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130
Cardiac Arrest during Long-Distance
Running Races
Jonathan H. Kim, M.D., Rajeev Malhotra, M.D., George Chiampas, D.O.,
Pierre d’Hemecourt, M.D., Chris Troyanos, A.T.C., John Cianca, M.D.,
Rex N. Smith, M.D., Thomas J. Wang, M.D., William O. Roberts, M.D.,
Paul D. Thompson, M.D., and Aaron L. Baggish, M.D.,
for the Race Associated Cardiac Arrest Event Registry (RACER) Study Group
From the Division of Cardiology ( J.H.K.,
R.M., T.J.W., A.L.B.) and the Department
of Pathology (R.N.S.), Massachusetts
General Hospital and Harvard Medical
School; the Division of Sports Medicine,
Children’s Hospital and Harvard Medical
School (P.D.); and the Boston Athletic
Association (C.T.) — all in Boston; the
Department of Emergency Medicine,
Northwestern University Feinberg School
of Medicine, Chicago (G.C.); the Depart-
ment of Physical Medicine and Rehabili-
tation, Baylor College of Medicine, Hous-
ton (J.C.); the Department of Family
Medicine, University of Minnesota Medi-
cal School, St. Paul ( W.O.R.); and the
Cardiology Division, Hartford Hospital,
University of Connecticut School of Med-
icine, Hartford (P.D.T.). Address reprint
requests to Dr. Baggish at the Massachu-
setts General Hospital, Cardiovascular Per-
formance Program, 55 Fruit St., YAW-5800,
Boston, MA 02114, or at abaggish@
partners.org.
N Engl J Med 2012;366:130-40.
Copyright © 2012 Massachusetts Medical Society.
A BS T R AC T
BACKGROUND
Approximately 2 million people participate in long-distance running races in the Unit-
ed States annually. Reports of race-related cardiac arrests have generated concern
about the safety of this activity.
METHODS
We assessed the incidence and outcomes of cardiac arrest associated with marathon
and half-marathon races in the United States from January 1, 2000, to May 31, 2010.
We determined the clinical characteristics of the arrests by interviewing survivors
and the next of kin of nonsurvivors, reviewing medical records, and analyzing post-
mortem data.
RESULTS
Of 10.9 million runners, 59 (mean [±SD] age, 42±13 years; 51 men) had cardiac arrest
(incidence rate, 0.54 per 100,000 participants; 95% confidence interval [CI], 0.41 to
0.70). Cardiovascular disease accounted for the majority of cardiac arrests. The in-
cidence rate was significantly higher during marathons (1.01 per 100,000; 95% CI,
0.72 to 1.38) than during half-marathons (0.27; 95% CI, 0.17 to 0.43) and among men
(0.90 per 100,000; 95% CI, 0.67 to 1.18) than among women (0.16; 95% CI, 0.07 to
0.31). Male marathon runners, the highest-risk group, had an increased incidence
of cardiac arrest during the latter half of the study decade (2000–2004, 0.71 per
100,000 [95% CI, 0.31 to 1.40]; 2005–2010, 2.03 per 100,000 [95% CI, 1.33 to 2.98];
P = 0.01). Of the 59 cases of cardiac arrest, 42 (71%) were fatal (incidence, 0.39 per
100,000; 95% CI, 0.28 to 0.52). Among the 31 cases with complete clinical data,
initiation of bystander-administered cardiopulmonary resuscitation and an underly-
ing diagnosis other than hypertrophic cardiomyopathy were the strongest predic-
tors of survival.
CONCLUSIONS
Marathons and half-marathons are associated with a low overall risk of cardiac ar-
rest and sudden death. Cardiac arrest, most commonly attributable to hypertrophic
cardiomyopathy or atherosclerotic coronary disease, occurs primarily among male
marathon participants; the incidence rate in this group increased during the past
decade.
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Ca rdiac A rres t dur ing Long-Dista nce Run ning Rac es
n engl j med 366;2 nejm.org january 12, 2012
131
P
articipation in long-distance run-
ning races has increased annually in the
United States. In 2010, there were approxi-
mately 2 million participants in marathon and
half-marathon races, as compared with fewer than
1 million participants in 2000.
1
This increase has
been driven in part by heightened public aware-
ness of the health benefits of regular physical
exercise. However, the growth of long-distance
running has been accompanied by studies docu-
menting post-race cardiac dysfunction
2,3
and nu-
merous reports of race-related cardiac arrest.
4-7
These unexpected tragedies attract considerable
media attention and have led to concerns regard-
ing the health risks of this activity.
8-11
Sudden death in young, competitive athletes
has been well characterized.
12,13
However, these
data may not apply to participants in long-distance
running races, who are an older population with
different cardiovascular risk factors and underly-
ing medical conditions. Prior studies have exam-
ined cases of cardiac arrest from only one or two
events
14,15
or have lacked detailed clinical infor-
mation.
