Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure
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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 = 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 = 0.02).
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.
KeywordsSex myocardial perfusion imaging: PET fatty acid imaging heart failure metabolism: PET
Myocardial blood flow
Positron emission tomography
Extracorporeal membrane oxygenation
Homeostasis model assessment of insulin resistance
Body surface area
The authors wish to thank the study subjects for their participation, Douglas L. Mann, MD and Kitty O’Callaghan for editorial assistance, and Ava Ysaguirre for assistance with manuscript preparation. We also wish to thank Karen Gillis Taylor for graciously allowing us to use her artwork on our recruitment flyers and posters.
This study was supported by Barnes-Jewish Hospital Foundation Grant (St. Louis, Missouri); American Society of Nuclear Cardiology (Bethesda, Maryland), Mentors in Medicine Grant (St. Louis, Missouri); and the National Institutes of Health (Bethesda, Maryland): UL1TR000448 (ICTS), and P30-DK020579 (DRTC), R01HL58878.
The authors have nothing to disclose related to this work.
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