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Heart Online First, published on November 29, 2012 as 10.1136/heartjnl-2012-302886
Editorial
Run for your life … at a
measured by peak performance on a tread-
mill, show a curvilinear relationship
whereby improvements from unfit to
comfortable speed and not too far moderately fit confer dramatic reductions
in morbidity and mortality (figure 2).8
However, fitness levels above 12 metabolic
James H O’Keefe,1,2 Carl J Lavie3,4 equivalents do not seem to translate into
additional gains in CV health and longev-
ity. Thus, if one is training to be able to
During the Greco-Persian War in 490 longevity improvements conferred by mod- run at speeds above 7.5 miles per hour,
BCE, Phidippides, a 40-year-old herald erate physical activity. Thus, even though this is being done for some reason other
messenger ( professional running-courier) chronic extreme exercise may not kill you, it than further improvements in life
ran the 26 miles from a battlefield near may erase many of the health advantages of expectancy.
Marathon, Greece, into Athens carrying regular moderate exercise.
momentous news of Greek victory. Upon Indeed, regular vigorous exercise is prob- CV DAMAGE FROM EXCESSIVE
arriving at the Acropolis, he proclaimed: ably the single best step a person can take EXERCISE
‘Joy, we have won!’ and then immedi- to ensure robust CV health. In a study of High-intensity exercise sessions lasting
ately collapsed and died.1 Fast-forward 416 000 adults followed for a mean of beyond 1–2 h cause acute volume over-
about 2500 years to an era when the 8 years, 40–50 min per day of vigorous load of the atria and right ventricle (RV),
baby-boomer’s came of age and long- exercise reduced risk of death by about which can bring about overstretching and
distance running boomed. The prevailing 40% (figure 1).7 In that study, at about micro-tears in the myocardium, as evi-
logic held that aerobic exercise is clearly 45 min, a point of diminishing returns is denced by a transient rise in cardiac bio-
good for one’s health and that, if some reached whereby longer exercise efforts do markers, including troponin and
is good, more must be better. In 1975, not appear to translate into lower death B-natriuretic peptide and a fall in the RV
Dr Thomas Bassler, a physician/runner, risk. Light to moderate physical activity ejection fraction.9 Although within
boldly proclaimed that, if you could run a reduced death rates too, albeit not as 1 week, these transitory abnormalities
marathon, you were immune to death strongly, but in this case more physical usually return to baseline,9 after years to
from coronary heart disease (CHD).2 This activity appeared to be better, with no decades of excessive exercise and repeti-
urban myth has long since been dispro- plateau out to 110 min daily. Indeed, if we tive injury, this pattern can lead to
ven; indeed an emerging body of evidence had a pill that confers all the benefits of patchy myocardial fibrosis, particularly in
suggests the opposite: extreme endurance exercise, many physicians might be the pliable walls of the heart such as the
exercise may exact a toll on cardiovascular looking for work. Approximately 30– atria and RV, creating a substrate for atrial
(CV) health. 45 min of daily vigorous exercise signifi- and potentially malignant ventricular
cantly reduces risks for many maladies arrhythmias.1 3–5 In addition, long-term
‘SHOW ME THE BODIES’ including early death, Alzheimer’s disease, excessive exercise may accelerate aging in
After our recent articles on this topic,1 3–5 CHD, diabetes, osteoporosis and depres- the heart, as evidenced by increased cor-
Amby Burfoot, winner of the 1968 Boston sion.4 5 Yet, as can be expected with any onary artery calcification, diastolic ven-
Marathon and Editor-at-Large for Runner’s potent drug, an insufficient dose will not tricular dysfunction, and large-artery wall
World Magazine, challenged our assertions confer the optimal benefits, while an stiffening.1 3–5
about the dangers of extreme endurance excessive dose can cause harm, and even At rest, the heart pumps about 5 litres/
efforts by demanding, ‘Show me the death in extreme overdoses. min; with strenuous aerobic exercise, the
bodies’. Amby has a good point: the risk of The ‘survival of the fittest’ concept cardiac output can rise 5–7-fold, pumping
dropping dead in a marathon is remote, does not fully apply to the modern world, up to 25–35 litres/min. This massive
about 0.5 to 1 in 100,000 participants.6 But where it appears that even the moderately increase in cardiac work is what the heart
the occasional marathoner or triathlete who fit have an excellent CV prognosis and is designed to do for short bursts, or even
dies while strenuously exercising is the superb longevity. Studies of CV fitness, as for up to as long as 30 or 50 min
‘canary in the coal mine’. Chronic extreme
exercise appears to cause excessive
‘wear-and-tear’ on the heart, inducing
adverse structural and electrical remodelling,
which offsets some of the CV benefits and
1
Saint Luke’s Mid America Heart Institute, Kansas City,
Missouri, USA; 2University Of Missouri-Kansas City
School of Medicine, Kansas City, Missouri, USA;
3
Department of Cardiology, John Ochsner Heart and
Vascular Institute, Ochsner Clinical School, The
University of Queensland School of Medicine, New
Orleans, Louisiana, USA; 4Pennington Biomedical
Research Center, Baton Rouge, Louisiana, USA
Correspondence to Dr James H O’Keefe, Saint Luke’s
Mid America Heart Institute,4330 Wornall Road, Suite
2000 Kansas City, MO 64111 phone: 816-751-8480
fax: 816-756-3645
jokeefe@saint-lukes.org Figure 1 Duration of daily exercise and reduction in long-term all-cause mortality.7
Copyright
Heart Month Article
0 Vol 0 No author
0 (or their employer) 2012. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
1
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Editorial
predisposition to dangerous ventricular
dysrhythmias that have been documented
in some veteran extreme endurance ath-
letes.14 Encouragingly, when the mice
were withdrawn from the ‘Iron-Mouse’
training regimen and allowed to resume
normal mouse physical activity levels,
their cardiac abnormalities showed
marked improvements, even showing
regression of myocardial fibrosis and reso-
lution of the tendency toward serious
ventricular dysrhythmias.14
PHIDIPPIDES CARDIOMYOPATHY
Born to Run is a non-fiction bestseller
Figure 2 Death rates as a function of cardiovascular fitness as measured by metabolic book published in 2009 that glamorises
equivalents achieved on maximal exercise treadmill testing.8 CVD, cardiovascular disease.
