Myocardial Structure, Function, and Remodeling in Mitral Regurgitation

严重、未纠正的二尖瓣返流（MR）的临床后果是死亡率和发病率过高。 慢性二尖瓣返流的手术时机仍然是最具挑战性的临床决策之一， 心脏手术对二尖瓣狭窄患者心室重构发病机制的认识 显然需要回流来改善临床结果。心室重构的经典模型 在容量超负荷中，肥大不能解释肥厚性重构的跨壁差异。我们 现在有了令人兴奋的初步结果，证明了心室壁重塑的跨壁梯度 其中在慢性MR期间，心外膜变薄30%，而内膜增厚近10%。 这项工作的总体假设是，慢性二尖瓣肥厚反应的跨壁差异 反流可能预示不良的临床结果。我近期的职业目标是发展必要的 实验，计算和理论工具，以测试心脏跨壁差异的假设， 二尖瓣返流的结构、功能和重塑。一个独特的研究环境对我来说是可用的 通过心胸外科部门之间的跨学科合作， 斯坦福大学的放射学。这个机会提供了深入了解心脏的能力， 除了进一步发展我在心脏磁共振方面的专业知识外， 显像我的职业规划包括在实验心脏生理学方面获得相当多的专业知识 研究，定量组织学方法，扩散张量磁共振成像（DTMRI），和 整合结构和功能数据的计算技术。我的长期职业目标是确保 终身教职，这样我就可以继续回答有关心脏结构，功能， 疾病中的重塑独立阶段的工作将开发第一个有限元模型， 使用从二尖瓣反流的啮齿动物模型获得的数据， MRI组织移位和DTMRI。这项研究提案的相关性涉及改善我们的 了解二尖瓣返流，这是心力衰竭的常见原因。这项研究的结果可能有助于 阐明从慢性二尖瓣返流进展为心脏过度的重要变化 失败，并可能刺激创新疗法的发展，以帮助治疗这种疾病。

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.