Myocardial Structure, Function, and Remodeling in Mitral Regurgitation

描述(由申请人提供)： 严重的、未纠正的二尖瓣反流(MR)的临床后果是过高的死亡率和发病率。手术干预慢性MR的时机仍然是心脏外科最具挑战性的临床决定之一。我们对二尖瓣关闭不全中的心室重构的发病机制的理解显然需要进一步完善，以改善临床结果。容量超负荷性肥厚的典型模型不能解释跨室壁肥厚重塑的差异。我们现在有了令人兴奋的初步结果，证明了在慢性二尖瓣反流期间，室壁重构存在跨壁梯度，其中心外膜变薄30%，心内膜增厚近10%。这项工作的总体假设是，对慢性二尖瓣反流的跨壁肥厚反应的差异可能预示着不良的临床结果。我的直接职业目标是开发必要的实验、计算和理论工具来测试有关心脏跨室壁差异的假说 二尖瓣反流的结构、功能和重构。通过心胸外科和心胸外科之间的跨学科合作，我可以获得一个独特的研究环境 斯坦福大学放射学专业。这一机会使我能够深入了解心脏病理生理学研究，并进一步发展我在心脏磁共振成像方面的专业知识。我的职业生涯规划包括在实验心脏生理学研究、定量组织学方法、扩散张量磁共振成像(DTMRI)以及整合结构和功能数据的计算技术方面获得丰富的专业知识。我的长期职业目标是获得一份终身教职，这样我就可以继续回答有关心脏结构、功能和疾病重塑的问题。独立阶段的工作将利用从MRI组织位移和DTMRI获得的数据，从二尖瓣关闭不全的啮齿动物模型开发第一个完整的心脏结构和功能的有限元模型。这项研究建议的相关性在于提高我们对二尖瓣返流的理解，二尖瓣返流是心力衰竭的常见原因。这项研究的结果可能有助于阐明从慢性二尖瓣反流到心力衰竭进展过程中的重要变化，并可能刺激创新疗法的发展，以帮助治疗这种疾病。(摘要结束)

DESCRIPTION (provided by applicant): The clinical consequence of severe, uncorrected mitral regurgitation (MR) is excess mortality and morbidity. The timing of surgical intervention in chronic MR remains one of the most challenging clinical decisions in cardiac surgery. A refinement in our understanding of the pathogenesis of ventricular remodeling in mitral regurgitation is clearly needed to improve clinical outcomes. The canonical model of ventricular remodeling in volume overload hypertrophy does not account for transmural differences in hypertrophic remodeling. We now have exciting preliminary results that demonstrate a transmural gradient in ventricular wall remodeling wherein the epicardium thins by 30% and the endocardium thickens by nearly 10% during chronic MR. The overall hypothesis of the work is that transmural differences in the hypertrophic response to chronic mitral regurgitation may portend a poor clinical outcome. My immediate career goal is to develop the necessary experimental, computational, and theoretical tools to test hypotheses about transmural differences in cardiac structure, function, and remodeling in mitral regurgitation. A unique research environment is available to me through an inter-disciplinary collaboration between the Departments of Cardiothoracic Surgery and Radiology at Stanford University. This opportunity affords the ability to gain a deep understanding of cardiac pathophysiology research in addition to further developing my expertise in cardiac magnetic resonance imaging. My career plan includes gaining considerable expertise in experimental cardiac physiology research, quantitative histologic methods, diffusion tensor magnetic resonance imaging (DTMRI), and computational techniques for integrating structure and function data. My long-term career goal is to secure a tenure-track faculty position so that I can continue to answer questions about cardiac structure, function, and remodeling in disease. Work during the Independent Phase will develop the first finite element model of integrated cardiac structure and function from a rodent model of mitral regurgitation using data acquired from MRI tissue displacement and DTMRI. The relevance of this research proposal regards improving our understanding of mitral regurgitation, a common cause of heart failure. The results of this research may help elucidate important changes that underlie the progression from chronic mitral regurgitation to over heart failure and may spur the development of innovative therapies to aid in the treatment of this disease. (End of Abstract)