Clinical outcomes of heart failure with improved ejection fraction in patients treated with angiotensin receptor–neprilysin inhibitor

Kim, Dong-Eon; Kong, Min Gyu; Kim, Saerom; Moon, Inki; Park, Hyun Woo; Choi, Hyung-Oh; Seo, Hye Sun; Cho, Yoon Haeng; Lee, Nae-Hee; Lee, Kwan Yong; Jang, Ho-Jun; Kim, Je Sang; Choi, Ik Jun; Suh, Jon

doi:2026.41.3.474

Korean J Intern Med > Volume 41(3); 2026 > Article

ORIGINAL ARTICLE

Cardiology

Korean J Intern Med. 2026;41(3):474-484. doi: https://doi.org/10.3904/kjim.2025.309

Clinical outcomes of heart failure with improved ejection fraction in patients treated with angiotensin receptor–neprilysin inhibitor

Dong-Eon Kim¹, Min Gyu Kong¹

, Saerom Kim¹, Inki Moon¹, Hyun Woo Park¹, Hyung-Oh Choi¹, Hye Sun Seo¹, Yoon Haeng Cho¹, Nae-Hee Lee¹, Kwan Yong Lee², Ho-Jun Jang³, Je Sang Kim⁴, Ik Jun Choi⁵, and Jon Suh¹

¹Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
²Cardiovascular Center and Division of Cardiology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
³Division of Cardiology, Department of Internal Medicine, Hanil General Hospital, Seoul, Korea
⁴Division of Cardiology, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
⁵Division of Cardiology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea

Corresponding Author: Min Gyu Kong , Tel: +82-32-621-6727, Email: mingyu.kong@schmc.ac.kr

Received: September 7, 2025; Revised: November 29, 2025; Accepted: January 12, 2026.

Abstract

Background/Aims: Improvement of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF) has been associated with favorable outcomes; however, corresponding data in patients treated with angiotensin receptor– neprilysin inhibitors (ARNIs) remain limited. This study aimed to examine the characteristics, predictors, and outcomes of HF with improved ejection fraction (HFimpEF) compared with persistent HFrEF in the RECORD-SV registry.
Methods: Patients with LVEF ≤ 40% in the RECORD-SV registry were classified based on echocardiographic assessments at baseline and 1-year follow-up. Patients with HFimpEF were defined as those with follow-up LVEF of > 40% with an absolute improvement of ≥ 10%, whereas the persistent HFrEF group included those who did not meet these criteria. Baseline characteristics, predictive factors, and clinical outcomes of the patients were analyzed. The primary composite outcome was allcause mortality and hospitalization for HF management, with secondary outcomes including each component of the primary outcome and frequency of urgent emergency room visits.
Results: Among 198 patients with HFrEF, 60 patients (30.3%) achieved HFimpEF after one year of ARNI-based therapy. Independent predictors of HFimpEF included female sex, non-ischemic etiology, and de novo HF. HFimpEF patients exhibited significantly lower risks in the primary composite outcome (HR 0.382, 95% CI 0.148–0.985) compared to those with persistent HFrEF, with a similar trend observed for secondary outcomes.
Conclusions: Patients achieving HFimpEF with ARNIs exhibited distinct clinical features and significantly lower risk of cardiovascular events compared to those with persistent HFrEF, highlighting the prognostic benefit of EF recovery with ARNI therapy.

Keywords: Heart failure ; Ventricular remodeling ; Neprilysin