Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T
Authors: 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 , Lopez-Ayala Pedro , Glarner Noemi , Shrestha Samyut , Manka Robert , Gawinecka Joanna , Piscuoglio Salvatore , Gallon John , Wiedemann Sophia , Sinnreich Michael , Mueller Christian , 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 
Published: April 2022

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.