Free fatty acid metabolism via beta-oxidation represents the major source of energy for the normal heart. Recently, a new sulphur substituted fatty acid analog, 14-18F-fluoro-6-thio-heptadecanoic acid (FTHA) has been proposed as a trapped fatty acid analog. This fatty acid tracer has demonstrated rates of trapping which are directly related to beta-oxidation rates of fatty acids. The minimal back- diffusion of the label following FTHA administration suggests the capability to quantitate beta-oxidation rates in a manner similar to fluorodeoxyglucose studies for determining glucose phosphorylation rates. Preliminary human studies have demonstrated excellent imaging characteristics for FTHA in normal human subjects. No studies, however, have been performed in humans with known coronary artery disease and recent infarction or ischemia and patients with ischemic cardiomyopathy. The initial aims of the proposal are to determine if changes in dietary intake have any effect on FTHA uptake, distribution, or retention in humans. This will be important to standardize further clinical protocols with FTHA. The study of patients with myocardial infarction will be performed to determine the ability of FTHA to define the location and extent of myocardial infarction. An assessment of the metabolic consequences of acute myocardial infarction will be determined using both a qualitative assessment of FTHA uptake and a quantitative assessment of defect size. Additionally, the study of patients with myocardial ischemia as demonstrated by ischemic perfusion using rest/stress sestamibi scans will be performed with FTHA. The ability of FTHA to determine fatty acid metabolism under conditions of ischemia and infarction following reperfusion therapy with myocardial revascularization or medical therapy will be determined. Finally, with long-term follow-up of patients with ischemic and nonischemic cardiomyopathy we hope to demonstrate the prognostic capability of FTHA for this subgroup of patients in terms of hospitalization rates, time to transplantation, and death rates. From a clinical perspective, evaluation of rates of beta-oxidation in humans will have important clinical implications. In patients with ischemic cardiomyopathy, for example, changes in fatty acid metabolism may have implications for identifying patients who may require early revascularization or transplantation. Additionally, the ability to assess viable myocardium which may recover after revascularization versus nonrecoverable myocardium is clinically important.
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