Content uploaded by Andre La Gerche
Author content
All content in this area was uploaded by Andre La Gerche
Content may be subject to copyright.
EDITORIAL
Atrial fibrillat ion in athletes and the interplay
betw een exer cise and health
Andre La Gerche
1,2
and Christian Marc Schmied
3
*
1
St Vincent’s Hospital Department of Medicine, University of Melbourne, Fitzroy, Australia;
2
Department of Cardiovascular Medicine, University of Leuven, Leuven, Belgium;
and
3
Cardiovascular Center, Division of Cardiology, University Hospital Zurich, Ra¨mistrasse 100, CH-8091 Zurich, Switzerland
This editorial refersto ‘Riskof arrhythmias in52 755 long-dis-
tance cross-country skiers: a cohort study’, by K. Andersen
et al., doi:10.1093/eurheartj/eht188
Exercise is one of the most powerful lifestyle intervention strategies
for the primary and secondary prevention of cardiovascular disease.
There is a wealth of evidence regarding the lower ranges of the exer-
cise dose–response relationshipproviding concrete evidence forthe
current recommendations of atleast 30min of moderate intensityex-
ercise on most days as a means of reducing cardiovascular events.
1
However, there is an increasing proportion of today’s society en-
gaging in sports practices which vastly exceed these guidelines, and
there has been very limited study of the upper ranges of the exercise
dose–response relationship.
2
On the one hand arestudies suggesting
that long-term health and life expectancy of well-trained athletes is
superior to that of the general population,
325
while, on the other,
there is evidence suggesting an increased prevalence of arrhythmias
and chronic structural remodelling of the athletic heart.
629
Atrial fibrillation (AF) may therefore represent the most intriguing
and best evidenced example of the interplay between exercise and
cardiac health. AF can be diagnosed in 1% of the population by age
60 and in . 10% whenolder than80 years,
10
makingit themost preva-
lent sustained arrhythmia in adults. In cohorts of young or middle-aged
subjects, AF is relatively uncommon, thus implying that large cohorts
would be required to provide sufficient power to identify any excess
in prevalence due to sports practice. In this context, it is not surprising
thatPellicciaet al.foundonlyvery fewcasesof AFdespitesignificantleft
atrial enlargement in a fairly large (n ¼ 1777) athletic cohort aged
24 + 6years.
11
In contrast, Baldesberger et al.wereabletoidentify
an excess of AF when comparing a small cohort of 62 former profes-
sional cyclists with 62 ex-golfers aged 66 + 7years.
6
Although one
must always consider type 1 errors (false discoveries) in studies of
small sample size, it may also be that a true exercise-induced excess
in AF prevalence becomes appreciable when the cohort reaches an
age in which AF is more common and when the amount of exercise
practised is relatively extreme. In this context, the recent study of
Andersen et al. is remarkable.
12
The group of participants in the
popular Vasaloppet 90 km cross-country ski race was young and
healthy when one considers the likelihood of identifying incident AF.
Lessthan 10% ofthe cohort wasaged .60 years and those with signifi-
cant co-morbidities were few, as evidenced by the exclusion of parti-
cipants with known cardiovascular disease and by the fact that the
cohort had better health behaviour and overall longevity than the
average Swedish population.
13
Many of the established risk factors
for AF, such as hypertension, heart failure, diabetes, and obesity,
14
are likely to be under-represented within this group of cross-country
ski enthusiasts and, thus, we might expect such a low prevalence of AF
that detecting any residual risk attributable to exercise dose would be
difficult. However,the very large cohortsize of 52 755 athletes andthe
creative measures of exercise enabled the authors to define a ‘dose–
response’ curve that provides further circumstantial evidence for the
premise that AF risk is increased in the very fittest athletes and in
those who perform exercise over many years. Andersen et al. investi-
gated the primary endpoint of any arrhythmia, which was a composite
of brady-and tachyarrhythmias, and determined that those completing
the race within 60% of the winner’s time were 1.3 times more likely to
be diagnosedwith anarrhythmiathanthosewhotookmorethan twice
the time to complete the race. Similarly, those who had completed the
race ≥5 times had a 1.3-fold increase in arrhythmic risk as compared
with those who completed the race only once. The primary endpoint
was 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 measures
and supraventricular arrhythmias other than AF/atrial flutter, and
therewere too few ventricular arrhythmic eventsto draw conclusions.
