DESCRIPTION (provided by applicant): Over the past 2 decades, major changes in the epidemiology of myocardial infarction (MI) have occurred. Progress in its acute treatment improved short term survival, but heart failure (HF) remains frequent after MI and leads to excess mortality. Hence, the acute treatment of MI aimed at restoring vessel patency is not sufficient to prevent HF, underscoring the importance of understanding the contemporary mechanisms leading to its development. The transition from the initial myocardial injury to ventricular dysfunction and HF is termed left ventricular remodeling and is characterized by progressive ventricular enlargement, alteration of systolic and diastolic function and occurrence of mitral regurgitation (MR). Remodeling is a dynamic entity, defined as a change over time, diagnosed at a stage where deleterious changes cannot be reversed. Hence, it must be predicted and prevented. Knowledge on cardiac remodeling after MI is incomplete, which hinders its prevention. Firstly, the exact incidence of remodeling remains to be defined as data pertain mostly to clinical trials, of uncertain clinical relevance. Secondly, the mechanisms of ventricular remodeling after MI remain to be defined with the goal of identifying novel predictors that could define targets for prevention and treatment. Thirdly, most imaging data on remodeling do not reflect state of the art methods or contemporary cohorts. Thus, addressing the frequency and mechanisms of remodeling after MI is needed to define strategies to prevent HF and requires relying on clinically relevant populations evaluated by rigorous imaging techniques integrated with measurements of novel biomarkers. Our 3 specific aims will help elucidate, within a prospective community cohort, the frequency and mechanisms of ventricular remodeling and the responsibilities of these mechanisms in the genesis of post MI HF. Aim 1 will measure the frequency and patterns of left ventricular remodeling after incident MI in a community-based population. Remodeling will be evaluated by two- and three-dimensional echocardiography and speckle tracking and defined as changes in systolic or diastolic function and MR. Aim 2 will assess the determinants of remodeling, including clinical characteristics and novel biomarkers. Aim 3 will test the value of the predictors of remodeling identified in Aim 2 to predict HF after MI. In Aims 1 and 2, we will recruit 420 patients to obtain serial two-dimensional and three-dimensional echocardiographic studies. Aim 3 will extend these findings to the entire population-based MI incidence cohort. Our proposed application comprises several key innovative aspects. Our ongoing surveillance of coronary disease will provide a strong recruitment platform and a robust backdrop to optimize the clinical relevance of our data. Rigorous imaging approaches will provide unique insights into the remodeling process. We will integrate imaging and biomarker data to identify predictors of remodeling that can be measured at index MI to enable risk prediction of HF in contemporary MI populations.
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