Quantitative Force Measurements to Optimize Valve Repair for Ischemic MR

描述（由申请人提供）：当结构正常的二尖瓣（MV）由于心肌梗死引起的左心室重构而导致功能不全时，发生缺血性二尖瓣反流（IMR）。IMR对160万到280万美国人的影响。二尖瓣成形术已成为二尖瓣修复的首选方法。然而，最近的研究表明，这种方法在手术6个月内的失败率为30%。大多数失败是由于渐进式小叶栓系和环成形术引起的环开裂，这意味着环和弦应力分布是其机制。这些不理想的应力分布部分是由于较小的环成形术可能会进一步损害左室的基本几何形状和功能，从而加剧左室重塑过程。小二尖瓣成形术的不足之处在于它未能满足卡彭蒂尔对成功修复二尖瓣的两个基本要求：它不能重建正常的环几何形状，也不能充分恢复小叶的活动力。初步的工作已经证明了鞍形环成形术和小叶增强术在改善IMR修复方面的前景。然而，目前还没有数据支持关于IMR最佳修复技术的共识。因此，我们设计了本项目的具体目标，以验证IMR修复技术的假设，即通过正常化环几何形状和恢复小叶流动性，通过促进更好的左室基础功能，减少左室重塑的恶化以及减少环和弦索应力分布，将导致更持久的修复。我们对这一关键临床问题的创新方法利用了我们团队独特的外科和工程专业知识的结合。利用体内和体外IMR模型，结合新型成像和力传感器技术，我们将评估环成形术形状和小叶组织增强对瓣膜力分布的影响。这样的实验方法允许临床前优化二尖瓣修复程序的IMR，所以只有最有前途的技术需要在患者身上进行测试。

DESCRIPTION (provided by applicant): Ischemic mitral regurgitation (IMR) occurs when a structurally normal mitral valve (MV) is rendered incompetent as a result of myocardial infarction induced left ventricular remodeling. IMR effects between 1.6 to 2.8 million Americans. Mitral valve repair with undersized flat ring annuloplasty has become the preferred treatment. However, recent studies have demonstrated this approach is associated with a failure rate of 30% within 6 months of surgery. Most failures result from progressive leaflet tethering and annuloplasty ring dehiscence which implicates annular and chordal stress distribution as a mechanism. These suboptimal stress profiles are due, in part, to the fact that undersized annuloplasty likely accentuates the LV remodeling process by further impairing basal LV geometry and function. The inadequacy of undersized annuloplasty results from its failure to fulfill two of Carpentier's fundamental requirements for successful mitral valve repair: it does no reestablish normal annular geometry nor does it adequately restore leaflet mobility. Preliminary work has demonstrated the promise of saddle-shaped annuloplasty and leaflet augmentation in improving IMR repair. However, there are currently no data to support a consensus as to the optimal repair technique for IMR. Therefore, we have designed the specific aims of this project to test the hypothesis that IMR repair techniques that normalize annular geometry and restore leaflet mobility will result in more durable repairs by promoting better basal LV function, less exacerbation of LV remodeling and reduced annular and chordal stress distribution. Our innovative approach to this critical clinical problem leverages our group's unique combination of surgical and engineering expertise. Using both in vivo and in vitro models of IMR in combination with novel imaging and force transducer technology, we will assess the effect annuloplasty shape and leaflet tissue augmentation on valvular force distribution. Such an experimental approach allows for the preclinical optimization of a mitral valve repair procedures for IMR so only the most promising techniques need to be tested in patients.