Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome

  • William Todd CadeEmail author
  • Richard Laforest
  • Kathryn L. Bohnert
  • Dominic N. Reeds
  • Adam J. Bittel
  • Lisa de las Fuentes
  • Adil Bashir
  • Pamela K. Woodard
  • Christina A. Pacak
  • Barry J. Byrne
  • Robert J. Gropler
  • Linda R. Peterson
Original Article



Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function.


Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of 15O-water and 1-11C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging. LV function and cardiac high-energy phosphate metabolism were examined via echocardiography and 31P magnetic resonance spectroscopy, respectively. Myocardial glucose extraction fraction (21 ± 14% vs 10 ± 8%, P = .03) and glucose utilization (828.0 ± 470.0 vs 393.2 ± 361.0 μmol·g−1·min−1, P = .02) were significantly higher in BTHS vs Control. Myocardial FA extraction fraction (31 ± 7% vs 41 ± 6%, P < .002) and uptake (0.25 ± 0.04 vs 0.29 ± 0.03 mL·g−1·min−1, P < .002) were significantly lower in BTHS vs Control. Altered myocardial metabolism was associated with lower cardiac function in BTHS.


Myocardial substrate metabolism is altered and may contribute to LV dysfunction in BTHS.

Clinical Trials #: NCT01625663.


Metabolic PET metabolism imaging agents cardiomyopathy 



Barth syndrome


Washington University in St. Louis


Left ventricular




Positron emission tomography


Phosphocreatine to adenosine triphosphate ratio



We thank the nursing staff at the WUSTL Institute for Clinical and Translational Sciences Clinical Research Unit for their hard work and altruism. We especially thank Kitty Krupp, RN, for her work with study radioisotope tracer administration and blood draws and the staff at the WUSTL CCIR for acquisition of the PET scans. Lastly, we thank the participants and their families for their dedication and effort to travel to St. Louis and participate in this study.



Supplementary material

12350_2019_1933_MOESM1_ESM.pdf (81 kb)
Supplementary material 1 (PDF 82 kb)
12350_2019_1933_MOESM2_ESM.pdf (26 kb)
Supplementary material 2 (PDF 27 kb)
12350_2019_1933_MOESM3_ESM.mp3 (2.4 mb)
Supplementary material 3 (MP3 2466 kb)


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Copyright information

© American Society of Nuclear Cardiology 2019

Authors and Affiliations

  • William Todd Cade
    • 1
    • 2
    Email author
  • Richard Laforest
    • 3
  • Kathryn L. Bohnert
    • 1
  • Dominic N. Reeds
    • 2
  • Adam J. Bittel
    • 1
  • Lisa de las Fuentes
    • 2
  • Adil Bashir
    • 3
    • 4
  • Pamela K. Woodard
    • 3
  • Christina A. Pacak
    • 5
  • Barry J. Byrne
    • 5
  • Robert J. Gropler
    • 3
  • Linda R. Peterson
    • 2
    • 3
  1. 1.Program in Physical TherapyWashington University School of MedicineSt. LouisUSA
  2. 2.Department of MedicineWashington University School of MedicineSt. LouisUSA
  3. 3.Department of RadiologyWashington University School of MedicineSt. LouisUSA
  4. 4.Department of Electrical and Computer EngineeringAuburn UniversityAuburnUSA
  5. 5.Department of PediatricsUniversity of FloridaGainesvilleUSA

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