Mitral regurgitation (MR) is present in one in five coronary artery disease (CAD) patients undergoing revascularization, conferring markedly increased morbidity and mortality. In prior research by our group and others, MR in patients with CAD has been strongly linked to ischemia and infarction in myocardium underlying the mitral valve. Ischemia can be reversed with revascularization, whereas infarction cannot. However, in clinical practice, MR response to revascularization is poorly understood. In nearly half of patients, MR improves with surgical or percutaneous coronary revascularization alone - in the remainder MR persists or worsens. Uncer- tainty as to which patients with MR will respond to revascularization alone limits the ability to optimize therapy. Cardiac magnetic resonance (CMR) imaging is a powerful tool to identity ischemia and infarction, as well as function and geometry. CMR tissue characterization is known to predict revascularization-induced improvement in LV function and remodeling, but has never before been tested as a planning tool for MR. Our central hypothesis is that MR response to revascularization can be predicted prior to therapy via CMR, with MR improvement dependent on presence and magnitude of ischemia in viable (alive) myocardium supporting the mitral valve. Additionally, we hypothesize that non-ischemic fibrosis in patients with CAD is associated with persistent MR after revascularization, attributable to adverse global myocardial remodeling that blunts the ability of the mitral valve to respond to revascularization. To test these hypotheses, we will study at least 156 CAD patients with advanced (?moderate) MR undergoing coronary revascularization alone. Stress perfusion CMR will be performed pre and post-revascularization to assess baseline myocardial tissue properties and revascularization induced change in ischemia. Echocardiography (pre, 3, and 6 months post) will be the reference for MR, so as to apply a well-validated standard concordant with prior NIH studies and widespread clinical practice.
Aim 1 will compare presence and magnitude of ischemia and infarction between patients with and without improved MR.
Aim 2 will compare non-ischemic fibrosis between groups, including focal mid-wall fibrosis and global extracellular volume.
Aim 3 will develop predictive models for MR response to revascularization, using both primary CMR data and finite element modeling. Our track record in CMR, echocardiography, mitral valve physiology, and computational modeling makes us uniquely poised to address these issues. The novel information to be gained from this research will enable development of predictive models to differentiate a priori those patients in whom MR will improve with revascularization alone from those in whom MR will persist (thereby warranting ancillary interventions to treat MR and potentially avoid its long term clinical consequences). Results will provide key foundational insights concerning MR physiology, and thus will inform the design of future research focused on optimization of established and emerging therapeutic strategies to treat MR in patients unresponsive to revascularization alone.

Public Health Relevance

Mitral regurgitation (MR) is present in approximately 1 out of 5 patients with coronary artery disease (CAD) and is of substantial public health importance, conferring increased risk for heart failure, arrhythmia, and death when untreated. Coronary revascularization can improve or resolve MR in some patients, but uncertainty as to which patients with MR will respond to revascularization limits the ability to optimize treatment. This study will use state of the art cardiac magnetic resonance imaging (MRI) and computational modeling technologies to identify tissue-based predictors of MR response to revascularization, towards the goal of improved treatment for the millions of patients at risk for MR and its serious consequences.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
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Evans, Frank
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Weill Medical College of Cornell University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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