RT Journal Article SR Electronic T1 Effect of Migalastat on cArdiac Involvement in FabRry Disease: MAIORA study JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmg-2022-108768 DO 10.1136/jmg-2022-108768 A1 Antonia Camporeale A1 Francesco Bandera A1 Maurizio Pieroni A1 Federico Pieruzzi A1 Marco Spada A1 Anna Bersano A1 Laura Econimo A1 Chiara Lanzillo A1 Marta Rubino A1 Renzo Mignani A1 Irene Motta A1 Iacopo Olivotto A1 Ilaria Tanini A1 Rea Valaperta A1 Kelvin Chow A1 Irene Baroni A1 Sara Boveri A1 Francesca Graziani A1 Silvia Pica A1 Lara Tondi A1 Marco Guazzi A1 Massimo Lombardi YR 2023 UL http://jmg.bmj.com/content/early/2023/01/19/jmg-2022-108768.abstract AB 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.