Review Article

Arrhythmogenesis of Sports: Myth or Reality?

Abstract

Regular exercise confers health benefits with cardiovascular mortality risk reduction through a variety of mechanisms. At a population level, evidence suggests that undertaking more exercise has greater benefits. In the modern era of sport, there has been an exponential rise in professional and amateur athletes participating in endurance events, with a progressively better understanding of the associated cardiac adaptations, collectively termed ‘athletes heart’. However, emerging data raise questions regarding the risk of potential harm from endurance exercise, with an increased risk of arrhythmia from adverse cardiac remodelling. Cross-sectional studies have demonstrated that athletes may exhibit a higher burden of AF, conduction tissue disease, ventricular arrhythmias, a cardiomyopathy-like phenotype and coronary artery disease. In an attempt to separate myth from reality, this review reports on the evidence supporting the notion of ‘too much exercise’, the purported mechanisms of exercise-induced cardiac arrhythmia and complex interplay with sporting discipline, demographics, genetics and acquired factors.

Disclosure: SF is funded by research grants from Cardiac Risk in the Young, which advocates for preparticipation cardiac screening of young athletes. MP has received research grants from Cardiac Risk in the Young.

Received:

Accepted:

Published online:

Correspondence: Michael Papadakis, Cardiovascular Clinical Academic Group, St George’s, University of London, Cranmer Terrace, London SW17 0RE, UK. E: mipapada@sgul.ac.uk

Open access:

This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

The health benefits of exercise are well established and extend beyond the cardiovascular system.1 These benefits accrue from the modulation of traditional risk factors for atherosclerotic cardiovascular disease, as well as through an anti-inflammatory effect on the vascular endothelium and changes in autonomic regulation.2 A meta-analysis in almost 900,000 individuals demonstrated that the physically active group had a 35% reduction in the risk of cardiovascular death and 33% reduction in all-cause mortality.3

The WHO recommends a minimum of 150 minutes of moderate-intensity exercise or 75 minutes of vigorous-intensity exercise per week. 4 A cohort of nearly 650,000 individuals participating in physical activity at half these recommended levels, at the recommended levels and at three times the recommended levels, gained 1.8, 3.4 and 4.3 years of life, respectively.5 Higher cardiorespiratory fitness levels correlate with greater benefit, with a mortality risk reduction of 13% for each additional metabolic equivalent (MET) increase in exercise capacity.6,7 These data suggest that, at the population level, a greater volume of exercise results in greater cardiovascular benefit. A more cautious approach is necessary in individuals with established heart disease, where the volume and intensity of exercise may need to be moderated.8

Endurance athletes routinely exercise far beyond the WHO recommendations.9,10 The sustained elevation of cardiac pressure and volume loads associated with regular exercise promote a series of electrical, structural and functional adaptations, collectively termed ‘athlete’s heart’. The nature and magnitude of changes vary by sporting discipline, ethnicity, age and sex, and can overlap with mild phenotypes of conditions associated with arrhythmias and sudden cardiac death (SCD).11 Extreme cavity dilatation, left ventricular (LV) hypertrophy, elevated coronary artery calcium (CAC) scores, acute cardiac biomarker release, myocardial fibrosis and cardiac arrhythmias have all been reported, raising concern of a reverse U-shaped relationship between the volume of exercise and cardiovascular health, with diminishing cardiovascular benefit and potential harm.12–15 Therefore, there is ongoing debate as to whether there is a threshold that constitutes ‘excess of exercise’, which may induce harm. To separate myth from reality, this review reports on the evidence supporting the notion of ‘too much exercise’ and the proposed mechanisms of exercise-induced cardiac arrhythmias in ostensibly healthy athletes.

AF

AF is the most common sustained arrhythmia in the general population; it is a major cause of ischaemic stroke, heart failure and impairment in cognition and quality of life, and increases the risk of death.16–18 The incidence of AF increases with age, given that age in itself is a determinant of AF. Moreover, advanced age is associated with cardiovascular risk factors, heart failure, structural heart disease, coronary artery disease and chronic kidney disease, all of which are linked with an increased risk of AF.19 It is well established that exercise mitigates such risk factors and, as such, regular exercise can prevent AF onset, as well as also improve symptoms, morbidity and mortality in those with established AF.20–22 A study of 6,000 veterans with a mean age of 56.8 years undergoing a symptom-limited exercise tolerance test found exercise capacity to be inversely related to the incidence of AF during a median follow-up of 8 years. The fittest individuals were found to have the lowest risk of developing AF, with a 21% decrease for each MET increase in exercise capacity.20 The Cardiovascular Health Study of 5,446 adults aged >65 years identified greater leisure time activity and walking as being associated with a lower incidence of AF, with progressively lower risk with greater activity levels, and a 44% risk reduction in those undertaking moderate physical activity.23 Importantly, however, risk reduction diminished in those undertaking high-intensity exercise (>6 METs).23

Characteristics of AF in Masters Athletes (Age >40 years)

