Project Topic
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Limited regenerative capacity of the human heart leads to remodelling, and eventually heart failure (HF). At present, heart transplantation or left ventricular assist device (LVAD) implantation are the only available treatment options. LVADs are currently used as a bridge to transplant or destination therapy; however, in a subset of patients, LVADs may serve as a bridge to recovery (BTR), where cardiac unloading and recovery of heart function enable LVAD explantation. Unfortunately, LVAD explantation is not a common practice at most cardiac centers, and during post-LVAD follow-up, dedicated protocols for promoting cardiac remodelling and monitoring of cardiac function are often lacking. Based on genome-wide epigenetic, transcriptomic, and proteomic analyses in LVAD patients and a mouse model of cardiac unloading, we aim to provide insights into the mechanisms associated with unloaded-mediated reverse cardiac remodelling (RCR) and identify biomarkers to predict cardiac recovery, which together with clinical characteristics could facilitate the identification of patients that may be candidates for BTR, allowing for appropriate post-LVAD monitoring of cardiac function, myocardial conditioning, and pharmacological therapy to improve outcomes and increase the likelihood of recovery and successful LVAD explantation. In addition, we will optimize a novel contact-free, non-invasive imaging technique based on live video cardiograms of cardiac contraction during open-chest cardiac surgery for monitoring of cardiac function during LVAD implantation surgery, expected to lead to better medical decision-making during surgery, improving post-operative care, and cardiac outcomes. Furthermore, we will study the effect of modulation of a number of 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 RCR.
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