16
The incidence, clinical profiles, and
outcomes of cardiac arrests that occur during
long-distance running races therefore remain un-
certain.
The Race Associated Cardiac Arrest Event Reg-
istry (RACER) was designed to address these is-
sues. The registry collected data from the most
recent decade of long-distance running races to
determine the incidence, clinical profile, and out-
comes of cardiac arrest in these events.
Met hod s
Study Design
We studied cases of cardiac arrest that occurred
during the running or at the finish-line recovery
area within 1 hour after the completion of a mar-
athon (26.2 mi) or half-marathon (13.1 mi) that
took place in the United States. A database of
cardiac arrests occurring during the period Janu-
ary 1, 2000, through May 31, 2010, was compiled
prospectively. All cases were verified retrospec-
tively at the conclusion of the study period. De-
tailed analyses were conducted for the subset of
cases with comprehensive clinical information.
The Partners Human Research Committee ap-
proved all aspects of the study before initiation.
The details of how informed consent was obtained
are outlined below.
Data Collection
Race-Participation Data
Running USA, a nonprofit running trade organi-
zation, provided participation statistics for each
year of the study period. This group uses a com-
prehensive, computerized cataloguing system to
compile accurate statistics for participation rates
in marathon and half-marathon races in the United
States. These data, including registered-participant
numbers categorized by sex and race distance,
are publicly available online and were confirmed
by direct contact with the publishing organization.
Cases of Cardiac Arrest
Cases of cardiac arrest were defined by an uncon-
scious state and an absence of spontaneous res-
pirations and pulse, as documented by a medical
professional. Nonsurvivors of cardiac arrest were
defined as persons who were not successfully re-
suscitated in the field or who died before hospital
discharge. Survivors of cardiac arrest were defined
as persons who were successfully resuscitated and
subsequently discharged from the hospital.
The cases of cardiac arrest and basic event in-
formation (age, sex, location of arrest, publicly re-
leased cause of arrest, and outcome) were identi-
fied and cross-referenced by means of a targeted
multistep algorithm through two independent
public search engines (LexisNexis and Google).
First, specific keywords and phrases, including
“marathon death,” “marathon fatality,” “sudden
cardiac death, marathon,” and “cardiac arrest,
marathon,” were entered into each search engine.
Second, a list of all long-distance races in the
United States was compiled from relevant web-
sites (e.g., coolrunning.com, runnersworld.com,
and marathonguide.com). We then performed ad-
ditional, targeted searches, using all identified
race names, the years 2000 through 2010, and all
previously mentioned keywords and phrases. Fi-
nally, online databases for the local newspapers
for all towns and cities with an identified mara-
thon or half-marathon were searched in a similar
fashion. Cases of cardiac arrest were retained for
final analysis if they were independently identi-
fied in three separate data sources or confirmed
with official race medical staff.
Letters describing the study were mailed to the
survivors of cardiac arrest and to the next of kin
of nonsurvivors. These mailings included formal
consent forms and opt-out forms. If no response
was obtained after 4 weeks, follow-up letters were
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sent, along with copies of the consent forms and
opt-out forms. A publicly available e-mail address
was used for a third attempt at contact if no re-
sponse was obtained after two mailings. Case
identification and enrollment are summarized in
Figure 1 in the Supplementary Appendix, available
with the full text of this article at NEJM.org.
The consenting survivors and next of kin of
nonsurvivors completed a questionnaire address-
ing demographic characteristics, history of run-
ning and other exercise, personal and family
medical history, and information about the cardiac
arrest. Permission was obtained to access perti-
nent medical records, including information re-
garding visits to primary care and specialist offices
and testing that took place before the cardiac ar-
rest, emergency-medical-service documentation of
care at the time of the cardiac arrest, and hospi-
tal, autopsy, and outpatient records after the car-
diac arrest.
Causes of Cardiac Arrest and Death
Cause of death was determined from cardiac-arrest
clinical care documentation and autopsy data. Hy-
pertrophic cardiomyopathy (left ventricular mass
>500 g) and possible hypertrophic cardiomyopa-
thy (left ventricular mass between 400 and 499 g
for men and between 350 and 499 g for women)
were diagnosed with the use of autopsy criteria
that integrate cardiac mass with findings that sup-
ported the diagnosis, including family history of
hypertrophic cardiomyopathy; characteristic fea-
tures of the gross anatomical cardiac architecture,
including marked asymmetry and mitral-valve
elongation; markedly increased left ventricular
wall thickness; and disease-specific histologic
findings.
13
Arrhythmogenic right ventricular car-
diomyopathy was defined by the presence of a
lipomatous transformation or a fibrolipomatous
transformation of the right ventricular free wall.
17
Diagnostic criteria for alternative causes of death
were adopted from clinical guidelines.
18-20
For
survivors, we used the diagnostic data document-
ed after the cardiac arrest to determine the cause
of the arrest.
