{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:35:57Z","timestamp":1792575357793,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,6,14]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability\/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We prospectively enrolled patients presenting with muscular complaints (\u22652 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT\/I and resulting cTnT\/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT\u2013Elecsys) and 3 hs-cTnI assays (hs-cTnI\u2013Architect, hs-cTnI\u2013Access, hs-cTnI\u2013Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies,\n                      <jats:italic>TNNT\/I1-3<\/jats:italic>\n                      mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT\/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). hs-cTnT\u2013Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng\/L [interquartile range (IQR), 7\u201332.5 ng\/L] versus 5 ng\/L [IQR, 3\u20139 ng\/L];\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI\u2013Architect, 2.5 ng\/L [IQR, 1.2\u20136.2 ng\/L] versus 2.9 ng\/L [IQR, 1.8\u20135.0 ng\/L]; hs-cTnI\u2013Access, 3.3 ng\/L [IQR, 2.4\u20136.1 ng\/L] versus 2.7 ng\/L [IQR, 1.6\u20135.0 ng\/L]; and hs-cTnI\u2013Vista, 7.4 ng\/L [IQR, 5.2\u201313.4 ng\/L] versus 7.5 ng\/L [IQR, 6\u201310 ng\/L]). hs-cTnT\u2013Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of\n                      <jats:italic>TNNT2<\/jats:italic>\n                      , encoding cTnT (but none for\n                      <jats:italic>TNNI3<\/jats:italic>\n                      , encoding cTnI) versus control subjects (n=16,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>Wald<\/jats:italic>\n                      <\/jats:sub>\n                      &lt;0.001); the expression correlated with pathological disease activity (\n                      <jats:italic>R<\/jats:italic>\n                      =0.59,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>t-statistic<\/jats:italic>\n                      <\/jats:sub>\n                      &lt;0.001) and circulating hs-cTnT concentrations (\n                      <jats:italic>R<\/jats:italic>\n                      =0.26,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>t-statistic<\/jats:italic>\n                      <\/jats:sub>\n                      =0.031).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03660969.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.121.058489","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T16:10:26Z","timestamp":1649347826000},"page":"1764-1779","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":120,"title":["Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T"],"prefix":"10.1161","volume":"145","clinical-trial-number":[{"clinical-trial-number":"nct03660969","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-1786","authenticated-orcid":true,"given":"Jeanne","family":"du Fay de Lavallaz","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5777-0418","authenticated-orcid":true,"given":"Alexandra","family":"Prepoudis","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-8807","authenticated-orcid":true,"given":"Maria Janina","family":"Wendebourg","sequence":"additional","affiliation":[{"name":"Neurology Clinic and Policlinic (M.J.W., E.K., M.S.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Kesenheimer","sequence":"additional","affiliation":[{"name":"Neurology Clinic and Policlinic (M.J.W., E.K., M.S.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Kyburz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology (D.K., T.D.), University Hospital of Basel, Switzerland."},{"name":"University of Basel, Switzerland (D.K., M.S., C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Daikeler","sequence":"additional","affiliation":[{"name":"Department of Rheumatology (D.K., T.D.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5657-6637","authenticated-orcid":true,"given":"Philip","family":"Haaf","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wanschitz","sequence":"additional","affiliation":[{"name":"Departments of Neurology (J.W., W.N.L.), Medical University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang N.","family":"L\u00f6scher","sequence":"additional","affiliation":[{"name":"Departments of Neurology (J.W., W.N.L.), Medical University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Departments of Neurology (B.S., M.K., H.H.J.), University Hospital of Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-8066","authenticated-orcid":true,"given":"Mira","family":"Katan","sequence":"additional","affiliation":[{"name":"Departments of Neurology (B.S., M.K., H.H.J.), University Hospital of Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans H.","family":"Jung","sequence":"additional","affiliation":[{"name":"Departments of Neurology (B.S., M.K., H.H.J.), University Hospital of Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Maurer","sequence":"additional","affiliation":[{"name":"Rheumatology (B.M.), University Hospital of Z\u00fcrich, Switzerland."},{"name":"Department of Rheumatology and Immunology, Inselspital Bern, Switzerland (B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Hammerer-Lercher","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Cantonal Hospital of Aarau, Switzerland (A.H.-L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-873X","authenticated-orcid":true,"given":"Agnes","family":"Mayr","sequence":"additional","affiliation":[{"name":"Radiology (A.M.), Medical University of Innsbruck, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Gualandro","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"Acket","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Neurology Clinic and Policlinic (M.J.W., E.K., M.S.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Puelacher","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4404-4956","authenticated-orcid":true,"given":"Jasper","family":"Boeddinghaus","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2173-5738","authenticated-orcid":true,"given":"Thomas","family":"Nestelberger","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Division of Cardiology, Vancouver General Hospital, University of British Columbia, Canada (T.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-0640","authenticated-orcid":true,"given":"Pedro","family":"Lopez-Ayala","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9651-8848","authenticated-orcid":true,"given":"Noemi","family":"Glarner","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samyut","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Manka","sequence":"additional","affiliation":[{"name":"Cardiology (R.M.), University Hospital of Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Gawinecka","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry (J. Gawinecka), University Hospital of Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2686-2939","authenticated-orcid":true,"given":"Salvatore","family":"Piscuoglio","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Biomedicine (S.P., J. Gallon, S.W.), University Hospital of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gallon","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Basel (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Cardiology (J.d.F.d.L., A.P., P.H., D.M.G., A.A., C.P., J.B., T.N., P.L.-A., N.G., S.S., S.P., J. Gallon, S.W., C.M.), University Hospital of Basel, Switzerland."},{"name":"Department of Biomedicine (S.P., J. 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