Download Etiology of Sudden Death in Sports

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 67, NO. 18, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2016.02.062
Etiology of Sudden Death in Sports
Insights From a United Kingdom Regional Registry
Gherardo Finocchiaro, MD,a Michael Papadakis, MBBS, MD,a Jan-Lukas Robertus, MD,b Harshil Dhutia, MBBS,a
Alexandros Klavdios Steriotis, MD, PHD,a Maite Tome, MD, PHD,a Greg Mellor, MBCHB,a Ahmed Merghani, MBBS,a
Aneil Malhotra, MBBCHIR,a Elijah Behr, MBBS, MD,a Sanjay Sharma, MBCHB, MD,a
Mary N. Sheppard, MBBCH, BAO, MDb
ABSTRACT
BACKGROUND Accurate knowledge of causes of sudden cardiac death (SCD) in athletes and its precipitating factors is
necessary to establish preventative strategies.
OBJECTIVES This study investigated causes of SCD and their association with intensive physical activity in a large
cohort of athletes.
METHODS Between 1994 and 2014, 357 consecutive cases of athletes who died suddenly (mean 29 11 years of age,
92% males, 76% Caucasian, 69% competitive) were referred to our cardiac pathology center. All subjects underwent
detailed post-mortem evaluation, including histological analysis by an expert cardiac pathologist. Clinical information
was obtained from referring coroners.
RESULTS Sudden arrhythmic death syndrome (SADS) was the most prevalent cause of death (n ¼ 149 [42%]).
Myocardial disease was detected in 40% of cases, including idiopathic left ventricular hypertrophy (LVH) and/or
fibrosis (n ¼ 59, 16%); arrhythmogenic right ventricular cardiomyopathy (ARVC) (13%); and hypertrophic cardiomyopathy (HCM) (6%). Coronary artery anomalies occurred in 5% of cases. SADS and coronary artery anomalies affected
predominantly young athletes (# 35 years of age), whereas myocardial disease was more common in older individuals.
SCD during intense exertion occurred in 61% of cases; ARVC and left ventricular fibrosis most strongly predicted SCD
during exertion.
CONCLUSIONS Conditions predisposing to SCD in sports demonstrate a significant age predilection. The strong
association of ARVC and left ventricular fibrosis with exercise-induced SCD reinforces the need for early detection
and abstinence from intense exercise. However, almost 40% of athletes die at rest, highlighting the need
for complementary preventive strategies. (J Am Coll Cardiol 2016;67:2108–15) © 2016 by the American College of
Cardiology Foundation.
S
udden cardiac death (SCD) is a tragic event that
post-mortem examination performed by an experi-
occasionally affects apparently healthy indi-
enced cardiac pathologist. A recent study comparing
viduals (1), including young (#35 years of
the interpretation of autopsy findings between a
age) athletes (2–5). A spectrum of cardiac diseases is
referring pathologist and a specialist cardiac patholo-
implicated in SCD, with variable prevalence depend-
gist demonstrated a 40% disparity with respect to
ing on the age and other demographics of the
actual cause of death (7).
cohort (6). Many reports regarding the causes of
Knowledge of precise causes and precipitating
SCD in athletes are limited by the lack of a detailed
factors of SCD may influence national strategies to
Listen to this manuscript’s
audio summary by
JACC Editor-in-Chief
Dr. Valentin Fuster.
From the aCardiovascular Sciences Research Centre, St. George’s, University of London, London, United Kingdom; and the
b
Cardiovascular Pathology Department, St. George’s, University of London, London, United Kingdom. Dr. Behr has received
research funds from Biotronik and St. Jude Medical; and fellowship support from McColl’s Retail Group. All other authors have
reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Sharma and Sheppard are joint
senior authors.
Manuscript received December 11, 2015; revised manuscript received February 12, 2016, accepted February 26, 2016.
Finocchiaro et al.
JACC VOL. 67, NO. 18, 2016
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Sudden Death in Athletes
prevent such events, including pre-participation
conducted in all cases in accordance with the
ABBREVIATIONS
screening methods and widespread availability of
usual investigation of sudden and unex-
AND ACRONYMS
automated
pected
participation
external
defibrillators
screening
with
(AEDs).
