p = 0.090). Although no significant heterogeneity was found in treatment effects by age, absolute reductions in event rates associated with rosuvastatin were greater in older persons. The relative rate of any serious adverse event among older persons in the rosuvastatin versus placebo group was 1.05 (CI, 0.93-1.17).
Conclusions: In apparently healthy older persons without hyperlipidemia but with elevated high-sensitivity CRP levels, rosuvastatin reduces the incidence of major cardiovascular events. Effect estimates from this exploratory analysis with age cut-point chosen after trial completion should be viewed in the context of the overall trial results.
Perspective: Previous studies have shown only modest benefits of statins in the elderly without coronary heart disease, and that the risk attributable to total and LDL-C is less than in younger persons. Impressively, the estimated number of older persons who needed treatment for 4 years to prevent one primary endpoint was 24 compared with 36 in the younger age group. There are important differences in JUPITER including identifying a higher risk cohort by including the criteria of a CRP >2 mg/L (despite an LDL-C <130 mg/dl), and the 20 mg dose of rosuvastatin, which has a much greater effect on both LDL-C and CRP than standard statin dosing. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Renal Outcomes With Different Fixed-Dose Combination Therapies in Patients With Hypertension at High Risk for Cardiovascular Events (ACCOMPLISH): A Prespecified Secondary Analysis of a Randomized Controlled Trial
Topic: Prevention/Vascular
Date Posted: 5/7/2010
Author(s): Bakris GL, Sarafidis PA, Weir MR, et al., on behalf of the ACCOMPLISH Trial Investigators.
Citation: Lancet 2010;375:1173-1181.
Clinical Trial: No
Related Resources
Trial: Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving With Systolic Hypertension (ACCOMPLISH)

Study Question: What is the comparative efficacy of initial antihypertensive therapy with benazepril plus amlodipine versus benazepril plus hydrochlorothiazide on progression of chronic kidney disease?
Methods: ACCOMPLISH was a double-blind randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). A total of 11,506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n = 5,744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n = 5,762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 ml/min/1.73 m2 or need for dialysis). Analysis was by intention to treat.
Results: The trial was terminated early (mean follow-up 2.9 years [standard deviation 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (hazard ratio, 0.52; 0.41-0.65; p < 0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral edema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-edema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group.
Conclusions: The authors concluded that initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent.
Perspective: This trial shows that in patients with hypertension at high risk for cardiovascular events, combination treatment with benazepril plus amlodipine reduces progression of chronic kidney disease more effectively than does benazepril plus hydrochlorothiazide. This benefit was also seen when cardiovascular or all-cause mortality was assessed. A limitation of the study is that the trial was not powered as a chronic kidney disease outcome study. A prospective adequately powered trial in patients with more advanced proteinuric nephropathy is needed to establish the superiority between these two different antihypertensive combination treatments on progression of chronic kidney disease. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Deterioration of Blood Pressure Control After Discontinuation of a Physician-Pharmacist Collaborative Intervention
Topic: Prevention/Vascular
Date Posted: 5/10/2010
Author(s): Carter BL, Doucette WR, Franciscus CL, Ardery G, Kluesner KM, Chrischilles EA.
Citation: Pharmacotherapy 2010;30:228-235.
Clinical Trial: No
Study Question: Is blood pressure (BP) control maintained after discontinuation of a physician-pharmacist collaborative intervention?
Methods: A total of 104 patients (65 in the intervention group and 39 in the control group) participated in a 9-month prospective, cluster-randomized efficacy trial and then were evaluated at 9 and 18 months after completion of the trial based on BPs abstracted from the medical record. The intervention included pharmacist-patient interviews at baseline and up to six times during the 9-month follow-up period, as well as pharmacist recommendations for optimizing drug therapy to improve BP control (according to Joint National Committee 7 guidelines) and patient adherence. To evaluate the effect of discontinuation of the pharmacist intervention on BP, data from patients who received the intervention were compared with the controls 9 and 18 months after the intervention was discontinued.
Results: At baseline, no patients in either group had BP in control. By the end of the intervention period, BP was controlled in 78.5% and 48.7% of the intervention and control groups, respectively (p = 0.0017). By 9 months after the end of the intervention, BP control in the intervention and control groups had fallen to 53.9% and 30.8%, respectively (p = 0.02), whereas rates at 18 months post-intervention were 55.4% and 35.9% (p = 0.05).
Conclusions: There was a sustained positive effect up to 18 months after discontinuation of a physician-pharmacist collaborative intervention, compared with the control group. However, BP deteriorated at a similar rate in both groups over time.
Perspective: These results suggest that a collaborative intervention between physicians and pharmacists, focused on BP-lowering strategies, results in significant improvements in BP control compared with those who did not receive the intervention. Because there was deterioration of BP control over the subsequent 18 months, interventions which include collaborative team-based approaches may need to be continued to maintain high rates of BP control. Suzanne Hughes, MSN, RN

Title: Myocardial Fibrosis Identified by Cardiac Magnetic Resonance Late Gadolinium Enhancement Is Associated With Adverse Ventricular Mechanics and Ventricular Tachycardia Late After Fontan Operation
Topic: Congenital Heart Disease
Date Posted: 5/10/2010
Author(s): Rathod RH, Prakash A, Powell AJ, Geva T.
Citation: J Am Coll Cardiol 2010;55:1721-1728.
Clinical Trial: No
Study Question: What is the relationship between myocardial fibrosis as identified by cardiac magnetic resonance (CMR) and ventricular mechanics and arrhythmias after the Fontan procedure?
Methods: A retrospective review was performed at a single center. All patients following the Fontan procedure who underwent CMR with myocardial delayed-enhancement sequences were identified.
Results: A total of 90 patients with a mean age of 23.1 ± 10.9 years were studied. Positive late gadolinium enhancement (LGE) was seen in 25 (28%) patients, and was associated with lower mean ejection fraction (45% as compared with 56%; p < 0.001), increased median end-diastolic volume (100 ml/body surface area [BSA]1.3 vs. 82 ml/BSA1.3, and higher frequency of regional wall motion abnormalities (52% vs. 28%; p = 0.05). Increased frequency of nonsustained ventricular tachycardia (NSVT) was also seen in patients with LGE with a rate of 36% as compared with 11% in those without LGE (p = 0.01). Multivariate regression analysis showed that more extensive positive LGE (expressed as percent LGE of total myocardial mass) was associated with lower ejection fraction (p = 0.002), increased end-diastolic volume (p < 0.001), and a higher frequency of NSVT (odds ratio, 1.2; 95% confidence interval, 1.1-1.4; p = 0.006).
Conclusions: Myocardial fibrosis is common in patients following the Fontan procedure and is associated with impaired ventricular mechanics and higher rate of NSVT. Further studies are necessary to assess the utility of the role of this measure for risk stratification and management of ventricular arrhythmias.
Perspective: This study addresses the prevalence and implications of late gadolinium enhancement in patients following the Fontan procedure. The mechanisms for development of these abnormalities are unclear. While the role for routine assessment for LGE is unclear, it may prove a useful modality for identifying patients at risk for ventricular arrhythmias or significant myocardial dysfunction. More importantly, an understanding of the etiology of these changes will be important for attempts at decreasing the incidence of myocardial scarring in this complex patient population. Timothy B. Cotts, M.D., F.A.C.C.

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Title: Impact of High-Dose N-Acetylcysteine Versus Placebo on Contrast-Induced Nephropathy and Myocardial Reperfusion Injury in Unselected Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial
Topic: Interventional Cardiology
Date Posted: 5/10/2010 5:00:00 PM
Author(s): Thiele H, Hildebrand L, Schirdewahn C, et al.
Citation: J Am Coll Cardiol 2010;55:2201-2209.
Clinical Trial: yes
Related Resources
JACC Article: Impact of High-Dose N-Acetylcysteine Versus Placebo on Contrast-Induced Nephropathy and Myocardial Reperfusion Injury in Unselected Patients With STEMI Undergoing Primary PCI: The LIPSIA-N-ACC Trial

Study Question: What is the effect of N-acetylcysteine on contrast-induced nephropathy (CIN) and reperfusion injury in ST-segment elevation myocardial infarction patients undergoing primary angioplasty with moderate contrast volumes?
Methods: Patients undergoing primary angioplasty were randomized to either high-dose N-acetylcysteine (2 x 1200 mg/day for 48 hours; n = 126) or placebo plus optimal hydration (n = 125). The two primary endpoints were: 1) the occurrence of >25% increase in serum creatinine level <72 hours after randomization; and 2) a reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging.
Results: The median volume of an iso-osmolar contrast agent during angiography was 180 ml (interquartile range [IQR], 140-230 ml) in the N-acetylcysteine and 160 (IQR, 120-220 ml) in the placebo group (p = 0.20). The primary endpoint, CIN, occurred in 14% of the N-acetylcysteine group and in 20% of the placebo group (p = 0.28). The myocardial salvage index was also not different between both treatment groups (43.5; IQR, 25.4-71.9 vs. 51.5; IQR, 29.5-75.3; p = 0.36). Activated oxygen protein products and oxidized low-density lipoprotein as markers for oxidative stress were reduced by as much as 20% in the N-acetylcysteine group (p < 0.05), whereas no change was evident in the placebo group.
Conclusions: The authors concluded that high-dose intravenous N-acetylcysteine does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration.
Perspective: In this prospective, randomized, single-blind trial, N-acetylcysteine was ineffective in preventing CIN and did not lead to a measurable benefit in reperfusion injury in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Furthermore, this lack of efficacy of N-acetylcysteine was independent of typical risk factors for the development of CIN. Based on the totality of evidence from multiple analyses, it appears that any incremental benefit of intravenous N-acetylcysteine administration in addition to hydration is likely to be small and not clinically relevant. Debabrata Mukherjee, M.D., F.A.C.C.

Title: The Transradial Approach to Percutaneous Coronary Intervention: Historical Perspective, Current Concepts, and Future Directions
Topic: Interventional Cardiology
Date Posted: 5/10/2010 5:00:00 PM
Author(s): Rao SV, Cohen MG, Kandzari DE, Bertrand OF, Gilchrist IC.
Citation: J Am Coll Cardiol 2010;55:2187-2195.
Clinical Trial: No
Related Resources
JACC Article: The Transradial Approach to Percutaneous Coronary Intervention: Historical Perspective, Current Concepts, and Future Directions

Study Question: What is the current status of the transradial approach to percutaneous coronary intervention (PCI)?
Perspective: Periprocedural bleeding after PCI has been associated with increased short- and long-term morbidity and mortality. A growing body of evidence supports the use of the radial artery over the femoral artery to achieve lower bleeding rates, and data demonstrate an association between the transradial approach and reduced costs and post-procedural length of stay. Despite these advantages, there are some limitations to this approach, such as the potential impact on radial artery patency and greater radiation exposure during the learning curve, one of the factors that has limited adoption of this technique. Greater utilization of the transradial approach will depend on the availability of educational programs for interventionalists and fellows, commitment from professional societies to support transradial PCI, and the generation of high-quality evidence to determine its true comparative effectiveness against the traditional femoral approach. A potential benefit of the greater use of the transradial approach is that it may allow higher, more effective doses of antithrombotics, which in turn may result in improved outcomes. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Myocardial Iodine-123 Meta-Iodobenzylguanidine Imaging and Cardiac Events in Heart Failure: Results of the Prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) Study
Topic: Heart Failure/Transplant
Date Posted: 5/11/2010
Author(s): Jacobson AF, Senior R, Cerqueira MD, et al., on behalf of the ADMIRE-HF Investigators.
Citation: J Am Coll Cardiol 2010;55:2212-2221.
Clinical Trial: No
Related Resources
JACC Article: Myocardial Iodine-123 Meta-Iodobenzylguanidine Imaging and Cardiac Events in Heart Failure: Results of the Prospective ADMIRE-HF Study

Study Question: What is the role of iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging for identifying symptomatic heart failure (HF) patients most likely to experience cardiac events?
Methods: A total of 961 subjects with New York Heart Association (NYHA) functional class II/III HF and left ventricular ejection fraction (LVEF) ≤35% were studied. Subjects underwent 123I-mIBG myocardial imaging (sympathetic neuronal integrity quantified as the heart/mediastinum uptake ratio [H/M] on 4-hour delayed planar images) and myocardial perfusion imaging, and were then followed up for up to 2 years. Time to first occurrence of NYHA functional class progression, potentially life-threatening arrhythmic event, or cardiac death was compared with H/M (either in relation to estimated lower limit of normal [1.60] or as a continuous variable) using Cox proportional hazards regression. Multivariable analyses using clinical, laboratory, and imaging data were also performed.
Results: A total of 237 subjects (25%) experienced events (median follow-up 17 months). The hazard ratio for H/M ≥1.60 was 0.40 (p < 0.001); the hazard ratio for continuous H/M was 0.22 (p < 0.001). Two-year event rate was 15% for H/M ≥1.60 and 37% for H/M <1.60; hazard ratios for individual event categories were as follows: HF progression, 0.49 (p = 0.002); arrhythmic events, 0.37 (p = 0.02); and cardiac death, 0.14 (p = 0.006). Significant contributors to the multivariable model were H/M, LVEF, B-type natriuretic peptide, and NYHA functional class. 123I-mIBG imaging also provided additional discrimination in analyses of interactions between B-type natriuretic peptide, LVEF, and late H/M.
Conclusions: The authors concluded that 123I-mIBG scintigraphy provides independent prognostic value in assessment of patients with HF.
Perspective: This study demonstrates the capacity of quantitation of sympathetic innervation of the myocardium, measured by 123I-mIBG scintigraphy, for predicting prognosis in subjects with HF and significant LV dysfunction. The study showed a highly significant relationship between time to HF-related events and H/M, which was independent of other commonly measured parameters such as LVEF and BNP, as well as demographic parameters such as age and renal function. The study also showed a clear association between severity of myocardial sympathetic neuronal dysfunction and risk for subsequent cardiac death. In appropriately selected patients, this imaging procedure could alert clinicians to the potential need for considering additional treatments such as more aggressive medical therapy or earlier use of resynchronization therapy. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Triglyceride-Mediated Pathways and Coronary Disease: Collaborative Analysis of 101 Studies
Topic: Prevention/Vascular
Date Posted: 5/11/2010
Author(s): Sarwar N, Sandhu MS, Ricketts SL, et al., on behalf of the Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration.
Citation: Lancet 2010;375:1634-1639.
Clinical Trial: No
Study Question: Are triglyceride-mediated pathways causally relevant to coronary heart disease (CHD)?
Methods: The study assessed the –1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of CHD. The disease risk was assessed for genetically-raised triglyceride concentration (20,842 patients with CHD and 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302,430 participants with no history of cardiovascular disease; 12,785 incident cases of CHD during 2.79 million person-years at risk). The authors also analyzed –1131T>C in 1,795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy.
Results: The minor allele frequency of –1131T>C was 8% (95% confidence interval, 7-9). –1131T>C was not significantly associated with several nonlipid risk factors or low-density lipoprotein (LDL) cholesterol; however, it was significantly but modestly associated with lower high-density lipoprotein cholesterol (HDL-C) (mean difference per C allele, 3.5%; lower apolipoprotein A-I [1.3%; 0.023 g/L]; and higher apolipoprotein B [3.2%; 0.027 g/L]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% or 0.25 mmol/L, higher (p = 4.4 Ч 10–24). The odds ratio for CHD was 1.18 (p = 2.6 Ч 10–7) per C allele, which was concordant with the hazard ratio of 1.10 per 16% higher triglyceride concentration recorded in prospective studies. –1131T>C was significantly associated with higher very LDL (VLDL) particle concentration (mean difference per C allele, 12.2 nmol/L; p = 9.3 Ч 10–8) and smaller HDL particle size (0.14 nmol; p = 7.0 Ч 10–5), factors that could mediate the effects of triglyceride.
Conclusions: The authors concluded that these data are consistent with a causal association between triglyceride-mediated pathways and CHD.
Perspective: The mechanisms considered for triglycerides increasing risk for CHD and CV events are thought to be the increase in VLDL triglyceride-rich remnant particles, small highly atherogenic LDL particles, less efficient small dense HDL particles, and prothrombosis. The finding that a genetic determinant of triglyceride levels appears to increase risk independent of other known risk factors including diabetes further supports the rationale for considering targeting triglycerides. Future drug trials should consider the impact of the –1131T>C (rs662799) promoter polymorphism of the APOA5 gene, which appears to impact the effect of both statins and fibrates. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Association of Temporal Trends in Risk Factors and Treatment Uptake With Coronary Heart Disease Mortality, 1994-2005
Topic: Prevention/Vascular
Date Posted: 5/11/2010 4:00:00 PM
Author(s): Wijeysundera HC, Machado M, Farahati F, et al.
Citation: JAMA 2010;303:1841-1847.
Clinical Trial: No
Study Question: Are trends in coronary heart disease (CHD) risk factors and management associated with mortality?
Methods: This was a prospective analytic study of the general population (age 25-84 years) residing in Ontario, Canada between 1994 and 2005, using the IMPACT model (which integrates data on population size, CHD mortality, risk factors, and treatment uptake). The association between CHD mortality and risk factors for eight separate CHD populations, and population trends in six risk factors was quantified using relative risks and regression coefficients from published literature. The main outcome of interest was number of deaths prevented or delayed in 2005. Secondary outcomes included improvements in medical treatments and trends in risk factors.
Results: Age-adjusted CHD mortality decreased by 35%, from 191 to 125 deaths per 100,000 inhabitants over the time period examined (1994-2005). This translated into an estimated 7,585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range 11-124%) of the total mortality decrease, most notably for acute myocardial infarction (8%, range -5% to 40%), chronic stable coronary artery disease (17%, range 7-35%), and heart failure occurring while in the community (10%, range 6-31%). Trends in risk factors accounted for 48% (range 28-64%) prevented or delayed CHD deaths or 3,660 fewer deaths. Improvements in total cholesterol and systolic blood pressure accounted for much of this mortality reduction. Increases in diabetes and body mass index (BMI) were associated with higher CHD mortality (6%, range 4-8% for diabetes and 2%, range 1-4% for BMI).
Conclusions: The authors concluded that decreases in CHD mortality observed between 1994 and 2005 were associated primarily with improvements in CHD risk factors, but also with improvements in medical management of heart disease.
Perspective: These findings support the continued primary and secondary prevention efforts to improve traditional risk factors in our population. This together with continued advancement in the treatment of CHD will likely assist in the continued reduction of CHD mortality rates. However, the epidemic of obesity and associated medical problems such as diabetes will retard progress in reducing mortality and morbidity related to CHD. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Antithrombotic Management of Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Coronary Stenting: Executive Summary—A Consensus Document of the European Society of Cardiology Working Group on Thrombosis, Endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI)
Topic: Interventional Cardiology
Date Posted: 5/12/2010
Author(s): Lip GY, Huber K, Andreotti F, et al.
Citation: Eur Heart J 2010;May 6:[Epub ahead of print].
Clinical Trial: No
Perspective: The following are 10 points to remember from this consensus document:

1. Approximately 70-80% of patients with atrial fibrillation (AF) have an indication for oral anticoagulation therapy (OAT). Coronary artery disease co-exists in 20-30% of these patients.

