The current study provides a comprehensive analysis of cardiac remodelling and the findings from CMR LGE and ECV assessment in asymptomatic highly trained endurance male and female athletes compared to age- and gender-matched controls.
The major findings of our study were: 1) as expected, highly trained endurance athletes showed an increase of biventricular and biatrial cavity sizes and a slight reduction of biventricular ejection fraction; 2) the presence of LGE, as a potential marker of focal fibrosis, was ten-fold more prevalent in athletes (both genders) as compared to controls, and it was always located in the inferior insertion point; 3) the presence of focal LGE did not result in significant differences in ventricular volumes and ejection fraction or in parameters of maximum aerobic capacity; and 4) athletes with LGE+ showed higher ECV values, despite they were globally still within the normal reference range.
Prevalence and distribution of LGE on contrast CMR in athletes
Our study provides additional evidence that highly trained endurance athletes show a significantly higher prevalence of focal LGE than age- and gender-matched control subjects [
4,
11,
23]. The prevalence of LGE, as a potential marker of focal fibrosis, was up to 37.6% in our group of athletes, ten-fold higher than that observed in the control group. This prevalence was significantly higher than reported in other series of athletes [
11,
24,
34]. Even though Tahir et al. [
34] did not find focal LGE in female athletes, we found a similar prevalence between male and female athletes (
p > 0.05), as also previously described in other reports [
24]; this could be due to the homogeneity of our cohort of athletes. Additionally, we did not find differences regarding training load between female and male athletes, unlike Tahir et al. [
34], who noted that their female athletes reported less training load.
In our study, all athletes with LGE showed a similar pattern, consisting of a small volume of focal LGE confined to the interventricular septum, commonly where the RV attaches to the septum (the inferior insertion point or hinge point). This pattern corresponds to a typical non-ischemic substrate. Other specific LGE patterns, such as subendocardial, transmural or subepicardial, were not identified in our population.
This observation may be because our population was constituted by completely asymptomatic, otherwise healthy, young athletes, while in previous studies the athlete’s cohort was older [
11,
12,
23,
34,
35] or had abnormal findings on their regular screening check-ups [
36]. Breuckman and colleagues [
11] studied a cohort of 102 veteran athletes and found that 12% had LGE, of which almost half showed a coronary artery disease pattern. Bohm et al. [
12] in 33 endurance athletes found 3 of them having subepicardial LGE, which is typical for old myocarditis/pericarditis. Wilson and colleagues [
23] in a small cohort of 12 veteran athletes found that 42% exhibited a non-coronary LGE pattern. They also included 17 young athletes in which no LGE was found. Likewise, Merghani et al. [
35] included 152 master athletes, of which 14% revealed LGE. Nevertheless, they did not find relationship between myocardial fibrosis and exercise intensity, years of training, or number of competitions. Only in the study of Schnell et al. [
36], athlete’s population was younger than ours. This study included 7 asymptomatic athletes who all showed LGE; including four with pathological T-wave inversions and two with ventricular arrhythmias on a screening exercise test. To our understanding, ours is the largest cohort of young, healthy and asymptomatic athletes published, and we assume that, unlike other studies, we probably did not find clearly pathological LGE patterns since our athletes were strictly recruited by invitation to participate in a research project, and not because they presented any type of clinical or electrical abnormality.
Regarding the presence of focal fibrosis in the insertion point, La Gerche et al. [
32] has suggested that the RV may remodel slightly more than the LV in endurance athletes, since RV wall stress increases more than LV wall stress during exercise and this places an additional pressure load on the RV. Focal LGE in the RV inferior interventricular septum has been related to RV pressure overload and systolic pulmonary hypertension [
37,
38]. Specifically, the presence of focal LGE in the RV inferior interventricular septum, as well as the extent of hyperenhancement, has been inversely related to measures of RV systolic function in patients with severe symptomatic pulmonary artery hypertension [
37]. However, the clinical significance and the real impact on outcome of the presence of small regions of LGE in the RV insertion point, in asymptomatic subjects, are still uncertain and these aforementioned prognostic implications should not be extrapolated.
Differences between LGE+ and LGE− athletes
LGE
+ athletes showed no significant differences in LV and RV volumes or function as compared to LGE
− athletes. However, other authors [
11,
23,
24,
34] have reported that those athletes with LGE had been competing in endurance sports for longer and had greater RV EDV and lower RVEF. Additionally, our athletes did not show a hypertensive response to exercise and, unlike Tahir et al. [
34], we did not find significant differences regarding the peak exercise systolic blood pressure between LGE+ and LGE- athletes.
Our data demonstrates balanced biventricular and biatrial dilatation with a slight reduction of biventricular ejection fraction in athletes with and without LGE; this may arise, given the inclusion criteria, from the fact that our athletes practise the same endurance sport discipline and have similar training load. Thus, all this data potentially suggests that this LGE pattern might be another feature of the athlete’s heart, related to local mechanical stress due to the exercise-induced cardiac overload. While LGE has been correlated to focal fibrosis in chronic infarction, LGE dynamics are still controversial and not fully understood in other settings. The presence of LGE indicates that the local matrix and fibre structure has changed, similarly to what happens indeed in histologic fibrosis and scar; however, LGE could also be present due to localized structural remodelling regardless of the presence of real fibrosis. Experimental models of endurance training might shed some light in the real clinical significance of the observed LGE in athletes.
T1 mapping sequence and ECV assessment
Considering that the increased LV mass, observed in athletes, is due to an expansion of the cellular compartment, a decreased ECV is to be expected [
39]. In fact, McDiarmid et al. presented data showing that increasing degrees of training load linearly increase myocyte hypertrophy and inversely ECV in the athletic group in a cohort of 30 athletes (athletes vs controls; 22.5% ± 2.6 versus 24.5% ± 2.2;
p = 0.02) [
39].
Nevertheless, in our study we did not find a decrease in ECV in athletes. And when we separately analysed those athletes with focal LGE confined to the inferior insertion point, we observed that they had slightly higher ECV at remote LV myocardium than those without LGE, despite still being within the limits of normality [
29,
30]. These data are in line with previous published literature [
34] suggesting that the potential myocardial fibrosis might involve the entire myocardium of athletes, with focal LGE, and would not be confined only to the LGE areas. There might be other explanations to the increase of ECV; Coelho-Filho and colleagues [
40] worked with hypertensive patients with LV mass within the gender-specific normal range, and found that their ECV was significantly higher than in controls. They suggested that expansion of the ECV could precede significant increase of LV mass. Nevertheless, our patients did not have hypertension, which indeed was an exclusion criterion for the study, and there were no significant differences in LV mass between LGE+ and LGE- athletes.
Further studies with long-term follow-up are clearly warranted to understand if these slightly higher ECV values are another feature of the athlete’s heart or if this may be able to early identify athletes who are starting to potentially develop diffuse interstitial fibrosis and have indeed an abnormal adaptation to training.
Study limitations
The quantification of the training load by assessing self-reported training load represents a potential limitation, because these parameters depend on the individual perception and accuracy of athletes. Currently, no long-term follow-up data on outcomes is available to assess the prognostic and clinical implications of the observed LGE. The T1 mapping sequence was available in only 30% of athletes, among whom 71% were female; thus, findings need to be confirmed in larger populations.