What is heart failure with improved ejection fraction?

What is heart failure with improved ejection fraction?

Heart failure with improved ejection fraction (HFimpEF) is heart failure with a baseline left ventricular ejection fraction of 40% or less, a 10 point or more increase from baseline left ventricular ejection fraction, and a second measurement of left ventricular ejection fraction of more than 40% [1]. This was known as of heart failure with recovered ejection fraction (HFrecEF) earlier [2]. The terminology has been revised as per the universal definition and classification of heart failure published in 2021. The universal definition and classification has been published by a joint writing committee of Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology and Japanese Heart Failure Society [1]. The definition has been endorsed by major heart failure societies world wide.

In the initial report cited as [2] above, of a total of 358 patients in their retrospective analysis, 121 had recovered left ventricular ejection fraction. They had the mildest reported heart failure symptoms and fewest previous heart failure hospitalizations.

The Penn Heart Failure Study was a prospective cohort of 1821 chronic heart failure patients recruited from tertiary heart failure clinics [3]. They defined heart failure with recovered ejection fraction if ejection fraction on enrollment was  50% or more, but prior ejection fraction was less than 40%. Many of them had abnormal biomarker profile at baseline including 44% with detectable troponin I. But median levels of brain natriuretic peptide, troponin I and creatinine were greater in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. The authors concluded that the group of heart failure with recovered ejection fraction had better event-free survival than the other two groups.

Normalization of left ventricular systolic function was associated with a significant improvement in health-related quality of life in another brief report [4]. They noted that for each 10% increase in left ventricular ejection fraction, the Kansas City Cardiomyopathy Questionnaire score improved by a mean  of 4.8 points (P = .003).

A word of caution is needed in the discussion on heart failure with improved ejection fraction. Recovered ejection fraction need not mean that the heart has recovered fully. TRED-HF study showed that many patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal [5]. The study had enrolled 51 patients in 2016-2017. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. 44% of those assigned to treatment withdrawal had relapse compared to none in the group assigned to continue treatment over the first 6 months. After 6 months 25 of the 26 patients initially assigned to continue treatment attempted its withdrawal. During the following 6 months, 9 of them had a relapse. No deaths were reported in either groups.

Based on these observations, JACC Scientific Expert Panel has recommended that guideline directed medical therapy should not be stopped in those with recovered ejection fraction [6]. The panel report also suggested that those already on an implantable cardioverter defibrillator (ICD) will benefit from the continued usage as a meta-analysis [7] had shown a 3.3% per year rate of appropriate ICD therapy among those with left ventricular ejection fraction of 45% or more. They also mentioned that as a rule, cardiac resynchronization therapy should be maintained because electrical dyssynchrony and forward left ventricular remodeling are known to recur with loss of resynchronization.

References

1. Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, Anker SD, Atherton J, Böhm M, Butler J, Drazner MH, Felker GM, Filippatos G, Fonarow GC, Fiuzat M, Gomez-Mesa JE, Heidenreich P, Imamura T, Januzzi J, Jankowska EA, Khazanie P, Kinugawa K, Lam CSP, Matsue Y, Metra M, Ohtani T, Francesco Piepoli M, Ponikowski P, Rosano GMC, Sakata Y, SeferoviĆ P, Starling RC, Teerlink JR, Vardeny O, Yamamoto K, Yancy C, Zhang J, Zieroth S. Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. 2021 Mar 1:S1071-9164(21)00050-6. doi: 10.1016/j.cardfail.2021.01.022. Epub ahead of print. PMID: 33663906.
2. Punnoose LR, Givertz MM, Lewis EF, Pratibhu P, Stevenson LW, Desai AS. Heart failure with recovered ejection fraction: a distinct clinical entity. J Card Fail. 2011 Jul;17(7):527-32. doi: 10.1016/j.cardfail.2011.03.005. Epub 2011 May 6. PMID: 21703523.
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5. 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.
6. Wilcox JE, Fang JC, Margulies KB, Mann DL. Heart Failure With Recovered Left Ventricular Ejection Fraction: JACC Scientific Expert Panel. J Am Coll Cardiol. 2020 Aug 11;76(6):719-734. doi: 10.1016/j.jacc.2020.05.075. PMID: 32762907.
7. Smer A, Saurav A, Azzouz MS, Salih M, Ayan M, Abuzaid A, Akinapelli A, Kanmanthareddy A, Rosenfeld LE, Merchant FM, Abuissa H. Meta-analysis of Risk of Ventricular Arrhythmias After Improvement in Left Ventricular Ejection Fraction During Follow-Up in Patients With Primary Prevention Implantable Cardioverter Defibrillators. Am J Cardiol. 2017 Jul 15;120(2):279-286. doi: 10.1016/j.amjcard.2017.04.020. Epub 2017 Apr 27. PMID: 28532779.