Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity

Abstract

Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. While cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research.

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

“…It has been suggested that enhanced membrane permeability promoted by the production of reactive oxygen species or alterations in calcium, pH, glucose/fat metabolism, or in communication between integrins, might explain the release of cTn into circulation after strenuous exercise [25,75]. Other authors suggest alternative mechanisms: increased cardiovascular stress, inflammation, release of troponin degradation products in "blebs", dehydration, impaired renal clearance, and cTn expression in skeletal muscle [25], although the latter seems to occur only in the case of cTnT [92,93].…”

Interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) axis in idiopathic inflammatory myopathies and its association with laboratory and clinical parameters: a pilot study

“…However, in patients with myositis coexistence of cardiac and muscular lesions may distort the results of laboratory tests. Elevated concentrations of cardiac troponin T (cTnT) and CK-MB may result not only from the injury of cardiomyocytes but also from regenerating skeletal myocytes [13][14][15]. High concentrations of cardiac cTnT might be associated with severe course of myopathy [16].…”

Effect of IL-6 receptor blockade on high-sensitivity troponin T and NT-proBNP in rheumatoid arthritis

“…In contrast, the baseline levels of hsTnT were near the limit of detection of the high sensitivity assay, and consequently the absolute reductions in hsTnT are small. One may speculate that the smaller decrease in hsTnT observed in tocilizumab treated patients could be due to a number of mechanisms including release of troponin T from non-cardiac origins; indeed, damaged or regenerating skeletal muscle may express troponin T [19], [20], [21]. RA patients who experience improved quality of life and lower disease activity through tocilizumab allocation might expect to increase muscle mass through increased subsequent physical activity.…”