From Continuous-Flow Mechanical Circulatory Support to Heart Transplantation: Hemodynamic, Immunometabolic, and Body...

Background: Continuous-flow left ventricular assist devices (LVADs) and heart transplantation (HTX) improve survival and quality of life in advanced heart failure. However, restoration of central hemodynamics does not consistently normalize exercise capacity, physical performance, or body composition. Persistent skeletal muscle dysfunction, endothelial abnormalities, metabolic disturbances, and adverse body composition changes frequently limit functional recovery. Methods: This narrative review examines determinants of rehabilitation outcomes across the transition from advanced heart failure to LVAD support and subsequent HTX. Particular emphasis is placed on restoration of pulsatile circulation, vascular and microcirculatory adaptation, immunosuppressive therapy, body composition remodeling, and emerging immunometabolic mechanisms. Results: Rehabilitation outcomes appear to be increasingly determined by peripheral rather than central cardiovascular factors. Continuous-flow LVAD support induces vascular, endothelial, autonomic, and microcirculatory adaptations that may persist after transplantation. Although HTX restores physiological pulsatile circulation and cardiac output, recovery is often limited by skeletal muscle dysfunction, impaired mitochondrial capacity, chronotropic abnormalities, and adverse body composition changes. Immunosuppressive therapies further influence muscle plasticity, adipose tissue distribution, insulin sensitivity, endothelial function, and exercise adaptation, contributing to phenotypes such as sarcopenia, myosteatosis, and sarcopenic obesity. Conclusions: Functional recovery after LVAD support and HTX is a multidimensional process extending beyond restoration of cardiac function. We propose a hemodynamic-immunometabolic framework in which vascular adaptation, skeletal muscle biology, body composition remodeling, and immunosuppressive therapy interact to determine rehabilitation success and may inform personalized rehabilitation strategies.