Abstract
Heart failure with reduced ejection fraction (HFrEF) is a prevalent kind of heart
failure in which a significant amount of the ejection fraction can be repaired, and
left ventricular remodeling and dysfunction can be reversed or even restored completely.
However, a considerable number of patients still present clinical signs and biochemical
features of incomplete recovery from the pathophysiology of heart failure and are
at risk for adverse outcomes such as re-deterioration of systolic function and recurrence
of HFrEF. Furthermore, it is revealed from a microscopic perspective that even if
partial or complete reverse remodeling occurs, the morphological changes of cardiomyocytes,
extracellular matrix deposition, and abnormal transcription and expression of pathological
genes still exist. Patients with “recovered ejection fraction” have milder clinical
symptoms and better outcomes than those with continued reduction of ejection fraction.
Based on the unique characteristics of this subgroup and the existence of many unknowns,
the academic community defines it as a new category-heart failure with recovered ejection
fraction (HFrecEF). Because there is a shortage of natural history data for this population
as well as high-quality clinical and basic research data, it is difficult to accurately
evaluate clinical risk and manage this population. This review will present the current
understanding of HFrecEF from the limited literature.
Keywords
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References
- Heart failure with reduced ejection fraction: a review.JAMA. 2020; 324: 488-504
- Dynamic trajectories of left ventricular ejection fraction in heart failure.J Am Coll Cardiol. 2018; 72: 591-601
- Heart failure with improved ejection fraction: is it possible to escape one's past?.JACC Heart Fail. 2018; 6: 725-733
- 2013ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2013; 62: e147-e239
- Heart failure with myocardial recovery - the patient whose heart failure has improved: what Next?.Prog Cardiovasc Dis. 2017; 60: 226-236
- Heart failure with recovered left ventricular ejection fraction: JACC scientific expert panel.J Am Coll Cardiol. 2020; 76: 719-734
- Variability in Ejection fraction measured by echocardiography, gated single-photon emission computed tomography, and cardiac magnetic resonance in patients with coronary artery disease and left ventricular dysfunction.JAMA Netw Open. 2018; 1e181456
- The continuous heart failure spectrum: moving beyond an ejection fraction classification.Eur Heart J. 2019; 40: 2155-2163
- ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for thediagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur Heart J. 2016; 37: 2129-2200
- Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction.Circ Heart Fail. 2012; 5: 720-726
- What have we learned about heart failure with mid-range ejection fraction one year after its introduction?.Eur J Heart Fail. 2017; 19: 1569-1573
- Epidemiology and natural history of recovery of left ventricular function in recent onset dilated cardiomyopathies.Curr Heart Fail Rep. 2013; 10: 321-330
- Myocardial recovery and the failing heart: myth, magic, or molecular targe?.J Am Coll Cardiol. 2012; 60: 2465-2472
- Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading.Circulation. 1995; 91: 2717-2720
- Reverse remodeling and myocardial recovery in heart failure.Nat Rev Cardiol. 2018; 15: 83-96
- Mixed messages: transcription patterns in failing and recovering human myocardium.Circ Res. 2005; 96: 592-599
- Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling.JCI Insight. 2016; 1: e86038
- Myocardial recovery after LVAD implantation: a vision or simply an illusion?.J Am Coll Cardiol. 2017; 70: 355-357
- The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review.Heart. 2001; 85: 499-504
- Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a meta-analytic approach.J Am Coll Cardiol. 2010; 56: 392-406
- Clinical outcomes for peripartum cardiomyopathy in North America: results of the IPAC Study (investigations of pregnancy-associated cardiomyopathy).J Am Coll Cardiol. 2015; 66: 905-914
- Heart failure with recovered ejection fraction: a distinct clinical entity.J Card Fail. 2011; 17: 527-532
