title: Cardiac energy metabolism is disturbed in Fabry disease and improves with enzyme replacement therapy using recombinant human galactosidase A.
abstract: OBJECTIVE
  In vitro studies have shown impairment of energy metabolism in cardiac fibroblasts from Fabry patients. A recent in vivo study reported an association between cardiac energy metabolism and increased myocardial mass in Fabry patients. We therefore assessed possible disturbances of cardiac energy metabolism in Fabry patients by in vivo (31)P-MR-spectroscopy. Additionally, the effect of enzyme replacement therapy (ERT) on cardiac energetics was tested.
  
  
  RESULTS
  Twenty-three patients (41 ± 9 years; 10 females) with genetically proven Fabry disease were examined with a 1.5 T Scanner, and compared with an age-matched healthy control group. Eight patients underwent ERT and had follow-up examinations after 3 and 14 months. The high-energy phosphate molecules phosphocreatine (PCr) and adenosine triphosphate (ATP) were quantified in localized 31P-spectra by SLOOP (spectral localization with optimum point spread function). Cine- and late gadolinium enhancement (LGE) studies were also performed. When compared with healthy controls, Fabry patients demonstrated reduced PCr- (6.1 ± 1.9 vs. 8.8 ± 2.6 mmol/kg; P = 0.003) and ATP concentrations (3.9 ± 1.5 vs. 4.6 ± 1.0 mmol/kg; P = 0.048). During ERT, PCr concentrations increased (7.1 ± 1.5 mmol/kg vs. 6.1 ± 1.9; P < 0.05) and left ventricular mass decreased (215 ± 55 vs. 185 ± 45 g; P = 0.012). Disturbances in cardiac energetics were not correlated to the presence or absence of cardiac fibrosis on LGE.
  
  
  CONCLUSIONS
  Cardiac energy metabolism is disturbed in Fabry disease; this may play an important role in the pathogenesis of Fabry cardiomyopathy. Enzyme replacement therapy ameliorates energetic depression.
authors.affiliation: Institut für Röntgendiagnostik, Universität Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Machann
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Jörn
authors.initials: J
authors.lastname: Sandstede
authors.forename: Dietbert
authors.initials: D
authors.lastname: Hahn
authors.forename: Herbert
authors.initials: H
authors.lastname: Köstler
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000187:drug effects*; D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000378:metabolism* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D000519:alpha-Galactosidase / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000519:alpha-Galactosidase