Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy
Niccolò Maurizi, Albina Nowak, Christiane Gruner, Mehdi Namdar, Christian Schmied, Alessandra Pia Porretta, Guillaume Barbey, Véronique Monzambani, Pierre Monney, Frédéric Barbey
Abstract
Background Enzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may still progress despite ERT over a long-term follow-up is still unclear. Methods Consecutive patients with AFD from the Independent Swiss-Fabry Cohort receiving ERT who were at least followed up for 5 years were included. Cardiac progression was defined as an increase of >10 g/m 2 in left ventricular mass index (LVMI) between the first and the last available follow-up transthoracic echocardiography. Results 60 patients (35 (23–48) years, 39 (65%) men) were followed up for 10.5 (7.2–12.2) years. 22 had LVH at ERT start (LVMI of 150±38 g/m 2 ). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7–17.6) g/m 2 per 100 patient-years, of these 7 (11%, 29±13 years) with no LVH at baseline. Three of them progressed to LVH. LVMI progression occurred mostly in men (17 of 39 (43%) vs 5 of 21 (24%), p<0.01) and after the age of 30 years (17 of 22 (77%)). LVH at ERT start was associated with LVMI progression (OR 1.3, 95% CI 1.1 to 2.6; p=0.02). A total of 19 (31%) patients experienced a major AFD-related event. They were predominantly men (17 of 19, 89%), older (45±11 vs 32±9 years) with baseline LVH (12 of 19, 63%), and 10 of 19 (52%) presented with LVMI progression. Conclusions Over a median follow-up of >10 years under ERT, 36% of the patients still had LVMI cardiac progression, and 32%, predominantly older men, experienced major AFD-related events. LVH at treatment initiation was a strong predictor of LVMI progression and adverse events on ERT.