Exploring pathophysiologic mechanisms to assess risk and optimize treatment outcomes in patients with mitral regurgitation

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Project Summary Disorders of the mitral valve are highly prevalent and increasing. Despite their prevalence, major unanswered questions remain regarding the effectiveness and safety of available treatment strategies and our ability to identify optimal treatment options for different patient sub-groups at critical points in the natural history of their disease. Over time, the Cardiothoracic Surgical Trials Network (CTSN) has developed a unique platform of research in valvular heart disease that includes cutting-edge trials in patients with mitral valve prolapse (MVP) and ischemic MR. In this application, the Network proposes to build on this research agenda in two ways. One is to add multimodality imaging and gene expression studies (using tissue specimens) to our recently launched PRIMARY trial comparing surgical mitral valve repair (MVr) to transcatheter-edge-to-edge repair (TEER) in patients with degenerative MR. These studies offer an opportunity to garner earlier insights into the pathophysiological process by which MVP puts patients at risk for arrhythmias and sudden death, and to identify treatments that target these abnormalities. The second proposal is to identify phenotypes among patients with mitral valve disease, both degenerative and ischemic, by applying machine learning and artificial intelligence methods to a repository of clinical and imaging data from hundreds of patients enrolled and followed in our mitral valve trials. Categorization of patients into groups of phenotypes will help identify individuals who may be candidates for MV intervention at earlier stages in the natural history of their disease than currently recommended in clinical practice guidelines. In addition, we will analyze large datasets to evaluate differences in annual utilization and outcomes of MVr and TEER in specific socio-demographic groups with MVP. Recent evidence suggests that women, and racial and ethnically diverse groups, may present later and are at worse outcomes. We will provide much-needed confirmatory evidence about the existence of variations in the diagnosis and management of MVP among these underrepresented subgroups, which may result in differential outcomes.