Cellular, molecular, genomic changes occurring in the heart under mechanical circulatory support.

Heart failure (HF) is a clinical syndrome that arises from any functional or structural impairment of one or two ventricles in either filling or ejection of blood. The clinical syndrome of HF results from disorders of the pericardium, myocardium, endocardium, heart valves or metabolic abnormalities, and manifests itself mainly as impaired left ventricular (LV) myocardial function (1). The clinical syndrome of HF is paralleled by significant molecular, cellular and histologic changes, known as “cardiac remodelling”. The long waiting times for donor organs and the need for treatment of end-stage HF unresponsive to medical therapy has required the development of LV assist devices (LVAD). LVADs provide volume and pressure unloading of the LV and restore function and allow myocardial recovery. Ventricular unloading enables a reversal of stress-related compensatory responses of the overloaded myocardium and normalizes systemic perfusion of organs. Thus, ventricular unloading activates a local and systemic neurohormonal and cytokine network and is associated with morphological and molecular changes in the myocardium, called “reverse remodelling”. However, molecular reverse remodelling does not always correspond to functional myocardial recovery, and in this case LVAD will act as a bridge to heart transplantation or to destination therapy. It is important to consider the etiology of HF to predict the recovery and reverse remodelling of the myocardium. For example, primary cardiomyopathy, which has a genetic etiology with an altered proteomic pattern, cannot undergo to myocardial recovery. We review the cellular, molecular and genetic changes during LV unloading (Figure 1).