This study showed that athletes with a positive ET result in the absence of obstructive CAD do not have a higher LV mass than athletes with normal ET results. These athletes, however, did show a smaller LVEDD, a higher RWT and asymmetric remodeling due to an increased IVS thickness, as well as a prolongation of the DT of the early filling velocity of the LV suggestive of an altered diastolic function. It should be acknowledged that these differences were small and values were still within the normal range. Therefore, these results suggest that sport-induced morphological adaptations only play a limited role in the development of STT changes during exercise.
To the authors’ knowledge, this is the first prospective study evaluating the relationship between LV remodeling and ET results in healthy asymptomatic athletes. In the present study, there was no significant difference in absolute LV mass and LV mass indexed to BSA between the athletes with abnormal ET results and the athletes with normal ET results. These findings are in line with previous studies [20, 21] that include smaller study populations. Despite the fact that the present study did not show a relationship between LV mass and abnormal ET results, the RWT was significantly higher in athletes with abnormal ET results than in athletes with a normal ET result (0.38 ± 0.06 versus 0.36 ± 0.06, p = 0.044). The present study also showed a significantly decreased LVEDD and increased IVS thickness at the end diastole in athletes with abnormal ET results, leading to a significantly higher IVS/PWT ratio. These findings suggest that athletes with abnormal ET result show a pattern of asymmetric cardiac remodeling.
The two groups of athletes in the present study showed no significant difference in the delivered maximal workload. However, a significantly higher maximum heart rate was observed in athletes with abnormal ET results. According to the Fick principle (V̇O2, max = cardiac output x [arterial - venous O2 difference]), one can assume that there is a reduced stroke volume (SV) in athletes with abnormal ET result, as there is a linear relationship between the workload and V̇O2 . A possible explanation of the reduced SV could be the presence of a smaller left ventricular cavity expressed as a reduction in the LVEDD due to the asymmetric remodeling seen in the present study. The findings of a significant higher achieved maximum heart rate reflect necessary physiological adaptations to the observed cardiac remodeling in order to obtain the necessary increase in cardiac output.
The asymmetric remodeling pattern may be explained by Poiseuille’s law (pressure = flow x resistance). During exercise, and especially in dynamic sports activities, cardiac output (flow) increases more than total peripheral resistance (TPR), resulting in an increase in LV afterload, which initiates cardiac remodeling. According to the law of Laplace, an increase in afterload causes an increase in wall stress. In order to reduce wall stress, concentric remodeling occurs with an increase in overall wall thickness. However, in some patients, asymmetric remodeling develops rather than concentric remodeling. In particular, asymmetric remodeling is commonly observed in patients with an increase in LV afterload due to aortic stenosis and systemic hypertension (10–25%) . This may be explained by the fact that the ventricular septum has a larger bending radius than the posterior wall. During contraction, this larger bending radius leads to greater myocardial stress of the septal wall. This initiates a more pronounced hypertrophic response leading to asymmetric remodeling of the septal wall . The same mechanism may be responsible for the findings in athletes in the present study. Yet, it remains unclear why only some of the athletes in this study express asymmetric remodeling. One could speculate that these athletes have a genetic predisposition for developing an increase in myocardial wall thickness in response to an increase in LV afterload . It is also known that an increase in afterload leads to an impairment of myocardial relaxation . This theory is supported by Hayashida et al. , who show that a greater impairment of myocardial relaxation is observed with increasing wall thickness. In this way, afterload and (asymmetric) cardiac remodeling can alter diastolic LV function and eventually lead to diastolic dysfunction.
This altered diastolic function could possibly be an explanation for the observed ST-segment depression in athletes without the presence of epicardial CAD. As shown in the present study, there was a significant prolongation of the DT of the early left ventricular filling velocity in athletes with abnormal ET results. This prolonged DT reflects an impaired left ventricular relaxation. Ventricular relaxation is one of the major determinants of diastolic filling and is characterized by the duration of the decrease of LV pressure after systole. A prolonged DT indicates that LV end diastolic pressure (LVEDP) is elevated. It is known that a minimal perfusion pressure is necessary to maintain patency of the coronary microvasculature . As a result of an elevated LVEDP, the critical closing pressure of the coronary microvasculature could be exceeded. Due to this phenomenon, the perfusion gradient is compromised, resulting in a reduced coronary flow. In turn, the reduced coronary flow leads to an ischemic response, which further aggravates the LVEDP through ischemia-induced alterations in the diastolic pressure–volume relationship.
