Delayed Enhancement MRI for Detection of Sub-Clinical Papillary Muscle Infarction

描述(申请人提供)：二尖瓣返流是急性心肌梗死(AMI)的严重并发症，因为它损害心脏功能，并增加心力衰竭和死亡等不良结局的风险。尽管急性心肌梗死的治疗取得了进展，但二尖瓣返流仍然很常见，据报道，超过50%的急性心肌梗死后患者发生了二尖瓣返流。乳头肌梗死--这可能是急性心肌梗死的后果--为二尖瓣返流提供了一种机制，心肌细胞坏死会导致乳头肌功能障碍、二尖瓣叶系留功能受损和返流。这项研究计划的目的是确定急性心肌梗死后乳头状梗死的发生率、预测因素和功能后果。这一建议的核心假设是，乳头状梗死将增加发生急性心肌梗死后二尖瓣反流的风险。为了研究这一点，我将使用多模式成像来研究广泛的急性心肌梗死后人群中的乳头状梗死.延迟增强磁共振成像(MRI)将用于检测亚临床乳头状肌梗死；这项技术能够以前所未有的方式在体内检测乳头状肌细胞坏死，提供与组织病理学紧密复制的非侵入性脑梗塞评估。两种延迟增强磁共振成像技术--屏气二维(2D)和自由呼吸三维(3D)成像--将用于评估乳头状梗死的发生率；这两种技术将进行比较，以确定3D成像与2D成像的发病率是否更高。将获得并分析综合的临床、血管造影和影像变量，以确定乳头状梗死的预测因素。在控制了传统的临床和影像预测指标后，系列随访超声心动图将用于评估乳头肌梗死是否独立预测急性心肌梗死后二尖瓣返流的长期风险。还将进行分析以评估乳头肌梗死与左房重构的关系。这项研究的结果可能为乳头肌梗死作为二尖瓣返流和心腔重构的预测因子在急性心肌梗死后环境中提供重要的见解。通过这个项目，结合了我对心血管成像和结果研究的兴趣，我将获得宝贵的指导，并在5年职业发展奖的背景下获得关键技能。我将通过临床调查硕士学位获得临床研究和统计分析原理的正式培训。我将接受先进的心脏核磁共振技术的教学和实践培训，重点是自由呼吸核磁共振。我将在心脏成像和流行病学研究领域的两位主要研究人员的指导下，实施我的研究研究。这一职业发展计划将增强我作为内科科学家的能力，并使我能够开发未来的独立项目，将心脏成像作为研究心脏病理生理学和改善患者护理的工具。 项目简介：二尖瓣返流是急性心肌梗死(AMI)的严重并发症，因为它损害心脏性能，增加心力衰竭和死亡等不良后果的风险。乳头肌梗死为二尖瓣返流提供了一种机制，可以使用心脏磁共振成像(MRI)来识别，这是一种强大的成像工具，可以检测出前所未有的乳头肌梗死。这项研究将使用心脏MRI来研究急性心肌梗死后乳头肌梗死的发生率、预测因素和功能后果。

DESCRIPTION (provided by applicant): 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. Project Narrative: 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.