Reversal mechanisms of left ventricular remodeling: lessons from left ventricular assist device experiments

The mechanical left ventricular assist device (LVAD) has become a reliable means of stabilizing the conditions of medically refractory patients with severe heart failure who are awaiting heart transplantation. At the same time, a substantial and growing body of evidence indicates that LVAD support triggers a multitude of adaptations within the failing human heart that seem to be triggered by hemodynamic unloading of the failing heart and changes in intracardiac and systemic neurohumoral activity. At the cell and tissue level, virtually every type of pathologic defect associated with failing human hearts demonstrates changes during LVAD support, and these adaptations are usually towards a less pathologic phenotype. This review summarizes the available literature concerning the phenomenology of so-called reverse remodeling. From this review it is clear that myocardial responses to LVAD support reveal the remarkable plasticity of even the most severely failing hearts. The composite literature on myocardial responses to LVAD support supports the thesis that mechanical overload is a primary factor sustaining the pathologic phenotype of the failing heart and suggests that the study of reverse remodeling provides a valuable opportunity to discover adaptive signaling pathways capable of mediating myocardial recovery.