Congestive heart failure (CHF) is one of the most prevalent and lethal diseases in the United States. The most common etiology of CHF is infarction-induced left ventricular (LV) remodeling secondary to coronary artery disease and myocardial infarction (Ml). Treatments for established CHF are of limited efficacy: over the past 50 years the 5-year mortality of CHF has stubbornly remained at approximately 50%. Currently medical and surgical therapy is only initiated after significant ventricular remodeling has occurred and symptoms have developed. Earlier intervention in high risk patients would likely improve treatment results. Developing strategies to reduce the burden to society of CHF will require a more complete understanding of the pathogenesis of infarction induced LV remodeling. Currently, adverse LV remodeling after Ml is poorly predicted by accepted techniques for patient risk stratification. This is in great part due to the inability of all current noninvasive imaging modalities to adequately describe full three dimensional (3D) myocardial function and perfusion. Magnetic resonance imaging (MRI), using our newly developed 3D myocardial tagging and first-pass perfusion techniques, now has the ability to simultaneously image LV geometry, regional myocardial function (i.e. borderzone function) and local myocardial perfusion throughout the entire ventricle. MRI is safe and non-invasive making it uniquely suited to the study of ischemic cardiac disease and the pathophysiology of LV remodeling. Using three ovine infarction models - one that results in adverse remodeling and the other two that result in a compensated ventricle - we plan to test the hypothesis that regional changes in myocardial function (especially in the normally perfused borderzone region adjacent to the infarct) that occur early after infarction (before heart failure develops) can predict the long-term outcome of infarction-induced remodeling. We will correlate potential early predictors of LV remodeling - including borderzone curvature, wall-thickness, changes in regional contractile function and alterations in myocardial perfusion - with the outcome of remodeling as assessed by traditional measures, including LV volumes and ejection fraction. Therefore, the primary objective of this project is to develop a novel, noninvasive method of identifying patients early after infarction who are at risk for developing adverse remodelinq and CHF, thereby allowing early, aggressive, and targeted therapy intended to prevent the remodeling process before it even begins. [unreadable] [unreadable] [unreadable]