Journal of Arrhythmia 31 (2015) 296301

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Journal of Arrhythmia
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Original Article

Clinical presentation and course of long QT syndrome in Thai children

Ankavipar Saprungruang, MDa, Kanyalak Vithessonthi, MDa, Vidhavas La-orkhun, MDa,
Pornthep Lertsapcharoen, MDa, Apichai Khongphatthanayothin, MDa,b,n
a
b

Division of Cardiology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Bangkok Heart Hospital, Bangkok, Thailand

art ic l e i nf o

a b s t r a c t

Article history:
Received 27 December 2014
Received in revised form
23 March 2015
Accepted 1 April 2015
Available online 28 May 2015

Background: Congenital long QT syndrome (LQTS) is a genetically transmitted cardiac channelopathy that
can lead to lethal arrhythmia and sudden cardiac death in healthy young people. The clinical
characteristics of LQTS are variable and depend on the subtype of long QT syndrome, which differ
among populations. This single hospital-based case review study examined the clinical presentation of
long QT syndrome and the outcomes of its treatment in 20 Thai children at King Chulalongkorn
Memorial Hospital in Bangkok, Thailand.
Methods: Inpatient and outpatient records of children (aged 014 years) diagnosed with long QT syndrome
from January 1, 1998, to September 30, 2013, were retrospectively reviewed. Presentation at diagnosis,
treatments, and clinical courses were collected and analyzed. In the 20 subjects, total Schwartz scores
totaled 5.270.9 points, and mean age at diagnosis was 7.674.4 years (range, 1 day13.8 years). The
patients were assigned to one of 3 groups based on trigger events: 50% of patients had events at rest (sleep
or at rest), 35% experienced adrenergic-mediated events (e.g., stress, exercise, startle), and 15% were
asymptomatic. Excluding the 3 patients who died at rst presentation, 100% of patients received a beta
blocker, and 47.1% were treated with an automatic implantable cardioverter-debrillator (AICD).
Results: At follow-up (median959 days; range, 14170 days), 4 patients (20%) were known to have died,
3 of whom died shortly after the diagnosis. Among patients who survived the initial event, 52.9% (9 of 17)
experienced cardiac events (appropriate AICD shock, death, and/or syncope) during the follow-up period.
The mean duration from diagnosis to cardiac event was 14207759 days (range, 4972499 days).
Conclusions: All 20 patients with LQTS were mostly symptomatic at presentation. Owing to the
geographical region and ethnicity of the Thai population, we conclude that the ratio of patients who
develop cardiac symptoms at rest or during sleep might be higher than in other Asian countries.
& 2015 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.

Keywords:
Cardiac arrest
Cardiac arrhythmia
Cardiac conditions of childhood
Congenital long QT syndrome
Syncope
Thai children

1. Introduction
Congenital long QT syndrome (LQTS) is an inheritable cardiac
condition that may lead to fatal cardiac arrhythmia (e.g., torsades de
pointes, ventricular brillation). Typical presentation consists of
syncope, seizure, or even sudden death in otherwise healthy young
people. A large neonatal screening study from Italy reported the
prevalence of long QT syndrome to be at least 1 in 2500 [1], but the
true prevalence of LQTS in other populations is still unknown. Some
studies suggest that LQTS might be an underrecognized rather than
a rare disease [2]. This underestimation might be the result of a
large number of silent-mutation carriers in the total population.
LQTS is classied into subtypes LQT1 to LQT13 based on the site of
genetic mutation. Each type possesses distinct clinical characteristics

n
Corresponding author at: Division of cardiology, Department of Pediatrics, King
Chulalongkorn Memorial Hospital, 1873 Rama IV Rd., Pratumwan, Bangkok 10330,
Thailand. Tel.: 66 89 155 5545; fax: 66 2 256 4911.
E-mail address: apichaik@yahoo.com (A. Khongphatthanayothin).

and a different prognosis. Treatment choice depends partly on

individual phenotype and partly on genotype. Among Asian countries, several reports have been published on the clinical characteristics and course of LQTS patients from Japan, Korea, and China, but
reports from other regions are rare [36].
Our study examined the clinical presentation and outcome of 20
LQTS patients who presented to the Pediatric Department at King
Chulalongkorn Memorial Hospital (KCMH) in Bangkok, Thailand,
between 1998 and 2013.

