Published December 27, 2022

NEJM Evid 2022; 2 (1)

DOI: 10.1056/EVIDra2200175

REVIEW ARTICLE | PHYSICAL ACTIVITY AND EXERCISE SERIES

Can the Heart Get an Overuse Sports Injury?

Paul D. Thompson, M.D.,1,2,3 Thijs M. H. Eijsvogels, Ph.D.,4,5 and Jonathan H. Kim, M.D., M.Sc.6,7

Abstract J. Sawalla Guseh, M.D., and

Aaron Baggish, M.D.,
Recent studies suggest that vigorous endurance exercise increases markers of cardiomyocyte
Series Editors
injury and that lifelong endurance exercise may increase myocardial scarring, coronary
artery atherosclerosis, AF, and aortic dilatation. This review summarizes the evidence link- C. Corey Hardin, M.D., Ph.D.,
ing these conditions with physical exertion and an approach to their management. Editor

Introduction

P
rofessor Jeremy Morris, leader of the London civil servant studies on the benefits
of exercise, called physical activity (PA) “the best buy in public health.”1 This
comment is justified by multiple epidemiologic studies documenting that the
most active individuals experience 40 to 50% fewer cardiovascular disease (CVD) events
compared with their least active counterparts.2 The large public health benefits of increased
PA are a result, in part, of the high prevalence of sedentary lifestyles in developed countries.
Epidemiologic studies demonstrate that the greatest reduction in CVD risk is between the least
and the slightly more active subgroups.2 Additional increases in PA are associated with addi-
tional, but progressively smaller, reductions in risk, and some studies suggest that there is a
flattening2 or a slight increase3 in risk with the highest volumes of PA. Such reports of
increased risk with prodigious amounts of exercise are limited by the paucity of individuals
performing large amounts of PA. Authors of the most recent Physical Activity Guidelines for
Americans emphasized the benefits of small increases in activity.4 These guidelines recom-
mend that Americans “move more and sit less,” perform 150 to 300 minutes of moderate
(i.e., brisk walking) or 75 to 150 minutes of vigorous (i.e., jogging) aerobic exercise weekly, plus
resistance exercise two times per week and some balance training for older individuals.4

Concerns about too much exercise have existed since ancient times. These concerns reap-
peared in Victorian England, when schools and universities for the socially elite started
competing in activities, such as running, cycling, and rowing, sports that had previously The author affiliations are listed at
been work-related competitions among the working class.5 Vigorous exercise in adults can the end of the article.
provoke acute myocardial infarction (AMI) and sudden cardiac death (SCD).6 Exercise-
Dr. Kim can be contacted at
related ST-segment elevation AMI is generally a result of acute coronary thrombosis sec- jonathan.kim@emory.edu or at
ondary to atherosclerotic plaque rupture or erosion, whereas SCD is associated with both Emory Clinical Cardiovascular
acute coronary plaque disruption and/or chronic coronary artery disease (CAD).7 SCDs in Research Institute, Emory
University School of Medicine,
young patients are rarely caused by atherosclerotic CAD and are most frequently a result 1462 Clifton Rd., NE, Suite 502,
of inherited, congenital, and acquired cardiac conditions.6 Recent studies have also suggested Atlanta, GA 30322.

