Clinical management of heart failure with improved ejection fraction: treatment and maintenance

doi:10.3969/j.issn.1674-8115.2025.04.012

Abstract

Abstract:

In patients with heart failure with reduced ejection fraction (HFrEF), some individuals demonstrate significant improvement in left ventricular ejection fraction (LVEF) during subsequent evaluations after treatment. The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) heart failure management guidelines introduced the term "heart failure with improved ejection fraction (HFimpEF)" to describe patients with prior LVEF≤40% that subsequently increased above 40% during follow-up. Studies indicate that HFimpEF patients exhibit lower all-cause mortalities and heart failure rehospitalization rates, with a significantly better prognosis compared to HFrEF patients, establishing HFimpEF as a staged therapeutic target for HFrEF. Current discussion on HFimpEF primarily focuses on two aspects: characteristics of the target population and effective methods for LVEF improvement, and maintenance strategies for cardiac function preservation in HFimpEF patients; particularly the latter lacks clear clinical-guideline recommendations. Therefore, reviewing existing research to systematically summarize therapeutic strategies that promote the HFrEF-to-HFimpEF transition and effective maintenance approaches for HFimpEF becomes crucial. This article comprehensively reviews the LVEF-improving effects of current pharmacological, device-based, and surgical interventions, along with monitoring and management strategies for HFimpEF patients. In HFrEF patients, clinical evidence suggests that β-blockers and cardiac resynchronization therapy can significantly improve LVEF beyond 40%. Regarding HFimpEF management, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and renin-angiotensin system inhibitors (RASi) demonstrate efficacy in maintaining LVEF and cardiac function. Additionally, this review identifies current research limitations in HFimpEF and proposes potential future research directions.

Key words: heart failure, heart failure with improved ejection fraction (HFimpEF), heart failure with reduced ejection fraction (HFrEF), prognosis

CLC Number:

R541.6

XU Tianyun, SHEN Yiming, JIANG Meng. Clinical management of heart failure with improved ejection fraction: treatment and maintenance[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(4): 493-499.

