Non-ischaemic myocardial fibrosis and ventricular arrhythmias in male master athletes: possibly common, but clinically trivial?

This editorial refers to ‘The timing and relationship of ventricular arrhythmia with exercise patterns in veteran male endurance athletes’, by W. Javed et al. https://doi.org/10.1093/eurjpc/zwag021. Until recently, running a marathon was considered the ultimate goal for a young athlete, something almost extreme and reserved for a small group of highly motivated individuals. Today, however, the 42 km race has almost become an entry-level challenge for a middle-aged amateur athlete and an increasing number engage in Ironman competitions, ultra-trail races, and other extreme endurance events. This growing population of master athletes (MA) was almost non-existent a few decades ago, but it has now become a relevant and rapidly expanding group.1 As sports cardiologists, we are increasingly confronted with an important question: can such intense and prolonged exercise, performed at an older age, carry potential adverse consequences? In the last months, two important studies have significantly improved our understanding of the spectrum of the MA’s heart in terms of tissue abnormalities (explored by contrast-enhanced cardiac magnetic resonance, Ce-CMR) and ventricular arrhythmias (VA): the British VENTOUX study2 and the Australian-Belgian Master@Heart study.3 These studies enrolled cohorts of endurance MA with long-standing exposure to high training volumes who volunteered to undergo Ce-CMR, exercise testing, and ambulatory electrocardiogram (ECG) monitoring. Both studies demonstrated a high prevalence of non-ischaemic myocardial fibrosis as suggested by late gadolinium enhancement (LGE) with subepicardial/midmural distribution and of exercise-induced VA. These results confirmed and extended previous observations reported mainly in male endurance athletes, showing that the prevalence of non-ischaemic LGE and VA is higher than in young elite athletes and middle-aged sedentary non-athletes.4 Importantly, the two new studies found a significant association between myocardial fibrosis and VA.2,3 Together with other well-known findings, such as the increased incidence of atrial fibrillation and the higher burden of coronary atherosclerotic plaques, these data suggest that the MA’s hearts are not as healthy as previously thought, although a direct cause–effect relationship between cardiovascular abnormalities and cumulative training cannot yet be demonstrated.4 Moreover, it remains to be proven that such changes negatively affect prognosis, as higher leisure-time exercise continues to be associated with lower mortality.5 In this issue of the European Journal of Preventive Cardiology, Javed et al.6 presented a sub-analysis of the VENTOUX study and focused specifically on the relationship between VA recorded with an implantable loop recorder (ILR) and physical activity. The study included more than 100 veteran endurance athletes, mainly cyclists or triathletes over 50 years of age, with more than 15 years of high-volume endurance training. Importantly, all participants had no history of cardiovascular disease and were asymptomatic at enrolment. According to the study protocol, athletes underwent a comprehensive baseline evaluation including resting ECG, maximal cardiopulmonary exercise testing, Ce-CMR with pharmacological stress, and long-term arrhythmic monitoring using an ILR. This unique design allowed continuous rhythm monitoring over a prolonged period, providing unprecedented insight into the burden and timing of VA in this population. The most striking finding was the high number of VA recorded during follow-up. One-quarter of athletes experienced episodes of non-sustained ventricular tachycardia, and notably, three athletes developed sustained ventricular tachycardia, including one who later received an implantable cardioverter defibrillator (ICD). Most arrhythmic events occurred during physical activity or shortly after exercise, reinforcing the well-known concept that exercise can act as a powerful arrhythmic trigger. At the same time, no significant differences in training volume, intensity, or training patterns were observed between athletes with and without VA. Furthermore, within the subgroup of athletes who experienced arrhythmic events, the training load and intensity in the weeks preceding the events were not significantly different from their usual training habits. However, athletes who developed VA showed a markedly higher prevalence of myocardial fibrosis on CMR, together with a more frequent occurrence of premature ventricular complexes (PVCs) with uncommon features during exercise testing. From a clinical perspective, these findings have several important implications. First, they support the idea that in MA, long-term endurance exercise may act as a substrate modifier in a subset of predisposed individuals, rather than exerting a uniform effect across all athletes. Despite comparable exposure to high-intensity and long-duration training, only some subjects appear to develop focal myocardial fibrosis and VA, suggesting an underlying individual susceptibility. Second, exercise itself clearly acts as a trigger for VA, as most non-sustained and all sustained ventricular tachycardias were temporally