title: Cardiac sympathetic activity in 22q11.2 deletion syndrome.
abstract: OBJECTIVE
  22q11.2 deletion syndrome (22q11.2DS) affects catechol-O-methyl-transferase (COMT), which involves the degradation of norepinephrine (NE). Clinically, adults with 22q11.2DS are at increased risk for sudden unexpected death. Although the causes are likely multifactorial, increased cardiac sympathetic activity with subsequent fatal arrhythmia, due to increased levels of NE, should be considered as a possible mechanism predisposing to this premature death. The purpose of this study was to determine whether cardiac sympathetic activity is increased in 22q11.2DS, both at baseline and following an acute NE depletion with alpha-methyl-para-tyrosine (AMPT).
  
  
  METHODS
  Five adults with 22q11.2DS and five age- and sex-matched healthy controls underwent 2 sessions with either AMPT or placebo administration before (123)I-mIBG scintigraphy. Heart-to-mediastinum ratios (H/M) were determined from the images 15min (early) and 4h (late) after administration of (123)I-mIBG and the washout (WO) was calculated as an indicator of adrenergic drive.
  
  
  RESULTS
  At baseline there were no significant differences in both early and late H/M between 22q11.2DS and controls. However, there was a significant difference in WO between 22q11.2DS and controls (-4.92±2.8 and -10.44±7.2, respectively; p=0.027), but a "negative WO" does not support an increased sympathetic drive. In addition there was a trend towards a higher late H/M after AMPT administration compared to baseline which was more pronounced in 22q11.2DS.
  
  
  CONCLUSIONS
  This study for the first time suggests normal cardiac sympathetic activity in adults with 22q11.2DS assessed by (123)I-mIBG scintigraphy. Although there is a small difference in adrenergic drive compared to healthy subjects, this most likely does not explain the increased unexpected death rate in the 22q11.2 DS population.
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Cardiology, Zaans Medical Center, Zaandam, The Netherlands. Electronic address: d.o.verschure@amc.uva.nl.
authors.forename: Derk O
authors.initials: DO
authors.lastname: Verschure
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; The Dalglish Family Hearts and Minds Clinic for Adults with 22q11.2 Deletion Syndrome, Toronto, Ontario, Canada.
authors.forename: Erik
authors.initials: E
authors.lastname: Boot
authors.affiliation: Department of Psychiatry and Psychology, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Thérèse A
authors.initials: TA
authors.lastname: van Amelsvoort
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Berthe L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.affiliation: Cardiology Centers of the Netherlands, Amsterdam, The Netherlands.
authors.forename: G Aernout
authors.initials: GA
authors.lastname: Somsen
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Verberne
mesh_terms: D019797:3-Iodobenzylguanidine / Q000008:administration & dosage; D000328:Adult; D004062:DiGeorge Syndrome / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D055815:Young Adult; D019805:alpha-Methyltyrosine / Q000008:administration & dosage*
chemical_list: D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D019805:alpha-Methyltyrosine
keywords: 22q11.2 deletion syndrome; AMPT; Cardiac sympathetic activity; Monoamine depletion; Planar MIBG myocardial scintigraphy