Echocardiographic response and predictors of reverse remodeling after sacubitril/valsartan in de novo heart failure with reduced ejection fraction: cohort study

Background: Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor, ARNI) improves outcomes in heart failure with reduced ejection fraction (HFrEF), yet treatment response varies and predictors of response remain incompletely defined. We aimed to evaluate real-world echocardiographic responses to ARNI and identify predictors of favorable response in patients with newly diagnosed HFrEF. Methods: Consecutive patients who initiated ARNI at Uijeongbu Eulji University Hospital between March 2021 and August 2024 were prospectively enrolled. Echocardiographic reverse remodeling was assessed by changes in left ventricular (LV) ejection fraction (EF). Based on the degree of echocardiographic response, patients were categorized as nonresponders [follow-up left ventricular ejection fraction (LVEF) <40% and an absolute increased in LVEF <10%], partial responders (follow-up LVEF ≥40% and <50%, or an absolute increase in LVEF ≥10% with follow-up LVEF <50%), or super responders (follow-up LVEF ≥50%). Clinical outcomes were assessed using Kaplan-Meier analysis, and predictors of response were evaluated using multivariable logistic regression. Results: Among 392 patients who completed follow-up echocardiography (median follow-up interval, 11.0 months), 116 (29.6%) were nonresponders, 110 (28.0%) were partial responders, and 166 (42.3%) were super responders with a recovery of LVEF ≥50%. During a median follow-up of 708 days, nonresponders experienced significantly higher rates of clinical events, including death or heart failure rehospitalization, compared with responders (P<0.001). In multivariable analysis, higher baseline systolic blood pressure [SBP; odds ratio (OR), 1.249; 95% confidence interval (CI): 1.120–1.400] and smaller LV end-diastolic volume (OR 0.919; 95% CI: 0.869–0.970) were independently associated with favorable echocardiographic response. Although a substantial proportion of patients did not achieve ARNI doses ≥200 mg/day, exploratory analysis did not demonstrate a significant association between ARNI dose and echocardiographic response or clinical outcomes. Conclusions: In this real-world cohort study, ARNI therapy was associated with substantial reverse remodeling and improved clinical outcomes despite low rates of target-dose attainment. Baseline SBP and LV remodeling parameters were associated with treatment response, supporting individualized ARNI titration strategies in clinical practice.