Case report—very high cardiac troponin I concentrations following endurance exercise: a complex finding

Abstract

Background

Exercise is known to increase cardiac troponin I (cTnI) concentrations, whereas the magnitude of exercise-induced elevations shows large inter-individual variability. Severely elevated cTnI concentrations post-exercise may be indicative of increased cardiac vulnerability and subclinical cardiovascular pathology.

Case summary

We present the case of a 66-year-old male recreational endurance athlete who showed remarkably high post-exercise cTnI concentrations after a long-distance walking event, but not after a cycling event. He did not experience any signs or symptoms of cardiac distress. Independent of his cTnI assessments, he underwent cardiac assessment, which revealed an intermediate stenosis of the proximal left anterior descending coronary artery, whereas functional testing did not reveal ischaemia or infarction.

Discussion

There is currently no consensus on the clinical interpretation of exercise-induced cTn elevations. Our athlete showed a very high cTnI concentration post-exercise, without evidence of ischaemia or myocardial infarction. Accordingly, we summarize other explanations that may have caused the elevated cTnI concentrations, including (1) progression of coronary atherosclerosis, (2) other underlying cardiac conditions, (3) exposure to exercise-related cardiac stress, (4) dehydration, and (5) cardiac vulnerability. This case with a large intra-individual difference in post-exercise cTn concentrations illustrates the challenging interpretation of exercise-induced cTn elevations. Future studies examining the underlying mechanisms of exercise-induced cTn release and its clinical sequelae are warranted to improve differentiation between physiological and pathological cTn elevations in athletes.

Learning points.

• Athletes can exhibit large intra-individual variation in post-exercise cardiac troponin concentrations without a clear explanation.

• Clinical interpretation of post-exercise cardiac troponin concentrations is challenging, given the large inter- and intra-individual variation across athletes and the multitude of factors that impact the magnitude of the response.

• Unravelling the mechanisms and clinical relevance of exercise-induced cardiac troponin concentrations is essential for distinguishing physiological from pathological responses following exercise.

Introduction

Exercise improves cardiac function, lowers the risk of cardiovascular events, and promotes longevity.^1,2 However, exercise can also produce elevations of circulating biomarkers, including cardiac troponin I (cTnI).^1,3 We previously showed that myocardial injury—defined as cTnI concentrations above the 99th percentile upper reference limit (URL)⁴—was associated with an increased risk of mortality and cardiovascular events in older long-distance walkers.⁵ Moreover, recreational cyclists with occult coronary artery disease (CAD) showed prolonged elevations of cTnI concentrations compared to their healthy counterparts.⁶ Therefore, significant elevations of cTnI concentrations following exercise may reflect cardiac vulnerability⁷ or subclinical cardiovascular pathology.⁸ Here, we present a case of an endurance athlete with a remarkably high post-exercise cTnI concentration, who coincidentally underwent cardiac evaluation (Figure 1).

Figure 1.

Summary figure. PVC, premature ventricular contraction; LVEF, left ventricular ejection fraction; CAC, coronary artery calcification; SPECT, single-photon emission tomography.

Summary figure

Case presentation

A 66-year-old male endurance athlete had a medical history of gastroesophageal reflux disease, treated with pantoprazole 40 mg once daily, and hypertension, adequately treated with amlodipine 10 mg once daily (RR 130/79 mmHg at rest). Since 2021, he reported experiencing sinus bradycardia at rest. Other than hypertension, he had no cardiovascular risk factors.

He practiced various sports since age 27, including running, mountain biking, fitness, and hiking. He completed 9 half-marathons, 65 long-distance cycling tours (≥120 km), and 35 long-distance walking events (50 km/day for 4 consecutive days). Upon enrolment in the TREAT study⁸ (May 2022), he was engaged in mountain biking (2 h/week) and long-distance walking (8 h/week).

