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

每年约有790万美国人患有心力衰竭。其中，近250万人发展为缺血性二尖瓣反流(IMR)，自1995年以来增加了33%。即使有如此高的患病率，人们对慢性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。已知的是，IMR是继发于患者左心室(LV)的粗大三维几何改变，导致二尖瓣(MV)的几何改变。目前恢复LV和MV几何结构的手术修复技术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。预后不佳的最重要原因是缺乏对导致IMR的患者MV的确切3D几何变化的了解，如果没有这些变化，适当的手术治疗是不可能的。这项建议的目的是描绘和了解导致IMR的MV的几何扭曲，并制定适当的修复程序，在不久的将来可以直接转化为临床实践。我们长期目标的中心假设是：缺血性二尖瓣返流与二尖瓣环和/或瓣下水平的自然二尖瓣几何改变密切相关。了解这些改变将澄清缺血性二尖瓣返流的几何决定因素，并有助于设计更好和有效的修复程序，从而导致更好的手术结果。我们的假设是基于佐治亚理工学院和宾夕法尼亚大学的实验室产生的强大的初步数据。这项拟议的研究包括一种复杂的方法学，结合了体外和体内的方法来设计一种有效的IMR模型，该模型不仅可以检验假说，还可以开发新的手术方法。IMR的体内模型虽然有效，但重复性很好，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变形。此外，体外模型将是一个潜在的试验台，有更多的研究(除了目前建议的两年实验)，以开发新的MV外科修复技术，可以很容易地转化为临床实践。

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.