One of the biggest limitations when trying to interpret the data of
Andersen et al. istrying to workout a reference point againstwhich to
interpret the described prevalence of arrhythmias. The lowest preva-
lence of arrhythmias was observed in the slowest athletes who had
raced least; but what is the critical ‘cut-off’ concerning the amount
of exercise that leads to an elevated risk for developing AF? We
are frequently asked: ‘How many hours of exercise and at what inten-
sity before I am at risk of AF?’, but there are numerous complexities
which make it difficult to give prescriptive guidelines. First, as sum-
marized in Figure 1, arrhythmias such as AF are the clinical expression
of an interplay between host, environmental, and disease-specific
* Corresponding author. Tel: +41-76 344 8308, Fax: +41-442558701, Email: christian.schmied@gmx.ch or christian.schmied@usz.ch
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
Published on behalf of the European Society of Cardiology. All rights reserved.
& The Author 2013. For permissions please email: journals.permissions@oup.com
European Heart Journal
doi:10.1093/eurheartj/eht265
European Heart Journal Advance Access published July 24, 2013
at University of Melbourne on July 24, 2013http://eurheartj.oxfordjournals.org/Downloaded from
factors. Host factors include age, gender, other genetic factors (from
single-gene mutations to multiple nucleotide polymorphisms),
obesity, alcohol consumption, sleep apnoea, and others.
15
Disease-
related factors includeatrial stretch,autonomic balance, and systemic
and local inflammation, while environmental factors include dietary
factors, concurrent illnesses, and exercise.
15
It is extremely difficult
to define the magnitude of the risk attributable to exercise in isola-
tion. In particular, the influence of gender is an important case in
point. A massive limitation of all exercise studies, including that of
Andersen et al., is the lack of data pertaining to females. There is cur-
rently no evidence that sports’ training constitutes a risk for AF in
females, but this is largely due to the gross under-representation of
females in sports cardiology research.
Thesecondissuein tryingtodefineclinical recommendationson the
perfect amount of exercise to minimize the risk of arrhythmias relates
to the difficulties in comparing measures of exercise dose across
studies.Variousquestionnaireshave beendeveloped to assessthe dur-
ation, frequency, and intensity ofphysical activity, but they remain fairly
coarse 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, for
example,willbe rated as 3/10 intensityby someoneof excellentfitness,
butas 7/10bysomeonewithpoor fitness.
17
Asimilareffectcanbeseen
when comparing literature across various disciplines; what is seen as
vigorous exertion in cardiovascular epidemiology studies would not
even be considered warm up tempo in sports science parlance.
18
The term ‘high intensity exercise’ can be used to describe walking up
a flight of stairs in some studies of AF
18
or, in the case of the study
of Andersen et al.,
12
can be applied to 90 km of cross-country ski
Figure 1 Interplay between environment, person, and disease
in 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 three
separate trials along the x-axis demonstrating an association between reducing prevalence of AF with increasing exercise of low intensity but then an
increasing risk of AF with moderate and intense exercise. The echocardiogram examples above demonstrate the progressive cardiac remodelling
from a typical sedentary subject (left), a leasure-time athlete (middle), and a professional cyclist (right). The 10 cm marker on the echocardiogram is
highlighted 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 and
the risk of AF increases. Whether or not there is a causal relationship between cardiac enlargement and arrhythmias is still to be determined.
