Premium
Cardiac energy metabolism is disturbed in Fabry disease and improves with enzyme replacement therapy using recombinant human galactosidase A
Author(s) -
Machann Wolfram,
Breunig Frank,
Weidemann Frank,
Sandstede Jörn,
Hahn Dietbert,
Köstler Herbert,
Neubauer Stefan,
Wanner Christoph,
Beer Meinrad
Publication year - 2011
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfq211
Subject(s) - enzyme replacement therapy , medicine , fabry disease , energy metabolism , recombinant dna , alpha galactosidase , enzyme , heart failure , cardiology , disease , biochemistry , biology , gene
Aims 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. Methods and 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. Conclusion 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.