Another possible explanation for the ST-segment depression could also be related to the observed cardiac remodeling. It is known that an increase in myocardial mass should be evenly compensated with an increase in angiogenesis to fulfill the requirements for increased oxygen consumption . However, this response has been found to be critically dependent on age , as angiogenesis does not outweigh the increase in LV mass in the elderly . The present study included athletes with a mean age of 52.9 years. It is feasible to think that there might be an imbalance between myocardial mass and angiogenesis, especially in the group of athletes with asymmetric cardiac remodeling.
It has also been shown that [27, 29] this imbalance leads to a reduced vasodilator reserve. A previous study  shows that an active vasomotor tone is required to maintain subendocardial perfusion by creating a flow gradient to the deeper myocardial layers. In the case of a defect in the vasomotor tone, there is an impaired regulation of myocardial perfusion due to the diminished gradient from epicardium to endocardium. This dysfunctional vasodilation may be caused by a reduction in availability of the endothelium-derived relaxing factor (EDRF), also known as nitric oxide (NO), and an increase of endothelin-1 (ET-1) levels. Due to the imbalance between vasodilation and vasoconstriction, an endothelial vasodilator dysfunction can develop . Therefore, endothelial dysfunction could be an explanation of exercise-induced ischemia in athletes, although previous studies show conflicting results of both increased endothelial function , similar  and reduced endothelial function  in athletes. In athletes, it is known that an increased myocardial blood transition time enables higher oxygen extraction levels together with a lower myocardial blood flow and higher vascular resistance . All these adaptations are key to deliver adequate oxygen supply to the myocardium in response to the needs during exercise in the athletic heart. In the case of an imbalance between myocardial mass and angiogenesis together with a reduced vasomotor tone, myocardial oxygen delivery is reduced, which can induce exercise-induced ischemia.
Myocardial ischemia with ST-segment depression can also occur due to cardiac compressive forces. During basal conditions, systolic contraction impedes myocardial blood flow resulting in primarily diastolic filling of the coronary vasculature. However, during exercise 40–50% of the coronary blood flow occurs during systole as the diastolic interval decreases with higher heart rates. It is feasible to think that the observed increase in septal wall thickness, together with the above-mentioned imbalance, compresses the coronary microvasculature. These factors, solely or combined, could cause the observed ST-segment depression as an expression of myocardial ischemia.
The high prevalence of abnormal ET results in athletes requires consideration, because an erroneous diagnosis may have important consequences. For instance, a false diagnosis of cardiac disease warrants unnecessary activity restriction or even disqualification from sports, while an incorrect diagnosis may jeopardize the life of an athlete . In addition, athletes with abnormal ET results undergo invasive diagnostic procedures, which are accompanied with higher health care costs. In order to reduce the high number of abnormal ET results, it is necessary to elucidate associated mechanisms and identify predictors that can be used to improve the positive predictive value of electrocardiography in asymptomatic athletes. This study shows a possible relationship between LV asymmetric remodeling and the occurrence of abnormal ET results. However, given the small differences in echocardiographic values between groups, cardiac remodeling only seems to play a limited role. Therefore, other sports-related mechanisms that may be related to the development of STT changes during exercise, such as microvascular dysfunction, insufficient density of myocardial capillaries relative to myocardial mass and compression of the microvascular arteries due to high ventricular filling pressure, should be explored.
There are several limitations that should be acknowledged. First, LV mass was measured via echocardiography. M-mode echocardiography is the most widely used technique in the evaluation of the LV mass, because of the relatively low costs and the rapid and non-invasive character. However, M-mode echocardiography has important limitations particularly in subjects with abnormal LV geometry as it is known that the accuracy of LV mass measurement declines in dilated left ventricles . Also, it is known that M-mode echocardiography overestimates LV mass when compared with magnetic Resonance Imaging (MRI) and there is a high test-retest variability in LV mass among one single individual of approximately 35 g (the smallest detectable change with 95% confidence interval) . Therefore, in order to detect a change in LV mass of at least 10 g, approximately 200 subjects per group would be necessary . Another limiting factor is the intra- and interobserver variability in the measurement of LV mass. Literature showed that there is an intraobserver variability of 19 g and an interobserver variability of 24 g . MRI is the gold standard for accurate assessment of the LV mass, but this technique is relatively expensive, time consuming and not feasible for all patients . Therefore, it is less suitable for routine clinical screening for cardiac remodeling in athletes. Second, the primary study was not powered to detect a difference in LV mass in athletes which could lead to a type II error in the present study. Finally, the study population consisted primarily of male athletes who practice high-static, high-dynamic sports. Therefore, it was not possible to make a reliable statement about the correlation of LV remodeling on abnormal ET results in female athletes and athletes who perform low-static, low-dynamic exercise or other types of sports.