Heart Failure With Improved Ejection Fraction (HFimpEF): Current Evidence, Clinical Implications, and Future Directions
Keywords:
HFimpEF; Heart Failure; Reverse Remodelling; Guideline-Directed Medical Therapy; Left Ventricular Ejection Fraction; PrognosisAbstract
Heart failure with improved ejection fraction (HFimpEF) has emerged in recent years as a distinct clinical phenotype within the spectrum of heart failure subtypes. Current evidence supports the hypothesis that HFimpEF represents a state of functional remission rather than a definitive cure, with important clinical implications, particularly for the continuation of guideline-directed medical treatment (GDMT) and decision-making regarding device therapies. Withdrawal or de-escalation of treatment is associated with high rates of recurrent systolic function deterioration, justifying the indefinite continuation of disease-modifying therapy. This review summarises the available evidence on the definition, epidemiology, pathophysiological mechanisms, left ventricular ejection fraction (LVEF) trajectories, advanced diagnostic tools, and therapeutic considerations in HFimpEF, and discusses the main knowledge gaps and future research directions. A better understanding of this phenotype will enable more effective risk stratification and progress towards more individualised management of patients with heart failure, with potential benefits for long-term patient outcomes and care.
Downloads
References
1. Liyan Huang, Ping Zhou, Mei Zhai, Jiayu Feng, Yan Huang, Qiong Zhou, Chunhui He, Xinqing Li, Anran Xin, Yuhui Zhang, Jian Zhang. Incidence, progression, and outcomes of heart failure with improved ejection fraction: The added value of longitudinally assessed ejection fraction, International Journal of Cardiology, ,https://doi.org/10.1016/j.ijcard.2024.132759.
2. Weiss, A., Flowers, A., Eisenberg, S. D., Wu, L., Rodriguez, M., Khawaja, M., Moras, E., Lavie, C. J., Fonarow, G. C., Tang, W. H. W., Bozkurt, B., & Krittanawong, C. (2025). A contemporary review on heart failure with improved ejection fraction. npj Cardiovascular Health, 2, Article 56. https://doi.org/10.1038/s44325-025-00093-3
3. Park H, Lee N, Hwang CH, Cho SG, Choi GH, Cho JY, Yoon HJ, Kim KH, Ahn Y. Prognosis After Withdrawal of Cardioprotective Therapy in Patients With Improved Cancer Therapeutics-Related Cardiac Dysfunction. JACC CardioOncol. 2024 Sep 17;6(5):699-710. doi: 10.1016/j.jaccao.2024.07.018. PMID: 39479323; PMCID: PMC11522502.
4. Pensa, A. V., Khan, S. S., Shah, R. V., & Wilcox, J. E. (2024). Heart failure with improved ejection fraction: Beyond diagnosis to trajectory analysis. International Journal of Cardiology. https://doi.org/10.1016/j.ijcard.2024.000148
5. Kodur, N, Tang, W. Management of Heart Failure With Improved Ejection Fraction: Current Evidence and Controversies. J Am Coll Cardiol HF. 2025 Apr, 13 (4) 537–553.https://doi.org/10.1016/j.jchf.2025.02.007
6. McElderry, B., O’Neill, T., Griffin, B. P., Kalahasti, V., Barzilai, B., & Brateanu, A. (2024). Factors associated with maintenance of an improved ejection fraction: An echocardiogram-based registry study. Journal of the American Heart Association, 13(X), e031093. https://doi.org/10.1161/JAHA.123.031093
7. Su, K., Li, M., Wang, L., Tian, S., Su, J., Gu, J., & Chen, S. (2024). Clinical characteristics, predictors, and outcomes of heart failure with improved ejection fraction. International Journal of Cardiology. https://doi.org/10.1016/j.ijcard.2024.00405
8. Schöps, L. B., Sengeløv, M., Modin, D., Jørgensen, P. G., Bruun, N. E., Fritz-Hansen, T., Gislason, G., Wolsk, E., Schou, M., & Biering-Sørensen, T. (2023). Parameters associated with improvement of systolic function in patients with heart failure. Heart (British Cardiac Society), 110(1), 49–56. https://doi.org/10.1136/heartjnl-2023-322371
9. Jiang, Y., Chen, X., Zhang, X., Dong, S., & Liu, Y. (2024). Dynamic trajectories of left ventricular ejection fraction in heart failure with improved ejection fraction. BMC Cardiovascular Disorders, 24, Article 4288. https://doi.org/10.1186/s12872-024-04288-x
10. Romero E, Baltodano AF, Rocha P, Sellers-Porter C, Patel DJ, Soroya S, Bidwell J, Ebong I, Gibson M, Liem DA, Jimenez S, Bang H, Sirish P, Chiamvimonvat N, Lopez JE, Cadeiras M. Clinical, Echocardiographic, and Longitudinal Characteristics Associated With Heart Failure With Improved Ejection Fraction. Am J Cardiol. 2024 Jan 15;211:143-152. doi: 10.1016/j.amjcard.2023.10.086. Epub 2023 Nov 2. PMID: 37923155; PMCID: PMC10869234.
