# Predictors of reverse cardiac remodeling after sacubitril/valsartan in heart failure with reduced ejection fraction

## TL;DR

This study finds that early treatment with sacubitril/valsartan and higher doses are linked to better heart recovery in patients with heart failure.

## Contribution

Identifies early initiation and higher dosing of sacubitril/valsartan as predictors of reverse cardiac remodeling in heart failure patients.

## Key findings

- Patients with heart failure duration <12 months had a higher rate of reverse remodeling (46.1% vs. 25.7%).
- Higher sacubitril/valsartan doses (≥200 mg/day) were associated with more reverse remodeling (44.0% vs. 31.9%).
- Low baseline ejection fraction, short heart failure duration, and higher drug dose were independent predictors of remodeling.

## Abstract

Sacubitril/valsartan (Sac/Val) is associated with reverse cardiac remodeling in heart failure with reduced ejection fraction (HFrEF). However, the predictors of reverse cardiac remodeling after Sac/Val have not yet been fully established. We aimed to evaluate the predictors of reverse cardiac remodeling in patients with HFrEF, with a focus on HF duration and the dose of Sac/Val. In this retrospective, multicenter cohort study, 600 patients with HFrEF who received a Sac/Val prescription were enrolled at six tertiary hospitals in Korea between February 2017 and April 2019. After excluding patients without baseline or 12-month follow-up echocardiographic data, 294 patients were enrolled. Reverse cardiac remodeling was defined by comparing the baseline and follow-up echocardiographic data: an absolute increase in left ventricular ejection fraction (LVEF) ≥ 10% and a relative decrease in left ventricular end-diastolic volume index ≥ 10%. The average daily Sac/Val dose was calculated during the first 6 and 12 months after initiation. Among the 294 patients, 107 presented with reverse cardiac remodeling at 12 months. Patients with HF duration < 12 months at the time of Sac/Val initiation showed a higher proportion of reverse cardiac remodeling than patients with HF duration ≥ 12 months (46.1% vs. 25.7%; P < 0.001). Patients with an average daily Sac/Val dose ≥ 200 mg/day over 6 months also had a higher proportion of reverse cardiac remodeling than patients with Sac/Val < 200 mg/day (44.0% vs. 31.9%; P < 0.001). Multivariable logistic regression revealed low baseline LVEF, HF duration < 12 months, and higher Sac/Val dose as independent predictors of reverse cardiac remodeling. In conclusion, early initiation of Sac/Val following HF diagnosis and higher Sac/Val doses were associated with a higher likelihood of reverse cardiac remodeling in HFrEF.

The online version contains supplementary material available at 10.1038/s41598-026-36361-0.