2. Patients with AF on OAT are often bridged with unfractionated heparin or low molecular weight heparin if they need coronary angiography or percutaneous coronary intervention (PCI). Use of bridging therapy is associated with increased risk of access site complications in some studies. Some observational studies suggest that coronary angiography or PCI can be safely performed without interrupting OAT, and may be associated with a lower rate of complications compared with bridging therapy.

3. In small series, the rate of complications in patients on OAT who undergo angiography or PCI via the femoral route has been low. However, the radial route should be preferred in patients on OAT.

4. There is no need for additional heparin in patients who undergo PCI while therapeutic on OAT (international normalized ratio [INR] 2-3).

5. Aspirin and clopidogrel should be administered prior to the procedure when PCI is performed in a patient on OAT.

6. The use of platelet glycoprotein IIb/IIIa inhibitors increases the risk of bleeding in patients on OAT 3- to 13-fold and the routine use of these agents should be avoided in patients on OAT.

7. Use of aspirin and warfarin does not provide sufficient protection against risk of stent thrombosis. Patients undergoing stent-based PCI should be treated with triple therapy consisting of aspirin, clopidogrel, and warfarin. This combination is associated with an increased risk of bleeding, and use of bare-metal stents should be considered in these patients to limit the duration of triple therapy.

8. In patients who need long-term OAT, use of drug-eluting stents should be restricted to patients at very high risk of restenosis (long lesions, small vessels, diabetes). Alternative therapies (coronary artery bypass grafting [CABG], medical therapy, bare-metal stents) should be considered before implanting drug-eluting stents in a patient who needs long-term OAT.

9. In patients on triple therapy, closer monitoring of INR targeted to 2.0-2.5 and use of proton pump inhibitors may help reduce the risk of bleeding.

10. There are limited data on safety of cardiac surgery in patients who are on OAT. Currently, these patients are bridged with heparin prior to surgery. In the event of need for emergent CABG in a patient on OAT, fresh frozen plasma and vitamin K may be used to reverse OAT and reduce the risk of bleeding. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: An Entirely Subcutaneous Implantable Cardioverter-Defibrillator
Topic: Arrhythmias
Date Posted: 5/12/2010 4:00:00 PM
Author(s): Bardy GH, Smith WM, Hood MA, et al.
Citation: N Engl J Med 2010;May 12:[Epub ahead of print].
Clinical Trial: No
Study Question: How effectively does a subcutaneous implantable cardioverter-defibrillator (ICD) system detect and terminate ventricular tachycardia (VT) and ventricular fibrillation (VF)?
Methods: This study describes the results of two short-term trials of a subcutaneous electrode system and two long-term trials of the subcutaneous ICD system. In the short-term trials, the best electrode configuration was identified in 78 patients and then compared to a transvenous ICD system in 49 patients. In the long-term trials, 61 patients underwent implantation of the subcutaneous ICD. The subcutaneous ICD system consisted of a pulse generator implanted in the anterior axillary region and a parasternal 8-cm tripolar electrode. The pulse generator delivered 80-J shocks, had a rate cut-off of 170 bpm, and was able to pace for ≤30 seconds after a shock if there was a >3.5 second pause after a shock.
Results: The mean defibrillation threshold was 11.1 J with the transvenous ICD and 31.1 J with the subcutaneous ICD. Among the 61 patients who received the subcutaneous ICD, two consecutive episodes of induced VF were successfully sensed and terminated by 65-J shocks in all but one patient. During a mean of 10 months of follow-up, a total of 12 episodes of VT in three patients were detected and successfully terminated by the subcutaneous ICD. Complications included lead dislodgement requiring repositioning in four patients.
Conclusions: The subcutaneous ICD system tested in this study accurately senses and terminates VT/VF in approximately 98% of patients.
Perspective: Elimination of radiation exposure and the need for vascular access make the subcutaneous ICD an attractive option. However, it is not capable of long-term pacing, antitachycardia pacing, or detection of VT <170 bpm. Further evaluation is needed to determine its clinical reliability and utility. Fred Morady, M.D., F.A.C.C.

Title: 22q11.2 Deletion Syndrome Is Under-Recognised in Adult Patients With Tetralogy of Fallot and Pulmonary Atresia
Topic: Congenital Heart Disease
Date Posted: 5/12/2010
Author(s): van Engelen K, Topf A, Keavney BD, et al.
Citation: Heart 2010;96:621-624.
Clinical Trial: No
Study Question: What is the prevalence of 22q11.2 Deletion Syndrome (22q11.2DS) in adults with pulmonary atresia with ventricular septal defect (PA/VSD) and tetralogy of Fallot (TOF)?
Methods: A review of the Dutch CONCOR (CONgenital CORvitia) registry was performed. The CONCOR registry includes both a clinical database and a DNA bank. The registry was searched for patients with TOF and PA/VSD, with DNA available for analysis. Multiplex ligation-dependent probe amplification was used to detect 22q11.2 microdeletions.
Results: A total of 558 patients (479 with TOF and 79 with PA/VSD) with a median age of 34.7 years were studied. In addition to 20 patients already known to be positive, 24 (54%) patients were found to have a previously unidentified 22q11.2 microdeletion. The prevalence of 22q11.2 deletion was 6.5% in patients with TOF and 16.5% in patients with PA/VSD.
Conclusions: 22q11.2 deletion is undiagnosed in more than one half of adult patients. Testing for 22q11.2 deletion should be considered.
Perspective: This study reports both the incidence of 22q11.2 deletion syndrome and the degree to which it remains diagnosed in adults with TOF and PA/VSD. The prevalence is similar to what has been previously reported (Beauchesne LM, et al., J Am Coll Cardiol 2005;45:595-8). Testing for 22q11.2 deletion should be considered in all adults, particularly those considering having children, given the 50% chance of transmission to offspring. Timothy B. Cotts, M.D., F.A.C.C.

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Title: 1) The Case for Routine Genotyping in Dual-Antiplatelet Therapy. 2) Genotyping: One Piece of the Puzzle to Personalize Antiplatelet Therapy.
Topic: General Cardiology
Date Posted: 5/13/2010
Author(s): 1) Damani SB, Topol EJ. 2) Gurbel PA, Tantry US, Shuldiner AR, Kereiakes DJ.
Citation: 1) J Am Coll Cardiol 2010;May 12:[Epub ahead of print]. 2) J Am Coll Cardiol 2010;May 12:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the current role of routine genotyping and platelet function testing for dual antiplatelet therapy?
Perspective: Recent data suggest that there are altered active metabolite levels of clopidogrel in patients harboring hepatic cytochrome gene variants. These variants, identified through genome-wide association as the dominant explanation for the marked heterogeneity of clopidogrel response, are linked to a significant increase in the risk for bleeding, stent thrombosis, myocardial infarction, and death. The impact of having two loss-of-function alleles [P450 (CYP) 2C19*2] has been recently highlighted in the ‘boxed warning’ issued by the U.S. Food and Drug Administration. In addition to genetic subtypes, high on-treatment platelet reactivity to adenosine diphosphate (ADP) during clopidogrel therapy is also a well-documented predictor of recurrent ischemic events in the percutaneous coronary intervention population. With several alternatives to clopidogrel now available, including higher clopidogrel maintenance and loading doses, prasugrel, and potentially ticagrelor in the future, clinicians may be able to effectively guide therapy in those with at-risk gene variants by simple genotyping. Based on available data, it seems reasonable to consider both genotyping and platelet function measurement to assess ischemic risk and to guide antiplatelet therapy. Ultimately, prospective randomized clinical trials will be needed to test specific personalized antiplatelet algorithms to provide the evidence base necessary prior to widespread adoption into clinical practice. Debabrata Mukherjee, M.D., F.A.C.C.

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Eating Nuts Improves Cholesterol Levels
Radiation Exposure from Noninvasive Imaging Studies
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Title: Early Identification of Mutation Carriers in Familial Hypertrophic Cardiomyopathy by Combined Echocardiography and Tissue Doppler Imaging
Topic: Heart Failure/Transplant
Date Posted: 5/13/2010
Author(s): Gandjbakhch E, Gackowski A, Tezenas du Montcel S, et al.
Citation: Eur Heart J 2010;May 3: [Epub ahead of print].
Clinical Trial: No
Study Question: Can hypertrophic cardiomyopathy (HCM) mutation status be predicted by echocardiography and tissue Doppler imaging (TDI) before the onset of hypertrophy?
Methods: Three subject groups were analyzed: HCM patients with hypertrophy (left ventricular hypertrophy [LVH]+, n = 48), mutation carriers without hypertrophy (LVH-/G+, n = 24), and normal control subjects (n = 48).
Results: Multivariate logistic regression identified only three independent echocardiographic/TDI parameters associated with genetic status: the interventricular septum/left posterior wall ratio (p = 0.006), relative wall thickness (p = 0.026), and septal E/Ea ratio (p = 0.008). An echo/TDI score determined after receiver operating characteristic analysis identified mutation carriers with 67% sensitivity and 96% specificity. In comparison, only 29% were identified by the previously proposed TDI criterion (lateral Ea velocity <14 cm/s) and only 33% by major electrocardiogram abnormalities.
Conclusions: The authors concluded that TDI velocities alone were not reliable enough to identify LVH-free mutation carriers in HCM. In contrast, abnormal LV remodeling was a frequent early manifestation of HCM. A new score was developed, combining echocardiographic and TDI parameters, that identifies mutation carriers before and independently of hypertrophy with high accuracy.
Perspective: Phenotypic heterogeneity of hypertrophy in patients with HCM often delays ability to establish genotype-phenotype correlations. Early identification of HCM in mutation carriers by improved myocardial imaging techniques could aid in genetic testing and management strategies. Previous studies have indicated that tissue Doppler characteristics are present in HCM mutation carriers before the onset of hypertrophy; however, this is controversial. Although this study did not find TDI velocities alone to be reliable, the authors did identify early remodeling changes in mutation carriers that may be useful with TDI parameters in predicting mutation status. Additional large studies in genetically diverse HCM populations are necessary to confirm these findings. Daniel T. Eitzman, M.D., F.A.C.C.

Title: Dronedarone in Patients With Congestive Heart Failure: Insights From ATHENA
Topic: Arrhythmias
Date Posted: 5/13/2010
Author(s): Hohnloser SH, Crijns HJ, van Eickels M, et al., on behalf of the ATHENA Investigators.
Citation: Eur Heart J 2010;April 30: [Epub ahead of print].
Clinical Trial: No
Related Resources
Trial: Effect of Dronedarone on Cardiovascular Outcomes in High-Risk Patients With Atrial Fibrillation or Atrial Flutter (ATHENA)

Study Question: Does dronedarone increase mortality or morbidity in patients with atrial fibrillation (AF) and congestive heart failure (CHF)?
Methods: This was a post-hoc analysis of a randomized clinical trial that compared dronedarone to placebo in 4,628 patients with AF. The 1° endpoint was a composite of time to first cardiovascular hospitalization or death.
Results: A total of 209 patients in the trial had New York Heart Association (NYHA) functional class II or III CHF and a left ventricular ejection fraction (LVEF) ≤40%. Dronedarone decreased the 1° endpoint by 22% in patients with CHF and by 24% in patients without CHF. The adverse events in patients with CHF who received dronedarone included bradycardia (3.2%), QT-prolongation (4.2%), and creatinine increase (10.5%). The prevalence of these adverse events did not differ significantly between patients with and without CHF. NYHA class IV CHF occurred during follow-up in 54 placebo patients and 42 dronedarone patients, with no difference in the mean time to hospitalization for CHF.
Conclusions: In the ATHENA trial, the reduction in time to first cardiovascular hospitalization or death associated with the use of dronedarone was not attenuated by the presence of class II-III CHF.
Perspective: Dronedarone is contraindicated in patients with NYHA class IV CHF or a recent episode of class II-III CHF. This is because mortality was increased by dronedarone when it was administered to patients with unstable CHF in the ANDROMEDA trial. The results of the present study suggest that dronedarone is safe in patients with stable class II-III CHF, with 'stable' generally defined as no exacerbation of CHF within the prior 3 months. Fred Morady, M.D., F.A.C.C.

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Title: Effect of Early Cerebral Magnetic Resonance Imaging on Clinical Decisions in Infective Endocarditis: A Prospective Study
Topic: Noninvasive Cardiology
Date Posted: 5/14/2010
Author(s): Duval X, Iung B, Klein I, et al., on behalf of the IMAGE (Resonance Magnetic Imaging at the Acute Phase of Endocarditis) Study Group.
Citation: Ann Intern Med 2010;152:497-504.
Clinical Trial: No
Study Question: Does early cerebral magnetic resonance imaging (MRI) affect the diagnosis and management of infective endocarditis in hospitalized adults?
Methods: In a single-center (tertiary care hospital in France) prospective study performed between June 2005 and October 2008, cerebral MRI with angiography was performed in 130 patients hospitalized with infective endocarditis up to 7 days after admission and before any surgical intervention. Two experts jointly established the endocarditis diagnostic classification (modified Duke criteria), and therapeutic plans just before and after MRI.
Results: Endocarditis was initially classified as definite in 77 patients, possible in 50, and was excluded in 3. Acute neurologic symptoms were present in 16 patients (12%). Cerebral lesions were detected on MRI in 106 patients (82% [95% confidence interval, 75-89%]), including ischemic lesions in 68, micro-hemorrhages in 74, and silent aneurysms in 10. Solely on the basis of MRI results and excluding micro-hemorrhages, diagnostic classification of 17 of 53 (32%) cases of nondefinite endocarditis was changed to either definite (14 patients) or possible (3 patients). MRI results led to modification of endocarditis therapeutic plan in 24 (18%) of 130 patients, including surgical plan modifications for 18 (14%). Overall, early MRI led to modifications of diagnosis or therapeutic plan in 36 patients (28% [confidence interval, 20-36%]). (Investigators did not assess whether MRI-related changes in diagnosis and therapeutic plans improved patient outcomes, or led to additional and potentially unnecessary procedures, and/or increased costs.)
Conclusions: Cerebral lesions were identified on MRI in many patients with endocarditis, but no neurologic symptoms. The MRI findings affected both diagnostic classifications and clinical management plans.
Perspective: Other recently published data similarly found very high rates of both subclinical brain embolus (~48%) and any acute brain embolus (~80%) among patients with left-sided infective endocarditis (Circulation 2009;120:585-91). The present study used these data to show an increase in the rate of diagnosis of infective endocarditis, and altered medical and/or surgical management in patients with evidence of subclinical brain pathology (ischemic lesions, aneurysms). However, as the authors note, it is not known whether the additional data actually should have altered therapy, or in any way improved outcomes. If existing diagnostic criteria and therapeutic recommendations include the presence or absence of clinically apparent embolic events, it does not logically follow that management necessarily should be altered by extrapolation to include subclinical events. It is clear that doing more tests will result in the detection of more abnormalities. However, improved clinical outcomes should remain the relevant endpoint. David S. Bach, M.D., F.A.C.C.

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Title: Prevention of Atrial Fibrillation by Renin-Angiotensin System Inhibition: A Meta-Analysis
Topic: Arrhythmias
Date Posted: 5/17/2010 5:00:00 PM
Author(s): Schneider MP, Hua TA, Bohm M, Wachtell K, Kjeldsen SE, Schmieder RE.
Citation: J Am Coll Cardiol 2010;55:2299-2307.
Clinical Trial: No
Study Question: Do angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) prevent atrial fibrillation (AF)?
Methods: This was a meta-analysis of 23 randomized trials in which the effects of ACEIs or ARBS on AF were evaluated in a total of 87,048 patients. Eleven were 1° prevention studies (six hypertension trials, two post-infarction trials, and three heart failure trials) and 12 were 2° prevention trials (eight studies after cardioversion and four studies in patients on medical therapy for AF).
Results: Overall, ACEIs and ARBs significantly decreased the odds of AF by 33%. The effects of ACEIs/ARBs were not uniform in all subgroups. In the hypertension and post-infarction trials, treatment with ACEIs/ARBs did not significantly reduce the odds of developing AF. In contrast, there was a 48% reduction in the probability of AF in the three heart failure trials, a 45% reduction in the eight post-cardioversion studies, and a 63% reduction in the four medical therapy studies. In the medical therapy studies, ACEIs or ARBs were used in combination with rhythm-control antiarrhythmic drugs.
Conclusions: The most consistent evidence that ACEIs and ARBs prevent AF is in studies on the 1° prevention of AF in patients with heart failure and on the 2° prevention of AF post-cardioversion and during medical therapy for paroxysmal AF.
Perspective: The results of this meta-analysis are consistent with a large body of experimental evidence indicating that the renin-angiotensin system plays a role in atrial structural and electrophysiological remodeling. For example, angiotensin II activates pathways leading to atrial fibrosis, and can affect outward potassium currents involved in the pathogenesis of AF. Fred Morady, M.D., F.A.C.C.

