Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial

Abstract

Objectives: This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF.

Background: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF).

Methods: We studied 1,767 patients with HFpEF (EF ≥45%) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death.

Results: During a median 3.0-year (25th to 75th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25th to 75th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25th to 75th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25th to 75th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25th to 75th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95% confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone.

Conclusions: SD accounted for ∼20% of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302.

Keywords: heart failure with preserved ejection fraction; risk prediction; sudden death.