Effect of Migalastat on cArdiac Involvement in FabRry Disease MAIORA study

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.Camporeale A等. 米加司他特对法布里病（Fabry disease）心脏受累的影响：MAIORA研究. J Med Genet. 2023 Sep;60(9):850-858. doi: 10.1136/jmg-2022-108768. Epub 2023 Jan 20. PMID: 36669872. 摘要 背景：已有研究报道，法布里病（Fabry disease）患者接受18个月米加司他特治疗后，左心室（left ventricular, LV）质量出现小幅但具有统计学意义的降低。本研究旨在评估米加司他特对法布里病心脏受累的影响，联合应用心脏磁共振（cardiac magnetic resonance, CMR）的左心室形态学与组织特征分析，以及心肺运动试验（cardiopulmonary exercise testing, CPET）进行评估。 方法：16例初治法布里病合并心脏受累患者（4例女性，年龄46.4±16.2岁），其心脏受累表现为心脏磁共振T1值降低和/或左心室肥厚。所有患者在米加司他特治疗前及治疗18个月后均接受心电图、超声心动图、肌钙蛋白T（troponin T）及N末端B型利钠肽原（NT-proBNP）检测、T1 mapping心脏磁共振检查及心肺运动试验。 结果：与基线相比，治疗18个月后左心室质量无显著变化（95.2 g/m²(66.0-184.0) vs 99.0 g/m²(69.0-121.0), p=0.55）。整体而言，室间隔T1值呈临界显著性升高（870.0 ms(848-882) vs 860.0 ms(833.0-875.0), p=0.056）。功能容量方面，无氧阈（anaerobic threshold）时摄氧量（VO2）显著升高（15.50 mL/kg/min(13.70-21.50) vs 14.50 mL/kg/min(11.70-18.95), p=0.02），预测峰值摄氧量（peak VO2）百分比呈升高趋势（72.0(63.0-80.0) vs 69.0(53.0-77.0), p=0.056）。其中7例患者（1例女性，年龄40.5(28.6-76.0)）出现T1值升高及左心室质量降低，与其余患者相比，该亚组患者年龄更小、疾病分期更早，且运动耐量改善更为显著。 结论：对于初治合并心脏受累的法布里病患者，18个月米加司他特治疗可稳定左心室质量，并与运动耐量改善趋势相关。心脏磁共振检测发现T1值呈升高趋势。相较于其余患者，从治疗中获得显著获益的患者心脏疾病分期更早。 试验注册编号：NCT03838237.