Following strenuous exercise, particularly endurance competitions, athletes may have elevated levels of circulating cTn.¹ Depending on the exercise exposure, study population, and assay used, cTn level elevations after exercise are seen in up to majority of study participants.¹ Hypotheses for the elevation of circulating cardiac troponins after exercise include increased membrane permeability of cardiomyocytes or integrin stimulation of troponin release, possibly related to right ventricular preload.¹ Study results have been mixed regarding correlation between an athlete's level of experience and the degree of enzyme elevation.¹ cTn levels typically peak for approximately 1-4 hours following exercise but can remain elevated for up to 72 hours following exercise.¹ Compared with the temporal trends of cTn level elevations in the setting of acute myocardial ischemia secondary to coronary disease, increases with exercise usually resolve more rapidly.¹ Thus, determining when a rise and fall in cTn levels is secondary to exercise requires multiple early samples.¹

In addition, elevated cTn levels can be seen in syndromes of systemic muscle breakdown such as rhabdomyolysis.^2-5 Although contemporary cardiac-specific assays for cardiac troponin T (cTnT) and cardiac troponin I (cTnI) have increased sensitivity for myocardial protein elevations, skeletal muscle release of troponin T can result in elevations in troponin T levels in assays from skeletal muscle cell death.^3,4 However, there is evidence that elevated cTn levels in the setting of rhabdomyolysis can be secondary to myocardial myocyte involvement secondary to toxic injury, subendocardial injury, or prior hemodynamic compromise.⁴

Chronically elevated cTn levels can be seen in patients in absence of imaging findings of inflammation, edema, scar, or infarction and may represent low-level myocyte necrosis that is below the detectable limits of contemporary cardiac imaging.⁵ Nonetheless, in the setting of cardiac imaging with unremarkable findings and persistently elevated cTn levels, other causes of cTn level elevations should be considered.

Several small molecules have been identified as causes of elevated cTn test results (either false-positives or disproportionate elevations).^6-8 These molecules include heterophile antibodies, antitroponin antibodies, and macrotroponin complexes.^6,8 Antibodies to cTnT and cTnI molecules can be found in patients with no known cardiac disease.^6-8 These antibodies can form immune complexes with low circulating levels of cardiac troponin and subsequently be measured on high-sensitivity troponin assays.^6-8 Clinicians who encounter patients with elevated cTn levels without a clear cause should consider these sources of analytical interference as a cause. Testing simultaneous samples with different assays can identify inconsistent results that may suggest analytical interference. However, this approach requires access to different analyzers/assays, which can be logistically complex, and results are not specific for the source of interference. More advanced laboratory testing is available at some highly specialized clinical laboratories to identify specific sources of analytical interference.⁶

In this patient, the initial elevation in cTnI levels was likely reflective of a combination of exercise exposure and perhaps rhabdomyolysis involving the heart. Although detailed cardiac imaging did not reveal an ongoing cardiac-specific source of elevated troponin levels, the possibility of a low-grade myocardial process resulting in persistent elevations on cTn assays weeks to months after the initial insult cannot be fully ruled out. Nonetheless, all initial troponin testing was performed on a single analyzer (Abbott Laboratories) for a single troponin molecule (cTnI). When an alternative analyzer (Beckman Coulter Diagnostics) was used and a simultaneous cTnT sample performed, both results were within the reference ranges. These findings suggest that the persistent elevations in cTnI on the Abbott Laboratories assay may have been the result of some form of analytical interference, although simultaneous samples were not able to be analyzed.

This patient underwent full cardiac and neuromuscular evaluation (including genetic testing), but no primary muscular, genetic, or neurologic condition was identified that would predispose her to severe rhabdomyolysis or persistent symptoms. Warm weather on the day of the race may have contributed to the development of rhabdomyolysis, particularly if hyperthermia was present (notably, no body temperature was taken in the medical tent). Her initial rhabdomyolysis followed by avoidance of physical activity may have led to deconditioning and exacerbated her symptoms of fatigue and dyspnea. Given the overall reassuring cardiac and neuromuscular workup in the months after the event, she was counseled to return gradually to exercise with careful attention to temperature, hydration status, and training/competition preparation.

References

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2. du Fay de Lavallaz J, Prepoudis A, Wendebourg MJ, et al. Skeletal muscle disorders: a noncardiac source of cardiac troponin T. Circulation. 2022;145(24):1764-1779. doi:10.1161/CIRCULATIONAHA.121.058489
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7. Lam L, Tse R, Gladding P, Kyle C. Effect of macrotroponin in a cohort of community patients with elevated cardiac troponin. Clin Chem. 2022;68(10):1261-1271. doi:10.1093/clinchem/hvac118
8. Salaun E, Drory S, Coté MA, et al. Role of antitroponin antibodies and macrotroponin in the clinical interpretation of cardiac troponin. J Am Heart Assoc. 2024;13(12):e035128. doi:10.1161/JAHA.123.035128