The Prognostic Significance of Heart Rate in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in Sinus Rhythm. Insights From the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) Trial.

Stephen J. Greene, Muthiah Vaduganathan, Jane E. Wilcox, Matthew E. Harinstein, Aldo P. Maggioni, Haris Subacius, Faiez Zannad, Marvin A. Konstam, Ovidiu Chioncel, Clyde W. Yancy, Karl Swedberg, Javed Butler, Robert O. Bonow, Mihai Gheorghiade*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)488-496
Number of pages9
JournalJACC: Heart Failure
Volume1
Issue number6
DOIs
StatePublished - Dec 2013

Funding

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.

Keywords

  • Heart failure
  • Heart rate
  • Hospitalization
  • Mortality
  • Prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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