Molecular- and Organelle-Based Predictive Paradigm Underlying Recovery by Left Ventricular Assist Device Support

Abstract

Advanced heart failure (HF) is a major cause of morbidity and mortality in the United States, and heart transplantation remains as the gold standard therapy. Because of scarcity of donor organs, the application of mechanical circulatory support devices has become a crucial approach in HF therapy as a bridge to transplantation. Therefore, mechanical circulatory support devices have existed both conceptually and experimentally for >40 years, along which an exponential evolution of mechanical circulatory support device technology has occurred. To mimic human physiology, the first generation of left ventricular assist devices (LVADs) were pulsatile volume displacement pumps (HeartMate XVE LVAS, Thoratec PVAD, and Novacor, etc). Insights demonstrating the inessentiality of the pulsatile nature of LVADs for survival from a physiological standpoint propelled the design of second-generation continuous flow devices (HeartMate II [Thoratec Inc], the Micromed DeBakey VAD, Berlin Heart Incor [Berlin Heart AG], and the Jarvik 2000 [Jarvik Heart Inc]), which emerged with superior safety and durability. Consequently, the HeartMate II was approved for bridge to transplantation and destination therapy in the United States.1 Recent reports2,3 have demonstrated a 2-year survival rate of 87% in destination therapy patients under intense surveillance, comparable with open heart transplantation survival statistics. In parallel, these promising outcomes of LVADs in HF therapy have spawned the translational research field of LV reverse remodeling, which has already shown great promise for elucidating underlying molecular and cellular mechanisms. HF is a highly complex clinical syndrome marked by a multitude of derangements, both in adult and pediatric populations.4 The clinical phenotype of HF begins with an injury or supranormal stressor on the heart and, through prolonged dyshomeostasis, eventuates in cellular and organ failure. The compensatory adaptive mechanisms including neurohormonal activation (eg, the …