Acute cardiac effects of marathon running

Justin E. Trivax, Barry A. Franklin, James A. Goldstein, Kavitha M. Chinnaiyan,

Michael J. Gallagher, Adam T. deJong, James M. Colar, David E. Haines and
Peter A. McCullough
J Appl Physiol 108:1148-1153, 2010. First published 11 February 2010;
doi:10.1152/japplphysiol.01151.2009

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J Appl Physiol 108: 11481153, 2010.
First published February 11, 2010; doi:10.1152/japplphysiol.01151.2009.
Acute cardiac effects of marathon running
Justin E. Trivax, Barry A. Franklin, James A. Goldstein, Kavitha M. Chinnaiyan, Michael J. Gallagher,
Adam T. deJong, James M. Colar, David E. Haines, and Peter A. McCullough
Department of Cardiovascular Medicine, William Beaumont Hospital, Royal Oak, Michigan
Submitted 8 October 2009; accepted in final form 8 February 2010
Trivax JE, Franklin BA, Goldstein JA, Chinnaiyan KM,
Gallagher MJ, deJong AT, Colar JM, Haines DE, McCullough
PA. Acute cardiac effects of marathon running. J Appl Physiol
108: 1148 1153, 2010. First published February 11, 2010;
doi:10.1152/japplphysiol.01151.2009.We sought to clarify the
significance of cardiac dysfunction and to assess its relationship with
elevated biomarkers by using cardiovascular magnetic resonance
imaging in healthy, middle-aged subjects immediately after they ran
26.2 miles. Cardiac dysfunction and elevated blood markers of myo-
cardial injury have been reported after prolonged strenuous exercise.
From 425 volunteers, 13 women and 12 men were randomly selected,
provided medical and training history, and underwent baseline car-
diopulmonary exercise testing to exhaustion. Blood biomarkers, car-
diovascular magnetic resonance imaging, and 24-h ambulatory elec-
trocardiography were performed 4 wk before and immediately after
the race. Participants were 38.7 9.0 yr old, had baseline peak
oxygen consumption of 52.9 5.6 mlkg1min1, and completed
the marathon in 256.2 43.5 min. Cardiac troponin I and B-type
natriuretic peptide increased following the race (P 0.001 and P
0.0001, respectively). Cardiovascular magnetic resonance-determined
pre- and postmarathon left ventricular ejection fractions were compa-
rable, 57.7 4.1% and 58.7 4.3%, respectively (P 0.32). Right
atrial volume index increased from 46.7 14.4 to 57.0 14.5 ml/m2
(P 0.0001). Similarly, right ventricular end-systolic volume index
increased from 47.4 11.2 to 57.0 14.6 ml/m2 (P 0.0001)
whereas the right ventricular ejection fraction dropped from 53.6
7.1 to 45.5 8.5% (P 0.0001). There were no morphological
changes observed in the left atrium or ventricle or evidence of
ischemic injury to any chamber by late gadolinium enhancement.
There were no significant arrhythmias. Marathon running causes
dilation of the right atrium and right ventricle, reduction of right
ventricular ejection fraction, and release of cardiac troponin I and
B-type natriuretic peptide but does not appear to result in ischemic
injury to any chamber.
prolonged strenuous exercise; gadolinium enhancement; biomarkers;
right ventricular dysfunction
MARATHON RUNNING has increased in popularity over the last
three decades with participation in the United States rising
from 25,000 runners in 1976 to nearly 470,000 in 2008 (36). It
is estimated that six to eight marathon runners will die while
running each year in the United States due to the combination
of occult cardiac disease and superimposed physical and/or
environmental stresses (36). In 2009, six runners died in the
United States while participating in half-marathons, with three
of the six dying in the same event (36).
Increased cardiorespiratory fitness and regular exercise are
associated with reduced all-cause and cardiovascular mortality
(11, 15, 27, 28). However, prolonged exercise has been re-
ported to have adverse cardiovascular consequences. Douglas
Address for reprint requests and other correspondence: J. E. Trivax, Dept. of
Cardiovascular Medicine, William Beaumont Hospital, 3601 W. 13 Mile Rd.,
Royal Oak, MI 48073 (e-mail: jtrivax@beaumont.edu).
1148 8750-7587/10 $8.00 Copyright 2010 the American Physiological Society
et al. (6) first described abnormalities in left ventricular (LV)
systolic and diastolic function after an ultraendurance race that
included a 2.4-mile swim, 112-mile bike ride, and 26.2-mile
run. Numerous subsequent studies have shown that endurance
exercise evokes abnormal cardiac biomarkers in both elite and
recreational athletes, including elevations in creatine kinase
(CK), creatine kinase MB isoenzyme, troponin, and B-type
natriuretic peptide (BNP) (31). Echocardiographically deter-
mined acute and chronic right ventricular (RV) dysfunction has
been reported in endurance athletes (30), which are associated
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with ventricular arrhythmias (9). The shortcomings of echo-
