Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.
BACKGROUND
Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited.


OBJECTIVE
This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease.


METHODS
Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2).


RESULTS
At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients.


CONCLUSIONS
Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.
Imbriaco
M
M
Department of Biomorphological and Functional Sciences, University Federico II, Naples, Italy. mimbriaco@hotmail.com
Pisani
A
A
Spinelli
L
L
Cuocolo
A
A
Messalli
G
G
Capuano
E
E
Marmo
M
M
Liuzzi
R
R
Visciano
B
B
Cianciaruso
B
B
Salvatore
M
M
D000328:Adult; D004334:Drug Administration Schedule; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology; D007527:Isoenzymes / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
D007527:Isoenzymes; D000519:alpha-Galactosidase; C459420:agalsidase beta