2. Materials and methods

2.1. Data collection
This study is a single hospital-based case review. Our study
population derived from patients who presented to the Pediatric
Department at KCMH with the diagnosis of congenital LQTS from
January 1, 1998, to September 30, 2013. Demographic data, family

http://dx.doi.org/10.1016/j.joa.2015.03.009
1880-4276/& 2015 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.

A. Saprungruang et al. / Journal of Arrhythmia 31 (2015) 296301

history, clinical presentation, echocardiogram ndings, and others

special investigations, treatments, and outcomes were collected.
Data were reviewed from outpatient and inpatient records at
KCMH. The ethics committee of the Faculty of Medicine at
Chulalongkorn University approved this study. Informed consent
was obtained from all surviving patients at the time of this study.
2.2. Diagnosis
The diagnosis of LQTS was made based on clinical background,
using the 2013 HRS/EHRS/APHRS consensus guidelines [7]. Only
patients who were diagnosed as having the congenital form of
LQTS were included. Those with cardiac arrest and/or a prolonged
QT interval from an identiable cause, such as myocardial ischemia, trauma, infection, electrolyte abnormalities, known history of
exposure to QT-prolonging medications, or known congenital
heart disease, were excluded. QT interval was measured in lead
II or V5 and corrected for differences in heart rate using Bazett's
formula [8].
2.3. Patients' clinical characteristics grouped by trigger events
The patients were divided into 3 groups based on trigger events:
those who experienced events occurring at rest (group 1), those
with adrenergic-mediated events (e.g., stress, exercise, and startle)
(group 2), and those who were asymptomatic (group 3).
2.4. Statistical analysis
Continuous data were expressed as mean 7SD, and nominal
data were expressed as percentages. Among the 3 groups, one-way
ANOVA was used to compare continuous data, and Chi-square
analysis was used to compare nominal data. Treatment outcomes
were presented using KaplanMeier survival curves, which
showed the cumulative event rates for death, cardiac arrest/
ventricular arrhythmia, and/or syncope. A log-rank test was used
to compare the groups' cumulative-event-free survival curves.

3. Results
3.1. Clinical characteristics
The clinical characteristics of the study subjects are summarized in Table 1.
A total of 20 patients were identied, most of whom had no
comorbid conditions. Nine patients (45%) were male. The mean
age at diagnosis was 7.674.4 years (range, 1 day13.8 years). The
subjects' total Schwartz score at presentation was 5.2 70.9 points
(range, 47 points). All patients were categorized as having a high
probability of LQTS based on their Schwartz score ( Z4 points).
Congenital anomalies were noted in 4 subjects (20%). Two
subjects had congenital sensorineural hearing loss, and after echocardiogram was performed in all patients to exclude structural
heart disease, 2 were found to have a left ventricular aneurysm
(1 patient) and a double aortic arch (1 patient). Coronary angiography was performed in the patient with left ventricular aneurysm
and the result was normal. Two patients had comorbid mental
retardation. The number of subjects with a family history of denite
LQTS was 4 (20%), and an additional 4 patients (20%) had a family
history of unexplained sudden cardiac death.

297

Table 1
Clinical characteristics of the study subjects (N 20).
Study subjects (N 20)

% of total

Male

45.0

Age at diagnosis (years)

Mean ( 7SD)
range

7.6 ( 7 4.4)
013.8

Comorbid conditions
Mental retardation

2
2

10.0
10.0

Congenital anomalies
Double aortic arch
Left ventricular aneurysm
SNHL BE

4
1
1
2

20.0
5.0
5.0
10.0

Family history
Denite LQTS
SCD
SNHL

4
4
2

20.0
20.0
10.0

Presenting symptoms
Asymptomatic
Stress-related
Sleep/rest-related

3
7
10

15.0
35.0
50.0

Mean ( 7SD)
range

5.2 ( 7 0.9)
47

3
1
5
3
6
Mean ( 7SD)
range
Mean ( 7SD)
Range

15.0
5.0
25.0
15.0
30.0
548.1 ( 7 61.5)
465707
79.9 ( 721.4)
46120

Total Schwartz score (points)

Electrocardiographic characteristics
Torsades de pointes
T-wave alternans
Notched T wave
Giant negative T wave
Bradycardia
QTc (ms)
HR (bpm)

Treatments (n 17; excluding patients who died shortly after diagnosis)

Beta blocker
17
100.0
Atenolol
8
47.1
Propanolol
9
52.9
AICD
8
47.1
Current status (n 20)
Alive
Died
Lost to follow-up

15
4
1

75.0
20.0
5.0

BE both ears; SNHL, sensorineural hearing loss; SCD, sudden cardiac death; QTc,
corrected QT interval; bpm, beat per minute; HR, heart rate; AICD, automatic
implantable cardioverter-debrillator.