Pre-
deaths
in
the
United
Kingdom.
electrocardiography
Comprehensive macroscopic examination of
(ECG) is useful for detecting quiescent inherited car-
the whole heart and histological analysis
diac diseases, particularly inherited cardiomyopa-
were performed in accordance with guide-
thies, and ion-channelopathies but has limited value
lines on “Autopsy practice for sudden death
AED = automatic external
defibrillator
ARVC = arrhythmogenic right
ventricular cardiomyopathy
CAD = coronary artery disease
in detecting athletes with coronary artery disease
with likely cardiac pathology” of the Royal
(CAD). AEDs appear to be more effective in the
College of Pathologists (10) and the Associa-
cardiomyopathy
termination of arrhythmias in athletes with CAD or
tion for European Cardiovascular Pathology
LV = left ventricular
coronary artery anomalies than in athletes with car-
(11). All cardiac structures were systemati-
LVH = left ventricular
diomyopathy (8,9).
cally examined. Heart weight was recorded in
hypertrophy
grams, and ventricular wall thickness and
SADS = sudden arrhythmic
SEE PAGE 2116
The objective of this study was to investigate the
HCM = hypertrophic
internal cavity dimensions were measured at
death syndrome
mid-ventricular level, excluding the papillary
SCD = sudden cardiac death
causes and circumstances of SCD in a large cohort of
muscles and fat. A minimum of 10 blocks of tissue
athletes, as determined by post-mortem examination
were taken for histological analysis as reported pre-
performed by an expert cardiac pathologist.
METHODS
The Cardiac Risk in the Young (CRY) center for cardiac
pathology is located at St. George’s University of
London. The center is led by an expert cardiac
pathologist (M.N.S.) and receives over 400 whole
hearts from cases of SCD across the United Kingdom
annually. General pathologists are likely to refer to
the CRY center when the clinical history is suggestive
of inherited cardiac disease, especially when the
viously (6,7). Sections of myocardium were fixed in
formalin, embedded in paraffin, and stained with
hematoxylin and eosin and with elastic Van Gieson
stain to highlight myocardial fibrosis.
Criteria for defining specific cardiac pathologies
have been previously described (6,12) and are summarized in Table 1. Sudden arrhythmic death syndrome (SADS) was a diagnosis of exclusion, defined as
a structurally normal heart with no evident abnormality on macroscopic and histological evaluation
and a negative result for toxicology screening (13–15).
death affects a young or athletic individual or when
CLINICAL INFORMATION. The referring coroner and
the cause of death is uncertain after the initial
pathologist were asked to complete a questionnaire
autopsy.
regarding the demographics of the deceased, medical
STUDY POPULATION. We retrospectively reviewed
history, family history, cardiac symptoms, nature and
cases from a database of 3,684 cases of SCD referred
level of physical activity, and exact circumstances of
to the CRY center for cardiac pathology between 1994
death. Data were derived from a number of sources
and 2014. SCD was defined as death occurring within
including: interviews with the family of the deceased,
12 h of apparent wellbeing. We retrieved a sub-
potential witnesses to the SCD, and reports from the
group of 357 cases (9.7%) of individuals who had
deceased’s family physician. Data were collected
engaged in regular sport activities, defined as >3 h of
prospectively and stored in an electronic database.
organized physical training per week. The majority
STATISTICAL
(84%) of referrals occurred between 2004 and 2014.
performed using PASW version 18.0 software (PASW,
ANALYSIS. Statistical
analysis
was
Competitive athletes were defined as those who were
Inc., Chicago, Illinois). Results are mean SD for
involved in organized sports requiring participation
continuous variables or numbers of cases and per-
in regular, formal competition. Circumstances of
centages for categorical variables. Comparison of
death were subdivided broadly into death occurring
groups was performed using Student t test for
during exercise and death during rest or sleep.
continuous variables with correction for unequal
POST-MORTEM EXAMINATION. All SCD cases under-
variance when necessary and chi-square test or Fisher
went a full post-mortem evaluation by the local
exact test, as appropriate for categorical variables.
pathologist. Following the exclusion of extra-cardiac
Univariate and multivariate logistic regression ana-
causes, the heart was sent to our center after writ-
lyses were used to determine the factors associated
ten consent of the coroner and the family of the
with death during exertion. Age, sex, and variables
deceased. The local pathologist also performed an
that were univariately correlated with the dependent
initial cardiac autopsy before referring the heart in
variable were selected and entered into the forward
58% of cases. A thorough toxicology screen was
stepwise multiple regression model.
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Finocchiaro et al.