Statistical Analysis
Continuous variables are presented as means (±SD),
and categorical variables as proportions. Compar-
isons between categorical and continuous vari-
ables were evaluated with Fisher’s exact test and
Student’s t-test. Incidence rates for the total num-
ber of cases and the fatal cases of cardiac arrest
were calculated as the simple proportion of events
divided by the number of participants for stated
time intervals. Ninety-five percent confidence in-
tervals for event rates were computed with the
use of a Poisson distribution. Cumulative inci-
dence rates from the initial 5 years of the study
period were compared with those from the final
5 years to assess temporal stability with the use
of a conservative approach involving chi-square
analysis to compare Poisson distributions of log-
transformed event rates.
21,22
Univariate and mul-
tivariate logistic-regression analyses were per-
formed to identify factors associated with the
outcome of cardiac arrest. Perfect predictors of
the outcome, with either survival or death per-
fectly stratified by the variable of interest, could
not be analyzed with logistic regression, and their
association with the cardiac-arrest outcome was
therefore assessed with Fisher’s exact test. Fac-
tors associated with the cardiac-arrest outcome
at a P value of less than 0.10 were tested in the
multivariate model by means of a backward step-
wise approach. Analyses were performed with the
use of Stata software, version 8.0 (StataCorp).
A P value of less than 0.05 was considered to in-
dicate statistical significance.
Re sults
Characteristics and Incidence of Cardiac
Arrest
We identified 59 cardiac arrests, 40 in marathons
and 19 in half-marathons, among 10.9 million
registered race participants. The mean age of run-
ners with cardiac arrest was 42±13 years, and 51
of the 59 runners (86%) were men. Data regard-
ing the point in the race course where the cardiac
arrest occurred are shown in Figure 1, and race-
participation numbers, absolute numbers of car-
diac arrests, and incidences of cardiac arrest as a
function of sex and race distance are summarized
in
Table 1
. The overall incidence of cardiac arrest
was 1 per 184,000 participants (0.54 per 100,000;
95% confidence interval [CI], 0.41 to 0.70). The
incidence was significantly higher during mara-
thons (1.01 per 100,000; 95% CI, 0.72 to 1.38) than
during half-marathons (0.27; 95% CI, 0.17 to 0.43;
P<0.001) and among men (0.90 per 100,000;
95% CI, 0.67 to 1.18) than among women (0.16;
95% CI, 0.07 to 0.31; P<0.001). The overall inci-
dence of cardiac arrest and the incidence as a func-
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Ca rdiac A rres t dur ing Long-Dista nce Run ning Rac es
n engl j med 366;2 nejm.org january 12, 2012
133
tion of race distance were similar during the initial
5 years of the study period and the final 5 years.
In contrast, the incidence of cardiac arrest among
men increased during the study period. Male mar-
athon participants, the highest-risk group (over-
all incidence of cardiac arrest, 1.41 per 100,000;
95% CI, 0.98 to 1.98), had a higher incidence dur-
ing the final 5 years of the study period than dur-
ing the initial 5 years (2.03 per 100,000 [95% CI,
1.33 to 2.98] from 2005 through 2010 vs. 0.71 per
100,000 [95% CI, 0.31 to 1.40] from 2000 through
2004, P = 0.01).
Outcomes of Cardiac Arrest
Of the 59 runners with cardiac arrest, 42 (71%)
died; the incidence of sudden death was 1.00 per
259,000 participants (0.39 per 100,000; 95% CI,
0.28 to 0.52). The mean age of the nonsurvivors
was 39±9 years, and the mean age of the survi-
vors was 49±10 years (P = 0.002). The incidence of
cardiac arrest resulting in death was significant-
ly higher during marathons (0.63 per 100,000;
95% CI, 0.41 to 0.93) than during half-marathons
(0.25 per 100,000; 95% CI, 0.14 to 0.39; P = 0.003)
and among men (0.62 per 100,000; 95% CI, 0.43
to 0.86) than among women (0.14 per 100,000;
95% CI, 0.06 to 0.29; P<0.001).
Causes of Cardiac Arrest and Death
The medical information necessary to determine
the cause of cardiac arrest was available for 31 of
the 59 runners with cardiac arrest. These 31 run-
ners did not differ significantly with respect to
age (mean, 39±12 years; range, 22 to 65) or sex
(26 [84%] were men) from the entire group of 59
runners described above or from the 28 for whom
consent or full medical records could not be ob-
tained. Of the 31 runners for whom complete
clinical data were obtained, 23 had died. Hyper-
trophic cardiomyopathy (in 8 of 23) and possi-
ble hypertrophic cardiomyopathy (in 7 of 23)
were the most common causes of death (Fig. 2
and Table 2). Notably, 9 of the 15 nonsurvivors
who had cardiac hypertrophy had an additional
clinical factor or postmortem finding: obstructive
coronary artery disease (in 3), myocarditis (in 2),
bicuspid aortic valve or coronary anomaly (in 2),
accessory atrioventricular nodal bypass tract (in 1),
or hyperthermia (in 1). Causes of death in the ab-
sence of left ventricular hypertrophy included hy-
ponatremia (in 1 person), hyperthermia (in 1), ar-
rhythmogenic right ventricular cardiomyopathy
(in 1), and no evident abnormality on autopsy or
presumed primary arrhythmia (in 2). Data from
the medical evaluation of survivors after cardiac
arrest are shown in
Table 2
. Ischemic heart dis-
ease (in 5 of 8 runners) was the predominant cause
of cardiac arrest among survivors. None of the run-
ners with serious coronary atherosclerosis had
angiographic evidence of acute plaque rupture or
thrombus.
