.Ischemic mitral regurgitation (IMR), or """"""""functional"""""""" MR as a consequence of coronary heart disease, continues to defy surgical attempts to repair the mitral valve in a predictable fashion because we still do not understand the mechanisms responsible for IMR. Postoperative survival is only about 55 percent after 5 years, and debate continues as to whether repair is preferable to replacement. While ring annuloplastyworks in most patients with annular dilation and normal leaflet motion, such an approach can be unreliable in those who have """"""""complex"""""""" MR jets and/or apical leaflet tethering, which results in restricted systolic leaflet motion. Our ignorance of the mechanisms responsible for IMR has been reduced by work in experimental models of acute IMR, but the real clinical problem and surgical challenge is patients with chronic I1 IR. Chronic animal experiments are rare due to high cost and the inescapable animal attrition that these preparations entail. Clinical progress, however, will continue to be tentative and empirical until controlled studies of chronic IMR are performed which tell us how and why these morphologically normal valves leak. We propose to apply our myocardial marker technology (which can measure submillimeter instantaneous changes in leaflet, annular, papillary muscle, and left ventricular 3-D geometry and dynamic motion throughout the cardiac cycle on a beat-to-beat basis) to determine the mechanisms responsible for chronic IMR in an ovine myocardial infarction model and to define how the therapeutic effects of ring annuloplasty differ from those of a novel trans-annular suture reparative technique (Septal-Lateral Annular Cinching, or """"""""SLAC""""""""), which we have shown can eliminate acute IMR. To address these issues, we set forth the following Specific Aims: #1) To elucidate the basic pathophysiology o chronic ischemic mitral regurgitation, with particular emphasis on the 3-D geometry of the mitral leaflets in relation t about one another and to the other components of the mitral valvular-ventricular complex. This work will define for the frst time the causal basis of chronic IMR as a function of the evolving interrelationships between leaflet, annular, and ventricular pathologic abnormalities. #2) To investigate in a randomized, controlled fashion a new surgical treatment, """"""""SLAC,"""""""" for chronic IMR and to determine the mechanistic basis for the beneficial effects conferred by either the conventional surgical approach (undersized ring annuloplasty) or this new SLAC technique based on differences in LV remodeling, interactions between leaflet, annular, and ventricular 3-D dynamics, and valvular competency. Comparison of the effects of ring annuloplasty and SLAC on LV geometry as well as leaflet and annular 3-D motion and dynamics will reveal why patients might benefit from one approach versus the other, beyond simply eliminating the MR. These experiments promise to add fundamental knowledge which will lead to more intelligent design of new, more effective, and more predictable surgical approaches for patients with CAD and chronic ischemic mitral regurgitation.
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