Author + information
- Received October 2, 2019
- Revision received January 6, 2020
- Accepted February 11, 2020
- Published online July 27, 2020.
- Jonathan W. Cunningham, MDa,
- Muthiah Vaduganathan, MD, MPHa,
- Brian L. Claggett, PhDa,
- Jenine E. John, MDa,
- Akshay S. Desai, MD, MPHa,
- Eldrin F. Lewis, MD, MPHa,
- Michael R. Zile, MDb,
- Peter Carson, MDc,
- Pardeep S. Jhund, MBChBd,
- Lars Kober, MD, DMSce,
- Bertram Pitt, MDf,
- Sanjiv J. Shah, MDg,
- Karl Swedberg, MDh,
- Inder S. Anand, MD, DPhili,
- Salim Yusuf, MDj,
- John J.V. McMurray, MDd,
- Marc A. Pfeffer, MD, PhDa and
- Scott D. Solomon, MDa,∗ ()
- aBrigham and Women’s Hospital, Boston, Massachusetts
- bRHJ Department of Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, South Carolina
- cVeterans Affairs Medical Center, Washington DC
- dBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
- eRigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
- fUniversity of Michigan School of Medicine, Ann Arbor, Michigan
- gNorthwestern University Feinberg School of Medicine, Chicago, Illinois
- hUniversity of Gothenburg, Gothenburg, Sweden
- iVA Medical Center and University of Minnesota, Minneapolis, Minnesota
- jHamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
- ↵∗Address for correspondence:
Dr. Scott D. Solomon, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115.
Objectives The authors investigated the relationship between past or incident myocardial infarction (MI) and cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF).
Background MI and HFpEF share some common risk factors. The prognostic significance of MI in patients with HFpEF is uncertain.
Methods The authors pooled data from 3 trials—CHARM Preserved (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity), I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function), and the Americas region of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) (N = 8,916)—and examined whether MI before or following enrollment independently predicted CV death and heart failure (HF) hospitalization.
Results At baseline, 2,668 patients (30%) had history of MI. Prior MI was independently associated with greater risk of CV death (4.7 vs. 3.5 events/100 patient-years [py], adjusted hazard ratio [HR]: 1.42 [95% confidence interval (CI): 1.23 to 1.64]; p < 0.001). Excess sudden death drove this difference (1.9 vs. 1.2 events/100 py, adjusted HR: 1.55 [95% CI: 1.23 to 1.97]; p < 0.001). There was no difference in HF hospitalization (5.9 vs. 5.5 events/100 py, adjusted HR: 1.05, 95% CI: 0.92 to 1.19) or HF death by prior MI. During follow-up, MI occurred in 336 patients (3.8%). Risk of CV death increased 31-fold in the first 30 days after first post-enrollment MI, and remained 58% higher beyond 1 year after MI. Risk of first or recurrent HF hospitalization increased 2.4-fold after MI.
Conclusions Prior MI in HFpEF is associated with greater CV and sudden death but similar risk of HF outcomes. Patients with HFpEF who experience MI are at high risk of subsequent CV death and HF hospitalization. These data highlight the importance of primary and secondary prevention of MI in patients with HFpEF. (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM Preserved]; NCT00634712; Irbesartan in Heart Failure With Preserved Systolic Function [I-Preserve]; NCT00095238; and Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)
The TOPCAT trial was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant HHSN268200425207C. Dr. Cunningham was supported by the NHLBI T32 postdoctoral training grant T32HL094301. Dr. Vaduganathan has been supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Institutes of Health/National Center for Advancing Translational Sciences Award UL 1TR002541). Dr. Vaduganathan has been a consultant or served on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, Relypsa, and Novartis. Dr. Claggett has been a consultant for Amgen, AOBiome, Biogen, Boehringer Ingelheim, Corvia, Gilead, and MyoKardia. Dr. Desai has received grants from Alnylam, AstraZeneca, and Novartis; and has been a consultant for Abbott, Alnylam, Amgen, AstraZeneca, Boehringer Ingelheim, Biofourmis, Boston Scientific, Corvidia, DalCor Pharmaceuticals, Merck, Novartis, Regeneron, and Relypsa. Dr. Lewis has received grants from the NHLBI, Novartis, Theracos, and Sanofi; and has been a consultant for Amgen, DalCor Pharmaceuticals, and Novartis. Dr. Zile has received grants from Novartis; and has been a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronics, Ironwood, Merck, Medtronic, MyoKardia, and V Wave. Dr. Jhund has been a consultant for AstraZeneca, Novartis, Boehringer Ingelheim, and Cytokinetics. Dr. Kober has received speaker fees from Novartis and AstraZeneca. Dr. Pitt has been a consultant for Amorcyte, AstraZeneca, Aurasense, Bayer, BG Medicine, Gambro, Johnson & Johnson, Mesoblast, Novartis, Pfizer, Relypsa, Sanofi/Lexicon, 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. Swedberg has served on advisory boards for AstraZeneca, Novartis, and Pfizer. Dr. Anand has been a consultant for AstraZeneca, ARCA, Amgen, Boston Scientific, Boehringer Ingelheim, Novartis, LivaNova, and Zensun. Dr. Yusuf has received research grants from AstraZeneca, Bayer, and Cadila. Dr. McMurray has received consulting payments through Glasgow University from Bayer, Cardiorentis, Amgen, Theracos, AbbVie, DalCor Pharmaceuticals, Pfizer, Merck, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Vifor-Fresenius, Kidney Research UK, Novartis, and Theracos; all payments were made through a consultancy with Glasgow University and were not personal payments. Dr. Pfeffer has been a consultant for AstraZeneca, DalCor Pharmaceuticals, GlaxoSmithKline, Innovative Science Solutions, Novo Nordisk, Pharmascience, Sanofi, Jazz, MyoKardia, Servier, Takeda, and Corvidia; has received research support from Novartis; and has stock options in DalCor Pharmaceuticals. Dr. Solomon has received research grants from Novartis, Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, MyoKardia, Theracos, Cytokinetics, Celladon, Bellerophon, Bayer, Ionis, Lone Star Heart, Mesoblast, Eidos, MyoKardia; National Institutes of Health/NHLBI, and Sanofi Pasteur; and personal/consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Daiichi Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Roche, Takeda, Quantum Genomics, Cardurion, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Novartis, and Theracos. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authora attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received October 2, 2019.
- Revision received January 6, 2020.
- Accepted February 11, 2020.
- 2020 American College of Cardiology Foundation
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