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An emerging body of evidence has since supported a link between long-term intense endurance exercise and AF in an ‘exercise paradox’ (Figure 1). Larger epidemiological studies and several meta-analyses have demonstrated that the incidence of AF is two- to fivefold greater in endurance athletes than in non-athletes.24–29 The elevated risk in the athletic group dissipates with increasing age (>55 years) and the presence of cardiovascular risk factors. There is evidence to support the notion that exercise intensity, duration and type of sport affect the onset of AF. In a study of 52,755 cross-country skiers participating in a 90 km cross-country skiing race, the participants who completed more than five races were at highest risk of AF, and were more likely to develop AF than those who undertook one race (HR 1.29).24 Similar findings have been observed among healthy, middle-aged male physicians, with those participating in higher-intensity jogging having a 53% higher risk of AF compared with men who did not exercise.30 This would suggest that the association between exercise and AF is not restricted to elite athletes, and is also observed in the general population. However, the exact dose of exercise that confers risk of AF remains unclear, with high-quality prospective studies with well-defined study populations still lacking. A figure of around 1,500–2,000 lifetime exercise hours has been suggested as the threshold at which AF risk increases, with a peak age of onset at >40 years.31 AF in younger athletes is unusual and should prompt evaluation for underlying heart disease.32,33

Most studies investigating the relationship between AF and exercise have focused on male elite athletes, who historically dominated the landscape of elite sports. The link between exercise and AF in female athletes is less clear. In a large cohort of more than 140,000 male and 160,000 female athletes, increasing levels of physical activity were associated with AF in male, but not female, participants.34 A meta-analysis of 22 studies identified an increased risk of AF in men undertaking intense exercise but, conversely, intense exercise was protective in women.25 Similarly, a more recent meta-analysis also concluded that the general risk of AF is lower in female than male athletes.27 However, there remains a lack of data on high-level female endurance athletes, who would surpass the level of exercise undertaken by the female participants of these studies.

The mechanism of AF in athletes is not well understood, with much of our knowledge based on animal models. Vagal tone, which is chronically elevated in athletes, is thought to be one of the most important contributors to the development of AF.35 In addition, atrial remodelling, in the form of atrial dilatation and fibrosis, is increasingly being recognised as an important factor. Atrial remodelling in athletes is considered to be a physiological response to exercise, because the overall reservoir function appears to be preserved with atrial dilatation; however, given that atrial dilatation in pathological conditions contributes to the development of AF, it remains to be seen how distinct atrial remodelling in athletes is from that seen in pathological states.36,37 AF episodes are most common during states of increased parasympathetic tone (rest, sleep), but sympathetic stimulation during exercise may also trigger AF, in association with atrial wall stretch and inflammatory cytokines.15 In a study of rat models of chronic endurance exercise, AF was induced after 16 weeks of training with identifiable atrial dilatation, fibrosis in the atria and right ventricle (RV) and autonomic changes, which did not fully resolve with detraining.14

Bradyarrhythmias

Sinus bradycardia and sinus pauses are common in endurance athletes. In a study of 62 former professional male cyclists, compared with 62 well-matched controls (male golfers), the former endurance athletes demonstrated more frequent sinus bradycardia, sinus node dysfunction and pacemaker implantation for bradyarrhythmias relative to the control group.38 This is widely believed to be a consequence of high vagal tone, although, because these findings can persist despite detraining, adverse remodelling and fibrosis of the conduction system are also thought to be contributing factors.38 More recently, evidence suggests significant electrical remodelling within the sinus node, with downregulation of potassium/sodium hyperpolarisation activated cyclic nucleotide-gated channel 4 (HCN-4).39,40 A possible dose–response relationship has also been suggested, with a study of cross-country skiers demonstrating that those who participated in more races had a higher risk of sinus node disease or third-degree atrioventricular block.24

Ventricular Arrythmias

Premature Ventricular Beats

Premature ventricular beats (PVB) are fairly common in athletes and are usually benign. However, they may be the only sign of heart disease, often leading to comprehensive evaluation. It is well established that PVBs may reflect the broader phenotype of cardiomyopathies and help differentiate pathology from physiological adaptation to exercise, particularly in athletes with mild phenotypic expression, often referred to as the ‘grey zone’.