ultra-endurance running. The story’s
hero is Micah True, an American who
dropped out of modern civilisation to
continuously. However, with protracted septum and RV (figure 3).12 Cardiologists
live and run with the Tarahumara
efforts, these high volumes can over- from Minnesota evaluated a group of
Indians in Mexico. Nicknamed Caballo
stretch the chambers, eventually disrupt- runners who had completed at least 25
Blanco, or white horse, for his legendary
ing cardiac muscle fibres and causing marathons over 25 years and found a 60%
running endurance, he routinely ran
micro-tears in the myocardium.10 The increase in coronary plaque burden com-
daily distances of 25–100 miles. This
presence of sustained exercise-induced ele- pared with sedentary age-matched con-
March on a 12-mile training run in New
vations in catecholamines and trols.1 These findings were replicated by a
Mexico, Micah True dropped dead at age
pro-oxidant free radicals worsen the situ- group from Germany, who showed
58. On autopsy, his heart was enlarged
ation by adding inflammation to the increased coronary plaque in 108 chronic
and thickened with ‘focal areas of inter-
injury, leading eventually to scarring and marathoners compared with sedentary
stitial chronic inflammatory infiltrate’ in
stiffening of the CV structures.10 controls.13 This scarring can set the stage
the myocardium; the coronary arteries
A trial randomised 60 male patients for dangerous heart rhythms, such as
were ‘focally thickened with mild coron-
with CHD to vigorous exercise sessions atrial fibrillation, which is increased
ary arteriosclerosis’. Chief Medical
of either 30 or 60 min.11 The 30 min exer- approximately fivefold in veteran endur-
Investigator Ross Zumwalt, MD sum-
cise workouts improved arterial elasticity ance athletes.10 Ventricular tachycardia
marised the findings as, ‘Unclassified car-
and produced minimal oxidant stress. In and sudden cardiac arrest can also be
diomyopathy, which resulted in a cardiac
contrast, the 60 min sessions increased seen in endurance athletes even in
dysrhythmia during exertion’.15 When
oxidant stress and worsened vascular the absence of CHD and hypertrophic
considered in the context of True’s
stiffness as measured by pulse wave vel- cardiomyopathy.1 5
decades-long lifestyle of daily ultra-
ocity, particularly in those over the age An enlightening study by Benito et al
marathon running, we suspect that the
of 50. MRI scans of runners who have reinforced the concept of cardiac damage
autopsy findings were an example of
been participating in marathons for from chronic excessive exercise. Mice
‘Phidippides cardiomyopathy’—the con-
decades show a threefold increased inci- after being forced to run to exhaustion
stellation of cardiac pathology that has
dence of scattered fibrosis and scarring in every day for 4 months showed the
been in observed in the hearts of some
the walls of the atria, interventricular same cardiac enlargement, scarring and
veteran extreme endurance athletes.1
Figure 3 MRI scans showing scattered scarring (red arrows) in the heart, especially in the interventricular septum.14
2 Heart Month 0 Vol 0 No 0
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Editorial
MODERATE EXERCISE: THE THE U-CURVE peak aerobic capacity are very different
SWEET-SPOT FOR LONGEVITY Hippocrates, the father of medicine and a from those that best confer CV health,
Two very recent studies presented in contemporary of Phidippides in ancient durability and overall longevity. So, if
abstract form at major national meetings Greece, taught, ‘The right amount of one’s goal in life is to compete in the
may revolutionise our thinking about nourishment and exercise, not too much, marathon or triathlon of the Rio
running and its health effects.16 17 One is not too little, is the safest way to Olympics in 2016, this will certainly
a prospective observational study that health’.1 If you listen to your body, this is require high-intensity exercise for hours a
followed 52 600 people for up to three just common sense. Yet, nothing we have day. But, for those whose goal is to be
decades.17 The 14 000 runners in that published previously has stirred so much alive and well while watching the 2052
study had a 19% lower risk of death com- controversy, especially among the general Olympics from the stands, then exercise
pared with the 42 000 non-runners. Yet, public. Increasingly our culture is one of and physical activity at lower intensities
when they sub-grouped the runners by extremes: during the past 30 years, and durations would be more ideal.
weekly mileage, those who ran over 20 or obesity has tripled in the USA and has
25 miles per week seemed to lose their increased in much of the Western World, CONCLUSION
survival advantage over the non-runners while during the same time the number The take home message for most is to
(figure 4). On the other hand, those who of people completing a marathon has limit one’s vigorous exercise to 30–
ran between 5 and 20 miles total per risen 20-fold. On one side of the U-curve, 50 min/day. If one really wants to do a
week enjoyed a 25% decrease in risk of the couch loungers/channel surfers marathon or full-distance triathlon etc, it
death during follow-up. The same embrace this message as justification for may be best to do just one or a few and
pattern emerged for speed of running: the continuing their sedentary lifestyle. And, then proceed to safer and healthier exer-
fast runners, those running typically over on the far end of the U-curve, the cise patterns. On the other hand, light or
8 miles an hour, appeared to get no mor- extreme exercise aficionados want to moderate intensity exercise does not
tality benefit compared with the non- ignore the message and instead kill the present the dose-dependent risks asso-
runners, whereas those who fared best messenger. As with many things in ciated with excessive endurance exercise.
usually ran about 6–7 miles per hour—a life, the safe and comfortable zone at A routine of moderate physical activity
comfortable jog for most people. In add- the bottom of the U curve—moderate will add life to your years, as well as
ition, the individuals who ran 6 or 7 days exercise—is the ‘sweet spot’ for which years to your life. In contrast, running
per week appeared to lose the mortality most should try to aim. too fast, too far, and for too many years
benefits, whereas the survival advantages Sitting is the new smoking; a sedentary may speed one’s progress towards the
accrued best for those who ran 2–5 days lifestyle will cause disability and disease, finish line of life.
per week.16 and will shorten life expectancy. We are Contributors JHO and CJL contributed.
The Copenhagen City Heart Study not so much born to run as born to walk.
showed remarkably similar results. After Ethnographic research indicates that, in Competing interests None.
following 20 000 Danes since 1976, they the environment of human evolution, our Provenance and peer review Commissioned;
found that the joggers lived about 6 years ancient ancestors walked 4–10 miles a internally peer reviewed.
longer than the non-runners, with a 44% day.4 Walking is superior to running for Author note A video presentation on this topic is
lower risk of death during the study.17 mechanical efficiency and musculoskeletal available on the internet: You Tube, TEDx Talk, James
Intriguingly, those who did best were the durability. Indeed, we advise our patients O’Keefe, Run for your life… at a comfortable pace and
not too far.
people who jogged at a slow to average that they can walk or garden hours a day
pace, for one to 2.5 h per week total, without concern about CV overuse injury. Heart 0;0:1–4. doi:10.1136/heartjnl-2012-302886
accumulated during two or three sessions. So while it is true that exercise confers
According to Dr Peter Schnohr, the powerful health benefits, the common REFERENCES
study’s director, ‘The relationship appears belief that more is better is clearly not 1. O’Keefe JH,PatilHR,LavieCJ,etal.Potential adverse
cardiovasculareffects fromexcessiveendurance
much like alcohol intakes—mortality is true. The unique and potent benefits of exercise.MayoClinicProc 2012;87:587–95.
lower in people reporting moderate exercise are best bestowed by moderate 2. Bassler TJ. Marathon running and immunity to
jogging than in non-joggers or those exercise and physical activity. The exer- atherosclerosis. Ann N Y Acad Sci
undertaking extreme levels of exercise’.17 cise patterns for maximising CV fitness/ 1977;301:579–92.
3. O’Keefe JH,PatilHR,LavieCJ.Exerciseandlife
expectancy.Lancet2012;379:799;author reply800–1.
4. O’Keefe JH, Vogel R, Lavie CJ, et al. Exercise like a
hunter-gatherer: a prescription for organic physical
fitness. Prog Cardiovasc Dis 2011;53:471–9.
5. Patil HR, O’Keefe JH, Lavie CJ, et al. Cardiovascular
damage resulting from chronic excessive endurane
exercise. Mo Med 2012;109:312–21.
