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 entail a more complete understanding of its natural history. The most common etiology of heart failure in the U.S. is coronary artery disease. Therefore, in this country, pathologic processes preceding the development of cardiac failure are commonly regional in nature. However, previous studies aimed at elucidating the pathophysiology of heart failure were limited to the utilization of global indices of LV dilatation and functional impairment, or used methods with poor reproducibility to quantify regional abnormalities of LV function. In addition, symptomatic heart failure frequently coexists with preserved systolic function, particularly in the elderly. For this condition, which is currently attributed to diastolic dysfunction associated with ventricular hypertrophy, coronary artery disease and aging, no sub-clinical markers are available. This study is designed to fill these knowledge gaps in the pathophysiology of heart failure by utilizing MRI tissue tagging to detect the earliest signs of systolic dysfunction, as well as diastolic regional and global impairment. We propose to study participants of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA) to assess regional myocardial systolic and diastolic dysfunction at baseline, and relate it to the development of global LV dysfunction, symptomatic heart failure and death over 6-8 years of MESA follow-up. The addition of MRI tagging to the MESA MRI protocol will entail only 5-10 extra minutes and analysis will be performed by a novel automated method. Finally, we also propose to study the impacts of left ventricular hypertrophy, clinical ischemic events and sub-clinical atherosclerosis on the predictive value of regional dysfunction for the development of sub-clinical and symptomatic heart failure. Sub-clinical atherosclerosis will be quantified as part of MESA by coronary calcification using CT, and carotid wall thickness using ultrasound. We anticipate to elucidate the precursors of sub-clinical heart failure caused by global systolic dysfunction, and develop novel indices of regional and/or global myocardial diastolic impairment, as sub-clinical markers of heart failure associated with preserved systolic dysfunction.
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