Heart failure is one of the most important causes of morbidity and mortality in the United States and strategies to reduce its burden to society require a greater understanding of human myocardial dysfunction and its natural history. The most common etiology of heart failure in the U.S. is coronary artery disease and thus the earliest manifestations of systolic myocardial dysfunction in humans are likely to be regional in nature. However, a large proportion of patients with heart failure have diastolic dysfunction with preserved systolic function. In these, hypertension and aging are established pre-disposing factors but early precursors of this condition remain unknown. Previous longitudinal studies aimed at elucidating the pathophysiology of heart failure were not structured to measure regional alterations of systolic and/or diastolic function directly. This study was specifically designed to fill this knowledge gap by obtaining MRI tagging studies in 2,126 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline for the purpose of detecting the earliest manifestations of systolic and diastolic myocardial dysfunction in humans. In this continuation study, we propose to repeat MRI tagging in 1,300 of those participants to define the natural history of changes in regional and global systolic and diastolic function relative to the development and progression of sub-clinical disease and risk factors over 3-5 years. In addition, we will also examine whether changes in regional function predict the development of global LV dysfunction, symptomatic congestive heart failure and death. Baseline cross-sectional analyses will be used to define markers and risk factors of interest. Pilot studies on the magnitude of regional function change from 60 participants over 1-2 years indicate that the proposed studies have ample power to test all specific aims. The same MRI protocol and analytical tools will be used to assure precise comparisons with baseline data. We expect to define the natural history of myocardial dysfunction in humans of different ethnicities and different exposures to risk factors. We anticipate that these studies will permit the identification of the earliest precursors of heart failure by demonstrating crucial relationships between sub-clinical disease and incident regional myocardial dysfunction, and between regional dysfunction and incident symptomatic failure. These findings will be pivotal to the design of future strategies to forestall progressive myocardial dysfunction and prevent the development of heart failure. [unreadable] [unreadable]