Highlights In this multicenter observational study of 211 prospectively enrolled patients with ≥2 weeks of muscle discomfort, high-sensitivity cardiac troponin T (hs-CTnT) concentrations were significantly higher among patients with skeletal muscle disease (SMD) compared with controls (16 ng/L vs 5 ng/L; P < 0.001), while hs-CTnI concentrations were similar between the two groups, regardless of the assay used. hs-CTnT concentrations were above the upper limit of normal in patients with MDS compared with controls (55% vs. 13%; P < 0.01). Examination of skeletal muscle biopsies revealed an eight-fold upregulation of TNNT2, which correlated with serum hs-CTnT concentrations, whereas no upregulation of TNNI3, which encodes CTnI, was observed. These data suggest that elevated hs-CTnT concentrations among patients with chronic active MDS are common, likely explained by CTnT re-expression in skeletal muscles, and generally not attributable to cardiac disease. However, assays using hs-CTnI may offer superior specificity for heart disease. |
Background
Cardiac troponin T (cTnT) and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a non-cardiac source of cTnT.
We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMD).
Methods
We prospectively enrolled patients presenting with muscle discomfort (≥2 weeks) for elective evaluation at four hospitals in two countries. After the cardiac study, patients were classified into three predefined categories of heart disease.
cTnT/I concentrations and resulting cTnT/I mismatches were evaluated using high-sensitivity cTnT (hs-cTnT-Elecsys) and three hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs- cTnI-Vista), and compared to non-MDS controls who presented with noncardiac chest pain adjudicated to the emergency department (n = 3508, mean age 55 years, 37% women).
In patients with available skeletal muscle biopsies, differential gene expression of TNNT/I1-3 mRNA was compared with biopsies obtained in non-MDS controls.
Results
Among 211 patients (mean age 57 years, 42% women), 108 (51%) had no heart disease, 44 (21%) had mild heart disease, and 59 (28%) had severe heart disease. hs-cTnT/I concentrations were significantly increased in all trials (all p<0.001) in patients without heart disease , compared with mild and severe heart disease.
hs-cTnT-Elecsys concentrations were significantly higher in patients with TME than in controls (median 16 ng/L (IQR 7-32.5) vs 5 ng/L (IQR 3-9), p< 0.001), while hs-cTnI concentrations were mostly similar (hs-cTnI-Architect 2.5 ng/l (IQR 1.2-6.2) vs. 2.9 ng/l (IQR 1.001). 8-5.0), hs-cTnI-Access 3.3 ng/l (IQR 2.4-6.1) vs 2.7 ng/l (IQR 1.6 -5.0) and hs-cTnI -Vista 7.4 ng/L (IQR 5.2-13.4) vs 7.5 ng/L (IQR 6-10)).
hs-cTnT-Elecsys concentrations were above the upper limit of normal (ULN) in 55% of MDS patients versus 13% of controls (p<0.01).
mRNA analyzes in skeletal muscle biopsies (n=33), primarily (n=24) from non-inflammatory myopathy and myositis, showed an 8-fold upregulation of TNNT2, which encodes cTnT (but none of TNNI3, which encodes cTnI); versus controls (n=16, pWald <0.001), expression was correlated with pathological disease activity (R=0.59, pt statistic <0.001) and circulating hs-cTnT concentrations (R=0.26, pt statistic = 0.031).
Conclusions
In patients with chronic active skeletal muscle disorders (MDS), elevations in cTnT concentrations are common and are not due to cardiac disease in the majority. This was not observed for cTnI and may be partly explained by re-expression of cTnT in skeletal muscle.