In June 2022, he participated in a single-day 120 km bike tour, and cTnI concentrations were measured pre- and post-exercise (Figure 1). He cycled for 4 h and 37 min with an average speed of 26.0 km/h and an average heart rate of 111 beats/min. cTnI concentration was 1.5 ng/L at baseline and increased to 26.7 ng/L at 1h53 min post-exercise and returned to 6.2 ng/L at 22h18min post-exercise.

In May 2023, he more profoundly noticed his bradycardia with palpitations at rest, mentioning that he required specific breathing to bring his heart rate up, for which he was referred to a cardiologist by his general practitioner. During the cardiology consultation, he also mentioned occasionally experiencing dyspnoea, palpitations, and dizziness during exercise. For this reason, a cycling test with stress ECG and Holter monitoring was ordered. An echocardiogram ordered by his general physician because of bradycardia from 2021 was available for review (see Supplementary Clips  S1–S6). Additionally, amlodipine was switched to nifedipine to exclude a specific amlodipine effect on his bradycardia symptoms. His physical examination and resting ECG were normal, and the echo demonstrated a structurally and functionally normal heart. The Holter registration showed sinus rhythm and sinus bradycardia (mean 60 bpm, min 48—max 101) without conductance abnormalities. Regular premature atrial contractions and sporadic premature ventricular contractions (PVC, 2 in 24 h) were observed, correlating with the experienced palpitations. During the cycling test, polymorphic PVCs appeared at submaximal exertion (200 W) but disappeared at maximal exertion (250 W), without ST deviations suggestive of ischaemia (Figure 2A). Because of exertional dyspnoea and polymorphic PVCs, a cardiac CT scan was scheduled to exclude significant coronary artery disease.

Figure 2.

A, exercise test with electrocardiography recording showing 2 premature ventricular contractions in these 10 s at sub-maximal exercise (200 Watts) and only upsloping lateral ST segment depression; B, coronary computed tomography angiography with intermediate stenosis in the proximal left anterior descending coronary artery.

In July 2023, he participated in a multi-day long-distance walking event. He walked 50 km in 8 h and 11 min with an average speed of 6.1 km/h. On the first day of the walking event, cTnI concentrations increased from 1.9 ng/L at baseline to 812 ng/L at 0h29min post-exercise, 31 times the assay-specific 99th percentile URL (i.e. 26 ng/L, ALINITY i-series analyser, Abbott Diagnostics, Illinois, USA). The athlete reported no signs or symptoms of cardiac distress, whereas no serial samples were obtained due to the multi-day nature of the event with repeated exercise exposure.

In August 2023, the CT scan revealed an intermediate stenosis (50–70%) in his proximal left anterior descending coronary artery from a calcified plaque (Figure 2B). The calcium score was 170 Agatston units. To exclude ischaemia, a SPECT scan was ordered. The athlete was temporarily advised to avoid peak exercise, and statin therapy was initiated (i.e. atorvastatin 40 mg once daily).

In October 2023, the SPECT scan showed no areas with ischaemia or infarction (see Supplementary material online, Figure). Exercise restrictions were lifted, and the athlete returned to his former exercise habits. Furthermore, he was informed that the palpitations accompanying his bradycardia were attributable to the premature contractions. The patient was relieved that severe pathology was ruled out.

Discussion

We describe a male recreational athlete who completed two mass-participation exercise events and showed a very high post-exercise cTn concentration following long-distance walking but not long-distance cycling. Unrelated to his cTnI assessments, he underwent evaluation at a cardiology department due to palpitations at rest. Clinical assessments revealed an intermediate proximal left anterior descending stenosis, negative for ischaemia on exercise SPECT. There is currently no professional guideline available on how to interpret exercise-induced cTn elevations.

