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Epidemiology of “Heart Failure with Recovered Ejection Fraction”: What do we do After Recovery?

  • Epidemiology of Heart Failure (J. Ho, Section Editor)
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Abstract

Improvement in functional status, long-term survival, and quality of life has always been the goal of therapy in patients with heart failure with reduced ejection fraction. Neurohormonal modulating medications help patients achieve these goals and, in a subgroup of patients, can promote “reverse remodeling” resulting in the recovery of left ventricular systolic function. In the era of durable mechanical support, myocardial recovery that leads to explantation of the ventricular assist device occurs in a minority of cases. Optimal medical therapy appears to be a key component of achieving myocardial recovery, with recovery more likely in patients with a shorter duration of heart failure and a non-ischemic etiology. However, little is known about future management of patients who attain myocardial recovery, either with or without mechanical support. This review explores the epidemiology, physiology, cellular biology, and long-term outcomes for this subgroup of heart failure patients and outlines areas for future study.

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References

  1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, 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. J Am Coll Cardiol. 2013;62(16):e147–239.

    Article  PubMed  Google Scholar 

  2. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16(6):e1–194.

    Article  PubMed  Google Scholar 

  3. McMurray JJV, Adamopoulos S, Anker SD, Auricchio A, Bohm M, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Eur Heart J. 2012;14:803–69.

    Article  CAS  Google Scholar 

  4. Basuray A, French B, Ky B, Vorovich E, Olt C, Sweitzer NK, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation. 2014;129(23):2380–7.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012;5(6):720–6.

    Article  PubMed Central  PubMed  Google Scholar 

  6. 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;17(7):527–32.

    Article  PubMed  Google Scholar 

  7. McNamara DM, Elkayam U, Alharethi R, Damp J, Hsich E, Ewald G, et al. Clinical outcomes for peripartum cardiomyopathy in North America: results of the IPAC study (Investigations of Pregnancy-Associated Cardiomyopathy). J Am Coll Cardiol. 2015;66(8):905–14.

    Article  PubMed  Google Scholar 

  8. Bybee KA, Kara T, Prasad A, Lerman A, Barsness GW, Wright RS, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Int Med. 2004;141(11):858–65.

    Article  PubMed  Google Scholar 

  9. Sjöblom J, Muhrbeck J, Witt N, Alam M, Frykman-Kull V. Evolution of left ventricular ejection fraction after acute myocardial infarction: implications for implantable cardioverter-defibrillator eligibility. Circulation. 2014;130(9):743–8.

    Article  PubMed  Google Scholar 

  10. Camici PG, Prasad SK, Rimoldi OE. Stunning, hibernation, and assessment of myocardial viability. Circulation. 2008;117(1):103–14.

    Article  PubMed  Google Scholar 

  11. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435–43.

    Article  CAS  PubMed  Google Scholar 

  12. Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357(9):885–96.

    Article  CAS  PubMed  Google Scholar 

  13. Drakos SG, Kfoury AG, Stehlik J, Selzman CH, Reid BB, Terrovitis JV, et al. Bridge to recovery: understanding the disconnect between clinical and biological outcomes. Circulation. 2012;126(2):230–41.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED, et al. Sixth INTERMACS annual report: a 10,000-patient database. J Heart Lung Transplant. 2014;33(6):555–64.

    Article  PubMed  Google Scholar 

  15. Goldstein DJ, Maybaum S, MacGillivray TE, Moore SA, Bogaev R, Farrar DJ, et al. Young patients with nonischemic cardiomyopathy have higher likelihood of left ventricular recovery during left ventricular assist device support. J Card Fail. 2012;18(5):392–5.

    Article  PubMed  Google Scholar 

  16. Frazier OH, Benedict CR, Radovancevic B, Bick RJ, Capek P, Springer WE, et al. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg. 1996;62(3):675–82.

    Article  CAS  PubMed  Google Scholar 

  17. Müller J, Wallukat G, Weng YG, Dandel M, Spiegelsberger S, Semrau S, et al. Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy. Circulation. 1997;96(2):542–9.

