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

Henri Lu; Brian L Claggett; Milton Packer; Marc A Pfeffer; Karl Swedberg; Jean Rouleau; Michael R Zile; Martin Lefkowitz; Akshay S Desai; Pardeep S Jhund; John J V McMurray; Scott D Solomon; Muthiah Vaduganathan

doi:10.1002/ejhf.3487

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

Eur J Heart Fail. 2024 Oct 22. doi: 10.1002/ejhf.3487. Online ahead of print.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Division of Cardiology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
³ Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, TX, USA.
⁴ Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Institut de Cardiologie de Montréal, Université de Montréal, Montréal, QC, Canada.
⁶ Medical University of South Carolina, Charleston, SC, USA.
⁷ Novartis, East Hanover, NJ, USA.
⁸ BHF Glasgow Cardiovascular Research Centre, Glasgow, UK.

PMID: 39439294
DOI: 10.1002/ejhf.3487

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).

Keywords: Heart failure; Heart rate; Prognosis.

Associated data

ClinicalTrials.gov/NCT01920711
ClinicalTrials.gov/NCT01035255

Grants and funding

Novartis