Gewählte Publikation:
Schmid, J.
Origin of Measured Plasma Cardiac Troponin T in Skeletal Muscle Disease.
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2020. pp. 104
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Binder Josepha Stephanie
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Quasthoff Stefan
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Rainer Peter
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- Abstract:
- Cardiac Troponin T (cTnT) is a pivotal laboratory test for the diagnosis of acute myocardial infarction. In patients with skeletal muscle diseases cTnT is frequently elevated, which may result in further, often invasive, diagnostic workup to exclude myocardial infarction. The origin of measured cTnT in these patients remains unclear. This study systematically evaluated the prevalence of cTnT elevation in skeletal myopathies and explored possible causes, such as cardiac involvement in myopathy, re-expression in diseased skeletal muscle or cross-reaction.
A cohort of 74 patients with different hereditary and acquired skeletal muscle diseases was prospectively enrolled. Patients underwent blood-sampling at baseline, 3 hours and 1 year with determination of cTnT, cardiac Troponin I (cTnI), both with high sensitive assays, CK and Myoglobin. 12-lead and 24-hour ECG, ambulatory blood pressure monitoring, echocardiography, cardiac magnetic resonance imaging, and if at increased risk for coronary artery disease computed tomography coronary angiography were performed. cTnT (median 24.0 [11.0-247.0] ng/L) was elevated in 69%, while cTnI (3.6 [2.4-22.1] ng/L) was elevated in 4% of patients. cTnT correlated with markers of skeletal muscle damage CK and Myogloben (r=0.679, p<0.001; r=0.786, p<0.001), while cTnI did not. There was a weak association of cTnT levels (p=0.025) with the presence of cardiac abnormalities (22.9%).
Western blots with healthy and diseased skeletal muscle and control tissue was performed applying the capture and detection antibodies of the commercial immunoassays. Both cTnT antibodies detected bands in healthy and diseased skeletal muscle that are compatible with skeletal TnT isoforms, which were also identified in the spectra of additional liquid-chromatography-tandem-mass-spectrometry of these bands. cTnT measurements in plasma with added skeletal muscle homogenates resulted in elevated measurement at high input concentrations. Cross-reaction with recombinant slow TnT was 0.02%.
Our results confirm reports of frequent cTnT elevation in skeletal muscle diseases, which is not observed in cTnI. This seems to be caused by a small cross-reaction of the cTnT assay with skeletal TnT isoforms that are abundant in serum of patients with skeletal myopathies.