Key Takeaways & Executive Findings
- •• HFrecEF patients have a significantly lower risk of death and heart failure hospitalization compared to those with persistent HFrEF. • Approximately one-quarter of HFrEF patients achieve LVEF recovery with optimal medical therapy. • LVEF deterioration occurs in nearly a quarter of HFrecEF patients and is associated with worse outcomes. • Ischemic etiology, diabetes, and non-adherence to therapy are independent predictors of LVEF deterioration in HFrecEF.
Abstract
Background: Heart failure with recovered ejection fraction (HFrecEF) is a distinct phenotype with unclear clinical characteristics and prognosis. Methods: We prospectively enrolled 1,234 patients with heart failure and reduced ejection fraction (HFrEF) from January 2015 to December 2018. After optimal medical therapy, 312 patients (25.3%) achieved recovery of left ventricular ejection fraction (LVEF) to ≥50% and were classified as HFrecEF. Clinical characteristics, medication use, and outcomes were compared with those who remained HFrEF. The primary outcome was a composite of all-cause death and heart failure hospitalization. Results: Compared with HFrEF patients, HFrecEF patients were younger, more likely to be female, had a higher prevalence of hypertension and atrial fibrillation, and had a shorter duration of heart failure. They had lower baseline levels of NT-proBNP and smaller left ventricular dimensions. Over a median follow-up of 3.2 years, HFrecEF patients had a significantly lower risk of the primary outcome (adjusted HR 0.45, 95% CI 0.32-0.63, p<0.001). However, 23.4% of HFrecEF patients experienced deterioration of LVEF during follow-up, and these patients had a worse prognosis compared with those who maintained recovery. Independent predictors of LVEF deterioration included ischemic etiology, diabetes, and non-adherence to guideline-directed medical therapy. Conclusions: HFrecEF is associated with a better prognosis than HFrEF, but a substantial proportion of patients may experience LVEF deterioration. Continued optimization of medical therapy and close monitoring are essential for this population.
1. Introduction
Heart failure (HF) is a global pandemic affecting over 26 million people worldwide, with substantial morbidity and mortality. Among the various phenotypes, heart failure with reduced ejection fraction (HFrEF) has been extensively studied, and guideline-directed medical therapy (GDMT) has been shown to improve outcomes. However, a subset of patients with HFrEF experience recovery of left ventricular ejection fraction (LVEF) to ≥50%, a condition now recognized as heart failure with recovered ejection fraction (HFrecEF). This phenotype has been associated with better prognosis compared to persistent HFrEF, yet the underlying clinical characteristics and long-term outcomes remain incompletely understood.
Recent studies have suggested that HFrecEF represents a distinct clinical entity with unique pathophysiological mechanisms, and that these patients may have a more favorable course. However, there is limited prospective data on the incidence, predictors, and prognostic implications of LVEF recovery, particularly in the era of modern GDMT. Moreover, the risk of subsequent LVEF deterioration in HFrecEF patients and its impact on outcomes is not well characterized. Therefore, we conducted a prospective cohort study to comprehensively evaluate the clinical characteristics, management, and outcomes of patients with HFrecEF, and to identify factors associated with LVEF deterioration.
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ZHANG Wei, LI Ming, WANG Fang, LIU Yang, CHEN Jing, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Lin, HUANG Rui, YANG Fan, GAO Peng, TANG Min, HE Yun, XU Jing, DENG Fei, CAO Xue, LUO Bin, GUO Tao, SONG Dan, XIE Jun, ZHENG Li, MA Chao, JIANG Wei, FENG Yu, HAN Xin, REN Bo, DONG Mei, BAI Xue, CUI Lin, SHEN Jia, YAO Lei, TIAN Hao, QIAN Yi, DU Juan, ZHU Min, XIAO Gang, LIANG Hua, KONG Fan, NIU Qiang, WEN Ting, ZOU Yan, DING Li, JIA Rui, PAN Jun, SHAO Ying, MENG Na, YIN Bo, XU Tao, CHEN Lin, GAO Yuan, WANG Lei, LIU Xin, ZHANG Jing, SUN Li, ZHOU Peng, WU Jun, ZHENG Yan, HUANG Wei, XU Fang, LI Na, YANG Bo, ZHAO Min, LIU Hui, CHEN Yu, WANG Tao, ZHANG Min, LI Qiang, LIU Na, WANG Jing, ZHANG Li, LIU Bo, WANG Xin, ZHANG Yan, LI Wei, LIU Jun, WANG Hong, ZHANG Tao, LI Na, LIU Yang, WANG Fang, ZHANG Wei, LI Ming (2025). Clinical Characteristics and Prognosis of Patients with Heart Failure with Recovered Ejection Fraction: A Prospective Cohort Study. Chinese Journal of New Drugs. https://doi.org/cast_zgxyzz_1236731785313317742
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Frequently Asked Questions
What is heart failure with recovered ejection fraction (HFrecEF)?
HFrecEF is a distinct phenotype of heart failure where patients initially present with reduced ejection fraction (HFrEF) but later improve their left ventricular ejection fraction (LVEF) to ≥50% after optimal medical therapy.
How common is LVEF recovery in HFrEF patients?
In our prospective cohort, approximately 25% of patients with HFrEF achieved LVEF recovery to ≥50% over a median follow-up of 3.2 years.
What is the prognosis of HFrecEF compared to persistent HFrEF?
HFrecEF patients have a significantly lower risk of all-cause death and heart failure hospitalization compared to those with persistent HFrEF, with an adjusted hazard ratio of 0.45.
Can HFrecEF patients experience deterioration of LVEF?
Yes, about 23% of HFrecEF patients in our study experienced deterioration of LVEF during follow-up, and these patients had a worse prognosis compared to those who maintained recovery.
What factors predict LVEF deterioration in HFrecEF?
Independent predictors of LVEF deterioration include ischemic etiology, diabetes, and non-adherence to guideline-directed medical therapy.
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