Visit‐to‐visit changes in heart rate in heart failure: A pooled participant‐level analysis of the PARADIGM‐HF and PARAGON‐HF trials

Abstract Aims Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit‐to‐visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well‐characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF). Methods and results PARADIGM‐HF and PARAGON‐HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM‐HF) or LVEF ≥45% (PARAGON‐HF). We analysed the association between ΔHR from the preceding visit with the primary endpoint of HF hospitalization (HFH) or cardiovascular death using covariate‐adjusted Cox proportional hazards models. A total of 13 194 patients (mean age 67 ± 11 years, 67% men, mean LVEF 40 ± 15%) were included. Over a median follow‐up of 2.5 years, 3114 patients experienced a first HFH or cardiovascular death event (10.4 events per 100 patient‐years). An increase in HR from the preceding visit, compared with no change, was associated with a higher risk (hazard ratio 1.12; 95% confidence interval [CI] 1.10–1.15; p < 0.001 per 5 bpm increase). Conversely, a drop in HR was associated with a lower risk (hazard ratio 0.97; 95% CI 0.94–1.00; p = 0.044 per 5 bpm drop). The prognostic implications of ΔHR were consistent across the range of LVEF and observed regardless of β‐blocker use or presence of a permanent pacemaker. Visit‐to‐visit increases in HR were especially prognostic in patients without atrial fibrillation ( p interaction = 0.006). Conclusion Across a broad spectrum of patients with chronic HF, increases in HR from a preceding visit independently predicted clinical outcomes. The detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events. Clinical Trial Registration; ClinicalTrials.gov NCT01035255 (PARADIGM‐HF), NCT01920711 (PARAGON‐HF).