cardiography include limited fields-of-view and effect of load-
ing conditions on Doppler measurements. Cardiovascular mag-
netic resonance (CMR) imaging has superior capabilities in the
evaluation of chamber morphology, function, edema, tissue
perfusion, dynamic myocardial contraction, and cardiac blood
flow. Moreover, the superb spatial resolution allows for CMR
to provide the most accurate evaluation of the RV; thus it is
considered the gold standard imaging modality for chamber
size and function. Recently, CMR was performed in 14 par-
ticipants within 3 days of running in a marathon (26). RV
systolic dysfunction occurred in all runners without evidence
of late gadolinium enhancement (LGE). In our study, we aimed
to describe the immediate cardiac biomarker and structural
effects of marathon running.
MATERIALS AND METHODS
Subjects. All enrollees in the 2008 Detroit Free Press/Flagstar
Marathon received an e-mail communication after registering for the
race that described the study and invited their participation. Responses
were received from 428 individuals; after verifying age (18 yr old)
and the absence of signs, symptoms, or medical history of heart
disease, including coronary artery disease (CAD) or structural heart
disease, 25 were randomly selected (concealed in opaque, sealed
envelopes) to participate. Additional exclusion criteria included preg-
nancy and allergy to gadolinium. Written informed consent was
obtained from all participants. The study protocol was approved by
the Human Investigation Committee at William Beaumont Hospital in
Royal Oak, Michigan.
Measurements. One to four weeks before the marathon, during the
tapering phase of training, participants provided a detailed medical
and training history and blood samples. Cardiac troponin I and BNP
(normal range 0 100 pg/ml) were measured using chemilumines-
cence immunoassays (Bayer Diagnostics, Tarrytown, NY). For car-
diac troponin I, the manufacturer reports the minimum detected
concentration 0.03 ng/ml, normal ranges 0.06 ng/ml, indeterminate
range 0.06 1.19 ng/ml, and suggestive of myocardial infarction 1.2
ng/ml. All subjects underwent 24-h ambulatory electrocardiography
(eCardio Diagnostics, Mortara Instrument, Milwaukee, WI) and peak
or symptom-limited cardiopulmonary exercise testing, where heart
rate and blood pressure were measured at rest, during each 3-min
stage of exercise utilizing the Bruce treadmill protocol (4), and
throughout a 6-min recovery. The electrocardiogram was monitored
continuously throughout exercise and recovery and with recordings at
http://www.jap.org
 CARDIAC EFFECTS OF MARATHON RUNNING
the end of each stage and at peak exercise. Metabolic data were
obtained using Medical Graphics CPX/D Systems (Medical Graphics,
Minneapolis, MN) with breath-by-breath analysis via a pneumota-
chometer and online 15-s calculations of oxygen consumption [VO2;
mlkg1min1 or metabolic equivalents (METs; 1 MET 3.5
mlkg1min1)], minute ventilation, carbon dioxide production
(VCO2), and respiratory exchange ratio (VCO2/VO2) were calculated.
At the finish line, runners provided a blood sample, and a 24-h
ambulatory electrocardiography monitor was reapplied. Participants
were instructed to follow their usual postrace hydration and nutrition
practices. The goal was for each participant to undergo repeat CMR
with LGE techniques within 7 h of completing the race, expecting
variation in finishers running times and logistical challenges of trans-
porting runners from the finish line 15 miles to William Beaumont
Hospital. Twenty-four hours later, each participant provided another
blood specimen.
Magnetic resonance imaging. Cardiac magnetic resonance imaging
was performed using a 1.5-T whole body magnetic resonance imaging
scanner (Sonata, Siemens Medical Solutions, Erlangen, Germany)
before and after the marathon. Cine bright-blood images in the
four-chamber, left-sided two-chamber, right-sided two chamber, and
1149
that were not normally distributed. Pearson correlations were used to
evaluate bivariate relationships. A P value 0.05 was considered
statistically significant.
RESULTS
Baseline parameters. A total of 25 runners, 13 women and
12 men, averaging 38.7 9.0 yr of age (range 2358 yr)
participated in the study. Baseline characteristics are reported
in Table 1. The average body mass index was 23.0 2.6
kg/m2. The mean training mileage over the previous 5 years
and over the previous 6 mo was 17.0 11.8 and 30.2 11.4
miles/wk, respectively. Of the 25 subjects, 7 were participating
in their first marathon and an additional 7 were participating in
their second. The remaining 11 runners had participated in
three or more previous marathons. The mean marathon finish-
ing time was 256.2 43.5 min, corresponding to an average
pace of 9.8 1.7 min per mile. The temperature at the start of
the marathon was 33F (1C).
Ambulatory electrocardiography and cardiopulmonary ex-

