Cardiovascular Medicine, Urology and Nephrology

When elevated cardiac troponin T leads to the wrong conclusion

Dr. Jeanne du Fay de Lavallaz

Universitätsspital Basel
Cardiovascular Research Institute Basel

Dr. Alexandra Prepoudis

Universitätsspital Basel
Cardiovascular Research Institute Basel

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI), two blood proteins, stemming from the heart are commonly used to diagnose an acute myocardial infarction (AMI). Up to now, both isoforms have been considered equivalently accurate and cardiac-specific diagnostic tools. However, concentrations of cTnT but not cTnI were recently found to be elevated in patients who had skeletal muscle diseases but did not show any cardiac involvement. Therefore, elevated cTnT could potentially lead to erroneous diagnoses of heart attacks in those patients. 

Based on these observations, the research group with Jeanne du Fay de Lavallaz and Alexandra Prepoudis aimed to examine the clinical validity of assessing cTnT or cTnI concentrations in patients with skeletal muscle diseases. They asked how often unexpected elevations of cTnT were seen in patients with skeletal muscle diseases and tried to uncover the underlying pathophysiology.

For this, the scientists enrolled patients with various active chronic muscle diseases and compared their blood concentration of cTnT and cTnI to the ones of patients with healthy hearts and no muscle problems. Furthermore, genes that might be responsible for the expression of cTnT in the patients’ skeletal muscles were investigated.

In patients with skeletal muscle diseases, cTnT levels were significantly more elevated than cTnI levels, even in patients with a healthy heart. The elevated cTnT levels could originate from the skeletal muscle, where the cTnT genes appeared more active than the cTnI genes. These results imply that special care needs to be taken when assessing a patient with skeletal muscle problems for a heart attack: In patients with noninflammatory myopathy and myositis, elevated cTnT might lead to erroneous diagnoses of heart attacks. The awardees suggest that in these patients, an alternative test looking at the cardiac Troponin I levels should be measured for an accurate diagnosis of heart attacks. 

These findings represent a considerable progress in the pathophysiological understanding of troponin molecules.

Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T. Jeanne du Fay de Lavallaz*, Alexandra Prepoudis*, Maria Janina Wendebourg, Eva Kesenheimer, Diego Kyburz, Thomas Daikeler, Philip Haaf, Julia Wanschitz, Wolfgang N Löscher, Bettina Schreiner, Mira Katan, Hans H Jung, Britta Maurer, Angelika Hammerer-Lercher, Agnes Mayr, Danielle M Gualandro, Annemarie Acket, Christian Puelacher, Jasper Boeddinghaus, Thomas Nestelberger, Pedro Lopez-Ayala, Noemi Glarner, Samyut Shrestha, Robert Manka, Joanna Gawinecka, Salvatore Piscuoglio, John Gallon, Sophia Wiedemann, Michael Sinnreich, Christian Mueller, BASEL XII Investigators. Circulation. 2022;145:1764–1779.
* Contributed equally