- Characteristics and outcomes of adult outpatients with heart failure and improved or recovered ejection fraction.JAMA Cardiol. 2016; 1: 510-518
- Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes.Circulation. 2014; 129: 2380-2387
- Heart failure with improved ejection fraction: clinical characteristics, correlates of recovery, and survival: results from the Valsartan Heart Failure Trial.Circ Heart Fail. 2016; 9e003123
- 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..Circulation. 2014; 130: 2278-2286
- Remission of left ventricular systolic dysfunction and of heart failure symptoms after cardiac resynchronization therapy: temporal pattern and clinical predictors.Am Heart J. 2008; 155: 507-514
- Identification and characterization of super-responders after cardiac resynchronization therapy.Am J Cardiol. 2010; 105: 1327-1335
- True complete left bundle branch block morphology strongly predicts good response to cardiac resynchronization therapy.Europace. 2013; 15: 1499-1506
- Recovered heart failure with reduced ejection fraction and outcomes: a prospective study.Eur J Heart Fail. 2017; 19: 1615-1623
- Factors associated with improvement in ejection fraction in clinical practice among patients with heart failure: findings from improve HF.Am Heart J. 2012; 163 (e2): 49-56
- Effect of sex on reverse remodeling in chronic systolic heart failure.JACC Heart Fail. 2017; 5: 735-742
- What we can learn from “super-responders”.Heart Fail Clin. 2017; 13: 225-232
- Predictors of super-response to cardiac resynchronization therapy and associated improvement in clinical outcome: the MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy) study.J Am Coll Cardiol. 2012; 59: 2366-2373
- Impaired recovery of left ventricular function in patients with cardiomyopathy and left bundle branch block.J Am Coll Cardiol. 2018; 71: 306-317
- NT-proBNP Goal achievement is associated with significant reverse remodeling and improved clinical outcomes in HFrEF.JACC Heart Fail. 2019; 7: 158-168
- Design and methods of the Pro-B type natriuretic peptide outpatient tailored chronic heart failure therapy (PROTECT) study.Am Heart J. 2010; 159: 532-538
- Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony.Eur Heart J. 2007; 28: 1592-1597
- Prediction of survival and magnitude of reverse remodeling using the ST2-R2 score in heart failure: a multicenter study.Int J Cardiol. 2016; 204: 242-247
- Biomarker-assist score for reverse remodeling prediction in heart failure: the ST2-R2 score.Int J Cardiol. 2015; 184: 337-343
- Concentrations of highly sensitive cardiactroponin-I predict poor cardiovascular outcomes and adverse remodeling in chronic heart failure.J Cardiovasc Transl Res. 2015; 8: 164-172
- Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure.JACC Heart Fail. 2014; 2: 65-72
- Galectin-3 as a predictor of left ventricular reverse remodeling in recent-onset dilated cardiomyopathy.Dis Markers. 2018; 20182958219
- MicroRNAs associated with reverse left ventricular remodeling in humans identify pathways of heart failure progression.Circ Heart Fail. 2018; 11e004278
- Measurement of novel biomarkers to predict chronic heart failure outcomes and left ventricular remodeling.J Cardiovasc Transl Res. 2014; 7: 250-261
- Circulating concentrations of orexin A predict left ventricular myocardial remodeling.J Am Coll Cardiol. 2016; 68: 2238-2240
- Prognostic relevance of gene-environment interactions in patients with dilated cardiomyopathy: applying the MOGE(S) classification.J Am Coll Cardiol. 2015; 66: 1313-1323
- Clinical phenotype and genotype associations with improvement in left ventricular function in dilated cardiomyopathy.Circ Heart Fail. 2018; 11e005220
- Progression of left ventricular dysfunction and remodelling under optimal medical therapy in CHF Patients: role of individual genetic background.Cardiol Res Pract. 2011; 2011: 1-6
- Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy.Eur J Heart Fail. 2017; 19: 512-521
- Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy.Heart. 2017; 103: 1704-1710
- Relationship between ultrasonic tissue characterization and myocardial deformation for prediction of left ventricular reverse remodelling in non-ischaemic dilated cardiomyopathy.Eur J Echocardiogr. 2011; 12: 887-894
