The Paradox of Left Ventricular Assist Device Unloading and Myocardial Recovery in End-stage Dilated Cardiomyopathy: Implications for Heart Failure in the Elderly

Overview

Journal Heart Fail Rev

Date 2012 Jan 20

PMID 22258830

Citations 6

Authors

Craig R Butler

Bodh I Jugdutt

Affiliations

Soon will be listed here.

Abstract

Dilated cardiomyopathy (DCM) is a common debilitating condition with limited therapeutic options besides heart transplantation or palliation. It is characterized by maladaptive remodeling of cardiomyocytes, extracellular collagen matrix (ECCM) and left ventricular (LV) geometry which contributes to further dysfunction. LV assist devices (LVADs) can reverse adverse remodeling in end-stage DCM. However, there is a disconnect between the benefits of prolonged unloading with LVAD at molecular and cellular levels and the low rate of bridge to recovery (BTR). Potential explanations for this paradox include insufficient reverse ECCM remodeling and/or excessive reverse cardiomyocyte remodeling with atrophy. LVAD therapy is associated with decreased collagen turnover and cross-linking and increased tissue angiotensin II (AngII), whereas LVAD combined with angiotensin-converting enzyme inhibition results in decreased tissue AngII and collagen cross-linking, normalizes LV end-diastolic pressure volume relationships and is associated with modestly higher rates of BTR. Much remains to be learned about ventricular reverse remodeling after LVAD. This can be facilitated through systematic collection and comparison of recovered and unrecovered myocardium. Importantly, vigilant monitoring for ventricular recovery among LVAD patients is needed, particularly in older patients receiving LVAD for destination therapy. In addition, prospective multicenter trials are needed to clarify the potential benefit of concomitant heart failure therapy with selective β2 agonism on ventricular recovery.

Citing Articles

Myocardial Recovery.

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Left ventricular assist device recovery: does duration of mechanical support matter?.

Pham B, Chaparro S Heart Fail Rev. 2018; 24(2):237-244.

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Use of Heart Failure Medical Therapies Among Patients With Left Ventricular Assist Devices: Insights From INTERMACS.

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Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation.

DAmico A, Ragusa R, Caruso R, Prescimone T, Nonini S, Cabiati M J Transl Med. 2014; 12:350.

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Heart failure in remission for more than 13 years after removal of a left ventricular assist device.

Segura A, Dris L, Massin E, Clubb F, Buja L, Frazier O Tex Heart Inst J. 2014; 41(4):389-94.

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References

Fujio Y, Kunisada K, Hirota H, Kishimoto T . Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes. J Clin Invest. 1997; 99(12):2898-905. PMC: 508141. DOI: 10.1172/JCI119484. View

Tsutamoto T, Hisanaga T, Fukai D, Wada A, Maeda Y, Maeda K . Prognostic value of plasma soluble intercellular adhesion molecule-1 and endothelin-1 concentration in patients with chronic congestive heart failure. Am J Cardiol. 1995; 76(11):803-8. DOI: 10.1016/s0002-9149(99)80231-8. View

Koshy S, Reddy H, Shukla H . Collagen cross-linking: new dimension to cardiac remodeling. Cardiovasc Res. 2003; 57(3):594-8. DOI: 10.1016/s0008-6363(02)00877-5. View

Klein I, Hong C, SCHREIBER S . Cardiac atrophy in the heterotopically transplanted rat heart: in vitro protein synthesis. J Mol Cell Cardiol. 1990; 22(4):461-8. DOI: 10.1016/0022-2828(90)91481-l. View

Maybaum S, Mancini D, Xydas S, Starling R, Aaronson K, Pagani F . Cardiac improvement during mechanical circulatory support: a prospective multicenter study of the LVAD Working Group. Circulation. 2007; 115(19):2497-505. DOI: 10.1161/CIRCULATIONAHA.106.633180. View

Nakano M, Knowlton A, Yokoyama T, LESSLAUER W, Mann D . Tumor necrosis factor-alpha-induced expression of heat shock protein 72 in adult feline cardiac myocytes. Am J Physiol. 1996; 270(4 Pt 2):H1231-9. DOI: 10.1152/ajpheart.1996.270.4.H1231. View

Heerdt P, Holmes J, Cai B, Barbone A, Madigan J, Reiken S . Chronic unloading by left ventricular assist device reverses contractile dysfunction and alters gene expression in end-stage heart failure. Circulation. 2000; 102(22):2713-9. DOI: 10.1161/01.cir.102.22.2713. View

Kirklin J, Naftel D, Kormos R, Stevenson L, Pagani F, Miller M . Third INTERMACS Annual Report: the evolution of destination therapy in the United States. J Heart Lung Transplant. 2011; 30(2):115-23. DOI: 10.1016/j.healun.2010.12.001. View

Rose E, Gelijns A, Moskowitz A, Heitjan D, Stevenson L, Dembitsky W . Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2002; 345(20):1435-43. DOI: 10.1056/NEJMoa012175. View

10.

Bruckner B, Razeghi P, Stetson S, Thompson L, Lafuente J, Entman M . Degree of cardiac fibrosis and hypertrophy at time of implantation predicts myocardial improvement during left ventricular assist device support. J Heart Lung Transplant. 2004; 23(1):36-42. DOI: 10.1016/s1053-2498(03)00103-7. View

11.

Kudoh S, Komuro I, Hiroi Y, Zou Y, Harada K, Sugaya T . Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1a receptor knockout mice. J Biol Chem. 1998; 273(37):24037-43. DOI: 10.1074/jbc.273.37.24037. View

12.

Mann D, Spinale F . Activation of matrix metalloproteinases in the failing human heart: breaking the tie that binds. Circulation. 1998; 98(17):1699-702. DOI: 10.1161/01.cir.98.17.1699. View

13.

Madigan J, Barbone A, Choudhri A, Morales D, Cai B, Oz M . Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device. J Thorac Cardiovasc Surg. 2001; 121(5):902-8. DOI: 10.1067/mtc.2001.112632. View

14.

Jugdutt B, Butler C . Ventricular unloading, tissue angiotensin II, matrix modulation, and function during left ventricular assist device support. J Am Coll Cardiol. 2007; 49(11):1175-7. DOI: 10.1016/j.jacc.2006.12.022. View

15.

Bruckner B, Stetson S, Youker K, Radovancevic B, Connelly J, Koerner M . Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support. J Heart Lung Transplant. 2001; 20(4):457-64. DOI: 10.1016/s1053-2498(00)00321-1. View

16.

Thohan V, Stetson S, Nagueh S, Rivas-Gotz C, Koerner M, Lafuente J . 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 Transplant. 2005; 24(5):566-75. DOI: 10.1016/j.healun.2004.02.017. View

17.

Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J . Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res. 1994; 75(3):434-42. DOI: 10.1161/01.res.75.3.434. View

18.

Burkhoff D, Klotz S, Mancini D . LVAD-induced reverse remodeling: basic and clinical implications for myocardial recovery. J Card Fail. 2006; 12(3):227-39. DOI: 10.1016/j.cardfail.2005.10.012. View

19.

Thompson E, Marino T, Uboh C, Kent R, Cooper 4th G . Atrophy reversal and cardiocyte redifferentiation in reloaded cat myocardium. Circ Res. 1984; 54(4):367-77. DOI: 10.1161/01.res.54.4.367. View

20.

Stull L, Sweet W, Smedira N, McCarthy P, Moravec C . Mechanical unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in the failing human heart. Circulation. 2001; 104(8):881-6. DOI: 10.1161/hc3301.094911. View