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that prolonged, vigorous aerobic exercise can produce acute
myocyte injury, myocardial scarring, coronary artery calcifi-
cation (CAC), atrial fibrillation (AF), and aortic dilatation.
This review summarizes the evidence linking exercise with
these conditions and briefly suggest an approach to their
management.
Increases in Cardiac Troponin
after Acute Endurance Exercise
The observation that creatine kinase (CK) levels increase
after completion of a 42-km footrace (a marathon) provided
the initial data that suggested that prolonged exercise could
produce cardiomyocyte injury. A study of 15 physicians run-
ning the 1979 Boston Marathon, performed when total CK
was used to diagnose AMI, observed that CK increased
from 161 U/l before the race to 3,424 U/l the day after
the race (nl,100 U/l).8 Subsequent studies using the more
cardiac-specific CK myocardial band (CK-MB) demon-
strated that CK-MB increased from 6.9–6.4 U/l before the
race to 105.3–99.3 IU/l after the race (nl,5 IU/l).9 Gastroc-
nemius muscle biopsy specimens from marathoners con-
tained more than two times the CK-MB concentration of
biopsy specimens from sedentary controls (8.9–1.3% vs.
3.3–0.7%),8 indicating that exercise training increases skel-
etal muscle CK-MB concentration. Satellite cells, which
repair injured skeletal muscle and can produce CK-MB,
were present in runners’ biopsy specimens.10,11 These find-
ings led to the theory that training injures skeletal muscle,
requiring satellite cell repair, which releases CK-MB during
subsequent exercise.10 The possibility of cardiomyocyte
injury was largely dismissed until assays for cardiac tropo-
nin (cTn) became available in 1996 and replaced CK-MB
as the biomarker of myocardial injury.12
Troponin (Tn) is part of the Tn-tropomyosin muscle con-
traction complex. Of the three Tn subunits — C, T, and
I — only T and I have skeletal and cardiac muscle–specific
subunits and are used to diagnose cardiac injury.12 cTnI
increases are more specific for cardiac muscle. In one
report, only 4 of 74 patients with skeletal myopathies had
resting cTnI values greater than the upper limit of normal,
whereas 67 patients had cTnT values greater than the
upper limit of normal.13
More than 200 publications have measured cTn after
exercise and repetitively demonstrated increases in both
cTnT and cTnI. These studies examined a variety of patients
after a variety of endurance exercise events. Levels of
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cTnT and cTnI after prolonged endurance events, such as
marathons, exceeded the diagnostic level for AMI in .50%
of participants.12 One marathon study demonstrated that
all runners had at least some increase in cTnI after the
race14 (Fig. 1). Increases in cTn are highly variable among
individuals as a result of many factors, including age, sex,
training status, health status, and environmental condi-
tions, but exercise intensity and duration are the most
important determinants.12,15,16
The mechanisms producing exercise-related increases in
cTn are not defined.12 Increases in cTnI are likely of cardiac
origin because we are unaware of any studies demonstrating
that training increases skeletal TnI subtype in a manner sim-
ilar to the increase in CK-MB. Tn is present in cardiomyo-
cytes bound to tropomyosin and also freely circulating in
the cytosol. Exercise causes the release of vesicles contain-
ing myokines, likely for intercellular signaling.17 Unbound
cTn or cTn fragments could be released systemically
because of changes in myocardial sarcolemma permeabil-
ity produced by stretch or reversible injury. Irreversible
myocardial cell apoptosis and/or necrosis have also been
postulated but are unlikely, given how commonly cTn
increases after endurance exercise.12
Exercise-related increases in cTn are considered benign,
but resting cTn levels are a cardiac risk marker. A review
identified 21 prospective studies that measured cTn in
64,855 asymptomatic individuals from the general popula-
tion.18 cTn levels greater than the 99th percentile were
found in 5% of the population and were associated with a
threefold increase in total and CVD mortality. Simply
Figure 1. Change in hsTnI Levels.
Data are for 71 participants in the 2011 Boston Marathon from
before to after the race. Each participant is shown as a bar on
the abscissa. hsTnI denotes high-sensitivity cardiac troponin I.
Reprinted with permission from Eijsvogels TM, et al.14
2
having a detectable cTn level was associated with a 30%
increase in CVD mortality, and risk increased progres-
sively with increasing cTn.18
To avoid overdiagnosing AMI, clinicians should know that
endurance events increase cTn, but the long-term implica-
tions of these findings are not clear. cTn levels were greater
than the 99th percentile in 63 of 725 participants (age 54 to
69 years) immediately after walking 30 to 55 km.19 A major
CVD event occurred during follow up in 7% and 27% of par-
ticipants whose postexercise cTn levels were less than or
greater than the 99th percentile, respectively (Fig. 2). Risk
remained higher (hazard ratio, 2.48; 95% confidence inter-
val, 1.29 to 4.78) after adjusting for age, sex, CVD risk fac-
tors, prior disease, and baseline cTnI. These data suggest
that elevated postexercise cTn levels may identify indivi-
duals who are at risk of CVD events, but this was an older
population and not endurance athletes, and such data
require confirmation.
Acute Effects of Endurance
Exercise on the Right Ventricle
Endurance exercise training decreases heart rate (HR)
and increases the size of all four cardiac chambers. This
exercise-induced cardiac remodeling facilitates an increased
stroke volume (SV) to maintain resting cardiac output and
Figure 2. Kaplan–Meier Outcome Plots.
Plots are for 725 participants walking 30 to 55 km with cardiac
troponin I value above (red) or equal to or below (blue) the 99th
percentile before or after the event. Reprinted with permission
from Aengevaeren VL, et al.19
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to augment cardiac output at peak exercise because exercise
training does not increase maximal HR.
Endurance exercise also produces acute cardiac changes.
Echocardiographic studies demonstrate only small acute
reductions in left ventricular (LV) systolic and diastolic
function, but significant reductions in right ventricle (RV)
function after prolonged exercise.15 An early examination
of athletes who completed the Hawaiian Ironman triathlon
observed decreases in LV and left and right atrial sizes
immediately after the event, whereas RV size increased,
suggesting decreased RV contractility.20 RV volumes
returned to prerace values 28 hours after the event. Sub-
sequent studies have confirmed that RV function
decreases more than the LV function after prolonged
exercise,21 and that decreases in RV function may be
inversely correlated with changes in cTnT22 and cTnI.23
The decrease in RV performance grows with the duration
of the exercise event and with the athletes’ maximal oxy-
gen uptake,23 meaning that those with the greatest exer-
cise capacity are most vulnerable to decreases in RV
performance.
The effects of endurance exercise on the RV may be a
result of differences in the vascular response to exercise.21
Pulmonary vascular resistance decreases only 30 to 50%
with exercise because of the pulmonary circulation’s lim-
ited vasodilatory capacity, whereas systemic vascular resis-
tance decreases .75% as a result of vasodilatation of the
exercising muscle.21 The estimated increase in RV wall
stress is approximately 170%, whereas the increase in LV
wall stress is only approximately 23%. Moreover, exercise
training increases systemic vasodilatory capacity, but it has
little effect on pulmonary vascular resistance.21 Exercise
training increases maximal SV and maximal oxygen uptake,
meaning that the best athletes have larger SVs ejected into
in an unchanged pulmonary circulation.
The acute and chronic effects of exercise on the RV are
clinically important in individuals with arrhythmogenic
RV cardiomyopathy. Inherited defects in desmosomal pro-
teins produce this cardiomyopathy, but with great variability
in phenotypic expression among individuals with similar
genetic mutations. Both murine24,25 and clinical studies26,27
of arrhythmogenic RV cardiomyopathy document that high
levels of exercise are associated with earlier disease expres-
sion and more rapid disease progression. Current guidelines
recommend against vigorous exercise in patients with or at
genetic risk for this cardiomyopathy.
3

