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CLINICAL RESEARCHElectrocardiology and Risk Stratification

Prevalence of hypertrophic cardiomyopathy onan electrocardiogram-based pre-participationscreening programme in a young male South-East Asian population: results from the SingaporeArmed Forces Electrocardiogram andEchocardiogram screening protocolChoon Ta Ng1, Tek Siong Chee2, Lee Fong Ling2, Yian Ping Lee2, Chi Keong Ching3,Terrance S.J. Chua3, Christopher Cheok4, and Hean Yee Ong2*

1Medical Classification Centre, Central Manpower Base, Singapore Armed Forces, 3 Depot Road, Singapore 109680, Singapore; 2Department of Cardiology, Khoo Teck PuatHospital, 90 Yishun Central, Singapore 768828, Singapore; 3National Heart Centre Singapore, 17 Third Hospital Avenue, Mistri Wing, Singapore 168752; and 4Department ofPsychological 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 compulsoryfor 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.

Methodsand results

From October 2008 to May 2009, all male military conscripts underwent pre-participation screening. For all con-scripts whose electrocardiogram (ECG) findings fulfilled any of these pre-specified criteria (Group A), direct referralfor a transthoracic echocardiogram was mandatory. Conscripts with ECG findings other than pre-specified 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 withsevere abnormalities; there was one case each of HCM, bicuspid aortic valve with significant aortic valve regurgitation,and atrial septal defect with right ventricular systolic dysfunction. The patient with HCM had left axis deviation onECG. 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 16–27) using an ECG-based screeningprotocol 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 thetrue 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: ong.hean.yee@alexandrahealth.com.sg

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2011. For permissions please email: journals.permissions@oup.com.

Europace (2011) 13, 883–888doi:10.1093/europace/eur051

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IntroductionSudden death in the young can be the first presentation of anunderlying cardiovascular disease.1,2 In young people ,35 yearsold, the incidence of sudden death from all causes is 1.5–6.5 per100 000 persons per year while sudden cardiac death (SCD)occurs in 0.3–3.6 per 100 000 persons per year.1– 11 The reportedincidence of sports-related sudden deaths in Singapore is 1 in 2 445250 persons from year 2000 to 2006.12 Although uncommon, SCDin a young person is a devastating event that attracts significantmedia coverage, perhaps due to the public perception that youthembodies health and invulnerability.13,14

Hypertrophic cardiomyopathy (HCM) is the leading cause of SCD inthe young during physical exertion in the USA.2,11,13–17 In a similarItalian population, arrhythmogenic right-ventricular cardiomyopathy(ARVC)wasthecommonest causeof SCD.18 The reportedprevalenceof HCM is 0.2 and 0.07% in unselected individuals and trained athletes,respectively.18,19 Pre-participation screening could potentially identifysubjects with lethal ‘silent’ cardiovascular disease, and their timely dis-qualification from rigorous physical activities may prevent SCD.11

In the Republic of Singapore, military service is compulsory forall young able-bodied male citizens between the ages of 17 and30. Although rare, sudden deaths have been reported to occuramong these soldiers during training.12 Prior to enlistment, allmale citizens undergo comprehensive medical screening in asingle centralized medical facility to evaluate the suitability of theconscripts for military service. Since 2000, the Singapore ArmedForces Electrocardiogram and Echocardiogram (SAFE) screeningprotocol, which incorporates a routine electrocardiogram (ECG)for all military conscripts, was introduced. The cardiac screeningprotocol was further revised in October 2008 to include a ECGchecklist similar to the Italian system;18 and to incorporate a clinicalpathway whereby direct referral for echocardiography was manda-tory for subjects whose ECG fulfilled these specific criteria. Thispaper evaluates the prevalence of HCM in a young male South-EastAsian population using results from the SAFE screening protocol.

