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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CLINICAL RESEARCH
Electrocardiology and Risk Stratication
Prevalence of hypertrophic cardiomyopathy on
an electrocardiogram-based pre-participation
screening programme in a young male South-
East Asian population: results from the Singapore
Armed Forces Electrocardiogram and
Echocardiogram screening protocol
Choon Ta Ng
1
, Tek Siong Chee
2
, Lee Fong Ling
2
, Yian Ping Lee
2
, Chi Keong Ching
3
,
Terrance S.J. Chua
3
, Christopher Cheok
4
, and Hean Yee Ong
2
*
1
Medical Classication Centre, Central Manpower Base, Singapore Armed Forces, 3 Depot Road, Singapore 109680, Singapore;
2
Department of Cardiology, Khoo Teck Puat
Hospital, 90 Yishun Central, Singapore 768828, Singapore;
3
National Heart Centre Singapore, 17 Third Hospital Avenue, Mistri Wing, Singapore 168752; and
4
Department of
Psychological Medicine, Khoo Teck Puat Hospital, 90 Yishun Central, Singapore 768828, Singapore
Received 17 June 2010; accepted after revision 7 February 2011; online publish-ahead-of-print 12 April 2011
Aims Hypertrophic cardiomyopathy is a leading cause of sudden cardiac death (SCD) in young people in the USA. Pre-
participation screening for athletes might reduce the incidence of SCD. In Singapore, military service is compulsory
for all young able-bodied male citizens. The Singapore Armed Forces Electrocardiogram and Echocardiogram (SAFE)
pre-participation screening protocol based on the Italian programme was introduced. This study evaluates the preva-
lence of hypertrophic cardiomyopathy (HCM) in a young male South-East Asian population.
Methods
and results
From October 2008 to May 2009, all male military conscripts underwent pre-participation screening. For all con-
scripts whose electrocardiogram (ECG) ndings fullled any of these pre-specied criteria (Group A), direct referral
for a transthoracic echocardiogram was mandatory. Conscripts with ECG ndings other than pre-specied criteria
(e.g. T-wave inversions, repolarization abnormalities) were referred for secondary screening by cardiologists
(Group B), which could include echocardiography. Out of 18 476 subjects screened during the study period, 988
(5.3%) subjects were fast tracked for echocardiogram (Group A). Of them, there were three (0.3%) cases with
severe abnormalities; there was one case each of HCM, bicuspid aortic valve with signicant aortic valve regurgitation,
and atrial septal defect with right ventricular systolic dysfunction. The patient with HCM had left axis deviation on
ECG. None of the 215 patients who underwent echocardiography following cardiology consult (Group B) had HCM.
Conclusion The prevalence of HCM in our young male population (mean age 19.5, range 1627) using an ECG-based screening
protocol was 0.005%; this appeared lower than published data from other geographical cohorts. Possible expla-
nations include a later age of phenotypic manifestation in our population, limitations of the ECG criteria for screening,
or a truly lower prevalence of HCM. More population-based longitudinal studies would be needed to ascertain the
true prevalence of HCM in our South-East Asian population.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Keywords Sudden cardiac death Hypertrophic cardiomyopathy Pre-participation screening Electrocardiogram (ECG)
Echocardiogram
* Corresponding author. Tel: +65 6602 2137, fax: +65 6602 3700, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2011. For permissions please email: [email protected].
Europace (2011) 13, 883888
doi:10.1093/europace/eur051

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Introduction
Sudden death in the young can be the rst presentation of an
underlying cardiovascular disease.
1,2
In young people ,35 years
old, the incidence of sudden death from all causes is 1.56.5 per
100 000 persons per year while sudden cardiac death (SCD)
occurs in 0.33.6 per 100 000 persons per year.
111
The reported
incidence of sports-related sudden deaths in Singapore is 1 in 2 445
250 persons from year 2000 to 2006.
12
Although uncommon, SCD
in a young person is a devastating event that attracts signicant
media coverage, perhaps due to the public perception that youth
embodies health and invulnerability.
13,14
Hypertrophic cardiomyopathy (HCM) is the leading cause of SCDin
the young during physical exertion in the USA.
2,11,1317
In a similar
Italian population, arrhythmogenic right-ventricular cardiomyopathy
(ARVC) wasthecommonest causeof SCD.
18
Thereportedprevalence
of HCMis 0.2 and 0.07%in unselected individuals and trained athletes,
respectively.