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References 49

1	Writing Committee Members, ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure[J]. J Card Fail, 2022, 28(5): e1-e167.
2	王华, 刘宇佳, 杨杰孚. 心力衰竭流行病学[J]. 临床心血管病杂志, 2023, 39(4): 243-247.
	WANG H, LIU Y J, YANG J F. Epidemiology of heart failure[J]. Journal of Clinical Cardiology, 2023, 39(4): 243-247.
3	HE Y B, LING Y H, GUO W, et al. Prevalence and prognosis of HFimpEF developed from patients with heart failure with reduced ejection fraction: systematic review and meta-analysis[J]. Front Cardiovasc Med, 2021, 8: 757596.
4	GULATI G, UDELSON J E. Heart failure with improved ejection fraction: is it possible to escape one's past?[J]. JACC Heart Fail, 2018, 6(9): 725-733.
5	WILCOX J E, FANG J C, MARGULIES K B, et al. Heart failure with recovered left ventricular ejection fraction: JACC scientific expert panel[J]. J Am Coll Cardiol, 2020, 76(6): 719-734.
6	FLOREA V G, RECTOR T S, ANAND I S, et al. Heart failure with improved ejection fraction: clinical characteristics, correlates of recovery, and survival: results from the valsartan heart failure trial[J]. Circ Heart Fail, 2016, 9(7): e003123.
7	PARK C S, PARK J J, MEBAZAA A, et al. Characteristics, outcomes, and treatment of heart failure with improved ejection fraction[J]. J Am Heart Assoc, 2019, 8(6): e011077.
8	CHUDÝ M, GONCALVESOVÁ E. Prediction of left ventricular reverse remodelling: a mini review on clinical aspects[J]. Cardiology, 2022, 147(5/6): 521-528.
9	TOPKARA V K, CHAMBERS K T, YANG K C, et al. Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling[J]. JCI Insight, 2016, 1(4): e86038.
10	JANSWEIJER J A, NIEUWHOF K, RUSSO F, et al. Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy[J]. Eur J Heart Fail, 2017, 19(4): 512-521.
11	JANWANISHSTAPORN S, CHO J Y, FENG S T, et al. Prognostic value of global longitudinal strain in patients with heart failure with improved ejection fraction[J]. JACC Heart Fail, 2022, 10(1): 27-37.
12	PENSA A V, KHAN S S, SHAH R V, et al. Heart failure with improved ejection fraction: beyond diagnosis to trajectory analysis[J]. Prog Cardiovasc Dis, 2024, 82: 102-112.
13	JØRGENSEN M E, ANDERSSON C, VASAN R S, et al. Characteristics and prognosis of heart failure with improved compared with persistently reduced ejection fraction: a systematic review and meta-analyses[J]. Eur J Prev Cardiol, 2018, 25(4): 366-376.
14	HO L T, JUANG J J, CHEN Y H, et al. Predictors of left ventricular ejection fraction improvement in patients with early-stage heart failure with reduced ejection fraction[J]. Acta Cardiol Sin, 2023, 39(6): 854-861.
15	BASURAY A, FRENCH B, KY B, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes[J]. Circulation, 2014, 129(23): 2380-2387.
16	PAOLINI C, MUGNAI G, DALLA VALLE C, et al. Effects and clinical implications of sacubitril/valsartan on left ventricular reverse remodeling in patients affected by chronic heart failure: a 24-month follow-up[J]. Int J Cardiol Heart Vasc, 2021, 35: 100821.
17	WANG Y W, ZHOU R, LU C, et al. Effects of the angiotensin-receptor neprilysin inhibitor on cardiac reverse remodeling: meta-analysis[J]. J Am Heart Assoc, 2019, 8(13): e012272.
18	SHAH A M, CLAGGETT B, PRASAD N, et al. Impact of sacubitril/valsartan compared with ramipril on cardiac structure and function after acute myocardial infarction: the PARADISE-MI echocardiographic substudy[J]. Circulation, 2022, 146(14): 1067-1081.
19	ENZAN N, MATSUSHIMA S, IDE T, et al. The use of angiotensin-converting enzyme inhibitors or angiotensin Ⅱ receptor blockers is associated with the recovered ejection fraction in patients with dilated cardiomyopathy[J]. Int Heart J, 2021, 62(4): 801-810.
20	SANTOS-GALLEGO C G, VARGAS-DELGADO A P, REQUENA-IBANEZ J A, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction[J]. J Am Coll Cardiol, 2021, 77(3): 243-255.
21	LEE M M Y, BROOKSBANK K J M, WETHERALL K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)[J]. Circulation, 2021, 143(6): 516-525.
22	OMAR M, JENSEN J, ALI M, et al. Associations of empagliflozin with left ventricular volumes, mass, and function in patients with heart failure and reduced ejection fraction: a substudy of the empire HF randomized clinical trial[J]. JAMA Cardiol, 2021, 6(7): 836-840.
23	SHEHRAM M, KHALID H, SHAFIQUE H M, et al. Efficacy and safety of cardiac resynchronization therapy in chemotherapy-induced cardiomyopathy: a systematic review[J]. Ann Noninvasive Electrocardiol, 2023, 28(5): e13070.
24	BASURAY A, FANG J C. Management of patients with recovered systolic function[J]. Prog Cardiovasc Dis, 2016, 58(4): 434-443.
25	RUWALD M H, SOLOMON S D, FOSTER E, et al. Left ventricular ejection fraction normalization in cardiac resynchronization therapy and risk of ventricular arrhythmias and clinical outcomes: results from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial[J]. Circulation, 2014, 130(25): 2278-2286.
