Skip to main content

Advertisement

Log in

Building a bridge to recovery: the pathophysiology of LVAD-induced reverse modeling in heart failure

  • Review Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Heart failure mainly caused by ischemic or dilated cardiomyopathy is a life-threatening disorder worldwide. The previous work in cardiac surgery has led to many excellent surgical techniques for treating cardiac diseases, and these procedures are now able to prolong the human lifespan. However, surgical treatment for end-stage heart failure has been under-explored, although left ventricular assist device (LVAD) implantation and heart transplantation are options to treat the condition. LVAD can provide powerful circulatory support for end-stage heart failure patients and improve the survival and quality of life after implantation compared with the existing medical counterparts. Moreover, LVADs play a crucial role in the “bridge to transplantation”, “bridge to recovery” and recently have served as “destination therapy”. The structural and molecular changes that improve the cardiac function after LVAD implantation are called “reverse remodeling”, which means that patients who have received a LVAD can be weaned from the LVAD with restoration of their cardiac function. This strategy is a desirable alternative to heart transplantation in terms of both the patient quality of life and due to the organ shortage. The mechanism of this bridge to recovery is interesting, and is different from other treatments for heart failure. Bridge to recovery therapy is one of the options in regenerative therapy which only a surgeon can provide. In this review, we pathophysiologically analyze the reverse remodeling phenomenon induced by LVAD and comment about the clinical evidence with regard to its impact on the bridge to recovery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Alshammary S, et al. Impact of cardiac stem cell sheet transplantation on myocardial infarction. Surg Today. 2013;43(9):970–6.

    Article  CAS  PubMed  Google Scholar 

  2. Akutsu T, Dreyer B, Kolff WJ. Polyurethane artificial heart valves in animals. J Appl Physiol. 1959;14:1045–8.

    CAS  PubMed  Google Scholar 

  3. Barnard CN. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. S Afr Med J. 1967;41(48):1271–4.

    CAS  PubMed  Google Scholar 

  4. Rose EA, et al. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med. 2001;345(20):1435–43.

    Article  CAS  PubMed  Google Scholar 

  5. Birks EJ, et al. Long-term outcomes of patients bridged to recovery versus patients bridged to transplantation. J Thorac Cardiovasc Surg. 2012;144(1):190–6.

    Article  PubMed  Google Scholar 

  6. Zafeiridis A, et al. Regression of cellular hypertrophy after left ventricular assist device support. Circulation. 1998;98(7):656–62.

    Article  CAS  PubMed  Google Scholar 

  7. Ishimaru KMS, Fukushima S, Ide H, Hoashi T, Shibuya T, Ueno T, Sawa Y. Functional and pathological characteristics of reversible remodeling in a canine right ventricle in responce to volume overloading and volume unloading. Surg Today. 2014;44(10):11.

    Article  Google Scholar 

  8. Razeghi P, et al. Mechanical unloading of the failing human heart fails to activate the protein kinase B/Akt/glycogen synthase kinase-3beta survival pathway. Cardiology. 2003;100(1):17–22.

    Article  PubMed  Google Scholar 

  9. Klotz S, et al. Mechanical unloading during left ventricular assist device support increases left ventricular collagen cross-linking and myocardial stiffness. Circulation. 2005;112(3):364–74.

    Article  CAS  PubMed  Google Scholar 

  10. Vatta M, et al. Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies and reversal in patients on assistance-device therapy. Lancet. 2002;359(9310):936–41.

    Article  CAS  PubMed  Google Scholar 

  11. Vatta M, et al. Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices. J Am Coll Cardiol. 2004;43(5):811–7.

    Article  CAS  PubMed  Google Scholar 

  12. Stetson SJ, et al. Improved myocardial structure following LVAD support: effect of unloading on dystrophin expression. J Heart Lung Transplant. 2001;20(2):240.

    Article  PubMed  Google Scholar 

  13. Rodrigue-Way A, et al. Sarcomeric genes involved in reverse remodeling of the heart during left ventricular assist device support. J Heart Lung Transplant. 2005;24(1):73–80.

    Article  PubMed  Google Scholar 

  14. de Jonge N, et al. Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading. An immunohistochemical analysis of the contractile myofilaments. J Am Coll Cardiol. 2002;39(6):963–9.