Predictors of Malignant Ventricular Premature Beats in Athletes

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Data supporting the notion that PVBs are more frequent in athletes and may represent a feature of athletic adaptation are contrasted by studies that show similar burden of ectopy in athletic and non-athletic individuals.41–43 Comparisons between studies are challenging due to differences in methodologies to record and report PVBs, as well as the absence of a standardised protocol guiding further investigation. PVBs have been reported in up to 14% of young athletes and 26% of veteran athletes, with no convincing association between sporting discipline, volume or intensity of exercise, years of sports participation and burden or complexity of PVBs.42–44 Furthermore, the overall burden of PVBs increases with age. These findings do not support the hypothesis that endurance sports activity increases the burden of ventricular arrhythmias.42–44

The PVB characteristics that imply association with disease are evolving (Figure 2). Traditionally, a frequency in excess of 2,000 PVBs/24 hours has been considered a red flag.41 Recently, however, evaluation of the morphology of PVBs, as a surrogate of ventricular origin, has emerged as the key factor in differentiating benign from potentially sinister PVBs.44–46 Frequent PVBs as a result of focal automaticity, emerging from the outflow tracts or from the fascicles of the left bundle branches, are relatively common and, in the absence of structural heart disease, should be considered benign.42,43 Other morphologies, such as PVBs with left or wide right bundle branch block or with intermediate or superior axis, are relatively uncommon and should be investigated further.46–48 Similarly, short coupling intervals, increasing PVB frequency during exercise and multifocal ectopy should prompt further evaluation. In particular, exercise-induced PVBs with multiple and/or alternating morphologies (bidirectional) may raise suspicion of underlying catecholaminergic polymorphic ventricular tachycardia.49

Effects on Ion Channels

Regular exercise exerts a significant effect on the expression and function of cardiac ion channels. Athletes exhibit longer QT intervals than sedentary individuals, with corrected QT intervals of 470 ms in male athletes and 480 ms in female athletes accepted as the upper limits of normal.8 Exercise-induced QT prolongation may confer an increased risk in individuals with underlying long QT syndrome (LQTS) because adrenergic surges and emotional stress may trigger arrhythmias in LQT1 and LQT2, respectively.50–53 Moreover, exercise-induced prolongation of the QT interval may pose considerable challenges in differentiating physiological adaptation from congenital LQTS, and potentially offering false reassurance to athletes at risk. A recent study demonstrated an exercise-induced QT prolongation phenotype, mimicking congenital LQTS, which reverts back to normal after a period of detraining.54 Although no arrhythmic events were recorded, more data are needed to fully understand the arrhythmic risk in individuals with acquired QT prolongation.54

Similarly, repolarisation patterns on the athlete’s ECG may overlap with the Brugada phenotype, causing a diagnostic conundrum.55 Although there are no clear data supporting a relationship between exercise and SCD in patients with Brugada syndrome, enhanced vagal tone at rest and in early recovery following exercise has been postulated as a precipitant of arrhythmia in athletes with Brugada syndrome.56

The Left Ventricle

Elevations in cardiac preload and afterload with chronic exercise are associated with cardiac chamber enlargement, with a 10–20% increase in wall thickness and 10–15% increase in ventricular cavity dimensions. Consequently, differentiation between athletic adaptation to exercise and a mild phenotype of primary cardiomyopathies may be challenging even for the most experienced of sports cardiologists. Male endurance athletes are typically observed with the largest cavity dimensions, with up to 14% exceeding 60 mm, a threshold that typically raises suspicion of a primary dilated cardiomyopathy.57 Ethnicity is important to consider in the evaluation of LV wall thickness. For example, an LV wall thickness of >13 mm is rare among white athletes, whereas it is more prevalent in black athletes (2% versus 12%, respectively).55,58 Crucially, regardless of ethnicity, a maximum wall thickness exceeding 16 mm is uncommon and should prompt consideration and further evaluation for hypertrophic cardiomyopathy. In addition, LV cavity dilatation and hypertrophy may persist in up to 20% of athletes, despite detraining, suggesting that extremes of cardiovascular adaptation to exercise may be irreversible.59 In a study by Finocchiaro et al., none of the first-degree relatives of decedents with unexplained LV hypertrophy (30% competitive athletes) were diagnosed with hypertrophic cardiomyopathy, suggesting that extreme LV hypertrophy may be a source of arrhythmias.60

The Right Ventricle

At rest, the RV functions against a very low resistance and high compliance pulmonary circulation. However, during exercise, RV wall stress increases 30-fold, reflecting a minimal reduction in pulmonary vascular resistance and a significant rise in pulmonary artery systolic pressures. This raises the possibility that repetitive intense exercise can induce structural changes and arrhythmias overlapping with arrhythmogenic right ventricular cardiomyopathy (ARVC), referred to as ‘exercise-induced ARVC’.61

Proposed Mechanisms of Adverse Cardiac Remodelling that May Predispose to Arrhythmias in Endurance Athletes