Title: The Long- and Short-Term Impact of Elevated Body Mass Index on the Risk of New Atrial Fibrillation: The WHS (Women’s Health Study)
Topic: Arrhythmias
Date Posted: 5/17/2010 5:00:00 PM
Author(s): Tedrow UB, Conen D, Ridker PM, et al.
Citation: J Am Coll Cardiol 2010;55:2319-2327.
Clinical Trial: No
Related Resources
For Patients: Weight Gain Increases Risk of Atrial Fibrillation
Trial: Women's Health Study: Low-Dose Aspirin in Primary Prevention
Trial: Women's Health Study: Vitamin E in Primary Prevention

Study Question: Is body mass index (BMI) associated with risk of atrial fibrillation (AF)?
Methods: Data from the Women’s Health Study (WHS) were used for the present analysis. WHS was a randomized controlled trial of low-dose aspirin and vitamin E. A total of 39,876 women with no evidence of cardiovascular disease at baseline comprised the study population. After the randomized controlled trial ended, 35,545 continued to be followed in an observation cohort. Women with AF at baseline were excluded. Baseline and follow-up questionnaires were used to assess self-reported BMI and occurrence of AF. Women who reported having AF, had medical charts reviewed for confirmation of the arrhythmia.
Results: A total of 34,309 women were included in the present study. Over the mean 12.9 years of follow-up, 834 confirmed cases of AF occurred. BMI was associated with AF risk with an increase of 4.7% (95% confidence interval [CI], 3.4-6.1) for each kg/m2. After adjustment for inflammatory markers, the risk was attenuated. Short-term risk of AF was highest for women who were obese (hazard ratio [HR], 1.65; 95% CI, 1.36-2.00), followed by women who were overweight (HR, 1.22; 95% CI, 1.02-1.45) compared to those who were normal weight, after adjustment of updated measures of BMI over time. Women who become obese during the first 60 months had a 41% adjusted increased risk for developing AF as compared to women who maintained a BMI <30 kg/m2. The adjusted proportion of incident AF attributable to short-term elevations in BMI was 18.3%.
Conclusions: The investigators concluded that BMI is associated with risk of AF among apparently healthy women.
Perspective: These findings add further evidence to the importance of maintaining a healthy weight. Additional information on the impact of fitness in relation to BMI and incident AF would provide further clinically relevant information. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Metabolic Syndrome and Risk of Acute Myocardial Infarction: A Case-Control Study of 26,903 Subjects From 52 Countries
Topic: Prevention/Vascular
Date Posted: 5/18/2010
Author(s): Mente A, Yusuf S, Islam S, et al., on behalf of the INTERHEART Investigators.
Citation: J Am Coll Cardiol 2010;55:2390-2398.
Clinical Trial: No
Related Resources
JACC Article: Metabolic Syndrome and Risk of Acute Myocardial Infarction: A Case-Control Study of 26,903 Subjects From 52 Countries
Trial: A Study of Risk Factors for First Myocardial Infarction in 52 Countries and Over 27,000 Subjects (INTERHEART)

Study Question: What is the risk of acute myocardial infarction (MI) conferred by the metabolic syndrome (MS) and its individual factors in multiple ethnic populations?
Methods: Participants in the INTERHEART study (n = 26,903) involving 52 countries were classified using the World Health Organization (WHO) and International Diabetes Federation (IDF) criteria for MS, and their odds ratios (ORs) for MI were compared with the individual MS component factors.
Results: The MS is associated with an increased risk of MI, both using the WHO (OR, 2.69; 95% confidence interval [CI], 2.45-2.95) and IDF (OR, 2.20; 95% CI, 2.03-2.38) definitions, with corresponding population attributable risks of 14.5% (95% CI, 12.7-16.3%) and 16.8% (95% CI, 14.8-18.8%), respectively. The associations are directionally similar across all regions and ethnic groups. Using the WHO definition, the association with MI by the MS is similar to that of diabetes mellitus (OR, 2.72; 95% CI, 2.53-2.92) and hypertension (OR, 2.60; 95% CI, 2.46-2.76), and significantly stronger than that of the other component risk factors. The clustering of ≥3 risk factors with subthreshold values is associated with an increased risk of MI (OR, 1.50; 95% CI, 1.24-1.81) compared with having component factors with “normal” values. The IDF definition showed similar results.
Conclusions: In this large-scale, multi-ethnic, international investigation, the risk of MS on MI is generally comparable to that conferred by some, but not all, of its component risk factors. The characterization of risk factors, especially continuous variables, as dichotomous will underestimate risk and decrease the magnitude of association between MS and MI.
Perspective: The risk of MI was not significantly associated with MS among North Americans, although subanalyses by ethnicity show that MS is consistently associated with MI. The authors suggested this may reflect the heterogeneity of the subjects recruited from Canada and the United States. Because fasting samples were not available, it is not possible to draw conclusions about the value of triglycerides as used in the Adult Treatment Panel III definition for the MS. An interesting and intuitive finding is that clinical clustering of subthreshold values for MS parameters is associated with an increased risk of MI, a finding that has considerable importance when discussing potential value of lifestyle changes in men and women. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Intravascular Ultrasound-Derived Measures of Coronary Atherosclerotic Plaque Burden and Clinical Outcome
Topic: Noninvasive Cardiology
Date Posted: 5/18/2010
Author(s): Nicholls SJ, Hsu A, Wolski K, et al.
Citation: J Am Coll Cardiol 2010;55:2399-2407.
Clinical Trial: No
Related Resources
JACC Article: Intravascular Ultrasound-Derived Measures of Coronary Atherosclerotic Plaque Burden and Clinical Outcome

Study Question: What is the relationship between intravascular ultrasound (IVUS)-derived measures of atherosclerosis and cardiovascular outcomes?
Methods: The authors evaluated coronary plaque progression as assessed by IVUS in 4,137 patients enrolled in six clinical trials, and assessed the association between baseline and change in percent atheroma volume (PAV) and total atheroma volume with incident major adverse cardiovascular events (MACE).
Results: There was an increase in PAV by 0.3% (p < 0.001) over the study period. MACE occurred in 19.9% of subjects, with most of the events being coronary revascularization (0.9% death, 1.8% myocardial infarction, 18.9% coronary revascularization). Patients with evidence of greater baseline PAVs were more likely to experience a myocardial infarction (PAV 42.2% vs. 38.6%), and coronary revascularization (41.2% vs. 38.1%). The average follow-up was 21 months. Greater increases in PAV were observed in subjects who experienced coronary revascularization compared with those who did not (0.96% vs. 0.46%, p < 0.001). After adjusting for other factors, independent predictors of MACE were baseline PAV, change in PAV, smoking, and hypertension.
Conclusions: There is a direct association between baseline burden of atherosclerosis, its progression, and occurrence of MACE.
Perspective: Multiple trials have used IVUS to assess change in plaque burden as a surrogate for anti-atherosclerotic efficacy of various therapeutic agents, although there are limited data to suggest that these changes in plaque correlate with reduction in hard clinical events. This study provides some evidence that slower progression of plaque may be associated with a reduction in clinical events, although this was driven predominantly by fewer myocardial revascularizations. Further studies are needed to clarify if plaque imaging can help predict hard events and whether it can be used as a surrogate marker for evaluation of hard clinical events. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Dual Antiplatelet Therapy and Heparin “Bridging” Significantly Increase the Risk of Bleeding Complications After Pacemaker or Implantable Cardioverter-Defibrillator Device Implantation
Topic: Arrhythmias
Date Posted: 5/18/2010
Author(s): Tompkins C, Cheng A, Dalal D, et al.
Citation: J Am Coll Cardiol 2010;55:2376-2382.
Clinical Trial: No
Related Resources
JACC Article: Dual Antiplatelet Therapy and Heparin “Bridging” Significantly Increase the Risk of Bleeding Complications After Pacemaker or Implantable Cardioverter-Defibrillator Device Implantation

Study Question: Do antiplatelet agents and heparin increase the risk of bleeding complications at the time of cardiac device implantation?
Methods: This was a retrospective study of 1,388 patients (mean age 65 years) who underwent implantation of a pacemaker or implantable cardioverter defibrillator (ICD). Antiplatelet therapy consisted of aspirin in 536 patients and the combination of aspirin plus clopidogrel in 139. Anticoagulant therapy consisted of warfarin with an international normalized ratio (INR) ≥1.5 in 45 patients and heparin in 155. A significant bleeding complication was defined as a pocket hematoma or other bleeding complication requiring a blood transfusion, pressure dressing, change in medical therapy, or prolonged hospitalization.
Results: A bleeding complication occurred in 5.1% of patients. The incidence was significantly higher in patients receiving aspirin plus clopidogrel (7.2%) than in patients receiving neither agent. Aspirin by itself did not significantly increase the bleeding risk. The strongest independent predictor of a bleeding complication was the use of heparin (odds ratio [OR], 9.9), followed by warfarin (OR, 5.6) and the combination of aspirin plus clopidogrel (OR, 3.8). The type of device implanted did not affect the bleeding risk.
Conclusions: Heparin, warfarin, and the combination of aspirin and clopidogrel significantly increase the risk of significant bleeding at the time of pacemaker or ICD implantation.
Perspective: The findings make a strong case for avoiding the use of heparin bridging in patients undergoing device implantation. In patients at high risk of thromboembolism, warfarin should be continued without interruption. Regarding aspirin plus clopidogrel, this combination increases the risk of bleeding and should be avoided unless needed because of a drug-eluting stent. Fred Morady, M.D., F.A.C.C.

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Title: ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 Expert Consensus Document on Coronary Computed Tomographic Angiography: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents
Topic: Noninvasive Cardiology
Date Posted: 5/17/2010 2:00:00 PM
Author(s): Mark DB, Berman DS, Budoff MJ, et al.
Citation: J Am Coll Cardiol 2010;May 17:[Epub ahead of print].
Clinical Trial: No
Perspective: Advances in computed tomography (CT) imaging technology, including the introduction of multi-detector row systems with electrocardiographic gating, have made imaging of the heart and the coronary arteries feasible. The potential to noninvasively obtain information comparable to that provided by invasive coronary angiography has been the major driving force behind the growth and dissemination of cardiac CT imaging. This expert consensus document focuses on the perspective of clinicians caring for patients with suspected or known coronary artery disease (CAD) in evaluating the potential current uses for cardiac CT angiography (CTA). The following are points to remember.

1. The best results are achieved with a slow, steady heart rate; intravenous contrast is administered, and periprocedural beta-adrenergic antagonists and/or nitroglycerin can help enhance image quality.

2. Coronary CTA provides information about the coronary lumen that attempts to approximate the information available from invasive coronary angiography. In addition, it provides information about the presence of nonobstructive plaque in the vessel walls.

3. Left ventricular (LV) systolic function can be estimated using CTA. LV assessment by CTA is based on use of retrospective gating with reconstruction of up to 20 phases of the cardiac cycle, including end-systole and end-diastole. Many of the desired LV functional calculations can be automated, although operator interaction with manual correction often is required.

4. Compared to invasive coronary angiography, studies evaluating the diagnostic accuracy of coronary CTA suggest that:
Studies demonstrating poorer performance are much less likely to be submitted to journals or favorably received by the peer review process.
≤5% of patients had nonevaluable scans.
Average per-patient sensitivity for identifying obstructive CAD was 98%, with average per-patient specificity of 88%.
Among populations tested with a mean prevalence of obstructive CAD of 61%, post-test probabilities for a negative test (negative predictive values) averaged 96%, and post-test probabilities for a positive test averaged 93% (range 64-100%).

5. Studies assessing the prognostic power of CTA among stable patients with suspected CAD suggest that the presence of plaque in greater numbers of coronary arteries, along with the severity of stenosis observed and the presence of plaque in the left main coronary artery, were predictors of mortality. A summary measure of the extent and severity of CAD (a modified Duke Coronary Disease Index) also has been shown to have independent prognostic power. Among patients with no detectable plaque by coronary CTA, mortality rate was 0.3% over the subsequent 15 months, suggesting that a completely negative study was associated with a very low risk of death.

6. Studies evaluating the use of coronary CTA among patients with acute chest pain were useful to reinforce data from the stable angina studies, showing that a negative coronary CTA study improves diagnostic certainty for ruling out significant CAD in a low-risk population.

7. Emerging applications of coronary CTA include assessment of noncalcified coronary plaque, assessing atherosclerotic burden, identification of vulnerable plaque, and assessment of LV enhancement patterns.

8. A substantial number of coronary CTA imaging studies result in incidental extracardiac findings. The literature describing the prevalence of extracardiac abnormalities in cardiac CT studies, the extent of their clinical significance, and the impact on patient health remains insufficient to answer important clinical and policy questions raised by this aspect of the test. Similarly, there is not a consensus regarding the use of coronary CTA as a screening test among people with known risk factors for, but no symptoms of, CAD.

9. Safety considerations associated with the use of coronary CTA include issues related to radiation exposure and radiation dose, and exposure to intravenous contrast agents.

10. The cost-effectiveness of coronary CTA could be favorable among low-risk patients presenting to the emergency department with chest pain, when compared with alternative management comprising observation, assessment of biomarkers, and stress testing. However, the overall cost-effectiveness of coronary CTA in a variety of clinical scenarios still requires evaluation. David S. Bach, M.D., F.A.C.C.

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Title: ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents
Topic: Noninvasive Cardiology
Date Posted: 5/17/2010 2:00:00 PM
Author(s): Hundley WG, Bluemke DA, Finn JP, et al.
Citation: J Am Coll Cardiol 2010;May 17:[Epub ahead of print].
Clinical Trial: No
Related Resources
JACC Article: ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents

Perspective: The following are 10 points to remember about this expert consensus document.

1. Cardiac magnetic resonance imaging (CMR) is based on detection of signals from hydrogen nuclei, which have a high concentration within the body. A magnetic field causes hydrogen nuclei to align along a fixed axis. Smaller magnetic pulses are then added (“pulse sequences”), which create an image of the protons. A variety of pulse sequences can be used for specific applications, which subsequently target moving blood or tissue. Magnetic field strengths are expressed in Tesla (T) and typical field strengths used for cardiovascular disease are 1.0, 1.5, and less frequently, 3.0 T. Higher strength fields produce higher spatial resolution.

2. CMR has several advantages, including absence of ionizing radiation or use of radioactive isotopes or iodinated contrast. A second advantage is the ability of CMR to evaluate the entire human body independent of body habitus (within physical limitations of a patient fitting within the scanner) or other disease, such as lung disease, which may interfere with echocardiographic imaging. Third, CMR is a family of examination techniques allowing assessment of anatomical features and function as well as blood flow.

3. Commonly used CMR techniques for evaluating cardiovascular disease include dark blood imaging. With this technique, pulse sequences detect slowly moving protons such as those within myocardium, while faster moving blood pool protons rapidly move out of the imaging plane and are not detected. Conversely, bright blood imaging specifically images the rapidly moving blood within chambers and vessels, and can provide a highly accurate measure of left ventricular (LV) size and function. Phase contrast data from CMR can be used to determine blood velocity from which intracardiac hemodynamics, such as one relevant for valvular heart disease, can be calculated. Tagging techniques allow extraction of highly detailed data regarding myocardial contraction from which strain and strain rate can be calculated. Gadolinium contrast is sequestered in the interstitium, and delayed gadolinium enhancement (LGE) is a highly accurate marker of myocardial fibrosis and scar.

4. CMR plays a valuable role in evaluation of patients with congestive heart failure. It provides a highly accurate assessment of left and right ventricular size, shape and function can identify highly specific morphology associated with diseases such as amyloidosis and myocardial noncompaction, among others. Contrast phase imaging can be used for determination of blood flow velocities from which diastolic function can be assessed. Identification of LGE representing myocardial scar provides prognostic information regarding ventricular arrhythmias.

5. CMR plays multiple roles in patients with known or suspected coronary artery disease (CAD), including determination of LV size and function and detection of occult myocardial infarction. CMR may be used for determining perfusion at rest and stress, and for determination of LV wall motion during dobutamine stress for detection of occult CAD.

6. The most valuable role that CMR plays in patients with valvular heart disease is in determination of left and right ventricular function with a lesser role for precise identification of valve anatomy such as identification of bicuspid aortic valves, vegetations, etc. Intracardiac hemodynamics regarding gradients can also be determined as part of the assessment of valvular heart disease.

7. CMR plays a unique and valuable role in simple and complex congenital heart disease. Its major advantage is that it simultaneously visualizes cardiac and extracardiac vascular structures, and is ideally suited for assessment of complex extracardiac vascular anatomy. It can play a valuable role in presurgical planning in patients with congenital heart disease where three-dimensional representation of a complex, anatomical relationship is routinely available.

8. CMR using magnetic resonance angiography (MRA) can play a valuable role in assessment of the vascular system including detection of disease of the aorta, including aortic dissection and aneurysm and carotid and renal disease. Both anatomical and functional information regarding intraluminal flow can be obtained.

9. Other clinically proven miscellaneous applications of CMR include identification of acute myocarditis, pulmonary angiography for detection of pulmonary embolus, assessment of pericardial disease, including pericardial constriction, and identification and characterization of both benign and malignant intracardiac masses.

