Congestive heart failure (CHF) contributes to the death of 250,000 Americans yearly. 70% of heart failure cases are now due to coronary artery disease (CAD) and post myocardial infarction (MI) ventricular remodeling. Current operations that restore the failing left ventricle (LV) to a more normal size and shape have been generally ineffective in improving survival in end stage CHF patients. In the initial funding period of this project, using well characterized ovine models of post infarction ventricular remodeling, we demonstrated that early infarct expansion (IE) or stretching is a powerful stimulus for adverse remodeling. In corollary, IE is a potential target for preventive surgical intervention. Ischemic mitral regurgitation (EMR) could not be demonstrated to exacerbate remodeling during early (8 weeks) remodeling. In this competitive renewal the efficacy of early ventricular restraint as a technique to prevent adverse remodeling and CHF will be assessed using clinically relevant experimental scenarios that employ long post MI follow up periods (8 months). The importance of IMR to long-term remodeling will also be studied. The efficacy and durability of flat and saddle-shaped annuloplasty devices used alone or in combination with ventricular wrapping in preventing remodeling associated with early IMR will be also be evaluated. The effect of ventricular wrapping on LV systolic and diastolic function will be measured serially over an 8 month period to confirm that stabilizing ventricular geometry correlates with preserved LV function and does not impair diastolic performance. The goal of the project is, therefore, to establish and optimize the major technical parameters for operations designed to prevent adverse remodeling by the early amelioration of infarct expansion and/or IMR. The acceptance and successful clinical implementation of early surgical intervention to prevent post infarction remodeling will be enhanced by an imaging modality that identifies patients early after MI that are at high risk for long-term adverse remodeling and CHF. We intend to develop real time contrast enhanced 3D echocardiography as such an imaging technique. The strength of this proposal and likelihood of success are greatly enhanced by industrial collaborative relationships that we have developed with Phillips Medical Systems (3D echocardiographic assessment of ventricular and mitral valve remodeling), Acorn Cardiovascular, Inc. (supply and design of cardiac restraint devices) and St. Jude Medical, Inc. (supply and design of saddle shaped annuloplasty devices).
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