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three-chamber planes were performed using a breath-hold balanced ercise testing. Ambulatory electrocardiography was performed
steady-state free precession sequence (true fast imaging with steady- in 24 participants for 20.5 4.2 h at baseline; 22 underwent a
state precession; repetition time 70 ms, echo time 1.2 ms, flip angle second recording for 21.5 3.5 h after the marathon. The
70, slice thickness 6 mm, matrix size 256 126). After the initial underlying baseline rhythm was sinus with minimum, average,
two- and four-chamber cine images were obtained, first past-perfusion
and maximum heart rates of 44.7 6.0, 71.5 10.3, and
imaging was performed. Gadolinium diethylenetriamine penta-acetic
acid (Omniscan, GE Healthcare, Chalfont St. Giles, UK) 0.15 126.2 20.4 beats/min, respectively. Similarly, after the race,
mmol/kg was injected at a rate of 4 ml/s. Multiple images (3 short axis sinus rhythm predominated with minimum, average, and max-
and 1 long axis) were acquired during a single cardiac cycle (turbo- imum heart rates of 46.8 6.5, 72.1 7.6, and 120.9 11.2
flash saturation recovery sequencing; inversion time 100 ms, repeti- beats/min, respectively. Premature atrial complexes were rare,
tion time 172 ms, echo time 1.3 ms, flip angle 72, slice thickness 8 with 0.2 0.2 per hour premarathon and 0.3 0.6 per hour
mm, matrix size 192 86). Cine steady-state free precession short-
axis images then encompassed the entire RV and LV from the base to
Table 1. Baseline characteristics of the study
the apex (stack of multiple sequential short-axis slices; repetition time
80 ms, echo time 1.2 ms, flip angle 70, slice thickness 8 mm, slice group (n 25)
gap 2 mm, matrix size 256 138) to obtain the RV and LV ejection Group Characteristics
fractions. LGE images were obtained after a minimum of 15 min after
the gadolinium injection using an inversion recovery fast low-angle Demographics
shot technique. Images were acquired sequentially in the short axis, Age, yr 38.7 9.0
followed by horizontal and vertical long-axis images (inversion time Male 12 (48%)
260 300 ms, repetition time 750 ms, echo time 4.3 ms, slice thickness Body mass index, kg/m2 23.0 2.6
8 mm, slice gap 2 mm, matrix 256 199). Quantitative analysis was Height, cm 172.5 0.1
performed using dedicated computer software (ARGUS; Siemens Weight, kg 68.9 13.7
Medical Solutions). Electrocardiographically gated techniques and Hypertension 1 (4%)
Diabetes mellitus 0 (0%)
standard inversion recovery cine images were obtained in short-axis
Prior smoking 1 (4%)
slices as well as three long axes: horizontal long axis, vertical long LDL cholesterol, mg/dl 104.2 25.0
axis, and the three-chamber view. End-diastolic short axis images HDL cholesterol, mg/dl 72.4 18.9
with epicardial and endocardial contours were drawn for the LV, and Average training mileage, miles/wk over previous 5 yr 17.0 11.8
endocardial contours were drawn for the RV. Left and right ventric- Number prior marathons 2.3 3.0
ular end-systolic and end-diastolic volumes and LV mass were cal-
Cardiopulmonary stress testing results
culated. Right atrial (RA) volume was calculated using the biplane
area-length method. All measurements were made by two physicians Baseline heart rate, beats/min 64.3 9.1
trained in level III CMR (KC, MG), blinded to the subjects clinical Baseline systolic BP, mmHg 121.5 18.6
information and subsequent analysis. Baseline diastolic BP, mmHg 76.2 12.1
Peak HR, beats/min 178.0 9.8
Statistical analysis. The primary endpoint was the change in
Percent predicted maximum HR, % 98.0 4.1
cardiac chamber volumes indexed to body surface area calculated Peak systolic BP, mmHg 192.8 22.8
from the prerace weight and height. With a sample size of 25, which Peak diastolic BP, mmHg 78.1 9.9
was the largest feasible number of individuals who could undergo VO2, l/min 3,690.8 838.0
CMR scanning within the time window after the race, the observed VCO2, l/min 3,970.6 984.9
power for detecting changes in any one of the cardiac chambers was VE, l/min 110.5 28.2
99% using the paired t-test, 0.01, two-tailed, and assumed SE RER 1.10 0.10
1.90 (derived from RA volume index mean 45 15 ml/m2 assuming % with RER 1.10 52.0%
the correlation between pre- and postmeasures was 0.80 or greater). Values are means SD. BP, blood pressure; HDL, high-density lipoprotein;
Univariate statistics were reported with means SD or counts with HR, heart rate; LDL, low-density lipoprotein; RER, respiratory exchange ratio;
proportions as appropriate. Comparisons were made using the paired VE, minute ventilation; VCO2, carbon dioxide production; VO2, oxygen con-
two-sample t-test or the paired Wilcoxon rank sum test for variables sumption.

