18 Prevalence of aortic root dilatation in patients with fabry disease: a single centre experience

Abstract

Introduction Fabry disease is an X linked lysosomal storage disorder resulting from deficiency of the enzyme alpha-galactosidase A. Multi-systemic effects are seen due to deposition and accumulation of glycosphingolipids. Although left ventricular hypertrophy is often the most commonly cited cardiac finding, cardiac manifestations can be widely varied, and vascular structural changes with increased thickening of the intima media and progressive vascular dilatation have been observed. Aortic root dilatation in affected males has in the past been reported in up to 30 – 56% using echocardiography, with varying criteria used to define dilatation. Purpose To establish the prevalence of aortic root and ascending aortic dilatation evaluated by echocardiography in our cohort of Fabry patients. Method We identified genotype positive Fabry patients from our single centre Fabry database who underwent echocardiography between January 2019 and January 2021. Data on basic demographics, history of hypertension, cardiac involvement and use of enzyme replacement therapy (ERT) were collected retrospectively. Cardiac involvement was defined as abnormalities detected on echocardiography, cardiovascular magnetic resonance imaging and /or elevated high sensitivity troponin I levels (reference limit >40ng/L for females and >58ng/L for males) not explained by another disease process. Imaging abnormalities included either left ventricular hypertrophy ≥13mm and / or evidence of fibrosis. The maximal aortic root dimension was assessed at the level of the sinus of Valsalva (SOV) and the proximal ascending aorta using echocardiography. Dimensions ≥40 mm, or with a Z3 score >2 (normalised for height by Devereux et al), were classed as dilated. Dimensions are quoted as mean ± standard deviation. Statistical analysis was through Chi-squared testing. Results 82 patients were identified (31 male, 51 female) ages ranging between 23 and 83 years (mean of 51 ± 16.1 years). 21% had treated hypertension (n = 17) and 62% had cardiac involvement from their Fabry disease (n = 51). 54% were on ERT (n = 44), of whom 70% (n = 31) were on intravenous enzyme replacement therapies and 30% (n = 13) were on oral chaperone therapy. The SOV dimensions ranged from 24 to 43 mm (mean 32 ± 4.4 mm). Aortic root dilatation was identified in 8.5% of the patient group (n = 7). Ascending aortic dimensions beyond the root were available in 72 patients. 2 patients had ascending diameters >40mm, but both also had aortic root dilatation. Table 1 outlines the prevalence of aortic root dilatation in our cohort grouped by gender, history of hypertension, cardiac involvement and use of ERT. The prevalence of aortic root dilatation in patients with cardiac involvement from their Fabry disease was significantly greater compared to patients with no cardiac involvement (p= 0.03). The prevalence of aortic root dilatation was not statistically different when grouped by gender, history of hypertension or use of ERT. Conclusion Fabry disease is a recognised lysosomal storage disorder associated with aortic root dilatation, although the exact mechanism remains incompletely understood. The prevalence of aortic root dilatation in our cohort was lower than previously reported. This may reflect advancements in treatment strategies and varying criteria used to define dilatation in previous studies. In our patient cohort the degree of aortic dilatation was mild, not reaching surgical requirement, and was not related to a history of hypertension. Although numbers were small, a higher prevalence was seen in patients with myocardial involvement by their Fabry disease, suggesting a possible link between the cardiac Fabry process and changes in the aortic wall. Conflict of Interest none