10. All medically available devices have been characterized as CMR safe, conditional, or unsafe. Prior to undergoing CMR, patients with medical devices should inform the examiner of the nature and presence of the device, the safety of which subsequently can be determined from published tables. The majority of coronary artery and peripheral vascular stents are weakly or non-ferromagnetic and are considered CMR safe. The potential risks of medical devices in a CMR field include: movement of the device, which is unlikely for non- or weakly ferromagnetic devices (especially if chronically implanted); device heating, which may be particularly relevant for retained transvenous pacemaker and defibrillator leads; or interference with device function, which is a significant consideration for pacemakers. In general, patients with implanted stents can safely undergo CMR, whereas it is recommended that those with pacemaker and defibrillator devices undergo CMR only in highly specialized centers with experience in CMR in these individuals, and the appropriate assembled team to handle any programming issues or complications that arise. William F. Armstrong, M.D., F.A.C.C.

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CardiosourceNews from Heart Rhythm 2010

Official Title: A Phase III Prospective Randomized Double-Blind Active Controlled, Multicenter Superiority Study of Vernakalant Injection versus Intravenous Amiodarone in Subjects with Recent Onset Atrial Fibrillation. The AVRO Trial
Event: Heart Rhythm 2010
Topic(s): Arrhythmias
Presenter: John Camm
Writer(s): Fred M. Kusumoto, M.D., F.A.C.C.
Date Posted: 5/14/2010
Summary
A Phase III Prospective Randomized Double-Blind Active Controlled, Multicenter Superiority Study of Vernakalant Injection versus Intravenous Amiodarone in Subjects with Recent Onset Atrial Fibrillation. The AVRO Trial.

Background
Vernakalant is an investigational antiarrhythmic agent that has been shown to be more effective than placebo for rapid conversion (within 90 minutes) of atrial fibrillation after cardiac surgery (vernakanat: 47% vs. placebo: 14%) (Kowey et al). Multiple antiarrhythmic medications including Class 1C drugs such as flecainide/propafenone and Class III drugs such as ibutilide and dofetilide have been used for rapid chemical conversion of atrial fibrillation with moderate success (20-60% depending on the population studied).

Study Design
The investigators randomized patients (n= 254) with recent onset sustained (3 -48 hours) atrial fibrillation in a double blind, active controlled, double blind manner to two serial doses of vernakalant (3 mg/kg followed by an additional 2 mg/kg dose if the patient remained in atrial fibrillation) or serial doses of amiodarone (5 mg/kg followed by a 50 mg dose if the patient remained in atrial fibrillation). The primary endpoint was proportion of patients with conversion to sinus rhythm in 90 minutes. and sSecondary endpoints included: Time to conversion, proportion of patients without symptoms due to atrial fibrillation at 90 minutes, and change in quality of life.

Results and Conclusions
Vernakalant was significantly more effective than amiodarone for converting atrial fibrillation to sinus rhythm within 90 minutes (vernakalant: 51.7% vs. amiodaone: 5.2%). Vernakalant was also more effective than amiodaone for eliminating symptoms due to atrial fibrillation within 90 minutes (vernakalant: 53.4 % vs. amiodarone: 32.8%). Vernakalant was safe and generally well tolerated although patients complained of transient symptoms such as dysgeusia (6.9%), cough (3.4%) and nausea (2.6%). One patient developed nonsustained ventricular tachycardia, but no episodes of Torsades de Pointes or sustained ventricular arrhythmias were observed.

Perspective
The AVRO study found that vernakalant is more effective than intravenous amiodarone for rapid conversion of atrial fibrillation to sinus rhythm. Vernakalant is a promising new (currently investigational) antiarrhythmic medication that may be a useful alternative for rapid conversion of atrial fibrillation to sinus rhythm.

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CardiosourceNews from Heart Rhythm 2010

Official Title: Fish Oil to Inhibit Supraventricular Arrhythmias after Cardiac Surgery: The FISH Trial
Event: Heart Rhythm 2010
Topic(s): Arrhythmias, Cardiovascular Surgery
Presenter: Chirag Sandesara
Writer(s): Fred M. Kusumoto, M.D., F.A.C.C.
Date Posted: 5/14/2010
Summary
Perioperative beta-3 polyunsaturated fatty acids (PUFA) do not reduce the incidence of atrial fibrillation after coronary artery bypass grafting surgery (CABG).

Background
Postoperative atrial arrhythmias develop in 20-55% of patients after cardiac surgery and are associated with increased morbidity, mortality, and cost (annual estimated cost exceeding one1 billion dollars). One randomized study found that PUFA given for five 5 days before and after surgery can significantly reduce the development of postoperative atrial fibrillation (Calo et al) that was not confirmed in two similarly sized more recent randomized studies (Heidarsdottir et al, Saravanan et al).

Study Design
In this multicenter, double blind randomized, placebo controlled study, 260 patients undergoing non-emergent CABG were randomized to PUFA (2 g twice daily with a minimum total dosage of 6 g preoperatively and a post operative dose of 2 g once daily) or placebo. The primary endpoint was clinically significant and ECG documented atrial fibrillation or atrial flutter within 14 days after surgery that required treatment. Secondary endpoints included hospital length-of-stay, rehospitalization for atrial fibrillation, perioperative myocardial infarction, stroke, or bleeding.

Results and Conclusions
Perioperative treatment with PUFA was not associated with a decrease in postoperative atrial fibrillation (PUFA: 30% vs. Placebo 33%). Similarly no differences in secondary endpoints such as hospital length-of-stay or perioperative complications were detected between PUFA and placebo. The PUFA doses used in this trial were associated with a significant increase in plasma concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and a decrease in the plasma ratio of -6/-3 from baseline (Screening: 9.10; Surgery: 6.44; POD 4: 6.18) that was not observed in the placebo group.

Perspective
In this modest sized randomized trial, Tthe FISH trial found no benefit with perioperative oral PUFA therapy for reducing the likelihood for developing clinically significant atrial fibrillation after CABG. Although questions on dosing and route (oral vs. intravenous) will continue, three of four studies have not been able to demonstrate a decrease in post-operative AF associated with oral PUFA.
References
Calт L, Bianconi L, Colivicchi F, , et al. N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol. 2005;45:1723-8.
Heidarsdottir R, Arnar DO, Skuladottir GV, , et al. Does treatment with n-3 polyunsaturated fatty acids prevent atrial fibrillation after open heart surgery? Europace. 2010;12:356-63.
Saravanan P, Bridgewater B, West AL, O'Neill SC, Calder PC, Davidson NC. Omega-3 fatty acid supplementation does not reduce risk of atrial fibrillation after coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial. Circ Arrhythm Electrophysiol. 2010;3:46-53.

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CardiosourceNews from Heart Rhythm 2010

Official Title: J-Rhythm II Study. A randomized study of Angiotensin II Type 1 Receptor Blocker vs. Dihydropyridine Ca Antagonist for Treatment of Paroxysmal Atrial Fibrillation in Patients with Hypertension
Event: Heart Rhythm 2010
Topic(s): Prevention/Vascular
Presenter: Takeshi Yamashita
Writer(s): Fred M. Kusumoto, M.D., F.A.C.C.
Date Posted: 5/14/2010
Summary
In patients with hypertension and paroxysmal atrial fibrillation, both candesartan and amlodipine reduce blood pressure and frequency of atrial fibrillation at one-year follow-up with no significant differences between the agents for decreasing arrhythmia burden.

Background
Atrial fibrillation is present in 5-7 million people in the United States and is associated with significant morbidity and increased mortality, particularly in those patients with cardiovascular risk factors (Miyasaka et al, Fuster et al). Although radiofrequency catheter ablation and antiarrhythmic medication can be effective for reducing symptoms in selected populations, defining optimal “upstream” strategies for reducing the development or progression of atrial fibrillation would have a far larger impact on overall healthcare.

Study Design
The J-RHYTHM II trial randomized 318 patients with hypertension and paroxysmal atrial fibrillation in an open label manner to candesartan (8-12 mg) or amlodipine (2.5-5 mg). Daily transtelephonic monitoring was performed for one month prior to randomization and during one-year follow-up. The primary endpoint was difference in the number of days per month with atrial fibrillation between baseline and the last month of follow-up. Secondary endpoints included development of persistent atrial fibrillation and/or requiring cardioversion, changes in left atrial dimension, and changes in quality-of-life indices.

Results and Conclusions
Both candesartan and amlodipine reduced the number of days that patients were in atrial fibrillation after one year of therapy as compared with the pre-treatment month-long monitoring period: (candesartan: Decrease in 1.5 days/month; amlodipine: Decrease in 2.5 days/month). There was with no significant difference detected between the two therapies. Both candesartan and amlodipine reduced blood pressure after one year relative to baseline, although amlodipine was more effective than candesartan. During the study period 8% of patients treated with candesartan and 15% of patients treated with amlodipine developed persistent atrial fibrillation or required cardioverion (p = 0.08). Both amlodipine and candesartan were associated with improvement in quality-of-life indices after one year of treatment.

Perspective
The results of the J_RHYTHM II trial emphasize the importance of blood pressure control in patients with hypertension and atrial fibrillation. Different hypertension treatment strategies were not associated with differences in arrhythmia burden. However, in this study population, 70% of patients were being treated with Class I antiarrhythmic medication. It is possible that there may be differences between hypertension treatments for the progression or development of atrial fibrillation in other populations where the arrhythmia hasd not yet developed or is less established.
References
Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119-25
ACC/AHA Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006;50:562-

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Title: A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis
Topic: General Cardiology
Date Posted: 5/18/2010 3:00:00 PM
Author(s): The Idiopathic Pulmonary Fibrosis Clinical Research Network.
Citation: N Engl J Med 2010;May 18:[Epub ahead of print].
Clinical Trial: yes
Study Question: What is the effect of sildenafil on walk distance, dyspnea, and quality of life in patients with advanced idiopathic pulmonary fibrosis?
Methods: The investigators conducted a double-blind, randomized, placebo-controlled trial (called the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis [STEP-IPF]) of sildenafil in two periods. The first period consisted of 12 weeks of a double-blind comparison between sildenafil and a placebo control. The primary outcome was the proportion of patients with an increase in the 6-minute walk distance of 20% or more. Key secondary outcomes included changes in oxygenation, degree of dyspnea, and quality of life. The second period was a 12-week open-label evaluation involving all patients receiving sildenafil.
Results: A total of 180 patients were enrolled in the study. The difference in the primary outcome was not significant, with 9 of 89 patients (10%) in the sildenafil group and 6 of 91 (7%) in the placebo group having an improvement of 20% or more in the 6-minute walk distance (p = 0.39). There were small but significant differences in arterial oxygenation, carbon monoxide diffusion capacity, degree of dyspnea, and quality of life favoring the sildenafil group. Serious adverse events were similar in the two groups.
Conclusions: The authors concluded that this study did not show benefit for sildenafil for the primary outcome in patients with advanced idiopathic pulmonary fibrosis.
Perspective: In this randomized clinical study, sildenafil did not show a significant improvement in the primary endpoint of 6-minute walk distance among patients with advanced idiopathic pulmonary fibrosis. There were small but significant differences in degree of dyspnea and quality of life, which may be of clinical significance. The data provide rationale for further research and studies of sildenafil in this difficult to treat patient cohort. Meanwhile, use of sildenafil in patients with advanced idiopathic pulmonary fibrosis should only be considered after a frank and thorough discussion with the patient regarding lack of evidence of improvement in the primary outcome despite the symptomatic improvement seen in this study and other small case series. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Time to Treatment With Intravenous Alteplase and Outcome in Stroke: An Updated Pooled Analysis of ECASS, ATLANTIS, NINDS, and EPITHET Trials
Topic: General Cardiology
Date Posted: 5/19/2010
Author(s): Lees KR, Bluhmki E, von Kummer R, et al., on behalf of the ECASS, ATLANTIS, NINDS, and EPITHET rt-Pa Study Group Investigators.
Citation: Lancet 2010;375:1695-1703.
Clinical Trial: No
Study Question: What is the contemporary effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk?
Methods: The authors added data from ECASS III (821 patients) and EPITHET (100 patients) trials to a pool of common data elements from six other trials of alteplase for acute stroke (2,775 patients). Multivariate logistic regression was used to assess the relation of stroke onset to start of treatment (OTT) with treatment on favorable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal hemorrhage. The presence of an arterial occlusion was inferred from the patient’s symptoms and absence of hemorrhage or other causes of ischemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 minutes were included in the analysis.
Results: Treatment was started within 360 minutes of stroke onset in 3,670 patients randomly allocated to alteplase (n = 1,850) or to placebo (n = 1,820). Odds of a favorable 3-month outcome increased as OTT decreased (p = 0.0269) and no benefit of alteplase treatment was seen after around 270 minutes. Adjusted odds of a favorable 3-month outcome were 2.55 (95% confidence interval, 1.44-4.52) for 0-90 minutes, 1.64 (1.12-2.40) for 91-180 minutes, 1.34 (1.06-1.68) for 181-270 minutes, and 1.22 (0.92-1.61) for 271-360 minutes in favor of the alteplase group. Large parenchymal hemorrhage was seen in 96 (5.2%) of 1,850 patients assigned to alteplase and 18 (1.0%) of 1,820 controls, with no clear relation to OTT (p = 0.4140). Adjusted odds of mortality increased with OTT (p = 0.0444) and were 0.78 (0.41-1.48) for 0-90 minutes, 1.13 (0.70-1.82) for 91-180 minutes, 1.22 (0.87-1.71) for 181-270 minutes, and 1.49 (1.00-2.21) for 271-360 minutes.
Conclusions: The authors concluded that patients with ischemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 hours.
Perspective: This updated pooled analysis suggests that treatment with thrombolysis until 4.5 hours from stroke onset enhances the chance of favorable outcome. Serious hemorrhage rates are independent of stroke onset to start of treatment (OTT), but mortality increases with OTT longer than 4.5 hours. Across the time window studied, this analysis showed that the greatest benefit comes from earlier treatment, since net benefit diminishes and is undetectable in beyond 4.5 hours. These findings should spur a renewed commitment by emergency physicians, neurologists, and policy makers to target very early intervention with a proposed door-to-needle time of <60 minutes in the great majority of patients. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Peripartum Cardiomyopathy as a Part of Familial Dilated Cardiomyopathy
Topic: Heart Failure/Transplant
Date Posted: 5/19/2010
Author(s): van Spaendonck-Zwarts KY, van Tintelen JP, van Veldhuisen DJ, et al.
Citation: Circulation 2010;121:2169-2175.
Clinical Trial: No
Study Question: What is the role of genetic factors in the pathogenesis of peripartum cardiomyopathy (PPCM)?
Methods: The investigators reviewed their database of 90 dilated cardiomyopathy (DCM) families, focusing specifically on the presence of PPCM patients. Then, in a reverse approach, they reviewed 10 PPCM patients seen in their clinic since the early 1990s and performed cardiological screening of the first-degree relatives of three PPCM patients who did not show a full recovery. Finally, they analyzed the genes known to be most commonly involved in DCM in the PPCM patients.
Results: The investigators identified a substantial number (5 of 90, 6%) of DCM families with PPCM patients. Second, cardiological screening of first-degree relatives of three PPCM patients who did not show full recovery revealed undiagnosed DCM in all three families. Finally, genetic analyses revealed a mutation (c.149A>G, p.Gln50Arg) in the gene encoding cardiac troponin C (TNNC1) segregating with disease in a DCM family with a member with PPCM, supporting the genetic nature of disease in this case.
Conclusions: The authors concluded that these findings strongly suggest that a subset of PPCM is an initial manifestation of familial DCM.
Perspective: In this study, the authors identified a substantial number of DCM families with PPCM patients. Furthermore, they found support for the genetic nature of disease in one DCM family with PPCM by identifying a mutation in TNNC1, suggesting that PPCM can be a manifestation of familial DCM. Additional research is needed to confirm these findings and to better understand the interaction between oxidative stress associated with the peripartum/postpartum period and genetic factors. Based on the study, it may be reasonable to do presymptomatic screening for covert DCM in first-degree relatives of PPCM patients using noninvasive techniques. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Carotid Artery Stent Placement
Topic: Cardiovascular Surgery
Date Posted: 5/19/2010
Author(s): White CJ.
Citation: JACC Cardiovasc Interv 2010;3:467-474.
Clinical Trial: No
Related Resources
JACC Cardiovasc Intv Article: Carotid Artery Stent Placement

Perspective: The following are 10 points to remember from this state-of-the-art paper on carotid artery stent placement:

1. Stroke is the third leading cause of death in the United States and the common cause of disability. Most strokes are ischemic in origin.

2. Asymptomatic carotid stenosis (>50%) occurs in 5-10% of patients over the age of 65 years. The prevalence of severe carotid stenosis is less than 1%.

3. The annual risk of stroke associated with a >50% asymptomatic carotid stenosis is ~1-4.3%. The risk is higher in those with severe stenosis or those with progressive increase in the degree of carotid narrowing.

4. Most strokes occur in patients with no prior symptoms. Occurrence of a TIA is associated with a 15% risk of stroke at 1 month. The risk of stroke associated with a symptomatic stenosis increases with the degree of carotid narrowing.

5. Carotid endarterectomy (CEA) is considered beneficial if the risk of perioperative stroke or death is 3% or less in an asymptomatic patient and ≤6% for symptomatic patients.

6. Studies comparing carotid stenting (CAS) to CEA have demonstrated disparate results, with trials with experienced interventionalists demonstrating little difference in outcome between the two strategies while others showing better outcomes with CEA. The recently reported CREST trial demonstrated no difference in the primary endpoint between the two strategies.

7. Most of the data suggest no difference in risk of major stroke, whereas minor strokes are increased with CAS. Conversely, the risk of myocardial infarction and cranial neuropathies is increased with CEA. There appears to be an age interaction, with younger patients (<69 years) demonstrating better outcomes with CAS and older patients better outcomes with CEA.

8. Long-term outcome appears similar between CEA and CAS irrespective of the trial.

9. Contemporary preventive therapy (statins and contemporary antihypertensive therapy) has not been compared with carotid revascularization, and it is not clear if the advantage of carotid revascularization in patients with asymptomatic carotid stenosis is still extant in patients treated with aggressive medical therapy.