    Article  PubMed  Google Scholar 

  18. Mancini DM, Beniaminovitz A, Levin H, Catanese K, Flannery M, DiTullio M, et al. Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure. Circulation. 1998;98(22):2383–9.

    Article  CAS  PubMed  Google Scholar 

  19. Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006;355(18):1873–84.

    Article  CAS  PubMed  Google Scholar 

  20. Dandel M, Weng Y, Siniawski H, Potapov E, Lehmkuhl HB, Hetzer R. Long-term results in patients with idiopathic dilated cardiomyopathy after weaning from left ventricular assist devices. Circulation. 2005;112(9 Suppl):I37–45.

    PubMed  Google Scholar 

  21. Segura AM, Dris L, Massin EK, Clubb FJ, Buja LM, Frazier OH, et al. Heart failure in remission for more than 13 years after removal of a left ventricular assist device. Tex Heart Inst J. 2014;41(4):389–94.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Birks EJ, George RS, Hedger M, Bahrami T, Wilton P, Bowles CT, 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.

    Article  CAS  PubMed  Google Scholar 

  23. Dandel M, Weng Y, Siniawski H, Potapov E, Drews T, Lehmkuhl HB, et al. Prediction of cardiac stability after weaning from left ventricular assist devices in patients with idiopathic dilated cardiomyopathy. Circulation. 2008;118(14 Suppl):S94–105.

    Article  PubMed  Google Scholar 

  24. Pruijsten RV, Lok SI, Kirkels HH, Klöpping C, Lahpor JR, De Jonge N. Functional and haemodynamic recovery after implantation of continuous-flow left ventricular assist devices in comparison with pulsatile left ventricular assist devices in patients with end-stage heart failure. Eur J Heart Fail. 2012;14(3):319–25.

    Article  PubMed  Google Scholar 

  25. Krabatsch T, Schweiger M, Dandel M, Stepanenko A, Drews T, Potapov E, et al. Is bridge to recovery more likely with pulsatile left ventricular assist devices than with nonpulsatile-flow systems? Ann Thorac Surg. 2011;91(5):1335–40.

    Article  PubMed  Google Scholar 

  26. Diakos NA, Selzman CH, Sachse FB, Stehlik J, Kfoury AG, Wever-Pinzon O, et al. Myocardial atrophy and chronic mechanical unloading of the failing human heart: implications for cardiac assist device-induced myocardial recovery. J Am Coll Cardiol. 2014;64(15):1602–12.

    Article  PubMed  Google Scholar 

  27. Adler E, Silva Enciso J. Functional improvement after ventricular assist device implantation: is ventricular recovery more common than we thought? J Am Coll Cardiol. 2013;61(19):1995–7.

    Article  PubMed  Google Scholar 

  28. Selzman CH, Madden JL, Healy AH, McKellar SH, Koliopoulou A, Stehlik J, et al. Bridge to removal: a paradigm shift for left ventricular assist device therapy. Ann Thorac Surg. 2015;99(1):360–7.

    Article  PubMed  Google Scholar 

  29. Dandel M, Weng Y, Siniawski H, Stepanenko A, Krabatsch T, Potapov E, et al. Heart failure reversal by ventricular unloading in patients with chronic cardiomyopathy: criteria for weaning from ventricular assist devices. Eur Heart J. 2011;32(9):1148–60.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Birks EJ, Drakos S, Selzman C, Starling R, Cunningham C, Slaughter M, et al. Remission from stage D heart failure (RESTAGE-HF): early results from a prospective multi-center study of myocardial recovery. J Heart Lung Transplant. 2015;34(4):S40–1.

    Article  Google Scholar 

  31. Frazier OH, Baldwin ACW, Demirozu ZT, Segura AM, Hernandez R, Taegtmeyer H, et al. Ventricular reconditioning and pump explantation in patients supported by continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2015;34(6):766–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Koitabashi N, Kass DA. Reverse remodeling in heart failure—mechanisms and therapeutic opportunities. Nat Rev Cardiol. 2012;9(3):147–57.

