Heart rate and prognosis of heart failure with reduced ejection fraction in women and men in sinus rhythm

Abstract Background Resting heart rate (HR) is a well-established therapeutic target for treating heart failure (HF). Beta-blockers are the primary drugs to reduce HR. Elevated HR is associated with higher mortality in heart failure with reduced ejection fraction (HFrEF). However, the influence of HR on mortality and predictors of death in women with HFrEF in sinus rhythm is not well understood. Purpose to analyse mortality for HR ≤60>bpm and ≤70>bpm in women and men. Methods From February 2017 to January 2022, we analysed the influence of resting HR (≤60> and ≤70>bpm) on mortality and predictors of death in women and men with HFrEF in sinus rhythm. Baseline data included clinical characteristics and echocardiographic findings. The HR used in the analysis was obtained at the closest outpatient visit to the death event. We used the adjustment for multiple comparisons for the log-rank test of Kaplan-Meier (K-M) and Cox proportional hazards methods to analyse mortality rates and search for death predictors for women and men. Results We analysed 2,984 patients, with a mean age of 61 ± 13.8 years, 1,922 (64.4%) men. Age, body mass index, myocardial infarction, diabetes, chronic kidney disease, stroke, carvedilol dosage, hospitalization, and initial left ventricular ejection fraction (LVEF) were similar in both genders. Over the follow-up period of 3.7±1.6 years, we observed an increase in LVEF in men (29.5%±6.7% vs. 36.7%±12.9%; p<0.001) and women (29.9%±6.4 vs. 38.0%±13.4%; p<0.001), and HR reduced in men (73.1±13.0 to 72.1±11.8 bpm; p=0.007) and women (72.8±12.7 to 71.8±11.3 bpm; p=0.026). Death incidence was higher in men (43.7% vs. 36.7%; p<0.001). The cumulative incidence of death was higher in men with HR>60bpm (K-M: log-rank p<0.001) and >70bpm (K-M: log-rank p=0.011) compared to women. Cox regression for death, adjusted for covariates with p<0.25, showed age (HR=1.01;95%CL:1.008-1.017; p<0.001), men (HR=0.80;95%CL:0.71-0.90; p<0.001), LVEF (HR=0.986;95%CL:0.98-0.99; p=0.001), and HR (HR=1.005;95%CL:1.00-1.01; p=0.025) as independent death variables. For men, the independent variables were age (HR=1.01;95%CL:1.01-1.02; p=0.002), LVEF (HR=0.98;95%CL:0.97-0.99; p=0.001), and HR (HR=1.008;95%CL:1.00-1.01; p=0.008), and for women, only the age (HR=1.02;95%CL:1.01-1.02; p<0.001). Conclusion Increased HR was an independent variable of death in men but not in women. Future studies are needed to determine the best reference HR for a chronotropic drug intervention to reduce mortality in women with HFrEF in sinus rhythm.