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T A B L E 1 Pathological Macroscopic and Microscopic Criteria Defining Main
Underlying Diseases
Pathology
participating in regular training and competition in
team (n ¼ 155 [43%]) or individual (n ¼ 90 [26%]) sports.
The rest of the cohort (n ¼ 112 [31%]) consisted of
Macroscopic Criteria
Microscopic Criteria
Left ventricular wall thickness
>15 mm circumferentially
or focally and/or heart
weight >500 g*†
Myocyte hypertrophy,
myocyte disarray
(>20% of myocardial
disarray in at least 2
tissue blocks of 4 cm2),
and interstitial fibrosis
Idiopathic left ventricular
hypertrophy
Left ventricular wall thickness
>15 mm and heart weight
>500 g*
Myocyte hypertrophy with
or without fibrosis in the
absence of myocyte
disarray
rugby (n ¼ 19 [5%]), tennis (n ¼ 6 [2%]), golf (n ¼ 6 [2%]),
Idiopathic left ventricular
fibrosis
Normal heart weight and wall
thickness with/without
scarring macroscopically
Fibrosis (>20% in at least
2 tissue blocks of 4 cm2)
with no myocyte
disarray
(n ¼ 288 [81%]). Of the 69 symptomatic athletes (29%),
Arrhythmogenic right
ventricular
cardiomyopathy
Right or left ventricular
thinning, fatty
replacement, fibrosis on
the epicardial surface or
outer wall
Fat and fibrosis (>20% in at
least 2 tissue blocks of
4 cm2) in the wall of the
right and/or left
ventricle, particularly in
outer wall, with
degenerative changes in
the myocytes
Hypertrophic
cardiomyopathy
Myocarditis
Normal or dilated ventricles
Anomalous coronary artery
Coronary atherosclerosis
Dilated cardiomyopathy
Mitral valve prolapse
Bicuspid aortic valve
Inflammation (>20% in at
least 2 tissue blocks of
4 cm2) with myocyte
necrosis
Anomalous origin of the
coronary artery,
coronary artery atresia,
stenosis
Fibrosis/acute/chronic
infarction in the left
ventricle
Atherosclerosis with
estimated luminal
narrowing >75%
Acute or chronic infarction
in the left ventricle
Increase in heart weight
(>500 g in males, >400 g
in females) with dilated
left ventricle (>4 cm) and
thin wall (<10 mm).
Absence of coronary
artery disease.
Diffuse interstitial and
replacement fibrosis
(>20% in at least
2 tissue blocks of 4 cm2)
in the left ventricle with
degenerative changes in
the myocytes
Prolapse of mitral valve above
the atrioventricular
junction with ballooning
between chordae in one or
both leaflets
Myxoid degeneration with
expansion in spongiosa
of leaflets and
destruction of fibrosa
layer
Normal
running
(n
¼
92
[25%];
40
participating
in
half-marathons and marathons), football (n ¼ 91
[25%]), cycling (n ¼ 30 [8%]), gymnastics (n ¼ 30 [8%]),
swimming (n ¼ 22 [6%]), weightlifting (n ¼ 20 [6%]),
boxing (n ¼ 5 [1%]), and other sports (n ¼ 36 [10%]).
The majority of the athletes were asymptomatic
27 (8%) had palpitations, 20 (6%) had chest pain,
18 (5%) had syncope, and 4 (1%) reported decreased
exercise tolerance. Five patients experienced palpitations due to paroxysmal atrial fibrillation, including
1 in the context of Wolff-Parkinson-White syndrome.
One athlete received a diagnosis of myocarditis 4 years
before death, and 1 athlete was hospitalized 4 months
prior to death for suspected myocarditis. There was a
family history of premature sudden death (defined as
death of a first-degree relative <50 years of age) in
28 cases (8%). The main comorbidities were asthma
(n ¼ 28%, 8%), epilepsy (n ¼ 5, 1%), and treated arterial
hypertension (n ¼ 4, 1%).
