Author + information
- Received February 6, 2018
- Revision received February 28, 2018
- Accepted February 28, 2018
- Published online July 30, 2018.
- Muthiah Vaduganathan, MD, MPHa,
- Brian L. Claggett, PhDa,
- Neal A. Chatterjee, MD, MScb,
- Inder S. Anand, MD, PhDc,
- Nancy K. Sweitzer, MD, PhDd,
- James C. Fang, MDe,
- Eileen O'Meara, MDf,
- Sanjiv J. Shah, MDg,
- Sheila M. Hegde, MD, MPHa,
- Akshay S. Desai, MD, MPHa,
- Eldrin F. Lewis, MD, MPHa,
- Jean Rouleau, MDf,
- Bertram Pitt, MDh,
- Marc A. Pfeffer, MD, PhDa and
- Scott D. Solomon, MDa,∗ ()
- aBrigham and Women’s Hospital, Boston, Massachusetts
- bMassachusetts General Hospital, Boston, Massachusetts
- cVA Medical Center and University of Minnesota, Minneapolis, Minnesota
- dUniversity of Arizona, Tucson, Arizona
- eUniversity of Utah, Salt Lake City, Utah
- fMontreal Heart Institute and University of Montreal, Montreal, Quebec, Canada
- gNorthwestern University, Chicago, Illinois
- hUniversity of Michigan School of Medicine, Ann Arbor, Michigan
- ↵∗Address for correspondence:
Dr. Scott D. Solomon, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
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
TOPCAT was supported by the National Heart, Lung, and Blood Institute (NHLBI) (HHSN268200425207C).
Dr. Vaduganathan was supported by the NHLBI T32 postdoctoral training grant (T32HL007604). Dr. Sweitzer was supported by research grants from the National Institutes of Health. Dr. O’Meara has received subventions/research support and consulting fees from Novartis, Bayer, AstraZeneca, Servier, and Amgen. Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, and Novartis; and has received consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Sanofi, and United Therapeutics. Dr. Desai has received research grant support from Novartis; and consulting fees from Novartis, AstraZeneca, Abbott, Relypsa, and DalCor Pharma. Dr. Lewis has received research grants from the NHLBI, Novartis, and Sanofi; and consulting fees from Novartis. Dr. Rouleau has been a consultant for Novartis, AstraZeneca, and Bayer. Dr. Pitt has received consulting fees from Amorcyte, AstraZeneca, Aurasense, Bayer, BG Medicine, Gambro, Johnson & Johnson, Mesoblast, Novartis, Pfizer, Relypsa, and Takeda; has received research grant support from Forest Laboratories; holds stock in Aurasense, Relypsa, BG Medicine, and Aurasense; and has a pending patent related to site-specific delivery of eplerenone to the myocardium. Dr. Pfeffer has received consulting fees from Amgen, AstraZeneca, Bayer, DalCor Pharma UK, Genzyme, Lilly, The Medicines Company, MedImmune, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Salix, Sanderling, Sanofi, Takeda, Teva, Thrasos, and Vericel; has received research grant support from Amgen, Celladon, Novartis, and Sanofi; and holds stock options in DalCor; Brigham and Women’s Hospital has patents for the use of inhibitors of the renin–angiotensin system in selected survivors of myocardial infarction with Novartis Pharmaceuticals on which Dr. Pfeffer is a co-inventor and his share of the licensing agreement is irrevocably transferred to charity. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Celladon, Gilead, GlaxoSmithKline, Ionis Pharmaceutics, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, Theracos; and has consulted for Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Corvia, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Pfizer, Takeda, and Theracos. All other authors report no other relationships relevant to the contents of this paper to disclose.
- Received February 6, 2018.
- Revision received February 28, 2018.
- Accepted February 28, 2018.
- 2018 American College of Cardiology Foundation