Myocardial Fibrosis in Athletes
Gadolinium with cardiac magnetic resonance imaging
(cMRI) can identify myocardial scar and fibrosis. Normal
myocardium does not retain gadolinium because of its lin-
ear sarcomeric structure, whereas fibrotic tissue retains gad-
olinium, producing late gadolinium enhancement (LGE).
A meta-analysis of cMRI studies in athletes included 14
studies with 1,342 participants.28 LGE was present in 16.6%
of athletes and 2.3% of control participants (P,0.001). LGE
was located at the insertion point of the RV into the intra-
ventricular septum in 7% of athletes and 0.3% of control
participants (P50.003; Fig. 3). LGE was still more prevalent
in athletes even when those with LGE at RV septal insertion
points were excluded. There was no increase in LGE in
female athletes, but only 119 female athletes and 82 control
participants were included. Unexplained LGE has also been
observed in young athletes. In a study of college athletes
convalesced from coronavirus disease 2019, 60 nonin-
fected control athletes also underwent cMRI and 10 (24%)
demonstrated LGE at RV insertion points.29 LGE was also
more prevalent in athletes younger than 40 years of age
(25.7%) than in those older than 40 years (14.6) in the
meta-analysis.28 The clinical significance of these findings
in young athletes is unknown.
The prevalence of LGE at RV insertion sites in endurance
athletes is consistent with the concept that acute increases
in RV volume and wall stress with exercise contribute to
fibrosis at this site. The clinical relevance of these findings,
however, is uncertain, and more rigorous follow-up studies
are required.30 Clinicians should be aware that asymptom-
atic athletes may have LGE at RV insertion sites. There
are reports of worse outcomes in runners with LGE, but
LGE in these participants was not limited to insertion
points and 40% of runners had LGE patterns that were
typical of CAD scarring.31
CAC in Endurance Athletes
Clarence DeMar won the Boston Marathon seven times
and ran competitively until the age of 69. He died of colon
cancer at age 70. Paul Dudley White, the esteemed Boston
cardiologist, reported DeMar’s autopsy results and noted
that DeMar’s coronary arteries were two to three times

Figure 3. cMRI of a Normal Participant and Five Endurance Athletes.

