Gerche, Andre La

Schmied, Christian Marc

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EDITORIALAtrial fibrillation in athletes and the interplaybetween exercise and healthAndre La Gerche1,2 and Christian Marc Schmied3*1St Vincent’s Hospital Department of Medicine, University of Melbourne, Fitzroy, Australia; 2Department of Cardiovascular Medicine, University of Leuven, Leuven, Belgium;and 3Cardiovascular Center, Division of Cardiology, University Hospital Zurich, Ra¨mistrasse 100, CH-8091 Zurich, SwitzerlandOnline publish-ahead-of-print 24 July 2013This editorial refers to ‘Risk of arrhythmias in 52 755long-distance cross-country skiers: a cohort study’†, byK. Andersen et al., on page 3624Exercise is one of the most powerful lifestyle intervention strategiesfor the primary and secondary prevention of cardiovascular disease.There is a wealth of evidence regarding the lower ranges of the exer-cise dose–response relationship providing concrete evidence for thecurrent recommendationsof at least 30minofmoderate intensityex-ercise on most days as a means of reducing cardiovascular events.1However, there is an increasing proportion of today’s society en-gaging in sports practices which vastly exceed these guidelines, andthere has been very limited study of the upper ranges of the exercisedose–response relationship.2 Onthe onehand are studies suggestingthat long-term health and life expectancy of well-trained athletes issuperior to that of the general population,325 while, on the other,there is evidence suggesting an increased prevalence of arrhythmiasand chronic structural remodelling of the athletic heart.629Atrial fibrillation (AF) may therefore represent the most intriguingand best evidenced example of the interplay between exercise andcardiac health. AF can be diagnosed in 1% of the population by age60 and in. 10%whenolder than80 years,10 making it themost preva-lent sustained arrhythmia in adults. In cohorts of young or middle-agedsubjects, AF is relatively uncommon, thus implying that large cohortswould be required to provide sufficient power to identify any excessin prevalence due to sports practice. In this context, it is not surprisingthatPellicciaetal. foundonlyvery fewcasesofAFdespite significant leftatrial enlargement in a fairly large (n ¼ 1777) athletic cohort aged24+6 years.11 In contrast, Baldesberger et al. were able to identifyan excess of AF when comparing a small cohort of 62 former profes-sional cyclists with 62 ex-golfers aged 66+7 years.6 Although onemust always consider type 1 errors (false discoveries) in studies ofsmall sample size, it may also be that a true exercise-induced excessin AF prevalence becomes appreciable when the cohort reaches anage in which AF is more common and when the amount of exercisepractised is relatively extreme. In this context, the recent study ofAndersen et al. is remarkable.12 The group of participants in thepopular Vasaloppet 90 km cross-country ski race was young andhealthy when one considers the likelihood of identifying incident AF.Less than10%of thecohortwasaged.60 years and thosewith signifi-cant co-morbidities were few, as evidenced by the exclusion of parti-cipants with known cardiovascular disease and by the fact that thecohort had better health behaviour and overall longevity than theaverage Swedish population.13 Many of the established risk factorsfor AF, such as hypertension, heart failure, diabetes, and obesity,14are likely to be under-represented within this group of cross-countryski enthusiasts and, thus, we might expect such a low prevalence of AFthat detecting any residual risk attributable to exercise dose would bedifficult. However, the very large cohort size of 52 755 athletes and thecreative measures of exercise enabled the authors to define a ‘dose–response’ curve that provides further circumstantial evidence for thepremise that AF risk is increased in the very fittest athletes and inthose who perform exercise over many years. Andersen et al. investi-gated the primary endpoint of any arrhythmia, which was a compositeofbrady- and tachyarrhythmias, and determined that those completingthe race within 60% of the winner’s time were 1.3 times more likely tobediagnosedwithanarrhythmiathan thosewhotookmore thantwicethe time to complete the race. Similarly, those who had completed therace ≥5 times had a 1.3-fold increase in arrhythmic risk as comparedwith those who completed the race only once. The primary endpointwas predominantly driven by AF, with a similar trend seen in bradyar-rhythmias (though fewer events, making definitive conclusions diffi-cult). There was no apparent association between exercise measuresand supraventricular arrhythmias other than AF/atrial flutter, andtherewere too few ventricular arrhythmic events todraw conclusions.One of the biggest limitations when trying to interpret the data ofAndersen et al. is trying toworkout a reference point againstwhich tointerpret the described prevalence of arrhythmias. The lowestpreva-lence of arrhythmias was observed in the slowest athletes who hadraced least; but what is the critical ‘cut-off’ concerning the amountof exercise that leads to an elevated risk for developing AF? Weare frequently asked: ‘How many hours of exercise and at what* Corresponding author. Tel: +41-76 344 8308, Fax: +41-442558701, Email: christian.schmied@gmx.ch or christian.schmied@usz.chThe opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.† doi:10.1093/eurheartj/eht188.Published on behalf of the European Society of Cardiology. All rights reserved.