Quantitative Methods for Optimizing IMR Repair

缺血性二尖瓣返流（IMR）发生在二尖瓣（MV）因缺血性二尖瓣返流（IMR） 心肌梗死（MI）引起的左心室（LV）重塑。IMR存在于 50%左心室功能降低的患者接受冠状动脉旁路移植术（CABG） 影响了至少30万美国人问题的严重性是重大的， 随着人口老龄化，预计在未来20年内将大幅增长。二尖瓣修复， 尺寸过小的瓣环成形术目前是IMR的首选治疗方法。然而，1/3的 以这种方式治疗的患者在12个月内出现明显的复发性IMR。利用我们的真实的时间 三维超声心动图（rt-3DE）图像软件，我们已经证明，IMR在人类是 异质的在某些患者中，IMR的原因是瓣环扩张和变平。而在 其它的小叶栓系是主要的病理学。在最近的工作中，我们已经证明，它是在 后一组，尺寸过小的瓣环成形术不能提供持久的IMR修复。有 现在一致认为，治疗瓣叶栓系引起的IMR需要采取预防性手术。 但对于最佳程序没有达成共识。尽管有很大的兴趣， 开发这些程序时，报告的数据来自小型、单中心回顾性研究 问题研究多中心登记和随机试验将是必要的，以证明 程序是上级。鉴于拟议程序的数量和复杂性， 在此类研究的持续时间内，IMR手术优化不太可能有效 以这种方式进行。因此，很明显，新的计算方法指导 对于优化的瓣环成形术环设计和瓣叶增大手术， 通过最小化试错法来显著减少浪费的时间。我们因此 假设我们最先进的MV计算模型，可以直接利用 与新型有效MV瓣叶和腱索（MVCT）结合的rt-3DE成像数据 结构，可以与临床适用的大型动物模型结合使用， 定量开发优化设备和程序来治疗传单继发的IMR 拴系。为了证明这一假设，以下具体目标将通过利用 本课题组在以下几个方面的专长：1）IMR的发病机制，2）IMR动物模型，3）rt-3DE MV 成像，4）瓣成形环设计，4）MV细胞-组织耦合模型，以及5）微和 宏观解剖学上精确的MV有限元模型。

Ischemic mitral regurgitation (IMR) occurs when a mitral valve (MV) is rendered incompetent by left ventricular (LV) remodeling induced by a myocardial infarction (MI). IMR is present in over 50% of patients with reduced LV function undergoing coronary artery bypass grafting (CABG) and affects at least 300,000 Americans. The magnitude of the problem is significant and is expected to grow substantially during the next 20 years as the population ages. MV repair with undersized ring annuloplasty is currently the preferred treatment for IMR. However, 1/3 of all patients treated this way develop significant recurrent IMR within 12 months. Using our real time 3D echocardiography (rt-3DE) image software we have demonstrated that IMR in humans is heterogeneous. In some patients the cause of IMR is annular dilatation and flattening. While in others leaflet tethering is the major pathology. In recent work we have demonstrated that it is in the latter group that undersized ring annuloplasty does not provide durable IMR repair. There is now agreement that adjunctive procedures are required to treat IMR caused by leaflet tethering. But there is no consensus regarding the best procedure. Despite significant interest in developing these procedures the reported data are from small, single center retrospective studies. Multi-center registries and randomized trials would be necessary to prove which procedure is superior. Given the number of proposed procedures and the complexity and duration of such studies it is highly unlikely that IMR procedure optimization could be effectively carried out this way. It is thus becoming clear that novel computational approaches directed towards optimized annuloplasty ring design and leaflet augmentation procedures can substantially reduce wasted time by minimizing trial-and-error approaches. We thus hypothesize that our state-of-the-art MV computational models, which can directly utilize rt-3DE imaging data coupled to novel effective MV leaflet and chordae tendonae (MVCT) structures, can be used in conjunction with clinically applicable large animal models to develop quantitatively optimize devices and procedures to treat IMR secondary to leaflet tethering. To prove this hypothesis the following specific aims will be achieved by leveraging our group's expertise in: 1) the pathogenesis of IMR, 2) IMR animal models, 3) rt-3DE MV imaging, 4) annuloplasty ring design, 4) MV cell-tissue coupled models, and 5) micro- and macro-anatomically accurate MV finite element models.