10. CEA and CAS should be viewed as complementary therapies since there are patients who clearly do better with one versus the other therapy, while a large group of patients could be treated with either strategy. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: Intravascular Ultrasound Findings in Patients With Very Late Stent Thrombosis After Either Drug-Eluting or Bare-Metal Stent Implantation
Topic: Interventional Cardiology
Date Posted: 5/20/2010
Author(s): Lee CW, Kang SJ, Park DW, et al.
Citation: J Am Coll Cardiol 2010;55:1936-1942.
Clinical Trial: No
Related Resources
JACC Article: Intravascular Ultrasound Findings in Patients With Very Late Stent Thrombosis After Either Drug-Eluting or Bare-Metal Stent Implantation

Study Question: What are the intravascular ultrasound (IVUS) findings at drug-eluting stent (DES) and bare-metal stent (BMS) sites in patients with very late stent thrombosis (VLST)?
Methods: A total of 30 consecutive VLST patients with acute myocardial infarction (DES, n = 23; BMS, n = 7) were enrolled in the study. Patients underwent IVUS examination before coronary angioplasty. The IVUS images were recorded on s-VHS videotape or computer disk and analyzed by personnel unaware of the type of stent implanted.
Results: The baseline characteristics were similar for the two groups, with the exception of reference vessel size, lesion length, stent length, minimal lumen diameter, and diameter stenosis after the procedure. Overall, VLST occurred at a mean 50.8 ± 36.2 months after the index procedure, and occurred earlier after DES than BMS (33.2 ± 12.5 months vs. 108.4 ± 26.5 months, p < 0.001). IVUS variables were generally similar for the two groups. However, plaque burden at the distal reference segment, stent, and neointimal area of the in-stent segment were smaller in the DES group. Stent malapposition was observed in 73.9% of DES patients, but in no BMS patients (p = 0.001). Disease progression with neointimal rupture within the stent was observed in 10 DES patients (43.5%) and 7 BMS patients (100%; p = 0.010).
Conclusions: The authors concluded that stent malapposition was unique to DES-related VLST, whereas disease progression with neointimal rupture was more common in BMS patients.
Perspective: These results suggest that different mechanisms underlie VLST depending upon the stent type. Stent malapposition plays a key role in DES-related VLST, whereas neoatherosclerosis with plaque rupture plays a key role in BMS-related VLST. Despite the limitations of a single-center retrospective analysis, the study provides important insight into the mechanism of stent thrombosis in different stent types. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Incremental Prognostic Value of Coronary CT Angiography in Patients With Suspected Coronary Artery Disease
Topic: Noninvasive Cardiology
Date Posted: 5/20/2010
Author(s): Russo V, Zavalloni A, Bacchi-Reggiani L, et al.
Citation: Circ Cardiovasc Imaging 2010;May 11:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the prognostic value of multi-detector computed tomographic coronary angiography (MDCTCA) in patients with suspected but undocumented coronary artery disease (CAD) and, in particular, the incremental prognostic value, as compared to clinical risk and calcium scoring (CCS)?
Methods: A total of 441 patients with suspected CAD underwent MDCTCA to evaluate the presence and severity of the disease. Indications for MDCTCA included typical or atypical chest pain, pathological or equivocal exercise test, high cardiovascular risk profile, and preoperative cardiac risk stratification before major surgery (34.5%). Persons with known CAD were excluded. A pretest likelihood of CAD was obtained using the Morise score, which includes clinical variables and risk factors together with the presence and type of symptoms (low likelihood of CAD = <30%, intermediate likelihood = 30-70%, and high likelihood of CAD = >70%). Patients were followed up for the occurrence of hard cardiac events (cardiac death, nonfatal myocardial infarction, and unstable angina requiring hospitalization).
Results: Mean age was 59.7 ± 11.6 years, 72.6% were male, 31.3% were smokers; 62% were asymptomatic, and 20.6% had atypical and 17.3% typical chest pain. Likelihood of CAD was low in 10.9%, intermediate in 69.4%, and high in 19.7%. Agatston CCS was ≤10 in 45%, 11-400 in 37%, and >400 in 18%. Coronary lesions were detected in 297 (67.3%) patients of whom 53% had at least one >50% stenosis. During a mean follow-up of 31.9 ± 14.8 months, 44 hard cardiac events occurred in 40 patients. The CCS had a modest incremental prognostic value as compared to a clinical risk model (p = 0.018), whereas MDCTCA provided an additional incremental prognostic value, as compared to a clinical risk model plus calcium scoring (hazard ratio, 2.445) when considering both nonobstructive versus obstructive CAD (p = 0.016) as well as plaque composition (calcified vs. noncalcified and/or mixed plaques, p = 0.0001). During follow-up, patients with normal coronary arteries had an annualized incidence rate of 0.88% as compared to those with mild CAD (3.89%) and to patients with significant CAD (8.09%). The presence of noncalcified or mixed plaques, regardless of lesion severity, was found to be the strongest predictor of events (p < 0.0001) as a potential marker of plaque vulnerability.
Conclusions: MDCTCA provides independent and incremental prognostic information, as compared to baseline clinical risk factors and calcium scoring in patients with suspected CAD.
Perspective: The robust results could have been influenced by the relatively high annual event rate (nearly 1% in those with normal coronary arteries and 4% in those without significant stenosis), and were obtained with a 16-slice MDCT scanner, which has limited resolution compared to 64-slice CT angiography. Except for the WISE study, which assessed the utility of various tests in symptomatic women, the ability of various diagnostic tools (nuclear and echo stress imaging) to detect and improve prognostication in coronary disease has never been subjected to rigorous clinical investigation. The clinical utility of combining CT angiography with CCS for characterizing risk in symptomatic and asymptomatic persons at risk is intuitive, but needs to be evaluated against other strategies such as simply aggressive medical treatment of all but the very low risk for CAD. Radiation dosing from a chest X-ray is 0.06 mSv, a mammogram 0.7 mSv, and CT angiography varies from 3.7-13 mSv, which is clearly associated with incremental risk for cancer. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Determinants of Coronary Calcium Conversion Among Patients With a Normal Coronary Calcium Scan: What Is the “Warranty Period” for Remaining Normal?
Topic: Noninvasive Cardiology
Date Posted: 5/20/2010
Author(s): Min JK, Lin FY, Gidseg DS, et al.
Citation: J Am Coll Cardiol 2010;55:1110-1117.
Clinical Trial: No
Related Resources
JACC Article: Determinants of Coronary Calcium Conversion Among Patients With a Normal Coronary Calcium Scan: What is the “Warranty Period” for Remaining Normal?

Study Question: What are the frequency and clinical predictors of conversion from normal to abnormal coronary artery calcium (CAC) scans?
Methods: CAC scanning was performed annually for 5 years in 442 patients with baseline CAC = 0. CAC and clinical predictors were compared to a cohort of 621 subjects with baseline CAC >0. CAC was expressed in Hounsfield units (HU), and clinical predictors of age, diabetes, smoking, and others were tabulated.
Results: CAC progressed from an initial value of 0 in 106 of the 422 subjects (25.1%) with a mean time to conversion to abnormal of 4.1 ± 0.9 years. The number of subjects converting at years 1-5 was 2 (0.5%), 5 (1.2%), 24 (5.7%), 26 (6.2%), and 49 (11.6%). Age, smoking, diabetes, and hypertension were all significantly associated with the risk of conversion to CAC >0, but did not relate to the time at which conversion occurred. At the time of conversion, the average CAC score was 19 ± 19. Compared to subjects with baseline CAC >0, those with CAC = 0 were younger (48.8 ± 8.9 vs. 56.6 ± 8.6 years). The prevalence of hypertension, diabetes, smoking, and lipid disorder in those with CAC = 0 was 46%, 9.5%, 32%, and 66.4% compared to 56.5%, 16.3%, 36.4%, and 76.7% (p = NS for smoking, otherwise p ≤ 0.002). For individuals with a baseline CAC >0, 497 of the 621 (80%) had progression over a mean of 1.9 ± 1.1 years of follow-up with an average CAC increase of 45.5 ± 89.6 HU. The progression was statistically related to male gender, lipid status, smoking, and baseline CAC score, with only CAC score remaining independently predictive on multivariable analysis. Among propensity-matched cohorts, those with baseline CAC >0 had a higher frequency of progression than those with CAC = 0.
Conclusions: Progression of CAC from baseline score of 0 occurs at a low frequency within the first 4 years, and the presence of conversion is related to traditional risk factors. No traditional risk factor, however, predicts the timing with which conversion occurs.
Perspective: CAC scoring has been used as both a diagnostic and prognostic technique. Numerous studies have demonstrated the progressive likelihood of the presence and severity of coronary disease based on CAC and, furthermore, a higher likelihood of events and higher prevalence of positive cardiovascular stress testing with higher CAC. This study essentially asks the question: 'What is the warranty of a normal CAC?' This study, performed in a population of patients at intermediate risk of coronary disease but without clinical evidence of such at baseline scanning, suggests that the likelihood of progression from a CAC of 0 to advanced coronary calcium is negligible within 5 years and that the likelihood of progression to CAC >0 is low within the first 2-3 years after establishing a baseline. It appears that all patients in this study received the benefit of aggressive medical therapy for risk factor modification including uniform use of statins in those with elevated lipids. Not evaluated in this study was any link between conversion from a CAC of 0 and occurrence of events or change in symptomatic status. Assuming a link between CAC and cardiovascular events and/or need for further cardiovascular testing, it appears that serial determination of CAC is unwarranted at intervals <3-4 years in individuals with a score of 0 at baseline. William F. Armstrong, M.D., F.A.C.C.

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Title: Conventional and Chest-Compression-Only Cardiopulmonary Resuscitation by Bystanders for Children Who Have Out-of-Hospital Cardiac Arrests: A Prospective, Nationwide, Population-Based Cohort Study
Topic: Arrhythmias
Date Posted: 5/21/2010
Author(s): Kitamura T, Iwami T, Kawamura T, et al., on behalf of the Implementation Working Group for All-Japan Utstein Registry of the Fire and Disaster Management Agency.
Citation: Lancet 2010;375:1347-1354.
Clinical Trial: No
Study Question: What is the optimal type of cardiopulmonary resuscitation (CPR) for pediatric patients with out-of-hospital cardiac arrest (OHCA)?
Methods: The data in this study were obtained from a nationwide registry of OHCAs in Japan. Children ages 17 years or younger were included in the study. The 1° outcome was favorable neurological outcome at 1 month of follow-up.
Results: Data from 5,170 children with OHCA were analyzed. The OHCA was from a noncardiac cause in 71% of patients. One-month survival with favorable neurological outcome was 3.2%. Twenty-seven percent of the OHCAs were witnessed by bystanders. When there was a noncardiac cause of OHCA, the 1° outcome was significantly more frequent after bystander CPR (5.1%) than with no bystander CPR (1.5%) and after conventional CPR (7.2%) than after compression-only CPR (1.6%). When there was a cardiac cause of OHCA, the incidence of the 1° outcome was significantly higher with bystander CPR (9.5%) than without bystander CPR (4.1%), but did not differ significantly after conventional CPR (9.9%) versus compression-only CPR (8.9%).
Conclusions: Rescue breaths provide incremental value compared to compression-only CPR in children with OHCA, but only when the cardiac arrest results from a noncardiac etiology.
Perspective: Observational studies in adults have indicated that compression-only CPR yields similar or better outcomes than does conventional CPR in adults with OHCA, and the American Heart Association now recommends compression-only CPR for OHCA of presumed cardiac origin. In children, OHCA is more often noncardiac in etiology (e.g., drowning, trauma, respiratory disease) than in adults. Therefore, unless there is a witnessed sudden collapse consistent with a cardiac-based OHCA, conventional CPR with rescue breaths is indicated. Fred Morady, M.D., F.A.C.C.

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Title: Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy: A Randomized Controlled Trial
Topic: General Cardiology
Date Posted: 5/21/2010
Author(s): House AA, Eliasziw M, Cattran DC, et al.
Citation: JAMA 2010;303:1603-1609.
Clinical Trial: yes
Study Question: Does therapy with B vitamins affect diabetic nephropathy?
Methods: This was a randomized, multicenter, double-blind, placebo-controlled trial, which randomized subjects to a combination of B vitamins (2.5 mg/d of folic acid, 25 mg/d of B6, and 1 mg/d of B12) or placebo, between May 2001 and July 2007. Subjects were known diabetics, either type 1 or 2. Potential subjects were excluded if they had advanced renal failure (creatinine clearance <30 mg/min or were on dialysis), were awaiting imminent dialysis, or women who were pregnant. The primary outcome of interest was changes in radionuclide glomerular filtration rate (GFR) between baseline and 36 months. Secondary outcomes included the occurrence of dialysis, and a composite outcome of myocardial infarction, stroke, revascularization, and all-cause mortality. Plasma total homocysteine was also measured from five university centers.
Results: A total of 238 subjects were included in the study. The mean follow-up was 31.9 months. At 36 months, GFR had decreased by a mean of 16.5 ml/min/1.73 m2 in those taking the B vitamins compared to 10.7 ml/min/1.73 m2 (p = 0.02). There was no difference between groups in the occurrence of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6); however, the composite cardiovascular disease outcome occurred more often in the B vitamin group (HR, 2.0; 95% CI, 1.0-4.0). Plasma total homocysteine decreased by a mean of 2.2 µmol/L at 36 months in the B vitamin groups, as compared to 2.6 µmol/L in the placebo group.
Conclusions: The investigators concluded that among patients with diabetic nephropathy, high-dose B vitamins were associated with a greater decrease in GFR and higher risk of vascular events.
Perspective: The results of this randomized controlled trial suggest that B vitamins do not have a role in the clinical management of diabetic patients with nephropathy. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Mood Food: Chocolate and Depressive Symptoms in a Cross-sectional Analysis
Topic: Prevention/Vascular
Date Posted: 5/21/2010
Author(s): Rose N, Koperski S, Golomb BA.
Citation: Arch Intern Med 2010;170:699-703.
Clinical Trial: No
Study Question: Is chocolate consumption associated with depression?
Methods: Data from 1,018 subjects (ages 20-85 years) residing in the San Diego area were used for the present analysis. Subjects using antidepressants were excluded from the study. Information on diet including chocolate intake was obtained through the Fred Hutchinson Food Frequency Questionnaire and the Statin Study Questionnaire (which asked participants how many times per week they consumed chocolate). Mood was assessed through the Center for Epidemiologic Studies Depression Scale (CES-D), with screening positive for possible depression as a CES-D score of 16 or greater.
Results: Of the 1,018 adults sampled, 324 were women, 80.4% were white, and the mean age of the cohort was 57.6 years. Mean body mass index was 27.8 kg/m2. Among 931 subjects who were not taking antidepressants and who provided information on chocolate consumption, the mean CES-D score was 7.7 (median 6.0) and mean chocolate consumption was 6.0 servings per month. Those who had a CES-D score ≥16 reported higher intake of chocolate compared to those who scored <16 (8.4 servings per month vs. 5.4 servings per month, p = 0.004). Subjects who had CES-D scores ≥20 reported an average of 11.8 servings of chocolate per month. These findings were similar for men and women when examined separately. No significance differences between groups were observed in regard to intake of fat, carbohydrates, or total energy intake.
Conclusions: The authors concluded that higher CES-D depression scores were positively associated with chocolate intake; however, further study would be needed to determine causality.
Perspective: These findings suggest men and women who have depressive symptoms may be using chocolate to modulate mood. Given the cross-sectional nature of this study, questions remain unanswered in terms of the direction of the association. In addition, the type of chocolate with respect to cocoa content was not addressed. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Pressure Frequency Characteristics of the Pericardial Space and Thorax During Subxiphoid Access for Epicardial Ventricular Tachycardia Ablation
Topic: Arrhythmias
Date Posted: 5/24/2010
Author(s): Mahapatra S, Tucker-Schwartz J, Wiggins D, et al.
Citation: Heart Rhythm 2010;7:604-609.
Clinical Trial: No
Study Question: Are pressure-frequency measurements helpful for identifying the pericardial space during percutaneous access procedures?
Methods: Pressure was measured for 2 minutes in the pericardial space and in the thorax during sheath withdrawal in 20 patients who underwent subxyphoid percutaneous access of the pericardial space for epicardial ablation of ventricular tachycardia (VT). All patients were intubated and ventilated at 12 breaths/minute. Spectral analysis of the pressure recordings was performed offline by fast Fourier transformation.
Results: The mean pressures in the thorax (7.7 mm Hg) and pericardial space (7.8 mm Hg) did not differ significantly. Spectral analysis demonstrated a single peak at a mean of 0.2 Hz in the thorax pressure recordings and a dominant frequency at a mean of 0.2 Hz plus a second, smaller peak at a mean of 1.16 Hz in the pericardial pressure recordings.
Conclusions: Spectral analysis of pressure recordings reflects the respiratory rate in the thorax and the respiratory rate plus the heart rate in the pericardial space. These pressure-frequency characteristics are useful for identifying the pericardial space during pericardial access procedures.
Perspective: One of the limiting factors for widespread adaptation of epicardial ablation into clinical practice is the risk of right ventricular perforation. Fluoroscopy with contrast injections is helpful but not foolproof. The technique described in this study may facilitate recognition of when the percutaneous needle has passed from the thorax into the pericardial space. However, use of this technique in clinical practice will require the availability of a needle that has a pressure sensor at its tip and the capability for online spectral analysis. Fred Morady, M.D., F.A.C.C.