11. Huang W, Nurhafizah A, Frederich A, Khairunnisa AR, Kezia C, Fathoni MI, Samban S, Flindy S. Risk and Protective Factors of Poor Clinical Outcomes in Heart Failure with Improved Ejection Fraction Population: A Systematic Review and Meta-Analysis. Curr Cardiol Rep. 2025 Jan 6;27(1):4. doi: 10.1007/s11886-024-02180-w. PMID: 39760806.
12. Stępień K, Nowak K, Kachnic N, Karcińska A, Del Carmen Yika A, Furczyński J, Platschek M, Skorupa M, Wyleciał Z, Zalewski J, Nessler J. Clinical characteristics and long-term outcomes of patients with heart failure with improved ejection fraction. First Polish experience from LECRA-HF registry. Adv Med Sci. 2024 Mar;69(1):132-138. doi: 10.1016/j.advms.2024.02.009. Epub 2024 Mar 4. PMID: 38447613.
13. Segev A, Avrahamy B, Fardman A, Matetzky S, Freimark D, Regev O, Kuperstein R and Grupper A (2024) Heart failure with improved ejection fraction: patient characteristics, clinical outcomes and predictors for improvement. Front. Cardiovasc. Med. 11:1378955. doi: 10.3389/fcvm.2024.1378955
14. Kim KA, Kim SH, Lee KY, Yoon AH, Hwang BH, Choo EH, Kim JJ, Choi IJ, Kim CJ, Lim S, Park MW, Yoo KD, Jeon DS, Ahn Y, Jeong MH, Chang K. Predictors and Long-Term Clinical Impact of Heart Failure With Improved Ejection Fraction After Acute Myocardial Infarction. J Am Heart Assoc. 2024 Aug 20;13(16):e034920. doi: 10.1161/JAHA.124.034920. Epub 2024 Aug 19. PMID: 39158557; PMCID: PMC11963921.
15. Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S, Jackson R, Rahneva T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu JN, Pantazis A, Cook SA, Ware JS, Baksi AJ, Pennell DJ, Rosen SD, Cowie MR, Cleland JGF, Prasad SK. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019 Jan 5;393(10166):61-73. doi: 10.1016/S0140-6736(18)32484-X. Epub 2018 Nov 11. PMID: 30429050; PMCID: PMC6319251.
16. L Cheng, D Hammersley, A Ragavan, S Javed, S Mukhopadhyay, J Gregson, J Han, J Ware, U Tayal, D J Pennell, J G F Cleland, S K Prasad, B P Halliday, Long-term follow-up of the TRED-HF trial, European Heart Journal, Volume 45, Issue Supplement_1, October 2024, ehae666.1076, https://doi.org/10.1093/eurheartj/ehae666.1076
17. Arbelo, E., Protonotarios, A., Gimeno, J. R., Arbustini, E., Barriales-Villa, R., Basso, C., Bezzina, C. R., Biagini, E., Blom, N. A., de Boer, R. A., De Winter, T., Elliott, P. M., Flather, M., Garcia-Pavia, P., Haugaa, K. H., Ingles, J., Jurcut, R. O., Klaassen, S., Limongelli, G., … ESC Scientific Document Group. (2023). 2023 ESC Guidelines for the management of cardiomyopathies. European Heart Journal, 44(37), 3503–3626. https://doi.org/10.1093/eurheartj/ehad194
18. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Skibelund AK; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023 Oct 1;44(37):3627-3639. doi: 10.1093/eurheartj/ehad195. Erratum in: Eur Heart J. 2024 Jan 1;45(1):53. doi: 10.1093/eurheartj/ehad613. PMID: 37622666.
19. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1. Erratum in: J Am Coll Cardiol. 2023 Apr 18;81(15):1551. doi: 10.1016/j.jacc.2023.03.002. PMID: 35379503.
20. Pabon MA, Vardeny O, Vaduganathan M, Desai AS, Claggett BL, Kulac IJ, Jhund PS, Lam CSP, Senni M, Shah SJ, Voors AA, Zannad F, Pitt B, Saldarriaga CI, Petrie MC, Merkely B, Borentain M, Mueller K, Viswanathan P, Amarante F, Morris A, McMurray JJV, Solomon SD. Finerenone in Heart Failure With Improved Ejection Fraction: The FINEARTS-HF Randomized Clinical Trial. JAMA Cardiol. 2025 Jul 1;10(7):740-745. doi: 10.1001/jamacardio.2025.1101. PMID: 40397470; PMCID: PMC12096322.
21. Solomon, S. D., McMurray, J. J. V., Claggett, B., de Boer, R. A., DeMets, D., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S. P., Martinez, F., Shah, S. J., Desai, A. S., Jhund, P. S., Belohlavek, J., Chiang, C.-E., Borleffs, C. J. W., Comin-Colet, J., Dobreanu, D., Drozdz, J., … DELIVER Trial Committees and Investigators. (2022). Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. The New England Journal of Medicine, 387(12), 1089–1098. https://doi.org/10.1056/NEJMoa2206286
22. Siqueira, S. R. O., Pabon, M. A., Vaduganathan, M., Claggett, B. L., Lam, C. S. P., Kosiborod, M. N., de Boer, R. A., Shah, S. J., Fang, J. C., Desai, A. S., Jhund, P. S., Inzucchi, S. E., Martinez, F., Hernandez, A. F., Petersson, M., McMurray, J. J. V., Solomon, S. D., & Vardeny, O. (2025). Achieved ejection fraction and effects of dapagliflozin in heart failure with improved ejection fraction. JACC. Heart Failure, 13(10), 102585. https://doi.org/10.1016/j.jchf.2025.102585
23. Chang DD, Pantlin PG, Benn FA, Ryan Gullatt T, Bernard ML, Elise Hiltbold A, Khatib S, Polin GM, Rogers PA, Velasco-Gonzalez C, Morin DP. Risk of ventricular arrhythmias following implantable cardioverter-defibrillator generator change in patients with recovered ejection fraction: Implications for shared decision-making. J Cardiovasc Electrophysiol. 2023 Jun;34(6):1405-1414. doi: 10.1111/jce.15913. Epub 2023 May 5. PMID: 37146210.
24. Adabag S, Patton KK, Buxton AE, Rector TS, Ensrud KE, Vakil K, Levy WC, Poole JE. Association of Implantable Cardioverter Defibrillators With Survival in Patients With and Without Improved Ejection Fraction: Secondary Analysis of the Sudden Cardiac Death in Heart Failure Trial. JAMA Cardiol. 2017 Jul 1;2(7):767-774. doi: 10.1001/jamacardio.2017.1413. PMID: 28724134; PMCID: PMC5710619.
25. Lyon, A. R., López-Fernández, T., Couch, L. S., Asteggiano, R., Aznar, M. C., Bergler-Klein, J., Boriani, G., Cardinale, D., Cordoba, R., Cosyns, B., Cutter, D. J., de Azambuja, E., de Boer, R. A., Dent, S. F., Farmakis, D., Gevaert, S. A., Gorog, D. A., Herrmann, J., Lenihan, D., … ESC Scientific Document Group. (2022). 2022 ESC guidelines on cardio-oncology developed in collaboration with the European hematology association (EHA), the European society for therapeutic radiology and oncology (ESTRO) and the international cardio-oncology society (IC-OS). European Heart Journal, 43(41), 4229–4361. https://doi.org/10.1093/eurheartj/ehac244
26. Herrmann J, Lerman A, Sandhu NP, Villarraga HR, Mulvagh SL, Kohli M. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin Proc. 2014 Sep;89(9):1287-306. doi: 10.1016/j.mayocp.2014.05.013. PMID: 25192616; PMCID: PMC4258909.
Published
Issue
Section
License
Copyright (c) 2026 The copyright to the submitted manuscript is held by the Author, who grants the Journal of Medical Science (JMS) a nonexclusive licence to use, reproduce, and distribute the work, including for commercial purposes.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

