Early detection of Fabry cardiomyopathy by tissue Doppler imaging

• Published in: Circulation (New York, N.Y.) Vol. 107; no. 15; pp. 1978 - 1984
• Main Authors: PIERONI, Maurizio, CHIMENTI, Cristina, RICCI, Roberta, SALE, Patrizio, RUSSO, Matteo Antonio, FRUSTACI, Andrea
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 22.04.2003; American Heart Association, Inc
• Subjects: Adult; alpha-Galactosidase - genetics; Arrhythmias, Cardiac - etiology; Biological and medical sciences; Biopsy; Cardiac Catheterization; Cardiology. Vascular system; Cardiomyopathies - diagnostic imaging; Cardiomyopathies - etiology; Cardiomyopathies - physiopathology; Diastole; Fabry Disease - complications; Fabry Disease - diagnosis; Fabry Disease - genetics; Female; Heart; Humans; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - etiology; Male; Medical sciences; Middle Aged; Mutation; Myocardial Contraction - genetics; Myocarditis. Cardiomyopathies; Myocardium - pathology; Myocardium - ultrastructure; Predictive Value of Tests; Systole; Ultrasonography, Doppler; Vacuoles - ultrastructure; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - etiology; Cardiomyopathy; echocardiography; Fabry disease; Cardiovascular disease; Lipids; tissue; Duplex ultrasonography; Enzymopathy; Myocardial disease; Genetic determinism; Vascular disease; Gene; Heart disease; Lipoidosis; Sonography; Human; Nervous system diseases; Clinical form; Metabolic diseases; Medical screening; Left ventricle; Genetic disease; biopsy; Medical imagery; Mutation; Hypertrophy
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000061952.27445.A0

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. 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. 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.