Title: Impact of Cytochrome P450 2C19 Loss-of-Function Polymorphism and of Major Demographic Characteristics on Residual Platelet Function After Loading and Maintenance Treatment With Clopidogrel in Patients Undergoing Elective Coronary Stent Placement
Topic: Interventional Cardiology
Date Posted: 5/24/2010 5:00:00 PM
Author(s): Hochholzer W, Trenk D, Fromm MF, et al.
Citation: J Am Coll Cardiol 2010;55:2427-2434.
Clinical Trial: No
Related Resources
JACC Article: Impact of Cytochrome P450 2C19 Loss-of-Function Polymorphism and of Major Demographic Characteristics on Residual Platelet Function After Loading and Maintenance Treatment With Clopidogrel in Patients Undergoing Elective Coronary Stent Placement

Study Question: What is the relative impact of demographic and clinical variables versus the cytochrome P450 2C19 (CYP2C19) polymorphism on antiplatelet effects of clopidogrel?
Methods: This analysis enrolled 760 patients undergoing elective coronary stent implantation after loading with 600 mg of clopidogrel. Residual platelet aggregation was determined by optical aggregometry (adenosine diphosphate 5 µmol/L) before discharge. The investigators analyzed the predictive value of the CYP2C19*2 polymorphism and baseline variables for an insufficient antiplatelet response by multivariable regression analysis and classification and regression trees analysis, and determined the proportion responsible for the antiplatelet response of these predictors by multivariable linear regression analysis.
Results: Major independent predictors for an insufficient antiplatelet response to clopidogrel were CYP2C19*2 carrier status (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.93-3.90) together with age (OR, 1.03; 95% CI, 1.01-1.05), diabetes mellitus (OR, 1.75; 95% CI, 1.19-2.56), and body mass index (OR, 1.06; 95% CI, 1.02-1.11). The classification and regression trees analysis demonstrated that CYP2C19*2 carrier status followed by diabetes mellitus was the best discriminator between a sufficient and an insufficient antiplatelet response to clopidogrel. The full linear regression model including all of these parameters could only explain 11.5% of the antiplatelet response (5.2% by CYP2C19*2 carrier status alone).
Conclusions: The authors concluded that in patients critically dependent on adequate platelet inhibition, genotyping alone or in combination with clinical factors cannot replace phenotyping of platelet function.
Perspective: The primary finding of this analysis is that the CYP2C19*2 loss-of-function polymorphism and several clinical variables (diabetes mellitus, age, and body mass index) show a statistical highly significant association with high on-clopidogrel residual platelet aggregation. However, despite confirming the strong impact of the CYP2C19 loss-of-function polymorphism on antiplatelet effect of clopidogrel, the current data suggest that genotyping for CYP2C19 is insufficient for clinical decision-making without platelet function testing. Furthermore, addition of clinical variables could not fully correct this shortcoming. Based on all available data, it seems reasonable to integrate both genotyping and platelet function measurement to assess ischemic risk and to guide antiplatelet therapy in appropriate high-risk patients. Debabrata Mukherjee, M.D., F.A.C.C.

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Title: Choice of Prosthetic Heart Valve in Adults: An Update
Topic: Cardiovascular Surgery
Date Posted: 5/24/2010 5:00:00 PM
Author(s): Rahimtoola SH.
Citation: J Am Coll Cardiol 2010;55:2413-2426.
Clinical Trial: No
Related Resources
JACC Article: Choice of Prosthetic Heart Valve in Adults: An Update

Perspective: The following are 10 points to remember about choice of prosthetic heart valve (PHV) in adults.

1. Patient survival after PHV has increased markedly and it is essential to consider the patient’s point of view regarding the ideal PHV.

2. At present, the choice of PHV in most clinical situations is between a mechanical PHV and a stented bioprosthesis. An important determining factor in the choice between these two PHVs is which of the two complications—anticoagulation therapy or structural valve deterioration (SVD)—one wants to avoid.

3. Mechanical PHVs that are approved by the Food and Drug Administration and have good and comparable outcomes at ≥15-20 years of follow-up will likely have good outcomes on very long-term follow-up.

4. Currently for the overwhelming majority of adult patients ages >60-65 years, the choice of a biological PHV is a stented bioprosthesis. However, there are exceptions; for example, for active infective endocarditis with an associated abscess or uncontrolled infection, a homograft valve may be chosen.

5. Anticoagulants are essential with the use of mechanical valves, and can be instituted and maintained in many patients with low risk. The disadvantages include lifetime needs of therapy and tests, difficulties in initiating and maintaining an adequate international normalized ratio in many patients, and major risks of bleeding.

6. The risks of bleeding are increased for patients ≥65 years old, greatly so for those ≥75 years old, and for those with CHADS2 score ≥3.

7. All biological valves are at risk for SVD. The age of the patient at the time of PHV implantation is the most important determinant of SVD.

8. Typically, in ‘young’ people, use of a biological valve will result in reoperation, probably in multiple reoperations.

9. There is no significant difference in valve areas at 6 months between a bileaflet mechanical valve and porcine bioprosthesis for valves with the same valve size.

10. The physicians involved in the decision-making process should be very knowledgeable about the patient outcomes with the use of the various PHV, and they should be completely discussed with the patient. The final choice of PHV should be a joint decision by the patient, cardiologist, and cardiac surgeon. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Impact of the ALLHAT/JNC7 Dissemination Project on Thiazide-Type Diuretic Use
Topic: Prevention/Vascular
Date Posted: 5/24/2010 4:00:00 PM
Author(s): Stafford RS, Bartholomew LK, Cushman WC, et al., on behalf of the ALLHAT Collaborative Research Group.
Citation: Arch Intern Med 2010;170:851-858.
Clinical Trial: No
Related Resources
Trial: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Study Question: What was the impact of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) results on physician practice patterns?
Methods: To improve discrimination and adoption of changes in practice management resulting from landmark trials and changes in guidelines, specific strategies are considered. Academic detailing incorporates several approaches used in pharmaceutical marketing including use of investigator-educators as opinion leaders, and communication of antihypertensive management through individualized small groups. Two national databases were used to evaluate this academic detailing model. The National Disease and Therapeutic Index is a physician-based survey, which surveys approximately 4,800 physicians every 3 months; data collection included prescribing information on antihypertensives. Data from this survey overlapped with academic detailing efforts in 176 counties from 38 states. The IMS Health Xponent database is a national computerized sample of approximately 36,000 retail pharmacies. Practice patterns prior to 2004 and in 2007 were compared. In addition, national trends in use of thiazide type diuretics were examined for an 8-year time period (2000-2008).
Results: The ALLHAT findings were published in 2002. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) was published in 2003. Survey data showed that thiazide-type diuretic use increased in most in US counties where academic detailing activity was the greatest (an increase from 37.9% to 46.5%, p < 0.05) compared to counties where activity was moderate or low. Pharmacy dispensing data showed that thiazide-type diuretic prescriptions increased by 8.7% in counties with dissemination project activities compared to 3.9% in counties without such activities (p < 0.001). On a national level, thiazide-type diuretic use did not increase between 2004 and 2008.
Conclusions: The investigators suggest the ALLHAT/JNC7 dissemination project was associated with a small effect on thiazide-type diuretic use, demonstrating that academic detailing may increase physician implementation of clinical trials.
Perspective: These findings suggest a modest adoption of thiazide diuretics, as recommended by the ALLHAT findings and JNC7. However, this project was initiated 2 years after the publication of ALLHAT; thus, antihypertensive management may have already undergone significant changes. Further research would be needed to understand specific factors related to the adoption of recommendations for control of blood pressure. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Overtime Work and Incident Coronary Heart Disease: The Whitehall II Prospective Cohort Study
Topic: Prevention/Vascular
Date Posted: 5/25/2010
Author(s): Virtanen M, Ferrie JE, Singh-Manoux A, et al.
Citation: Eur Heart J 2010; May 11:[Epub ahead of print].
Clinical Trial: No
Study Question: Is working overtime associated with increased risk of heart disease?
Methods: Data from the Whitehall cohort were used for the present study. British civil servants working in London, England, who were between the ages of 31-61, worked full-time, and were free of coronary heart disease (CHD) at baseline were included in this analysis. Questions regarding hours of work per day were originally asked in the 1991-94 questionnaires. Follow-up extended through 2002-2004. The primary outcome of interest was fatal CHD, nonfatal myocardial infarction (MI), or angina. Models adjusting for multiple factors including sociodemographic factors, CHD risk factors, and job grade were used to examine risk associated with levels of overtime work including, 1 hour, 2 hours, and 3-4 hours with no overtime defined as the reference group.
Results: A total of 4,262 men and 1,752 women were included in the analysis. Mean follow-up was 11.2 years. Within the cohort, 54% reported no overtime work, 21% reported approximately 1 hour of overtime, 15% reported 2 hours of overtime, and 10% reported 3-4 hours of regular overtime. Workers who reported regular overtime work were more often male, married, smokers, drank alcohol, and in higher occupational grades. They also reported more psychological stress and type A behavior. Workers who reported regular overtime were more likely to have lower high-density lipoprotein cholesterol levels. Subjects who reported working 3-4 hours of overtime had an increased risk of CHD death, nonfatal MI, or angina (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.15-2.23), which was not significantly attenuated after adjustment for cardiovascular risk factors (HR, 1.56; 95% CI, 1.11-2.19). A similar result was observed when just CHD mortality and nonfatal MI was used as the outcome. A significant interaction between decision latitude and overtime work was observed, such that subjects with low-decision latitude but higher overtime work had a higher risk of CHD events (HR, 1.78; 95% CI, 1.10-2.89), whereas those with a higher decision latitude and overtime work had a lower nonsignificant risk of CHD events (HR, 1.26; 95% CI, 0.77-2.04).
Conclusions: The investigators concluded that overtime work is associated with increased risk for CHD events, independently of CHD risk factors.
Perspective: These findings suggest that clinicians may want to ask patients about occupational work habits and counsel them regarding regular overtime work. Longer work hours often translate into reduction in leisure time activities. Since leisure time activities can decrease stress and promote physical activity, the results of this study are not surprising. Elizabeth A. Jackson, M.D., F.A.C.C

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Title: Frequency of Late Drug-Eluting Stent Thrombosis With Non-Cardiac Surgery
Topic: General Cardiology
Date Posted: 5/25/2010
Author(s): Chia KK, Park JJ, Postle J, Cottrill A, Ward MR.
Citation: Am J Cardiol 2010;May 17:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the risk for late stent thrombosis (LAST) with cessation of antiplatelet therapy prior to noncardiac surgery?
Methods: Using billing data from two large health funds, members who had drug-eluting stent (DES) insertion (n = 9,321) with subsequent noncardiac surgery (n = 4,126) were mailed a questionnaire regarding their noncardiac procedures, antiplatelet use, and subsequent coronary events. All events were verified with the medical records.
Results: From 1,086 returned, 710 were suitable for inclusion, identifying 11 patients (1.5%) with perioperative myocardial infarctions confirmed by medical records. Angiography showed that only two had stent thromboses, whereas seven had a new culprit lesion (two patients did not undergo angiography). Before their noncoronary procedures, 66% were receiving dual antiplatelet therapy, and 30% were taking single agents. Surgery was performed on dual therapy in 18%, on single agents in 23%, and with no antiplatelet therapy in 59%. The mean time to surgery from stent implantation was 348 days, with 56% in <12 months.
Conclusions: The authors concluded that noncardiac surgery after DES implantation is frequent and appears to have low cardiac morbidity despite variable antiplatelet cessation.
Perspective: This study suggests that noncardiac surgery after DES implantation is performed frequently, that the acute coronary syndrome event rate is low, and that most events occur because of new culprit lesions. These data also suggest that concerns regarding the risks of LAST in this setting may have been overestimated. An important limitation of this study was the low response rate, with only a quarter or so of patients responding. For now, premature cessation of antiplatelet therapy should be considered as a strong predictor of stent thrombosis, and patients scheduled to undergo noncardiac surgery within a year should not undergo DES implantation. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Racial and Ethnic Differences in the Treatment of Acute Myocardial Infarction. Findings From the Get With The Guidelines–Coronary Artery Disease Program
Topic: General Cardiology
Date Posted: 5/25/2010
Author(s): Cohen MG, Fonarow GC, Peterson ED, et al.
Citation: Circulation 2010;121:2294-2301.
Clinical Trial: No
Study Question: Are the well documented racial/ethnic differences in evidence-based acute myocardial infarction (AMI) care eliminated in hospitals participating in a national quality improvement program?
Methods: This study assessed care in 142,593 AMI patients (121,528 whites, 10,882 blacks, and 10,183 Hispanics) at 443 hospitals participating in the Get With the Guidelines–Coronary Artery Disease (GWTG-CAD) program between January 2002 and June 2007. Individual and overall composite rates of defect-free care, defined as the proportion of patients receiving all eligible performance measures, were examined, as well as temporal trends in use of performance measures according to race/ethnicity by calendar quarter.
Results: Overall, individual performance measure use was high, ranging from 78% for use of angiotensin-converting enzyme inhibitors to 96% for use of aspirin at discharge. Use of each of these improved significantly over the 5 years of study. Overall, defect-free care was 80.9% for whites, 79.5% for Hispanics (adjusted odds ratio vs. whites, 1.00; 95% confidence interval, 0.94-1.06; p = 0.94), and 77.7% for blacks (adjusted odds ratio vs. whites, 0.93; 95% confidence interval, 0.87-0.98; p = 0.01). A significant gap in defect-free care was observed for blacks mostly during the first half of the study, which was no longer present during the remainder of the study. Overall, progressive improvements in defect-free care were observed regardless of race/ethnic groups.
Conclusions: Among hospitals engaged in a national quality monitoring and improvement program, evidence-based care for AMI appeared to improve over time for patients irrespective of race/ethnicity, and differences in care by race/ethnicity care were reduced or eliminated.
Perspective: This very important study demonstrates how discharge protocols requiring opt out of care standards can improve quality and eliminate disparities by ethnicity, race, and socioeconomic variables. The next and major step is to assess the short- and long-term compliance with discharge recommendations and methods to improve outcome by enhancing compliance. This costly process should be helped by the promised national health care database. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Relationship of Functional Mitral Regurgitation to New-Onset Atrial Fibrillation in Acute Myocardial Infarction
Topic: Arrhythmias
Date Posted: 5/26/2010
Author(s): Bahouth F, Mutlak D, Furman M, et al.
Citation: Heart 2010;96:683-688.
Clinical Trial: No
Study Question: Does functional mitral regurgitation (FMR) occurring after acute myocardial infarction (AMI) promote atrial fibrillation (AF) by producing left atrial volume overload?
Methods: A total of 1,920 patients admitted with AMI were studied; patients with known AF were excluded. FMR using echocardiography was classified into three groups: none, mild FMR, and moderate or severe FMR. The relationship between FMR and AF occurring at any time during the hospital course was examined using multivariable logistic regression.
Results: Mild FMR was present in 744 patients (38.8%) and moderate or severe FMR was present in 150 patients (7.8%). AF developed in 51 (5.0%), 83 (11.2%), and 28 (18.7%) patients with no FMR, mild FMR, and moderate or severe FMR, respectively (p < 0.001). In multivariable logistic regression, both mild (odds ratio [OR], 1.6; 95% CI, 1.1-2.3; p = 0.02) and moderate or severe FMR (OR, 2.1; 95% CI, 1.2-3.6; p = 0.007) were independent predictors of AF. There was a significant interaction between the left ventricular ejection fraction and FMR (p = 0.003), such that mild FMR was predictive of AF only in patients with a reduced (<45%) ejection fraction. After discharge, new AF complicating AMI was strongly associated with subsequent readmission for heart failure (hazard ratio, 3.7). Although subsequent mortality also was higher among patients with new AF complicating AMI, independent predictors of mortality were renal insufficiency, Killip class, ejection fraction, and severity of FMR.
Conclusions: The authors concluded that there is a graded independent association between the severity of FMR and the new onset of AF in patients with AMI.
Perspective: It makes sense that increased left atrial volume and increased left atrial pressure associated with FMR (as well as impaired left ventricular systolic function) predispose to the development of AF among patients presenting with AMI. Although mortality after hospital discharge was significantly worse among patients with AF, AF was not an independent predictor of mortality in this study. It remains to be seen whether (and it seems unlikely that) restoration of sinus rhythm would improve prognosis. Rather, new AF during admission for AMI should be considered a marker for other conditions that define a poor prognosis. David S. Bach, M.D., F.A.C.C.

Title: Transapical Transcatheter Aortic Valve Implantation: Follow-up to 3 Years
Topic: Cardiovascular Surgery
Date Posted: 5/26/2010
Author(s): Ye J, Cheung A, Lichtenstein SV, et al.
Citation: J Thorac Cardiovasc Surg 2010;139:1107-1113.
Clinical Trial: No
Study Question: What are the clinical and echocardiographic outcomes of transapical aortic valve implantation?
Methods: Between October 2005 and February 2009, 71 patients (44 female) underwent transcatheter transapical aortic valve implantation with either 23- or 26-mm Edwards Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic stenosis were declined for conventional aortic valve replacement owing to unacceptable operative risks and were not candidates for transfemoral aortic valve implantation because of poor arterial access. Clinical and echocardiographic follow-up was performed before discharge, at 1 and 6 months, and then yearly. Mean follow-up was 12.9 ± 11.5 months, with a total follow-up of 917.3 patient-months.
Results: Mean age was 80.0 ± 8.1 years; predicted operative mortality was 34.5% ± 20.4% by logistic EuroSCORE and 12.1% ± 7.7% by the Society of Thoracic Surgeons Risk Calculator. Valves were successfully implanted in all patients. Twelve patients died within 30 days (30-day mortality: 16.9% in all patients, 33% in the first 15 patients, and 12.5% in the remainder), and 10 patients died subsequently. Overall survival at 24 and 36 months was 66.3% ± 6.4% and 58.0% ± 9.5%, respectively. Among 59 patients who survived at least 30 days, 24- and 36-month survivals were 79.8% ± 6.4% and 69.8% ± 10.9%, respectively. Late valve-related complications were rare. New York Heart Association functional class improved significantly from preoperative 3.3 ± 0.8 to 1.8 ± 0.8 at 24 months. The aortic valve area and mean gradient remained stable at 24 months (1.6 ± 0.3 cm2 and 10.3 ± 5.9 mm Hg, respectively).
Conclusions: The results suggest that transapical transcatheter aortic valve implantation provides sustained clinical and hemodynamic benefits for up to 36 months in selected high-risk patients with symptomatic severe aortic stenosis.
Perspective: Physicians and patients in Europe and Canada have had access to, and have been using for several years, approved devices for transcatheter aortic valve replacement (TAVI). Reserved for patients with very high or prohibitive estimated operative risks, these devices offer a form of therapy for patients with a mortal disease and no other realistic option. Although transfemoral retrograde TAVI might be suitable for the majority of patients, vascular access limits this approach in some. A transapical approach serves as an alternative means for TAVI in such patients. As valves and their delivery systems evolve, with smaller and more flexible systems, vascular access for transfemoral retrograde TAVI might be expected to be less prohibitive. These data suggest that the transapical approach, in the right hands and after a significant initial learning curve, appears to be a viable option for what may be the highest risk patients––inoperable patients with vascular access inadequate for retrograde TAVI. David S. Bach, M.D., F.A.C.C.