J Appl Physiol VOL 108 MAY 2010 www.jap.org

1150 CARDIAC EFFECTS OF MARATHON RUNNING

Table 2. Biochemical data at baseline, immediately after the marathon, and 24 h later
Variable Baseline Immediately Postmarathon 24 h Postmarathon Greatest Change in Value P Value

BNP, pg/ml 15.3 11.3 18.7 15.8 44.8 31.2 28.5 35.6 0.0001
BUN, mg/dl 15.6 3.1 24.0 4.8 17.0 3.3 8.4 5.1 0.0001
Serum creatinine, mg/dl 0.9 0.1 1.2 0.2 0.8 0.1 0.3 0.2 0.0001
Serum sodium, meq/l 140.9 3.4 141.3 3.3 141.2 2.2 0.4 4.3 0.69
Serum potassium, meq/l 4.3 0.2 5.5 0.6 4.3 0.4 1.3 0.6 0.0001
Blood glucose, mg/dl 91.9 11.7 108.9 26.9 91.3 16.7 17.0 24.5 0.004
CK, U/l 186.4 132.7 675.3 497.7 1,984.8 2,031.0 1,802.0 1,976.1 0.0001
CK-MB, U/l 2.6 1.6 10.1 5.1 16.4 9.8 13.8 9.6 0.0001
Cardiac troponin I, ng/ml 0.03 0.003 0.2 0.3 0.1 0.2 0.2 0.3 0.001
Aldolase, U/l 5.9 1.7 15.2 5.0 13.4 7.5 9.3 4.8 0.0001
Values are means SD. BNP, B-type natriuretic peptide; BUN, blood urea nitrogen; CK, creatine kinase; CK-MB, creatine kinase MB isoenzyme.

