Endurance exercise and myocardial injury

A rise and fall pattern in cardiac troponin (cTn) values above the 99th percentile, with and without evidence of myocardial ischaemia, has been defined as myocardial injury by the ‘Fourth universal definition of myocardial infarction’.1 The definition recognizes strenuous exercise as a systemic condition that may cause myocardial injury.1 Over the past two decades, numerous studies have demonstrated increased cTn to be a common finding following strenuous physical exercise in healthy individuals.2 Therefore, most researchers consider exercise-induced cTn elevation to be a physiological phenomenon.2 The cardiac troponin I assay was first described by Cummins et al. in 1987, and cTn testing was made commercially available during the mid-1990s.3,4 Troponin increase was initially considered to be caused exclusively by myocyte necrosis.3 However, following the demonstration of exercise-induced cTn increase in healthy individuals, it has been hypothesized that cTn can be released due to reversible myocyte injury.3 The concept of reversible myocyte injury, however, is poorly understood. Several studies have attempted to identify the predictors of exercise-induced cTn release. However, less than 10% of the expected variance was explained by multivariable models constructed by Eijsvogels et al.5 A more comprehensive, multifactorial approach may therefore be necessary to understand the underlying mechanisms of exercise-induced cTn release. Potential factors that may be involved in the exercise-induced cTn release may include: increased wall tension and ventricular strain due to volume overload, neuro-hormonal stimulation and reversible ischaemia due to increased myocardial energy demands.2,6,7 In this issue of the European Journal of Preventive Cardiology, Kosowski et al. present a study of 33 marathon runners using a novel high-sensitivity cTnI assay by Singulex (Erenna immunoassay system, Singulex, Inc., Alameda, USA).8 Study subjects were assessed by echocardiography before and immediately following a marathon run. Treadmill cardiopulmonary exercise test (CPx) was carried out in 28 subjects. Venous blood samples were obtained at baseline (4–8 weeks before the marathon, V1), immediately after the competition (V2) and seven days after the marathon (V4). Additional samples were obtained at 72–96 h in a subset of 12 runners who volunteered to undergo cardiac magnetic resonance imaging (V3). In accordance with previous studies, the authors report a significant exercise-induced cTn increase, with 88% of subjects exceeding the 99th percentile of cTnI. There was no significant correlation between cTn increase and echocardiographic parameters, finishing time, index of heart rate achieved during marathon run or CPx parameters. The authors reported higher post-race cTn increase in subjects with less training experience. This finding is in accordance with a previous study of non-elite participants in the Boston Marathon.9 However, due to a small sample size, and the single sampling time-point during the first 72 h following the marathon, it is difficult to evaluate the dynamics and the interaction between different variables and the exercise-induced cTnI response in the present study. Recently, several groups have reported a prevalence of coronary artery disease (CAD) of 40–63% in master athletes.10–12 We have reported elevated post-exercise cTn values following strenuous exercise in asymptomatic subjects with occult CAD.6 Subjects included in the present study were 50–74 years of age. Therefore, a significant prevalence of CAD may be expected in the present cohort. The exercise-induced cTn response is expected to normalize within 72 h following strenuous exercise.13 Interestingly, in the study’s Figure 1, a markedly elevated cTnI is shown seven days after the marathon in at least one runner. This finding should probably not be interpreted as ‘physiological’ as it does not fit with current knowledge of post-exercise cTn kinetics. Following the marathon there was an increase in N-terminal pro B-type natriuretic peptide and endothelin-1, reaching the highest recorded values immediately following exercise. There was no significant association with the increase in these markers and echocardiographic parameters. Of note, no blood sampling was performed between immediately after and 72 h after the competition. It is therefore not possible to determine the peak of these biomarkers, and a precise relationship between these markers and the other parameters therefore cannot be established. In the present study echocardiography following the marathon showed increased right atrial maximal volume and reduced left atrial maximal volume. In contrast to previous reports, no changes in ventricular volumes or function were found. During exercise, there is a disproportionate amount of wall stress on the right ventricle (RV), as compared with the left ventricle.14 A number of researchers have reported decreased RV function following endurance events, and the degree of RV impairment has been reported to be associated with both duration and intensity of exercise.14–16 Decreased RV function has also been reported to be significantly associated with the cTn increase.9,16 The reason that no changes in RV function were observed in this cohort is not clear from the presented data. However, it should be noted that most previous imaging studies have reported on younger populations compared with the present study.9,15,16 There is much to be learned about the causes and consequences of exercise-induced cTn release. The present study adds to the increasing number of studies addressing the potential mechanisms and clinical role of exercise-induced cTn increase. However, despite the large number of publications addressing this issue, the main questions remain unanswered: what are the mechanisms causing the exercise-induced cTn increase? What are the long-term consequences of this increase? Can we separate a physiological from a pathological cTn response following exercise? We need to answer these questions to bring this field forward. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.