Chest pain is a common presenting complaint in the paediatric emergency department. Reference Rowe, Dulberg, Peterson, Vlad and Li1 In paediatric patients, chest pain is unlikely to be caused by a cardiac condition, however, since the opposite is true for adults, the initial evaluation for many patients often focuses on cardiac evaluation, including a cardiac troponin (cTn) level. Reference Dionne, Kheir, Sleeper, Esch and Breitbart2–Reference Harris and Gossett4 An elevated cTn level could signify a serious condition, such as myocardial infarction, myocarditis, or myopericarditis. Regardless of the reason for an abnormal result, an elevated cTn level can lead to hospitalisation, months of activity restrictions, and expensive further testing, so it is important to identify potential confounding factors. Studies have shown that cTn levels increase during strenuous aerobic exercise in adolescent and adult athletes. Reference Cirer-Sastre, Legaz-Arrese and Corbi5–Reference Aengevaeren, Baggish and Chung9 There are currently no studies investigating the effect short burst, high intensity aerobic exercise has on cTn levels in children. We sought to determine the behaviour of cTn levels in healthy children and adolescent patients after short burst, high-intensity aerobic exercise.
Materials and method
Ethical approval for this study was obtained from the Institutional Review Board. Subjects without CHD who were referred by a physician for a treadmill exercise stress test (EST) were recruited. cTn levels were collected prior to exercise and 4 hours post-exercise, which has previously been shown to be the timepoint at which cTn levels peak after exercise. Reference Cirer-Sastre, Legaz-Arrese and Corbi5,Reference Ma, Liu and Liu6,Reference Cirer-Sastre, Legaz-Arrese and Corbi8,Reference Aengevaeren, Baggish and Chung9 The Siemens Dimension Vista® conventional cTnI assay (Siemens Healthineers, Erlangen, Germany) was used. The lower limit of detection was 0.015– ng/ml and normal values were considered to be less than 0.1 ng/ml. Treadmill EST was conducted according to the standard Bruce protocol. Reference Bruce, Blackmon, Jones and Strait10 Clinical data collected included age, sex, and diagnosis/reason for referral for testing. EST data included exercise duration, endurance percentile for age, pre-test heart rate, peak heart rate, percentage of age predicted maximal heart achieved, reason for stopping test, and any arrhythmias or exercise electrocardiogram abnormalities. Standard, previously published, normal values were used to assess EST performance, including endurance percentile and predicted maximal heart rate, in paediatric patients. Reference Cumming, Everatt and Hastman11
Prior to subject recruitment, calculation of the proposed sample size was based on the likelihood of measuring a detectable cTn rise after exercise. A planned enrollment of 13 patients was calculated to achieve greater than 80% power to detect a cTn rise using a two-sided alpha level of 0.05 assuming an event rate of 40%. This event rate was selected to increase the sensitivity to detect cTn rise based on previously published reports of 50% of healthy subjects exhibiting cTn elevation after exercise. Reference Cirer-Sastre, Legaz-Arrese and Corbi8
Categorial data are reported as counts and percentages and continuous variables are expressed as medians (interquartile range). Univariable analysis of continuous variables was performed using two sample Student’s t-tests. Two-sided p-values <0.05 were considered statistically significant. Analyses were performed with Graphpad Prism version 9.2.0 for Windows (GraphPad Software, San Diego, California).
Results
A total of 13 patients referred for an EST consented to participate in this study (Table 1). None of the 13 subjects had structural heart disease, prior cardiac surgery, or known uncontrolled arrhythmia syndromes. Participants’ ages ranged from 9 to 17 years with a median of 15 years and 62% were female. The reason for referral to EST was exertional syncope in six patients, chest pain in four patients, and long QT syndrome (without a history of a sentinel cardiac event) in three patients.
Table 1. Patient demographics
The EST results are summarised in Table 2. The median EST endurance time was 12.9 (9.9–13.7) minutes. The exercise time in the standard Bruce protocol for each participant corresponded to a median endurance percentile, grouped for age and sex, of 50 (25–75). The median pre-test heart rate was 85 (56–99) beats per minute (bpm) with an increase to a median peak heart rate of 190 (154–198) bpm. The group achieved a peak heart rate equal to 92 (74–98) percent of their age-predicted maximal heart rate.
Table 2. Exercise stress test results
The reasons for ending testing were fatigue in eight participants, chest pain in three, and dizziness in two. There were no ischaemic changes on exercise ECG and no patients had an arrhythmia. There was no difference between male and female participants when comparing age and sex-adjusted endurance percentile, 50 (17.5–90) versus 37.5 (13.75–86.25) (p = 0.77), or predicted peak heart rate percentage achieved, 93 (89.5–97)% versus 87 (65.25–95)% (p = 0.14).