6. Kim JH, Malhotra R, Chiampas G, et al. Cardiac
arrest during long-distance running races. N Engl J
Med 2012;366:130–40.
7. Wen CP, Wai JP, Tsai MK, et al. Minimum amount of
physical activity for reduced mortality and extended
life expectancy: a prospective cohort study. Lancet
2011;378:1244–53.
8. ChurchTS,LaMonteMJ,BarlowCE,etal.
Cardiorespiratoryfitnessandbodymassindexaspredictors
ofcardiovasculardiseasemortalityamongmenwith
diabetes.ArchInternMed2005;165:2114–20.
9. Ector J, Ganame J, van der Merwe N, et al.
Figure 4 All-cause mortality by running distance per week.16 Reduced right ventricular ejection fraction in
Heart Month 0 Vol 0 No 0 3
Downloaded from heart.bmj.com on January 11, 2013 - Published by group.bmj.com
Editorial
endurance athletes presenting with ventricular 13. Mohlenkamp S, Lehmann N, Breuckmann F, et al. ed. Medicine & Science in Sports & Exercise.
arrhythmias: a quantitative angiographic assessment. Running: the risk of coronary events : Prevalence and American College of Sports Medicine San Francisco,
Eur Heart J 2007;28:345–53. prognostic relevance of coronary atherosclerosis in CA: 2012:S699.
10. La GA, Burns AT, Mooney DJ, et al. Exercise-induced marathon runners. Eur Heart J 2008;29:1903–10. 17. Schnohr P. Assessing prognosis: a glimpse of the
right ventricular dysfunction and structural 14. Benito B, Gay-Jordi G, Serrano-Mollar A, et al. future. Jogging healthy or hazard? In: Cardiology ESo,
remodelling in endurance athletes. Eur Heart J Cardiac arrhythmogenic remodeling in a rat model of ed. EuroPRevent 2012. Dublin, Ireland: European
2012;33:998–1006. long-term intensive exercise training. Circulation Heart Journal, 2012.
11. Michaelides AP, Soulis D, Antoniades C, et al. 2011;123:13–22. 18. O'Keefe JH, Patil HR, Lavie CJ, et al. In reply.
Exercise duration as a determinant of vascular 15. Zumwalt R. Autopsy Report TRUE, MICAH RANDALL. Potential, but unobserved, adverse cardiovascular
function and antioxidant balance in patients with In: Investigator OotM, ed. Albuquerque: University of effects from endurance exercise. Mayo Clin Proc
coronary artery disease. Heart 2011;97:832–7. New Mexico Health Sciences Center, 2012:5. http:// 2012 Nov;87(11):1133-4.
12. Breuckmann F, Mohlenkamp S, Nassenstein K, extremelongevity.net/wp-content/uploads/
et al. Myocardial late gadolinium enhancement: 2401-12AutRpt.pdf accessed august 24, 2012
prevalence, pattern, and prognostic relevance in 16. Lee DC, Pate RR, Lavie CJ. Running and all-cause
marathon runners. Radiol 2009;251:50–7. mortality risk—is more better? In: Medicine ACoS,
4 Heart Month 0 Vol 0 No 0
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Run for your life … at a comfortable speed
and not too far
James H O'Keefe and Carl J Lavie
Heart published online November 29, 2012
doi: 10.1136/heartjnl-2012-302886
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References This article cites 14 articles, 5 of which can be accessed free at:
http://heart.bmj.com/content/early/2012/11/21/heartjnl-2012-302886.full.html#ref-list-1
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Potential Adverse Cardiovascular Effects From
Excessive Endurance Exercise
James H. O’Keefe, MD; Harshal R. Patil, MD; Carl J. Lavie, MD; Anthony Magalski, MD;
Robert A. Vogel, MD; and Peter A. McCullough, MD, MPH
Abstract
A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and
improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce
pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and
competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long
distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient
reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal
within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy
myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial
and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary
artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical
and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low
mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance
exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate
physical fitness regimens for conferring optimal CV health and longevity.
© 2012 Mayo Foundation for Medical Education and Research 䡲 Mayo Clin Proc. 2012;87(6):587-595
R
egular exercise is one of the cornerstones of Similarly, a 15-year observational study of 52,000
therapeutic lifestyle changes for producing adults found that runners had a 19% lower risk of
optimal cardiovascular (CV) and overall all-cause mortality compared with nonrunners, with From Mid America Heart
health. Physical exercise, though not a drug, pos- U-shaped mortality curves for distance, speed, and fre- Institute of Saint Luke’s Hos-
sesses many traits of a powerful pharmacological quency. Running distances of about 1 to 20 miles per pital of Kansas City, MO
(J.H.O., H.R.P., A.M.); John
agent. A routine of daily physical activity (PA) stim- week, speeds of 6 to 7 miles per hour, and frequencies
Ochsner Heart and Vascular
ulates a number of beneficial physiologic changes in of 2 to 5 days per week were associated with lower Institute, Ochsner Clinical
the body and can be highly effective for prevention all-cause mortality, whereas higher mileage, faster School–The University of
and treatment of many of our most prevalent and paces, and more frequent runs were not associated Queensland School of Medi-
pernicious chronic diseases, including coronary with better survival.7 A randomized crossover trial as- cine, New Orleans, LA, and
Pennington Biomedical Re-
heart disease (CHD), hypertension, heart failure, signed 60 male patients with CHD to ET sessions of search Center, Louisiana
obesity, depression, and diabetes mellitus.1 People either 30 or 60 minutes. The 30-minute exercise ses- State University System, Ba-
who exercise regularly have markedly lower rates of sions produced less oxidant stress and improved arte- ton Rouge (C.J.L.); University
disability and a mean life expectancy that is 7 years rial elasticity, whereas 60-minute sessions worsened of Maryland, Baltimore
(R.A.V.); and St. John Provi-
longer than that of their physically inactive contem- oxidant stress and increased vascular stiffness as mea-
dence Health System Provi-
poraries.2,3 Accordingly, physicians are increasingly sured by pulse wave velocity, mainly in older patients.8 dence Park Heart Institute,
prescribing regular exercise training (ET) for their Thus, the benefits of ET are attainable with Novi, MI (P.A.M.).
patients. The potential benefits of regular ET are comparatively modest levels of PA. Highly trained
listed in Table 1.4 endurance athletes often perform strenuous aerobic
However, as with any pharmacological agent, a exercise for several hours daily, often accumulating
safe upper-dose limit potentially exists, beyond workloads of 200 to 300 metabolic equivalent hours
which the adverse effects (musculoskeletal trauma, (metabolic equivalents ⫻ hours) per week, which is
metabolic derangements, CV stress, etc) of physical approximately 5- to 10-fold greater than the stan-
ET may outweigh its benefits. A very large recent dard ET dose recommended for prevention of
study found that in sedentary individuals, even a CHD.1,9 The aim of this review is to explore the
modest dose of PA, as little as 15 minutes per day,5 hypothesis that long-term excessive endurance ET
confers substantial health benefits and that these in some individuals may induce adverse CV struc-
benefits accrue in a dose-dependent fashion up to tural and electrical remodeling that might diminish
about an hour per day of vigorous PA, beyond which some of the benefits conferred by more moderate
more ET does not yield further benefits (Figure 1).5,6 intensities and durations of ET.
Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005 䡲 © 2012 Mayo Foundation for Medical Education and Research 587
www.mayoclinicproceedings.orgMAYO CLINIC PROCEEDINGS
ARTICLE HIGHLIGHTS TABLE 1. Potential Benefits of Exercise Training
People who exercise regularly have markedly lower rates of disability Related to coronary heart disease risk factors
and a mean life expectancy that is 7 years longer than that of their Increases serum high-density lipoprotein
cholesterol levels
physically inactive contemporaries. However, a safe upper-dose limit
Reduces serum triglyceride and possibly low-
potentially exists, beyond which the adverse effects of exercise may
density lipoprotein cholesterol levels
outweigh its benefits.
Reduces indices of obesity
Chronic intense and sustained exercise can cause patchy myocardial
Reduces arterial blood pressure
fibrosis, particularly in the atria, interventricular septum, and right ven- Improves insulin sensitivity and glucose levels
tricle, creating a substrate for atrial and ventricular arrhythmias. Improves endothelial function
Chronic excessive sustained exercise may also be associated with Helps with smoking cessation efforts
coronary artery calcification, diastolic dysfunction, and large-artery wall Reduces psychological stress
stiffening. Hematologic
Veteran endurance athletes in sports such as marathon or ultramara- Decreases hematocrit and blood viscosity
thon running or professional cycling have been noted to have a 5-fold Expands blood plasma volume
increase in the prevalence of atrial fibrillation. Increases red blood cell deformability and tissue-
Intense endurance exercise efforts often cause elevation in biomarkers level perfusion
of myocardial injury (troponin and B-type natriuretic peptide), which Increases circulatory fibrinolytic activity
were correlated with transient reductions in right ventricular ejection Other
fraction. Increases coronary flow reserve
Increases coronary collateral circulation
Increases tolerance of ischemia
Increases myocardial capillary density
SUDDEN CARDIAC DEATH AND ENDURANCE ET Increases ventricular fibrillation thresholds
Over the past 35 years, the number of Americans Reduces atherosclerosis
participating in a marathon annually has risen 20- Possibly increases epicardial coronary artery size
fold; in 2010, an estimated half-million runners Reduces major morbidity and mortality
completed a marathon in the United States.10 Sud-
From Mayo Clin Proc.4
den cardiac death (SCD) among marathoners is very
rare, with 1 event per 100,000 participants.6,7,11,12
Although that per-participant risk has not changed
over the decades, absolute mortality rates have in- The causes of SCD during or after extreme ex-
creased as the number of participants has risen. The ertion in individuals younger than 30 years most
final 1 mile of the marathon course represents less commonly include genetic causes such as hypertro-
than 5% of the total distance of 26.2 miles yet ac- phic cardiomyopathy, anomalous coronary arteries,
counts for almost 50% of the SCDs during the dilated cardiomyopathy, and congenital long QT
syndrome. In athletes older than 30 years, CHD and
race.12,13
acute myocardial infarction16 and ischemia are the
The fatality rate for triathlons is approximately
predominant causes of exercise-related SCD.17-23
twice that of marathons, largely because of increased
CV events and drownings during the swim portion
of the races.14 The incidence of SCD among colle- ANIMAL STUDIES
giate athletes during competition is about 1 per In an elegant animal model of excessive endurance
40,000 participants per year for all athletes.15 It is ET, rats were trained (in part by prodding with elec-
extremely important to keep in mind that the occur- trical shocks to maintain high-intensity effort) to
rence of SCD during marathons, triathlons, and col- run strenuously and continuously for 60 minutes
legiate athletic events is rare and should not deter daily for 16 weeks, and then they were compared
individuals from participating in vigorous ET; the with control sedentary rats.8,24 The running rats de-
benefits of regular PA to the individual and to veloped hypertrophy of the left ventricle (LV) and
society as a whole far outweigh potential risks. At the right ventricle (RV), diastolic dysfunction, and
the same time, long-term training for and compet- dilation of the left atria and the right atria (RA); they
ing in extreme endurance events may predispose also showed increased collagen deposition and fi-
to CV issues that are not seen in more moderate brosis in both the atria and ventricles (Figure 2).
forms of PA. Ventricular tachycardia was inducible in 42% of the
588 Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005
www.mayoclinicproceedings.orgCARDIOVASCULAR EFFECTS OF ENDURANCE EXERCISE
running rats vs only 6% of the sedentary rats (P⫽.05).
Importantly, the fibrotic changes caused by 16 weeks 50
All-cause mortality reduction (%)
of intensive ET had largely regressed to normal by 8
weeks after the daily running regimen ceased. 40
35%
This animal study found that daily excessive,
29%
strenuous, uninterrupted running replicated the ad- 30
verse cardiac structural remodeling and proarrhyth- 20%
mia substrate noted in observational studies of ex- 20
treme endurance athletes. These findings support 14%
Vigorous
the hypothesis that in some individuals, long-term 10 Moderate
strenuous daily endurance ET, such as marathon Total
running or professional long-distance cycling, in 0
some individuals may cause cardiac fibrosis (espe- 0 10 20 30 40 50 60 70 80 90 100 110
cially in the atria and the RV and interventricular
Daily physical activity duration (min)
septum), diastolic dysfunction, and increased suscep-
tibility to atrial and ventricular arrhythmias. Many pre-
vious animal studies have also found acute, adverse FIGURE 1. Relationship between dose of physical activity and reduction
cardiac effects of prolonged (up to 6 hours) endurance in all-cause mortality. The mortality benefits of exercise appear with even
exercise, sometimes employing a rat model of cold- small amounts of daily exercise and peak at 50 to 60 minutes of vigorous
water swimming in which the animals were forced to exercise per day. From Lancet,5 with permission.
