TY - JOUR T1 - Effect of Migalastat on cArdiac Involvement in FabRry Disease: MAIORA study JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmg-2022-108768 SP - jmg-2022-108768 AU - Antonia Camporeale AU - Francesco Bandera AU - Maurizio Pieroni AU - Federico Pieruzzi AU - Marco Spada AU - Anna Bersano AU - Laura Econimo AU - Chiara Lanzillo AU - Marta Rubino AU - Renzo Mignani AU - Irene Motta AU - Iacopo Olivotto AU - Ilaria Tanini AU - Rea Valaperta AU - Kelvin Chow AU - Irene Baroni AU - Sara Boveri AU - Francesca Graziani AU - Silvia Pica AU - Lara Tondi AU - Marco Guazzi AU - Massimo Lombardi Y1 - 2023/01/20 UR - http://jmg.bmj.com/content/early/2023/01/19/jmg-2022-108768.abstract N2 - Background A small but significant reduction in left ventricular (LV) mass after 18 months of migalastat treatment has been reported in Fabry disease (FD). This study aimed to assess the effect of migalastat on FD cardiac involvement, combining LV morphology and tissue characterisation by cardiac magnetic resonance (CMR) with cardiopulmonary exercise testing (CPET).Methods Sixteen treatment-naïve patients with FD (4 women, 46.4±16.2 years) with cardiac involvement (reduced T1 values on CMR and/or LV hypertrophy) underwent ECG, echocardiogram, troponin T and NT-proBNP (N-Terminal prohormone of Brain Natriuretic Peptide) assay, CMR with T1 mapping, and CPET before and after 18 months of migalastat.Results No change in LV mass was detected at 18 months compared to baseline (95.2 g/m2 (66.0–184.0) vs 99.0 g/m2 (69.0–121.0), p=0.55). Overall, there was an increase in septal T1 of borderline significance (870.0 ms (848–882) vs 860.0 ms (833.0–875.0), p=0.056). Functional capacity showed an increase in oxygen consumption (VO2) at anaerobic threshold (15.50 mL/kg/min (13.70–21.50) vs 14.50 mL/kg/min (11.70–18.95), p=0.02), and a trend towards an increase in percent predicted peak VO2 (72.0 (63.0–80.0) vs 69.0 (53.0–77.0), p=0.056) was observed. The subset of patients who showed an increase in T1 value and a reduction in LV mass (n=7, 1 female, age 40.5 (28.6–76.0)) was younger and at an earlier disease stage compared to the others, and also exhibited greater improvement in exercise tolerance.Conclusion In treatment-naïve FD patients with cardiac involvement, 18-month treatment with migalastat stabilised LV mass and was associated with a trend towards an improvement in exercise tolerance. A tendency to T1 increase was detected by CMR. The subset of patients who had significant benefits from the treatment showed an earlier cardiac disease compared to the others.Trial registration number NCT03838237.Data are available upon reasonable request. Most of the data relevant to the study are included in the article or uploaded as supplementary information. Further data are available upon reasonable request to the corresponding author. ER -