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Review
. 2025 Jun 24;85(24):2401-2415.
doi: 10.1016/j.jacc.2025.03.544.

Heart Failure With Improved Ejection Fraction: Definitions, Epidemiology, and Management

Mauro Riccardi  1 , Maria A Pabon  2 , Ankeet S Bhatt  3 , Gianluigi Savarese  4 , Marco Metra  5 , Maurizio Volterrani  6 , Carlo M Lombardi  1 , Muthiah Vaduganathan  2 , Scott D Solomon  2 , Orly Vardeny  7 , Riccardo M Inciardi  8
Affiliations
Review

Heart Failure With Improved Ejection Fraction: Definitions, Epidemiology, and Management

Mauro Riccardi et al. J Am Coll Cardiol. .

Abstract

Heart failure with improved ejection fraction (HFimpEF) has gained increasing recognition as a distinct phenotype within the spectrum of heart failure, characterized by previously reduced left ventricular ejection fraction (≤40%) that subsequently improves to >40%. HFimpEF remains relatively understudied, and uncertainty persists regarding its long-term prognosis and optimal management. Contemporary registries and clinical trials suggest a rising prevalence, likely reflecting both the increased implementation of guideline-directed medical therapy and evolving consensus definitions for its identification. Despite left ventricular ejection fraction recovery, patients with HFimpEF remain at risk for adverse outcomes, and their management remains an area of active investigation. The aim of this review is to provide an in-depth evaluation of HFimpEF, including its epidemiology, pathophysiology, prognosis, and treatment strategies. The authors also highlight existing clinical gaps and propose future research directions to refine risk stratification and therapeutic approaches for this evolving population.

Keywords: GDMT; HFimpEF; LVEF; reverse remodeling.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Pabon has received support from the American Heart Association (24CDA1272604) and the Doris Duke Charitable Foundation (2023-0212). Dr Bhatt has received research grant support to his institution from the National Heart, Lung, and Blood Institute, the National Institute on Aging, the American College of Cardiology Foundation, and the Centers for Disease Control and Prevention; and has received prior consulting fees from Sanofi Pasteur and Novo Nordisk. Dr Savarese has received grants and personal fees from Vifor, Boehringer Ingelheim, AstraZeneca, Novartis, Cytokinetics, and Pharmacosmos; has received personal fees from Servier, Medtronic, Teva, Abbott, Edwards Lifesciences, INTAS, and Abbott; and has received grants from Boston Scientific, Merck, and Bayer, outside of the submitted work. Dr Metra has received consulting honoraria as a member of trial committees or advisory boards for Abbott Vascular, Actelion, Amgen, Bayer, Edwards Therapeutics, Servier, Vifor Pharma, and Windtree Therapeutics. Dr Vaduganathan has received research grant support from American Regent, Amgen, AstraZeneca, Bayer, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has served on advisory boards or had speaker engagements or other support from Amgen, AstraZeneca, Galmed, Novartis, Bayer, Occlutech, and Impulse Dynamics (clinical trial committees) outside the submitted work. Dr Solomon has received research grants (paid to the institution) from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Eli Lilly, Mesoblast, MyoKardia, the National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, Us2.ai; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Eli Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, and Valo. Dr Vardeny has received grants from AstraZeneca and Bayer; has received personal fees from Cardior; and is a steering committee member with institutional support from Cardurion. Dr Inciardi has received consulting fees from AstraZeneca, Bayer, Novo Nordisk, Boehringer Ingelheim, Novartis, Daiichi-Sankyo, Bruno Pharma, AstraZeneca, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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