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Heart has the highest metabolic demands than any other organs. To maintain contractile function of the heart, constant and rapid production of adenosine triphosphate (ATP) is needed. Fatty acid (FA) and glucose are the main fuels for production of the ATPs by mitochondrial oxidative phosphorylation. In normal condition, 60% to 90% of total ATP is made from FA and the other from glucose or lactate. In a failing heart, cardiac metabolism is profoundly altered, and majority of the studies suggest that FA metabolism decreases. However, it is not clear and still in controversy whether the alteration in cardiac metabolism in a failing heart is an adaptation or maladaptation.– In this issue of the Journal, Kadkhodayan et al compared myocardial blood flow (MBF), FA metabolism, and glucose metabolism between men and women with nonischemic HF, and found that MBF and FA metabolism were higher in women than men, which were independent of age, obesity, and insulin resistance. Although higher MBF and FA metabolism in women are well known, this study firstly showed that the sex difference of MBF and FA metabolism still stands true in subjects with nonischemic HF. Also the authors found that high MBF was associated with the prognosis. Although, FA metabolism did not show significant association with survival in this study, there has been a hypothesis that decreased FA metabolism in nonischemic HF is a maladaptation. In particular, recent mouse studies indicate that lower FA metabolism can exacerbate nonischemic heart failure. Also, ‘obesity paradox’ is supporting the hypothesis, which is the observation that obese heart failure patients have better prognosis than nonobese heart failure patients even though obesity is risk factor for heart failure. In this study, it is hard to conclude the association between high FA metabolism and prognosis, because the size of this study was too small and potential confounding factors including perfusion reserve were not evaluated. Thus, the hypothesis on association between FA metabolism and prognosis in nonischemic HF should be confirmed in a larger study with adjustment of other prognostic markers especially sex and perfusion reserve. In young and healthy subjects, women have lower glucose extraction fraction and utilization than men, in contrast, sex difference of glucose metabolism was not found in patients with nonischemic HF in this study. This result could reinforce the previous finding that FA and glucose metabolism are not always counterbalanced in HF. Previous studies on glucose metabolism in HF are less consistent, and the consequence of shifting toward high glucose metabolism in HF is also in controversy. In several studies using mice, increased glucose utilization showed favorable cardiac outcome. In contrast, one recent prospective clinical study showed that high FDG uptake in right ventricle predicted worse outcome in patients with pulmonary arterial hypertension. Meanwhile, FDG PET/CT or MR can also be utilized to assess inflammatory activity in Reprint requests: Gi Jeong Cheon, MD, PhD, Department of Nuclear Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea; larrycheon@ gmail.com J Nucl Cardiol 2017;24:1236–8. 1071-3581/$34.00 Copyright 2016 American Society of Nuclear Cardiology.

Sex difference in cardiac metabolism in nonischemic heart failure: Insight for prognostic value of altered cardiac metabolism