Novel screening for Fabry disease in patients with cardiovascular phenotype: a multi-centre, prospective study

초록

Background: Fabry disease in cardiac phenotype typically presents left ventricular hypertrophy (LVH) of 13mm or more. Cardiovascular screening of Fabry disease limited to LVH may underestimate mild or moderate cardiac phenotype with less progressed LVH. Purpose: We investigated the prevalence of Fabry disease in patients with cardiac phenotype based on left ventricular mass index (LVMI) and electrical findings. Methods: This is a multi-centre, prospective study of cardiovascular screening cohort for Fabry disease (2017–2024). Patients were eligible if they had LVMI ≥115g/m2 (≥95g/m2 in female) with diastolic dysfunction in echocardiography or electrical abnormalities in electrocardiography, or had a family history of Fabry disease. Leukocyte α-galactosidase A activity or/and plasma lyso-Gb3 assay was assessed, and consecutive GLA gene sequencing was performed to confirm Fabry disease. Results: A total of 1,702 patients were enrolled from 7 institutions. Mean age was 63.1 years old, and 982 (57.7%) were female. Among Seven (0.4%) patients who were confirmed as Fabry disease, 4 had left ventricular wall thickness ≥13mm, and 6 were indicated for enzyme replacement therapy. Compared with patients without Fabry disease (n=1,695), those with Fabry disease had elevated lyso-Gb3 (6.5 ± 3.3 vs. 1.0 ± 0.1 ng/mL, p=0.004), lower serum creatinine (0.8 ± 0.2 vs. 1.2 ± 1.2 mg/dL, p=0.009), shorter PR interval (139.0 ± 26.8 vs. 173.3 ± 31.5 msec, p=0.03), and higher left ventricular ejection fraction (60.0 ± 2.7 vs. 53.3 ± 9.8 %, p=0.002). However, there is no significant difference in intraventricular septum thickness between two group (11.9 ± 3.2 vs. 11.8 ± 3.2 mm). Conclusion: This large-scale prospective study suggests that cardiovascular phenotypic screening using LVMI with diastolic dysfunction or electrical abnormality may provide early detection of late-onset Fabry disease, regardless of LVH, although the prevalence is relatively low.