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

Abstract Background 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 in men and women. Objectives We aimed to investigate sex-differences in the association between LVH degree and cardiovascular outcomes in patients with FD. Methods In this Italian 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 ischemic stroke. Results Women had lower LV wall thickness and LV mass than men and these differences were confirmed also indexing by body surface area or height (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 versus women (33% versus 11%; p=0.015). Values of LVMWT>10 mm were associated with an increased risk of the composite endpoint in women, while a LVMWT prognostic threshold of 13 mm 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. Conclusions In FD patients, sex-specific prognostic thresholds of LVH were identified, with women experiencing cardiovascular events at significantly lower values of LVMWT than men.Kaplan Meier for women (A) and men (B)