79.9 721.4 bpm (range 46120 bpm). Six patients (30%) had
bradycardia compared with age-matched normal individuals.
Torsades de pointes was documented in 3 patients (15%). Notched
T wave in at least 3 leads (Fig. 1A) was found in 5 patients (25%).
One patient (5%) had T-wave alternans (Fig. 1B). Giant negative
T-wave with prolonged QT intervals was observed in 3 patients
(15%) (Fig. 1C).
3.3. Triggers for cardiac events
Among the 20 patients, cardiac symptoms developed at rest or
sleep in 10 (50%) and during stress in 7 (35%). The remaining
3 patients (15%) were asymptomatic at presentation: 1 patient was
diagnosed based on a family screening (a sibling with congenital
LQTS with sensorineural hearing loss), 1 patient was diagnosed
because of fetal bradycardia, and 1 patient presented with bradycardia compared with age-matched normal individuals.

3.2. Electrocardiographic characteristics

3.4. Treatment and outcome

The mean QTc interval at the rst presentation was

548.17 61.5 ms (range 465707), and the mean heart rate was

Excluding the 3 patients who died shortly after presentation, all

17 patients (100%) received a beta blocker; 8 patients received

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A. Saprungruang et al. / Journal of Arrhythmia 31 (2015) 296301

Fig. 1. Example of T-wave abnormalities in the study subjects. (A) Notched T-wave; QTc interval 623 ms (group 2: catecholamine mediated). (B) T-wave alternans; QTc
interval 764 ms (group 1: events at rest/sleep). (C) Giant negative T-wave; QTc interval 723 ms (group 1: events at rest/sleep).

atenolol, and 9 patients received propanolol. One patient was

prescribed phenytoin (Dilantin) after a standard dose of propranolol (5 mg/kg/day) failed to control ventricular arrhythmia. Mexiletine is not available in Thailand; therefore, no patient was
administered this medication. Eight patients (47.1%) were treated
with automated implantable cardioverter-debrillators (AICDs);
7 of these 8 patients presented with ventricular arrhythmia during
sleep. In this retrospective study, 1 patient (5%) was lost to followup after the initial clinic visit, but the remaining 19 patients'
follow-up data were available.
Four patients (20%) had died at the time of this report. Three
died shortly after the diagnosis (duration from diagnosis to death

was o1 day for 2 patients and 48 days for 1 patient). One patient
treated with an AICD died 2499 days after the diagnosis and had
been lost to follow-up for 4.3 years before death. Nine of 20 patients
(45%) experienced cardiac events during the follow-up period.
Excluding the 3 patients who died shortly after diagnosis, the
mean time to cardiac event was 14207759 days (range, 497
2499 days).
3.5. Patients' clinical characteristics grouped by trigger events
The patients were divided into 3 groups: 10 patients (50%) who
had cardiac events occurring at rest (group 1), 7 patients (35%)

A. Saprungruang et al. / Journal of Arrhythmia 31 (2015) 296301

299

Table 2
Clinical characteristics of subjects based on trigger events (N 20).
Subjects (N 20)

Group 1 events at rest or

sleep

P-value

10

Male

Age at diagnosis (years)

33.3

0.069

Range
0.1
12.3

Mean ( 7 SD)
3.5 ( 7 3.3)

Range
06.5

0.149

0
0

0.0
0.0

0
0

0.0
0.0

0.329

10.0
10.0
0.0
0.0

1
0
1
0

14.3
0.0
14.3
0.0

2
0
0
2

66.7
0.0
0.0
66.7

0.088

2
4
0

20.0
40.0
0.0

0
0
0

0.0
0.0
0.0

2
0
2

66.7
0.0
66.7

0.054
0.082
0.002

Mean ( 7 SD)
5.1 (7 0.88)

Range
46.5

Mean ( 7 SD)
5.6 ( 7 0.85)

Range
57

Mean ( 7 SD)
4.5 ( 7 0.0)

Range
4.5

0.139

2
0
1
0
1
Mean ( 7 SD)
535.9 ( 7 69.1)

72.4 ( 717.9)

28.6
0.0
14.3
0.0
14.3
Range
467
650
56
120

0
0
1
1
1
Mean ( 7 SD)
527.3 ( 7 40.9)

