The ability of the failing human heart to recover after mechanical unloading with left ventricular assist devices (LVADs) has been insufficiently exploited. To fill this void, we engineered the Pressure Unloading LVAD (PULVAD) system, designed to promote myocardial recovery. The overall objective of the proposed translational investigation is to evaluate the feasibility, safety and efficacy of this innovative pressure unloading approach as a bridge to recovery from heart failure. We will first investigate the effects of short-term PULVAD support on systemic hemodynamics and left ventricular mechanoenergetics in a large animal model of acute heart failure. We will then perform a pivotal randomized controlled study to investigate the safety and efficacy of long-term PULVAD support in promoting sustained cardiac recovery in a large animal model of chronic heart failure. If validated, this new technology has the potential to improve quality of life and ease the socioeconomic burden of advanced heart failure. In addition, histological, cellular and molecular analysis of paired myocardial biopsies obtained pre/post-PULVAD unloading will provide insight into mechanisms underlying cardiac reverse remodeling and myocardial recovery.