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Original research
Effect of Migalastat on cArdiac Involvement in FabRry Disease: MAIORA study
  1. Antonia Camporeale1,
  2. Francesco Bandera2,3,
  3. Maurizio Pieroni4,
  4. Federico Pieruzzi5,6,
  5. Marco Spada7,
  6. Anna Bersano8,
  7. Laura Econimo9,
  8. Chiara Lanzillo10,
  9. Marta Rubino11,
  10. Renzo Mignani12,
  11. Irene Motta13,14,
  12. Iacopo Olivotto15,
  13. Ilaria Tanini15,
  14. Rea Valaperta16,
  15. Kelvin Chow17,
  16. Irene Baroni18,
  17. Sara Boveri19,
  18. Francesca Graziani20,
  19. Silvia Pica1,
  20. Lara Tondi1,
  21. Marco Guazzi2,21,
  22. Massimo Lombardi1
  1. 1Multimodality Cardiac Imaging Section, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  2. 2Department of Biomedical Sciences for Health, University of Milan, Milano, Italy
  3. 3University Cardiology Department, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  4. 4Department of Cardiology, San Donato Hospital, Arezzo, Italy
  5. 5Nephrology and Dialysis Unit, San Gerardo Hospital, Monza, Italy
  6. 6Department of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy
  7. 7Department of Pediatrics, University of Turin, Torino, Italy
  8. 8Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
  9. 9Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili di Brescia, Brescia, Italy
  10. 10Cardiology Department, Policlinico Casilino, Roma, Italy
  11. 11Inherited and Rare Cardiovascular Disease, Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
  12. 12Nephrology and Dialysis Department, Infermi Hospital, Rimini, Italy
  13. 13Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  14. 14Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy
  15. 15Cardiomyopathy Unit, University Hospital Careggi, Firenze, Italy
  16. 16Operative Unit of Laboratory Medicine 1 - Clinical Pathology, Department of Pathology and Laboratory Medicine, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  17. 17Siemens Medical Solutions USA, Malvern, Pennsylvania, USA
  18. 18Clinical Research Unit, Cardiovascular Department, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  19. 19Scientific Directorate, IRCCS Policlinico San Donato, San Donato Milanese, Italy
  20. 20Department of Cardiovascular Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
  21. 21Cardiology Division, San Paolo Hospital, Milan, Italy
  1. Correspondence to Dr Antonia Camporeale, Multimodality Cardiac Imaging Section, IRCCS Policlinico San Donato, San Donato Milanese 20097, Italy; antonia.Camporeale{at}grupposandonato.it

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.

  • Fabry Disease
  • Cardiac Magnetic Resonance
  • Migalastat

Data availability statement

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.

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Data availability statement

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.

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Footnotes

  • Contributors AC, MP and ML conceived the presented idea. AC conceived the study and was in charge of the overall direction and planning. SP, FB and LT carried out the clinical assessments. SB and FB analysed the data. IB assisted with the clinical assessments and with the submission of the manuscript. KC worked out the technical details. FP, MS, FG, MG, AB, LE, CL, MR, RM, IM, IO and IT were involved in the enrolment of the patients. RV processed the biological samples. Finally, all the authors discussed the results within periodic meetings and contributed to the final manuscript. Guarantor: AC.

  • Funding This study was supported by a research grant from Amicus Therapeutics. This study was partially supported by Ricerca Corrente funding from the Italian Ministry of Health to IRCCS Policlinico San Donato.

  • 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.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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