Wanninayake Subadra, Kalaria Tejas, Ochoa-Ferraro Antonio, Roy Ashwin, Steeds Richard, Geberhiwot Tarekegn, Dawson Charlotte
Department of Inherited Metabolic Disorders Queen Elizabeth Hospital Birmingham Birmingham UK.
Department of Chemical Pathology The Royal Wolverhampton NHS Trust Birmingham UK.
JIMD Rep. 2025 Aug 12;66(5):e70008. doi: 10.1002/jmd2.70008. eCollection 2025 Sep.
Fabry disease (FD) is an X-linked lysosomal storage disease resulting in lysosomal accumulation of glycosphingolipids in multiple organs. In this study, we (1) compare high-sensitivity cardiac troponins I and T (hs-cTnI and hs-cTnT) as markers of Fabry cardiomyopathy (FC), and (2) evaluate the role of hs-cTn in monitoring early-stage FC to establish if there is a threshold at which significant FC can be reliably excluded. Data were collected retrospectively from clinical records of adults with FD seen in the Inherited Metabolic Disorders service, Birmingham, UK. Patients with cardiac magnetic resonance imaging and concurrent hs-cTnT and/or hs-cTnI measurement(s) were included. FC was defined as the cardiac magnetic resonance imaging features of LVH and/or late gadolinium enhancement and low/pseudonormal T1. One hundred thirty-three patients (male = 54) were included (hs-cTn incidences = 259), 62 patients had significant FC, and 71 did not have FC. hs-cTnI and hs-cTnT were compared by expressing as the fractional ratio (FRTn=hs-cTn concentration/age- and sex-specific 99th percentile). The distribution of FRTnI and FRTnT was not different (median [interquartile range], 0.89 [0.52-2.02] vs. 1.02 [0.47-1.9], = 0.270), including in patients with and without cardiomyopathy. In differentiating patients with FC from those without, the area under the curve (AUC) for hs-cTn was higher (AUC = 0.974; 95% CI: 0.959-0.990; < 0.001) than for FRTn (AUC = 0.897) and NT-proBNP (AUC = 0.939). A threshold hs-cTn < 8.5 ng/L was optimal to exclude FC (sensitivity 97.8% and negative predictive value 97.2%) with comparable performance of hs-cTnT and hs-cTnI at this threshold. The degree of serum hs-cTn elevation correlated with the severity of cardiac involvement. We conclude that serial hs-cTn monitoring is superior to NTproBNP for monitoring for early FC. cMRI scans to identify features of FC that are indicators to start treatment can be prioritised to patients with hs-cTn > 8.5 ng/L.
法布里病（FD）是一种X连锁溶酶体贮积病，可导致糖鞘脂在多个器官的溶酶体中蓄积。在本研究中，我们（1）比较高敏心肌肌钙蛋白I和T（hs-cTnI和hs-cTnT）作为法布里心肌病（FC）的标志物，（2）评估hs-cTn在监测早期FC中的作用，以确定是否存在一个阈值，在该阈值下可以可靠地排除显著的FC。数据从英国伯明翰市遗传性代谢疾病服务中心诊治的成年FD患者的临床记录中回顾性收集。纳入有心脏磁共振成像以及同时进行hs-cTnT和/或hs-cTnI测量的患者。FC定义为左心室肥厚和/或延迟钆增强以及低/假性正常T1的心脏磁共振成像特征。共纳入133例患者（男性54例）（hs-cTn检测次数=259次），62例患者有显著FC，71例患者无FC。通过表示为分数比（FRTn=hs-cTn浓度/年龄和性别特异性第99百分位数）来比较hs-cTnI和hs-cTnT。FRTnI和FRTnT的分布无差异（中位数[四分位间距]，0.89[0.52 - 2.02]对1.02[0.47 - 1.9]，P = 0.270），包括有和没有心肌病的患者。在区分有FC和无FC的患者时，hs-cTn的曲线下面积（AUC）（AUC = 0.974；95%CI：0.959 - 0.990；P < 0.001）高于FRTn（AUC = 0.897）和NT-proBNP（AUC = 0.939）。hs-cTn < 8.5 ng/L的阈值最适合排除FC（敏感性97.8%，阴性预测值97.2%），在此阈值下hs-cTnT和hs-cTnI的表现相当。血清hs-cTn升高程度与心脏受累严重程度相关。我们得出结论，对于早期FC的监测，连续hs-cTn监测优于NTproBNP。对于hs-cTn > 8.5 ng/L的患者，可以优先进行心脏磁共振成像扫描以识别FC特征，这些特征是开始治疗的指标。