    Article  CAS  Google Scholar 

  33. Kramer DG, Trikalinos TA, Kent DM, Antonopoulos GV, Konstam MA, Udelson JE. 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. J Am Coll Cardiol. 2010;56(5):392–406.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Wohlschlaeger J, Levkau B, Brockhoff G, Schmitz KJ, von Winterfeld M, Takeda A, et al. Hemodynamic support by left ventricular assist devices reduces cardiomyocyte DNA content in the failing human heart. Circulation. 2010;121(8):989–96.

    Article  CAS  PubMed  Google Scholar 

  35. Agnetti G, Kaludercic N, Kane LA, Elliott ST, Guo Y, Chakir K, et al. Modulation of mitochondrial proteome and improved mitochondrial function by biventricular pacing of dyssynchronous failing hearts. Circ Cardiovasc Genet. 2010;3(1):78–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Wang S-B, Foster DB, Rucker J, O’Rourke B, Kass DA, Van Eyk JE. Redox regulation of mitochondrial ATP synthase: implications for cardiac resynchronization therapy. Circ Res. 2011;109(7):750–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Sachse FB, Torres NS, Savio-Galimberti E, Aiba T, Kass DA, Tomaselli GF, et al. Subcellular structures and function of myocytes impaired during heart failure are restored by cardiac resynchronization therapy. Circ Res. 2012;110(4):588–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Ibrahim M, Navaratnarajah M, Siedlecka U, Rao C, Dias P, Moshkov AV, et al. Mechanical unloading reverses transverse tubule remodelling and normalizes local Ca(2+)-induced Ca(2+)release in a rodent model of heart failure. Eur J Heart Fail. 2012;14(6):571–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Moon J, Ko Y-G, Chung N, Ha J-W, Kang S-M, Choi E-Y, et al. Recovery and recurrence of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy. Can J Cardiol. 2009;25(5):e147–50.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Park J-S, Kim J-W, Seo K-W, Choi B-J, Choi S-Y, Yoon M-H, et al. Recurrence of left ventricular dysfunction in patients with restored idiopathic dilated cardiomyopathy. Clin Cardiol. 2014;37(4):222–6.

    Article  PubMed  Google Scholar 

  41. Hopper I, Samuel R, Hayward C, Tonkin A, Krum H. Can medications be safely withdrawn in patients with stable chronic heart failure? Systematic review and meta-analysis. J Card Fail. 2014;20(7):522–32.

    Article  PubMed  Google Scholar 

  42. Naksuk N, Saab A, Li J-M, Florea V, Akkaya M, Anand IS, et al. Incidence of appropriate shock in implantable cardioverter-defibrillator patients with improved ejection fraction. J Card Fail. 2013;19(6):426–30.

    Article  PubMed  Google Scholar 

  43. Kini V, Soufi MK, Deo R, Epstein AE, Bala R, Riley M, et al. Appropriateness of primary prevention implantable cardioverter-defibrillators at the time of generator replacement: are indications still met? J Am Coll Cardiol. 2014;63(22):2388–94.

    Article  PubMed  Google Scholar 

  44. Zhang Y, Guallar E, Blasco-Colmenares E, Butcher B, Norgard S, Nauffal V, 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 Am Coll Cardiol. 2015;66(5):524–31.

    Article  PubMed  Google Scholar 

  45. Ruwald MH, Solomon SD, Foster E, Kutyifa V, Ruwald A-C, Sherazi S, 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. Circulation. 2014;130(25):2278–86.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Tufts Medical Center, 800 Washington Street, Boston, MA, 02111, USA

    Johny S. Kuttab, Michael S. Kiernan & Amanda R. Vest

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  1. Johny S. Kuttab
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  2. Michael S. Kiernan
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  3. Amanda R. Vest
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Correspondence to Amanda R. Vest.

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Johny S Kuttab, Michael S Kiernan, and Amanda R Vest declare that they have no conflict of interest.

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

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This article is part of the Topical Collection on Epidemiology of Heart Failure

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Kuttab, J.S., Kiernan, M.S. & Vest, A.R. Epidemiology of “Heart Failure with Recovered Ejection Fraction”: What do we do After Recovery?. Curr Heart Fail Rep 12, 360–366 (2015). https://doi.org/10.1007/s11897-015-0274-4

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