DESCRIPTION (provided by applicant): Heart failure (HF) remains a leading cause of morbidity and mortality in the United States. With the majority of new HF diagnoses occurring in adults over age 75 years, HF is now recognized as a life course disease. It logically follows that a person's increasing risk for HF should manifest with progressive cardiac abnormalities that can be tracked over time, in relation to advancing age and cumulative risk exposures. However, conventional imaging methods have limited ability to discriminate between individuals more or less likely to develop clinical HF. We and others have shown that advanced ultrasonic measures of cardiac microstructure can reliably quantify tissue-level alterations in the cellular and extracellular composition of the myocardium, including fibrosis. Based on our prior work and preliminary data, we hypothesize that changes in cardiac microstructure over time are influenced by cumulative exposure to risk factors and that distinct patterns of change in cardiac microstructure can differentiate individuals at greater or lesser risk for HF. Therefore, we propose to use a novel ultrasonic method to study the changes in cardiac microstructure that occur over the life course and leading up to the development of HF and related adverse outcomes. Specifically, we will investigate: (1) the natural history and correlates of change in cardiac microstructure with aging, (2) the extent to which progressive alterations in cardiac microstructure predispose specifically to HF, and (3) the potential utility of cardiac microstructure to serve as a prognostic marker of risk for adverse outcomes across the spectrum of HF among persons living in the community. The overall contribution of the proposed research is expected to include: a comprehensive understanding of how cardiac microstructure is altered during the progression from risk factors to the onset of HF outcomes; and evaluation of a novel imaging-based measure of cardiac microstructure that could serve as a widely-accessible and cost-effective tool for predicting HF in individuals at risk. These contributions will be significant because they will lay groundwork for developing targeted interventions to reduce HF related morbidity and mortality in the population at large.