swim to avoid drowning.25 These studies are of uncer-
tain clinical relevance because of the excessively stress-
ful nature of the imposed exercise. atine kinase MB, and B-type natriuretic peptide,
have been documented to increase in up to 50% of
participants during and after marathon run-
ATHLETE’S HEART ning7,10-14 (Figure 3).9,12,37-40 Additionally, tran-
Chronic ET imposes increased hemodynamic de- sient renal dysfunction has been observed with ex-
mands that alter the loading conditions of the heart, treme endurance ET efforts causing volume
particularly among athletes participating in sports re- depletion and diminished renal filtration, with ele-
quiring sustained elevations in cardiac work, such as vations in serum urea nitrogen, serum creatinine,
long-distance running, rowing, swimming, and cy- and cystatin C.41 Increased levels of cardiac bio-
cling.26 Highly trained individuals develop cardiac ad- markers including troponin after extreme ET endur-
aptations including enlarged LV and RV volumes, in- ance events, such as marathons, may reflect myocar-
creased LV wall thickness and cardiac mass, and dial cell damage at the sites of myocyte slippage of
increased left atrial size.21-23 In the general population, one cell along another due to loss of integrity of des-
these structural changes are associated with poor car- mosomal connections.15,42 However, the significance
diac prognosis.27 However, these structural altera- of the elevated cardiac biomarkers after endurance ef-
tions, together with a preserved LV ejection fraction forts remains uncertain, and it has been argued that
(EF), have been considered typical findings of the “ath- these may be entirely benign transient increases result-
lete’s heart.”18-20,28 Of concern, accumulating infor- ing from CV adaptations to long-term ET.12,16,38,43
mation suggests that some of the remodeling that
occurs in endurance athletes may not be entirely
benign.17,29-32 For example, in elite athletes, cardiac ADVERSE STRUCTURAL REMODELING
dimensions do not completely regress to normal levels Accumulating evidence suggests that the adverse ef-
even several years after the athlete has retired from fects of both short-term intense PA and cumulative
competition and heavy ET.33 endurance exercise are most apparent in the right-
sided cardiac chambers. Cardiac output at rest is
approximately 5 L/min but typically increases 5-fold
BIOMARKER EVIDENCE FOR CARDIAC DAMAGE to about 25 L/min during vigorous ET.21 Long-term
WITH EXTREME ENDURANCE ET daily sessions of hours of continuous strenuous PA
Running is a prototypical natural PA and often plays cause dilation of the RA and RV. During the postex-
an integral and important role in an active, healthy ercise period, the cardiac geometric dimensions are
lifestyle.9,34-36 However, uninterrupted very long restored, but with this recurrent stretch of the cham-
distance running as is generally done while training bers and reestablishment of the chamber geometry,
for and participating in marathons and other ex- some individuals may be prone to the development
treme endurance events may produce adverse CV of chronic structural changes including chronic di-
effects in susceptible individuals. Serologic markers latation of the RV and RA with patchy myocardial
of cardiac damage, including cardiac troponin, cre- scarring in response to the recurrent volume over-
Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005 589
www.mayoclinicproceedings.orgMAYO CLINIC PROCEEDINGS
4 wk 8 wk 16 wk
Sedentary
RV FW sections
200 µm
Exercise
A
6 4 wk 6 8 wk 6 16 wk
5 5 5 *
Sedentary
Fibrosis (%)
Fibrosis (%)
Fibrosis (%)
4 4 4
Exercise
3 3 3
2 2 2
1 1 1
0 0 0
B RV FW IVS LV FW RV FW IVS LV FW RV FW IVS LV FW
FIGURE 2. A, Picrosirius-stained photomicrographs of RV sections. By 16 weeks, the RVs of exercising
rats show widespread interstitial collagen deposition with disarray of myocardial architecture (arrows).
B, Mean ⫾ standard error of the mean collagen content in RV FW, IVS, and LV FW. *P⬍.05 (exercising
vs sedentary rats). FW ⫽ free wall; IVS ⫽ interventricular septum; LV ⫽ left ventricle; RV ⫽ right
ventricle. From Circulation,24 with permission.
load and excessive cardiac strain.17-19,29,44 These were seen most often in races of longer durations
abnormalities are often asymptomatic and probably (Figure 5). Of this cohort of endurance athletes, 5
accrue over many years; they might predispose to (12.5%) had myocardial scarring as detected by fo-
serious arrhythmias such as atrial fibrillation and/or cal gadolinium enhancement on cardiac magnetic
ventricular arrhythmias (VAs). resonance imaging (MRI) (Figure 6). The myocar-
A prospective study of 25 runners (13 women dial scarring and chronic RV remodeling were more
and 12 men) found that running a marathon caused common in athletes with the largest cumulative ex-
acute dilation of the RA and RV, with a sudden de- perience in competitive endurance events.45 In
crease in the RVEF.32 La Gerche et al45 studied a summary, this study suggests that intense endur-
cohort of 40 highly trained aerobic athletes after ance exercise induces acute RV dysfunction while
competing in endurance events including marathon largely sparing the LV. Even when short-term RV
(mean time to completion, 3 hours), half-ironman recovery appears complete, long-term training for
triathlon (5.5 hours), full-ironman triathlon (11 and competing in extreme endurance exercise may
hours), and alpine bicycle race (8 hours). They lead to myocardial fibrosis and remodeling in a
found that these intense endurance exercise efforts small subgroup.9,20,21,45
caused elevations in biomarkers of myocardial in- Ector et al29 reported that the decrease in RVEF
jury (troponin and B-type natriuretic peptide), is less significant in athletes with no symptoms of
which were correlated with reductions in RVEF arrhythmia than in endurance athletes who have
(Figure 4), but not LVEF, on immediate (mean, 45 symptoms of arrhythmias, in whom the RV size in-
minutes) post-race echocardiography. The reduc- creases and the RVEF is significantly lower. Another
tions in RVEF and the increases in RV volumes, study of endurance athletes who have symptoms of
which returned entirely to baseline within 1 week, VAs found that 50% of them had RV structural ab-
590 Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005
www.mayoclinicproceedings.orgCARDIOVASCULAR EFFECTS OF ENDURANCE EXERCISE
normalities by MRI.46 This RV dysfunction is likely
induced by recurrent extreme and sustained high-
100
level PA, with marked elevations in pulmonary
artery pressures of up to 80 mm Hg in some ath-
letes,9 which eventually may cause scattered areas of
myocardial injury (as evidenced by the increases in
troponin) with subsequent fibrotic scarring, typi-
cally in the RV and atria.17,22,23,29,31,32 These 75
observations have led to speculation about the exis-
hs-cTnT concentration (ng/L)
tence of a syndrome of exercise-induced arrhythmo-
genic RV cardiomyopathy that shares some features
with the familial RV disease but is caused by chronic
high-level endurance ET rather than a genetic
50
predisposition.9
Another study using MRI to assess the effects of
long-term very long distance running on myocardial
structure31 comprised 102 ostensibly healthy male
runners ranging in age from 50 to 72 years who had
completed at least 5 marathons during the previous 25 Upper
3 years, compared with 102 age-matched con- reference
limit (14 ng/L)
trols.31 Approximately 12% of these apparently
healthy marathon runners have evidence of
patchy myocardial scarring, manifested as late gado-
linium enhancement; this was 3-fold more common
0
than in age-matched controls. Of additional concern,
the CHD event rate during 2-year follow-up was sig-
nificantly higher in the marathon runners than in con- 1 wk Immediately 24 h 72 h
trols (P⬍.0001).31 A similar smaller study found before race after race after race after race
pathologic myocardial fibrosis by cardiac MRI in 6 of
12 asymptomatic men (50%) who were lifelong vet- FIGURE 3. High-sensitivity cardiac troponin T (hs-cTnT) concentrations
eran endurance athletes, but no cases in younger en- before, immediately after, and 24 and 72 hours after marathon race. From
durance athletes and age-matched controls.24 Med Sci Sports Exerc,40 with permission.
Aortic stiffness and arterial pulse wave velocity,
which are markers for adverse CV prognosis,47,48
may be increased in veteran ultraendurance athletes.