CAUSES. The main causes of death are shown in the
Central Illustration. A normal post-mortem indicative
of SADS was the most common finding and accounted
for 149 deaths (42%). Myocardial disease was present
in 130 cases (35%). Among these cases, idiopathic left
ventricular
hypertrophy
(LVH)
and/or
fibrosis
accounted for 59 deaths (16%), followed by arrhythmogenic right ventricular cardiomyopathy (ARVC)
(n ¼ 48 [13%]), and hypertrophic cardiomyopathy
(HCM) (n ¼ 23 [6%]). The majority of individuals with
ARVC also demonstrated LV involvement, with 17
Fusion of 2 aortic cusps, with
or without presence of a
raphe often with
significant valve stenosis
Morphologically normal
heart
recreational athletes. Sporting disciplines included
cases (35%) exhibiting fibrofatty infiltration of the LV
and 41 cases (85%) showing evidence of left ventricNormal
*Heart weight >400 g in women. †In this cohort, heart weight was normal in 39% of HCM cases. In a small
proportion of cases, HCM was diagnosed on the basis of the presence of myocyte hypertrophy, myocardial
disarray, and fibrosis on microscopy, despite normal heart weight and wall thickness on macroscopic evaluation.
ular (LV) fibrosis. Coronary artery pathology occurred
in 7% of cases, with coronary artery anomalies accounting for the majority of the cases.
CAUSES OF DEATH BY AGE AND SEX. The prevalence
of specific cardiac pathologies varied with age (Central
Illustration). SADS was most common in younger cases
RESULTS
and showed a reduced trend with increasing age
(Figure 1). A structurally normal heart was reported in
CLINICAL CHARACTERISTICS. The mean age at death
56% of children and adolescents (<18 years), 44% of
of the 357 athletes was 29 11 years (range: 7 to
young adults (18 to 35 years of age), and 26% of older
67 years; median: 27 years), with a large male pre-
individuals (>35 years of age; p <0.001 comparing <18
dominance (n ¼ 330, 92%). The average body mass in-
and >35 years of age; p ¼ 0.004 comparing 18 to 35
dex and body surface area were 25 5 kg/m 2 and 2.2 years of age and those >35 years of age). Coronary ar-
0.4 m 2, respectively. A significant proportion of in-
tery anomalies were also more prevalent in younger
dividuals were competitive athletes (n ¼ 245 [69%]),
individuals, accounting for 11% of deaths in children
Finocchiaro et al.
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Sudden Death in Athletes
CENTRAL ILLUSTRATION Sudden Death in Athletes: Causes of Sudden Cardiac Death
Finocchiaro, G. et al. J Am Coll Cardiol. 2016;67(18):2108–15.
Sudden death is shown in the overall population (A), in subjects <18 years of age (B), subjects 18 to 35 years of age (C), and subjects >35 years of age (D). In the overall
population, the subgroup classified as “Other” (n ¼ 43) comprised: mitral valve abnormalities/prolapse; n ¼ 7, myocardial infarction with normal coronaries; n ¼ 4,
bicuspid aortic valve; n ¼ 3, aortic dissection; n ¼ 3, cocaine/steroid use; n ¼ 2, cardiac sarcoidosis; n ¼ 1, atrium septal defect (ASD). In the remaining 23 cases, the cause
of death could not be attributed to a single disease entity or condition and the post-mortem findings were considered of uncertain significance. LVH ¼ left ventricle
hypertrophy; RV ¼ right ventricle.
and adolescents compared to only 2% in adults >35
Mean heart weight was 421 110 g. Seventy hearts
years of age. In contrast, diseases of the myocardium
(20%) exhibited an absolute value of >500 g. Of these,
were
the majority were diagnosed with idiopathic LVH
more
common
in
older
athletes
(Central
Illustration). Idiopathic LVH and/or fibrosis was pre-
with or without fibrosis (n ¼ 30 [42%]), followed by
sent in 10% of individuals <18 years of age and in 26%
HCM (n ¼ 13 [19%]), and ARVC (n ¼ 12 [17%])
of those >35 years of age (p ¼ 0.01). ARVC was detected
(Figure 1).
in only 4% of individuals <18 years of age and in 18% of
those >35 years of age (p ¼ 0.009).
There were only 27 females in our cohort. The
majority (55%) showed a normal heart at post-mortem
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F I G U R E 1 Heart Weight Distribution in the Overall Cohort
140
Idiopathic LVH/fibrosis
120
Hypertrophic cardiomyopathy
13%
2%
4%
Arrhythmogenic RV cardiomyopathy
Coronary artery anomaly
1%
42%
Coronary atheroma
Dilated cardiomyopathy
100
Other
17%
80
19%
n
60
n=70 (20%)
40
20
0
100
200
300
400
500
600
Heart Weight
700
800
900
1000
Histogram shows distribution of heart weights in the overall cohort. Individuals with a heart weight $500 g are represented in red columns.