    Article  PubMed  Google Scholar 

  15. Aquila LA, et al. Cytoskeletal structure and recovery in single human cardiac myocytes. J Heart Lung Transpl. 2004;23(8):954–63.

    Article  Google Scholar 

  16. Birks EJ, et al. Gene profiling changes in cytoskeletal proteins during clinical recovery after left ventricular-assist device support. Circulation. 2005;112(9 Suppl):I57–64.

    PubMed  Google Scholar 

  17. Noguchi T, et al. Thin-filament-based modulation of contractile performance in human heart failure. Circulation. 2004;110(8):982–7.

    Article  PubMed  Google Scholar 

  18. Klotz S, et al. The impact of angiotensin-converting enzyme inhibitor therapy on the extracellular collagen matrix during left ventricular assist device support in patients with end-stage heart failure. J Am Coll Cardiol. 2007;49(11):1166–74.

    Article  CAS  PubMed  Google Scholar 

  19. Liang H, et al. Changes in myocardial collagen content before and after left ventricular assist device application in dilated cardiomyopathy. Chin Med J (Engl). 2004;117(3):401–7.

    Google Scholar 

  20. Bruggink AH, et al. Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern. J Heart Lung Transpl. 2006;25(9):1091–8.

    Article  Google Scholar 

  21. Li YY, et al. Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices. Circulation. 2001;104(10):1147–52.

    Article  CAS  PubMed  Google Scholar 

  22. Matsumiya G, et al. Who would be a candidate for bridge to recovery during prolonged mechanical left ventricular support in idiopathic dilated cardiomyopathy? J Thorac Cardiovasc Surg. 2005;130(3):699–704.

    Article  PubMed  Google Scholar 

  23. McCarthy PM, et al. Structural and left ventricular histologic changes after implantable LVAD insertion. Ann Thorac Surg. 1995;59(3):609–13.

    Article  CAS  PubMed  Google Scholar 

  24. Taketani S, et al. Myocardial histological changes in dilated cardiomyopathy during a long-term left ventricular assist device support. Heart Vessels. 1997;12(2):98–100.

    Article  CAS  PubMed  Google Scholar 

  25. Scheinin SA, et al. The effect of prolonged left ventricular support on myocardial histopathology in patients with end-stage cardiomyopathy. Asaio J. 1992;38(3):M271–4.

    Article  CAS  PubMed  Google Scholar 

  26. Muller J, et al. Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy. Circulation. 1997;96(2):542–9.

    Article  CAS  PubMed  Google Scholar 

  27. Thompson LO, et al. Plasma neurohormone levels correlate with left ventricular functional and morphological improvement in LVAD patients. J Surg Res. 2005;123(1):25–32.

    Article  CAS  PubMed  Google Scholar 

  28. Thohan V, et al. Cellular and hemodynamics responses of failing myocardium to continuous flow mechanical circulatory support using the DeBakey-Noon left ventricular assist device: a comparative analysis with pulsatile-type devices. J Heart Lung Transpl. 2005;24(5):566–75.

    Article  Google Scholar 

  29. Akgul A, et al. Role of mast cells and their mediators in failing myocardium under mechanical ventricular support. J Heart Lung Transpl. 2004;23(6):709–15.

    Article  Google Scholar 

  30. Bruggink AH, et al. Type IV collagen degradation in the myocardial basement membrane after unloading of the failing heart by a left ventricular assist device. Lab Invest. 2007;87(11):1125–37.

    Article  CAS  PubMed  Google Scholar 

  31. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med. 2005;9(2):267–85.

    Article  CAS  PubMed  Google Scholar 

  32. Moshal KS, et al. Early induction of matrix metalloproteinase-9 transduces signaling in human heart end stage failure. J Cell Mol Med. 2005;9(3):704–13.

    Article  CAS  PubMed  Google Scholar 

  33. Jinga DC, et al. MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors. J Cell Mol Med. 2006;10(2):499–510.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Spinale FG, et al. Myocardial matrix degradation and metalloproteinase activation in the failing heart: a potential therapeutic target. Cardiovasc Res. 2000;46(2):225–38.