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Data from an animal model of endurance training demonstrated training-dependent RV fibrosis and tendency to arrhythmia following a 16-week exercise regime, which reversed after 8 weeks of exercise cessation.62 In a study of more than 300 athletes, RV enlargement meeting criteria for ARVC was seen in up to 45% of black athletes and 59% of white athletes, although none was diagnosed with ARVC.63 Studies have also reported transient RV dysfunction following endurance exercise, with greater dysfunction associated with more prolonged intense exercise, such as ultra-endurance events. In most studies there was no associated LV dysfunction, but there was correlation between the degree of RV dysfunction and elevation of troponin levels.64–66 Moreover, an evaluation of 46 endurance athletes presenting with arrhythmias by Heidbüchel et al. reported that 80% of arrhythmias were of RV origin and 89% of athletes fulfilled either definite (59%) or borderline/possible (30%) diagnostic criteria for ARVC.67 During a median follow-up of 5 years, 40% of athletes experienced major arrhythmic events defined as SCD, ICD shock or ventricular tachycardia. Subsequent genetic analysis of genes associated with ARVC, identified pathogenic variants in only 12.8% of athletes, compared with 30–50% expected in ARVC.68 Although these studies support the notion of exercise-induced ARVC, it is important to note that they included a highly selected cohort of athletes presenting with ventricular arrhythmias, and the genetic yield in ARVC may be far lower than 50% in the context of sporadic rather than familial disease. Moreover, other studies in elite Olympic athletes competing over many years have failed to demonstrate significant pathological RV remodelling, suggesting that this may be applicable to the very extremes of endurance training in individuals with some genetic predisposition, although it may not represent the classic ARVC genotype.69

By the same token, repetitive exercise in those with an established diagnosis of ARVC is well recognised to increase the risk of SCD through the acceleration of RV dysfunction and induction of ventricular arrhythmias.70,71 A North American multidisciplinary study reported that patients engaging in competitive sports were at a twofold increased risk of ventricular tachyarrhythmias or death and earlier presentation of symptoms than patients who participated in recreational sports and sedentary individuals.72 Similar results have been confirmed in desmosomal mutation carriers with no phenotypic expression, underscoring the impact of exercise on the RV.73 Further studies and longitudinal data are required to better understand the interplay between exercise and the RV in health and disease states.

Myocardial Fibrosis

In patient populations, the presence of late gadolinium enhancement (LGE) is an established adverse risk factor for malignant arrhythmia, and in athletes has been associated with a risk of complex VA.47,48,74,75

A small number of studies have demonstrated myocardial fibrosis in ostensibly fit male masters athletes engaging in endurance exercise. In a study of 102 middle-aged marathon runners, 12% demonstrated myocardial fibrosis (compared with 4% of controls), of which 42% demonstrated a pattern consistent with MI predominantly in the territory of the left anterior descending artery.15 Furthermore, there was suggestion of a dose–response relationship because participation in a greater number of marathons was an independent predictor for the presence of LGE.76 Similarly, in a study of 106 male masters endurance athletes, 14% demonstrated myocardial fibrosis, with almost half demonstrating a pattern consistent with a previous MI.13 Of those with evidence of MI, only half demonstrated coronary stenosis in the relevant coronary artery, raising the possibility of subclinical infarction, due to demand ischaemia, coronary spasm or plaque rupture.13

In a study of 83 asymptomatic middle-aged triathletes, participation in longer swimming distances and cycling races was an independent predictor for the presence of non-ischaemic LGE, affecting 17% of male athletes but none of the female athletes.77 A recent meta-analysis concluded that the incidence of LGE was almost sevenfold higher in middle-aged endurance athletes compared with non-athletes, with most of this due to mid-myocardial or subepicardial LGE, with the next most common pattern being insertion point fibrosis.78 Further longitudinal studies are required to better understand the temporal association of non-ischaemic fibrosis with acquired risk factors, such as an episode of myocarditis, and its clinical relevance in masters athletes. This is relevant in the era of the COVID-19 pandemic, which has ignited interest about the prevalence and potential implications of asymptomatic (subclinical) myocardial inflammation in elite athletes. A recent registry of 1,597 competitive collegiate athletes infected with COVID-19 reported symptomatic (clinical) myocarditis in five athletes (0.3%).79 The routine use of cardiac MRI (CMR) in all athletes increased the diagnostic yield of myocarditis by 7.4-fold to 2.3%.79 Importantly, follow-up CMR in 27 of the 37 athletes diagnosed with myocarditis (73.0%) demonstrated resolution of myocardial oedema (T2 elevation) in all, and LGE indicative of myocardial fibrosis in 11 (41%).79 Similarly, in a cohort of more than 3,000 athletes with COVID-19 infection, myocarditis was identified in 0.5% of those who underwent clinically indicated CMR following clinical assessment, but in 3% of the cohort of 198 athletes who underwent screening CMR.80

