Cardiovascular magnetic resonance to evaluate cardiopulmonary remodelling in endurance athletes: can we predict adaptation to exercise?

Physical exercise has been associated with multiple cardiovascular benefits; thus, all scientific societies recommend regular physical activity for the prevention and treatment of cardiovascular diseases.1,2 These benefits have been established for low and moderate-intensity exercise;3,4 however, it cannot be assumed that this observed benefit can be generalised to high-intensity training which is also associated with cardiovascular structural changes and ventricular remodelling. Nevertheless, high-intensity training has become a trend in recent years due to social demand for the best possible physical exercise in the shortest time and with the greatest benefits. However, recent studies have revealed little or no additional benefit of daily strenuous exercise instead of less frequent or less intense exercise.3,4 Athletic training on a regular basis is associated with cardiac structural, functional and electrical remodeling, known as athlete's heart.5,6 This remodelling is necessary for an athlete to develop physical activity more efficiently than a sedentary individual and may appear in early adulthood (preadolescence). In a recent study, Bjerring et al. showed that preadolescent athletes (aged 12 ± 0.2 years) already presented with greater left and right ventricular chamber dimensions and left ventricular mass compared with controls; however, no differences in left or right ventricular function were reported (with the exception of a decrease in right ventricular global longitudinal strain).7 Although these changes are physiological, myocardial damage can occur when exercise is strenuous and prolonged, and although either of the two ventricles can be involved, the right ventricle (RV) is the most commonly affected.8 The degree of right ventricular dysfunction seems to depend on the intensity and duration of the physical activity,8,9 and in some clinical studies has been correlated with biomarkers of myocardial injury such as cardiac troponins or B-type natriuretic peptide.8 Right ventricular involvement is usually transient and function normalises days after the high-intensity training; however, in some athletes fatigue and recurrent RV lesions may predispose to chronic damage and the onset of ventricular arrhythmias.10 This damage can develop even when underlying demonstrable genetic abnormalities are absent, resulting in what is known as exercise-induced right ventricular arrhythmogenic cardiomyopathy,11 possibly leading to a proarrhythmic state similar to that induced by genetic cardiomyopathy. Endurance athletes may present with right ventricular dilation, electrocardiogram repolarisation abnormalities and ventricular ectopia. In order to differentiate these physiological findings from arrhythmogenic cardiomyopathy, a series of differential morphological criteria has been established with the use of different cardiac imaging techniques (such as cardiovascular magnetic resonance; CMR). In athletes, a diastolic volume ratio of the RV/diastolic volume of the left ventricle by CMR greater than 1.2, a right ventricular ejection fraction (RVEF) of 40% or less, wall motion abnormalities of the RV and fibrosis/myocardial fat infiltration suggest arrhythmogenic cardiomyopathy rather than a right ventricular adaptation to exercise.12 Furthermore, with CMR, late gadolinium enhancement (LGE) has also been reported in 10% of athletes. The main causes include myocarditis, genetically induced cardiomyopathy, drug use (steroids) or the effect of strenuous exercise. Different LGE patterns have been described: subepicardial, intramyocardial or at the junction of the ventricular septum. Evaluation of the LGE pattern is clinically significant because the presence of subepicardial or intramyocardial fibrosis is associated with a higher incidence of ventricular arrhythmias at follow-up.13 Whether the presence of LGE in a competitive athlete should imply his or her withdrawal from competition is under debate. Physical exercise not only implies adaptive changes in both ventricular chambers but also induces haemodynamic changes that affect the pulmonary circulation (what is known as RV–pulmonary artery coupling). During physical activity, cardiac output undergoes a three to fivefold increase, compared with baseline which must be assumed by the pulmonary circulation. This is possible the result of a pulmonary system of low resistance and high compliance, pulmonary vascular vasodilation and increased perfusion of the upper pulmonary lobes.14 During exercise, these factors combine to reduce pulmonary resistance by approximately 30%. However, although ventricular remodelling (both left ventricle and RV) has been more studied and described in athletes, data on the haemodynamic changes in the pulmonary circulation remain scarce. In this regard, CMR, using conventional two-dimensional velocity-encoded phase-contrast sequences, has the potential to evaluate changes in pulmonary flow. In addition, using conventional cine sequences, it enables the evaluation of the biomechanical properties of the pulmonary circulation. Pulmonary distensibility and pulmonary vascular resistance (PVR) have been the most commonly used parameters in clinical practice.15 On this subject, a decrease in the pulmonary vascular distensibility or an increase in the PVR can be associated with an impaired aerobic exercise capacity and RV–pulmonary arterial uncoupling.16 In this issue of the European Journal of Preventive Cardiology, Domenech-Ximenos et al.17 evaluated the ventricular remodelling induced by endurance exercise together with pulmonary function in 93 athletes between 20 and 45 years of age and highly trained (minimum of 12 hours a week in the last 5 years). The authors also analysed their results based on sex differences and compared their findings with a control population of 72 age and sex-matched individuals. Individuals with structural heart diseases, a family history of cardiomyopathy or pneumopathy, intake of illicit substances or being under cardiological treatment were excluded from the study. All individuals underwent a detailed anamnesis, physical examination, a 12-lead surface