Heart Failure with Recovered EF and Heart Failure with Mid-Range EF: Current Recommendations and Controversies

  • Peter Unkovic
  • Anupam Basuray
Heart Failure (W Tang, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Heart Failure


Purpose of review

This review explores key features and potential management controversies in two emerging populations in heart failure: heart failure with recovered ejection fraction (HF-recovered EF) and heart failure with mid-range ejection fraction (HFmrEF).

Recent findings

While HF-recovered EF patients have better outcomes than heart failure with reduced ejection fraction (HFrEF), they continue to have symptoms, persistent biomarker elevations, and abnormal outcomes suggesting a continued disease process. HFmrEF patients appear to have features of HFrEF and heart failure with preserved ejection fraction (HFpEF), but have a high prevalence of ischemic heart disease and may represent a transitory phase between the HFrEF and HFpEF. Management strategies have insufficient data to warrant standardization at this time.


HF-recovered EF and HFmrEF represent new populations with unmet needs and expose the pitfalls of an EF basis for heart failure classification.


Heart failure Recovered ejection fraction Mid-range ejection fraction 


Compliance with Ethical Standards

Conflict of Interest

Peter Unkovic and Anupam Basuray each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Yancy C, Jessup M, Bozkurt B, Butler J, Casey D Jr, Drazner M, et al. 2013 ACCF/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. Circulation. 2013;128:e240–327.CrossRefPubMedGoogle Scholar
  2. 2.
    • Punnoose L, Givertz M, Lewis E, Pratibhu P, Stevenson L, Desai A. Heart failure with recovered ejection fraction: a distinct clinical entity. J Card Fail. 2011;17(7):527–32. This paper was the first to describe HF-Recovered EF out of a group of patients who were labeled as HFpEF, suggesting that HFrEF patients who improve ejection fraction are a distinct population.CrossRefPubMedGoogle Scholar
  3. 3.
    • Basuray A, French B, Ky B, Vorovich E, Olt C, Sweitzer N, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers and outcomes. Circulation. 2014;129(23):2380–7. This paper was the first to demonstrate that despite a normalized LVEF, patients with a recovered EF were not normal as demonstrated by clinical charactersitics, biomarkers, and outcomes.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ponikowski P, Voors A, Anker S, Bueno H, Cleland J, Coats A, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2129–200.CrossRefPubMedGoogle Scholar
  5. 5.
    Cohn J, Ferrari R, Sharpe N. Cardiac remodeling—concepts and clinical implications: a concensus paper from an international forum on cardiac remodeling. Behalf of an international forum on Cardiac remodeling. J Am Coll Cardiol. 2000;35(3):569–82.CrossRefPubMedGoogle Scholar
  6. 6.
    Merlo M, Stolfo D, Anzini M, Negri F, Pinamonti B, Barbati G, et al. Persistent recovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long-term follow-up: does real healing exist? J Am Heart Assoc. 2015;4(1).Google Scholar
  7. 7.
    Kubanek M, Sramko M, Maluskova J, Kautznerova D, Weichet J, Lupinek P, et al. Novel predictors of left ventricular reverse remodeling in individuals with recent-onset dilated cardiomyopathy. J Am Coll Cardiol. 2013;61:54–63.CrossRefPubMedGoogle Scholar
  8. 8.
    Semigran M, Thaik C, Fifer M, Boucher C, Palacios I, Dec G. Exercise capacity and systolic and diastolic ventricular function after recovery from acute dilated cardiomyopathy. J Am Coll Cardiol. 1994;24(2):462–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Zecchin M, Proclemer A, Magnani S, Vitali-Serdoz L, Facchin D, Muser D, et al. Long-term outcome of ‘super-responder’ patients to cardiac resynchronization therapy. Europace. 2014;16:363–71.CrossRefPubMedGoogle Scholar
  10. 10.
