Heart failure (HF) represents a major public health problem with high morbidity and mortality. Health care expenditure for HF exceeds those of all cancers and myocardial infarctions combined. We aim to investigate structural, cellular and molecular changes of the failing human heart before and after non-pulsatile,continuous flow,left ventricular assist devices (LVAD) - induced unloading and to correlate them with changes in myocardial function.Tissue analysis will focus on 3 key myocardial remodeling features (fibrosis, microvasculature/endothelium and cardiomyocyte hypertrophy) which appear to be mechanistically associated during the remodeling process that eventually leads to HF (“endothelial to mesenchymal transition”).
This translational investigation will a)formulate a standardized approach to acquire and evaluate myocardial tissue data along with clinical and functional data in HF patients before and after mechanical unloading and b)establish a baseline for the basic biologic effects of continuous flow LVAD unloading on the function and structure of the failing human heart.
We emphasize that two major outcomes are possible, and both are important. The first outcome is that we observe significant degree of improvement in myocardial function induced by non-pulsatile LVADs. In this case our study will provide the basis for identifying the hallmarks that are associated with unloading-induced recovery. The second possible outcome is that the unloading-induced myocardial recovery is minimal or rare. This would further encourage investigations that combine LVAD use with adjuvant therapies. Our results would provide the clinical, functional and pathologic baseline necessary for investigations of the impact of pharmacologic or cell-based or other advanced therapies added to LVADs. In either case we believe our investigation is likely to provide a comprehensive starting point for the new coming era of regenerative medicine and serve as springboard for future studies.
Fields of science
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Funding SchemeMC-IRG - International Re-integration Grants (IRG)
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