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Journal of Nuclear Cardiology

, Volume 24, Issue 4, pp 1226–1235 | Cite as

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. PetersonEmail author
Original Article

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.

Keywords

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

Abbreviations

HF

Heart failure

FA

Fatty acid

ATP

Adenosine triphosphate

MBF

Myocardial blood flow

PET

Positron emission tomography

ECMO

Extracorporeal membrane oxygenation

HOMA-IR

Homeostasis model assessment of insulin resistance

BSA

Body surface area

Notes

Acknowledgments

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.

Funding sources

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.

Disclosures

The authors have nothing to disclose related to this work.

Supplementary material

12350_2016_467_MOESM1_ESM.pptx (5.8 mb)
Supplementary material 1 (PPTX 5984 kb)

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Copyright information

© American Society of Nuclear Cardiology 2016

Authors and Affiliations

  • Ana Kadkhodayan
    • 1
    • 2
  • C. Huie Lin
    • 3
    • 4
  • Andrew R. Coggan
    • 5
  • Zulfia Kisrieva-Ware
    • 5
  • Kenneth B. Schechtman
    • 6
  • Eric Novak
    • 3
  • Susan M. Joseph
    • 3
  • Víctor G. Dávila-Román
    • 3
  • Robert J. Gropler
    • 5
  • Carmen Dence
    • 5
  • Linda R. Peterson
    • 3
    Email author
  1. 1.Department of MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Cardiovascular Division, Department of MedicineMayo ClinicRochesterUSA
  3. 3.Cardiovascular Division, Department of MedicineWashington University School of MedicineSt. LouisUSA
  4. 4.Debakey Cardiovascular AssociatesHouston Methodist HospitalHoustonUSA
  5. 5.Mallinckrodt Institute of RadiologyWashington University School of MedicineSt. LouisUSA
  6. 6.Division of BiostatisticsWashington University School of MedicineSt. LouisUSA

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