Author + information
- Received February 7, 2013
- Revision received August 1, 2013
- Accepted August 9, 2013
- Published online December 1, 2013.
- Stephen J. Greene, MD∗,
- Muthiah Vaduganathan, MD, MPH†,
- Jane E. Wilcox, MD‡,
- Matthew E. Harinstein, MD§,
- Aldo P. Maggioni, MD‖,
- Haris Subacius, MA‡,
- Faiez Zannad, MD, PhD¶,
- Marvin A. Konstam, MD#,
- Ovidiu Chioncel, MD∗∗,
- Clyde W. Yancy, MD‡,
- Karl Swedberg, MD, PhD††,
- Javed Butler, MD, MPH‡‡,
- Robert O. Bonow, MD∗,
- Mihai Gheorghiade, MD∗∗ (, )
- EVEREST Trial Investigators
- ∗Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- †Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- ‡Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- §Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- ‖ANMCO Research Center, Florence, Italy
- ¶INSERM CIC 9501 and U961, Université de Lorraine, CHU Cardiology, Nancy, France
- #The CardioVascular Center, Tufts Medical Center, Boston, Massachusetts
- ∗∗Cardiology 1, Institut de Boli Cardiovasculare C.C. Iliescu, Bucharest, Romania
- ††Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- ‡‡Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
- ↵∗Reprint requests and correspondence:
Dr. Mihai Gheorghiade, Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 201 East Huron Street, Galter 3-150, Chicago, Illinois 60611.
Objectives The purpose of this study was to characterize the relationship between heart rate and post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction (EF) in sinus rhythm.
Background A reduction in heart rate improves clinical outcomes in patients with chronic heart failure and in sinus rhythm, but the association between heart rate and post-discharge outcomes in patients with HHF is presently unclear.
Methods This post-hoc analysis of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) trial examined 1,947 patients with HHF and EF ≤40% not in atrial fibrillation/flutter or pacemaker dependent.
Results The median follow-up period was 9.9 months. At baseline, patients with a higher heart rate tended to be younger with lower EF and were more likely to have worse New York Heart Association functional class and higher natriuretic peptide levels. After adjustment for clinical risk factors, baseline heart rate was not predictive of all-cause mortality (p ≥ 0.066). However, at ≥70 beats/min, every 5-beat increase in 1-week post-discharge heart rate was independently associated with increased all-cause mortality (hazard ratio: 1.13 [95% confidence interval: 1.05 to 1.22]; p = 0.002). Similarly, every 5-beat increase ≥70 beats/min in 4-week post-discharge heart rate was predictive of all-cause mortality (hazard ratio: 1.12 [95% confidence interval: 1.05 to 1.19]; p = 0.001).
Conclusions In this large cohort of patients with HHF with reduced EF and in sinus rhythm, baseline heart rate did not correlate with all-cause mortality. In contrast, at ≥70 beats/min, higher heart rate in the early post-discharge period was independently predictive of death during subsequent follow-up. Further study of post-discharge heart rate as a potential therapeutic target in this high-risk population is encouraged.
Otsuka Inc. (Rockville, Maryland) provided financial and material support for the EVEREST trial. Database management was performed by the sponsor. Haris Subacius conducted all final analyses for this manuscript with funding from the Center for Cardiovascular Innovation (Northwestern University Feinberg School of Medicine, Chicago, Illinois). Dr. Zannad has served as a steering committee member for Bayer, Boston Scientific, Gambro, Janssen, Novartis, Pfizer, ResMed, and Takeda; served as an event committee member for Biotronik; served as a consultant/advisory board member for Servier; and received grant support from Roche Diagnostics. Dr. Konstam has served as a consultant for Amgen, Johnson & Johnson, Novartis Pharma AG, Otsuka Pharmaceuticals, and Merck & Co., Inc.; and received research support from Otsuka Pharmaceuticals. Dr. Butler has received research support from the National Institutes of Health, the European Union, the Health Resource Services Administration, and the Food and Drug Administration; and has served as a consultant for Alere, Amgen, Bayer, BG Medicine, Celladon, Covis, Gambro, GE Healthcare, Janssen, Medtronic, Novartis, Ono, Relypsa, Stemedica, Trevena, and Takeda. Dr. Gheorghiade has served as a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, Corthera, Cytokinetics, Debiopharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck & Co., Inc., Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, PeriCor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceuticals, and Trevena Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 7, 2013.
- Revision received August 1, 2013.
- Accepted August 9, 2013.
- American College of Cardiology Foundation