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

Abstract

Background

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.

Methods/Results

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.

Conclusions

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

Clinical Trials #: NCT01625663.

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Abbreviations

BTHS:

Barth syndrome

WUSTL:

Washington University in St. Louis

LV:

Left ventricular

2D:

Two-dimensional

PET:

Positron emission tomography

PCr/ATP:

Phosphocreatine to adenosine triphosphate ratio

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Acknowledgments

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.

Disclosures

None.

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Correspondence to William Todd Cade PT, PhD.

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Funding

This work was supported by the National Institutes of Health R01HL107406-01, K01EB010171, P30DK056341, P30DK020579, HD007434, S10RR024532, and UL1TR000448 from the National Center for Research Resources and NIH Roadmap for Medical Research. Additional support provided by the Barnes-Jewish Hospital Foundation to the Cardiovascular Imaging and Clinical Research Core Laboratory.

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Cade, W.T., Laforest, R., Bohnert, K.L. et al. Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome. J. Nucl. Cardiol. 28, 1649–1659 (2021). https://doi.org/10.1007/s12350-019-01933-3

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  • DOI: https://doi.org/10.1007/s12350-019-01933-3

Keywords

  • Metabolic
  • PET
  • metabolism imaging agents
  • cardiomyopathy