Cardiac magnetic resonance imaging (cMRI) demonstrates late gadolinium enhancement of the intraventricular septum, often at
insertion points of the right ventricle into the intraventricular septum. Reprinted with permission from La Gerche A, et al.23

NEJM EVIDENCE 4
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normal size, but that the left main showed “a fair degree of
atherosclerosis of the wall, but still with a good lumen.”32
Subsequent reports affirmed the benefits of exercise train-
ing on coronary size33 and vasoreactivity,34 but recent reports
have examined the possibility that life-long exercise train-
ing increases CAC and atherosclerosis. A review of the
association between endurance exercise training and coro-
nary atherosclerosis measured by CAC and computerized
tomographic coronary angiography concluded that CAC
and coronary atherosclerosis are greater in middle-aged
endurance athletes than in control participants and highest
in the most active athletes.35 The athletes’ coronary pla-
ques are more often calcified and less often noncalcified or
mixed, implying a more stable atherosclerotic plaque pro-
file36 (Fig. 4). There are few studies in women, but those
available show no increase in atherosclerosis.
The prognosis of increased plaque in athletes is unclear.
Calcified plaques are considered to be more stable, although
a small study suggests that soft plaque development is
stimulated by prodigious amounts of exercise.37 The Race
Across America is a 140-day foot race in which individuals
run 25.7 miles per day with 1 day of rest each week. Eight of
10 participants completed the race and had computerized
tomographic coronary angiographies performed the day
before and after the race. CAD did not progress in those
without baseline disease, but all participants with baseline
Figure 4. Comparison of Coronary Atherosclerotic
Plaque Characteristics Between Endurance
Athletes and Controls.
Reprinted with permission from Merghani A, et al.36
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CAD had more CAD after the race, predominantly because
of an increase in noncalcified plaque.37
At least one study has examined the prognosis of in-
creased CAC among asymptomatic, active male partici-
pants.38 CAC scores were higher in the most active
participants, but this was not associated with a statistically
significant increased total or CAD mortality. Nevertheless,
the CVD death rate in the most active group was ninefold
higher (1.8 and 0.2 per 1000 person-years) in those with
CAC scores greater than or less than 100 Agatston units,
respectively. This was not statistically significant, possibly
because of the low event rate, but it suggests that the
increased CAC scores are not benign even in highly active
individuals.
The factors responsible for increases in atherosclerosis
and CAC in endurance athletes are uncertain. Acute in-
creases in HR and blood pressure during exercise could
increase arterial shear stress. Prolonged exercise also acutely,
but transiently, increases inflammatory markers.39 Cyclists
seem to have less plaque than do runners, raising the possi-
bility that foot strike–induced changes in arterial hemody-
namics or calcium metabolism contribute to the process.40
Exercise also acutely increases parathyroid hormone levels,41
which could accelerate atherosclerotic calcification but
would not explain the increase in atherosclerosis. The
increased heart size of endurance athletes could increase
the excursion and flexing of the coronary arteries, creating
more turbulent flow and accelerating cholesterol deposition.
Management of athletes with asymptomatic CAC and coro-
nary atherosclerosis is based on consensus recommenda-
tions, but it should include excluding exercise-induced
ischemia and aggressive CAD risk factor management.42
Permitting continued athletic participation in such people is
dependent on the risk associated with an exercise-related
CAD event and shared decision-making with the athlete.
AF
The relationship between PA and AF is complex,43 but it
seems to follow a U-shaped pattern, at least in males,44
meaning that AF decreases with low-to-moderate levels of
PA activity, but is not different or increases with greater
amounts of PA and/or high-intensity exercise. Females, in
contrast, seem to have a reduction in AF risk at all levels
of activity.44 A meta-analysis of studies examining the risk
5
of AF in athletes concluded that AF is increased fivefold in
athletes.45 Another meta-analysis of 19 studies demon-
strated a reduction in AF risk in individuals performing
5 to 20 metabolic-equivalent hours per week of PA com-
pared with less active individuals, but no reduction in AF
risk in individuals performing more than 20 metabolic-
equivalent hours per week.46
AF also increases with exercise performance as shown by
a study in Sweden’s Vasaloppet cross-country ski races.
Clinical outcomes for skiers and matched control partici-
pants were compared using national medical databases.47
Female skiers had less AF than did nonskiers. Male skiers
had higher rates of AF after adjustment for AF risk factors.
AF risk was also higher in men who completed the most
races and had the best performance times (Fig. 5). There
were fewer strokes in both male and female skiers, but
strokes were more frequent in skiers with AF than in skiers
and nonskiers without AF, indicating that AF in athletes is
not benign.
The mechanisms increasing AF in endurance athletes are
not clear. Increased parasympathetic tone from exercise
training and sympathetic tone from acute exercise could
increase AF risk. Inflammation from the acute effects of
exercise is also possible. Exercise performance is an indi-
cator of increased SV, and because AF increased among
the most active and successful athletes, the increased
atrial size that occurs with endurance exercise training
could be a factor. Management of AF in athletes should
follow AF guidelines for the general population.
Aortic Enlargement
Athletic participation has little effect on aortic size in
young athletes. A meta-analysis of studies reporting aortic
size in athletes and control participants found that aortic
size at the sinus of Valsalva and aortic annulus was only
3.2 and 1.6 mm larger in athletes (P50.02 and P50.04),
respectively, but even these small changes may have long-
term significance.48
Computed tomography imaging comparing the size of the
midascending aorta in former professional American foot-
ball players and control participants (mean age, 57.1 and
53.6 years, respectively) found that aortic size was larger
in former players (38–5 mm vs. 34–4 mm; P,0.001).49
More players had aortic diameters .40 mm, the 99th
percentile (29.6% vs. 8.6%; P,0.0001); however, this
enlargement may not be related to the sport, but to other
factors including hypertension, which is prevalent among
active American football players.50 An echocardiographic
study of mostly retired Australian rugby players (mean
age, 45–13 years) documented that 41% had an aortic
diameter .40 mm and 58% had anterior effacement of
the aortic sinotubular junction, an indicator of abnormal
aortic enlargement.51 Aortic dilatation was associated with
the length of the player’s career, whereas effacement was
more common in elite players.
These studies examined participants in sports whose
training and competition primarily require resistance

