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. 2023 Sep;60(9):850-858.
doi: 10.1136/jmg-2022-108768. Epub 2023 Jan 20.

Effect of Migalastat on cArdiac InvOlvement in FabRry DiseAse: MAIORA study

Antonia Camporeale  1 , Francesco Bandera  2   3 , Maurizio Pieroni  4 , Federico Pieruzzi  5   6 , Marco Spada  7 , Anna Bersano  8 , Laura Econimo  9 , Chiara Lanzillo  10 , Marta Rubino  11 , Renzo Mignani  12 , Irene Motta  13   14 , Iacopo Olivotto  15 , Ilaria Tanini  15 , Rea Valaperta  16 , Kelvin Chow  17 , Irene Baroni  18 , Sara Boveri  19 , Francesca Graziani  20 , Silvia Pica  21 , Lara Tondi  21 , Marco Guazzi  2   22 , Massimo Lombardi  21
Affiliations

Effect of Migalastat on cArdiac InvOlvement in FabRry DiseAse: MAIORA study

Antonia Camporeale et al. J Med Genet. 2023 Sep.

Abstract

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.

Keywords: Cardiac Magnetic Resonance; Fabry Disease; Migalastat.

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Conflict of interest statement

Competing interests: AC: honoraria for presentations and board meetings from Amicus Therapeutics, Sanofi Genzyme and Shire; research grant from Amicus Therapeutics. MP: speaker and advisory board honoraria and travel support from Sanofi Genzyme, Amicus Therapeutics and Shire. FP: honoraria from Sanofi Genzyme, Shire and Amicus Therapeutics. MS: honoraria for speaking fees for symposia and meetings and for advisory board attendance from Sanofi Genzyme and Shire International. AB: travel sponsor from Genzyme, Shire and Amicus. CL: travel sponsor from Genzyme, Shire and Amicus. MR: travel sponsor from Genzyme, Shire and Amicus. RM: travel sponsor, honoraria and expert witness with Sanofi Genzyme and Amicus. IM: travel sponsor from Genzyme, Shire and Amicus. IO: advisory board for Amicus, Cytokinetics, Tenaya and BMS; research grant from Amicus, Genzyme, Shire, BMS, Cytokinetics, Menarini International, Bayer and Boston Scientific. IT: travel sponsor from Genzyme, Shire and Amicus. KC: full-time employee of Siemens Medical Solutions USA. FG: travel sponsor from Genzyme, Shire and Amicus; honoraria speaker for Takeda-Shire and Genzyme. ML: honoraria for presentations from Shire.

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