Cumulative resting heart rate load and cardiovascular risk in patients with heart failure: a secondary analysis of five randomized clinical trials

Background Resting heart rate is a readily available vital sign with important prognostic significance. However, traditional measures overlook both the magnitude and duration of elevated heart rate over time. Purpose This study aims to assess the association between cumulative resting heart rate load and risk of adverse outcomes among patients with chronic heart failure (HF) in sinus rhythm, and compare its prognostic value against other heart rate measures in this population. Methods Data from 5 randomized controlled trials (BEST, GUIDE-IT, HF-ACTION, RELAX, and TOPCAT) were analyzed. Cumulative heart rate load was calculated as the area under the curve (AUC) for heart rate ≥70 beats per minute (bpm), relative to the total AUC prior to outcomes. The primary outcome was major adverse cardiac events (MACE), defined as the composite of cardiovascular death and hospitalization for HF. Cox proportional hazards regression models were used to examine associations with outcomes. Results A total of 5428 patients were included. Higher cumulative resting heart rate load was significantly associated with increased risk of MACE (hazard ratio [HR], 1.31; 95% CI, 1.24-1.38), cardiovascular death (HR, 1.17; 95% CI, 1.08-1.27), hospitalization for HF (HR, 1.34; 95% CI, 1.26-1.43), all-cause death (HR, 1.20; 95% CI, 1.12-1.29), and any hospitalization (HR, 1.20; 95% CI, 1.15-1.25). These findings were consistent across HF with preserved ejection fraction and HF with reduced ejection fraction subgroups. Moreover, cumulative resting heart rate load showed superior predictive value for all outcomes compared with baseline heart rate, mean heart rate, heart rate standard deviation, and heart rate time in the target range with improvements in C-statistics, net reclassification improvement, and integrated discrimination improvement when added to base models. Conclusion Cumulative resting heart rate load has a stronger predictive value for adverse events compared to traditional measures of heart rate in patients with chronic HF. Its significant association with increased risks of clinical outcomes underscores the importance of routine heart rate monitoring in this population. These findings highlight the need for further research to refine heart rate management strategies in chronic HF patients.