Figure 5. Risk of Atrial Fibrillation in Male and Female Competitors in the Vasaloppet Country Ski Races.
Reprinted with permission from Svedberg N, et al.47

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exercise, which acutely increases systolic blood pres-
sure. An echocardiographic study of 442 rowers and
runners aged 61–6 years found that 31% of men and 6%
of women had aortic dimensions .40 mm.52 Increased
aortic size was found more frequently in elite athletes.
Aortic size also increased with years of exercise
training.
The clinical significance of these observations is unknown.
Superior athletic performance was directly associated with
the magnitude of the aortic increase, again raising the pos-
sibility that the amount of exercise training or the in-
creased SV required to achieve elite performance contributes
to the aortic enlargement. Management of aortic enlarge-
ment in athletes should follow guidelines developed for
the general population.
Conclusion
Increasing amounts of PA and exercise are associated with
reduced cardiovascular morbidity and mortality. There is
increasing evidence, however, that endurance exercise
acutely increases markers of myocardial injury and acutely
decreases RV function. Chronic exercise training is also
associated with mild myocardial fibrosis, increased coro-
nary atherosclerosis and CAC, increased incidence of AF,
and increased aortic size. The clinical significance of these
possible effects of large amounts of exercise training are
uncertain but provide an opportunity for additional investiga-
tion of the long-term health effects of high-volume exercise
training. Clinicians should be aware of these possible
exercise-induced training effects to provide appropriate
reassurance and management to middle-aged athletes with
these abnormalities.
Disclosures
Author disclosures are available at evidence.nejm.org.
Author Affiliations
1 DOI: 10.1152/jappl.1985.59.1.149.
Hartford Hospital, Hartford, CT
2 12. Aengevaeren VL, Baggish AL, Chung EH, et al. Exercise-induced cardiac
University of Connecticut, Farmington, CT
3
Massachusetts General Hospital, Boston
4
Radboud Institute for Health Sciences, Department of Physiology,
Nijmegen, the Netherlands
5
Radboud University Medical Center, Nijmegen, the Netherlands
6
Emory University School of Medicine, Atlanta
7
Emory Clinical Cardiovascular Research Institute, Atlanta
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