The magnitude of exercise-induced cTnI elevations is importantly dependent on exercise intensity.⁹ Up to 9% of long-distance walkers,⁷ 69% of marathon athletes¹⁰ and 96% of long-distance cyclists⁶ previously reported cTnI concentrations exceeding the URL. The cTnI concentration of 812 ng/L that was found in our athlete is, however, significantly higher than typically observed after prolonged walking¹¹ or endurance exercise sports at vigorous intensities.⁶ cTnI concentrations of this magnitude are typically found in a clinical setting, e.g., in patients with a myocardial infarction, myocarditis, or critical illness.^12,13 However, he did not report signs or symptoms of cardiac distress during or following the bout of walking exercise.

The difference in the magnitude of exercise-induced elevations in cTnI concentrations following 50 km of walking (ΔcTnI: 810 ng/L) vs. 120 km of cycling (ΔcTnI: 25 ng/L) is remarkable and not easily explained. We postulate the following hypotheses: First, it may be attributable to the progression of his coronary atherosclerosis, which may have produced a silent oxygen supply-demand mismatch during the prolonged bout of walking exercise. However, both SPECT and the regular exercise test were negative for ischaemia at exercise intensities far above values for walking exercise (∼70% HR_max).⁷ The involvement of the left anterior descending artery only makes a false negative SPECT unlikely (i.e. no balanced ischaemia). Second, the magnitude of exercise-induced cTn elevations may not be associated with coronary atherosclerosis¹¹ but with other cardiac conditions instead. However, echocardiography and cardiac CT did not reveal structural or functional abnormalities, and his resting cTnI value was low. Exercise-induced cardiac conditions such as coronary spasm, dissection, embolus, or arrhythmias are possible, but less likely to produce such cTnI values without symptoms. Third, it may be possible that very high concentrations of cTn post-exercise are not associated with cardiac pathology. Instead, the large inter-individual and intra-individual variation in the magnitude of cTn responses to exercise exposure may be predominantly dependent on variation in physiological factors, such as exercise characteristics, environmental conditions, and athlete characteristics (i.e. age, training status, health status). Fourth, exercise-induced changes in hydration status may explain some of the variance.¹⁴ Changes in albumin concentrations during the cycling event (38.5 to 41.0 g/L) and walking event (42.1 to 39.6 g/L) were, however, mild and unlikely to explain the difference in cTn responses between the exercise events. Fifth, the post-exercise increase in cTnI may have been caused at least in part by the increased cardiomyocyte membrane permeability and subsequent leakage of cardiac troponin fragments into the bloodstream.¹⁵ Prospective studies are needed to confirm this hypothesis.

Conclusion

cTn concentrations show large inter- and intra-individual variation in athletes, which is not fully explained by currently known predictors. Hence, clinical interpretation of very high post-exercise cTnI concentrations is challenging. Future studies unravelling the mechanisms and clinical relevance of exercise-induced cTn concentrations are eagerly anticipated as they will improve our understanding of their physiological vs. pathological nature.

Lead author biography

My name is Masha Padi, and I study medicine at Radboud University in Nijmegen. I am currently in my first year of clinical rotations. I have completed an internship at NTNU in Trondheim, Norway, where I studied the cardiometabolic effects of endurance exercise in post-partum women. I am passionate about sports cardiology, cardiac physiology, and coronary heart disease.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports online.

Author contributions

Masha Padi (Investigation, Visualization, Writing-review & editing), Sylvan L.J.E. Janssen (Conceptualization, Investigation, Supervision, Writing-original draft, Writing-review & editing), Thijs M.H. Eijsvogels (Conceptualization, Investigation, Supervision, Writing-original draft, Writing-review & editing), Vincent L. Aengevaeren (Conceptualization, Investigation, Supervision, Writing-original draft, Writing-review & editing)

Consent: The authors confirm that written consent for submission and publication of this case report, including images and associated text, has been obtained from the patient, in line with COPE guidance.

Funding

S.L.J.E.J. was financially supported by a Radboud University Medical Center grant and a grant from the Academic Alliance Fund. T.M.H.E. was supported by an Established Investigator E-Dekker grant (#03-002-2023-0036) and FIT-HEART consortium grant (#01-001-2024-0621) of the Dutch Heart Foundation.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.