Pie chart presents the cause of death in individuals with a heart weight $500 g (n ¼ 70). RV ¼ right ventricle.
examination. Idiopathic fibrosis accounted for 11% of
and those of athletes who died at rest were similar,
deaths, ARVC for 7%, and HCM for 4% of the other
and only a minority of subjects (8%) had a family
deaths. None of the female athletes showed idio-
history of sudden death. Patients who died at rest
pathic LVH.
were more likely to demonstrate a normal heart at
CIRCUMSTANCES OF DEATH. The majority of ath-
post-mortem examination (Table 2). Conversely, ath-
letes died during exertion (n ¼ 219 [61%]), including a
letes who died during exertion were more likely to
small proportion of individuals (n ¼ 14 [4%]) who
have ARVC (20% vs. 3%, respectively; p < 0.001), LV
died during altercation. Of the 138 subjects who died
fibrosis (39% vs. 22%, respectively; p < 0.001), and
at rest, 47 (34%) died during sleep. The age and sex
coronary artery anomalies (7% vs. 1%, respectively;
distributions of athletes who died during exertion
p ¼ 0.01).
Multivariate analysis identified ARVC (hazard ratio
[HR]: 6.01; 95% confidence interval [CI]: 1.97 to 18.32;
T A B L E 2 Characteristics of the Population According to
p ¼ 0.001) as the strongest independent predictor of
Circumstances of Death
SCD during exercise, followed by LV fibrosis (HR: 2.11;
Total
(N ¼ 357)
Died on Exertion
(n ¼ 219)
Died at Rest
(n ¼ 138)
Age, yrs
29 11
29 12
29 11
0.944
Males
326 (92)
201 (92)
125 (91)
0.673
Family history of SD
p Value
95% CI: 1.15 to 3.88; p ¼ 0.01) (Table 3).
DISCUSSION
28 (8)
17 (8)
11 (8)
0.911
This study reports on a large number of young
421 110
413 107
434 115
0.086
LV fibrosis
85 (39)
30 (22)
<0.001
athletes dying suddenly in the United Kingdom for
115 (32)
SADS
149 (42)
75 (34)
74 (54)
<0.001
Heart weight, g
HCM
23 (6)
13 (6)
10 (7)
0.237
ARVC
48 (13)
44 (20)
4 (3)
<0.001
ILVH and/or fibrosis
59 (16)
34 (15)
25 (18)
Coronary artery anomaly
18 (5)
16 (7)
Coronary artery atheroma
8 (2)
6 (3)
whom all post-mortem examinations were conducted
by a cardiac pathologist with expertise in conditions
predisposing to SCD. In comparison to a smaller study
0.548
published by our group (6), the large sample size of
2 (1)
0.01
almost 70% competitive athletes allowed for a greater
2 (1)
0.521
degree of certainty relating to the impact of specific
Values are mean SD or n (%).
ARVC ¼ arrhythmogenic right ventricular cardiomyopathy; HCM ¼ hypertrophic cardiomyopathy;
ILVH ¼ idiopathic left ventricular hypertrophy; LV ¼ left ventricular; SADS ¼ sudden arrhythmic
death syndrome; SD ¼ sudden death.
pathologies associated with SCD during intensive
exercise.
CAUSES OF SCD IN ATHLETES. In agreement with
our earlier study (6) and with studies in U.S.
Finocchiaro et al.
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Sudden Death in Athletes
collegiate athletes (16) and young military personnel
(17), a normal heart indicative of a diagnosis of SADS
T A B L E 3 Multivariate Analysis of Death During Exercise
Univariate Analysis
was present in a significant proportion of athletes. A
p Value
Male
1.29 (0.58–2.81)
0.534
0.946
structurally normal heart accounted for 42% of the
overall cohort in this study, compared to the 23% we
reported previously (6). Although the high prevalence
Multivariate Analysis
Hazard Ratio
(95% CI)
Hazard Ratio
(95% CI)
Age at death
0.99 (0.98–1.12)
of SADS in our cohort may be partly explained by a
Caucasian ethnicity
1.09 (0.43–2.72)
0.85
referral bias, its high prevalence in U.S. cohorts (31%
Family history of SD
0.96 (0.43–2.12)
0.93
in collegiate athletes and 41% in young military
Competitive athlete
1.13 (0.71–1.8)
0.59
personnel) underscores the importance of inherited
LV fibrosis
2.43 (1.48–4.01)
<0.001
primary arrhythmia syndromes as a major cause of
Heart weight*
0.96 (0.95–0.97)
0.001
SCD in athletes (16,17).
