Author + information
- Received February 6, 2018
- Revision received February 28, 2018
- Accepted February 28, 2018
- Published online March 11, 2018.
- Muthiah Vaduganathan, MD MPH1,
- Brian L. Claggett, PhD1,
- Neal A. Chatterjee, MD MSc2,
- Inder S. Anand, MD PhD3,
- Nancy K. Sweitzer, MD PhD4,
- James C. Fang, MD5,
- Eileen O'Meara, MD6,
- Sanjiv J. Shah, MD7,
- Sheila M. Hegde, MD MPH1,
- Akshay S. Desai, MD MPH1,
- Eldrin F. Lewis, MD MPH1,
- Jean Rouleau, MD6,
- Bertram Pitt, MD8,
- Marc A. Pfeffer, MD PhD1 and
- Scott D. Solomon, MD1,∗ ()
- 1Brigham and Women’s Hospital, Boston, MA, USA
- 2Massachusetts General Hospital, Boston, MA, USA
- 3VA Medical Center and University of Minnesota, Minneapolis, MN, USA
- 4University of Arizona, Tucson, AZ, USA
- 5University of Utah, Salt Lake City, UT, USA
- 6Montreal Heart Institute and University of Montreal, Montreal, QC, Canada
- 7Northwestern University, Chicago, IL, USA
- 8University of Michigan School of Medicine, Ann Arbor, MI, USA
- ↵∗Address for Correspondence: Scott D. Solomon, MD Cardiovascular Division Brigham and Women’s Hospital 75 Francis St Boston, MA 02115 Tel: 857-307-1960 Fax: 857-307-1944.
Background Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF).
Objectives To investigate rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF.
Methods We studied 1,767 patients with HFpEF (EF≥45%) enrolled in the Americas region of the TOPCAT trial. We identified independent predictors of composite SD/ACA with step-wise backward selection using competing risks regression analysis accounting for non-sudden causes of death.
Results During median 3.0 (1.9-4.4) year follow-up, 77 patients experienced SD/ACA and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 (1.1-1.8) and 5.8 (5.1-6.4) events/100 patient-years. SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 (0.9-1.7) vs. 1.6 (1.2-2.2) events/100 patient-years; subdistributional HR 0.74 95% CI 0.47-1.16; P=0.19. After accounting for competing risks of non-sudden death, 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, LBBB, 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 identify patients at higher risk for SD/ACA with modest discrimination. These data may guide future SD-preventative efforts in HFpEF.
Dr. Vaduganathan is supported by the NHLBI T32 postdoctoral training grant (T32HL007604).
Dr. Sweitzer has received research grants from the NIH.
Dr. O’Meara has received subventions/research support and consulting fees from Novartis, Bayer, Astra Zeneca, Servier, and Amgen.
Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, and Novartis; and 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. Pitt reports receiving consulting fees from Amorcyte, AstraZeneca, Aurasense, Bayer, BG Medicine, Gambro, Johnson & Johnson, Mesoblast, Novartis, Pfizer, Relypsa, and Takeda; receiving research grant support from Forest Laboratories; and holding stock in Aurasense, Relypsa, BG Medicine, and Aurasense.
Dr. Pitt reports 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, Medicines Company, MedImmune, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Salix, Sanderling, Sanofi, Takeda, Teva, Thrasos and Vericel and having received research grant support from Amgen, Celladon, Novartis, Sanofi. The 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. 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.
TOPCAT was supported by the NHLBI (HHSN268200425207C).
- Received February 6, 2018.
- Revision received February 28, 2018.
- Accepted February 28, 2018.
- 2018 American College of Cardiology Foundation