postmarathon. Three participants experienced runs of su-
praventricular tachycardia [2 persons with 3 runs (heart rate
during salvos 100, 151 beats/min), 1 participant with 6 runs
(peak heart rate during salvos 152 beats/min)]. The longest
nitrogen and serum creatinine both increased significantly with
baseline and peak values of 15.6 3.1 to 24.0 4.8 mg/dl and
0.9 0.1 to 1.2 0.2 mg/dl, respectively (P 0.0001), for
each pairwise comparison. Finally, there was a rise in potas-
sium levels immediately after crossing the finish line, 4.3 0.2

Downloaded from jap.physiology.org on September 30, 2011

run of supraventricular tachycardia was 11 beats. Premature
ventricular complexes were also sparsely recorded with 0.1
0.3 and 0.1 0.1 per hour before and after the race. No
ventricular arrhythmias were noted after the marathon.
Detailed results from baseline exercise testing are reported
in Table 1. The average duration of exercise was 15.5 2.0
min on a standard Bruce protocol. The highest achieved heart
rate averaged 178.0 9.8 beats/min, corresponding to 98% of
the age-predicted maximum value. Peak systolic and diastolic
blood pressures were 192.8 22.8 mmHg and 78.1 9.9
mmHg, respectively. The mean maximal oxygen consumption
and minute ventilation were 52.9 5.6 mlkg1min1 (15.2 1.6
METs) and 110.5 28.2 l/min. There were no signs or
symptoms of myocardial ischemia or significant exercise-in-
duced arrhythmias observed.
Laboratory data. Laboratory data are shown in Table 2.
There was a significant rise in cardiac troponin I from baseline
levels to levels immediately after the race (0.03 0.003 to
0.20 0.30 ng/ml), P 0.001. Serial changes in cardiac
troponin I for each participant are displayed in Fig. 1. Creatine
kinase and CK-MB isoenzyme increased from baseline values
of 186.4 132.7 and 2.6 1.6 U/l, respectively, to 1,984.8
2,031.0 and 16.4 9.8 U/l (P 0.0001 for each paired
comparison). Serum aldolase also increased from 5.9 1.7 to
15.2 5.0 U/l immediately after the race (P 0.0001). BNP
more than doubled from mean baseline to peak values (15.3
11.3 to 44.8 31.2 pg/ml) (P 0.0001). Serial changes in
BNP for each participant are shown in Fig. 1. Blood urea
to 5.5 0.6 meq/l (P 0.0001).
CMR imaging. The postmarathon CMR was performed an
average of 242.5 97.4 (range 50 to 421) min after crossing
the finish line in 24 participants. One additional participant was
imaged 24.5 h after completing the race and included in the
final data set. The imaging findings are summarized in Table 3.
Premarathon LV ejection fraction, end-diastolic volume index,
end-systolic volume index, and stroke volume CMR were 57.7
4.1%, 79.1 13.7 ml/m2, 33.5 6.7 ml/m2, and 83.2 22.2
ml, respectively. The mean LV mass index was 63.8 14.4
g/m2. Six subjects (4 men, 2 women) had LV mass above the
normal range by CMR (1). No significant differences between
the pre- and post-CMRs were seen regarding LV ejection
fraction or volumes. Overall, resting cardiac output, which is
dependent on the heart rate, increased after the marathon (6.3 1.7
vs. 5.4 1.8 l/min premarathon). The baseline left atrial
volume index was elevated 48.0 9.4 ml/m2 at baseline and
remained unchanged after the race. RV ejection fraction de-
creased from 53.6 7.1% to 45.5 8.5% (P 0.0001) (Fig. 2),
signifying a 510% reduction in 7 subjects (28%) and 10%
in 10 (40%). RV end-systolic volume index also increased
significantly from 47.4 11.2 to 57.0 14.5 ml/m2, repre-
senting a relative increase of 16.8% (P 0.0001) (Fig. 2). RA
volume index increased significantly after the marathon from
46.7 14.4 to 57.0 14.5 ml/m2 with a relative change in
volume index of 18.1% (P 0.0001). No LGE was detected in
any chamber.

