The Utility of High-Sensitivity Troponin to Detect Cardiomyopathy in Patients With Fabry Disease

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], p = 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; p < 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.