18,19
Pre-participation screening could potentially identify
subjects with lethal silent cardiovascular disease, and their timely dis-
qualication from rigorous physical activities may prevent SCD.
11
In the Republic of Singapore, military service is compulsory for
all young able-bodied male citizens between the ages of 17 and
30. Although rare, sudden deaths have been reported to occur
among these soldiers during training.
12
Prior to enlistment, all
male citizens undergo comprehensive medical screening in a
single centralized medical facility to evaluate the suitability of the
conscripts for military service. Since 2000, the Singapore Armed
Forces Electrocardiogram and Echocardiogram (SAFE) screening
protocol, which incorporates a routine electrocardiogram (ECG)
for all military conscripts, was introduced. The cardiac screening
protocol was further revised in October 2008 to include a ECG
checklist similar to the Italian system;
18
and to incorporate a clinical
pathway whereby direct referral for echocardiography was manda-
tory for subjects whose ECG fullled these specic criteria. This
paper evaluates the prevalence of HCM in a young male South-East
Asian population using results from the SAFE screening protocol.
Methods
From October 2008 to May 2009, 18 476 male military conscripts con-
secutively underwent pre-participation screening at a single military
medicine screening facility. The pre-participation screening consisted
of medical and family history, clinical examination, chest X-ray, blood
pressure, and a 12-lead resting ECG. A signicant family history was
dened as the presence of premature SCD of a rst-degree relative
below the age of 65 years old for females, and 55 years old for
males, hypertrophic or dilated cardiomyopathy, long QT syndrome,
Marfan syndrome, or clinically important arrhythmias in family
members. The medical history was considered signicant if there
was exertional chest discomfort, palpitations, dyspnea, or unexplained
syncope during physical exertion. Physical ndings such as cardiac
murmurs, Marfanoid habitus, and blood pressure of .140/90 mmHg
were considered to be signicant. The resting ECG was then reviewed
against a standardized checklist by the medical ofcer.
Electrocardiogram
Standard 12-lead resting ECG was performed by trained personnel
with the subject in supine position using the Schiller AT2-Plus or
Mortara Eli 250 system. The checklist criteria for an abnormal ECG
included (i) frontal-plane axis deviation: right axis deviation 1208
or left axis deviation 230 to 2908; (ii) increased voltage: amplitude
of R or S wave in a standard lead 2 mV, S wave in lead V1 or V2
3 mV or R wave in lead V5 or V6 3 mV; and (iii) abnormal Q
wave: 0.04 s in duration or 25%, or QS pattern in two or more
leads; (iv) right or left bundle branch block with QRS duration
0.12 s; and (v) R or R
1
wave in lead V1 0.5 mV in amplitude and
R:S ratio 1. For all conscripts whose ECG ndings fullled any of
these pre-specied criteria (Group A), direct referral for a transthor-
acic echocardiogram was mandatory, followed by assessment by cardi-
ologists at a single cardiology centre in Singapore.
Conscripts with other ECG ndings (e.g. T-wave inversions in two
or more leads, ST segment changes, Brugada sign, Wolff Parkinson
White pattern, long QTc) were referred for secondary screening by
cardiologists in public institutions (Group B), which could include
echocardiography, based on the judgement of the cardiologist.
Subjects with normal ECG ndings (Group C) but with symptoms
raising the possibility of cardiac disease were referred for cardiology
consultation and further investigation as needed.
Echocardiogram
Echocardiographic images were acquired in the standard parasternal
and apical views by experienced sonographers using GE Vingmed
Vivid i or Vivid 7 Pro systems (GE Ultrasound Europe, Horten,
Norway). All 2D, M-mode and Doppler measurements were obtained
using standard views and techniques.
20,21
Apart from standard 2D and
colour Doppler views of the cardiac chambers and valves, all subjects
had assessment of their diastolic function using analysis of their mitral
inow pattern integrated with pulmonary and hepatic vein ow pat-
terns as well as septal tissue Doppler velocity. All images were inter-
preted by cardiologists trained in echocardiography. Septal Doppler
tissue velocity was also measured in all subjects. Septal E/e

was
derived from the mitral inow E wave velocity and the septal e

vel-
ocity. The denitive diagnosis of HCM was made based on the demon-
stration of a hypertrophic, non-dilated left ventricle wall thickness of
13 mm in the absence of another cardiac or systemic disease that
could result in hypertrophy.
18
Hypertrophic cardiomyopathy was
also suspected if the wall thickness was in the intermediate value
(.10.0 and ,13.0 mm) and was associated with abnormal diastolic
lling patterns, including an abnormal septal E/e

ratio of .8.
22
Abnor-
mal ndings on echocardiogram were categorized into severe if they
were potentially life threatening and required follow-up, moderate if
they were not life threatening but required follow-up, or mild if they
were neither. The ndings on the echocardiogram were regarded as
normal if they had normal chamber sizes, ejection fraction, diastolic
lling patterns, aortic root dimensions, and no signicant valvular
incompetency or stenosis.
Results
Of the 18 476 conscripts who underwent medical screening (mean
age 19.5, range 1627), 1203 (6.5%) were referred for echocardio-
graphy because of ECG ndings. In all, 988 of these referrals
(Group A) were the result of detection of specic ECG ndings
on a checklist (based on the Italian approach) mandating direct
referral to echocardiography. Another 297 conscripts (Group B)
were referred to cardiology consultation for ECG ndings other
than the pre-specied protocol (such as long QT, Wolff-Parkin-
son-White (WPW) pattern, repolarization abnormalities, ST
C.T. Ng et al. 884

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segment changes, T-wave inversions). Of these 297 conscripts, 215
(72.4%) were referred to echocardiography following consultation.
Thus, of the 18 476 conscripts screened during the study period,
7.0% (n 1285) had ECG ndings prompting further investigation,
and echocardiography was performed for 93.6% of these con-
scripts (n 1203). In addition, 2029 conscripts with normal
ECGs (Group C) were referred for further investigation as a
result of symptoms that raised the possibility of cardiac disease.
In Group A, the most common ECG criteria fullled were that
of increased limb lead voltages (n 448, 45.3%), followed by
increased pre-cordial lead voltages (n 334, 33.8%) and frontal
axis deviation (n 163, 16.5%). Table 1 illustrates the distribution
of the ECG abnormalities in the 988 conscripts who were referred
for an echocardiogram based on this approach.
Of the 988 conscripts (Group A) who underwent a transthoracic
echocardiogram based on ECG criteria, 68 (6.9%) had abnormal
ndings (3 severe, 6 moderate, and 59 mild abnormalities). There
were three (0.3%) cases with severe abnormalities; there was one
case each of HCM, bicuspid aortic valve (BAV) with signicant
aortic regurgitation, atrial septal defect (ASD) with right ventricular
(RV) systolic dysfunction. There were six (0.6%) cases with mod-
erate echocardiogram abnormalities including BAV without signi-
cant aortic root dilatation or aortic valve regurgitation (n 4),
ASD without RV dysfunction (n 1), and mild left ventricular
(LV) dilation attributed to athletes heart (n 1). Finally, there
were 59 (6.0%) subjects with mild echocardiogram abnormalities;
54 had mitral valve prolapse with no signicant regurgitation, and
4 had atrial septal aneurysm and 1 had a dilated coronary sinus.
There were no cases of ARVC found. Table 2 summarizes the clini-
cal characteristics of conscripts with severe and moderate ndings
on transthoracic echocardiogram. The conscript with HCM had
left anterior fascicular block with left axis deviation of 2648
with normal limb and pre-cordial voltages on ECG.
No cases of HCM or ARVC were also detected in the 215
patients referred to echocardiography following referral for cardi-
ology consultation for other ECG abnormalities (Group B). None
of the 2029 conscripts with symptoms but normal ECG ndings
(Group C) were found to have HCM on further testing.
Discussion
The prevalence of HCM in our cohort of young South-East Asian
males (mean age 19.5, range 1627) diagnosed using an ECG-
based pre-participation screening protocol was 0.005%. This
appears low compared with the reported prevalence of 0.05 and
0.07% in a young Italian male military population and athletes,
respectively (mean age 19 +5 years).
18,19
Possible explanations
include later age of phenotypic manifestation of HCM in the
study population, limitations of the ECG screening criteria for
detecting HCM, or a truly lower prevalence of HCM in the South-
East Asian population.
The median age of our cohort was 20 years old, and it is possible
that the local HCM phenotype may present later in adult life, as
was described by Zou et al.
23
In the study of 8080 adults in
China, Zou et al. observed that HCM was only detected in subjects
.30 years of age, and that none of the 1369 subjects aged
between 18 and 29 had HCM. Recent studies have also suggested
that the disease penetrance of HCM is age dependent, and might
not manifest even at an advanced age.
24,25
Christiaans et al.
24
reported that the majority of mutation carriers were diagnosed
with HCM after the age of 50 years. Thus, the lower prevalence
of HCM in our study could be attributable to a later age of pheno-
typic manifestation of HCM in the South-East Asian population.
In another study of pre-participation screening using echocar-
diography on 351 Chinese athletes (mean age 23+3.8, range
1333) in China, there was no denite HCM detected, although
three cases were identied to have mild ventricular septal hyper-
trophy (1314 mm) attributed to athletes heart.
26
A large pro-
spective population-based epidemiological study in China
suggested an age-adjusted prevalence of 80 per 100 000 persons
(0.08%); in that study, there was only one case of HCM in those
aged ,39 years old and most of the cases of HCM were aged
between 40 and 59 years old.
23
A Japanese hospital-based epide-
miological study, which included adults of all ages, suggested a
prevalence of 0.014%.
27
Epidemiological data from far eastern
cohorts have consistently shown a lower than previously published
prevalence of 0.2% in unselected North American cohorts aged
2335 years old from the prospective coronary artery risk devel-
opment in (young) adults study
28
and 0.02% from a hospital-based
epidemiological study from Olmstead County, Minnesota.
29
Fur-
thermore, pre-participation screening of 1074 junior athletes
(mean age 15.8, range 1027) in the UK, and of 5615 athletes in
Nevada, USA did not nd any cases of HCM.
30,31
Although the
echocardiography referral rate of 6.5% in our cohort was also
comparable with that of 7.9% in the Italian military, we found
much fewer cases of HCM.
19
Since the introduction of the
routine pre-participation ECG in 2000, there have been no
reported deaths from HCM in the Singapore Armed Forces.
12
This may suggest a true lower prevalence of HCM in the
far-eastern population, or a milder manifestation of disease.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 1 Distribution of electrocardiogram
abnormalities in the 988 conscripts
ECG abnormality Number of
conscripts (n)
1. Frontal-plane axis deviation
Right axis deviation 1208 or left axis deviation
230 to 2908
163 (16.5%)
2. Increased voltage
Amplitude of R or S wave in a standard lead 2 mV 448 (45.3%)
S wave in lead V1 or V2 3mV or R wave in lead V5
or V6 3 mV
334 (33.8%)
3. Abnormal Q wave
0.04 s in duration or 25%, or QS pattern in two
or more leads
20 (2.0%)
4. Complete bundle branch block with QRS duration 0.12 s
Right bundle branch block (RBBB) 62 (6.3%)
Left bundle branch block (LBBB) 3 (0.3%)
5. R or R
1
wave in lead V1 0.5 mV in amplitude
and R:S ratio 1
58 (5.9%)
Prevalence of hypertrophic cardiomyopathy 885

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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 2 Clinical and electrocardiographic ndings in conscripts with severe and moderate transthoracic echocardiogram abnormalities
Diagnosis ECG Clinical signs or symptoms/history Echocardiogram findings Age BMI BP
(mmHg)
Pulse rate
(beats/ min)
Race
Severe
HCM Left anterior fascicular block with left
axis deviation 2648
Nil IVSd: 17 mm, Septal E/e

:9 (.8) 21 33.0 123/64 95 Chinese

BAV Amplitude of R wave in lead II and III
2 mV, S wave in V2 3 mV
Random, non-exertional sharp chest
pain
Dilated aortic root and moderate aortic
regurgitation
22 18.4 110/60 70 Chinese
Secundum ASD Incomplete RBBB and left posterior
fascicular block right axis deviation
1218.
Nil RV dysfunction 20 21.5 132/78 79 Malay
Moderate
BAV Amplitude of R wave in lead II 2 mV Nil Mild aortic regurgitation 21 24.6 117/72 70 Chinese
BAV Amplitude of R wave in V5 or
V6 3 mV
Family history of early acute myocardial
infarction in father ,55 years old
No aortic regurgitation; mitral valve prolapse
with trivial mitral regurgitation
20 19.6 132/74 62 Chinese
BAV Amplitude of S wave in V2 3 mV Nil Mild aortic regurgitation 20 20.6 100/60 60 Malay
BAV Amplitude of R wave in lead II 2 mV,
V5 3 mV
Nil Mild aortic regurgitation 20 21.0 119/60 50 Chinese
Secundum ASD Amplitude of R wave in lead II 2 mV,
R wave in V5 3 mV
Nil Normal RV size and function 20 22.3 100/61 63 Malay
LV dilatation Amplitude of R wave in lead II 2 mV Nil Mildly dilated LV size with normal systolic
ejection fraction, Mild tricuspid regurgitation
21 23.0 121/60 76 Malay
HCM, hypertrophic cardiomyopathy; BAV, bicuspid aortic valve; ASD, atrial septal defect; LV, left ventricle; RV, right ventricle.
C
.
T
.
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8
6
b y g u e s t o n A u g u s t 2 8 , 2 0 1 4h t t p : / / e u r o p a c e . o x f o r d j o u r n a l s . o r g /D o w n l o a d e d f r o m
The use of ECG in routine pre-participation screening remains
highly controversial, with the American Heart Association recom-
mending history taking and physical examination only, and the
European Society of Cardiology advocating routine ECG.
32
Con-
cerns over the cost of screening, lack of validated ECG interpret-
ation guidelines for athletes, lack of randomized trials need to be
addressed before full-scale ECG pre-participation screening can
be introduced in the USA.
33
In our study, most of the conscripts
with moderate-to-severe structural heart abnormalities were
asymptomatic and had no obvious clinical signs on standard cardi-
ovascular examination. Pre-participation screening limited to
medical history and physical examination was reported to have
low sensitivity, as it failed to identify a signicant number of ath-
letes with increased risk for adverse cardiac events.
33,34
In contrast,
the ECG-based pre-participation screening helped to identify con-
scripts with silent underlying heart disease, and their timely dis-
qualication from strenuous exercise might be life-saving.
11
Moreover, the nding of a normal ECG can be regarded as reason-
able evidence of the absence of potentially lethal underlying
cardiac disease.
35
Given the relatively high false-positive rates of
ECG screening for HCM in our study, more sensitive and specic
ECG parameters may need to be developed to suit local disease
patterns.
34,36
The challenge therein lies in distinguishing physiologi-
cal vs. pathological changes on ECG.
37
Limitations of our study
The ECG checklist used in our study is an abridged version of the
Italian checklist
18
and some subjects may not have had an echocar-
diogram because of that. However, conscripts with other ECG
ndings (such as T-wave inversions and ST segment changes, con-
duction blocks, Brugada pattern, WPW pattern, prolonged QTc)
not included in the checklist were referred to cardiologists on a
second clinical pathway (Group B) as briey described above. At
least 72.4% of these subjects (or 93.6% of conscripts with ECG
ndings) underwent a transthoracic echocardiographic study but
none was subsequently diagnosed to have HCM.
Because we used the resting 12-lead ECG to guide the use of
echocardiography, it is possible that there were some individuals
with HCM whose resting ECG did not full our criteria for
abnormality. The ECG can only reliably diagnose 7095% of
patients with HCM,
33,38,39
and some cases are discovered due to
symptoms. In our study population, there was no case of HCM
found on secondary testing for conscripts with symptoms but
with normal ECG ndings (Group C). Moreover, other authors
have used similar strategies to yield a higher prevalence of HCM.
19
Although we did not detect any case of ARVC in our study, this
could be attributed to the inherent limitations of an ECG and
echocardiographic-based screening protocol to detect this con-
dition.
40
Since the diagnosis of ARVC depends on the demon-
stration of structural, functional, and electrophysiological
abnormalities, no single test is sufciently sensitive enough to
make a diagnosis.
40,41
In fact, multiple modalities including resting
ECG, signal-averaged ECG, echocardiography, exercise testing,
ambulatory ECG monitoring, magnetic resonance imaging,
genetic study, and endomycardial biopsy may be required to diag-
nose ARVC.
40,41
These tests would be impractical and costly to
perform in a large population-based screening protocol, but
should be considered in subjects with ECG abnormalities sugges-
tive of ARVC (such as T-wave inversions in the right pre-cordial
leads and ectopy of RV origin).
While it is a legal requirement for all males to enter military
service, females are exempted and the prevalence of HCM in
this group is not known. Therefore, our results are only applicable
to the young male population in Singapore. It was shown in earlier
studies that females have a lower prevalence of ECG abnormalities
compared with males, and this may be partly due to a lesser degree
of LV remodelling.
42,43
Keeping these caveats in mind, our results suggest that the
prevalence of HCM might be lower in a South-East Asian popu-
lation than in a European or North American population. More
population-based studies would be needed to ascertain the true
prevalence of HCM in a South-East Asian population and the
data will have implications for authorities planning mass pre-
participation screening programmes especially in populations
with diverse ethnic origins.
Conict of interest: none declared.
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