Fig. 1. Cardiac biomarkers at baseline, peak

(immediately after crossing the finish line),
and recovery (24 h after marathon). A: cardiac
troponin I values for each participant. B: B-
type natriuretic peptide values for each partic-
ipant.

J Appl Physiol VOL 108 MAY 2010 www.jap.org

 CARDIAC EFFECTS OF MARATHON RUNNING
Table 3. Cardiovascular magnetic resonance imaging data before and after marathon
Variable Baseline
LVEF, % 57.7 4.1
LVEDV index, ml/m2 79.1 13.7
LVESV index, ml/m2 33.5 6.7
LA volume index, ml/m2 48.0 9.4
RVEF, % 53.6 7.1
RVEDV index, ml/m2 101.7 17.8
RVESV index, ml/m2 47.4 11.2
RA volume index, ml/m2 46.7 14.4
Values are means SD. LA, left atrium; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular
end-systolic volume; RA, right atrium; RVEDV, right ventricular end-diastolic volume; RVEF, right ventricular ejection fraction; RVESV, right ventricular
end-systolic volume.
The Pearson correlation between baseline cardiorespiratory
fitness [maximal oxygen consumption (VO2 max)] and reduction
in RV ejection fraction was r 0.35, P 0.09. The correla-
tions between VO2 max and change in cardiac troponin I and
BNP were r 0.04, P 0.87, and r 0.07, P 0.73,
respectively. Stepwise multiple regression was performed to
evaluate absolute and percent change in RA volume index and
absolute and percent change in RV end-systolic volume index.
There were no statistically significant variables for changes in
these outcomes, including VO2 max, metabolic equivalents
achieved during premarathon stress testing, percent increase in
troponin (baseline to peak), percent increase in BNP (baseline
to recovery), number of marathons completed, finishing time of
marathon, the time interval from crossing finishing line to
CMR imaging, or any other baseline variable.
DISCUSSION
In this study, two-thirds of healthy, well-trained runners had
evidence of right heart dysfunction with significant dilation of
the RA and RV and hypokinesis of the RV immediately after
completing a marathon irrespective of age, sex, cardiorespira-
tory fitness, or previous marathon experience. In addition, most
subjects demonstrated a significant reduction in RV ejection
fraction and biochemical evidence of cardiac myonecrosis,
including a transient, small rise in cardiac troponin I that did
not follow the excursion or time course consistent with acute
myocardial infarction (21). Moreover, there was no evidence of
LGE in any chamber to suggest myocardial infarction nor any
significant arrhythmias observed.
To date, our study is the first to comprehensively evaluate
the acute cardiovascular effects of marathon running using
multiple diagnostic modalities: premarathon cardiopulmonary
J Appl Physiol VOL
1151
Postmarathon Change in Value P Value
58.7 4.3 1.0 4.9 0.32
78.8 11.5 0.3 1.7 0.88
32.6 6.0 0.9 1.0 0.36
49.8 9.8 1.8 10.2 0.38
45.5 8.5 8.1 7.5 0.0001
104.2 19.7 2.5 14.3 0.40
57.0 14.5 9.6 11.3 0.0001
57.0 14.5 10.3 11.3 0.0001
exercise stress testing, blood biomarkers, ambulatory electro-
cardiography, and CMR. Our data support the smaller (n 14)
study by Mousavi and colleagues (26) who also found right-
sided chamber dilatation but no LV LGE by MRI in runners
after a marathon. Recently, Wilson and colleagues (34) dem-
Downloaded from jap.physiology.org on September 30, 2011
onstrated changes in LV diastolic function by MRI that did not
correlate with blood biomarkers (troponin I, NH2-terminal
pro-B-type natriuretic peptide) after marathon running. How-
ever, this group did not evaluate changes in right-sided cham-
ber function (34). Using echocardiography, Douglas et al. (7)
evaluated 41 Ironman triathletes before the event, immediately
after the race, and 12 days later and reported significant,
transient RV dilation. Neilan and associates (30) evaluated 60
nonelite marathon runners using similar methodology during
consecutive Boston Marathons (2004 and 2005) and docu-
mented transient increases in echocardiographically estimated
pulmonary artery pressure, RV dilation, and RV dysfunction.
La Gerche et al. (20) studied 27 athletes participating in the
2004 Australian Ironman and found ephemeral impairment in
RV function, signified by postrace reductions in RV fractional
area. Thus our data are consistent with prior studies in the
