IRCCS Policlinico San Donato
Published January 31, 2024 | Version v1
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Effect of Migalastat on cArdiac Involvement in FabRry Disease MAIORA study

Authors/Creators

  • 1. Multimodality Cardiac Imaging Section, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  • 2. Department of Biomedical Sciences for Health, University of Milan, Milano, Italy
  • 3. University Cardiology Department, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  • 4. Department of Cardiology, San Donato Hospital, Arezzo, Italy
  • 5. Nephrology and Dialysis Unit, San Gerardo Hospital, Monza, Italy
  • 6. Department of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy
  • 7. Department of Pediatrics, University of Turin, Torino, Italy
  • 8. Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
  • 9. Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy
  • 10. Cardiology Department, Policlinico Casilino, Roma, Italy
  • 11. Inherited and Rare Cardiovascular Disease, Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
  • 12. Nephrology and Dialysis Department, Infermi Hospital, Rimini, Italy
  • 13. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 14. Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy
  • 15. Cardiomyopathy Unit, University Hospital Careggi, Firenze, Italy
  • 16. Operative Unit of Laboratory Medicine 1 - Clinical Pathology, Department of Pathology and Laboratory Medicine, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  • 17. Siemens Medical Solutions USA, Malvern, Pennsylvania, USA
  • 18. Clinical Research Unit, Cardiovascular Department, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  • 19. Scientific Directorate, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  • 20. Department of Cardiovascular Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
  • 21. Cardiology Division, San Paolo Hospital, Milan, Italy

Description

Camporeale A, Bandera F, Pieroni M, Pieruzzi F, Spada M, Bersano A, Econimo L, Lanzillo C, Rubino M, Mignani R, Motta I, Olivotto I, Tanini I, Valaperta R, Chow K, Baroni I, Boveri S, Graziani F, Pica S, Tondi L, Guazzi M, Lombardi M. Effect of Migalastat on cArdiac InvOlvement in FabRry DiseAse: MAIORA study. J Med Genet. 2023 Sep;60(9):850-858. doi: 10.1136/jmg-2022-108768. Epub 2023 Jan 20. PMID: 36669872.

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.

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