T Stands for Trouble
Because Troponin T Can Come From More Than the Heart
Below is a graph showing “cardiac” troponin T (cTnT) and I (cTnI) levels in 74 patients with various skeletal muscle myopathies including myotonic dystrophy, dystrophic myopathy, non-dystrophic myotonia, inflammatory myositis, and others.(1) The dotted lines give the upper limits of normal (ULN) for cTnT on the x-axis and cTnI on the y-axis. Only four of the patients had cTnI levels above the ULN value, but look at all the skeletal myopathy patients with elevated cTnT levels.
A study performed in 211 patients with skeletal muscle disease had similar results.(2) TnT was more frequently elevated than TnI. TnT levels correlated with CK levels. TnT elevations were more frequent in patients with noninflammatory myopathy and myositis. Muscle biopsies from 33 individuals with primarily non-inflammatory myopathies and myositis showed an eight fold increase in expression for the gene encoding for cTnT, but no increase in the gene encoding for cTnI. Such results suggest that cTnT is increased in patients undergoing skeletal muscle repair.
This makes sense especially if you know the history of myocardial injury markers and marathon running. Some of the earliest work on this topic was done by Dr. Arthur Siegel, a Harvard-affiliated internist and former marathon runner. Art and others reported creatine kinase (CK) levels in 15 physicians before and the day after they ran the 1979 Boston Marathon. CK values increased from 161 U/L to 3424 U/L after the race.(3) We now know that muscle injury caused this elevation in CK, but this study was done when CK levels were used to diagnose myocardial infarction. The results raised some concern. The myocardial band of CK (CKMB) replaced CK as the marker of myocardial injury in the 1980’s. Siegel’s group repeated their studies and found that CK-MB also increased after the Boston race. They suspected that the CK-MB was from skeletal muscle so they biopsied the lateral gastrocnemius in 25 marathon runners and 10 controls. The runners had twice the concentration of CK-MB in their muscle than the controls did.(4) The biopsies also showed the presence of “satellite cells” in the runners’ muscles. Satellite cells are pluripotential cells that repair skeletal muscle, and these cells are capable of making “cardiac enzymes”.(5) Siegel postulated that runners were repetitively injuring skeletal muscle during training, which was repaired by satellite cells, and that these cells released CK-MB when they were injured.
cTnI is more specific to the heart, but both cTnT and cTnI increase after exercise. (6) We documented that every one of 71 runners increased their high sensitivity cTnI level after the 2011 Boston marathon and 54% had a post-exercise value above that used to diagnose an acute cardiac event.(7) We did not compare increases in cTnT and cTnI, values, but given the experience with muscle disease it’s likely that cTnT would have been even worse as a marker of myocardial injury. Why cTnI increases is an area of intense research.
Clinicians should know that skeletal muscle diseases can increase cTnT so that patients with increases in cTnT should not all be labelled as having a non-ST elevation myocardial infarction (NSTEWI), unless there is other evidence supporting that diagnosis.
So, what are he take-home messages:
- “Cardiac” TnT increases more than cTnI with skeletal muscle injury and repair.
- Don’t diagnose NSTEMI based on cTn alone.
- So, T stands for trouble.
1. Schmid J, Liesinger L, Birner-Gruenberger R, Stojakovic T, et.al. Elevated Cardiac Troponin T in Patients With Skeletal Myopathies. J Am Coll Cardiol. 2018 Apr 10;71(14):1540–1549. PMID: 29622161
2. Jeanne du Fay de Lavallaz # 1 2, Alexandra Prepoudis # 1 2, Maria Janina Wendebourg, et.al. Skeletal muscle disorders: a Noncardiac source of Cardiac Troponin T. Circulation. 2022 Jun 14;145(24):1764–1779.
3. A J Siegel, L M Silverman, R E Lopez. Creatine kinase elevations in marathon runners: relationship to training and competition. Yale J Biol Med.. 1980 Jul-Aug;53(4):275–9. PMID: 7445533
4. Siegel AJ, Silverman LM, Evans WJ.Elevated skeletal muscle creatine kinase MB isoenzyme levels in marathon runners. JAMA. 1983 Nov 25;250(20):2835–7.PMID: 6644963
5. Warhol MJ, Siegel AJ, Evans WJ, Silverman LM.Skeletal muscle injury and repair in marathon runners after competition. Am J Pathol. 1985 Feb;118(2):331–9.PMID: 3970143
6. Aengevaeren VL, Baggish AL, Chung EH, George K, Kleiven Ø, Mingels AMA, Ørn S, Shave RE, Thompson PD, Eijsvogels TMH. Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance. Circulation. 2021 Dec 14;144(24):1955–1972..PMID: 34898243
7. Eijsvogels TM, Januzzi JL, Taylor BA, Isaacs SK, D’Hemecourt P, Zaleski A, Dyer S, Troyanos C, Weiner RB, Thompson PD, Baggish AL Impact of statin use on exercise-induced cardiac troponin elevations. .Am J Cardiol. 2014 Aug 15;114(4):624–8..PMID: 25015693