    de Groote P, Fertin M, Pentiah A, Goeminne C, Lamblin N, Bauters C. Long-term functional and clinical follow-up of patients with heart failure with recovered left ventricular ejection fraction after beta-blocker therapy. Circ Heart Fail. 2014;7:434–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Moon J, Ko YG, Chung N, et al. Recovery and recurrance of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy. Can J Cardiol. 2009;25:e147–50.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Adamo L, Perry A, Novak E, Makan M, Lindman B, Mann D. Abnormal global longitudinal strain predicts future deterioration of left ventricular function in heart failure patients with a recovered left ventricular ejection fraction. Circ Heart Fail. 2017;10(6):e003788.CrossRefPubMedGoogle Scholar
  13. 13.
    •• Mann D, Barger P, Burkhoff D. Myocardial recovery and the failing heart: myth, magic, or molecular target? J Am Coll Cardiol. 2012;60(24):2465–72. Excellent explanation of existing data and propositions for future studies on the mechanism of myocardial recovery. It is also a comprehensive review of the myocardial recovery literature.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Drakos S, Kfoury A, Stehlik J, Selzman C, Reid B, Terrovitis J, et al. Bride to recovery, understanding the disconnect between clinical and biological outcomes. Circulation. 2012;126(2):230–41.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Frazier O, Benedict C, Radovancevic B, Bick R, Capek P, Springer W, et al. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg. 1996;62(3):675–81.CrossRefPubMedGoogle Scholar
  16. 16.
    Ahmad T, Wang T, O’Brien E, Samsky M, Pura J, Lokhnygina Y, et al. Effects of left ventricular assist device support on biomarkers of cardiovascular stress, fibrosis, fluid homeostasis, inflammation, and renal injury. JACC Heart Fail. 2015;3(1):30–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Felker G, Anstrom K, Adams K, Ezekowitz J, Fiuzat M, Houston-Miller N, et al. Effect of natriuretic peptide–guided therapy on hospitalization or cardiovascular mortality in high risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2017;318(8):713–20.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Birks E, Tansley P, Hardy J, George R, Bowles C, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. NEJM. 2006;355(18):1873–84.CrossRefPubMedGoogle Scholar
  19. 19.
    • Birks E, George R, Hedger M, Bahrami T, Wilton P, Bowles C, et al. Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: a prospective study. Circulation. 2011;123(4):381–90. LVAD data showing that myocardial recovery leading to LVAD explantation can be achieved with proper patient selection and intense medical management.CrossRefPubMedGoogle Scholar
  20. 20.
    Kirklin J, Pagani F, Kormos R, Stevenson L, Blume E, Myers S, et al. Eigth annual INTERMACS report: Special focus on framing the impact of adverse events. J Heart Lung Tranplant. 2014;36(10):1080–6.CrossRefGoogle Scholar
  21. 21.
    Basuray A, Fang J. Management of patients with recovered systolic function. Prog Cardiovasc Dis. 2015;58(4):434–43.CrossRefGoogle Scholar
  22. 22.
    •• Shah K, Xu H, Matsouaka R, Bhatt D, Heidenreich P, Hernandez A, et al. Heart failure with preserved, borderline, and reduced ejection fraction 5-year outcomes. J Am Coll Cardiol. 2017;70(20):2476–86. This article was pertinent because it used a large cohort to demonstrate that mortality after a HF hospitalization was uniformly associated with poor event-free survival regardless of EF.CrossRefPubMedGoogle Scholar
  23. 23.
    Vedin O, Lam C, Koh A, Benson L, Teng T, Tay W, et al. Significance of ischemic heart disease in patients with heart failure and preserved, midrange, and reduced ejection fraction: a nationwide cohort study. Circ Heart Fail. 2017;10(6):e003875.CrossRefPubMedGoogle Scholar
  24. 24.
    Chioncel O, Lainscak M, Seferovic P, Anker S, Crespo-Leiro M, Harjola V, et al. Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2017;19:1574–85.CrossRefPubMedGoogle Scholar
  25. 25.
    Rickenbacher P, Kaufmann B, Maeder M, Bernheim A, Goetschalckx K, Pfister O, et al. Heart failure with mid-range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF). Eur J Heart Fail. 2017;19:1586–96.CrossRefPubMedGoogle Scholar
  26. 26.
    Kapoor J, Kapoor R, Ju C, Heidenreich P, Eapen Z, Hernandez A, et al. Precipitating clinical factors, heart failure characterization, and outcomes in patients hospitalized with heart failure with reduced, borderline, and preserved ejection fraction. JACC Heart Fail. 2016;4(6):464–72.CrossRefPubMedGoogle Scholar
  27. 27.
