Sex-specific prognostic thresholds of left ventricular hypertrophy in fabry disease

Left ventricular hypertrophy (LVH) is one of the main prognostic factors in Fabry disease (FD). Despite the known impact of sex on the phenotypic expression of the disease, a ‘fixed’ threshold of left ventricular maximal wall thickness (LVMWT) > 12 mm is conventionally used for defining overt cardiac involvement. We aimed to investigate sex-differences in the association between LVH degree and cardiovascular outcomes in FD.

In this multicenter retrospective study, 347 patients with FD (57% women) were enrolled and echocardiographic data collected. The study endpoint was defined as the composite of mortality, hospitalization for heart failure, atrial fibrillation, major brady- or tachy-arrhythmias and ischaemic stroke. Women had lower LV wall thickness and LV mass than men and these differences were confirmed also indexing for body surface area (BSA) (all P < 0.001). After a median follow-up of 53 (IQR: 26–90) months, 64 patients (18%) met the study endpoint. The composite-event rate at 8 years was significantly higher in men vs. women (33% vs. 11%; P = 0.015). Values of LVMWT > 10 mm (or indexed LVMWT > 6.1 mm/m²) were associated with an increased risk of the composite endpoint in women, while a LVMWT prognostic threshold of 13 mm (or 6.9 mm/m²) was identified in men (both P < 0.001). These cut-off values were independently associated with outcomes, after adjustment for age, exposure to specific therapy and renal function.

In FD patients, sex-specific prognostic thresholds of LVH were identified, with women experiencing cardiovascular events at significantly lower values of LVMWT than men, even after accounting for BSA.