Left ventricular assist device unloading effects on myocardial structure and function: current status of the field and call for action

Abstract

Purpose of review: Myocardial remodeling driven by excess pressure and volume load is believed to be responsible for the vicious cycle of progressive myocardial dysfunction in chronic heart failure. Left ventricular assist devices (LVADs), by providing significant volume and pressure unloading, allow a reversal of stress-related compensatory responses of the overloaded myocardium. Herein, we summarize and integrate insights from studies which investigated how LVAD unloading influences the structure and function of the failing human heart.

Recent findings: Recent investigations have described the impact of LVAD unloading on key structural features of cardiac remodeling - cardiomyocyte hypertrophy, fibrosis, microvasculature changes, adrenergic pathways and sympathetic innervation. The effects of LVAD unloading on myocardial function, electrophysiologic properties and arrhythmias have also been generating significant interest. We also review information describing the extent and sustainability of the LVAD-induced myocardial recovery, the important advances in understanding of the pathophysiology of heart failure derived from such studies, and the implications of these findings for the development of new therapeutic strategies. Special emphasis is given to the great variety of fundamental questions at the basic, translational and clinical levels that remain unanswered and to specific investigational strategies aimed at advancing the field.

Summary: Structural and functional reverse remodeling associated with LVADs continues to inspire innovative research. The ultimate goal of these investigations is to achieve sustained recovery of the failing human heart.

Figures

Figure 1. Increased fibrosis (Masson’s stain–collagen content stains blue) post LVAD-induced unloading

Panel a (normal donor heart), panel b (pre-LVAD), panel c (post-LVAD); 200× magnification; LVAD, left ventricular assist device (modified with permission from ref. [31]).

Figure 2. Effect of LVAD on H/M late MIBG image

H/M (heart-to-mediastinum) uptake ratio in late image at baseline (pre-LVAD, zoom factor 1 ×) and after 3 months of LVAD support (post-LVAD, zoom factor 1, 2×). H/M, heart-to-mediastinum; LVAD, left ventricular assist device; MIBG, I-123 meta-iodobenzylguanidine (modified with permission from [75]).