Factors Associated with Cardiac-Arrest
Outcome
The 23 nonsurvivors and 8 survivors for whom
complete clinical information was obtained are
compared in
Table 3
. Survivors were older than
nonsurvivors (53.1±6.5 vs. 33.9±9.5 years, P<0.001)
and had completed more long-distance running
races. Survivors were also more likely to have had
a primary care physician and established athero-
sclerotic cardiac risk factors before the cardiac
arrest. The strongest predictors of survival of car-
diac arrest were initiation of bystander-adminis-
tered cardiopulmonary resuscitation (CPR) (P = 0.01
by Fisher’s exact test) and an underlying diagnosis
other than hypertrophic cardiomyopathy (P = 0.01
by Fisher’s exact test). In a multivariate logistic-
regression model in which these two factors had
Absolute No. of Cardiac Arrests
40
30
35
25
20
10
5
15
0
Q1
Q1
Q2
Q2
Q3
Q3
Q4
Q4
Race Quartile
Survivors
(N= 17)
Nonsurvivors
(N= 42)
Start 1/4 1/2 3/4 Finish
Figure 1. Location of Cardiac Arrest According to Race Quartile.
To account for differences in race distance between the marathon (26.2 mi)
and half-marathon (13.1 mi), the point in the race course where the cardiac
arrest occurred was examined as a function of the total race-distance quar-
tile. Q1 denotes 0 to 6.5 mi (marathon) and 0 to 3.3 mi (half-marathon),
Q2 6.5 to 13.1 mi (marathon) and 3.3 to 6.5 mi (half-marathon), Q3 13.1 to
20 mi (marathon) and 6.5 to 10 mi (half-marathon), and Q4 20 mi to finish
(marathon) and 10 mi to finish (half-marathon).
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Table 1. Participant Numbers, Absolute Number of Cardiac Arrests, and Incidence of Cardiac Arrest during Long-Distance Running Races in the United States, 2000–2010.
Variable 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009–2010* Total
All participants (in thousands)
Marathon — total no. (% men) 353 (65) 334 (64) 354 (64) 365 (62) 386 (59) 395 (60) 410 (60) 412 (59) 425 (59) 515 (59) 3949 (61)
Half-marathon — total no. (% men) 482 (53) 515 (52) 550 (51) 572 (52) 612 (51) 658 (47) 724 (47) 796 (45) 900 (44) 1113 (42) 6922 (48)
Total — no. 835 849 904 937 998 1053 1134 1208 1325 1628 10,871
Cardiac arrests
Marathon — total no. (no. of men) 3 (3) 3 (1) 3 (1) 3 (2) 1 (1) 2 (2) 9 (9) 5 (5) 6 (5) 5 (5) 40 (34)
Half-marathon — total no. (no. of men) 0 0 1 (1) 4 (4) 1 (1) 0 1 (1) 2 (2) 0 10 (8) 19 (17)
Total — no. (no. of men) 3 (3) 3 (1) 4 (2) 7 (6) 2 (2) 2 (2) 10 (10) 7 (7) 6 (5) 15 (13) 59 (51)
2000–2004 2005–2010* P Value 2000–2010*
Incidence of cardiac arrest — no./100,000
(95% CI)†
Marathon‡ 0.73 (0.39–1.24) 1.25 (0.83–1.82) 0.11 1.01 (0.72–1.38)
Half-marathon‡ 0.22 (0.08–0.48) 0.31 (0.17–0.53) 0.48 0.27 (0.17–0.43)
Male sex§ 0.55 (0.30–0.93) 1.17 (0.83–1.62) 0.02 0.90 (0.67–1.18)
Female sex§ 0.27 (0.09–0.63) 0.09 (0.02–0.27) 0.15 0.16 (0.07–0.31)
Total 0.42 (0.25–0.66) 0.63 (0.45–0.86) 0.15 0.54 (0.41–0.70)
* Data for 2010 include only the first 5 months (January 1 through May 31, 2010).
† Incidence rates were calculated as the simple proportion of events divided by the number of participants for stated time intervals. The 95% confidence intervals for event rates were
computed with the use of a Poisson distribution. P values are for the incidence rates for 2000–2004 as compared with those for 2005–2010 and were computed with the use of a chi-
square analysis of log-transformed Poisson event rates.