EditorialPage 2 of 4
at University of Melbourne on July 24, 2013http://eurheartj.oxfordjournals.org/Downloaded from
racing. With this in mind, we have tried to construct a ‘guestimate’ of
relativeexercisedosesinthreelandmarkstudiesinvestigatingthe inter-
action between exercise and AF incidence. Our best attempt at trying
to integrate data across very disparate studies is presented in Figure 2.
The risk of AF decreases as one engages in regular physical activity of
mild to moderate exertion, as evidenced by the study of elderly sub-
jects by Mozaffarian et al.
19
However, as reported by Aizer et al.,
when thelevel ofexertionis equivalent to jogging, thena greater preva-
lence ofAF is appreciable in those jogging dailyas compared with those
jogging 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 the
sporting spectrum by describing people mostly of moderate to ex-
tremely high physical conditioning. Thus, some picture of the exercise
dose–response curve emerges, with a U-shaped pattern suggesting
thatregularmildto moderateexercisemayprovidea degreeof protec-
tion from AF while more sustained vigorous exertion represents a risk
factor. This is supported by a number of case–control studies which
have 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 regarding
the dose of exercise required to promote AF. Perhaps they also
provide a clinical clue that we should be advising our athletes with
AF to reduce their training intensity and volumes, but certainly not
to cease exercise practice all together. The wisdom of such advice
will really only be known after well-designed studies specifically
address the efficacy of such interventions.
Whilst the studyof Andersen et al. helps to expand our understand-
ing of the epidemiology of exercise-induced arrhythmias, it does not
provide any insights into underlying mechanisms. However, recent
studies in animals and humans support the premise that exercise
may serve as a trigger, a modulator, and contribute to the underlying
substrate for the promotion of arrhythmias. A collaboration
between the Barcelona group of Lluis Mont and the Montreal group
of Stanley Nattel has demonstrated that a model of endurance training
in rats (the ‘marathon rat’) can be used to demonstrate increased in-
flammation and fibrosis, and enhanced vagal responsiveness affecting
the atria and right ventricle (curiously sparing the left ventricle)
whichpredisposestheanimalsto both AFandrightventriculararrhyth-
mias.
28,29
This resembles some of the observations in human athletes.
Heidbuchel and La Gerche observed that endurance exercise can
promote remodelling and arrhythmias which seems to favour the
right ventricle disproportionately,
8,9
whereas Luthi et al.,
30
amongst
others, have demonstrated biatrial remodelling. The other intrigue
to which these studies are drawn is whether the remodelling asso-
ciated with exercisetraining (theso-called‘athlete’sheart’) is anentire-
ly physiological process. As detailed in Figure 2, increasing exercise
training is associated with cardiac remodelling which can be profound.
It remains to be determined whether those athletes with the biggest
hearts are at greatest risk of arrhythmias.
Conflict of interest: none declared.
References
1. Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, Dallongeville J,
De Backer G, Ebrahim S, Gjelsvik B, Herrmann-Lingen C, Hoes A, Humphries S,
Knapton M, Perk J, Priori SG, Pyorala K, Reiner Z, Ruilope L, Sans-Menendez S,
Scholte op Reimer W, Weissberg P, Wood D, Yarnell J, Zamorano JL, Walma E,
Fitzgerald T, Cooney MT, Dudina A, Vahanian A, Camm J, De Caterina R, Dean V,
Dickstein K, Funck-Brentano C, Filippatos G, Hellemans I, Kristensen SD,
McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Altiner A, Bonora E,
Durrington PN, Fagard R, Giampaoli S, Hemingway H, Hakansson J, Kjeldsen SE,
Larsen ML, Mancia G, Manolis AJ, Orth-Gomer K, Pedersen T, Rayner M, Ryden L,
Sammut M, Schneiderman N, Stalenhoef AF, Tokgozoglu L, Wiklund O,
Zampelas A. European guidelines on cardiovascular disease prevention in clinical
practice: executive summary. Eur Heart J 2007;28:2375 – 2414.