finding that approximately one-third of marathon runners ex-
perience transient dilation of the RA, RV, and a reduction in
RV ejection fraction.
The findings in our study of right heart overload and a
modest rise in biomarkers can be explained by both increased
preload and afterload. Contrary to previous reports that stroke
volume plateaus during exercise at 40% of VO2 max, recent
studies have shown that in endurance athletes, stroke volume
increases to 75% of VO2 max secondary to enhanced diastolic
filling and ventricular emptying (12, 18, 32). While increased
stroke volume is an effective means to increase cardiac output,
Fig. 2. Changes in right ventricular ejection
fraction and right heart volumes before and
after the marathon. A: mean change in right
ventricular fraction. B: mean change in right
heart volumes before and after the marathon.
RA, right atrium; RVESV, right ventricular
end-systolic volume.
108 MAY 2010 www.jap.org
1152 CARDIAC EFFECTS OF MARATHON RUNNING
the RV may be overwhelmed with excessive, prolonged vol-
ume overload resulting in RV dysfunction. In addition, with
prolonged strenuous exercise, pulmonary artery pressures may
increase by as much as 70% over baseline values and likely
remain elevated throughout a marathon (2, 7). The RV re-
sponds differently to prolonged strenuous exercise than the
LV, with increased RV dimensions and greater dependence on
atrial systole. RV work load increases 3.6- to 5.2-fold, whereas
the same exercise results in a 2.1- to 2.8-fold increase in the LV
work load (7, 13). Thus the RV is differentially overworked
compared with the LV and is susceptible to fatigue and
exhaustion in the setting of marathon running and probably
other comparable aerobic endurance challenges.
Cardiac magnetic resonance imaging allowed us to explore
ischemia and microinfarction as a possible mechanism by
which the RA and RV sustain transient injury. Prior studies
have established that CMR cannot only identify large, trans-
mural infarctions with characteristic findings of LGE and
microvascular obstruction, but also smaller, subendocardial
infarctions with a high specificity at 24 or more hours after the
event (33, 35). Moreover, CMR techniques using LGE can
diagnose RV infarction with good interobserver reliability,
high sensitivity (19), and high negative predictive value (5).
Our findings suggest that RA or RV ischemia and or infarction
is not the mechanism of injury. We found an absence of LGE
in all subjects, effectively ruling out infarction of myocardial
tissue as an explanation for the changes in cardiac imaging and
blood biomarkers seen in our data and prior studies (6, 7, 20,
29, 31). We believe the sustained increase in cardiac output
over 4 h leads to increases in RA and RV wall tension, and,
in susceptible individuals, dilation of those chambers second-
ary to myocyte changes and possibly due to slippage of
myocytes within cardiac tissue. Loss of integrity of the inter-
cellular junctions may lead to chronic changes in activity of
pericytes and myofibroblasts that participate in cardiac fibrosis.
Recently, Brueckmann and colleagues (3) demonstrated
chronic patterns of LV LGE in 12 and 4% of male marathon
runners and normal controls, respectively, some of which were
clearly not related to CAD or prior infarction. These data, in
aggregate, suggest that repetitive transient chamber dilatation
with extreme exhaustion may lead to cardiac fibrosis and thus
be the etiology of nonischemic sudden arrhythmic death in
marathon runners (3).
Our observations provide additional clarity on the issue of
training effect. In two prior studies, exercise-induced RV
changes were inversely related to self-reported training mile-
age and marathon experience (10, 29). Neither study measured
baseline cardiorespiratory fitness. We found that measured
baseline cardiorespiratory fitness, i.e., peak VO2 (and training
mileage), was not related to the frequency or severity of
right-sided chamber dilatation nor elevation of cardiac biomar-
kers. Thus we believe that inherent susceptibility to chamber
dilatation and biomarker release is a more plausible explana-
tion for our findings than variation in adaptive fitness.
Our postrace period of cardiac monitoring did not demon-
