Sex affects myocardial blood ﬂow and fatty acid
substrate metabolism in humans with
nonischemic heart failure
Ana Kadkhodayan, MD,
C. Huie Lin, MD, PhD,
Andrew R. Coggan, PhD,
Zulﬁa Kisrieva-Ware, MD, PhD,
Kenneth B. Schechtman, PhD,
Eric Novak, MS,
Susan M. Joseph, MD,
ctor G. Da
Robert J. Gropler, MD,
Carmen Dence, MS,
and Linda R. Peterson, MD, FAHA
Department of Medicine, Washington University School of Medicine, St. Louis, MO
Cardiovascular Division, Department of Medicine, Mayo Clinic, Rochester, MN
Cardiovascular Division, Department of Medicine, Washington University School of Medicine,
St. Louis, MO
Debakey Cardiovascular Associates, Houston Methodist Hospital, Houston
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO
Received Dec 27, 2015; accepted Feb 25, 2016
Background. In animal models of heart failure (HF), myocardial metabolism shifts from
high-energy fatty acid (FA) metabolism toward glucose. However, FA (vs glucose) metabolism
generates more ATP/mole; thus, FA metabolism may be especially advantageous in HF. Sex
modulates myocardial blood ﬂow (MBF) and substrate metabolism in normal humans. Whether
sex affects MBF and metabolism in patients with HF is unknown.
Methods and Results. We studied 19 well-matched men and women with nonischemic HF
(EF £ 35%). MBF and myocardial substrate metabolism were quantiﬁed using positron
emission tomography. Women had higher MBF (mL/g/minute), FA uptake (mL/g/minute), and
FA utilization (nmol/g/minute) (P < 0.005, P < 0.005, P < 0.05, respectively) and trended
toward having higher FA oxidation than men (P 5 0.09). These ﬁndings were independent of
age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial
glucose uptake or metabolism. Higher MBF was related to improved event-free survival (HR
0.31, P 5 0.02).
Conclusions. In nonischemic HF, women have higher MBF and FA uptake and metabolism
than men, irrespective of age, obesity, or insulin resistance. Moreover, higher MBF portends a
better prognosis. These sex-related differences should be taken into account in the development
and targeting of novel agents aimed at modulating MBF and metabolism in HF. (J Nucl Cardiol
Key Words: Sex
Æ myocardial perfusion imaging: PET Æ fatty acid imaging Æ heart failure Æ
Electronic supplementary material The online version of this
article (doi:10.1007/s12350-016-0467-6) contains supplementary
material, which is available to authorized users.
Drs Ana Kadkhodayan and C. Huie Lin are co-ﬁrst authors.
Reprint requests: Linda R. Peterson, MD, FAHA, Cardiovascular Divi-
sion, Department of Medicine, Washington University School of
Medicine, Campus Box 8086, St. Louis, MO 63110; lpeterso@DOM.
Clinical Trials #: NCT00776035.
Copyright Ó 2016 American Society of Nuclear Cardiology.