Coronary Artery Disease

Exercise is well established to reduce traditional risk factors for coronary artery disease, although masters athletes have been demonstrated to show elevated CAC scores, which is a powerful adjunctive predictor of future cardiovascular events in non-athletes.13,76,81 In a study of 152 masters endurance athletes with low Framingham risk scores (mean age 54 years), 19% of male athletes had a CAC score ≥100 Agatston units, compared with 4% among the controls, and 11% of athletes had a CAC score >300 Agatston units, compared with none among the controls.13 Furthermore, male athletes demonstrated twice as many atherosclerotic plaques (44% versus 22%), and 7.5% of male athletes demonstrated a luminal stenosis >50%, compared with none of the controls.13 Importantly, the significance of the elevated CAC scores may be mitigated by the plaque composition among athletes, which demonstrate a greater proportion of calcified plaques, which are considered more stable and less prone to rupture. In a study of 284 athletes, divided by lifelong exercise volume (<1,000, 1,000–2,000 and >2,000 MET-min/week), Aengevaeren et al. demonstrated that the most active athletes had a higher CAC score and more atherosclerotic plaque, but also a higher prevalence of calcified plaque.82 The longer-term longitudinal outcomes of endurance athletes remain unknown and further studies are warranted. In the Cooper Centre Longitudinal Study of more than 20,000 male participants, those performing >3,000 MET-min of exercise per week were more likely to have CAC, without increased all-cause or cardiovascular mortality after a decade of follow-up.83 Another study reported on 8,425 men who underwent an assessment of cardiorespiratory fitness and CAC and, over a 8.4-year follow-up, identified that each additional MET of fitness corresponded to a 14% lower risk of cardiovascular death in an adjusted model and attenuated the risk associated with higher CAC levels.84

Conclusion

Exercise remains one of the most potent, cost-effective treatments against cardiovascular disease and cardiovascular mortality. Currently, evidence suggests that even high-intensity, high-volume exercise, and the associated lifestyle of elite endurance athletes, confers significant benefits, with athletes gaining an average of 5–7 years of life compared with sedentary individuals.85 Life-threatening arrhythmias remain overwhelmingly low, and mostly reflect underlying hereditary or congenital cardiac disease. Nevertheless, extremes of exercise may pose detrimental effects in an ‘exercise paradox’, with several routes of enquiry that require further study (Figure 3). Life-long endurance athletes seem to be at increased risk of AF in their 40s and a small number who participate in the most extreme of endurance sports may be predisposed to RV-related arrhythmias. More research is needed in better-defined cohorts with long-term follow-up.

Clinical Perspective

  • The incidence of life-threatening arrhythmias in endurance athletes is low, and commonly reflects hereditary or congenital cardiac disease.
  • Extremes of exercise may pose a detrimental effect; the proposed mechanisms are complex, with several routes of further enquiry ongoing.
  • Athletes are at a higher risk of developing AF than non-athletes, particularly in their 40s, with both mixed and endurance sports conferring risk.
  • Premature ventricular beats are common in athletes and are usually benign. Although ventricular arrhythmias have been associated with an exercise-induced arrhythmogenic phenotype, this seems to be applicable to the very extremes of endurance training in individuals with genetic predisposition.
  • Further research is needed to ascertain the long-term significance of autonomic regulation and ion channel expression in endurance athletes, including extreme structural adaptations, coronary calcification, myocardial fibrosis and acute biomarker release.

