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的原因和进展知之甚少，导致目前这些患者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）的总体三维几何结构改变，导致二尖瓣（MV）的几何结构改变。目前用于恢复天然LV和MV几何形状的外科修复技术缺乏令人满意的长期患者结局。因此，与许多类型的癌症相比，IMR的长期生存率很差。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，否则不可能进行适当的手术治疗。本提案的目的是描述和了解导致IMR的MV几何失真，并开发可在不久的将来直接转化为临床实践的适当修复程序。驱动我们长期目标的中心假设是：缺血性二尖瓣返流与自体二尖瓣在瓣环和/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，并将有助于设计更好和更有效的修复手术，从而获得更好的手术结局。我们的假设是基于我们在格鲁吉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。拟议的研究包括一个复杂的方法结合体外和体内的方法来设计一个有效的IMR模型，不仅可以测试的假设，但也开发新的手术方法。尽管IMR的体内模型是有效的，但其可重复性非常好，并且仅模拟了人类IMR疾病的一种表现。体外IMR模型是一种通用模型，可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平台，具有额外的研究（超出目前提出的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。