Sex difference in cardiac metabolism in
nonischemic heart failure: Insight for prognostic
value of altered cardiac metabolism
Hyung-Jun Im, MD, PhD,
and Gi Jeong Cheon, MD, PhD
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of
Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul
National University, Seoul, Korea
Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea
Received Mar 25, 2016; accepted Mar 25, 2016
See related article, pp. 1226–1235
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 glu-
cose 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 metabo-
lism, 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
this study ﬁrstly showed that the sex dif-
ference 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 nonis-
chemic HF is a maladaptation. In particular, recent
mouse studies indicate that lower FA metabolism can
exacerbate nonischemic heart failure.
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.
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,
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
Previous studies on glucose metabolism in HF
are less consistent,
and the consequence of shifting
toward high glucose metabolism in HF is also in con-
In several studies using mice, increased
glucose utilization showed favorable cardiac out-
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@
J Nucl Cardiol 2017;24:1236–8.
Copyright Ó 2016 American Society of Nuclear Cardiology.