ARVC
8.36 (2.93–23.84) <0.001 6.01 (1.97–18.32)
Myocardial disease accounted for 40% of cases.
Idiopathic LVH and/or fibrosis and ARVC were the
Coronary artery anomaly 5.32 (1.20–23.51)
2.11 (1.15–3.88)
0.008
SADS
0.44 (0.29–0.68)
0.002
HCM
0.80 (0.34–1.88)
0.613
predominant diagnoses. The significance of idiopathic LVH is uncertain. The entity may be an innocent bystander, but the possibility of pathological
*For every 10 g increase.
CI ¼ confidence interval; other abbreviations as in Table 3.
LVH as a variant of HCM, cannot be excluded,
particularly in the presence of LV fibrosis (12). Idiopathic LVH may also be a trigger for arrhythmia in
intense exercise may be a causal factor. Studies
individuals with underlying primary arrhythmia
have previously reported raised serum concentration
syndrome. In a recent study by our group, familial
of biomarkers of myocyte injury following endurance
evaluation of victims of SCD with autopsy findings
events,
consistent with idiopathic LVH, identified primary
fibrosis on cardiac magnetic resonance and a higher
arrhythmia syndromes in 6 of 13 (46%) families and
burden of atrial and ventricular arrhythmias in vet-
probable HCM in only 1 family (12). In such circum-
eran endurance athletes (20–22). More than 80% of
stances, a false diagnosis of HCM has potentially
athletes died suddenly without warning symptoms,
significant implications for surviving relatives who
underscoring the possible limitations of cardiac
may be subjected to targeted screening for cardio-
screening based only on medical history and physical
myopathy rather than the extensive evaluation,
examination (23).
including
pharmacological
provocation
tests,
to
detect primary arrhythmia syndromes (18).
In this study, HCM contributed to only 6% of
deaths. That is in contrast to the established perception that HCM is the commonest cause of SCD in
athletes (4,19). This may partly reflect the stringent
diagnostic criteria applied by our group, which requires the presence of >20% of myocardial disarray in
at least 2 tissue blocks of 4 cm 2 (14). In contrast,
nonspecialist pathologists may attribute exerciseinduced adaptations such as LVH to HCM (7)
without conducting a detailed histological analysis
of the heart. This probability highlights the importance that post-mortem examinations in athletes
should be performed by pathologists with a high level
of experience in conditions predisposing to SCD. We
cannot disregard the possibility of selection bias, as
an
increased
prevalence
of
myocardial
EFFECT OF AGE. In agreement with previous studies
(6,24), SADS exhibited a significant age predilection.
SADS accounted for more than one-half of all deaths
in children and adolescents, but for only 26% of
deaths in individuals older than 35 years of age. In
contrast, myocardial disease was more prevalent
with advancing age. ARVC, a condition commonly
associated with SCD in young athletes, was rarely
detected in children and adolescents (4%) but
accounted 18% of deaths in individuals >35 years.
Our results are consistent with a large autopsy study
in 200 cases of ARVC (25), where the average age of
death was at 33 years and almost 40% of deaths
occurred after age 35. Interestingly, ARVC was
associated with an increased heart weight in 25% of
cases.
general pathologists may be less inclined to refer
RELATIONSHIP BETWEEN SUDDEN CARDIAC DEATH
diseases such as HCM to our center if they are confi-
AND EXERCISE. As reported previously (4,26), we
dent about the diagnosis.
demonstrated that SCD in athletes occurs more
An important minority (8%) showed idiopathic
frequently during exercise. The strongest predictor
fibrosis. Possible explanations include healed myo-
for SCD during exertion was ARVC. Athletes with
carditis or incomplete expression of cardiomyopathy.
