Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T

Author:

du Fay de Lavallaz Jeanne12ORCID,Prepoudis Alexandra12ORCID,Wendebourg Maria Janina3ORCID,Kesenheimer Eva3,Kyburz Diego45,Daikeler Thomas4,Haaf Philip1ORCID,Wanschitz Julia6,Löscher Wolfgang N.6,Schreiner Bettina7,Katan Mira7ORCID,Jung Hans H.7,Maurer Britta89,Hammerer-Lercher Angelika10,Mayr Agnes11ORCID,Gualandro Danielle M.12,Acket Annemarie13,Puelacher Christian12,Boeddinghaus Jasper12ORCID,Nestelberger Thomas1212ORCID,Lopez-Ayala Pedro12ORCID,Glarner Noemi12ORCID,Shrestha Samyut12,Manka Robert13,Gawinecka Joanna14,Piscuoglio Salvatore1215ORCID,Gallon John1215,Wiedemann Sophia1215ORCID,Sinnreich Michael35,Mueller Christian125ORCID,Zehntner Tibor,Giger Raoul,Stoll Thomas,Schöpfer Hadrien,Jordan Fabian,Carigiet Michael,Haeni Nicola,Gysin Vincent,Gafner Michele Sara,Wussler Desiree,Koechlin Luca,Freese Michael,Ruiz Christian,Strauch Olivia,Zimmermann Tobias,Strebel Ivo,Walker Ulrich A.,Vogt Thomas,Hartmann Martina,Kahles Timo,Hasler Paul,Seidel Funda,Zavtsyea Xenia,Rentsch Katharina,Mitrovic Sandra,von Eckardstein Arnold,Mair Johannes,Schreinlechner Michael,Wallimann Wijstke,Dietrich Manuel,Roah Tania Carrillo,Knoll Markus,Fuchs Alexander,Bruske Ellen,Munz Matthias,Kunzelmann Stefan,Albert Gesa,Becher Tobias,Kastner Peter,Shinjo Samuel Katsuyuki

Affiliation:

1. 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.

2. 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.

3. Neurology Clinic and Policlinic (M.J.W., E.K., M.S.), University Hospital of Basel, Switzerland.

4. Department of Rheumatology (D.K., T.D.), University Hospital of Basel, Switzerland.

5. University of Basel, Switzerland (D.K., M.S., C.M.).

6. Departments of Neurology (J.W., W.N.L.), Medical University of Innsbruck, Austria.

7. Departments of Neurology (B.S., M.K., H.H.J.), University Hospital of Zürich, Switzerland.

8. Rheumatology (B.M.), University Hospital of Zürich, Switzerland.

9. Department of Rheumatology and Immunology, Inselspital Bern, Switzerland (B.M.).

10. Department of Laboratory Medicine, Cantonal Hospital of Aarau, Switzerland (A.H.-L.).

11. Radiology (A.M.), Medical University of Innsbruck, Austria.

12. Division of Cardiology, Vancouver General Hospital, University of British Columbia, Canada (T.N.).

13. Cardiology (R.M.), University Hospital of Zürich, Switzerland.

14. Institute of Clinical Chemistry (J. Gawinecka), University Hospital of Zürich, Switzerland.

15. Department of Biomedicine (S.P., J. Gallon, S.W.), University Hospital of Basel, Switzerland.

Abstract

Background: 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). Methods: We prospectively enrolled patients presenting with muscular complaints (≥2 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–Elecsys) and 3 hs-cTnI assays (hs-cTnI–Architect, hs-cTnI–Access, hs-cTnI–Vista) 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, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD. Results: 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 P <0.001). hs-cTnT–Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7–32.5 ng/L] versus 5 ng/L [IQR, 3–9 ng/L]; P <0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI–Architect, 2.5 ng/L [IQR, 1.2–6.2 ng/L] versus 2.9 ng/L [IQR, 1.8–5.0 ng/L]; hs-cTnI–Access, 3.3 ng/L [IQR, 2.4–6.1 ng/L] versus 2.7 ng/L [IQR, 1.6–5.0 ng/L]; and hs-cTnI–Vista, 7.4 ng/L [IQR, 5.2–13.4 ng/L] versus 7.5 ng/L [IQR, 6–10 ng/L]). hs-cTnT–Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects ( P <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 TNNT2 , encoding cTnT (but none for TNNI3 , encoding cTnI) versus control subjects (n=16, P Wald <0.001); the expression correlated with pathological disease activity ( R =0.59, P t-statistic <0.001) and circulating hs-cTnT concentrations ( R =0.26, P t-statistic =0.031). Conclusions: 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. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03660969.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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