title: Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year.
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-[(18)F]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 in FDG uptake were related to changes in echocardiographic parameters or to measures of HIF activation.
  
  
  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.
authors.affiliation: Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Lundgrin
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Park
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sharp
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: James D
authors.initials: JD
authors.lastname: Thomas
authors.forename: Kewal
authors.initials: K
authors.lastname: Asosingh
authors.forename: Suzy A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Frank P
authors.initials: FP
authors.lastname: DiFilippo
authors.forename: Donald R
authors.initials: DR
authors.lastname: Neumann
authors.forename: Laura
authors.initials: L
authors.lastname: Davis
authors.forename: Brian B
authors.initials: BB
authors.lastname: Graham
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Iva
authors.initials: I
authors.lastname: Dostanic
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015687:Cell Hypoxia / Q000187:drug effects; D004452:Echocardiography / Q000379:methods; D004921:Erythropoietin / Q000097:blood; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D015203:Reproducibility of Results; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D015703:Antigens, CD; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019788:Fluorodeoxyglucose F18; D004921:Erythropoietin; D005947:Glucose