2. Shiroma EJ, Lee IM. Physical activity and cardiovascular health: lessons learned from
epidemiological studies across age, gender, and race/ethnicity. Circulation 2010;
122:743–752.
3. Clarke PM, Walter SJ, Hayen A, Mallon WJ, Heijmans J, Studdert DM. Survival of the
fittest: retrospective cohort study of the longevity of Olympic medallists in the
modern era. BMJ 2012;345:e8308.
4. Sarna S, Sahi T, Koskenvuo M, Kaprio J. Increased life expectancy of world class male
athletes. Med Sci Sports Exerc 1993;25:237 –244.
5. Teramoto M, Bungum TJ. Mortality and longevity of elite athletes. J Sci Med Sport
2010;13:410 –416.
6. Baldesberger S, Bauersfeld U, Candinas R, Seifert B, Zuber M, Ritter M, Jenni R,
Oechslin E, Luthi P, Scharf C, Marti B, Attenhofer Jost CH. Sinus node disease and
arrhythmias in the long-term follow-up of former professional cyclists. Eur Heart J
2008;29:71–78.
7. Mohlenkamp S, Lehmann N, Breuckmann F, Brocker-Preuss M, Nassenstein K,
Halle M, Budde T, Mann K, Barkhausen J, Heusch G, Jockel KH, Erbel R. Running:
the risk of coronary events: prevalence and prognostic relevance of coronary ath-
erosclerosis in marathon runners. Eur Heart J 2008;29:1903–1910.
8. La Gerche A, Burns AT, Mooney DJ, Inder WJ, Taylor AJ, Bogaert J, Macisaac AI,
Heidbuchel H, Prior DL. Exercise-induced right ventricular dysfunction and struc-
tural remodelling in endurance athletes. Eur Heart J 2012;33:998–1006.
9. Heidbuchel H, Hoogsteen J, Fagard R, Vanhees L, Ector H, Willems R, Van Lierde J.
High prevalence of right ventricular involvement in endurance athletes with ven-
tricular arrhythmias. Role of an electrophysiologic study in risk stratification. Eur
Heart J 2003;24:1473 –1480.
10. Go AS,Hylek EM, Phillips KA, Chang Y, Henault LE,Selby JV, Singer DE. Prevalence of
diagnosed atrial fibrillation in adults: national implications for rhythm management
and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation
(ATRIA) Study. JAMA 2001;285:2370– 2375.
11. Pelliccia A, Maron BJ, Di Paolo FM, Biffi A, Quattrini FM, Pisicchio C, Roselli A,
Caselli S, Culasso F. Prevalence and clinical significance of left atrial remodeling in
competitive athletes. J Am Coll Cardiol 2005;46:690 –696.
12. Andersen K, Farahmand B, Ahlbom A, Held C, Ljunghall S, Michae¨lsson K,
Sundstro¨m J. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a
cohort study. Eur Heart J 2013; doi:10.1093/eurheartj/eht188. Published online
ahead of print 11 June 2013.
13. Farahmand BY, Ahlbom A, Ekblom O, Ekblom B, Hallmarker U, Aronson D,
Brobert GP. Mortality amongst participants in Vasaloppet: a classical long-distance
ski race in Sweden. J Intern Med 2003;253:276– 283.
14. Schnabel RB, Sullivan LM, Levy D, Pencina MJ, Massaro JM, D’Agostino RB Sr,
Newton-Cheh C, Yamamoto JF, Magnani JW, Tadros TM, Kannel WB, Wang TJ,
Ellinor PT, Wolf PA, Vasan RS, Benjamin EJ. Development of a risk score for atrial
fibrillation (Framingham Heart Study): a community-based cohort study. Lancet
2009;373:739 –745.
15. Potpara TS, Lip GY. Lone atrial fibrillation: what is known and what is to come.
Int J Clin Pract 2011;65:446– 457.