& The Author 2013. For permissions please email: journals.permissions@oup.comEuropean Heart Journal (2013) 34, 3599–3602doi:10.1093/eurheartj/eht265intensity before I am at risk of AF?’, but there are numerous complex-ities which make it difficult to give prescriptive guidelines. First, assummarized in Figure1, arrhythmias such as AFare the clinical expres-sion of an interplay between host, environmental, and disease-specific factors. Host factors include age, gender, other geneticfactors (from single-gene mutations to multiple nucleotide poly-morphisms), obesity, alcohol consumption, sleep apnoea, andothers.15 Disease-related factors include atrial stretch, autonomicbalance, and systemic and local inflammation, while environmentalfactors include dietary factors, concurrent illnesses, and exercise.15It is extremely difficult to define the magnitude of the risk attributableto exercise in isolation. In particular, the influence of gender is an im-portant case in point. A massive limitation of all exercise studies, in-cluding that of Andersen et al., is the lack of data pertaining tofemales. There is currently no evidence that sports’ training constitu-tes a risk for AF in females, but this is largely due to the gross under-representation of females in sports cardiology research.Thesecond issue in trying todefineclinical recommendationsontheperfect amount of exercise to minimize the risk of arrhythmias relatesto the difficulties in comparing measures of exercise dose acrossstudies.Variousquestionnaireshavebeendevelopedtoassess thedur-ation, frequency, and intensity of physical activity, but they remain fairlycoarse estimates for defining exercise exposure subject to consider-able bias.16 For example, the subjective assessment of exercise inten-sity is inversely associated with a person’s fitness, such that jogging, forexample,will be ratedas3/10 intensitybysomeoneofexcellentfitness,but as7/10bysomeonewithpoorfitness.17 A similareffect canbeseenwhen comparing literature across various disciplines; what is seen asvigorous exertion in cardiovascular epidemiology studies would notFigure 1 Interplay between environment, person, and diseasein the clinical expression of atrial fibrillation.Figure 2 U-shaped relationship between the exercise dose and the relative risk of developing atrial fibrillation (AF). Composite data from threeseparate trials along the x-axis demonstrating an association between reducing prevalence of AF with increasing exercise of low intensity but then anincreasing risk of AF with moderate and intense exercise. The echocardiogram examples above demonstrate the progressive cardiac remodellingfrom a typical sedentary subject (left), a leasure-time athlete (middle), and a professional cyclist (right). The 10 cm marker on the echocardiogram ishighlighted with a red circle and the images have been scaled relative to this. The inference is that as exercise dose increases, the heart gets bigger andthe risk of AF increases. Whether or not there is a causal relationship between cardiac enlargement and arrhythmias is still to be determined.Editorial3600even be considered warm up tempo in sports science parlance.18 Theterm ‘high intensity exercise’ can be used todescribe walking up aflightof stairs in somestudies of AF18 or, in the caseof the study ofAndersenet al.,12 can be applied to 90 km of cross-country ski racing. With this inmind, we have tried to construct a ‘guestimate’ of relative exercisedoses in three landmark studies investigating the interactionbetween exercise and AF incidence. Our best attempt at trying to in-tegrate data across very disparate studies is presented in Figure 2. TheriskofAFdecreases asoneengages in regularphysical activityofmild tomoderate exertion, as evidenced by the study of elderly subjects byMozaffarian et al.19 However, as reported by Aizer et al., when thelevel of exertion is equivalent to jogging, then a greater prevalence ofAF is appreciable in those jogging daily as compared with thosejogging 1–2 times/week.20 A reasonable ‘guestimate’ when consider-ing the level of physical conditioning required to compete in the Vasa-loppet ski race would suggest that Andersen et al. complete thesporting spectrum by describing people mostly of moderate to ex-tremely high physical conditioning. Thus, some picture of the exercisedose–response curve emerges, with a U-shaped pattern suggestingthat regularmild tomoderateexercisemayprovideadegreeofprotec-tion from AF while more sustained vigorous exertion represents a riskfactor. This is supported by a number of case–control studies whichhave demonstrated a consistent association between endurance exer-cise and AF/atrial flutter.6,21227 With considerable caveats noted,these studies provide us with some idea to guide our answer regardingthe dose of exercise required to promote AF. Perhaps they alsoprovide a clinical clue that we should be advising our athletes withAF to reduce their training intensity and volumes, but certainly notto cease exercise practice all together. The wisdom of such advicewill really only be known after well-designed studies specificallyaddress the efficacy of such interventions.Whilst the study of Andersen et al. helps to expand our understand-ing of the epidemiology of exercise-induced arrhythmias, it does notprovide any insights into underlying mechanisms. However, recentstudies in animals and humans support the premise that exercisemay serve as a trigger, a modulator, and contribute to the underlyingsubstrate for the promotion of arrhythmias. A collaborationbetween the Barcelona group of Lluis Mont and the Montreal groupof Stanley Nattel has demonstrated that a model of endurance trainingin rats (the ‘marathon rat’) can be used to demonstrate increased in-flammation and fibrosis, and enhanced vagal responsiveness affectingthe atria and right ventricle (curiously sparing the left ventricle)whichpredisposestheanimals tobothAFandright ventriculararrhyth-mias.28,29 This resembles some of the observations in human athletes.Heidbuchel and La Gerche observed that endurance exercise canpromote remodelling and arrhythmias which seems to favour theright ventricle disproportionately,8,9 whereas Luthi et al.,30 amongstothers, have demonstrated biatrial remodelling. The other intrigueto which these studies are drawn is whether the remodelling asso-ciated with exercise training (theso-called ‘athlete’s heart’) is anentire-ly physiological process. As detailed in Figure 2, increasing exercisetraining is associated with cardiac remodelling which can be profound.It remains to be determined whether those athletes with the biggesthearts are at greatest risk of arrhythmias.Conflict of interest: none declared.References1. 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