References

  1. McTiernan A, Kooperberg C, White E, et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women’s Health Initiative cohort study. JAMA 2003;290:1331–6.
    Crossref | PubMed
  2. Kasiakogias A, Sharma S. Exercise: the ultimate treatment to all ailments? Clin Cardio 2020;43:817–26.
    Crossref | PubMed
  3. Nocon M, Hiemann T, Müller-Riemenschneider F, et al. Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil 2008;15:239–46.
    Crossref | PubMed
  4. Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020;54:1451–62.
    Crossref | PubMed
  5. Moore SC, Patel AV, Matthews CE, et al. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med 2012;9:e1001335.
    Crossref | PubMed
  6. Kokkinos P, Myers J, Kokkinos JP, et al. Exercise capacity and mortality in black and white men. Circulation 2008;117:614–22.
    Crossref | PubMed
  7. Mandsager K, Harb S, Cremer P, et al. Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing. JAMA Netw Open 2018;1:e183605.
    Crossref | PubMed
  8. Pelliccia A, Sharma S, Gati S, et al. ESC guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021;42:17–96.
    Crossref | PubMed
  9. Lubbers M, Dedic A, Coenen A, et al. Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial. Eur Heart J 2016;37:1232–43.
    Crossref | PubMed
  10. Marijon E, Uy-Evanado A, Reinier K, et al. Sudden cardiac arrest during sports activity in middle age. Circulation 2015;131:1384–91.
    Crossref | PubMed
  11. Drezner JA, Malhotra A, Prutkin JM, et al. Return to play with hypertrophic cardiomyopathy: are we moving too fast? A critical review. Br J Sports Med 2021;55:1041–7.
    Crossref | PubMed
  12. Schnohr P, O’Keefe JH, Marott JL, et al. Dose of jogging and long-term mortality: the Copenhagen City Heart study. J Am Coll Cardiol 2015;65:411–9.
    Crossref | PubMed
  13. Merghani A, Maestrini V, Rosmini S, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile. Circulation 2017;136:126–37.
    Crossref | PubMed
  14. Guasch E, Benito B, Qi X, et al. Atrial fibrillation promotion by endurance exercise: demonstration and mechanistic exploration in an animal model. J Am Coll Cardiol 2013;62:68–77.
    Crossref | PubMed
  15. Breuckmann F, Möhlenkamp S, Nassenstein K, et al. Myocardial late gadolinium enhancement: prevalence, pattern, and prognostic relevance in marathon runners. Radiology 2009;251:50–7.
    Crossref | PubMed
  16. Arbelo E, Aktaa S, Bollmann A, et al. Quality indicators for the care and outcomes of adults with atrial fibrillation. Europace 2021;23:494–5.
    Crossref | PubMed
  17. Wyndham CRC. Atrial fibrillation: the most common arrhythmia. Tex Heart Inst J 2000;27:257–67.
    PubMed
  18. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics – 2019 update: a report from the American Heart Association. Circulation 2019;139:e56–528.
    Crossref | PubMed
  19. Hindricks G, Potpara T, Dagres N, et al. ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021;42:373–498.
    Crossref | PubMed
  20. Faselis C, Kokkinos P, Tsimploulis A, et al. Exercise capacity and atrial fibrillation risk in veterans: a cohort study. Mayo Clin Proc 2016;91:558–66.
    Crossref | PubMed
  21. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF Cohort study. J Am Coll Cardiol 2014;64:2222–31.
    Crossref | PubMed
  22. Pathak RK, Elliott A, Middeldorp ME, et al. Impact of CARDIOrespiratory FITness on arrhythmia recurrence in obese individuals with atrial fibrillation: the CARDIO-FIT study. J Am Coll Cardiol 2015;66:985–96.
    Crossref | PubMed
  23. Mozaffarian D, Furberg CD, Psaty BM, Siscovick D. Physical activity and incidence of atrial fibrillation in older adults the cardiovascular health study. Circulation 2008;118:800–7.
    Crossref | PubMed
  24. Andersen K, Farahmand B, Ahlbom A, et al. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study. Eur Heart J 2013;34:3624–31.
    Crossref | PubMed
  25. Mohanty S, Mohanty P, Tamaki M, et al. Differential association of exercise intensity with risk of atrial fibrillation in men and women: evidence from a meta-analysis. J Cardiovasc Electrophysiol 2016;27:1021–9.
    Crossref | PubMed
  26. Nielsen JR, Wachtell K, Abdulla J. The relationship between physical activity and risk of atrial fibrillation – a systematic review and meta-analysis. J Atr Fibrillation 2013;5:789.
    Crossref | PubMed
  27. Newman W, Parry-Williams G, Wiles J, et al. Risk of atrial fibrillation in athletes: a systematic review and meta-analysis. Br J Sports Med 2021;55:1233–8.
    Crossref | PubMed
  28. Gerche A La, Schmied CM. Atrial fibrillation in athletes and the interplay between exercise and health. Eur Heart J 2013;34:3599–602.
    Crossref | PubMed
  29. Li X, Cui S, Xuan D, et al. Atrial fibrillation in athletes and general population: a systematic review and meta-analysis. Medicine 2018;97:e13405.
    Crossref | PubMed
  30. Aizer A, Gaziano JM, Cook NR, et al. Relation of vigorous exercise to risk of atrial fibrillation. Am J Cardiol 2009;103:1572–7.
    Crossref | PubMed
  31. Abdulla J, Nielsen JR. Is the risk of atrial fibrillation higher in athletes than in the general population? A systematic review and meta-analysis. Europace 2009;11:1156–9.
    Crossref | PubMed
