AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
The Interplay Among Natriuretic Peptide Reduction, Ejection Fraction Recovery, All-Cause Mortality, and Rhythm Control in Heart Failure with Reduced Ejection Fraction and Atrial Fibrillation
By Lo SW, Augusto S, Kodur N et al.
Background: Atrial fibrillation (AF) and HFrEF frequently coexist, yet the longitudinal interplay between rhythm control, serial natriuretic peptide trajectories, and left ventricular recovery remains incompletely characterized. Hypothesis: We hypothesized that successful rhythm control would be associated with greater NT-proBNP reduction and LVEF recovery, thereby, improving all-cause mortality. Methods: We performed a retrospective multicenter study using EHR data from 2009-2024. Patients with HFrEF, baseline NT-proBNP >1,000 pg/mL, and documented AF history were included. Patients were classified into four rhythm trajectories by cross-classifying baseline and follow-up ECG rhythm ascertained within ±90 days of nadir NT-proBNP: No AF→No AF (Sustained Rhythm Control), AF→No AF (Successful Rhythm Control), No AF→AF (AF Relapse), and AF→AF (Persistent AF). The primary outcome was all-cause mortality. NT-proBNP changes, LVEF recovery (LVEF ≥50%), and survival were compared across groups. Multivariable Cox models adjusted for age, sex, BMI, eGFR, LVEF ≥50%, and follow-up NT-proBNP were used to assess whether rhythm trajectory retained independent prognostic significance after accounting for NT-proBNP. Results: Among 1,729 patients (median age 71 years, 69.6% male), achievement of NT-proBNP <1,000 pg/mL differed by rhythm trajectory (overall p<0.001). Successful Rhythm Control had a higher proportion achieving NT-proBNP <1,000 than Persistent AF (42.4% vs 20.9%, p<0.001), and Sustained Rhythm Control exceeded AF Relapse (32.1% vs 19.4%, p=0.02). Similarly, LVEF recovery varied across groups (overall p<0.001), occurring more often with Successful Rhythm Control than Persistent AF (34.0% vs 21.2%, p=0.001), while Sustained Rhythm Control was numerically higher than AF Relapse (21.8% vs 19.4%) without statistical significance (p>0.05). In unadjusted Cox models (reference: Sustained Rhythm Control), Successful Rhythm Control was associated with lower mortality (HR 0.74, 95% CI 0.60-0.90; p=0.003), whereas AF Relapse was associated with higher mortality (HR 1.35, 95% CI 1.04-1.76; p=0.025); Persistent AF did not differ significantly (HR 1.07, 95% CI 0.89-1.29; p=0.473). After multivariable adjustment, rhythm trajectory was no longer independently associated with mortality, whereas follow-up NT-proBNP remained strongly prognostic (HR 1.38, 95% CI 1.32-1.44; p=0.001). Conclusions: Successful rhythm control in HFrEF patients with AF is associated with greater NT-proBNP reduction and LVEF recovery compared with persistent AF or AF relapse. The survival advantage of rhythm control appears to be mediated by a reduction in myocardial wall stress, as reflected by NT-proBNP, rather than by rhythm normalization per se. These findings support NT-proBNP as a mechanistic intermediary linking rhythm control to improved outcomes in HFrEF.