Diseased Skeletal Muscle A Noncardiac Source of Increased Circulating Concentrations of Cardiac Troponin T

Objectives The purpose of this study was to determine whether there is immunoreactive cardiac troponin T (cTnT) expression in diseased skeletal muscle that might cause possible false-positive increases in cTnT. Background Cardiac troponin (I or T) is the biomarker of choice for the diagnosis of cardiac injury. Recently, we were presented with a case that challenged the specificity of cTnT. Methods Patients with myopathies seen in the Neuromuscular Clinic at the Mayo Clinic were screened for increases in cTnT. If present, an assay for cTnI was performed. If normal, skeletal biopsy tissue was obtained for Western blot analysis using the capture and detection antibodies from both the fourth-generation and high-sensitivity cTnT assays. Results were compared with findings in normal cardiac tissue. Results Sixteen patients had increases in cTnT but not cTnI. All had a myopathy by clinical evaluation, clinical testing, and biopsy. Four residual biopsy samples were obtained. All 3 antibodies used in the cTnT (M11.7, M7) and high-sensitivity cTnT (5D8, M7) assays were immunoreactive with a 37-to 39-kDa protein in all 4 diseased skeletal muscle biopsy specimens and in cardiac tissue. A second immunoreactive isoform (34 to 36 kDa) was also found in 1 patient. None of the noncardiac control tissues expressed immunoreactive protein. Conclusions These results document that there are forms in diseased skeletal muscle that could cause increases in circulating levels of cTnT. These increases could reflect re-expressed isoforms. Clinicians need to be aware of the possibility that noncardiac increases in cTnT may occur and lead to a possible false-positive diagnosis of cardiac injury when skeletal muscle pathology is present. (J Am Coll Cardiol 2011;58:1819-24) (C) 2011 by the American College of Cardiology Foundation