Sudden Cardiac Death in Heart Failure Trial - SCD-HeFT
Contribution To Literature:
The SCD-HeFT trial showed that among patients with NYHA class II or III CHF and reduced LVEF, treatment with an ICD was associated with a reduction in all-cause mortality compared with placebo, but there was no difference between amiodarone and placebo.
The goal of the trial was to evaluate the effectiveness of amiodarone therapy or an implantable cardioverter-defibrillator (ICD) with placebo in patients with New York Heart Association (NYHA) class II and III congestive heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) ≤35%.
Patients Enrolled: 2,521
NYHA Class: 70%; NYHA class II and 30% class III
Mean Follow-Up: Median follow-up 45.5 months
Median Patient Age: 60 years
1) 18 years of age or older.
2) Heart failure for at least 3 months and treated with a vasodilator.
3) Symptomatic CHF (NYHA class II and III) due to ischemic or nonischemic dilated cardiomyopathy.
4) LVEF ≤35% within 3 months of enrollment.
5) All patients are requested, but not required, to have had a coronary angiogram to document the nature of their disease. The definition of ischemic cardiomyopathy will be systolic LV dysfunction in the presence of ≤75% luminal coronary artery or insignificant coronary artery disease with definitive evidence of myocardial infarction (MI).
6) Patients with chronic atrial fibrillation must be anticoagulated with warfarin, with documented international normalized ratios of at least 2.0 for ≥21 days prior to randomization.
1) Symptomatic ventricular arrhythmias.
2) LVEF >35% or asymptomatic LV dysfunction.
3) NYHA class IV CHF.
4) History of cardiac arrest or a spontaneous episode of sustained ventricular tachycardia (VT) (≥30 seconds at rates of >100 bpm) not associated with an acute Q-wave MI. (Sustained VT or an aborted cardiac arrest within 48 hours of an MI is not an exclusion criterion).
5) Any noncardiac disease that may cause death within 12 months.
6) Females who are pregnant or have childbearing potential and are not using reliable methods of contraception.
7) History of restrictive, infiltrative, or hypertrophic cardiomyopathy; constrictive pericarditis; acute myocarditis; congenital heart disease; surgically correctable valvular disease; and/or inoperable obstructive valvular disease.
8) History of mechanical prosthetic cardiac valves.
9) History of a major psychiatric disorder, active alcohol/drug abuse, or noncompliance.
10) Contraindication for taking amiodarone for any reason or currently taking amiodarone.
11) Indication for antiarrhythmic drugs.
12) Atrial fibrillation requiring catheter ablation of the atrioventricular conduction system or amiodarone for rate control.
13) Unexplained syncope within the last five years.
14) Patients unable to accommodate ICD placement in the left infraclavicular region.
15) Expected to undergo cardiac transplantation within 12 months.
16) Permanent pacemaker.
17) Liver function tests (>2.5 times normal or a serum creatinine >2.5 mg/dl).
18) Currently receiving antibiotics.
1) Arrhythmic cardiac mortality.
2) Nonarrhythmic cardiac mortality.
3) Composite of all-cause mortality and rehospitalization for CHF.
4) Health-related quality of life.
5) Cost of care and calculate incremental cost-effectiveness ratios.
Patients were randomized in a double-blind manner to either: 1) Conventional CHF therapy and placebo, 2) conventional CHF therapy plus amiodarone, or 3) conventional CHF therapy plus a conservatively programmed single lead ICD. Amiodarone was dosed at 800 mg during the first week, 400 mg during weeks 2-4, and chronically at 200 mg/day if <150 lbs, 300 mg/day if 150-200 lbs, and 400 mg/day if >200 lbs.
ICDs were programmed for ventricular fibrillation (VF) treatment only. Patients underwent a six-minute walk test and Holter monitoring.
At the end of follow-up, medication use included 72% on angiotensin-converting enzyme inhibitors, 78% on beta-blockers, 80% on loop diuretics, and 55% on aspirin. Baseline median six-minute walk was 1,130 feet. Prior duration of CHF was 24.5 months at baseline.
There was no difference in all-cause mortality between the amiodarone and placebo arm (28% vs 29%, hazard ratio [HR] 1.06, 97.5% confidence interval [CI] 0.86-1.30, p=0.53), but mortality was lower in the ICD arm compared with placebo (22% vs 29%, HR 0.77, 97.5% CI 0.62-0.96, p=0.007). Subgroup analysis showed similar results for the amiodarone versus placebo comparison in the prespecified subgroups, with the exception of NYHA class III, which had an increased mortality in the amiodarone group (HR 1.44, 97.5% CI 1.05-1.97; n=497).
Long-term follow-up: Median follow-up was 11 years, available for approximately 90% of patients. Total crossover to ICD arm was approximately 57%. Ten-year mortality for ICD vs. placebo: 52.5% vs. 57.2% (HR 0.87, 95% CI 0.76-0.98; p = 0.028); for amiodarone vs. placebo: 52.7% vs. 57.2% (HR 0.96, 95% CI 0.85-1.09; p = 0.54). When treatment benefit was examined as a function of time from randomization, attenuation of the ICD benefit was observed after 6 years (p for interaction = 0.0015). For ICD vs. placebo, the greatest benefit was noted for patients with ischemic cardiomyopathy and NYHA class II patients. Ischemic HF: HR 0.81, 95% CI 0.69-0.95; p = 0.009; nonischemic HF: HR 0.97, 95% CI 0.79-1.20; p = 0.80. NYHA functional class II: HR 0.76, 95% CI 0.65-0.90; p = 0.001; NYHA functional class III: HR 1.06, 95% CI 0.86-1.31; p = 0.58.
Among patients with NYHA class II or III CHF and reduced LVEF, treatment with an ICD was associated with a reduction in all-cause mortality compared with placebo, but there was no difference between amiodarone and placebo. The ICD was programmed for VF treatment only.
On long-term follow-up, there was potentially some attenuation in benefit beyond 6 years, although the crossover rate to the ICD arm was >50%. Benefit was highest among patients with ischemic cardiomyopathy and NYHA class II symptoms.
Poole JE, Olshansky B, Mark DB, et al., on behalf of the SCD-HeFT Investigators. Long-Term Outcomes of Implantable Cardioverter-Defibrillator Therapy in the SCD-HeFT. J Am Coll Cardiol 2020;76:405-15.
Editorial Comment: Stecker EC, Nazer B, Dewland TA. Primary Prevention ICDs in Nonischemic Cardiomyopathy: Time to Put the Toothpaste Back in the Tube? J Am Coll Cardiol 2020;76:432-4.
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure. N Engl J Med 2005;352:225-37.
Presented by Dr. Gust H. Bardy at the American College of Cardiology Annual Scientific Session, March 2004.
Bardy GH, Lee KL, Mauk DB, and the SCD-HeFT Pilot Investigators. The Sudden Cardiac Death in Heart Failure Trial: pilot study. PACE 1997;20:1148 (Abstract).
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure
Keywords: Early Intervention (Education), Coronary Artery Disease, Myocardial Infarction, Ventricular Fibrillation, Sodium Potassium Chloride Symporter Inhibitors, Vasodilator Agents, International Normalized Ratio, Heart Failure, Stroke Volume, Electrocardiography, Ambulatory, Ventricular Dysfunction, Left, Death, Sudden, Cardiac, Cardiomyopathy, Dilated, Defibrillators, Implantable
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