Quantitative Methods for Optimizing IMR Repair

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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.