Usefulness of tissue Doppler on early detection of cardiac disease in Fabry patients and potential role of enzyme replacement therapy (ERT) for avoiding progression of disease.

AIMS: Cardiac involvement, including progressive cardiomyopathy, is common in Fabry disease and is a leading cause of premature mortality. We sought to determine if tissue Doppler imaging (TDI) could identify Fabry disease patients at risk for the development of cardiomyopathy and if enzyme replacement therapy (ERT) with agalsidase alfa might slow or prevent the progression of cardiac involvement.

METHODS AND RESULTS: Fabry disease patients were enrolled in this prospective, observational study. Echocardiography was performed at baseline and periodically throughout the study. A single investigator, blinded to both the type of assessment (baseline or follow-up) and enzyme replacement status of the patient, evaluated all echocardiograms. Seventy-six patients (26 male, 50 females) were enrolled in the study. Twenty men and 13 women were treated with agalsidase alfa during the study. At baseline, increasing interventricular septum thickness was significantly associated with decreasing TDI velocities. Twenty-nine patients >18 years old (23 females) had no evidence of cardiac involvement at baseline (normal LVM and normal TDI velocities). In this cohort, 80% (16 of 20) of patients not on ERT progressed to demonstrating an abnormal TDI velocity during follow-up, whereas only 33% (3 of 9) of patients on ERT progressed to TDI abnormalities (P= 0.031).

CONCLUSION: In Fabry disease, reduced TDI velocity seems to be the initial sign of cardiac involvement that occurs before the development of cardiac hypertrophy. ERT with agalsidase alfa delays the onset of cardiac involvement and should be considered at an earlier stage of the disease, even in the absence of left ventricular hypertrophy.