Early detection of Fabry cardiomyopathy by tissue Doppler imaging.
BACKGROUND
Fabry cardiomyopathy is diagnosed by detection of left ventricular hypertrophy (LVH) in patients with alpha-Galactosidase A deficiency. Conventional noninvasive tools are unable to provide a preclinical diagnosis allowing prompt institution of enzymatic therapy.


RESULTS
We studied three groups of patients: 10 patients with causal mutations for Fabry disease and LVH, 10 mutation-positive patients without LV, and 10 healthy relatives without causal mutations and no LVH. All patients with LVH and 6 patients with Fabry disease without LVH with complex repetitive ventricular arrhythmias underwent biventricular endomyocardial biopsy to assess cardiac involvement. In all patients 2-dimensional echocardiography with tissue Doppler analysis in the pulsed Doppler mode was performed: systolic (Sa), early diastolic (Ea), and late diastolic (Aa) velocities were measured, and the Ea/Aa ratio and the dimensionless parameter E/Ea were computed at both corners of the mitral annulus. Histology and electron microscopy studies showed glycosphingolipid deposits in all cases. All mutation-positive patients had significant reduction of Sa, Ea, and Aa velocities at both corners of the mitral annulus compared with normal control subjects. Ea/Aa ratio was significantly lower and E/Ea ratio significantly higher in mutation-positive patients than in control subjects. Patients with LVH showed significantly lower contraction and relaxation tissue Doppler velocities, lower Ea/Aa ratio, and higher E/Ea ratio in comparison with mutation-positive patients with no LVH.


CONCLUSIONS
Fabry cardiomyopathy is characterized by reduced myocardial contraction and relaxation tissue Doppler velocities, detectable even before development of LVH. Tissue Doppler imaging can provide a preclinical diagnosis of Fabry cardiomyopathy, allowing early institution of enzyme replacement therapy.
Pieroni
Maurizio
M
Department of Cardiology, Catholic University, Rome, Italy.
Chimenti
Cristina
C
Ricci
Roberta
R
Sale
Patrizio
P
Russo
Matteo Antonio
MA
Frustaci
Andrea
A
D000328:Adult; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001706:Biopsy; D006328:Cardiac Catheterization; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D003971:Diastole; D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009200:Myocardial Contraction / Q000235:genetics; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D011237:Predictive Value of Tests; D013599:Systole; D018608:Ultrasonography, Doppler; D014617:Vacuoles / Q000648:ultrastructure; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology; D000519:alpha-Galactosidase / Q000235:genetics
D000519:alpha-Galactosidase