Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year

Erika L. Lundgrin, Margaret M. Park, Jacqueline Sharp, W. H Wilson Tang, James D. Thomas, Kewal Asosingh, Suzy A. Comhair, Frank P. DiFilippo, Donald R. Neumann, Laura Davis, Brian B. Graham, Rubin M. Tuder, Iva Dostanic, Serpil C. Erzurum*

*Corresponding author for this work

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Background: The development of tools to monitor the right ventricle in pulmonary arterial hypertension (PAH) is of clinical importance. PAH is associated with pathologic expression of the transcription factor hypoxia-inducible factor (HIF)-1α, which induces glycolytic metabolism and mobilization of proangiogenic progenitor (CD34+CD133+) cells. We hypothesized that PAH cardiac myocytes have a HIF-related switch to glycolytic metabolism that can be detected with fasting 2-deoxy-2-[ 18F]fluoro-D-glucose positron emission tomography (FDG-PET) and that glucose uptake is informative for cardiac function. Methods: Six healthy control subjects and 14 patients with PAH underwent fasting FDG-PET and echocardiogram. Blood CD34+CD133+cells and erythropoietin were measured as indicators of HIF activation. Twelve subjects in the PAH cohort underwent repeat studies 1 year later to determine if changes inFDGuptake were related to changes in echocardiographic parameters or to measures of HIF activation. Measurements and Results: FDG uptake in the right ventricle was higher in patients with PAH than in healthy control subjects and correlated with echocardiographic measures of cardiac dysfunction and circulating CD34 +CD133+ cells but not erythropoietin. Among patients with PAH, FDG uptake was lower in those receiving β-adrenergic receptor blockers. Changes in FDG uptake over time were related to changes in echocardiographic parameters and CD34+CD133+ cell numbers. Immunohistochemistry of explanted PAH hearts of patients undergoing transplantation revealed that HIF-1α was present in myocyte nuclei but was weakly detectable in control hearts. Conclusions: PAH hearts have pathologic glycolytic metabolism that is quantitatively related to cardiac dysfunction over time, suggesting that metabolic imaging may be useful in therapeutic monitoring of patients.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalAnnals of the American Thoracic Society
Volume10
Issue number1
DOIs
StatePublished - Feb 2013

Keywords

  • Alpha subunit
  • Fluorodeoxyglucose F18
  • Heart failure
  • Hypoxia-inducible factor 1
  • Positron emission tomography
  • Right ventricle

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Lundgrin, E. L., Park, M. M., Sharp, J., Tang, W. H. W., Thomas, J. D., Asosingh, K., Comhair, S. A., DiFilippo, F. P., Neumann, D. R., Davis, L., Graham, B. B., Tuder, R. M., Dostanic, I., & Erzurum, S. C. (2013). Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Annals of the American Thoracic Society, 10(1), 1-9. https://doi.org/10.1513/AnnalsATS.201206-029OC