Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the sudden cardiac death in heart failure trial.

BACKGROUND: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. METHODS AND RESULTS: SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. CONCLUSIONS: ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected] CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Where patients with mild to moderate heart failure die: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: Common locations of death in patients with congestive heart failure (CHF) are unknown. In the SCD-HeFT, mortality of patients with CHF was assessed after randomization to an implantable cardioverter/defibrillator (ICD), amiodarone, or placebo. The aim of this study was to evaluate the location of deaths in SCD-HeFT. METHODS: Among SCD-HeFT patients whose location of death was identified, we used logistic regression to assess the relationship of randomized treatment arm and other baseline predictors with the location of death. Cause of death was adjudicated by a therapy-blinded events committee. RESULTS: In SCD-HeFT, 666 (26%) of 2521 patients died. Of the 604 (91%) for whom location of death was known, 58% died in hospital and 29% died at home. Patients randomized to receive an ICD were less likely to die at home than patients randomized to placebo (P = .002). Fewer patients randomized to ICDs died; even fewer randomized to ICDs died at home. Age, sex, etiology of heart failure, left ventricular ejection fraction, and New York Heart Association functional class were not associated with location of death. Sudden cardiac death represented 52% of all out-of-hospital deaths but in hospital deaths exceeded out-of-hospital deaths. CONCLUSION: Deaths in SCD-HeFT, a well-treated CHF population, were most often in hospital. ICDs were associated with lower total and sudden death rates at home and in hospital. Development of methods to identify which patients will not respond to optimal treatment, including an ICD, remain a challenge.

Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials.

PURPOSE: An independent Adjuvant Cardiac Review and Evaluation Committee (ACREC) systematically reviewed cases of symptomatic heart failure events to uniformly define the cardiac event rate across two large trials (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-31 and North Central Cancer Treatment Group [NCCTG] N9831) that assessed the addition of trastuzumab to standard adjuvant chemotherapy. PATIENTS AND METHODS: The committee was composed of six independent oncologists and cardiologists. A retrospective review of patients with a cardiac event was performed by the primary investigators of the trials. The ACREC prospectively established criteria for determining a symptomatic heart failure event. Recovery status was determined from documented resolution of signs and symptoms. Potential risk factors were also assessed. RESULTS: Medical records for a total of 173 patients were reviewed: 40 in the chemotherapy-alone arm and 133 in the trastuzumab arm. Trastuzumab-treated patients had a 2.0% incidence of symptomatic heart failure events compared with 0.45% in the chemotherapy-alone arm. Complete or partial recovery was observed in 86.1% of trastuzumab-treated patients with symptomatic heart failure events. Of five patients who died, only one patient had received trastuzumab. Independent predictors for cardiac events were age older than 50 years, a low ejection fraction at the start of paclitaxel treatment, and trastuzumab treatment. CONCLUSION: The incidence of symptomatic heart failure events is 2.0% in patients treated with adjuvant trastuzumab, and the majority of these patients recover with appropriate treatment.