Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure

Ana Kadkhodayan, C. Huie Lin, Andrew R. Coggan, Zulfia Kisrieva-Ware, Kenneth B. Schechtman, Eric Novak, Susan M. Joseph, Víctor G. Dávila-Román, Robert J. Gropler, Carmen Dence, Linda R. Peterson

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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 = 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). 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.

Original languageEnglish
Pages (from-to)1226-1235
Number of pages10
JournalJournal of Nuclear Cardiology
Volume24
Issue number4
DOIs
StatePublished - Aug 1 2017

Keywords

  • Sex
  • fatty acid imaging
  • heart failure
  • metabolism: PET
  • myocardial perfusion imaging: PET

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