Cardiac Reverse Remodeling and Clinical Outcomes Following Angiotensin Receptor‐Neprilysin Inhibitor Therapy in Heart Failure With Reduced Ejection Fraction

Background Cardiac reverse remodeling and associated clinical outcomes following angiotensin receptor‐neprilysin inhibitor (ARNI) therapy in patients with heart failure (HF) with reduced ejection fraction (EF) remain unclear. We investigated differences in 1‐year echocardiographic response after ARNI therapy and predictors of clinical outcomes. Methods This study involved patients with HF with reduced EF and ARNI therapy for more than 6 months, using data from a 2‐center registry. Echocardiographic data were analyzed at baseline and 1 year after ARNI initiation. Responders were defined as patients with a ≥30% reduction in left ventricular end‐systolic volume at 1 year; all others were nonresponders. The primary outcome was cardiovascular death, and secondary outcomes were hospitalization for HF and all‐cause death. Time‐by‐group interactions in echocardiographic parameters were evaluated using linear mixed‐effects models. Results Among 1002 patients (mean age: 64.2±13.7 years; 70.8% men), 451 (45.0%) were responders and 551 (55.0%) were nonresponders. Responders had a lower baseline left ventricular EF but higher left ventricular EF at 1 year (27.0% [95% CI, 22.0–33.0] and 48.0% [95% CI, 42.0–55.0]). Both groups showed improvements in diastolic parameters, with more pronounced changes in responders. In multivariable analysis, nonresponders had a significantly higher risk of cardiovascular death, hospitalization for HF, and all‐cause death (all P <0.001). Male sex and a higher baseline left ventricular EF were independent predictors of nonresponse, whereas systolic blood pressure ≥110 mm Hg and atrial fibrillation were associated with better outcomes. Conclusions Cardiac reverse remodeling after ARNI therapy varies among patients with HF with reduced EF. Positive responders to ARNI therapy at 1 year experienced more favorable clinical outcomes.