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.
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.
Greene, SJ; Vaduganathan, M; Wilcox, JE; Harinstein, ME; Maggioni, AP; Subacius, H; Zannad, F; Konstam, MA; Chioncel, O; Yancy, CW; Swedberg, K; Butler, J; Bonow, RO; Gheorghiade, M; EVEREST Trial Investigators,
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