Every participant had an undetectable serum cTn level (<0.015 ng/ml) immediately prior to testing. Additionally, every subject had an undetectable cTn level 4 hours after the completion of their test.
Discussion
This is the first study to prospectively measure the effects of short burst, high-intensity aerobic exercise on cTn levels in healthy children and adolescents. Multiple studies have demonstrated clear elevations in serum cTn levels in paediatric patients after intense, longer duration, aerobic exercise. Reference Cirer-Sastre, Legaz-Arrese and Corbi5–Reference Cirer-Sastre, Legaz-Arrese and Corbi8 However, in these studies the amount of exercise ranged from running a half marathon to an hour-long competitive soccer match. The physician asked to assess a paediatric patient with an elevated cTn level after exercise is often seeing an individual who did not adhere to a well-defined, intense exercise regimen prior to presentation. Therefore, it is useful to understand the effects varying levels of exertion have on cTn levels to help guide clinical decision making.
Prior studies have demonstrated that exercise duration, exercise intensity, and amount of prior training correlate with the presence and degree of cTn elevation in adult patients. Reference Serrano-Ostáriz, Terreros-Blanco and Legaz-Arrese12–Reference Fortescue, Shin and Greenes15 The current data shows that cTn elevation is more likely after longer duration, higher intensity exercise in less-conditioned subjects. Since the paediatric studies to date have only assessed patients after a longer duration of intense exercise, it can be difficult to extrapolate the likelihood of cTn release from adult data since paediatric patients are often not highly trained athletes and often participate in high intensity, short bursts of exercise during routine play.
The underlying mechanisms that cause cTn rise after exercise in otherwise healthy subjects are not completely understood. Reference Aengevaeren, Baggish and Chung9 Most leading theories agree that the rise in cTn in these patients is likely not the result of significant myocardial injury or necrosis. Reference Aengevaeren, Froeling and Hooijmans16–Reference Trivax, Franklin and Goldstein18 Therefore, since the underlying process is thought to be benign, a physician caring for a patient who presents with an elevated cTn level after exercise may wonder if the patient could be spared further cardiac evaluation, intervention, or restriction if the abnormal lab value is indeed secondary to their activity. For patients presenting after intense, long duration aerobic exercise, results of prior studies have suggested that this may in fact be the case. Reference Cirer-Sastre, Legaz-Arrese and Corbi5–Reference Cirer-Sastre, Legaz-Arrese and Corbi8,Reference Trivax, Franklin and Goldstein18 This pilot project demonstrates that a short burst of high-intensity exercise is not expected to elicit a detectable serum cTn level. Therefore, it would likely be inaccurate to assume these patients have an abnormal lab value attributable to exercise and potential cardiac pathology should be considered.
While this study is strengthened by its prospective approach to evaluation of cTn levels in paediatric patients after exercise, there are limitations. First, while the power analysis presented above was based on prior studies evaluating cTn levels in paediatric patients after exercise, this is the first study to evaluate shorter duration exercise, and therefore, the true event rate of cTn rise in this population was unknown. We attempted to account for this by assuming a lower assumed event rate in the population. Since the subjects recruited were not referred for a cardiopulmonary exercise test with breath-by-breath analysis, the intensity of the exercise performed had to be based on endurance time and peak heart rate achieved rather than Respiratory Quotient (RQ). Thus, subjects may have given a more sub-maximal effort than their heart rate and run time would suggest and led to an artificially low troponin value. Finally, a standard cTn level was used in our study and newer, more sensitive cTn assays are currently being developed. Given the typical presentation of paediatric chest pain in the emergency department it would be of interest to conduct a study assessing high sensitivity troponin levels in healthy patients after a variety of activities not currently described in the literature, such as an American football game.
Acknowledgements
The authors are grateful to David Groscost, MHSA, RN for his assistance in sample collection, managing funds, and overall logistical support. We would also like to thank the staff of the Children’s Hospital of Pittsburgh Exercise Lab for their assistance.
Financial support
This work was supported by the Sang C. Park, MD, Endowed Fellowship Fund for Cardiology Fellows Research and in part by the National Institutes of Health through Grant Number UL1-TR-001857.
Conflicts of interest
None.
Ethical standards
This study was approved by the University of Pittsburgh Institutional Review Board. Written consent was obtained from all participants in this study and their parents or legal guardians.