- Myocardial interstitial remodelling in non-ischaemic dilated cardiomyopathy: insights from cardiovascular magnetic resonance.Heart Fail Rev. 2015; 20: 731-749
- Clinical significance of endomyocardial biopsy in conjunction with cardiac magnetic resonance imaging to predict left ventricular reverse remodeling in idiopathic dilated cardiomyopathy.Heart Vessels. 2016; 31: 1960-1968
- Longitudinal strain combined with delayed-enhancement magnetic resonance improves risk stratification in patients with dilated cardiomyopathy.Heart. 2017; 103: 679-686
- Late gadolinium enhancement as a predictor of functional recovery, need for defibrillator implantation and prognosis in non-ischemic dilated cardiomyopathy.Int J Cardiol. 2018; 250: 195-200
- Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study.Circ Cardiovasc Imaging. 2013; 6: 790-799
- Late gadolinium enhancement on cardiac magnetic resonance images predicts reverse remodeling in patients with nonischemic cardiomyopathy treated with carvedilol.Int J Cardiol. 2013; 168: 1588-1589
- Reliability of ventricular remodeling as a surrogate for use in conjunction with clinical outcomes in heart failure.Am J Cardiol. 2005; 96: 867-871
- Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group.Circulation. 1993; 87: VI17-VI23
- Long-term functional and clinical follow-up of patients with heart failure with recovered left ventricular ejection fraction after β-blocker therapy.Circ Heart Fail. 2014; 7: 434-439
- Heart failure and midrange ejection fraction: implications of recovered ejection fraction for exercise tolerance and outcomes.Circ Heart Fail. 2016; 9e002826
- Recurrence of left ventricular dysfunction in patients with restored idiopathic dilated cardiomyopathy.Clin Cardiol. 2014; 37: 222-226
- Frequency of recovery and relapse in patients with nonischemic dilated cardiomyopathy on guideline-directed medical therapy.Am J Cardiol. 2014; 114: 883-889
- Recovery and relapse of left ventricular systolic dysfunction in hospitalized patients with dilated cardiomyopathy: frequency and related factors.Zhonghua Xin. Xue Guan Bing Za Zhi. 2015; 43: 1034-1039
- Very long-term follow-up data of non-ischemic idiopathic dilated cardiomyopathy after beta-blocker therapy: recurrence of left ventricular dysfunction and predictive value of I-metaiodobenzylguanidine scintigraphy.Heart Vessels. 2019; 34: 259-267
- Left ventricular reverse remodeling in dilated cardiomyopathy- maintained subclinical myocardial systolic and diastolic dysfunction.Int J Cardiovasc Imaging. 2017; 33: 605-613
- Can medications be safely withdrawn in patients with stable chronic heart failure? systematic review and meta-analysis.J Card Fail. 2014; 20: 522-532
- Recovery and recurrence of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy.Can J Cardiol. 2009; 25: e147-e150
- Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial.Lancet. 2019; 393: 61-73
- Stopping medication for heart failure with improved ejection fraction.Lancet. 2019; 393: 8-10
- Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure.Circulation. 2002; 105: 438-445
- Incidence of appropriate shock in implantable cardioverter-defibrillator patients with improved ejection fraction.J Card Fail. 2013; 19: 426-430
- 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; 2: 767-774
- Changes in Follow-up left ventricular ejection fraction associated with outcomes in primary prevention implantable cardioverter-defibrillator and cardiac resynchronization therapy device recipients.J Am Coll Cardiol. 2015; 66: 524-531
- Appropriateness of primary prevention implantable cardioverter-defibrillators at the time of generator replacement: are indications still met?.J Am Coll Cardiol. 2014; 63: 2388-2394
- Outcomes following implantable cardioverter-defibrillator generator replacement in patients with recovered left ventricular systolic function: the National Cardiovascular Data Registry.Heart Rhythm. 2019; 16: 733-740
- Genetic evaluation of cardiomyopathy-a heart failure Society of America Practice Guideline.J Card Fail. 2018; 24: 281-302
Article Info
Publication History
Published online: September 06, 2022
Accepted:
July 12,
2022
Received:
August 23,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
