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

Muthiah Vaduganathan, Brian L. Claggett, Neal A. Chatterjee, Inder S. Anand, Nancy K. Sweitzer, James C. Fang, Eileen O'Meara, Sanjiv J. Shah, Sheila M. Hegde, Akshay S. Desai, Eldrin F. Lewis, Jean Rouleau, Bertram Pitt, Marc A. Pfeffer, Scott D. Solomon*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)653-661
Number of pages9
JournalJACC: Heart Failure
Volume6
Issue number8
DOIs
StatePublished - Aug 2018

Keywords

  • heart failure with preserved ejection fraction
  • risk prediction
  • sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Vaduganathan, M., Claggett, B. L., Chatterjee, N. A., Anand, I. S., Sweitzer, N. K., Fang, J. C., O'Meara, E., Shah, S. J., Hegde, S. M., Desai, A. S., Lewis, E. F., Rouleau, J., Pitt, B., Pfeffer, M. A., & Solomon, S. D. (2018). Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial. JACC: Heart Failure, 6(8), 653-661. https://doi.org/10.1016/j.jchf.2018.02.014