ARVC were 6 times more likely to die on exertion
However, it is also possible that long-standing
compared to those with other cardiac pathologies
p Value
0.01
0.001
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Sudden Death in Athletes
(92% experienced SCD on the athletic field). LV
athletes is a rare event, the large number of
fibrosis
of
post-mortem examinations performed in our unit in
exercise-induced SCD. Coronary artery anomalies
this cohort suggests that the results are a genuine
were a rare cause of SCD, but the majority of deaths
representation of the type and frequency of cardiac
occurred during exertion. Although HCM is consid-
diseases implicated in SCD in young athletes.
was
also
an
independent
predictor
ered the leading cause of exercise induced SCD in
It is possible that subtle or incomplete expressions
athletes, deaths from HCM in our cohort did not show
of cardiomyopathy may have been misclassified as
any predilection for exercise. Our results, however,
SADS; however, considering our thorough laboratory
should be interpreted with caution given the rela-
protocol, it is highly unlikely that such cases
tively low numbers of HCM-related deaths in this
accounted for a significant proportion of deaths
study. In agreement with current published reports,
attributed to SADS.
SADS accounted for the majority of deaths at rest
Our study does not include data relating to survi-
(54%) compared to a third of deaths (34%) during
vors of sudden cardiac arrest. As such, it is possible
exertion.
that the results are biased toward lethal causes of
CLINICAL IMPLICATIONS. Given that almost 40%
of athletes died outside the context of exercise,
including 13% during sleep, it is highly unlikely
that the provision of AEDs in public venues would
have prevented these deaths. Many of the SCDs during
sudden cardiac arrest such as cardiomyopathies and
primary arrhythmia syndromes, whereas diseases
more amenable to survival following cardiac arrest
are under-represented (8,9).
CONCLUSIONS
rest were related to SADS and possibly to primary
arrhythmia syndromes that are often detectable
Conditions predisposing to SCD in sport demonstrate
with
individuals.
significant age predilection. SADS accounts for most of
Pre-participation screening may therefore be useful in
the deaths in the very young, whereas cardiomyopa-
this scenario. With ARVC, ECG may be abnormal in
thies predominate with increasing age. Although the
55%
ECG-based
majority of athletes die during exertion, almost 40%
pre-participation screening might be effective at
die at rest, highlighting the need for complementary
detecting athletes with the condition. Immediate
preventative strategies in addition to provision of
availability
potentially
AED. The strong association of ARVC with exercise-
life-saving for cases that are not detected during
induced SCD reinforces the need for competitive
pre-participation screening. Finally, LV fibrosis is
sport restriction in athletes with the condition.
increasingly recognized in athletes but is not consid-
Finally, the high prevalence of idiopathic LVH or
ered in isolation as a reason for exercise restriction.
fibrosis underscores the need for further research in
This study suggests that LV fibrosis is a trigger for
the field in order to delineate their significance.
an
to
ECG
75%
of
of
in
asymptomatic
cases
an
AED
(27–29),
could
and
be
exercise induced fatal arrhythmias in some athletes
and warrants longitudinal assessment of asymptom-
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
atic athletes with isolated LV fibrosis (30).
Sanjay Sharma, Cardiovascular Sciences, St. George’s
STUDY LIMITATIONS. The CRY Centre for Cardiac
Pathology at St George’s University of London is
more likely to receive hearts from subjects where the
clinical history is suggestive of an inherited cardiac
disease. Local pathologists are more likely to refer
challenging cases, such as athletes with ambiguous
autopsy findings or athletes for whom an obvious
cause of death cannot be established. These facts
introduce a potential referral bias; pathologies such
as coronary artery atherosclerosis and HCM may be
under-represented in this cohort. Similarly, the
prevalence of less well-defined entities such as idiopathic LVH and a morphologically normal heart may
be overestimated. Nevertheless, we receive a high
volume of unexpected SCD referrals (>400 per year);
58% are in individuals <35 years of age at death,
including athletes. Considering that SCD in young
University of London, Cranmer Terrace, London SW17
0RE, United Kingdom. E-mail: [email protected].
PERSPECTIVES
COMPETENCY IN MEDICAL KNOWLEDGE:
Causes of sudden death in athletes vary with age.
SADS is prevalent in children and adolescents,
whereas cardiomyopathies are the most common
cause in adults. ARVC is strongly associated with
sudden death during exertion.
TRANSLATIONAL OUTLOOK: Further studies are
needed to better understanding the causes and circumstances of sudden death to facilitate development
of preventive strategies.
Finocchiaro et al.
JACC VOL. 67, NO. 18, 2016
MAY 10, 2016:2108–15
Sudden Death in Athletes
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KEY WORDS arrhythmogenic right
ventricular cardiomyopathy, athletes,
sudden death
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