Left ventricular twist as an early marker of cardiac involvement in fabry disease: insights from a monocentric study including adult and pediatric patients using echocardiography and cardiac MRI

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme α-galactosidase A, leading to the accumulation of globotriaosylceramide (Gb3) in various tissues, including the heart. Cardiac involvement typically manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which significantly reduce quality of life and are among the leading causes of death in affected individuals. The progressive thickening of the left ventricular walls due to Gb3 deposition profoundly impacts the heart’s mechanical properties, particularly its twisting during systole and diastole. Early detection of myocardial dysfunction is therefore essential to initiate timely and potentially disease-modifying treatment. Aims To evaluate echocardiographic parameters in a monocentric cohort of adult and pediatric patients with genetically diagnosis oc Fabry disease, assess the prevalence of LVH, and investigate LV twist in patients with and without LVH, exploring its role as an early marker of cardiac involvement. Tissue-level data from CMR were used for morphological and functional validation. Methods 30 FD patients (mean age 32.7 ± 15.6 years; 6 pediatric) were prospectively enrolled and compared to age- and sex-matched healthy controls. All patients underwent a complete echocardiographic study.LVEF was determined using Simpson's biplanar method.Left ventricular torsion parameters Twist, were calculated as the difference between end-systolic rotation values at the apical and basal segments. 8 patients with echocardiographic LVH underwent CMR with evaluation of LV mass, volumes, and native T1 and LGE. Result LVEF was preserved in all patients (mean 62 ± 4%). LVH was detected in 8 patients (27%), who were significantly older than those without LVH (49 ± 7.7 vs 28 ± 14.2 years, p < 0.01). LV twist was significantly lower in FD patients than controls (6 ± 3° vs 13 ± 5°, p < 0.001), with greater reduction in patients with LVH (p = 0.013). Even FD patients without LVH had lower twist than controls (7 ± 3° vs 13 ± 5°, p = 0.005), despite normal LVEF, indicating early functional impairment. Among the 8 patients undergoing CMR, all showed increased LV mass (mean 95 ± 18 g/m²) and concentric remodeling. None had LGE, but 4 showed elevated native T1 values,associated with the lowest twist values, supporting the presence of early tissue involvement. Conclusion The integration of LV twist analysis into routine echocardiographic evaluation may enhance early diagnosis and guide personalized management in both adult and pediatric FD patients.