‡ Values represent pooled data for male and female participants.
§ Values represent pooled data for marathon and half-marathon participants.
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135
to be excluded owing to perfect prediction, fac-
tors that were independently associated with sur-
vival of cardiac arrest were an initial cardiac
rhythm of ventricular fibrillation or tachycardia
(odds ratio, 0.040; 95% CI, 0.003 to 0.556) and the
number of previous long-distance running races
completed (odds ratio, 0.533; 95% CI, 0.291 to
0.979).
Discussion
We calculated that the incidence rates of cardiac
arrest and sudden death during long-distance run-
ning races were 1 per 184,000 and 1 per 259,000
participants, respectively. We estimate that this
translates into 0.2 cardiac arrests and 0.14 sud-
den deaths per 100,000 runner-hours at risk, us-
ing average running times of 4 and 2 hours for
the marathon and half-marathon, respectively.
Thus, event rates among marathon and half-mar-
athon runners are relatively low, as compared with
other athletic populations, including collegiate ath-
letes (1 death per 43,770 participants per year),
23
triathlon participants (1 death per 52,630 partici-
pants),
24
and previously healthy middle-aged jog-
gers (1 death per 7620 participants).
25
These data
suggest that the risk associated with long-distance
running events is equivalent to or lower than the
risk associated with other vigorous physical ac-
tivity.
This study provides several insights into race-
related cardiac arrest. First, the absolute number
of race-related cardiac arrests each year increased
over the past decade. This is best explained by the
parallel increase in participation, because overall
annual incidence rates of cardiac arrest were sta-
ble. Second, men were more likely than women to
have cardiac arrest and sudden death. This finding
is consistent with reports on other populations
and reaffirms a male predisposition to exertional
cardiac arrest.
12,13,25-27
A plausible explanation for
this observation is the higher prevalence of both
occult hypertrophic cardiomyopathy and early-
onset atherosclerosis in men.
28,29
The finding that
event rates among male marathon runners in-
creased during the study period is troubling and
may indicate that long-distance racing has recently
been attracting more high-risk men with occult
cardiac disease who seek the health benefits of
routine physical exercise. Future work is needed
to further characterize this group and to deter-
mine useful prevention strategies. Third, race dis-
tance was a determinant of the incidence of car-
diac arrest and death, with rates for marathons
that were three to five times as high as the rates
for half-marathons. A possible explanation is that
longer races involve more physiological stress and
thus a higher likelihood of precipitating an ad-
verse event in a predisposed participant. Finally,
cardiovascular disease accounted for the majority
of cardiac arrests. Hypertrophic cardiomyopathy,
the primary cause of death in young competitive
athletes,
12,13
was also the leading cause of death
in this population. Alternative race-related disor-
ders, including hyponatremia
30
and hyperther-
mia,
31
remain important concerns but are uncom-
mon causes of cardiac arrest and sudden death.
The overall case fatality rate was 71%. This
compares favorably with previous data on out-of-
hospital cardiac arrests (median case fatality rate,
92%).
32
This may be due to the fact that running
HCM+,
16%
HCM,
10%
PHCM+,
13%
PHCM,
10%
Presumed
dysrhyth-
mia,
7%
No autopsy,
7%
Hyponatremia,
7%
Cardiomyopathy,
3%
Hyperthermia,
3%
Myocardial
ischemia,
16%
Nonischemic
ventricular
tachycardia,
7%
Unknown,
3%
Nonsurvivors
(blue shades)
Survivors
(red shades)
Figure 2. Causes of Cardiac Arrest among Nonsurvivors and Survivors.
HCM denotes hypertrophic cardiomyopathy; HCM+ denotes HCM and
additional diagnoses, including coronary artery disease (in 2 persons),
myocarditis (in 2), and bicuspid aortic-valve and coronary anomaly (in 1).
PHCM denotes possible hypertrophic cardiomyopathy. PHCM+ denotes
PHCM and additional diagnoses, including coronary artery disease
(in 1 person), accessory atrioventricular nodal bypass tract (in 1), hyper-
thermia (in 1), and bicuspid aortic-valve and coronary anomaly (in 1). One
nonsurvivor with hyponatremia was also found to have myxomatous valvu-
lar disease of the tricuspid, mitral, and aortic valves. Data include arrhyth-
mogenic right ventricular cardiomyopathy (in 1 person). Because of round-
ing, percentages do not add up to 100.