RV ejection fraction (%)
55
A study of 47 individuals who trained extensively
for and competed in marathons found that pulse 50 P=.050
wave velocity and aortic stiffness were significantly 45,47
higher in the group of marathoners compared with
controls.49 It is possible that the sustained shear 40
stress caused by protracted endurance efforts even-
tually may induce fibrotic changes and decreases in 35
Baseline Post-race Delayed
arterial wall elasticity. Diastolic dysfunction of both
the RV and LV has also been observed in individuals Marathon (3 h) Alpine cycling (8 h)
doing long-term extreme ET and racing.50,51 Endurance triathlon (5.5 h) Ultratriathlon (11 h)
FIGURE 4. Duration-dependent effect of endur-
CORONARY ARTERY CHANGES
ance events on right ventricular (RV) ejection frac-
Veteran endurance marathon runners in one study tion. From Eur Heart J,45 with permission.
had coronary arteries that, at resting baseline, were
similar in size to those of sedentary controls, but the
marathoners had greater coronary artery dilating ca-
pacity.52 Mohlenkamp et al30 studied 108 middle- follow-up the adverse CV event rates in the mara-
aged German long-term marathon runners and thoners were equivalent to those in a population
compared them with matched nonrunner controls. with established CHD.30 In a similar study,
They observed a greater atherosclerotic burden in Schwartz et al53 reported on a US cohort of long-
the marathoners as documented by higher coronary term marathon runners, defined as individuals who
artery calcium (CAC) scores. Additionally, during completed at least 25 marathons over the previous
Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005 591
www.mayoclinicproceedings.orgMAYO CLINIC PROCEEDINGS
PATHOPHYSIOLOGY OF LONG-TERM EXTREME ET
Baseline Post-race
Figure 7 shows the pathophysiology and possible
adverse CV consequences (fibrosis, atrial arrhyth-
mias, VAs, and SCD) associated with endurance
ET and competition, such as marathon running.
Individuals who do long-term ET and race over
End-diastolic 170 150 +9 mL –7 mL very long distances induce sustained (often for 1
volume ±30 mL ±23 mL P=.015 P=.003 to several hours daily) elevations in heart rate,
blood pressure, cardiac output, and cardiac
chamber volumes.9 Heavy and sustained ET gen-
erates large quantities of free radicals55 that likely
outstrip the buffering capacity of the system, leav-
ing these individuals susceptible to oxidative
stress and transient cardiomyocyte dysfunction.45
This repetitive cycle may stimulate immune cells,
including lymphocytes, macrophages, and mast
cells, to secrete cytokines that signal the myofi-
End-systolic 66 +13 mL –5 mL broblasts to proliferate and secrete procollagen,
volume 83 P=.011 which is then cross-linked to form mature colla-
±14 mL PCARDIOVASCULAR EFFECTS OF ENDURANCE EXERCISE
septum.20,29,46,65,66 The patchy myocardial fibrosis
Normal
(fibrillary collagen deposition) that may develop as a
reparative response to damaged myocardium can
favor reentry, which is well established as a substrate
for arrhythmia.29,51
Long-term extreme endurance ET and competi-
tion also stimulate multiple other disruptions, includ-
ing episodic release of excessive catecholamines with
resultant coronary vasoconstriction, chronic elevations
of heart rate, changes in free fatty acid metabolism,
lactic acidosis, and metabolic derangements.41
RISK STRATIFICATION FOR ENDURANCE
ATHLETES
Currently, we have no proven screening methods
for detecting potential CV pathologic changes asso-
ciated with extreme endurance ET. A logical strategy
for now might be to deploy postcompetition cardiac
biomarkers, echocardiography, and/or advanced im- FIGURE 6. Delayed gadolinium enhancement in 5 athletes. Images of 5
aging such as cardiac MRI to identify individuals at risk athletes in whom focal delayed gadolinium enhancement was identified in
for and/or with subclinical adverse structural remodel- the interventricular septum (arrows), compared with a normal study in an
ing and substrate for arrhythmias, but the cost would athlete (top left). From Eur Heart J,45 with permission.
likely be prohibitive.65 Computed tomography for
CAC scoring may be useful, particularly for those older
than 50 years who have been training extensively for
and competing in extreme endurance events. Exercise Extreme exercise efforts
(eg, marathon)
↑
testing generally has not been found to be helpful in
screening extreme endurance athletes, nor has cost- Catecholamine
O2 Demand
effectiveness or clinical yield been found with the other
↑↑↑Preload
↑↑↑ and ↑afterload
testing described earlier.
↑Troponin, ↑CK-MB, ↑BNP
An obligatory pattern of compulsive and exces-
sive daily exercise has been described that may have Immediate effects
↑
adverse long-term mental and physical health con- Chronic training
LV dilatation Right heart strain
sequences.67 A questionnaire developed to identify RA/RV dilatation
LV hypertrophy
obligatory exercisers may be useful for screening ↑LV mass RV hypokinesis
veteran endurance athletes.68 Diastolic dysfunction
CONCLUSION Long-term effects
In some individuals, long-term excessive endurance ET ↑Cardiac chamber sizes
Patchy areas of fibrosis Subacute effects
↑
may cause adverse structural and electrical cardiac re-
↑ Atrial arrhythmias
modeling, including fibrosis and stiffening of the atria, Cardiac fibrosis
↑ Ventricular arrhythmias
RV, and large arteries. This theoretically might provide a ↑ Incidence of SCD
substrate for atrial and ventricular arrhythmias and in-
crease CV risk. Further investigation is warranted to iden-
FIGURE 7. Proposed pathogenesis of cardiomyopathy in endurance ath-
tify the exercise threshold for potential toxicity, screening
letes. BNP ⫽ B-type natriuretic peptide; CK-MB ⫽ creatine kinase MB;
for at-risk individuals, and ideal ET regimens for optimiz-
LV ⫽ left ventricle; RA ⫽ right atrium; RV ⫽ right ventricle; SCD ⫽
ing CV health. For now, on the basis of animal and hu-
sudden cardiac death.
man data, CV benefits of vigorous aerobic ET appear to
accrue in a dose-dependent fashion up to about 1 hour
daily, beyond which further exertion produces diminish-
ing returns and may even cause adverse CV effects in
some individuals.
Consensus Guidelines for Physical Activity and
Public Health from the American Heart Association
Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005 593
www.mayoclinicproceedings.orgMAYO CLINIC PROCEEDINGS
and American College of Sports Medicine call for at 13. Sheppard MN. The fittest person in the morgue? Histopathol-
least 150 minutes per week of moderate ET or 75 ogy. 2012;60(3):381-396.
minutes per week of vigorous ET in the general adult 14. Harris KM, Henry JT, Rohman E, Haas TS, Maron BJ. Sudden
death during the triathlon. JAMA. 2010;303(13):1255-1257.
population.1 Those guidelines also suggest that
15. Harmon KG, Asif IM, Klossner D, Drezner JA. Incidence of
larger doses of ET may be necessary in some groups,
sudden cardiac death in National Collegiate Athletic Associa-
such as those with or at risk for CHD (30 to 60
tion athletes. Circulation. 2011;123(15):1594-1600.
minutes daily), adults trying to prevent the transi- 16. Albano AJ, Thompson PD, Kapur NK. Acute coronary throm-
tion to overweight or obesity (45 to 60 minutes per bosis in Boston marathon runners. N Engl J Med. 2012;366(2):
day), and formerly obese individuals trying to pre- 184-185.
vent weight regain (60 to 90 minutes per day). The 17. Maron BJ, Pelliccia A, Spirito P. Cardiac disease in young
guidelines also caution that high-intensity ET in- trained athletes: insights into methods for distinguishing ath-
creases risk of musculoskeletal injuries and adverse lete’s heart from structural heart disease, with particular em-
CV events.1 phasis on hypertrophic cardiomyopathy. Circulation. 1995;
91(5):1596-1601.
