For heart failure, heart transplantation or Left Ventricular Assist Device (LVAD) implantation are the only available treatment options. LVADs typically serve as a bridge-to-transplant or destination therapy. In some patients, LVADs may serve as a bridge to recovery (BTR), where cardiac unloading and recovery of heart function enable LVAD explantation. Biomarkers are needed for the upfront identification of patients that are BTR candidates. We will perform epigenetic, transcriptomic, and proteomic analyses in a cohort of LVAD patients to address this shortcoming. Moreover, we will characterize a mouse model of cardiac unloading to understand its mechanistic foundations. Further, we will optimize a non-invasive imaging technique of cardiac contraction during open-chest cardiac surgery to improve outcomes. Lastly, we will study long non-coding RNAs that are dysregulated in HF and normalized after unloading, to determine whether they may represent targets for therapies, which alone or in conjunction with LVAD-support can promote cardiac recovery.