HR (bpm)

10
10
30
20
40
Range
465
707
46120

0.0
0.0
33.3
33.3
33.3
Range
494
573
75
109

0.420
0.591
0.714
0.329
0.518

QTc (ms)

1
1
3
2
4
Mean ( 7 SD)
550.3 ( 7 65.3)

0.871

Group 2 catecholamine
mediated

Group
3 asymptomatic

70.0

14.3

Mean ( 7 SD)
9.1 (7 4.2)

Range
Mean ( 7 SD)
0.813.9 7.3 ( 7 4.2)

Comorbid conditions
Mental retardation

2
2

20.0
20.0

Congenital anomalies
Double aortic arch
Left ventricular aneurysm
SNHL BE

1
1
0
0

Family history
Denite LQTS
SCD
SNHL
Total Schwartz score (points)
Electrocardiographic characteristics
Torsades de pointes
T-wave alternans
Notched T wave
Giant negative T wave
Bradycardia for age

84.3 ( 7 25.4)

94.7 ( 7 17.6)

Treatments (N 17) (excluding 3 patients who died shortly after diagnosis)

Beta blocker
10
100.0
Atenolol
5
50.0
Propanolol
5
50.0
AICD
7
70.0

4
2
2
1

100.0
50.0
50.0
25.0

3
1
2
0

100.0
33.3
66.7
0

Current status
Alive
Died
Lost to follow-up
Events
Available data
Died shortly after diagnosis
Death, syncope, AICD shock
(excluding patients who died shortly after
diagnosis)
Time to event (days)

0.879
0.239

0.062
0.056

9
1
0

90.0
10.0
0.0

4
3
0

57.1
42.9
0.0

2
0
1

66.7
0.0
33.3

10
0
7.0
Mean ( 7 SD)

100.0
0
70.0
Range

7
3
0
Mean ( 7 SD)

100.0
42.9
0.0
Range

2
0
2
Mean ( 7 SD)

66.7
0
66.7
Range

1109.1 ( 7 693.3)

267
2499
267
2768

1820.0 (7 1784.5)

94170 2195.0 ( 7 1276.0)

1820.0 (7 1784.5)

94170 1876.7 ( 7 1625.3)

Duration until last follow-up or death (days) 1277.7 ( 7 836.0)

0
2225
0
2830

0.052

0.861
0.653

BE Both ears; SNHL, sensorineural hearing loss; SCD, sudden cardiac death; QTc, corrected QT interval; bpm, beats per minute; HR, heart rate; AICD, automatic implantable
cardioverter-debrillator.

with adrenergic-mediated events (group 2), and 3 patients (15%)

who were asymptomatic (group 3). The clinical characteristics of
each group are shown in Table 2.
Patients who experienced events at rest (group 1) were older at
presentation (P 0.149) and were more likely to be male
(P 0.069), though these differences were not statistically signicant. The corrected QT interval, incidence of T-wave abnormalities,
and Schwartz score did not signicantly differ among the 3 groups.
Patients who developed symptoms during rest/sleep (group 1)
underwent more AICD implantations than the other groups
(P 0.062). Event-free survival times after treatment in symptomatic patients are shown in Fig. 2. Note that none of the group
2 patients developed symptoms of cardiac event after treatment

with a beta blocker, whereas in group 1 patients, the incidence of

recurrent cardiac events was much higher; however, the difference
was not statistically signicant (P 0.057).

4. Discussion
Cardiac ion channels, including potassium, calcium, and
sodium, are crucial for transporting ions across cell membranes,
resulting in cardiac depolarization and repolarization. Defective
ion channels can lead to abnormal repolarization, prolonged QT
interval, and ventricular tachyarrhythmia.

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A. Saprungruang et al. / Journal of Arrhythmia 31 (2015) 296301

Fig. 2. KaplanMeier curve demonstrating freedom from cardiac events (death,

appropriate AICD discharge, and/or syncope) from the time of diagnosis in
symptomatic patients (excluding patients who died shortly after diagnosis) divided
into groups according to triggered event. Curve 1 patients who developed
symptoms during rest/during sleep (group 1). Curve 2patients who developed
symptoms during exercise/adrenergic-mediated events (group 2).

