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

描述（由申请人提供）：二尖瓣返流是急性心肌梗死（AMI）的一种严重并发症，因为它会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AMI的治疗取得了进展，但二尖瓣返流仍然很常见，超过50%的AMI后患者报告了二尖瓣返流。乳头肌梗死（可能是AMI的后果）提供了二尖瓣返流的机制，由此肌细胞坏死产生乳头肌功能障碍、二尖瓣瓣叶系留受损和反流。本研究的目的是确定AMI后乳头状梗死的发病率、预测因素和功能后果。该建议的核心是假设乳头状梗死将增加AMI后二尖瓣返流的风险。为了研究这一点，我将采用多模态成像来研究广泛的AMI后人群的乳头状梗死。延迟增强磁共振成像（MRI）将用于检测亚临床乳头状梗死;该技术能够以前所未有的方式在人体内检测乳头状肌细胞坏死，提供非侵入性梗死评估，密切复制组织病理学。两种延迟增强MRI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;将比较这些技术以确定3D成像与2D成像的发生率是否更高。将获得并分析全面的临床、血管造影和影像学变量，以确定乳头状梗死的预测因素。在控制传统临床和影像学预测因素后，将使用连续随访超声心动图评估乳头肌梗死是否独立预测AMI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心房重构之间的关系。本研究的结果可能提供关于乳头肌梗死作为AMI后二尖瓣返流和心腔重塑的预测因子的重要见解。通过这个项目，它整合了我在心血管成像和成果研究的兴趣，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。我将通过临床研究硕士学位获得临床研究和统计分析原则的正式培训。我将接受先进心脏MRI技术的教学和实践培训，特别关注自由呼吸MRI。我将在心脏成像和流行病学研究领域的两位主要研究者的指导下实施我的研究。这个职业发展计划将提高我作为一名医生-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。 项目叙述：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。乳头肌梗死是二尖瓣返流的一种机制，可以通过心脏磁共振成像（MRI）来识别，MRI是一种强大的成像工具，可以检测到以前从未见过的乳头肌梗死。本研究将使用心脏MRI研究AMI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.