related to physical activity. This dual role of exercise, both as a substrate modifier and as a trigger, may suggest that, at least in predisposed individuals, a U-shaped relationship between arrhythmic risk and training load exists. Importantly, athletes who experienced VA also showed a significantly higher prevalence of PVCs with uncommon features during exercise testing. This finding reinforces the clinical value of exercise testing as a screening tool for MA, a population in whom advancing age is known to increase not only the prevalence of coronary artery disease but also the arrhythmic risk.7 Perhaps the most challenging message of this study relates to exercise prescription. In daily clinical practice, when managing patients with known or suspected cardiac disease, physicians often try to identify a ‘safe threshold’ of exercise. This is usually done by relying on concepts derived from ischaemic heart disease, such as keeping exercise intensity below the lactate threshold or to a certain percentage of heart rate reserve.8 The underlying assumption is that by avoiding excessive intensity or duration, the risk of arrhythmias can be reduced while still allowing patients to remain physically active. However, whether this methodology reduces the risk of life-threatening VA in athletes with pathological myocardial substrates remains to be demonstrated. Indeed, the present study showed that VA did not cluster around particularly intense training sessions, extreme heart rates, or unusually high training loads but they occurred in a rather random fashion during routine exercise sessions. As a result, exercise prescription in MA with myocardial fibrosis or VA remains uncertain, and the balance between allowing continued physical activity and reducing arrhythmic risk becomes particularly delicate. This uncertainty should be clearly acknowledged when counselling athletes with arrhythmogenic diseases. In a recent study, we reported the follow-up of 40 asymptomatic athletes with large (>5% of the left ventricular mass) non-ischaemic scars who were prescribed beta-blockers and provided a detailed non-competitive exercise prescription plan. Nevertheless, two experienced major events (cardiac arrest and syncopal ventricular tachycardia) during follow-up.9 Finally, a word of caution is essential when interpreting myocardial fibrosis in MA (Figure 1). A decade ago, the detection of non-ischaemic myocardial fibrosis in athletes was often interpreted as the consequence of healed myocarditis and frequently dismissed as a benign or trivial finding. Later, these scars were recognized as important arrhythmic substrates associated with exercise-related sudden cardiac arrest.10,11 Now, despite the growing evidence of an association between endurance exercise and myocardial fibrosis, we should not repeat the same error and interpret any non-ischaemic scar as a physiological feature of the athlete’s heart. In the studies on male MA discussed here, myocardial fibrosis was typically very focal, involving on average around 1% of the myocardial mass.2–4 In addition, a precise description of PVCs morphology was lacking, which does not allow firm conclusions regarding the correlation between such limited myocardial fibrosis and the arrhythmic events. Larger or more extensive areas of fibrosis, particularly in young and female athletes and when associated with positive family history, suspicious symptoms, ECG abnormalities (particularly lateral T-wave inversion and low QRS voltages in limb leads), and complex arrhythmias with a morphology suggesting origin from the scar (typically right-bundle-branch-block, superior axis, and QRS duration >130 ms), should still be regarded as potentially pathological.12,13 In these cases, the non-ischaemic left ventricular scar may represent the expression of an underlying cardiac disease, particularly genetic cardiomyopathy, and therefore, thorough diagnostic evaluation and appropriate strategies for sudden cardiac death prevention remain mandatory. Key features supporting the differential diagnosis between non-ischaemic left ventricular scars commonly observed in endurance athletes, potentially exercise-related, and scar patterns suggestive of an underlying cardiomyopathy at higher arrhythmic risk. In middle-aged or senior male athletes, small subepicardial or mid-myocardial areas of late gadolinium enhancement have been frequently reported by recent studies and are often associated with long-standing endurance training. This pattern should be clearly differentiated from non-ischaemic left ventricular scars typical of cardiomyopathies at risk of sudden cardiac death, particularly left-dominant arrhythmogenic cardiomyopathy (classified among non-dilated left ventricular cardiomyopathies), which are characterized by multi-segmental late gadolinium enhancement and associated clinical features such as positive family history, symptoms, and electrocardiogram abnormalities. In these cases, a thorough diagnostic evaluation to assess the cause and arrhythmic risk is mandatory. Alessandro Zorzi (Conceptualization [lead]; Writing—original draft [lead]), Domenico Corrado (Conceptualization [supporting]; Writing—review & editing [supporting]), and Francesca Graziano (Conceptualization [supporting]; Writing—original draft [supporting])