26	ZECCHIN M, PROCLEMER A, MAGNANI S, et al. Long-term outcome of 'super-responder' patients to cardiac resynchronization therapy[J]. Europace, 2014, 16(3): 363-371.
27	SINGH J P, SOLOMON S D, FRADLEY M G, et al. Association of cardiac resynchronization therapy with change in left ventricular ejection fraction in patients with chemotherapy-induced cardiomyopathy[J]. JAMA, 2019, 322(18): 1799-1805.
28	FADOL A P, MOUHAYAR E, REYES-GIBBY C C. The use of cardiac resynchronization therapy in cancer patients with heart failure[J]. J Clin Exp Res Cardiol, 2017, 3(1): 10.15744/2394-10.15744/6504.3.105.
29	LI Q, QIAO Y, TANG J, et al. Frequency, predictors, and prognosis of heart failure with improved left ventricular ejection fraction: a single-centre retrospective observational cohort study[J]. ESC Heart Fail, 2021, 8(4): 2755-2764.
30	MOSS A J, ZAREBA W, JACKSON HALL W, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction[J]. N Engl J Med, 2002, 346(12): 877-883.
31	ZHANG Y Y, GUALLAR E, BLASCO-COLMENARES E, et al. Changes in follow-up left ventricular ejection fraction associated with outcomes in primary prevention implantable cardioverter-defibrillator and cardiac resynchronization therapy device recipients[J]. J Am Coll Cardiol, 2015, 66(5): 524-531.
32	NAKSUK N, SAAB A, LI J M, et al. Incidence of appropriate shock in implantable cardioverter-defibrillator patients with improved ejection fraction[J]. J Card Fail, 2013, 19(6): 426-430.
33	SCHAER B, THEUNS D A, STICHERLING C, et al. Effect of implantable cardioverter-defibrillator on left ventricular ejection fraction in patients with idiopathic dilated cardiomyopathy[J]. Am J Cardiol, 2010, 106(11): 1640-1645.
34	SCHLIAMSER J E, KADISH A H, SUBACIUS H, et al. Significance of follow-up left ventricular ejection fraction measurements in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation trial (DEFINITE)[J]. Heart Rhythm, 2013, 10(6): 838-846.
35	ZELLER J, HUBAUER U, SCHOBER A, et al. Heart failure with recovered ejection fraction (HFrecEF): a new entity with improved cardiac outcome[J]. Pacing Clin Electrophysiol, 2021, 44(12): 2015-2023.
36	HEIDENREICH P A, BOZKURT B, AGUILAR D, et al. 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]. Circulation, 2022, 145(18): e895-e1032.
37	KLEIN N, KUNTZ T, DHEIN S. Avoiding implantation of a cardioverter-defibrillator by bridging with wearable defibrillator vest[J]. Herz, 2021, 46(2): 172-177.
38	KLEIN H U, GOLDENBERG I, MOSS A J. Risk stratification for implantable cardioverter defibrillator therapy: the role of the wearable cardioverter-defibrillator[J]. Eur Heart J, 2013, 34(29): 2230-2242.
39	TODA K, MACKENZIE K, MEHRA M R, et al. Revascularization in severe ventricular dysfunction (15%≤LVEF≤30%): a comparison of bypass grafting and percutaneous intervention[J]. Ann Thorac Surg, 2002, 74(6): 2082-2087.
40	ADABAG S, CARLSON S, GRAVELY A, et al. Improvement of left ventricular function with surgical revascularization in patients eligible for implantable cardioverter-defibrillator[J]. J Cardiovasc Electrophysiol, 2022, 33(2): 244-251.
41	HALLIDAY B P, WASSALL R, LOTA A S, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial[J]. Lancet, 2019, 393(10166): 61-73.
42	MANN D L, BARGER P M, BURKHOFF D. Myocardial recovery and the failing heart: myth, magic, or molecular target?[J]. J Am Coll Cardiol, 2012, 60(24): 2465-2472.
43	VARDENY O, FANG J C, DESAI A S, et al. Dapagliflozin in heart failure with improved ejection fraction: a prespecified analysis of the DELIVER trial[J]. Nat Med, 2022, 28(12): 2504-2511.
44	PABON M, CLAGGETT B L, WANG X W, et al. Influence of background medical therapy on efficacy and safety of dapagliflozin in patients with heart failure with improved ejection fraction in the DELIVER trial[J]. Eur J Heart Fail, 2023, 25(9): 1663-1670.
45	MCELDERRY B, O'NEILL T, GRIFFIN B P, et al. Factors associated with maintenance of an improved ejection fraction: an echocardiogram-based registry study[J]. J Am Heart Assoc, 2023, 12(21): e031093.
46	CHEN Y J, QIU Z P, JIANG J, et al. Outcomes of spironolactone withdrawal in dilated cardiomyopathy with improved ejection fraction[J]. Front Cardiovasc Med, 2021, 8: 725399.
47	YU C M, CHAU E, SANDERSON J E, et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure[J]. Circulation, 2002, 105(4): 438-445.
48	BAMAN J R, PATIL K D, MEDHEKAR A N, et al. Primary prevention implantable cardioverter-defibrillator therapy in heart failure with recovered ejection fraction[J]. J Card Fail, 2021, 27(5): 585-596.
49	CHEN X, WU M F. Heart failure with recovered ejection fraction: current understanding and future prospects[J]. Am J Med Sci, 2023, 365(1): 1-8.

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