MethodsFrom October 2008 to May 2009, 18 476 male military conscripts con-secutively underwent pre-participation screening at a single militarymedicine screening facility. The pre-participation screening consistedof medical and family history, clinical examination, chest X-ray, bloodpressure, and a 12-lead resting ECG. A significant family history wasdefined as the presence of premature SCD of a first-degree relativebelow the age of 65 years old for females, and 55 years old formales, hypertrophic or dilated cardiomyopathy, long QT syndrome,Marfan syndrome, or clinically important arrhythmias in familymembers. The medical history was considered significant if therewas exertional chest discomfort, palpitations, dyspnea, or unexplainedsyncope during physical exertion. Physical findings such as cardiacmurmurs, Marfanoid habitus, and blood pressure of .140/90 mmHgwere considered to be significant. The resting ECG was then reviewedagainst a standardized checklist by the medical officer.

ElectrocardiogramStandard 12-lead resting ECG was performed by trained personnelwith the subject in supine position using the Schiller AT2-Plus or

Mortara Eli 250 system. The checklist criteria for an abnormal ECGincluded (i) frontal-plane axis deviation: right axis deviation ≥1208or left axis deviation 230 to 2908; (ii) increased voltage: amplitudeof 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 Qwave: ≥0.04 s in duration or ≥25%, or QS pattern in two or moreleads; (iv) right or left bundle branch block with QRS duration≥0.12 s; and (v) R or R1 wave in lead V1 ≥0.5 mV in amplitude andR:S ratio ≥1. For all conscripts whose ECG findings fulfilled any ofthese pre-specified 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 findings (e.g. T-wave inversions in twoor more leads, ST segment changes, Brugada sign, Wolff–Parkinson–White pattern, long QTc) were referred for secondary screening bycardiologists in public institutions (Group B), which could includeechocardiography, based on the judgement of the cardiologist.

Subjects with normal ECG findings (Group C) but with symptomsraising the possibility of cardiac disease were referred for cardiologyconsultation and further investigation as needed.

EchocardiogramEchocardiographic images were acquired in the standard parasternaland apical views by experienced sonographers using GE VingmedVivid i or Vivid 7 Pro systems (GE Ultrasound Europe, Horten,Norway). All 2D, M-mode and Doppler measurements were obtainedusing standard views and techniques.20,21 Apart from standard 2D andcolour Doppler views of the cardiac chambers and valves, all subjectshad assessment of their diastolic function using analysis of their mitralinflow pattern integrated with pulmonary and hepatic vein flow pat-terns as well as septal tissue Doppler velocity. All images were inter-preted by cardiologists trained in echocardiography. Septal Dopplertissue velocity was also measured in all subjects. Septal E/e′ wasderived from the mitral inflow E wave velocity and the septal e′ vel-ocity. The definitive 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 thatcould result in hypertrophy.18 Hypertrophic cardiomyopathy wasalso suspected if the wall thickness was in the intermediate value(.10.0 and ,13.0 mm) and was associated with abnormal diastolicfilling patterns, including an abnormal septal E/e′ ratio of .8.22 Abnor-mal findings on echocardiogram were categorized into severe if theywere potentially life threatening and required follow-up, moderate ifthey were not life threatening but required follow-up, or mild if theywere neither. The findings on the echocardiogram were regarded asnormal if they had normal chamber sizes, ejection fraction, diastolicfilling patterns, aortic root dimensions, and no significant valvularincompetency or stenosis.

ResultsOf the 18 476 conscripts who underwent medical screening (meanage 19.5, range 16–27), 1203 (6.5%) were referred for echocardio-graphy because of ECG findings. In all, 988 of these referrals(Group A) were the result of detection of specific ECG findingson a checklist (based on the Italian approach) mandating directreferral to echocardiography. Another 297 conscripts (Group B)were referred to cardiology consultation for ECG findings otherthan the pre-specified protocol (such as long QT, Wolff-Parkin-son-White (WPW) pattern, repolarization abnormalities, ST

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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 ¼ 1285) had ECG findings prompting further investigation,and echocardiography was performed for 93.6% of these con-scripts (n ¼ 1203). In addition, 2029 conscripts with normalECGs (Group C) were referred for further investigation as aresult of symptoms that raised the possibility of cardiac disease.

In Group A, the most common ECG criteria fulfilled were thatof increased limb lead voltages (n ¼ 448, 45.3%), followed byincreased pre-cordial lead voltages (n ¼ 334, 33.8%) and frontalaxis deviation (n ¼ 163, 16.5%). Table 1 illustrates the distributionof the ECG abnormalities in the 988 conscripts who were referredfor an echocardiogram based on this approach.

Of the 988 conscripts (Group A) who underwent a transthoracicechocardiogram based on ECG criteria, 68 (6.9%) had abnormalfindings (3 severe, 6 moderate, and 59 mild abnormalities). Therewere three (0.3%) cases with severe abnormalities; there was onecase each of HCM, bicuspid aortic valve (BAV) with significantaortic 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 signifi-cant aortic root dilatation or aortic valve regurgitation (n ¼ 4),ASD without RV dysfunction (n ¼ 1), and mild left ventricular(LV) dilation attributed to athlete’s heart (n ¼ 1). Finally, therewere 59 (6.0%) subjects with mild echocardiogram abnormalities;54 had mitral valve prolapse with no significant regurgitation, and4 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 findingson transthoracic echocardiogram. The conscript with HCM hadleft anterior fascicular block with left axis deviation of 2648with normal limb and pre-cordial voltages on ECG.

No cases of HCM or ARVC were also detected in the 215patients referred to echocardiography following referral for cardi-ology consultation for other ECG abnormalities (Group B). Noneof the 2029 conscripts with symptoms but normal ECG findings(Group C) were found to have HCM on further testing.

DiscussionThe prevalence of HCM in our cohort of young South-East Asianmales (mean age 19.5, range 16–27) diagnosed using an ECG-based pre-participation screening protocol was 0.005%. Thisappears low compared with the reported prevalence of 0.05 and0.07% in a young Italian male military population and athletes,respectively (mean age 19+5 years).18,19 Possible explanationsinclude later age of phenotypic manifestation of HCM in thestudy population, limitations of the ECG screening criteria fordetecting 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 possiblethat the local HCM phenotype may present later in adult life, aswas described by Zou et al.23 In the study of 8080 adults inChina, Zou et al. observed that HCM was only detected in subjects.30 years of age, and that none of the 1369 subjects agedbetween 18 and 29 had HCM. Recent studies have also suggestedthat the disease penetrance of HCM is age dependent, and mightnot manifest even at an advanced age.24,25 Christiaans et al.24

reported that the majority of mutation carriers were diagnosedwith HCM after the age of 50 years. Thus, the lower prevalenceof 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, range13–33) in China, there was no definite HCM detected, althoughthree cases were identified to have mild ventricular septal hyper-trophy (13–14 mm) attributed to athlete’s heart.26 A large pro-spective population-based epidemiological study in Chinasuggested an age-adjusted prevalence of 80 per 100 000 persons(0.08%); in that study, there was only one case of HCM in thoseaged ,39 years old and most of the cases of HCM were agedbetween 40 and 59 years old.23 A Japanese hospital-based epide-miological study, which included adults of all ages, suggested aprevalence of 0.014%.27 Epidemiological data from far easterncohorts have consistently shown a lower than previously publishedprevalence of 0.2% in unselected North American cohorts aged23–35 years old from the prospective coronary artery risk devel-opment in (young) adults study28 and 0.02% from a hospital-basedepidemiological study from Olmstead County, Minnesota.29 Fur-thermore, pre-participation screening of 1074 junior athletes(mean age 15.8, range 10–27) in the UK, and of 5615 athletes inNevada, USA did not find any cases of HCM.30,31 Although theechocardiography referral rate of 6.5% in our cohort was alsocomparable with that of 7.9% in the Italian military, we foundmuch fewer cases of HCM.19 Since the introduction of theroutine pre-participation ECG in 2000, there have been noreported deaths from HCM in the Singapore Armed Forces.12

This may suggest a true lower prevalence of HCM in thefar-eastern population, or a milder manifestation of disease.

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Table 1 Distribution of electrocardiogramabnormalities in the 988 conscripts

ECG abnormality Number ofconscripts (n)

1. Frontal-plane axis deviation

Right axis deviation ≥1208 or left axis deviation230 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 V5or V6 ≥3 mV

334 (33.8%)

3. Abnormal Q wave

≥0.04 s in duration or ≥25%, or QS pattern in twoor 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 R1 wave in lead V1 ≥0.5 mV in amplitudeand R:S ratio ≥1

58 (5.9%)

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Table 2 Clinical and electrocardiographic findings 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 leftaxis 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 chestpain

Dilated aortic root and moderate aorticregurgitation

22 18.4 110/60 70 Chinese

Secundum ASD Incomplete RBBB and left posteriorfascicular block right axis deviation1218.

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 orV6 ≥3 mV

Family history of early acute myocardialinfarction in father ,55 years old

No aortic regurgitation; mitral valve prolapsewith 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 systolicejection 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.

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The use of ECG in routine pre-participation screening remainshighly controversial, with the American Heart Association recom-mending history taking and physical examination only, and theEuropean 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 beaddressed before full-scale ECG pre-participation screening canbe introduced in the USA.33 In our study, most of the conscriptswith moderate-to-severe structural heart abnormalities wereasymptomatic and had no obvious clinical signs on standard cardi-ovascular examination. Pre-participation screening limited tomedical history and physical examination was reported to havelow sensitivity, as it failed to identify a significant 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-qualification from strenuous exercise might be life-saving.11

Moreover, the finding of a normal ECG can be regarded as reason-able evidence of the absence of potentially lethal underlyingcardiac disease.35 Given the relatively high false-positive rates ofECG screening for HCM in our study, more sensitive and specificECG parameters may need to be developed to suit local diseasepatterns.34,36 The challenge therein lies in distinguishing physiologi-cal vs. pathological changes on ECG.37

Limitations of our studyThe ECG checklist used in our study is an abridged version of theItalian checklist18 and some subjects may not have had an echocar-diogram because of that. However, conscripts with other ECGfindings (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 asecond clinical pathway (Group B) as briefly described above. Atleast 72.4% of these subjects (or 93.6% of conscripts with ECGfindings) underwent a transthoracic echocardiographic study butnone was subsequently diagnosed to have HCM.

Because we used the resting 12-lead ECG to guide the use ofechocardiography, it is possible that there were some individualswith HCM whose resting ECG did not fulfil our criteria forabnormality. The ECG can only reliably diagnose 70–95% ofpatients with HCM,33,38,39 and some cases are discovered due tosymptoms. In our study population, there was no case of HCMfound on secondary testing for conscripts with symptoms butwith normal ECG findings (Group C). Moreover, other authorshave used similar strategies to yield a higher prevalence of HCM.19

Although we did not detect any case of ARVC in our study, thiscould be attributed to the inherent limitations of an ECG andechocardiographic-based screening protocol to detect this con-dition.40 Since the diagnosis of ARVC depends on the demon-stration of structural, functional, and electrophysiologicalabnormalities, no single test is sufficiently sensitive enough tomake a diagnosis.40,41 In fact, multiple modalities including restingECG, 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 toperform 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-cordialleads and ectopy of RV origin).

While it is a legal requirement for all males to enter militaryservice, females are exempted and the prevalence of HCM inthis group is not known. Therefore, our results are only applicableto the young male population in Singapore. It was shown in earlierstudies that females have a lower prevalence of ECG abnormalitiescompared with males, and this may be partly due to a lesser degreeof LV remodelling.42,43

Keeping these caveats in mind, our results suggest that theprevalence of HCM might be lower in a South-East Asian popu-lation than in a European or North American population. Morepopulation-based studies would be needed to ascertain the trueprevalence of HCM in a South-East Asian population and thedata will have implications for authorities planning mass pre-participation screening programmes especially in populationswith diverse ethnic origins.

Conflict of interest: none declared.

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