Reverse remodeling following insertion of left ventricular assist devices (LVAD): A review of the morphological and molecular changes

Left ventricular assist devices (LVAD) are used to bridge patients with end-stage heart failure until transplantation of a donor heart can be performed (bridge to transplantation). However, in a subset of patients, support by LVAD sporadically results in improved cardiac function, with heart transplantation no longer necessary even after removal of the LVAD (bridge to recovery). Also, LVAD appears to be an optional treatment alternative to heart transplantation in patients with contraindications for organ replacement (destination therapy). The processes resulting in these effects have descriptively been termed reverse remodeling. Although the molecular mechanisms are incompletely understood at present, there are several aspects of the reverse remodeling process that have been identified in the past. Alterations of many molecular pathways are involved in the development of chronic heart failure. Some of these appear to be reversible and have been shown to be regulated by LVAD treatment. LVAD lead to lowered cardiac pressure and volume overload in the myocardium followed by decreased ventricular wall tension, reduced cardiomyocyte hypertrophy, improved coronary perfusion and decreased chronic ischemia. Improved coronary flow and myocardial perfusion as well as decreased ventricular wall tension may possibly alter the molecular systems involved in the development of chronic cardiac insufficiency. Aside from describing the morphological changes, this review focuses on the roles of signal transduction, transcriptional regulation, apoptosis, stress proteins, matrix remodeling, and neurohormonal signaling in the failing human heart before and after mechanical circulatory support. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.