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Title: Is Early Antithrombotic Therapy Necessary in Patients With Bioprosthetic Aortic Valves in Normal Sinus Rhythm?
Topic: Cardiovascular Surgery
Date Posted: 5/26/2010
Author(s): ElBardissi AW, DiBardino DJ, Chen FY, Yamashita MH, Cohn LH.
Citation: J Thorac Cardiovasc Surg 2010;139:1137-1145.
Clinical Trial: No
Study Question: Is early antithrombotic therapy necessary in patients undergoing isolated bioprosthetic aortic valve replacement (AVR), who are discharged in normal sinus rhythm?
Methods: From December 2001 to October 2008, 1,131 patients underwent isolated bioprosthetic AVR at one academic center. After exclusion of patients who underwent concomitant operations (n = 138, 12%), patients who were anticoagulated preoperatively (n = 4, 0.4%), and patients who experienced postoperative refractory atrial fibrillation requiring anticoagulation at discharge (n = 128, 11%), the study cohort comprised 861 patients. Patients were followed for 90 days postoperatively for the occurrence of thromboembolism, including stroke, transient ischemic attack, peripheral thromboembolic events, and bleeding complications.
Results: Of 861 patients included in this study, 133 (15%) were anticoagulated with warfarin postoperatively (AC+) and 728 (85%) were not (AC–). Patients who received postoperative anticoagulation were older; had a higher incidence of hypertension, cerebrovascular accident, and pulmonary vascular disease; and were more symptomatic at presentation. The 90-day risk of thromboembolism (cerebrovascular accident, transient ischemic attack, or peripheral thromboembolism) after surgery was 5% (n = 6) in those who were anticoagulated and 5% (n = 39) in those who were not (p = 0.67). Independent predictors of thromboembolism were increasing age (odds ratio [OR], 1.03; p = 0.03), female gender (OR, 2.23; p = 0.005), short stature (OR, 0.97; p = 0.002), smoking status (p = 0.05), New York Heart Association class III/IV (OR, 1.77; p = 0.04), and a 19-mm bioprosthetic aortic valve prosthesis (OR, 2.22; p = 0.03). Evaluation of each predictor with postoperative acetylsalicylic acid use (ASA+) and AC+ interaction terms revealed that female patients (OR, 0.75; p = 0.03 AC+; OR, 0.66; p = 0.02 ASA+) and patients with a 19-mm bioprosthetic aortic valve (OR, 0.65; p = 0.02 AC+; OR, 0.36; p = 0.01 ASA+) had a reduction in the incidence of thromboembolism when administered ASA or warfarin. Patients who were in New York Heart Association class III/IV also had a reduction of thromboembolism when treated with warfarin (OR, 0.73; p = 0.04); a similar trend was observed in patients treated with ASA (odds ratio, 0.34; p = 0.06).
Conclusions: Early anticoagulation after isolated bioprosthetic AVR in patients in normal sinus rhythm does not seem to reduce the risk of thromboembolism, except in high-risk groups. In this study, the only patients who may benefit from anticoagulation are those who are female, those who are highly symptomatic, and those with a small aortic prosthesis.
Perspective: Current American Heart Association/American College of Cardiology guidelines recommend anticoagulation and antiplatelet therapy during the first 90 postoperative days after bioprosthetic AVR; however, there is wide variability in practice. This retrospective, observational, single-center study suggests that a practice of using warfarin after bioprosthetic AVR might be reasonably reserved for patients at increased risk of thromboembolism, including women, patients with more advanced preoperative symptoms, and patients who underwent AVR with a small bioprosthesis. David S. Bach, M.D., F.A.C.C.

Title: Processes of Care Associated With Acute Stroke Outcomes
Topic: Prevention/Vascular
Date Posted: 5/26/2010
Author(s): Bravata DM, Well CK, Lo AC, et al.
Citation: Arch Intern Med 2010;170:804-810.
Clinical Trial: No
Study Question: What factors related to the management of stroke are associated with outcomes such as mortality?
Methods: This was a retrospective cohort study of patients admitted to the hospital for ischemic stroke or transient ischemic attack (TIA) onset within 2 days of admission, and a neurologic deficit on admission. Patients were excluded if they resided in a skilled nursing facility, were transferred from another hospital, or were already admitted to the hospital. Seven processes of care were evaluated: fever management, hypoxia management, blood pressure management, neurological evaluation, swallowing evaluation, deep vein thrombosis (DVT) prophylaxis, and early mobilization. Processes of care were determined through review of recommendations of the National Expert Stroke Panel and a national organization interested in stroke care, prior evidence of improved mortality or reduced institutionalization, and inclusion in management of acute stroke care. The primary outcome of interest was a combined outcome, which included in-hospital mortality, discharge to hospice, or discharge to a skilled nursing facility. Models were adjusted for age, comorbidities, concomitant medical illness present at admission, preadmission symptom course, prestrike functional status, modified APACHE (Acute Physiology and Chronic Health Evaluation) III score, and admission brain imaging findings.
Results: A total of 1,487 patients, ages 18 or older (mean age 74 years), were included in the study. A total of 1,363 patients experienced definite stroke, 34 had definite TIA, 28 had stroke versus TIA, and 62 had a probably stroke or TIA. The primary outcome was observed in 239 (16%) patients. In-hospital death was experienced by 91 patients. Neurologic worsening or death was experienced by 208 patients. After adjustment for age, comorbidities, and stroke severity, the process of care associated with improved outcomes included swallowing evaluation (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43-0.94), DVT prophylaxis (OR, 0.60; 95% CI, 0.37-0.96), and treatment of all hypoxic episodes with supplemental oxygen (OR, 0.26; 95% CI, 0.09-0.73).
Conclusions: The authors concluded that improvement in outcomes among stroke patients can be observed with attention to specific processes of care including swallowing evaluation, DVT prophylaxis, and treatment of hypoxia.
Perspective: This study suggests simple, cost-effective management, which can improve outcomes among patients with ischemic stroke. Quality improvement initiatives should consider inclusion of these processes of care for patients with ischemic stroke. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Advances in Antiplatelet Treatment for Acute Coronary Syndromes
Topic: General Cardiology
Date Posted: 5/28/2010
Author(s): Eshaghian S, Shah PK, Kaul S.
Citation: Heart 2010;96:656-661.
Clinical Trial: No
Perspective: The following are 10 points to remember about antiplatelet treatment for acute coronary syndromes (ACS).

1. Dual antiplatelet inhibition with aspirin and clopidogrel has been shown to result in a reduction in cardiovascular events in a variety of settings.

2. Attempts to improve outcomes further have led to the development of more potent antiplatelet agents, but at a cost of increased bleeding complications.

3. The search for an antiplatelet agent with optimal ischemic protection and an acceptable bleeding risk remains the ‘holy grail’ of antiplatelet drug development.

4. Prasugrel is a new and more potent thienopyridine. Similar to clopidogrel, it irreversibly binds and blocks the ADP P2Y12 receptor. It has a more rapid onset of action and a stronger inhibitory effect than clopidogrel.

5. Ticagrelor is an orally active drug that binds the P2Y12 receptor. Unlike clopidogrel and prasugrel, it is not a thienopyridine; rather, it is a new class of antiplatelet agent termed ‘cyclopentyl-triazolo-pyrimidine.’ More importantly, its binding to the P2Y12 receptor is reversible. Distinct from previous agents, it does not require metabolic conversion or hepatic activation to an active form.

6. Clopidogrel is the only P2Y12 antagonist that has been approved for the medical management of patients with non-ST-elevation ACS. It also appears to have the best safety profile among the P2Y12 antagonists. Therefore, clopidogrel should be considered the treatment of choice in patients at high risk of bleeding (elderly, low body weight, history of transient ischemic attack or strokes) undergoing medical or invasive therapy.

7. Prasugrel, because of its faster onset of action, should be the preferred agent in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention because of short time window to preload clopidogrel in these patients, or in patients who continue to have recurrent ischemic events, particularly stent thrombosis, despite treatment with clopidogrel (so-called ‘clopidogrel-resistant’ patients).

8. Another group of patients in whom prasugrel might provide superior efficacy are patients with diabetes who are at high risk of thrombotic events (although the evidence base is not robust, as it is derived from a post-hoc analysis).

9. As a result of its reversible nature of platelet inhibition, ticagrelor should be the preferred agent in patients in whom coronary anatomy is unknown and/or urgent coronary artery bypass grafting cannot be deferred. Ticagrelor should be discouraged or used cautiously in patients who develop acute severe dyspnea on treatment or those with a history of severe dyspnea/chronic obstructive pulmonary disease, hyperuricaemia, moderate to severe renal insufficiency, and bradyarrhythmias unprotected by a pacemaker.

10. Prasugrel and ticagrelor are potent agents with improved ischemic benefits in comparison with clopidogrel. The improved benefit comes with the price of increased bleeding. As such, careful patient selection and balancing of benefit–risk is warranted to optimize their use in clinical practice. Debabrata Mukherjee, M.D., F.A.C.C.

Title: The Effects of Growth Hormone on Body Composition and Physical Performance in Recreational Athletes: A Randomized Trial
Topic: General Cardiology
Date Posted: 5/27/2010
Author(s): Meinhardt U, Nelson AE, Hansen JL, et al.
Citation: Ann Intern Med 2010;152:568-577.
Clinical Trial: yes
Study Question: What are the effects of growth hormone alone, or in combination with testosterone, on body composition and measures of athletic performance?
Methods: In a randomized, placebo-controlled, blinded study sponsored by the World Anti-Doping Agency, 96 recreationally trained athletes (63 men and 33 women, mean age 27.9 ± 5.7 years) underwent treatment for 8 weeks followed by a 6-week washout period. Men were randomly assigned to receive placebo, growth hormone (2 mg/d subcutaneously), testosterone (250 mg/wk intramuscularly), or combined growth hormone and testosterone. Women were randomly assigned to receive either placebo or growth hormone (2 mg/d). Body composition (fat mass, lean body mass, extracellular water mass, and body cell mass) and physical performance variables (endurance [maximum oxygen consumption], strength [dead lift], power [jump height], and sprint capacity [Wingate value]) were assessed.
Results: Body cell mass was correlated with all measures of performance at baseline. In men, growth hormone co-administered with testosterone significantly reduced fat mass, increased lean body mass through an increase in extracellular water, and increased body cell mass. Growth hormone significantly increased sprint capacity by 0.71 kJ (95% confidence interval [CI], 0.1-1.3 kJ, relative increase 3.9% [CI, 0.0%-7.7%]) in men and women combined, and by 1.7 kJ (CI, 0.5-3.0 kJ, relative increase 8.3% [CI, 3.0%-13.6%]) when co-administered with testosterone in men; other performance measures did not significantly change. The increase in sprint capacity was not maintained 6 weeks after discontinuation of the drug. The authors note that growth hormone dosage may have been lower than that used covertly by competitive athletes; the athletic significance of the observed improvements in sprint capacity is unclear; and the study was too small to draw conclusions about safety.
Conclusions: Growth hormone supplementation influenced body composition and increased sprint capacity when administered alone and in combination with testosterone.
Perspective: Growth hormone is widely abused by athletes, frequently in combination with androgenic steroids. Although I suppose there could be surprises in the world, this study serves to confirm that people do things for a reason. Growth hormone makes you faster. David S. Bach, M.D., F.A.C.C.

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Title: Comparison of Shunt Types in the Norwood Procedure for Single-Ventricle Lesions
Topic: Congenital Heart Disease
Date Posted: 5/27/2010
Author(s): Ohye RG, Sleeper LA, Mahoney L, et al., on behalf of the Pediatric Heart Network Investigators.
Citation: N Engl J Med 2010;362:1980-1992.
Clinical Trial: No
Study Question: In patients undergoing single-ventricle palliations, are outcomes better with a modified Blalock-Taussig (MBT) shunt or a right ventricle-to-pulmonary artery (RVPA) shunt?
Methods: A prospective, multicenter, randomized, controlled trial was performed. A total of 549 patients were randomized, with 275 patients receiving an MBT shunt and 274 patients receiving an RVPA shunt. The primary endpoint was death or cardiac transplantation 12 months after randomization. Multiple secondary endpoints were studied, including the need for nonplanned cardiac interventions, RV size and function at 14 months, and transplant-free survival for all enrolled patients until the final enrolled patient reached 14 months of age.
Results: Patients undergoing RVPA shunt at the time of the Norwood procedure had greater transplant-free survival 12 months after randomization (74% as compared with 64% in the MBT shunt group, p = 0.01). Patients undergoing the RVPA shunt had a higher rate of unintended interventions, often attributable to stenting or ballooning of the shunt or branch pulmonary arteries after discharge from the Norwood procedure (p = 0.003). There was no difference in RV size and function between groups at 14 months of age. At longer-term follow-up (mean 32 ± 11 months), the transplant-free survival benefit for the RVPA shunt was no longer significant (p = 0.06).
Conclusions: Transplant-free survival at 12 months is higher with infants undergoing MBT shunt as compared with RVPA shunt at the time of the Norwood procedure, although this difference is no longer significant beyond 12 months of age.
Perspective: This paper reports the results of the first randomized, controlled, multicenter trial comparing two surgical techniques in congenital heart surgery. The benefit of the RVPA shunt over the MBT shunt has been postulated to be improved hemodynamic stability in the early postoperative period because of lack of diastolic runoff and the potential for 'coronary steal.' The concerns for the RVPA shunt have been long-term effects on RV function and PA growth. The MBT shunt was superior for the primary endpoint of death/transplant-free survival at 12 months of age. This effect was no longer significant after extension of follow-up. An extension of the original study is in progress to further understand the intermediate- and long-term differences in outcomes between the two shunt types. This study is extremely important in proving the feasibility of a large-scale, multicenter trial comparing surgical approaches in congenital heart disease, where most studies are limited by sample size and retrospective study design. The study also shows room for further investigation of the multiple practice pattern variations that occur between centers as well as individual surgeons. Such variations may have as much an impact on survival as the type of shunt chosen at the initial surgery. Timothy B. Cotts, M.D., F.A.C.C.

Title: Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus: A Systematic Review and Meta-Analysis
Topic: Prevention/Vascular
Date Posted: 5/27/2010
Author(s): Micha R, Wallace SK, Mozaffarian D.
Citation: Circulation 2010;121:2271-2283.
Clinical Trial: No
Study Question: Is red or processed meat consumption associated with risk for cardiovascular disease and diabetes?
Methods: A systematic review and meta-analysis was performed, which included 1,598 abstracts, of which 20 studies were included (17 prospective cohorts, and 3 case-control studies). Random-effects generalized least squares models of trend estimation were used to derive pooled dose-response estimates.
Results: Of the 20 studies selected, 1,218,380 subjects were included. Cardiovascular events included 23,889 coronary heart disease (CHD) cases, 2,280 strokes, and 10,797 cases of diabetes. Red meat was not associated with heart disease (relative risk [RR] per 100 gram serving per day, 1.00; 95% confidence interval [CI], 0.81-1.23) or diabetes mellitus (RR, 1.16; 95% CI, 0.92-1.46). In contrast, processed meat intake was associated with a significantly increased risk of CHD (RR per 50 gram serving per day, 1.42; 95% CI, 1.07-1.89) and diabetes (RR, 1.19; 95% CI, 1.11-1.27). Associations were intermediate for total meat intake. Only three studies evaluated incidence of stroke and meat consumption. Intake of red meat was not associated with stroke (RR, 1.17; 95% CI, 0.40-3.43); neither were processed meats (RR, 1.14; 95% CI, 0.94-1.39).
Conclusions: The authors concluded that consumption of processed meats, rather than red meats, was associated with increased incidence of heart disease and diabetes.
Perspective: These findings support the importance of a diet low in processed foods. A cardiac healthy diet does not necessarily mean a vegetarian one; however, moderation in consumption of foods such as meat and reductions in processed foods are likely to translate into improved wellness. Elizabeth A. Jackson, M.D., F.A.C.C.