    Article  CAS  PubMed  Google Scholar 

  35. Thomas CV, et al. Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy. Circulation. 1998;97(17):1708–15.

    Article  CAS  PubMed  Google Scholar 

  36. Oh J, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell. 2001;107(6):789–800.

    Article  CAS  PubMed  Google Scholar 

  37. Polyakova V, et al. Atrial extracellular matrix remodelling in patients with atrial fibrillation. J Cell Mol Med. 2008;12(1):189–208.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. de Jonge N, et al. Cardiomyocyte death in patients with end-stage heart failure before and after support with a left ventricular assist device: low incidence of apoptosis despite ubiquitous mediators. J Heart Lung Transpl. 2003;22(9):1028–36.

    Article  Google Scholar 

  39. Francis GS, et al. Apoptosis, Bcl-2, and proliferating cell nuclear antigen in the failing human heart: observations made after implantation of left ventricular assist device. J Card Fail. 1999;5(4):308–15.

    Article  CAS  PubMed  Google Scholar 

  40. Patten RD, et al. Ventricular assist device therapy normalizes inducible nitric oxide synthase expression and reduces cardiomyocyte apoptosis in the failing human heart. J Am Coll Cardiol. 2005;45(9):1419–24.

    Article  CAS  PubMed  Google Scholar 

  41. Mann DL, Young JB. Basic mechanisms in congestive heart failure. Recognizing the role of proinflammatory cytokines. Chest. 1994;105(3):897–904.

    Article  CAS  PubMed  Google Scholar 

  42. Kubota T, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res. 1997;81(4):627–35.

    Article  CAS  PubMed  Google Scholar 

  43. Torre-Amione G, et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 1996;27(5):1201–6.

    Article  CAS  PubMed  Google Scholar 

  44. Torre-Amione G, et al. Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support : a potential mechanism for cardiac recovery. Circulation. 1999;100(11):1189–93.

    Article  CAS  PubMed  Google Scholar 

  45. Bartling B, et al. Myocardial gene expression of regulators of myocyte apoptosis and myocyte calcium homeostasis during hemodynamic unloading by ventricular assist devices in patients with end-stage heart failure. Circulation. 1999;100(19 Suppl):II216–23.

    CAS  PubMed  Google Scholar 

  46. Wong SYC, et al. Induction of cyclooxygenase-2 and activation of nuclear factor-κB in myocardium of patients with congestive heart failure. Circulation. 1998;98:100–3.

    Article  CAS  PubMed  Google Scholar 

  47. Grabellus F, et al. Reversible activation of nuclear factor-kappaB in human end-stage heart failure after left ventricular mechanical support. Cardiovasc Res. 2002;53(1):124–30.

    Article  CAS  PubMed  Google Scholar 

  48. Baba HA, et al. Dynamic regulation of MEK/Erks and Akt/GSK-3beta in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism. Cardiovasc Res. 2003;59(2):390–9.

    Article  CAS  PubMed  Google Scholar 

  49. Flesch M, et al. Differential regulation of mitogen-activated protein kinases in the failing human heart in response to mechanical unloading. Circulation. 2001;104(19):2273–6.

    Article  CAS  PubMed  Google Scholar 

  50. Hall JL, et al. Genomic profiling of the human heart before and after mechanical support with a ventricular assist device reveals alterations in vascular signaling networks. Physiol Genomics. 2004;17(3):283–91.

    Article  CAS  PubMed  Google Scholar 

  51. Dipla K, et al. Myocyte recovery after mechanical circulatory support in humans with end-stage heart failure. Circulation. 1998;97(23):2316–22.

    Article  CAS  PubMed  Google Scholar 

  52. Milting H, et al. Selective upregulation of beta1-adrenergic receptors and dephosphorylation of troponin I in end-stage heart failure patients supported by ventricular assist devices. J Mol Cell Cardiol. 2006;41(3):441–50.

    Article  CAS  PubMed  Google Scholar 

  53. Kittleson MM, et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation. 2004;110(22):3444–51.

    Article  CAS  PubMed  Google Scholar 

  54. Chen Y, et al. Alterations of gene expression in failing myocardium following left ventricular assist device support. Physiol Genomics. 2003;14(3):251–60.

