Annular and Sub-Valvular Repair Techniques for Ischemic Mitral Regurgitation: In-

每年大约有790万美国人患有心力衰竭。其中，近250万人发生缺血性二尖瓣返流（IMR），自1995年以来增加了33%。即使有如此高的患病率，对慢性IMR的病因和进展知之甚少，导致目前缺乏针对这些患者的有效医疗选择。可以肯定的是，IMR是继发于患者左心室（LV）的三维几何改变，导致二尖瓣（MV）的几何改变。目前的外科修复技术，以恢复原生左室和中室几何形状缺乏令人满意的长期患者结果。因此，与许多类型的癌症相比，IMR的长期存活率很低，甚至更差。结果不佳的最重要原因是缺乏对导致IMR的患者中动脉的确切三维几何变化的了解，没有这些知识，就不可能进行适当的手术治疗。本提案的目的是描述和理解导致IMR的中MV的几何扭曲，并制定适当的修复程序，以便在不久的将来直接转化为临床实践。推动我们长期目标的中心假设是：缺血性二尖瓣反流与先天性二尖瓣环和/或瓣下水平的几何改变密切相关。了解这些改变将澄清缺血性二尖瓣返流的几何决定因素，并有助于设计更好、更有效的修复程序，从而获得更好的手术效果。我们的假设是基于我们在佐治亚理工学院和宾夕法尼亚大学的实验室中产生的强有力的初步数据而制定的。本研究采用了一种复杂的方法，结合体外和体内方法来设计一个有效的IMR模型，不仅可以验证假设，还可以开发新的手术入路。IMR的体内模型虽然有效，但可重复性很好，只模拟了人类IMR疾病的一种表现。体外IMR模型是一种多功能模型，可以精确控制施加在瓣膜上的几何扭曲。此外，体外模型将是一个潜在的试验台，可以进行额外的研究（超出目前提议的2年实验），以开发新的中压手术修复技术，这些技术可能很容易转化为临床实践。

Approximately 7.9 million Americans suffer from heart failure every year. Among these, nearly 2.5 million develop Ischemic Mitral Regurgitation (IMR), a 33% increase since 1995. Even with such high prevalence, little is known of the cause and progression of chronic IMR, resulting in the current lack of effective medical options for these patients. What is known for certain is that IMR is secondary to gross three dimensional geometric alterations of the patient’s Left Ventricle (LV), resulting in alterations in the geometry of the Mitral Valve (MV). Present surgical repair techniques to restore native LV and MV geometries lack satisfactory long-term patient outcomes. Consequently, long-term survival rates for IMR are poor and worse as compared to many types of cancer. The most important reason for the poor outcome is the lack of knowledge of the exact 3D geometric alterations of the patient’s MV responsible for IMR, without which appropriate surgical treatment is not possible. The objective of this proposal is to delineate and understand the geometric distortions of the MV that lead to IMR and develop appropriate repair procedures that can be directly translated to clinical practice in the near future. The central hypothesis driving our long objectives is: Ischemic Mitral Regurgitation is strongly related to geometric alterations of the native mitral valve at the annular and/or sub-valvular levels. Understanding these alterations will clarify the geometric determinants of Ischemic Mitral Regurgitation and will help in designing better and efficient repair procedures thus leading to better surgical outcomes. Our hypothesis has been formulated based on strong preliminary data produced in our laboratories at Georgia Tech and the University of Pennsylvania. The proposed study consists of a sophisticated methodology combining in-vitro and in-vivo approaches to design an efficient IMR model that can not only test the hypothesis but also develop novel surgical approaches. The in-vivo model of IMR though effective is very reproducible and mimics only one representation of the human IMR disease. The in-vitro IMR model is a versatile model that provides precise control over the geometric distortions imposed on the valve. Also, the in-vitro model will be a potential test-bed with additional studies (beyond the currently proposed 2 year experiments) for developing novel MV surgical repair techniques that may be easily translated to clinical practice.