Enzyme replacement therapy with agalsidase β improves cardiac involvement in Fabry's disease

TLDR

Fabry disease, an X‑linked lysosomal storage disorder caused by α‑galactosidase deficiency, leads to glycosphingolipid accumulation and severe concentric left‑ventricular hypertrophy, the main cause of death, yet data on enzyme replacement therapy’s cardiac effects are scarce. Nine Fabry cardiomyopathy patients were evaluated clinically, electrocardiographically, and echocardiographically—including Doppler transmitral and pulmonary flow—at baseline and after 6 and 12 months of algasidase β treatment. Enzyme replacement therapy reduced interventricular septal thickness and left‑ventricular mass (p < 0.025 and p < 0.001), improved LV stiffness, and shortened the pulmonary vein flow duration difference, without altering heart rate, arterial pressure, or LV diameters.

Abstract

Fabry's disease is an X‐linked lysosomal storage disease caused by a deficiency of α‐galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase β (Fabrazyme ® ). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p &lt; 0.025) and in LV mass (p &lt; 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p &lt; 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness.