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Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement
Niccolo Maurizi1, Albina Nowak2, Christiane Gruner3
1Department of Cardiology, University Hospital of Lausannne, Lausanne, Switzerland.
Insights
Enzyme replacement therapy (ERT) did not prevent left ventricular hypertrophy (LVH) progression in 36% of Anderson-Fabry disease (AFD) patients over 10 years. Baseline LVH predicted worse outcomes, underscoring the need for early intervention in AFD.
Area of Science:
- Cardiology
- Genetics
- Pharmacology
Background:
- Anderson-Fabry disease (AFD) is a rare genetic disorder.
- Enzyme replacement therapy (ERT) is a treatment option for AFD.
- The impact of ERT on left ventricular hypertrophy (LVH) progression in AFD requires further investigation.
Purpose of the Study:
- To evaluate the long-term efficacy of ERT in preventing cardiac progression, specifically LVH, in AFD patients.
- To identify predictors of LVH progression and major AFD-related events during ERT.
Main Methods:
- A cohort of 60 AFD patients receiving ERT with a minimum 5-year follow-up was analyzed.
- Cardiac progression was defined as an increase in left ventricular mass index (LVMI) >10 g/m².
- Transthoracic echocardiography was used to assess LVMI at baseline and during follow-up.
Main Results:
- Over a median follow-up of 10.5 years, 36% of patients showed LVMI progression.
- LVMI progression was more common in men and individuals over 30 years old.
- Baseline LVH (OR 1.3, p=0.02) and male sex were significant predictors of LVMI progression.
Conclusions:
- A significant proportion of AFD patients experience LVMI progression despite long-term ERT.
- Early LVH at ERT initiation is a strong predictor of cardiac progression and adverse events.
- These findings highlight the importance of early diagnosis and intervention in AFD management.
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/m2 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/m2). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7-17.6) g/m2 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.
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