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The paradox of left ventricular assist device unloading and myocardial recovery in end-stage dilated cardiomyopathy: implications for heart failure in the elderly

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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.

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Acknowledgments

This work was supported in part by grant # IAP-99003 from the Canadian Institutes of Health Research, Ottawa, ON. We thank Catherine Jugdutt for assistance.

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  1. Division of Cardiology, 2C2 Walter C. Mackenzie Health Sciences Center, University of Alberta, 8440-112 Street, Edmonton, AB, T6G 2B7, Canada

    Craig R. Butler & Bodh I. Jugdutt

  2. Cardiovascular Research Group, University of Alberta, Edmonton, AB, Canada

    Bodh I. Jugdutt

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  1. Craig R. Butler
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  2. Bodh I. Jugdutt
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Correspondence to Craig R. Butler.

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Butler, C.R., Jugdutt, B.I. The paradox of left ventricular assist device unloading and myocardial recovery in end-stage dilated cardiomyopathy: implications for heart failure in the elderly. Heart Fail Rev 17, 615–633 (2012). https://doi.org/10.1007/s10741-012-9300-8

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