    Sartipy U, Dahlström U, Fu M, Lund L. Atrial fibrillation in heart failure with preserved, mid-range, and reduced ejection fraction. JACC: Heart Fail. 2017;5:565–74.Google Scholar
  28. 28.
    Sato T, Yoshihisa A, Kanno Y, Suzuki S, Yamaki T, Sugimoto K, et al. Cardiopulmonary exercise testing as prognostic indicators: comparisons among heart failure patients with reduced, mid-range and preserved ejection fraction. Eur J Prev Cardiol. 2017;24(18):1979–87.CrossRefPubMedGoogle Scholar
  29. 29.
    • Nadruz W, West E, Santos M, Skali H, Groarke J, Forman D, et al. Heart failure and midrange ejection fraction implications of recovered ejection fraction for exercise tolerance and outcomes. Circ: Heart Fail. 2016;9(4):e002826. First study to suggest HFmrEF group is heterogeneous and that those who recovered from HFrEF have a more favorable phenotype.Google Scholar
  30. 30.
    Tromp J, Khan M, Mentz R, O’Connor C, Metra M, Dittrich H, et al. Biomarker profiles of acute heart failure patients with a mid-range ejection fraction. JACC: Heart Fail. 2017;5(7):507–17.Google Scholar
  31. 31.
    Rastogi A, Novak E, Platts A, Mann D. Epidemiology, pathophysiology and clinical outcomes for heart failure patients with a mid-range ejection fraction. Eur J Heart Fail. 2017;19:1597–605.CrossRefPubMedGoogle Scholar
  32. 32.
    Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, et al. Characterization of heart failure patients with mid-range left ventricular ejection fraction—a report from the CHART-2 Study. Eur J Heart Fail. 2017;19:1258–69.CrossRefPubMedGoogle Scholar
  33. 33.
    Lam C, Solomon S. Fussing over the middle child. Circulation. 2017;135:1279–80.CrossRefPubMedGoogle Scholar
  34. 34.
    Dunlay S, Roger V, Weston S, Jiang R, Redfield M. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012;5(6):720–6.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Paulus W, Tschope C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62(4):263–71.CrossRefPubMedGoogle Scholar
  36. 36.
    Florea V, Rector T, Anand I, Cohn J. Heart failure with improved ejection fraction: clinical characteristics, correlates of recovery, and survival results from the Valsartan Heart Failure Trial. Circ Heart Fail. 2016;9(7):e003123.CrossRefPubMedGoogle Scholar
  37. 37.
    Hsu J, Boback Z, Fonarow G. Heart failure with mid-range (borderline) ejection fraction clinical implications and future directions. JACC: Heart Fail. 2017;5:763–71.Google Scholar
  38. 38.
    Vaduganathan M, Patel R, Michel A, Shah S, Senni M, Gheoghiade M. Mode of death in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2017;69(5):556–69.CrossRefPubMedGoogle Scholar
  39. 39.
    Solomon S, Claggett B, Lewis E, Desai A, Anand I, Sweitzer N, et al. Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction. Eur Heart J. 2016;37(5):455–62.CrossRefPubMedGoogle Scholar
  40. 40.
    Cleland J, Bunting K, Flather M, Altman D, Holmes J, Coats A, et al. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. Eur Heart J. 2018;39(1):26–35.CrossRefPubMedGoogle Scholar
  41. 41.
    Kotecha D, Flather M, Altman D, Holmes J, Rosano G, Wikstrand J, et al. Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure. J Am Coll Cardiol. 2017;69(24):2885–96.CrossRefPubMedGoogle Scholar
  42. 42.
    Savarese G, Donal E, Hage C, Oger E, Persson H, Daubert J, et al. Changes in natriuretic peptides after acute hospital presentation for heart failure with preserved ejection fraction: a feasible surrogate trial endpoint? A report from the prospective Karen study. Int J Cardiol. 2017;226:65–70.CrossRefPubMedGoogle Scholar
  43. 43.
    Kutyifa V, Beck C, Brown M, Cannom D, Daubert J, Estes M, et al. Multicenter automatic defibrillator implantation trial-subcutaneous implantable cardioverter defibrillator (MADIT S-ICD); design and clinical protocol. Am Heart J. 2017;189:158–66.CrossRefPubMedGoogle Scholar
  44. 44.
    Stevenson L. Heart failure better EF: a modern diagnosis. Circulation. 2014;129:2364–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Packer M. Heart failure with a mid-range ejection fraction: a disorder that a psychiatrist would love. JACC: Heart Fail. 2017;5(11):805–7.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Peter Unkovic
    • 1
  • Anupam Basuray
    • 1
  1. 1.ColumbusUSA

Personalised recommendations