  32. Vlachos K, Mascia G, Martin CA, et al. Atrial fibrillation in Brugada syndrome: current perspectives. J Cardiovasc Electrophysiol 2020;31:975–84.
    Crossref | PubMed
  33. Pelliccia A, Maron BJ, Di Paolo FM, et al. Prevalence and clinical significance of left atrial remodeling in competitive athletes. J Am Coll Cardiol 2005;46:690–6.
    Crossref | PubMed
  34. Thelle DS, Selmer R, Gjesdal K, et al. Resting heart rate and physical activity as risk factors for lone atrial fibrillation: a prospective study of 309 540 men and women. Heart 2013;99:1755–60.
    Crossref | PubMed
  35. Guasch E, Mont L. Diagnosis, pathophysiology, and management of exercise-induced arrhythmias. Nat Rev Cardiol 2017;14:88–101.
    Crossref | PubMed
  36. Seko Y, Kato T, Haruna T, et al. Association between atrial fibrillation, atrial enlargement, and left ventricular geometric remodeling. Sci Rep 2018;8:6366.
    Crossref | PubMed
  37. D’Ascenzi F, Anselmi F, Focardi M, Mondillo S. Atrial enlargement in the athlete’s heart: assessment of atrial function may help distinguish adaptive from pathologic remodeling. J Am Soc Echocardiogr 2018;31:148–57.
    Crossref | PubMed
  38. Baldesberger S, Bauersfeld U, Candinas R, et al. Sinus node disease and arrhythmias in the long-term follow-up of former professional cyclists. Eur Heart J 2008;29:71–8.
    Crossref | PubMed
  39. D’souza A, Bucchi A, Johnsen AB, et al. Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nat Commun 2014;5:3775.
    Crossref | PubMed
  40. Mesirca P, Nakao S, Nissen SD, et al. Intrinsic electrical remodeling underlies atrioventricular block in athletes. Circ Res 2021;129:e1–20.
    Crossref | PubMed
  41. Biffi A, Pelliccia A, Verdile L, et al. Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2002;40:446–52.
    Crossref | PubMed
  42. Zorzi A, De Lazzari M, Mastella G, et al. Ventricular arrhythmias in young competitive athletes: prevalence, determinants, and underlying substrate. J Am Heart Assoc 2018;7:e009171.
    Crossref | PubMed
  43. Zorzi A, Mastella G, Cipriani A, et al. Burden of ventricular arrhythmias at 12-lead 24-hour ambulatory ECG monitoring in middle-aged endurance athletes versus sedentary controls. Eur J Prev Cardiol 2018;25:2003–11.
    Crossref | PubMed
  44. Pelliccia A, De Martino L, Borrazzo C, et al. Clinical correlates and outcome of the patterns of premature ventricular beats in Olympic athletes: a long-term follow-up study. Eur J Prev Cardiol 2021;28:1038–47.
    Crossref | PubMed
  45. Corrado D, Drezner JA, D’Ascenzi F, Zorzi A. How to evaluate premature ventricular beats in the athlete: critical review and proposal of a diagnostic algorithm. Br J Sports Med 2020;54:1142–8.
    Crossref | PubMed
  46. Verdile L, Maron BJ, Pelliccia A, et al. Clinical significance of exercise-induced ventricular tachyarrhythmias in trained athletes without cardiovascular abnormalities. Heart Rhythm 2015;12:78–85.
    Crossref | PubMed
  47. Zorzi A, Marra MP, Rigato I, et al. Nonischemic left ventricular scar as a substrate of life-threatening ventricular arrhythmias and sudden cardiac death in competitive. Circ Arrhtyhm Electrophysiol 2016;9:e004229.
    Crossref | PubMed
  48. Crescenzi C, Zorzi A, Vessella T, et al. Predictors of left ventricular scar using cardiac magnetic resonance in athletes with apparently idiopathic ventricular arrhythmias. J Am Heart Assoc 2021;10:e018206.
    Crossref | PubMed
  49. Haugaa KH, Leren IS, Berge KE, et al. High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening. Europace 2010;12:417–23.
    Crossref | PubMed
  50. Schnell F, Behar N, Carré F. Long-QT syndrome and competitive sports. Arrhythm Electrophysiol Rev 2018;7:187–92.
    Crossref | PubMed
  51. Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype–phenotype correlation in the long-QT syndrome. Circulation 2001;103:89–95.
    Crossref | PubMed
  52. Mascia G, Arbelo E, Solimene F, et al. The long-QT syndrome and exercise practice: the never-ending debate. J Cardiovasc Electrophysiol 2018;29:489–96.
    Crossref | PubMed
  53. Marrakchi S, Kammoun I, Bennour E, et al. Inherited primary arrhythmia disorders: cardiac channelopathies and sports activity. Herz 2020;45:142–57.
    Crossref | PubMed
  54. Dagradi F, Spazzolini C, Castelletti S, et al. Exercise training-induced repolarization abnormalities masquerading as congenital long QT syndrome. Circulation 2020;142:2405–15.
    Crossref | PubMed
  55. Papadakis M, Carre F, Kervio G, et al. The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin. Eur Heart J 2011;32:2304–13.
    Crossref | PubMed
  56. Arai Y, Saul JP, Albrecht P, et al. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol Heart Circ Physiol 1989;256:h132–41.
    Crossref | PubMed
  57. Pelliccia A, Culasso F, Di Paolo FM, Maron BJ. Physiologic left ventricular cavity dilatation in elite athletes. Ann Intern Med 1999;130:23–31.
    Crossref | PubMed
  58. Pelliccia A, Maron BJ, Spataro A, et al. The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes. N Engl J Med 1991;324:295–301.
    Crossref | PubMed
  59. Pelliccia A, Maron BJ, De Luca R, et al. Remodeling of left ventricular hypertrophy in elite athletes after long-term deconditioning. Circulation 2002;105:944–9.
    Crossref | PubMed