    Article  PubMed  Google Scholar 

  55. Jahanyar J, et al. Increased expression of stem cell factor and its receptor after left ventricular assist device support: a potential novel target for therapeutic interventions in heart failure. J Heart Lung Transpl. 2008;27(7):701–9.

    Article  Google Scholar 

  56. Deng MC, et al. Mechanical circulatory support device database of the International Society for Heart and Lung Transplantation: second annual report—2004. J Heart Lung Transpl. 2004;23(9):1027–34.

    Article  Google Scholar 

  57. Rockman HA, et al. Acute fulminant myocarditis: long-term follow-up after circulatory support with left ventricular assist device. Am Heart J. 1991;121(3 Pt 1):922–6.

    Article  CAS  PubMed  Google Scholar 

  58. Levin HR, et al. Transient normalization of systolic and diastolic function after support with a left ventricular assist device in a patient with dilated cardiomyopathy. J Heart Lung Transpl. 1996;15(8):840–2.

    CAS  Google Scholar 

  59. Helman DN, et al. Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable? Ann Thorac Surg. 2000;70(4):1255–8.

    Article  CAS  PubMed  Google Scholar 

  60. Mancini DM, 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 

  61. El-Banayosy A, et al. Hemodynamic exercise testing reveals a low incidence of myocardial recovery in LVAD patients. J Heart Lung Transpl. 2001;20(2):209–10.

    Article  Google Scholar 

  62. Liden H, et al. The feasibility of left ventricular mechanical support as a bridge to cardiac recovery. Eur J Heart Fail. 2007;9(5):525–30.

    Article  PubMed  Google Scholar 

  63. Farrar DJ, et al. Long-term follow-up of thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function. J Heart Lung Transpl. 2002;21(5):516–21.

    Article  Google Scholar 

  64. Grinda JM, et al. Fulminant myocarditis in adults and children: bi-ventricular assist device for recovery. Eur J Cardiothorac Surg. 2004;26(6):1169–73.

    Article  PubMed  Google Scholar 

  65. Hoy FB, et al. Bridge to recovery for postcardiotomy failure: is there still a role for centrifugal pumps? Ann Thorac Surg. 2000;70(4):1259–63.

    Article  CAS  PubMed  Google Scholar 

  66. Birks EJ, 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 

  67. Barton PJ, et al. Myocardial insulin-like growth factor-I gene expression during recovery from heart failure after combined left ventricular assist device and clenbuterol therapy. Circulation. 2005;112(9 Suppl):I46–50.

    PubMed  Google Scholar 

  68. Hon JK, Yacoub MH. Bridge to recovery with the use of left ventricular assist device and clenbuterol. Ann Thorac Surg. 2003;75(6 Suppl):S36–41.

    Article  PubMed  Google Scholar 

  69. George I, et al. Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support. J Heart Lung Transpl. 2006;25(9):1084–90.

    Article  Google Scholar 

  70. Maybaum S, et al. Cardiac improvement during mechanical circulatory support: a prospective multicenter study of the LVAD Working Group. Circulation. 2007;115(19):2497–505.

    Article  PubMed  Google Scholar 

  71. Khan T, et al. Dobutamine stress echocardiography predicts myocardial improvement in patients supported by left ventricular assist devices (LVADs): hemodynamic and histologic evidence of improvement before LVAD explantation. J Heart Lung Transpl. 2003;22(2):137–46.

    Article  Google Scholar 

  72. Miyagawa S, et al. Analysis of sympathetic nerve activity in end-stage cardiomyopathy patients receiving left ventricular support. J Heart Lung Transpl. 2001;20(11):1181–7.

    Article  CAS  Google Scholar 

  73. Bruckner BA, et al. Degree of cardiac fibrosis and hypertrophy at time of implantation predicts myocardial improvement during left ventricular assist device support. J Heart Lung Transpl. 2004;23(1):36–42.

    Article  Google Scholar 

  74. Tijsen AJ, et al. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010;106(6):1035–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshiki Sawa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miyagawa, S., Toda, K., Nakamura, T. et al. Building a bridge to recovery: the pathophysiology of LVAD-induced reverse modeling in heart failure. Surg Today 46, 149–154 (2016). https://doi.org/10.1007/s00595-015-1149-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-015-1149-8

Keywords

Navigation