Skeletal Muscle Disorders: A Non-cardiac Source of Cardiac Troponin T.

du Fay de Lavallaz, Jeanne; Prepoudis, Alexandra; Wendebourg, Maria Janina; Kesenheimer, Eva; Kyburz, Diego; Daikeler, Thomas; Haaf, Philip; Wanschitz, Julia; Löscher, Wolfgang N; Schreiner, Bettina; Katan, Mira; Jung, Hans H; Maurer, Britta; Hammerer-Lercher, Angelika; Mayr, Agnes; Gualandro, Danielle M; Acket, Annemarie; Puelacher, Christian; Boeddinghaus, Jasper; Nestelberger, Thomas; ... (2022). Skeletal Muscle Disorders: A Non-cardiac Source of Cardiac Troponin T. Circulation, 145(24), pp. 1764-1779. American Heart Association 10.1161/CIRCULATIONAHA.121.058489

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Background: Cardiac troponin T (cTnT) and cTnI are considered cardiac-specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a non-cardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMD). Methods: We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in four hospitals in two countries. After cardiac work-up, patients were adjudicated into three predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed using high-sensitivity cTnT (hs-cTnT-Elecsys) and three hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista), and compared to controls without SMD presenting with adjudicated non-cardiac chest pain to the emergency department (n=3508, mean age 55y, 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared to biopsies obtained in controls without SMD. Results: Among 211 patients (mean age 57y, 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) mild and 59 (28%) severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no versus mild versus severe cardiac disease for all assays (all p<0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus controls (median 16ng/L (IQR 7-32.5) versus 5ng/L (IQR 3-9), p<0.001) while hs-cTnI concentrations were mostly similar (hs-cTnI-Architect 2.5ng/L (IQR 1.2-6.2) versus 2.9ng/L (IQR 1.8-5.0), hs-cTnI-Access 3.3ng/L (IQR 2.4-6.1) versus 2.7ng/L (IQR 1.6-5.0) and hs-cTnI-Vista 7.4ng/L (IQR 5.2-13.4) versus 7.5ng/L (IQR 6-10)). hs-cTnT-Elecsys concentrations were above the upper-limit of normal (ULN) in 55% of patients with SMD vs 13% of controls (p<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from non-inflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2, encoding cTnT (but none for TNNI3, encoding cTnI); versus controls (n=16, pWald <0.001), the expression correlated with pathological disease activity (R=0.59, pt-statistic <0.001) and circulating hs-cTnT concentrations (R=0.26, pt-statistic =0.031). Conclusions: In patients with active chronic SMD, elevations in cTnT concentrations are common and not due to cardiac disease in the majority. This was not observed for cTnI, and may in part be explained by re-expression of cTnT in skeletal muscle.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Maurer, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1524-4539

Publisher:

American Heart Association

Language:

English

Submitter:

Pubmed Import

Date Deposited:

08 Apr 2022 10:12

Last Modified:

30 May 2023 14:42

Publisher DOI:

10.1161/CIRCULATIONAHA.121.058489

PubMed ID:

35389756

BORIS DOI:

10.48350/169147

URI:

https://boris.unibe.ch/id/eprint/169147

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