LVAD support in end-stage heart failure induces significant cellular and molecular reverse remodelling, though functional recovery depends on the underlying etiology.
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). Figure 1 Pathway of reverse remodelling during LVAD unloading. See description in the text. LVAD, left ventricular assist devices; ECM, extracellular matrix; MMPs, matrix metalloproteinases; TIMPs, tissue inhibitors of metalloproteinases; PINP, propeptides of ... Cardiomyocyte Morphology and contractility The unloading achieved with LVADs results in a reduction in the LV dilation seen in end-stage HF and several studies have shown that prolonged mechanical support leads to decreased LV diastolic diameter, LV end-diastolic pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance, as well as increased ejection fraction (EF), mean aortic pressure, and cardiac index (2,3). In a study of myocytes obtained from patients with HF etiology was both ischemic cardiomyopathy (ICD) and dilated cardiomyopathy (DCD) at the time of transplant, the myocytes from patients supported with an LVAD had a greater degree of shortening, faster time to peak contraction and faster time to shortening (4). Another study obtained in DCM demonstrated a significant improvement in LV and myocyte size during LVAD support, but there was only partial recovery of EF and myocyte contractility (5). These conflicting results may suggest that the myocyte recovery is pathology-related: primary cardiomyopathy with an altered proteomic pattern presents as a congenitally impaired myocardial contraction system. Mechanical unloading has also been associated with a specific pattern of changes in sarcomeric, non-sarcomeric and membrane-associated proteins. These changes in expression of cytoskeletal proteins require further study to better explain the differences in myocyte contractility seen with different etiologies of cardiomyopathy (6).
Gallo et al. (2014) studied this question.