16. Lamb KL, Brodie DA. The assessment of physical activity by leisure-time physical ac-
tivity questionnaires. Sports Med 1990;10:159 –180.
17. Aadahl M, Kjaer M, Jorgensen T. Perceived exertion of physical activity: negative as-
sociation with self-rated fitness. Scand J Public Health 2007;35:403 –409.
18. La Gerche A, Prior DL, Heidbuchel H. Strenuous endurance exercise: is more better
for everyone? Our genes won’t tell us. Br J Sports Med 2011;45:162– 164.
19. 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 –807.
20. Aizer A,Gaziano JM, CookNR, Manson JE, Buring JE, Albert CM. Relation of vigorous
exercise to risk of atrial fibrillation. Am J Cardiol 2009;103:1572 –1577.
21. Karjalainen J, Kujala UM, Kaprio J, Sarna S, Viitasalo M. Lone atrial fibrillation in
vigorously exercising middle aged men: case –control study. BMJ 1998;
316:1784–1785.
22. Grimsmo J, Grundvold I, Maehlum S, Arnesen H. High prevalence of atrial fibrillation
in long-term endurance cross-country skiers: echocardiographic findings and pos-
sible predictors—a 28– 30 years follow-up study. Eur J Cardiovasc Prev Rehabil
2010;17:100 –105.
23. Molina L, Mont L, Marrugat J, Berruezo A, Brugada J, Bruguera J, Rebato C, Elosua R.
Long-term endurance sport practice increases the incidence of lone atrial fibrillation
in men: a follow-up study. Europace 2008;10:618– 623.
Editorial Page 3 of 4
at University of Melbourne on July 24, 2013http://eurheartj.oxfordjournals.org/Downloaded from
24. MontL, SambolaA, BrugadaJ, VaccaM,MarrugatJ, ElosuaR, PareC, AzquetaM, SanzG.
Long-lasting sport practice and lone atrial fibrillation. Eur Heart J 2002;23:477 – 482.
25. Elosua R, Arquer A, Mont L, Sambola A, Molina L, Garcia-Moran E, Brugada J,
Marrugat J. Sport practice and the risk of lone atrial fibrillation: a case –control
study. Int J Cardiol 2006;108:332– 327.
26. Heidbuchel H, Anne W, Willems R, Adriaenssens B, Van de Werf F, Ector H. Endur-
ance sports is a risk factor for atrial fibrillation after ablation for atrial flutter. Int J
Cardiol 2006;107:67 –72.
27. Claessen G, Colyn E, La Gerche A, Koopman P, Alzand B, Garweg C, Willems R,
Nuyens D, Heidbuchel H. Long-term endurance sport is a risk factor for develop-
ment of lone atrial flutter. Heart 2011;97:918– 922.
28. Guasch E, Benito B, Qi X, Cifelli C, Naud P, Shi Y, Mighiu A, Tardif JC, Tadevosyan A,
Chen Y, Gillis MA, Iwasaki YK, Dobrev D, Mont L, Heximer S, Nattel S. Atrial fibril-
lation promotion by endurance exercise: demonstration and mechanistic explor-
ation in an animal model. J Am Coll Cardiol 2013;62:68 –77.
29. Benito B, Gay-Jordi G, Serrano-Mollar A, Guasch E, Shi Y, Tardif JC, Brugada J,
Nattel S, Mont L. Cardiac arrhythmogenic remodeling in a rat model of long-term
intensive exercise training. Circulation 2011;123:13 –22.
30. Luthi P, Zuber M, Ritter M, Oechslin EN, Jenni R, Seifert B, Baldesberger S, Attenho-
fer Jost CH. Echocardiographic findings in former professional cyclists after
long-term deconditioning of more than 30 years. Eur J Echocardiogr 2008;9:
261– 267.
EditorialPage 4 of 4
at University of Melbourne on July 24, 2013http://eurheartj.oxfordjournals.org/Downloaded from