Abbreviations and Acronyms: CAC ⴝ coronary artery 18. Pluim BM, Zwinderman AH, van der Laarse A, van der Wall
calcium; CHD ⴝ coronary heart disease; CV ⴝ cardiovascu- EE. The athlete’s heart: a meta-analysis of cardiac structure and
lar; EF ⴝ ejection fraction; ET ⴝ exercise training; LV ⴝ left function. Circulation. 2000;101(3):336-344.
ventricular; MRI ⴝ magnetic resonance imaging; PA ⴝ phys- 19. Maron BJ, Pelliccia A. The heart of trained athletes: cardiac
ical activity; RA ⴝ right atrium; RV ⴝ right ventricular; remodeling and the risks of sports, including sudden death.
SCD ⴝ sudden cardiac death; VA ⴝ ventricular arrhythmia Circulation. 2006;114(15):1633-1644.
Correspondence: Address to James H. O’Keefe, MD, 4330 20. Spirito P, Pelliccia A, Proschan MA, et al. Morphology of the
Wornall Rd, Ste 2000, Kansas City, MO 64111 (jokeefe@ ”athlete’s heart” assessed by echocardiography in 947 elite ath-
saint-lukes.org). letes representing 27 sports. Am J Cardiol. 1994;74(8):802-806.
21. Pelliccia A, Culasso F, Di Paolo FM, Maron BJ. Physiologic left
ventricular cavity dilatation in elite athletes. Ann Intern Med.
REFERENCES 1999;130(1):23-31.
1. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public 22. Pelliccia A, Maron BJ, Di Paolo FM, et al. Prevalence and clinical
health: updated recommendation for adults from the Ameri- significance of left atrial remodeling in competitive athletes.
can College of Sports Medicine and the American Heart J Am Coll Cardiol. 2005;46(4):690-696.
Association. Circulation. 2007;116(9):1081-1093. 23. Pelliccia A, Maron BJ, Spataro A, Proschan MA, Spirito P. The
2. Sarna S, Sahi T, Koskenvuo M, Kaprio J. Increased life expec- upper limit of physiologic cardiac hypertrophy in highly trained
tancy of world class male athletes. Med Sci Sports Exerc. 1993; elite athletes. N Engl J Med. 1991;324(5):295-301.
25(2):237-244. 24. Benito B, Gay-Jordi G, Serrano-Mollar A, et al. Cardiac arrhyth-
3. Chakravarty EF, Hubert HB, Lingala VB, Fries JF. Reduced mogenic remodeling in a rat model of long-term intensive
disability and mortality among aging runners: a 21-year longi- exercise training. Circulation. 2011;123(1):13-22.
tudinal study. Arch Intern Med. 2008;168(15):1638-1646. 25. Praphatsorna P, Thong-Ngama D, Kulaputanaa O, Klaikaewb
4. Lavie CJ, Thomas RJ, Squires RW, Allison TG, Milani RV. N. Effects of intense exercise on biochemical and histological
Exercise training and cardiac rehabilitation in primary and changes in rat liver and pancreas. Asian Biomedicine. 2010;4(4):
secondary prevention of coronary heart disease. Mayo Clin 619-625.
Proc. 2009;84(4):373-383. 26. Middleton N, Shave R, George K, et al. Altered left ventricular
5. Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical diastolic filling following a marathon is a reproducible phenom-
activity for reduced mortality and extended life expectancy: a enon. Int J Cardiol. 2007;122(1):87-89.
prospective cohort study. Lancet. 2011;378(9798):1244-1253. 27. Patel DA, Lavie CJ, Milani RV, Ventura HO. Left atrial volume
6. O’Keefe JH, Patil HR, Lavie CJ. Exercise and life expectancy. index predictive of mortality independent of left ventricular
Lancet. 2012;379(9818):799; author reply 800-801. geometry in a large clinical cohort with preserved ejection
7. Lee J, Patte R, Lavie CJ, Blair SN. Running and all-cause mortality fraction. Mayo Clin Proc. 2011;86(8):730-737.
risk: is more better? Med Sci Sports Exerc. 2012;44(6):990-994. 28. Maron BJ. Hypertrophic cardiomyopathy and other causes of
8. Michaelides AP, Soulis D, Antoniades C, et al. Exercise dura- sudden cardiac death in young competitive athletes, with con-
tion as a determinant of vascular function and antioxidant siderations for preparticipation screening and criteria for dis-
balance in patients with coronary artery disease. Heart. 2011; qualification. Cardiol Clin. 2007;25(3):399-414, vi.
97(10):832-837. 29. Ector J, Ganame J, van der Merwe N, et al. Reduced right
9. Sharma S, Zaidi A. Exercise-induced arrhythmogenic right ven- ventricular ejection fraction in endurance athletes presenting
tricular cardiomyopathy: fact or fallacy? Eur Heart J. 2012;33(8): with ventricular arrhythmias: a quantitative angiographic as-
938-940. sessment. Eur Heart J. 2007;28(3):345-353.
10. USA Marathoning: 2007 Overview. MarathonGuide.com Web 30. Mohlenkamp S, Lehmann N, Breuckmann F, et al. Running: the
site. http://www.marathonguide.com/features/Articles/2007 risk of coronary events; prevalence and prognostic relevance
RecapOverview.cfm. Accessed January 23, 2012. of coronary atherosclerosis in marathon runners. Eur Heart J.
11. Redelmeier DA, Greenwald JA. Competing risks of mortality 2008;29(15):1903-1910.
with marathons: retrospective analysis. BMJ. 2007;335(7633): 31. Breuckmann F, Mohlenkamp S, Nassenstein K, et al. Myocar-
1275-1277. dial late gadolinium enhancement: prevalence, pattern, and
12. Kim JH, Malhotra R, Chiampas G, et al. Cardiac arrest during prognostic relevance in marathon runners. Radiology. 2009;
long-distance running races. N Engl J Med. 2012;366(2):130-140. 251(1):50-57.
594 Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005
www.mayoclinicproceedings.orgCARDIOVASCULAR EFFECTS OF ENDURANCE EXERCISE
32. Trivax JE, Franklin BA, Goldstein JA, et al. Acute cardiac effects 50. Wilson M, O’Hanlon R, Prasad S, et al. Diverse patterns of
of marathon running. J Appl Physiol. 2010;108(5):1148-1153. myocardial fibrosis in lifelong, veteran endurance athletes.
33. Pelliccia A, Maron BJ, De Luca R, Di Paolo FM, Spataro A, J Appl Physiol. 2011;110(6):1622-1626.
Culasso F. Remodeling of left ventricular hypertrophy in elite 51. Oxborough D, Birch K, Shave R, George K. ”Exercise-induced
athletes after long-term deconditioning. Circulation. 2002; cardiac fatigue”: a review of the echocardiographic literature.
