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

缺血性二尖瓣反流的环形和瓣下修复技术：In-

• 批准号: 7727112
• 负责人: AJIT P YOGANATHAN
• 金额: $ 39.43万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7727112
• 关键词: American; Anatomy; Animal Experiments; Animal Model; Animal Testing; Animals; Automobile Driving; Beds; Cardiac Surgery procedures; Chronic; Clinical Data; Color; Communities; Congestive Heart Failure; Data; Data Reporting; Dilatation - action; Disease; Failure; Functional disorder; Funding; Future; Grant; Heart failure; High Prevalence; Human; In Vitro; Individual; Knowledge; Laboratories; Lead; Left; Left ventricular structure; Measurement; Measures; Mechanics; Medical; Methodology; Mitral Valve; Mitral Valve Insufficiency; Modeling; Operative Surgical Procedures; Outcome; Patients; Pennsylvania; Procedures; Role; Secondary to; Severities; Shapes; Simulate; Structure; Survival Rate; Symptoms; Techniques; Testing; Time; TimeLine; Translating; United States National Institutes of Health; Universities; Ventricular; Work; base; cancer type; clinical practice; design; hemodynamics; in vitro Model; in vivo; in vivo Model; mortality; novel; papillary muscle; repaired; research study; valve replacement

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.

每年大约有 790 万美国人患有心力衰竭。其中，近 250 万人患有缺血性二尖瓣反流 (IMR)，自 1995 年以来增加了 33%。即使患病率如此之高，但对慢性 IMR 的病因和进展知之甚少，导致这些患者目前缺乏有效的医疗选择。可以肯定的是，IMR 继发于患者左心室 (LV) 的总体三维几何改变，导致二尖瓣 (MV) 的几何改变。目前恢复左心室和二尖瓣几何形状的手术修复技术缺乏令人满意的长期患者治疗效果。因此，与许多类型的癌症相比，IMR 的长期生存率很低，甚至更差。结果不佳的最重要原因是缺乏对导致 IMR 的患者 MV 的确切 3D 几何改变的了解，否则就不可能进行适当的手术治疗。该提案的目的是描述和理解导致 IMR 的 MV 几何变形，并开发适当的修复程序，在不久的将来可以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环状和/或瓣膜下水平的天然二尖瓣的几何改变密切相关。了解这些改变将阐明缺血性二尖瓣反流的几何决定因素，并将有助于设计更好、更有效的修复程序，从而获得更好的手术结果。我们的假设是根据佐治亚理工学院和宾夕法尼亚大学实验室产生的强有力的初步数据制定的。拟议的研究包括一种复杂的方法，结合体外和体内方法来设计有效的 IMR 模型，该模型不仅可以测试假设，还可以开发新的手术方法。 IMR 体内模型虽然有效，但重复性非常好，并且仅模拟人类 IMR 疾病的一种表现形式。体外 IMR 模型是一种多功能模型，可以精确控制施加在阀门上的几何变形。此外，体外模型将成为一个潜在的试验台，可进行额外的研究（超出目前提议的 2 年实验），用于开发可轻松转化为临床实践的新型 MV 手术修复技术。