electrocardiogram, CMR, a stress test with an upright cycle ergometer and a complete echocardiogram at rest and immediately post-exercise. Through CMR, ventricular volumes, ejection fraction, pulmonary artery area and pulsatility, pulmonary flow, pulmonary flow velocity and PVR (estimated according to García-Álvarez et al.)18 were assessed. The results of this study reinforce the data currently available on endurance athletes because the authors observed that these individuals presented dilation of both ventricles and a slight decrease in biventricular function; these changes were also observed after dividing the population by sex.5,6,8,9 Furthermore, the authors reported an increase in myocardial fibrosis in athletes compared with controls (37.6% vs. 2.8%, respectively, P = 0.001) as previously reported in other series.13 However, in the present paper, all athletes with LGE presented with the most benign pattern of fibrosis at the junction of the ventricular septum, with no other foci associated with ventricular arrhythmias such as subepicardial or intramyocardial patterns. The same pattern was also described in patients with pulmonary hypertension; however, the authors found no relationship between the pulmonary haemodynamic parameters and the LGE pattern. In addition, Domenech-Ximenos et al.17 provided information on the changes produced in the pulmonary circulation as a consequence of physical exercise. The authors stated that endurance athletes had a greater pulmonary vascular tree diameter (determined as a larger pulmonary area) compared with controls, a reduction in the flow velocity in the pulmonary artery and an increase in flow PVR. These changes in the pulmonary circulation were attributed to physical activity and not as a consequence of an underlying subclinical pulmonary disease. This was proved as athletes did not present with differences in the biomechanical properties of the pulmonary artery (determined by pulmonary pulsatility artery) compared with controls (P = 0.853), which demonstrated a compliant pulmonary vascular tree and, also, because athletes presented with higher oxygen consumption in the stress test compared with controls (P = 0.032), showing better aerobic physical condition and greater relative intensity on physical exercise capacity. Therefore, in addition to the direct stress of endurance exercise on the myocardium, it has been hypothesised that the greater right ventricular remodelling could be determined by vascular pulmonary hyperflow and PVR increase to which these athletes are exposed. One of the most interesting findings of this work is that the authors identified 9.3% of athletes who presented with an abnormal increase in PVR (>4.2 Wood units). Those athletes presented no differences in age, sex, training load, maximum oxygen consumption or cardiorespiratory efficiency during exercise compared with athletes with normal PVR. However, they did present with greater dilation of the pulmonary vascular tree, reduced pulmonary artery pulsatility (alteration in its biomechanical properties), greater right ventricular dilation (increase in right ventricular end-systolic volume) and a lower RVEF. Therefore, the identification of this subgroup of athletes is of great interest because it allows individuals with worse adaptation to physical exercise and who may also evolve to greater right ventricular remodelling with prognostic implications such as greater right ventricular dysfunction and induction of ventricular arrhythmias to be detected.10,11 These changes in PVR were secondary to intrinsic alterations of the pulmonary vasculature and not to left ventricular disease. This was ruled out because athletes with higher PVR did not have larger left ventricular volumes, presented with normal left ventricular systolic function and did not have a higher incidence of myocardial fibrosis or left ventricular diastolic dysfunction. Although the current paper does not investigate possible aetiological causes that could justify these biomechanical changes in the pulmonary circulation, in normal conditions athletes are known to have greater pulmonary and systemic vasodilation capacity19 due to a reduction in endostatin production (antiangiogenic factor)20 and an increase in nitric oxide production through increased function of endothelial nitric oxide synthetase.21 However, it has also been reported that endurance exercise can increase the production of inflammatory cytokines22 and angiotensin II,23 which could induce vascular changes and favour poor adaptation to physical exercise. One of the main limitations of the present study is that the formula used for PVR calculation was derived from a heart failure population,18 and has not been validated in healthy individuals or athletes. However, regardless of whether the value obtained by this formula does not correspond to the real PVR value in athletes, it does highlight that a subgroup of them have abnormally high PVR values and greater right ventricular remodelling that could benefit from closer monitoring and follow-up. Whether these findings will result in greater right ventricular remodelling with a significantly increased risk of ventricular arrhythmias or cardiovascular events remains to be established. To this end, follow-up studies on this population are required to assess the main clinical implications of these findings. The present study by Domenech-Ximenos et al.17 emphasises the significant role of CMR in the evaluation of endurance athletes because, in the same examination, we can obtain data on biventricular volumes and ejection fraction, the presence of myocardial fibrosis (with prognostic implications and associated with a higher incidence of ventricular arrhythmias), and, in addition, evaluate pulmonary vascular circulation and the PVR. This information can be obtained without an excessive increase in examination time as the data necessary for PVR estimation are obtained by the conventional sequences used in CMR in routine clinical practice. The clinical significance of these findings and how often athletes should be evaluated remain to be defined. Follow-up studies will shed more light on this field that is generating growing interest in the scientific community. 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.