Quantitative Force Measurements to Optimize Valve Repair for Ischemic MR

描述（由申请人提供）：缺血性二尖瓣返流（IMR）发生在心肌梗死诱导的左心室重塑导致结构正常的二尖瓣（MV）功能不全时。IMR影响160万至280万美国人。采用尺寸过小的平环瓣环成形术进行二尖瓣修复已成为首选治疗方法。然而，最近的研究表明，这种方法在手术后6个月内的失败率为30%。大多数失效是由于进行性瓣叶拴系和瓣环成形术环裂开导致的，其机制涉及瓣环和腱索应力分布。这些次优应力分布部分是由于尺寸过小的瓣环成形术可能通过进一步损害基础LV几何形状和功能而加重LV重塑过程。尺寸过小的瓣环成形术的不足是由于其未能满足Carpentier成功二尖瓣修复的两个基本要求：它不能重建正常的瓣环几何形状，也不能充分恢复瓣叶活动度。初步工作已经证明鞍形瓣环成形术和瓣叶扩张术在改善IMR修复中的前景。然而，目前没有数据支持关于IMR最佳修复技术的共识。因此，我们设计了本项目的具体目的，以检验以下假设：使瓣环几何结构正常化并恢复瓣叶活动度的IMR修复技术将通过促进更好的基础LV功能、更少的LV重构恶化以及减少瓣环和腱索应力分布，实现更持久的修复。我们对这一关键临床问题的创新方法利用了我们集团独特的外科和工程专业知识。使用IMR的体内和体外模型，结合新型成像和力传感器技术，我们将评估瓣环成形术形状和瓣叶组织增强对瓣膜力分布的影响。这种实验方法允许临床前优化用于IMR的二尖瓣修复手术，因此仅需要在患者中测试最有前途的技术。

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.