  60. Finocchiaro G, Dhutia H, Gray B, et al. Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy. Europace 2020;22:632–42.
    Crossref | PubMed
  61. D’Ascenzi F, Pisicchio C, Caselli S, et al. RV remodeling in Olympic athletes. JACC Cardiovasc Imaging 2017;10:385–93.
    Crossref | PubMed
  62. Benito B, Gay-Jordi G, Serrano-Mollar A, et al. Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training. Circulation 2011;123:13–22.
    Crossref | PubMed
  63. Zaidi A, Ghani S, Sharma R, et al. Physiological right ventricular adaptation in elite athletes of African and Afro-Caribbean origin. Circulation 2013;127:1783–92.
    Crossref | PubMed
  64. Elliott AD, La Gerche A. The right ventricle following prolonged endurance exercise: are we overlooking the more important side of the heart? A meta-analysis. Br J Sports Med 2015;49:724–9.
    Crossref | PubMed
  65. La Gerche A, Burns AT, Mooney DJ, et al. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J 2012;33:998–1006.
    Crossref | PubMed
  66. La Gerche A, Claessen G, Dymarkowski S, et al. Exercise-induced right ventricular dysfunction is associated with ventricular arrhythmias in endurance athletes. Eur Heart J 2015;36:1998–2010.
    Crossref | PubMed
  67. Heidbüchel H, Hoogsteen J, Fagard R, et al. High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias: role of an electrophysiologic study in risk stratification. Eur Heart J 2003;24:1473–80.
    Crossref | PubMed
  68. La Gerche A, Robberecht C, Kuiperi C, et al. Lower than expected desmosomal gene mutation prevalence in endurance athletes with complex ventricular arrhythmias of right ventricular origin. Heart 2010;96:1268–74.
    Crossref | PubMed
  69. Aengevaeren VL, Caselli S, Pisicchio C, et al. Right heart remodeling in Olympic athletes during 8 years of intensive exercise training. J Am Coll Cardiol 2018;72:815–7.
    Crossref | PubMed
  70. Finocchiaro G, Barra B, Molaro S, et al. Prevalence and clinical correlates of exercise-induced ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy. Int J Cardiovasc Imaging 2021 2022;38:389–96.
    Crossref | PubMed
  71. Saberniak J, Hasselberg NE, Borgquist R, et al. Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members. Eur J Heart Fail 2014;16:1337–44.
    Crossref | PubMed
  72. Ruwald AC, Marcus F, Estes NAM, et al. Association of competitive and recreational sport participation with cardiac events in patients with arrhythmogenic right ventricular cardiomyopathy: results from the North American multidisciplinary study of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2015;36:1735–43.
    Crossref | PubMed
  73. James CA, Bhonsale A, Tichnell C, et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol 2013;62:1290–7.
    Crossref | PubMed
  74. Giusca S, Kelle S, Nagel E, et al. Differences in the prognostic relevance of myocardial ischaemia and scar by cardiac magnetic resonance in patients with and without diabetes mellitus. Eur Heart J Cardiovasc Imaging 2016;17:812–20.
    Crossref | PubMed
  75. Schnell F, Claessen G, La Gerche A, et al. Subepicardial delayed gadolinium enhancement in asymptomatic athletes: let sleeping dogs lie? Br J Sports Med 2016;50:111–7.
    Crossref | PubMed
  76. Möhlenkamp S, Lehmann N, Breuckmann F, et al. Running: the risk of coronary events: prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J 2008;29:1903–10.
    Crossref | PubMed
  77. Tahir E, Starekova J, Muellerleile K, et al. Myocardial fibrosis in competitive triathletes detected by contrast-enhanced CMR correlates with exercise-induced hypertension and competition history. JACC Cardiovasc Imaging 2018;11:1260–70.
    Crossref | PubMed
  78. Zhang CD, Xu SL, Wang XY, et al. Prevalence of myocardial fibrosis in intensive endurance training athletes: a systematic review and meta-analysis. Front Cardiovasc Med 2020;7:585692.
    Crossref | PubMed
  79. Daniels CJ, Rajpal S, Greenshields JT, et al. Prevalence of clinical and subclinical myocarditis in competitive athletes with recent SARS-CoV-2 infection: results from the Big Ten COVID-19 cardiac registry. JAMA Cardiol 2021;6:1078–87.
    Crossref | PubMed
  80. Moulson N, Petek BJ, Drezner JA, et al. SARS-CoV-2 cardiac involvement in young competitive athletes. Circulation 2021;144:256–66.
    Crossref | PubMed
  81. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860–70.
    Crossref | PubMed
  82. Aengevaeren VL, Mosterd A, Braber TL, et al. Relationship between lifelong exercise volume and coronary atherosclerosis in athletes. Circulation 2017;136:138–48.
    Crossref | PubMed
  83. Defina LF, Radford NB, Barlow CE, et al. Association of all-cause and cardiovascular mortality with high levels of physical activity and concurrent coronary artery calcification. JAMA Cardiol 2019;4:174–81.
    Crossref | PubMed
  84. Radford NB, DeFina LF, Leonard D, et al. Cardiorespiratory fitness, coronary artery calcium, and cardiovascular disease events in a cohort of generally healthy middle-age men: results from the Cooper Center longitudinal study. Circulation 2018;137:1888–95.
    Crossref | PubMed
  85. Sanchis-Gomar F, Olaso-Gonzalez G, Corella D, et al. Increased average longevity among the Tour de France cyclists. Int J Sports Med 2011;32:644–7.
    Crossref | PubMed