title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Wilcox
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Harinstein
authors.affiliation: ANMCO Research Center, Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Haris
authors.initials: H
authors.lastname: Subacius
authors.affiliation: INSERM CIC 9501 and U961, Université de Lorraine, CHU Cardiology, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: The CardioVascular Center, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.affiliation: Cardiology 1, Institut de Boli Cardiovasculare C.C. Iliescu, Bucharest, Romania.
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Chioncel
authors.affiliation: Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Clyde W
authors.initials: CW
authors.lastname: Yancy
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Bonow
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address: m-gheorghiade@northwestern.edu.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use; D004812:Epidemiologic Methods; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D011379:Prognosis; D013318:Stroke Volume / Q000502:physiology; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: heart failure; heart rate; hospitalization; mortality; prognosis