Future directions of myocardial fatty acid imaging

Abstract

The hierarchy of cardiac fuel consumption forms the basis of fatty acid (FA) imaging of the myocardium in acute and chronic ischemic heart disease. FAs are the predominant (70%-80%) steady-state energy substrate used by the myocardium for adenosine triphosphate (ATP) production. 1 In the setting of ischemia or hypoxia, the metabolism of FAs through -oxidation is reduced, and the metabolism of glucose becomes the primary source of energy. 2 This adaptive switch in energy substrate utilization is a functional response to metabolic stress, as oxidation of glucose over FAs results in 11% greater ATP production per mole of oxygen consumed. The switch to glucose metabolism therefore provides for more efficient energy production in an oxygen-deprived state. During ischemia or hypoxia, high free FA levels also have numerous deleterious effects. Such effects include increased myocardial oxygen consumption, inhibition of both glycolytic flux and the repletion of citric acid cycle intermediates (anaplerosis), impairment of calcium and hydrogen ion homeostasis (potentially contributing to cell membrane damage and arrhythmia), and accumulation of toxic intracellular FA derivatives such as acyl carnitine and acyl coenzyme A. 2 After percutaneous revascularization in the setting of acute myocardial infarction (AMI), increased myocyte FA levels enhance ischemic injury upon reperfusion. The substrate pattern of oxidative metabolism early during reperfusion may influence the severity of postischemic injury. 1 Accordingly, metabolic pharmacotherapy to protect the myocardium after acute ischemia, including such agents as dichloroacetate and ranolazine, focuses on enhancing the switch to glucose utilization over free FAs, mainly through activation of the pyruvate dehydrogenase complex. 3-5 The switch to glucose utilization in the setting of limited oxygen supply is therefore an adaptive, functional, and protective mechanism. This process provides an opportunity and a platform for diagnostic imaging of myocardial metabolism through the use of radiolabeled free FA analogs. Recent data support the concept that FA imaging successfully demonstrates a metabolic imprint of an ischemic episode and thus may provide an important diagnostic tool in the evaluation of acute chest pain. 6 In the setting of heart failure, FA imaging may also provide important predictive information regarding prognosis, risk stratification for future adverse events, and identification of candidates for further revascularization or adjunctive therapy. This report describes the potential for such clinical applications of evaluating metabolic patterns of energy substrate utilization through radionuclide FA imaging, with a focus on the potential for imaging via widely available single photon emission computed tomography (SPECT) cameras.