Multiple genes encoding these cardiac ion channels have been

identied as causes of congenital LQTS, which has been historically
divided into two main subtypes: RomanoWard syndrome (autosomal dominant) and Jervell and LangeNielsen syndrome (autosomal recessive with neurosensory deafness) [7,9]. Both subtypes
are now further subclassied based on genotype. This classication system provides an important guide for selecting proper
treatment and preventive method for specic patients. Unfortunately, clinical presentation, heart rate, QTc interval, and Schwartz
score cannot be used with certainty to differentiate among
subtypes of LQTS [10]. Instead, ECG phenotypes have been used
to predict the genotypes of LQTS based on differentiate T-wave
morphology and ST-T segment. However, the application of this
method is not specic to all types of LQTS [11].
4.1. Genotypephenotype correlation of LQTS
RomanoWard syndrome is the most common form of LQTS. It
is classied numerically as LQT1 to LQT13 according to various
sites of mutation in the gene loci. LQT1, LQT2, and LQT3 account
for 92% of cases in which gene mutations are found [7]. LQT1
features a heterogeneous mutation in the KCNQ1 gene, which
encodes the alpha subunit of the cardiac slow delayed rectier
potassium channel. Most arrhythmia events are triggered by
strong emotional stimuli or exercise. LQT2 is characterized by a
defect in the KCNH2 gene, which encodes the alpha subunit of the
rapid delayed rectier potassium channel. Ventricular arrhythmia
in patients with LQT2 is often triggered by strong emotional or
auditory stimuli. LQT3 features a defect in the SCN5A gene, which
causes a gain-of-function mutation in the cardiac sodium channel.
Patients with LQT3 often develop cardiac arrhythmia during rest
or sleep.
Genetic screening by sequencing the protein-coding region of
the genes responsible for LQTS is the best method of differentiating among genotypes. Genetic testing has shown to be benecial
in the prognostication, diagnosis, and treatment of patients with
LQTS [7,12]. However, genetic testing is not always available in
Thailand and many other developing countries. Therefore, data on
the phenotype (clinical presentation, ECG ndings, etc.) may be
used as an alternative in order to elicit differences in LQTS subtype
among Thai patients and those in other developing countries;
these data were not previously available for Thailand.
Studies from Caucasian populations [1] as well as Northern
Asian countries [3,6,9] have demonstrated that the LQT1 and LQT2

genotypes of LQTS are more common than LQT3. For example, a

study of 54 patients from a Chinese registry using ECG (morphology of ST-T wave) criteria suggested that the LQT1 and LQT2
phenotypes are more common than the LQT3 phenotype [5]. In
this study, cardiac events were more frequently triggered by
exercise (50.0%) or emotional stress (41.7%) than by rest or sleep
(14.8%). These results contradict with our nding that the proportion of Thai children with LQTS who develop symptoms during
rest/sleep (50%) is higher than that of patients who present with
stress-induced events (35%). This discrepancy might be because of
the ethnic differences between our population and those in other
Asian countries.
According to the phenotype and genotype correlation, most
patients with LQT1 experienced cardiac events after catecholamine-mediated triggers, such as exercise or emotional stress.
Patients with LQT2 developed cardiac events after startle, auditory
stimuli, or even at rest. Those with LQT3 were more likely to
develop symptoms during sleep. We hypothesize that the subtypes of LQTS in our population might differ from those in other
Asian countries. Further studies to investigate the genotypes of our
LQTS patients are needed to answer these questions.
4.2. Study limitations
Among its limitations, rst, our study was based on singlehospital data; therefore, generalizing its results to the entire Thai
population may not seem appropriate. However, our hospital is
one of the major referral centers for children with cardiac
arrhythmia in Thailand, and our patients came from all parts of
the country. Thus, our data are representative of the Thai
population.
Second, the number of patients was small, as only those who
presented to the hospital were included. However, this population
may not include those patients who did not receive medical
attention and/or those who were asymptomatic or minimally
symptomatic.
Third, classication of LQTS patients based on phenotype has
important limitations for some subtypes, such as LQT2. In these
patients, either rest or exercise (including strong emotional or
auditory stimuli) can trigger arrhythmia. Thus, further genetic
testing would be benecial in our cohort.

5. Conclusion
Our study is the rst to describe the clinical characteristics,
treatment, and outcomes of congenital LQTS patients in Thailand.
Most patients in our study developed cardiac symptoms at rest or
during sleep, which was higher than that reported in other
countries. Further studies are needed to identify the genotypes
of people with LQTS in the Thai population.

Conict of interest
The authors have no conicts of interest to disclose.
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