105(8):944-949. Echocardiography. 2010;27(9):1130-1140.
34. Seifi-Skishahr F, Siahkohian M, Nakhostin-Roohi B. Influence of 52. Haskell WL, Sims C, Myll J, Bortz WM, St Goar FG, Alderman
aerobic exercise at high and moderate intensities on lipid EL. Coronary artery size and dilating capacity in ultradistance
peroxidation in untrained men. J Sports Med Phys Fitness. runners. Circulation. 1993;87(4):1076-1082.
2008;48(4):515-521. 53. Schwartz J, Merkel-Kraus S, Duval S. Does elite athleticism
enhance or inhibit coronary artery plaque formation? Paper
35. O’Keefe JH, Vogel R, Lavie CJ, Cordain L. Achieving hunter-
presented at: American College of Cardiology 2010 Scientific
gatherer fitness in the 21(st) century: back to the future. Am J
Sessions; March 16, 2010; Atlanta, GA.
Med. 2010;123(12):1082-1086.
54. Goel R, Majeed F, Vogel R, et al. Exercise-induced hyperten-
36. O’Keefe JH, Vogel R, Lavie CJ, Cordain L. Exercise like a
sion, endothelial dysfunction, and coronary artery disease in a
hunter-gatherer: a prescription for organic physical fitness. Prog
marathon runner. Am J Cardiol. 2007;99(5):743-744.
Cardiovasc Dis. 2011;53(6):471-479.
55. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of
37. Neilan TG, Januzzi JL, Lee-Lewandrowski E, et al. Myocardial
cardiovascular events and all-cause mortality with arterial stiff-
injury and ventricular dysfunction related to training levels
ness: a systematic review and meta-analysis. J Am Coll Cardiol.
among nonelite participants in the Boston marathon. Circula-
2010;55(13):1318-1327.
tion. 2006;114(22):2325-2333.
56. Mont L, Elosua R, Brugada J. Endurance sport practice as a risk
38. Shave R, Baggish A, George K, et al. Exercise-induced cardiac factor for atrial fibrillation and atrial flutter. Europace. 2009;
troponin elevation: evidence, mechanisms, and implications. 11(1):11-17.
J Am Coll Cardiol. 2010;56(3):169-176. 57. Westrol MS, Kapitanyan R, Marques-Baptista A, Merlin MA.
39. Neumayr G, Gaenzer H, Pfister R, et al. Plasma levels of Causes of sudden cardiac arrest in young athletes. Postgrad
cardiac troponin I after prolonged strenuous endurance exer- Med. 2010;122(4):144-157.
cise. Am J Cardiol. 2001;87(3):369-371, A310. 58. Rector RS, Rogers R, Ruebel M, Hinton PS. Participation in
40. Scherr J, Braun S, Schuster T, et al. 72-h kinetics of high- road cycling vs running is associated with lower bone mineral
sensitive troponin T and inflammatory markers after mara- density in men. Metabolism. 2008;57(2):226-232.
thon. Med Sci Sports Exerc. 2011;43(10):1819-1827. 59. Mont L, Sambola A, Brugada J, et al. Long-lasting sport practice
41. McCullough PA, Chinnaiyan KM, Gallagher MJ, et al. Changes and lone atrial fibrillation. Eur Heart J. 2002;23(6):477-482.
in renal markers and acute kidney injury after marathon run- 60. Elosua R, Arquer A, Mont L, et al. Sport practice and the risk
ning. Nephrology. 2011;16(2):194-199. of lone atrial fibrillation: a case-control study [published cor-
42. La Gerche A, Robberecht C, Kuiperi C, et al. Lower than rection appears in Int J Cardiol. 2007;123(1):74]. Int J Cardiol.
expected desmosomal gene mutation prevalence in endur- 2006;108(3):332-337.
ance athletes with complex ventricular arrhythmias of right 61. Molina L, Mont L, Marrugat J, et al. Long-term endurance sport
ventricular origin. Heart. 2010;96(16):1268-1274. practice increases the incidence of lone atrial fibrillation in
43. Harper RW. Exercise-induced troponin elevation: not neces- men: a follow-up study. Europace. 2008;10(5):618-623.
sarily a benign phenomenon. J Am Coll Cardiol. 2010;56(25): 62. Mont L, Tamborero D, Elosua R, et al. Physical activity, height,
2145; author reply 2145-2146. and left atrial size are independent risk factors for lone atrial
fibrillation in middle-aged healthy individuals. Europace. 2008;
44. Nassenstein K, Breuckmann F, Lehmann N, et al. Left ventric-
10(1):15-20.
ular volumes and mass in marathon runners and their associ-
63. Aizer A, Gaziano JM, Cook NR, Manson JE, Buring JE, Albert
ation with cardiovascular risk factors. Int J Cardiovasc Imaging.
CM. Relation of vigorous exercise to risk of atrial fibrillation.
2009;25(1):71-79.
Am J Cardiol. 2009;103(11):1572-1577.
45. La Gerche A, Burns AT, Mooney DJ, et al. Exercise-induced
64. Kirchhof P, Lip GY, Van Gelder IC, et al. Comprehensive risk
right ventricular dysfunction and structural remodelling in en-
reduction in patients with atrial fibrillation: emerging diagnostic
durance athletes. Eur Heart J. 2012;33(8):995-1006.
and therapeutic options—a report from the 3rd Atrial Fibril-
46. Heidbuchel H, Hoogsteen J, Fagard R, et al. High prevalence of
lation Competence NETwork/European Heart Rhythm Asso-
right ventricular involvement in endurance athletes with ven-
ciation consensus conference. Europace. 2012;14(1):8-27.
tricular arrhythmias: role of an electrophysiologic study in risk
65. Biffi A, Pelliccia A, Verdile L, et al. Long-term clinical signifi-
stratification. Eur Heart J. 2003;24(16):1473-1480. cance of frequent and complex ventricular tachyarrhythmias in
47. Agabiti-Rosei E, Mancia G, O’Rourke MF, et al. Central blood trained athletes. J Am Coll Cardiol. 2002;40(3):446-452.
pressure measurements and antihypertensive therapy: a con- 66. Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical rele-
sensus document. Hypertension. 2007;50(1):154-160. vance in atrial fibrillation. J Am Coll Cardiol. 2008;51(8):802-809.
48. Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus 67. Wilson JN, Markey CN, Markey PM. Fitness correlates of
document on arterial stiffness: methodological issues and clin- obligatory versus health motives for exercise: an examination
ical applications. Eur Heart J. 2006;27(21):2588-2605. of men in the military. Psychol Sport Exer. 2012;13(4):371-377.
49. Vlachopoulos C, Kardara D, Anastasakis A, et al. Arterial 68. Griffiths MD, Szabo A, Terry A. The exercise addiction inven-
stiffness and wave reflections in marathon runners. Am J Hy- tory: a quick and easy screening tool for health practitioners.
pertens. 2010;23(9):974-979. Br J Sports Med. 2005;39(6):e30.
Mayo Clin Proc. 䡲 June 2012;87(6):587-595 䡲 http://dx.doi.org/10.1016/j.mayocp.2012.04.005 595
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