Ana Haridevara

Visit-to-visit changes in heart rate in heart failure: A pooled participate-level analysis of the PARADIGM-HF and PARAGON-HF Trials

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 (pinteraction =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.