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136
Table 2. Autopsy and Clinical Data for Nonsurvivors of Cardiac Arrest and Survivors of Cardiac Arrest.*
Participant No. Age Sex Autopsy
Performed Primary Autopsy Findings and Causes of Death Additional Clinical and Autopsy Data
yr
Participants who
died
1 33 Male Yes Hypertrophic cardiomyopathy —
2 35 Male Yes Hypertrophic cardiomyopathy —
3 23 Male Yes Hypertrophic cardiomyopathy —
4 28 Male Yes Hypertrophic cardiomyopathy, myocarditis Myocarditis with diffuse mononuclear-cell inflammation and
intercellular fibrosis
5 32 Male Yes Hypertrophic cardiomyopathy, myocarditis Myocarditis with eosinophil and granulocyte infiltration
6 45 Male Yes Hypertrophic cardiomyopathy, coronary artery disease 75% proximal left anterior descending stenosis, 90% proximal
right coronary-artery stenosis
7 44 Male Yes Hypertrophic cardiomyopathy, coronary artery disease 85% proximal left anterior descending stenosis, 40% proximal
right coronary-artery stenosis
8 30 Male Yes Hypertrophic cardiomyopathy, bicuspid aortic valve,
coronary anomaly Absent left circumflex artery
9 26 Male Yes Possible hypertrophic cardiomyopathy —
10 25 Male Yes Possible hypertrophic cardiomyopathy —
11 29 Female Yes Possible hypertrophic cardiomyopathy Markedly reduced BMI of 14.9
12 40 Male Yes Possible hypertrophic cardiomyopathy, bicuspid aortic valve,
coronary anomaly Abnormal left main and right coronary-artery origin with “slit-
like” ostia
13 23 Male Yes Possible hypertrophic cardiomyopathy, accessory atrio-
ventricular pathway Fragmented atrioventricular node with discrete bands of con-
duction tissue
14 38 Male Yes Possible hypertrophic cardiomyopathy, coronary artery
disease 75% proximal left anterior descending stenosis
15 22 Male Yes Possible hypertrophic cardiomyopathy, hyperthermia Diffuse alveolar hemorrhage, pulmonary edema, clinical docu-
mentation of hyperthermia at the time of cardiac arrest
16 23 Male Yes Hyperthermia Diffuse alveolar hemorrhage, pulmonary edema, clinical docu-
mentation of hyperthermia at the time of cardiac arrest
17 32 Female Yes Arrhythmogenic right ventricular cardiomyopathy, coronary
artery disease Diffuse right ventricular adipose infiltration, 70% left ante rior
descending stenosis
18 29 Female Yes Hyponatremia Documented altered mental status and seizures, brain-stem
herniation at autopsy, myxomatous polyvalvular (mitral,
tricuspid, aortic) heart disease
19 35 Female Yes Hyponatremia Clinical documentation of profound hyponatremia during
resuscitation efforts, autopsy report unavailable
20 45 Male Yes Presumed cardiac dysrhythmia —
21 36 Male Yes Presumed cardiac dysrhythmia —
22 46 Male No NA —
23 60 Male No NA —
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n engl j med 366;2 nejm.org january 12, 2012
137
Age Sex Cause of Cardiac Arrest Findings on Cardiac Catheterization Echocardiographic Data
yr
Participants who
survived
1 48 Female Nonischemic ventricular
tachycardia No coronary arterial luminal narrowing, normal left ventri-
cular function (ejection fraction, 68%) Normal left ventricular structure and function; septal thickness,
11 mm; posterior-wall thickness, 11 mm; left ventricular
end-diastolic diameter, 52 mm; left ventricular ejection
fraction, 60%
2 48 Male Nonischemic ventricular
tachycardia No coronary arterial luminal narrowing, normal left ventri-
cular function (ejection fraction 62%) Mild left ventricular dilatation†; septal thickness, 11 mm; poste-
rior wall thickness, 11 mm; left ventricular end-diastolic diam-
eter, 59 mm; left ventricular ejection fraction, 66%
3 55 Male Myocardial ischemia 95% mid-left anterior descending stenosis Normal left ventricular morphology and function; septal thick-
ness, 10 mm; posterior wall thickness, 11 mm; left ventricu-
lar end-diastolic diameter, 50 mm; left ventricular ejection
fraction, 55%
4 60 Male Myocardial ischemia 95% mid-left circumflex stenosis Mild left ventricular dilatation; septal thickness, 11 mm; poste-
rior wall thickness, 11 mm; left ventricular end-diastolic di-
ameter, 57 mm; left ventricular ejection fraction, 50%
5 49 Male Myocardial ischemia 95% distal right coronary-artery stenosis, 80% proximal right
coronary-artery stenosis, 95% proximal left circumflex
stenosis
Echocardiography not performed
6 47 Male Myocardial ischemia 85% proximal left anterior descending stenosis Mild left ventricular concentric hypertrophy; septal thickness,
12 mm; posterior wall thickness, 10 mm; left ventricular
end-diastolic diameter, 49 mm; left ventricular ejection
fraction, 50%
7 65 Male Myocardial ischemia 90% mid-left anterior descending stenosis, 80% postero-
lateral-artery stenosis Mild left ventricular concentric hypertrophy; septal thickness,
13 mm; posterior wall thickness, 11 mm; left ventricular
end-diastolic diameter, 52 mm; left ventricular ejection frac-
tion, 45%
8 53 Male Unknown‡ Catheterization not performed Mild left ventricular concentric hypertrophy; septal thickness,
13 mm; posterior wall thickness, 13 mm; left ventricular
end-diastolic diameter, 51 mm; left ventricular ejection
fraction, 65%
* BMI denotes body-mass index (the weight in kilograms divided by the square of the height in meters), and NA not available.
