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      Using serum troponins to screen for cardiac involvement and assess disease activity in the idiopathic inflammatory myopathies

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          Abstract

          Objectives

          Limitations in the methods available for identifying cardiac involvement and accurately quantifying disease activity in the idiopathic inflammatory myopathies (IIMs) may contribute to poor outcomes. We investigated the utility of different serum muscle damage markers [total creatine kinase (CK), cardiac troponin T (cTnT) and cardiac troponin I (cTnI)] to address these issues.

          Methods

          We assessed disease activity and cardiac involvement using the International Myositis Assessment and Clinical Studies Group core set measures in 123 participants with confirmed adult-onset IIM from the UK and Denmark. Total CK, cTnT and cTnI were measured. Associations were assessed using logistic regression and Spearman’s ranked correlation.

          Results

          Cardiac involvement ( n = 18) was associated with higher cTnI levels, independent of overall disease activity [adjusted odds ratio 1.03 (95% CI 1.01, 1.05); P = 0.002]. An abnormal cTnI had the highest specificity and positive predictive value for cardiac involvement (95% and 62%, respectively). In those with a normal CK but elevated cTnT or cTnI, an association with increased disease activity scores was observed. Serum cTnT correlated with the physician (ρ = 0.39) and patient-assessed (ρ = 0.28) global visual analogue scales and HAQ (ρ = 0.41) more strongly than CK or cTnI levels. cTnT was the only marker to correlate with manual muscle testing scores (ρ = −0.24).

          Conclusion

          Serum cTnI testing may have a role in screening for cardiac involvement in IIMs. Abnormal levels of serum cTnT and cTnI are associated with increased disease activity, including in those with a normal CK.

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          Most cited references14

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          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.

          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.
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            Serum cardiac troponin T, but not troponin I, is elevated in idiopathic inflammatory myopathies.

            To study the association of serum cardiac troponin T (cTnT) and cardiac troponin I (cTnI) with creatine kinase (CK) in patients with idiopathic inflammatory myopathies (IIM).
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              Cardiac troponin T composition in normal and regenerating human skeletal muscle.

              Cardiac troponin T (cTnT), measurement of which has been recommended for diagnosing myocardial infarction, was initially believed to be specific for the heart. However, recent publications have reported cTnT in sera of patients without cardiac disease; therefore, we investigated whether cTnT could be found in human skeletal muscle tissues. Using immunohistochemistry, Western blot, and quantitative cTnT ELISA, we assayed human heart (n = 3), normal human skeletal muscle (n = 6), and diseased skeletal muscle samples from patients with polymyositis (PM, n = 13) and Duchenne muscular dystrophy (DMD, n = 6). All heart specimens contained cTnT, but the expression of cTnT in normal skeletal muscle samples varied widely, ranging from no expression (quadriceps femoris) to expression by up to 20% of the muscle fibers (diaphragm). Immunohistochemistry detected cTnT in skeletal muscle of 8 of the PM patients and all of the DMD patients. Mean myofibrillar cTnT concentrations (mg/g myofibrillar protein) were: cardiac = 10.0, normal skeletal = 0.8, PM skeletal = 0.7, and DMD skeletal = 4.37, confirming the results of immunohistochemistry. Western blot analysis also confirmed the expression of cTnT in muscle from DMD patients. These findings provide evidence that cTnT is not 100% cardiac-specific but also is expressed in regenerating (PM and DMD) as well as in normal (nonregenerating) skeletal muscle.
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                Author and article information

                Journal
                Rheumatology (Oxford)
                Rheumatology (Oxford)
                brheum
                Rheumatology (Oxford, England)
                Oxford University Press
                1462-0324
                1462-0332
                June 2018
                12 March 2018
                12 March 2018
                : 57
                : 6
                : 1041-1046
                Affiliations
                [1 ]Centre for Musculoskeletal Research, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK
                [2 ]Greater Manchester Neuroscience Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK
                [3 ]Department of Cardiology, Odense University Hospital, Odense, Denmark
                [4 ]Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
                [5 ]Department of Biochemistry, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK
                [6 ]Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
                [7 ]MRC-ARUK Centre for Integrated Research into Musculoskeletal Ageing, University of Liverpool, Liverpool, UK
                [8 ]Rheumatology Department, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK
                [9 ]Department of Rheumatology, Odense University Hospital, Odense, Denmark
                [10 ]NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
                Author notes

                Louise P. Diederichsen and Hector Chinoy contributed equally to this study.

                Correspondence to: Hector Chinoy, Salford Royal NHS Foundation Trust, Stott Lane, Salford, UK. E-mail: hector.chinoy@ 123456manchester.ac.uk
                Author information
                http://orcid.org/0000-0002-9230-4137
                http://orcid.org/0000-0002-9000-4413
                http://orcid.org/0000-0001-6492-1288
                Article
                key031
                10.1093/rheumatology/key031
                5965080
                29538753
                72cc0daa-e381-4230-a944-3df9030a869b
                © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 August 2017
                : 25 January 2018
                Page count
                Pages: 6
                Funding
                Funded by: Arthritis Research UK 10.13039/501100000341
                Award ID: 18474
                Funded by: Medical Research Council 10.13039/501100000265
                Award ID: MR/N003322/1
                Categories
                Clinical Science

                Rheumatology
                autoimmune diseases,cardiovascular disease,dermatomyositis,disease activity,idiopathic inflammatory myopathy,polymyositis

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