strate an increase in any form of arrhythmia. However, we
acknowledge this observation cannot be applied to possible
arrhythmias that occurred during the race itself. Right-sided
chamber enlargement and dysfunction after prolonged endur-
ance exercise may be the substrate for arrhythmias (9, 16, 17,
24). In a longitudinal prospective study, the incidence of atrial
J Appl Physiol VOL
fibrillation was 5.3% in endurance athletes vs. 0.9% among
control subjects (17). In addition, in a 10-yr follow-up of
participants in the Barcelona Marathon, runners were found to
have a fourfold increased incidence of atrial fibrillation when
compared with sedentary healthy individuals (24). The sug-
gested substrates for atrial arrhythmias in endurance athletes
include pressure and volume overload, atrial stretch, and myo-
cyte alterations from repetitive atrial dilation, inflammation,
and fibrosis (25). Despite our demonstration of postexercise
RA and RV dilation substantiating these earlier investigations,
no significant arrhythmias were observed in our cohort.
We recognize several limitations to this small observational
study, including the lack of a control group. The temporal
relationships to the race suggest it was the marathon effort
itself that induced the evidence of myocardial dysfunction and
elevation in cardiac biomarkers that we observed. We recog-
nize that marathon runners are very different from healthy
controls, and both biomarkers and CMR findings in part may
have reflected long-term changes in skeletal and myocyte
Downloaded from jap.physiology.org on September 30, 2011
adaptive changes (e.g., relatively larger CK-MB fractions). We
did not measure right-sided pressures and could not evaluate
pressure overload as a possible mechanism. Echocardiography
was not performed on our subjects and we therefore do not
have measures of diastolic function. Cardiac magnetic reso-
nance imaging has not been validated in the assessment of
diastolic dysfunction. In addition, while we have indirect
measurement of postmarathon dehydration with measurement
of blood urea nitrogen and serum creatinine, we do not have
indirect measure of plasma volume loss, measurements of body
weight, or postrace hydration or nutrition. We did not adjust for
the time range during which the postrace CMR was performed,
nor did we perform serial postrace CMR to identify the time
course of resolution of chamber dilatation. While we did not
present long-term follow-up data for either variable, several
studies have shown the exercise-induced cardiac dysfunction to
be transient with systolic and diastolic abnormalities resolving
within 48 h and 1 mo, respectively (8, 30). Finally, our results
cannot be extrapolated to individuals participating in shorter or
longer distance races or nonrunning events.
Marathon running causes acute dilation of the RA and RV,
reduces RV ejection fraction, but does not appear to result in
ischemic injury to any chamber. We postulate that increased
wall tension, dilation of the right-sided chambers, or both,
account for the elevation in cardiac biomarkers associated with
prolonged endurance running, rather than of ischemic damage
or infarction. Future research is needed to clarify the long-term
sequelae: possibly cardiac fibrosis in susceptible individuals,
and the risks of arrhythmias and sudden death.
ACKNOWLEDGMENTS
We are indebted to Ralph Gentry for CMR acquisition and image construc-
tion and Amy Murawka and Barbara Pruetz for phlebotomy services at
baseline evaluation, finish line, and at the follow-up visit.
All of the authors listed in this manuscript substantially contributed to the
conception and design, acquisition of data, or analysis and/or interpretation of
the data. All of the authors were involved in the drafting of the manuscript and
in the final approval of this version.
The ClinicalTrials.gov number for this study is NCT00752752.
GRANTS
We are grateful to The Beaumont Foundation for providing funding for the
costs of laboratory, exercise testing, and CMR studies. eCardio Diagnostics
(Milwaukee, WI) provided Holter monitor devices and related equipment.
108 MAY 2010 www.jap.org
 CARDIAC EFFECTS OF MARATHON RUNNING
DISCLOSURES
No conflicts of interest are declared by the authors.
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