† Echocardiographic data were obtained 6 months after the cardiac arrest.
‡ The participant was found unconscious before losing pulse, underwent cardiopulmonary resuscitation, and then regained pulse before the first rhythm analysis. The electrocardiogram
and blood work were unrevealing. The echocardiogram revealed no wall-motion abnormalities, and no further workup was performed.
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o f
me di ci ne
n engl j med 366;2 nejm.org january 12, 2012
138
Table 3. Demographic Characteristics, Running History, Clinical Characteristics, Emergency Medical Treatment, and Cause of Cardiac Arrest
among Nonsurvivors and Survivors.*
Variable Nonsurvivors
(N = 23) Survivors
(N = 8) P Value† Odds Ratio
(95% CI)‡
Demographic characteristics
Male sex — no. (%) 19 (83) 7 (88) 0.75
Age — yr 33.9±9.5 53.1±6.5 0.02 0.78 (0.64–0.95)
BMI 24.8±3.7 25.6±2.3 0.54
Running history
No. of years of running 11±8 20±17 0.09 0.94 (0.87–1.01)
No. of previous long-distance running races completed§ 1.5±1.9 3.5±1.5 0.02 0.57 (0.35–0.92)
Training regimen
No. of mi/wk 41±16 53±10 0.18
Longest distance run (% of expected race distance)¶ 86±32 80±18 0.64
Clinical characteristics — no. (%)
Established relationship with primary care physician 10 (43) 8 (100) 0.01‖
Family history of sudden cardiac death 1 (4) 0 0.74‖
Family history of premature coronary artery disease 4 (17) 0 0.28‖
History of tobacco use 2 (9) 2 (25) 0.26
Hypertension 4 (17) 5 (63) 0.02 0.13 (0.02–0.76)
Hyperlipidemia 5 (22) 5 (63) 0.04 0.17 (0.03–0.95)
Diabetes mellitus 0 (0) 0 NA
Previous positive cardiovascular review of systems** 6 (26) 4 (50) 0.22
Recent viral prodrome†† 3 (13) 0 0.39‖
Emergency medical treatment
Bystander-administered CPR performed — no. (%) 10 (43) 8 (100) 0.01‖
Time to initiation of CPR — min 5.2±4.0 1.5±1.4 0.06 1.51 (0.99–2.30)
Time to emergency-medical-service arrival — min 7.7±6.7 3.9±2.7 0.13
Initially documented cardiac rhythm — no. (%)
Ventricular fibrillation or ventricular tachycardia 6 (26) 7 (88) 0.01 0.05 (0.01–0.50)
Pulseless electrical activity, asystole, or other 17 (74) 1 (13) 0.01 19.8 (2.0–196.4)
Automatic external defibrillator used on scene 8 (35) 7 (88) 0.03 0.08 (0.01–0.73)
Autopsy and clinical findings after cardiac arrest — no. (%)
Definite or probable hypertrophic cardiomyopathy 15 (65) 0 0.002‖
Ischemic heart disease 4 (17) 5 (63) 0.02 0.13 (0.02–0.76)
* Plus–minus values are means ±SD. Data are from the 31 cases for which complete clinical information was obtained. BMI denotes body-
mass index, CPR cardiopulmonary resuscitation, and NA not applicable.
† Univariate logistic regression for predictors of nonsurvival was used to determine P values.
‡ Univariate odds ratios are provided for P values of less than 0.10.
§ The number of previous long-distance races was scored as follows: 0 (none), 1 (1 race), 2 (2 races), 3 (3 races), 4 (4 races), or 5 (≥5 races).
¶ Distance was calculated as the peak distance of the longest training run (in miles) divided by the distance of the upcoming race (mara-
thon or half-marathon). To convert values for distance to kilometers, multiply by 1.6.
‖ P values for variables that were perfect predictors were determined with the use of Fisher’s exact test.
** A positive cardiovascular review of systems was defined as chest pain, dizziness or syncope, or palpitations within 2 weeks before the race.
†† Viral prodrome symptoms were defined as generalized weakness, fatigue, or respiratory congestion within 2 weeks before the race.
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139
races often have a high density of spectators as
well as on-site medical services that facilitate
timely emergency intervention. The finding that
early bystander-administered CPR and use of au-
tomated defibrillators at the scene of the arrest
were common for survivors of cardiac arrest un-
derscores the notion that the race environment
contributed to high resuscitation rates. There was
also an association between age and cardiac-arrest
outcome, with survival more common among par-
ticipants who were 40 years of age or older (15 of
32, 47%) than among those younger than 40 years
of age (2 of 27, 7%). This is best explained by the
age-specific pattern of underlying cardiac disease.
