title: Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure.
abstract: 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.
  
  
  
  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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.|Cardiovascular Division, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Kadkhodayan
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.|Debakey Cardiovascular Associates, Houston Methodist Hospital, Houston, USA.
authors.forename: C Huie
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Coggan
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Zulfia
authors.initials: Z
authors.lastname: Kisrieva-Ware
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Schechtman
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Novak
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Joseph
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Dávila-Román
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gropler
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Dence
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA. lpeterso@DOM.wustl.edu.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
mesh_terms: D000328:Adult; D003326:Coronary Circulation; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012727:Sex Characteristics
chemical_list: D005227:Fatty Acids
keywords: Sex; fatty acid imaging; heart failure; metabolism: PET; myocardial perfusion imaging: PET