Heart Failure
Clinical Problem: Mitral regurgitation causes back flow of blood through the mitral valve into the left atrium in each cardiac cycle. It imposes a volume overload on the ventricle that leads to a series of left ventricular compensatory adaptations and adjustments that vary with time. Early compensatory changes are replaced by maladaptive permanent changes in the ventricular structure and function, ultimately resulting in congestive heart failure. Most patients present to the hospital at various stages of this ventricular remodeling spectrum, and techniques to identify the status of their ventricle in the temporally evolving remodeling process are few. Thus timing of mitral valve repair and its benefit to the left ventricular function is rather random. Our laboratory is interested in mapping the changes in the left ventricle imposed by mitral regurgitation, and identify the optimal timing of mitral valve repair.
Structure-Function Relationship: Using a high-throughput rodent model of mitral regurgitation we are studying the temporal relationship between left ventricular function and underlying structural changes in the extracellular matrix and cellular response. Mitral regurgitation is induced in this model either via a transapical needle that punctures the mitral valve leaflets, or via an atrial-ventricular extracardiac conduit. In this model, we are investigating the impact of controlled mitral regurgitation and its early and late repair on left ventricular dysfunction and failure. Hearts explanted from these subjects are decellularized to study the extracellular matrix, while the cells are used to study their failure mechanisms. |