Younger persons who have cardiac arrest are more
likely to have had hypertrophic cardiomyopathy,
and resuscitation in cases of hypertrophic cardio-
myopathy is reportedly less successful than in
other conditions.
33
In contrast, older persons who
have cardiac arrest are more likely to have had
ischemic heart disease. In our study, runners with
ischemic heart disease, most of whom were suc-
cessfully resuscitated, had coronary angiographic
and autopsy data suggesting a mismatch between
oxygen supply and demand, not acute plaque
rupture.
The absence of coronary plaque rupture in
these persons was surprising, because prior data
34,35
and expert consensus documents
36
have suggested
that exercise-induced acute coronary syndromes
result from atherosclerotic plaque disruption and
coronary thrombosis. In contrast, our findings
suggest that demand ischemia (i.e., ischemia due
to an imbalance between oxygen supply and de-
mand) may be operative in exercise-related acute
coronary events during long-distance running rac-
es. Although further work is warranted to clarify
the mechanism (or mechanisms) that lead to car-
diac arrest in runners with fixed coronary steno-
sis, this finding may have important clinical im-
plications. Routine exercise testing in adults before
exercise participation has not been recommended
because of the low rates of exercise-related car-
diac events, the high rates of false positive results
in asymptomatic persons, and the concept that
acute plaque rupture is the dominant cause of
exercise-related cardiac events.
36
However, our ob-
servations suggest that preparticipation exercise
testing, by virtue of its ability to accurately detect
physiologically significant coronary-artery steno-
sis,
37
may be useful for identifying some persons
at high risk, including middle-aged and older men
with exertion-induced symptomatic or asymptom-
atic myocardial ischemia; this speculation re-
quires further research for validation before it
can be considered directive. The absence of plaque
rupture also has important implications regard-
ing the controversy of prophylactic aspirin use be-
fore exercise to prevent an acute event.
38,39
Our
data suggest that taking aspirin before running a
race may have limited efficacy, because acute coro-
nary arterial thrombosis does not appear to be an
important cause of race-related cardiac arrest.
This study has several limitations. First, our
ascertainment method may have failed to detect
all race-related cardiac arrests during the study
period. However, the use of Internet search en-
gines, plus direct outreach to race organizers,
should have minimized this possibility. Second, we
were unable to obtain complete clinical data on
45% of the nonsurvivors and on 53% of the sur-
vivors and thus cannot be certain that the de-
tailed clinical characteristics and autopsy findings
apply to all the runners who had cardiac arrest
during the study period. However, age and sex
were similar between those with and those with-
out complete information, suggesting that the
more comprehensively evaluated runners are rep-
resentative of the entire group. Third, we exam-
ined the incidence of cardiac arrest as a function
only of race distance and sex. Thus, we cannot
comment on the risk or outcomes of cardiac ar-
rest in specific populations, such as elite athletes,
first-time race participants, or runners with pre-
existing medical conditions. Finally, some runners
may have run multiple races during the decade-
long study period, thereby diluting the incidence
figures and leading to an underestimation of risk
for an individual participant.
Findings from the RACER initiative indicate
that marathons and half-marathons are associat-
ed with a low overall risk of cardiac arrest or sud-
den death. However, event rates have risen over the
past decade among male marathon runners. Clini-
cians evaluating potential race participants should
be aware of the risks of hypertrophic cardiomy-
opathy and atherosclerotic disease in this patient
population.
Dr. Roberts reports holding a board membership with UCare
Minnesota, receiving writing fees from Runner’s World, and serv-
ing as an unpaid, volunteer medical director for the Medtronic
Twin Cities Marathon; and Dr. Thompson, receiving consulting
fees from Regeneron, Furiex Pharmaceuticals, and Lupin Phar-
maceuticals, legal fees for expert testimony in cases related to
cardiac arrest in exercise- and statin-related muscle injury, grant
funding from GlaxoSmithKline, Genomas, Novartis, Furiex
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140
Ca rdiac A rres t dur ing Long-Dista nce Run ning Rac es
Pharmaceuticals, B. Braun, and Aventis, lecture fees from Merck,
Pfizer, AstraZeneca, Kowa, Abbott, and GlaxoSmithKline, sup-
port for the development of educational presentations from
Merck, and holding stock in Zoll Medical, J.A. Wiley Publishing,
General Electric, Zimmer, Medtronic, Johnson & Johnson,
Sanofi-Aventis, and Abbott. No other potential conflict of inter-
est relevant to this article was reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Ryan Lamppa at Running USA for providing race-
participation numbers; Deborah McDonald for her assistance
with participant correspondence and data retrieval; and, most im-
portant, the cardiac-arrest survivors and the families of deceased
runners for helping us obtain the data necessary for this study.
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