Association between resting heart rate and clinical outcomes in heart failure with preserved ejection fraction: age stratified insights from the KUNIUMI Registry

Abstract

Elevated resting heart rate (HR) is an established prognostic marker and therapeutic target in heart failure (HF) with reduced ejection fraction. In contrast, its clinical significance in HF with preserved ejection fraction (HFpEF) remains uncertain, particularly in very elderly patients who represent a growing proportion of the HF population. Age-related alterations in autonomic regulation and myocardial function may modify the prognostic relevance of HR in HFpEF. In addition, the impact of HR may differ according to cardiac rhythm, especially in the presence of atrial fibrillation (AF). However, data examining the prognostic significance of resting HR in very elderly HFpEF patients and its interaction with rhythm status are limited.

To evaluate the prognostic impact of elevated resting HR on cardiovascular outcomes in HFpEF patients aged ≥80 years using data from a single-center prospective registry. We compared these findings with patients aged <80 years to determine whether the association between resting HR and adverse cardiovascular events differs by age. Patients were further stratified by cardiac rhythm (sinus rhythm [SR] vs AF).

We prospectively studied 1,109 HFpEF patients from 1,646 consecutive HF patients in the KUNIUMI Registry chronic cohort between March 2019 and March 2021. Resting HR was measured using a standard 12-lead electrocardiogram under stable conditions at enrolment. Elevated HR was defined as ≥70 bpm. Patients were stratified by age (≥80 vs <80 years) and rhythm (SR vs AF). The primary endpoint was a composite of cardiovascular death and HF hospitalization over a median follow-up of 2.0 years.

During a median follow-up of 2.0 years, 132 patients (11.9%) experienced the primary endpoint. Among HFpEF patients in SR aged < 80 years, HR ≥70 bpm was significantly associated with worse cardiovascular outcomes (log-rank P<0.01; Figure 1A). However, this association was attenuated in those aged ≥ 80 years in SR (log-rank P=0.11; Figure 1B). In contrast, among patients with AF, there was no significant difference in cardiovascular outcomes between the HR ≥70 bpm and HR <70 bpm group, regardless of age (Figure 2). Multivariable cox proportional hazards analysis revealed that HR ≥70 bpm was independently associated with adverse cardiovascular outcomes in patients aged <80 years in SR.

Resting HR was differentially associated with clinical outcomes in HFpEF patients according to age and cardiac rhythm. Elevated HR was independently associated with worse cardiovascular outcomes in HFpEF patients aged <80 years with SR, but not in those aged ≥80 years or in HFpEF patients with AF. These findings support an individualized approach to risk assessment and challenge the applicability of universal HR targets in elderly HFpEF populations.