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Title: Diagnostic Accuracy and Clinical Utility of Noninvasive Testing for Coronary Artery Disease
Topic: Noninvasive Cardiology
Date Posted: 5/28/2010
Author(s): Weustink AC, Mollet NR, Neefjes LA, et al.
Citation: Ann Intern Med 2010;152:630-639.
Clinical Trial: No
Study Question: What is the relative accuracy and clinical utility of stress testing and computed tomographic coronary arteriography (CTCA) for identifying patients who require invasive coronary angiography (ICA)?
Methods: This observational study was conducted in patients referred for chest pain in a single academic center. In 2004 to 2006, 297 patients underwent stress testing with electrocardiogram (ECG) and nuclear imaging (exercise or pharmacologic), CTCA, and ICA. In 2006 to 2008, all 220 patients who met eligibility criteria underwent stress testing and CTCA. The 141 patients with a normal stress ECG and imaging and normal CTCA were considered to have no coronary disease. Diagnostic accuracy of stress testing and CTCA was compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or post-test probability that suggests how to proceed with testing (no further testing if ≤5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if ≥90%). For both CTCA and ICA, significant coronary stenosis was defined as >50% luminal narrowing in all coronary segments.
Results: Mean age was 58.9 years, and 61% were men; chest pain was typical angina in 43.1%, atypical angina in 21.5%, and nonangina in 35%. Significant obstructive CAD on ICA was present in 53%, nonsignificant in 11%, and no CAD in 35%. Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (≤20%) pretest probability of disease, negative stress test, or CTCA results suggested no need for ICA. In patients with an intermediate (20-80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (post-test probability, 93%), and a negative result suggested no need for further testing (post-test probability, 1%). Physicians could proceed directly with ICA in patients with a high (≥80%) pretest probability (91%).
Conclusions: The authors concluded that CTCA seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need ICA. These findings need to be confirmed before CTCA can be routinely recommended for these patients.
Perspective: The authors correctly commented that referral and verification bias might have influenced findings; and stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging. The study does little to add to the decision process for invasive coronary arteriography, particularly in the post-COURAGE trial era, but does add to the body of literature that CTCA can be very useful in the evaluation of chest pain. If it were not for relatively high radiation exposure (8-13 mSv), it would be the diagnostic tool of choice both for accuracy and ability to identify plaque burden that is not hemodynamically significant. Melvyn Rubenfire, M.D., F.A.C.C.

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Title: Prospective Associations Between Early Childhood Television Exposure and Academic, Psychosocial, and Physical Well-Being by Middle Childhood
Topic: Prevention/Vascular
Date Posted: 5/28/2010
Author(s): Pagani LS, Fitzpatrick C, Barnett TA, Dubow E.
Citation: Arch Pediatr Adolesc Med 2010;164:425-431.
Clinical Trial: No
Study Question: Is watching television during early childhood associated with health behaviors several years later?
Methods: This was a longitudinal study of child development, which included infants born between 1997 and 1998 in Quebec, Canada. Parents were asked to report on weekly hours of television exposure at 29 and 53 months of age. Outcomes of interest included parental and teacher reports of the children’s academic, psychosocial, health behaviors, and body mass index (BMI) at 10 years of age.
Results: A total of 1,314 children were included in this analysis. Television exposure at 29 months was a mean of 8.82 hours per week; however, 11% of the cohort viewed 2 or more hours of television daily. After adjustment for pre-existing individual and family factors, each additional hour of television exposure correlated with a 7% unit decrease in classroom engagement (p ≤ 0.05) and a 6% decrease in math achievement (p ≤ 0.05). Increases in victimization by classmates (p < 0.001), and decreases in time spent doing weekend physical activity (-13% units, 95% confidence interval, 0.81-2.25) were also noted. Higher consumption for soft drinks and snacks also correlated with exposure to television at a young age.
Conclusions: The authors concluded that long-term risks associated with higher levels of exposure to television may include increased BMI and unhealthy behaviors in adolescence.
Perspective: These findings are concerning regarding the long-term implications of television. This study, together with prior studies which have found associations between television watching and increased weight and poor diet, suggest that clinicians should counsel families to limit television exposure. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Right Ventricular Failure in Patients With the HeartMate II Continuous-Flow Left Ventricular Assist Device: Incidence, Risk Factors, and Effects on Outcomes
Topic: Heart Failure/Transplant
Date Posted: 5/28/2010
Author(s): Kormos RL, Teuteberg JJ, Pagani FD, et al., on behalf of the HeartMate II Clinical Investigators.
Citation: J Thorac Cardiovasc Surg 2010;139;1316-1324.
Clinical Trial: No
Study Question: What is the cumulative incidence of postoperative right ventricular failure (RVF) development following HeartMate II left ventricular assist device (LVAD) placement, and what are preoperative risks for RVF?
Methods: A retrospective analysis of clinical, laboratory, and cardiopulmonary hemodynamic data from 484 patients enrolled into the HeartMate II bridge-to-transplant trial was conducted. RVF had three definitions: RVAD requirement, need for intravenous inotropes >14 days after LVAD placement (combined with former group into an “early RVF group”), or inotrope requirement beginning >14 days after LVAD. Preoperative variables in those with and without postoperative RVF were compared to identify correlates of early RVF development.
Results: Ninety-eight (20%) subjects developed postoperative RVF: 30 (6%) required an RVAD, 35 (7%) required inotrope support for >14 days immediately after implant, and 33 (7%) required initiation of delayed inotrope support. The 180-day survival for those with and without early RVF was 66 ± 0.06% and 85 ± 0.02%, respectively, and individuals with RVF had longer bypass times, more perioperative bleeding, and longer hospital stays. Several preoperative univariable correlates (central venous pressure [CVP], CVP/pulmonary capillary wedge pressure [WP] ratio, RVSWi, ventilator support, blood urea nitrogen [BUN], AST, Right Ventricular Failure Risk Score) of “early RVF” development were identified, but only an elevated preoperative AST was associated with late RVF onset. Multivariable correlates of “early RVF” included a preoperative CVP/WP ratio >0.63 (odds ratio [OR], 2.3 [1.2-4.3]), preoperative ventilator support (OR, 5.5 [2.3-13.2]), and BUN >39 mg/dl (OR, 2.1 [1.1-4.1]).
Conclusions: The authors concluded that RVF continues to be a problem following continuous-flow LVAD support. Preoperative optimization of RV function or planned biventricular support may be beneficial.
Perspective: While the morbidity and mortality associated with post-LVAD RVF is well known, this is the first study examining RVF in a large cohort of individuals undergoing implant of a commonly employed, contemporary, continuous-flow device. Preoperative univariable predictors may have been correlated, variable dichotomization was potentially biased, and power was limited to perform detailed multivariable analyses required to identify truly independent RVF risk predictors. Regardless, this study again highlights the importance of closely examining preoperative laboratory and cardiopulmonary hemodynamics in order to gauge RVF risk. It also identifies a weakness in predicting delayed RVF in LVAD patients. As we design future trials and registries of LVAD support, a consensus definition of RVF will be critical to allow comparison of results across studies. Likewise, longer-term follow-up of RV function in patients on prolonged LVAD support (especially those on destination therapy) is warranted. Jennifer Cowger, M.D.

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Title: Evidence That D-Dimer Levels Predict Subsequent Thromboembolic and Cardiovascular Events in Patients With Atrial Fibrillation During Oral Anticoagulant Therapy
Topic: Arrhythmias
Date Posted: 5/31/2010
Author(s): Sadanaga T, Sadanaga M, Ogawa S.
Citation: J Am Coll Cardiol 2010;55:2225-2231.
Clinical Trial: No
Related Resources
JACC Article: Evidence That D-Dimer Levels Predict Subsequent Thromboembolic and Cardiovascular Events in Patients With Atrial Fibrillation During Oral Anticoagulant Therapy

Study Question: Is an elevated D-dimer level associated with adverse outcomes in patients with atrial fibrillation (AF)?
Methods: The subjects of this prospective study were 269 patients (mean age 74 years) with AF who were anticoagulated with warfarin. The D-dimer level was measured upon entry into the study. The endpoints were thromboembolic events and combined cardiovascular events (thromboembolic events, cerebral hemorrhage, myocardial infarction, and cardiovascular deaths). The mean duration of follow-up was 25 months.
Results: The mean international normalized ratio (INR) at entry was 1.93 and there was no relationship between INR and D-dimer level. The incidence of thromboembolic events was 1.8%/year and the incidence of cardiovascular events was 4.8%/year. D-dimer levels were categorized as high (≥0.5 µg/ml) in 63/269 patients. The independent predictors of a high D-dimer level were heart failure, age ≥75 years, and history of stroke. The strongest predictor of thromboembolic events was a high D-dimer level (hazard ratio [HR], 15.7). The strongest predictor of cardiovascular events was heart failure (HR, 19.2) followed by a high D-dimer level (HR, 7.6).
Conclusions: A D-dimer level ≥0.5 µg/ml is predictive of thromboembolic and cardiovascular events in patients with AF.
Perspective: A modest elevation in D-dimer level reflects mild increases in coagulation, thrombin formation, and fibrin turnover. Along with stasis in the left atrial appendage, an increase in coagulation factors has been implicated in the pathophysiology of thromboembolic events during AF, explaining the elevated D-dimer levels. The clinically-relevant and unanswered question is whether the heightened risk of thromboembolic events in patients with a high D-dimer level can be attenuated by more intense anticoagulation with warfarin. Fred Morady, M.D., F.A.C.C.

Title: Altered Na+ Currents in Atrial Fibrillation: Effects of Ranolazine on Arrhythmias and Contractility in Human Atrial Myocardium
Topic: Arrhythmias
Date Posted: 5/31/2010
Author(s): Sossalla S, Kallmeyer B, Wagner S, et al.
Citation: J Am Coll Cardiol 2010;55:2330-2342.
Clinical Trial: No
Related Resources
JACC Article: Altered Na+ Currents in Atrial Fibrillation: Effects of Ranolazine on Arrhythmias and Contractility in Human Atrial Myocardium

Study Question: Is atrial fibrillation (AF) associated with altered peak or late Na+ current (INa) or altered Na+ channel expression, and what are the effects of ranolazine on INa in atrial myocardium?
Methods: The right atrial appendage was excised during open heart surgery in 23 patients with persistent AF and 79 patients in sinus rhythm (SR). INa, protein expression, and the effects of ranolazine were studied in vitro.
Results: Peak INa was significantly reduced by 16% in patients with AF compared to SR, but late INa was significantly greater by 26% in the AF patients. Ranolazine reduced both peak and late INa in patients with SR. In AF patients, ranolazine preferentially reduced late INa over peak INa. Exposure of isolated atrial trabeculae to calcium induced atrial ectopy significantly less frequently in preparations that were pre-treated with ranolazine (9% vs. 32%).
Conclusions: Persistent AF is associated with alterations in the function of sodium channels, with an increase in late INa that is preferentially blocked by ranolazine.
Perspective: Ranolazine is an antianginal agent, and was found to reduce the incidence of AF in a large clinical trial in patients with acute coronary syndromes. This sodium channel blocker has generated interest as a possible antiarrhythmic drug because it selectively blocks the late component of INa. This may reduce the risk of ventricular proarrhythmia that is associated with other sodium channel blockers such as quinidine. Fred Morady, M.D., F.A.C.C.

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Title: Radiation Safety Among Cardiology Fellows
Topic: Interventional Cardiology
Date Posted: 6/1/2010
Author(s): Kim C, Vasaiwala S, Haque F, Pratap K, Vidovich MI.
Citation: Am J Cardiol 2010;May 17:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the current level of fellow training with respect to radiation exposure minimization and management?
Methods: The authors invited 2,545 general and subspecialty cardiology fellows to participate in a survey on knowledge and practice of radiation safety.
Results: The survey was returned by 10.5% of the cohort. Of the 267 respondents, 82% had undergone formal radiation safety training. Approximately 60% of the fellows were aware of their hospital’s pregnancy radiation policy and knew how to contact the hospital’s radiation safety officer. Over half (52%) of the fellows always wore a dosimeter, yet most (81%) did not know their level of radiation exposure in the previous year. Formal training was associated with a greater awareness of institutional radiation pregnancy policy, knowledge of the contact information of the radiation safety officer, awareness of safe levels of radiation exposure, and consistent use of dosimeters and RadPads.
Conclusions: There are significant lacunae in the education of cardiology fellows with respect to radiation safety.
Perspective: This survey, despite its small sample, raises real concerns. Lack of fellow education likely results in increased radiation exposure, not only to the fellows, but also to patients and to others involved in the procedure. Hopefully this paper will lead to fellowship programs across the country examining their radiation safety education and rectifying the shortcomings that may exist therein. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

Title: Excimer Laser to Open Refractory Subclavian Occlusion in 12 Consecutive Patients
Topic: Cardiovascular Surgery
Date Posted: 6/2/2010
Author(s): Worley SJ, Gohn DC, Pulliam RW.
Citation: Heart Rhythm 2010;7:634-638.
Clinical Trial: No
Study Question: What is the safety and efficacy of using laser to treat chronic occlusion of the subclavian vein?
Methods: The authors describe their experience in treating 12 subclavian vein occlusions in patients requiring device upgrades.
Results: The authors successfully used laser to cross wire refractory subclavian vein occlusions in 11 of 12 cases. There were no major complications. The laser was required for an average of 19.9 mm of occlusion. Contrast stains were seen in eight patients and were mild in three (<1 cm), and moderate in another three (1-2 cm).
Conclusions: Chronic subclavian occlusions can be safely and successfully treated with excimer laser.
Perspective: Venous stenosis is an uncommon problem, and perhaps because of that, there are limited devices available to treat these patients. The authors have pioneered the use of laser to treat subclavian occlusions successfully and without any major complications. Further studies are needed to evaluate the safety of the procedure, as it is used in centers with less experienced operators. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: US Trends in Prevalence, Awareness, Treatment, and Control of Hypertension, 1988-2008
Topic: Prevention/Vascular
Date Posted: 6/2/2010
Author(s): Egan BM, Zhao Y, Axon RN.
Citation: JAMA 2010;303:2043-2050.
Clinical Trial: No
Study Question: Has the prevalence, awareness, and treatment of hypertension (HTN) changed over the past 20 years?
Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2008 were used for the present analysis. A total of 42,856 adults ages 18 years or older were included in a probability sample, which is representative of the general US population. Hypertension was defined as either systolic blood pressure (SBP) of 140 mm Hg or greater, diastolic blood pressure (DBP) of 90 mm Hg or greater, or self-reported use of antihypertensive medications. Controlled HTN was defined as SBP <140 mm Hg and DBP <90 mm Hg. All results were age-adjusted for the year 2000 US population.
Results: HTN has increased over time from 23.9% (95% confidence interval [CI], 22.7%-25.2%) in 1988-1994 to 28.5% (95% CI, 25.9%-31.3%) in 1999-2000 (p < 0.0001). From 1999-2000 to 2007-2008, no change in the rate of HTN was observed. HTN control increased from 27.3% (95% CI, 25.6%-29.1%) in 1988-1994 to 50.1% (95% CI, 46.8%-53.5%) in 2007-2008 (p = 0.006). Blood pressure among adults with HTN decreased from 143.0/80.4 mm Hg to 135.2/74.2 mm Hg (p = 0.02 for SBP and p < 0.001 for DBP). Blood pressure control improved significantly more in absolute percentages between 1999-2000 and 2007-2008 versus 1988-1994 and 1999-2000. Better control reflected improvements in awareness, treatment, and proportion of patients who were treated and had controlled HTN. HTN control improved significantly across age, race, and sex groups, but was lower among individuals ages 18-39 years (vs. 40-59 years, p < 0.001) and 60 years or greater (p < 0.001), and in Hispanic versus white individuals (p = 0.004).
Conclusions: The authors concluded that blood pressure control in patients with HTN has improved with most of the improvement observed after 1999-2000. HTN is lower among young adults as compared to middle-aged and older adults, and in Hispanics as compared to whites.
Perspective: These findings suggest improved awareness and control of HTN in the United States. Understanding what factors explain the reduction in uncontrolled HTN will allow for further gains in the management of HTN to be made. It is likely that increased prevalence of quality assessment has assisted in general improvements. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Reducing Consumption of Sugar-Sweetened Beverages Is Associated With Reduced Blood Pressure: A Prospective Study Among United States Adults
Topic: Prevention/Vascular
Date Posted: 6/2/2010
Author(s): Chen L, Caballero B, Mitchell DC, et al.
Citation: Circulation 2010;121:2398-2406.
Clinical Trial: No
Related Resources
Trial: PREMIER

Study Question: Is consumption of sweetened beverages associated with increases in blood pressure?
Methods: Data from the PREMIER study were used for this analysis. The PREMIER study was an 18-month randomized controlled trial of two behavioral interventions to reduce blood pressure. Adults with systolic blood pressures (SBP) between 120 and 159 mm Hg and diastolic blood pressures (DBP) 80 to 95 mm Hg were included from four study centers in the United States. Subjects were randomized into three groups: advice only; lifestyle modification which focused on weight loss, increased physical activity, and reducing sodium intake; and the DASH dietary pattern with lifestyle modification. Diet was assessed through two 24-hour recall measures at baseline, 6 months, and 18 months, for a total of six dietary recalls. Blood pressure was measured at baseline, 3, 6, 12, and 18 months.
Results: A total of 810 subjects, ages 25-79, participated. Mean sugar-sweetened beverage consumption was 0.9 ± 1.0 servings per day, and mean SBP was 134.0 ± 9.6 mm Hg, and mean DBP was 84.8 ± 4.1 mm Hg. Sugar-sweetened beverage consumption was associated with younger age, being less fit, lower household income, and less consumption of alcohol. Men had higher intake of sugar-sweetened beverages compared to women, and blacks had higher intake compared to whites. A reduction in sugar-sweetened beverages of one serving per day was associated with a 1.8 mm Hg reduction in SBP (95% confidence interval [CI], 1.2-2.4), and a 1.1 mm Hg reduction in DBP (95% CI, 0.7-1.4) over the 18 months of the study, after adjustment for multiple confounders. After additional adjustment for weight change over the 18 months, reducing sugar-sweetened beverages remained significantly associated with reductions in both SBP and DBP (p < 0.05). Reduction in the intake of sugar in general was associated with an improvement in blood pressure. No association was observed for diet beverages or caffeine intake and blood pressure.
Conclusions: The authors concluded the sugar-sweetened beverages were associated with reductions in blood pressure, suggesting that this may be an important dietary strategy in lowering blood pressure.
Perspective: These findings support the recommendation to avoid sweetened drinks as one component of reducing risk of cardiovascular risk factors such as blood pressure. Elizabeth A. Jackson, M.D., F.A.C.C.