Heart rate and atrial fibrillation/flutter in HFmrEF/HFpEF: a participant-level analysis across five randomized clinical trials

AIMS: While elevated heart rate is an established marker of risk in HF, the prognostic relevance of heart rate is less certain in patients with comorbid atrial fibrillation/flutter (AFF). We investigated the associations between heart rate and outcomes according to AFF status in 5 HFmrEF/HFpEF clinical trials. METHODS: In a participant-level pooled analysis of the CHARM-Preserved, I-PRESERVE, TOPCAT-Americas, PARAGON-HF, and DELIVER trials, associations between baseline heart rate and outcomes according to AFF status on ECG at enrolment were assessed with multivariable Cox and Poisson regression models. The primary outcome was CV death or HF hospitalization. RESULTS: Among 19 975 participants, 5816 (29%) had AFF on baseline ECG. Patients with AFF were older, more frequently male, had a higher baseline heart rate (75 vs 68 bpm, P < .001), and had an increased risk for the primary outcome (adj HR 1.19 [1.10-1.27]). A significant interaction between heart rate, AFF status, and clinical outcomes was observed, such that patients in sinus rhythm had higher event rates with increasing heart rates, while the incident rates for participants in AFF were similar across the range of baseline heart rate (Pinteraction < .001 for the primary outcome). This relationship was not further modified by concomitant β-blocker use. CONCLUSIONS: In this analysis of five HFmrEF/HFpEF trials, baseline heart rate was associated with significantly higher rates of events only in patients in sinus rhythm but not in those with AFF. The optimal management of AFF in the context of HFmrEF/HFpEF requires a dedicated study.