Mitral regurgitation is a serious complication of acute myocardial infarction (AMI) as it impairs cardiac performance and confers increased risk for adverse outcomes such as heart failure and death. Despite advances in treatment of AMI, mitral regurgitation remains common and has been reported in over 50% of post-AMI patients. Papillary muscle infarction - which can be a consequence of AMI - provides a mechanism for mitral regurgitation, whereby myocyte necrosis produces papillary muscle dysfunction, impaired tethering of the mitral valve leaflets, and regurgitant flow. The goal of this research proposal is to identify incidence, predictors, and functional consequences of papillary infarction following AMI. Central to this proposal is the hypothesis that papillary infarction will confer increased risk for development of post-AMI mitral regurgitation. To investigate this, I will employ multimodality imaging to study papillary infarction a broad post-AMI population. Delayed enhancement magnetic resonance imaging (MRI) will be used to detect sub-clinical papillary infarction;This technique enables in-vivo detection of papillary myocyte necrosis in a manner never before possible in humans, providing non-invasive infarct assessment that closely replicates histopathology. Two delayed enhancement MRI techniques - breath-held two dimensional (2D) and free-breathing three dimensional (3D) imaging - will be used to assess incidence of papillary infarction;The techniques will be compared to determine whether incidence is greater with 3D vs. 2D imaging. Comprehensive clinical, angiographic, and imaging variables will be obtained and analyzed to identify predictors of papillary infarction. Serial follow-up echocardiography will be used to assess whether papillary muscle infarction independently predicts long-term risk for post-AMI mitral regurgitation after controlling for traditional clinical and imaging predictors. Analysis will also be performed to assess the relationship between papillary muscle infarction and left atrial remodeling. The results of this study may provide important insights regarding papillary muscle infarction as a predictor of mitral regurgitation and cardiac chamber remodeling in the post-AMI setting. Through this project, which integrates my interests in cardiovascular imaging and outcomes research, I will receive valuable mentorship and attain critical skills within the context of a 5 year career development award. I will obtain formal training in principles of clinical research and statistical analysis through a Master's degree in clinical investigation. I will receive didactic and hands-on training in advanced cardiac MRI techniques, with specific focus on free breathing MRI. I will implement my research study with mentorship provided by two leading investigators in cardiac imaging and epidemiologic research. This career development plan will enhance my capabilities as a physician-scientist and will enable me to develop future independent projects that employ cardiac imaging as a tool to study cardiac pathophysiology and improve patient care.
Mitral regurgitation is a serious complication of acute myocardial infarction (AMI) as it impairs cardiac performance and confers increased risk for adverse outcomes such as heart failure and death. Papillary muscle infarction, which provides a mechanism for mitral regurgitation, can be identified using cardiac magnetic resonance imaging (MRI) - a powerful imaging tool that enables detection of papillary infarcts never before seen. This study will use cardiac MRI to study incidence, predictors, and functional consequences of papillary muscle infarction following AMI.
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