Clinical research

European Heart Journal (2006) 27, 24402447

doi:10.1093/eurheartj/ehl185

Arrhythmia/electrophysiology

Short QT syndrome: clinical ndings and

diagnostictherapeutic implications
Carla Giustetto1*, Fernando Di Monte1, Christian Wolpert2, Martin Borggrefe2, Rainer Schimpf2,
Pascal Sbragia3, Gianpiero Leone4, Philippe Maury5, Olli Anttonen6, Michel Haissaguerre7,
and Fiorenzo Gaita1
1

Department of Cardiology, Cardinal Massaia Hospital, Asti, Italy; 2 Department of Medicine-Cardiology, University Hospital
Mannheim, Germany; 3 Division of Cardiology, Hopital Nord, Marseille, France; 4 Division of Cardiology, Hospital, Aosta, Italy;
5
Federation of Cardiology, University Hospital Rangueil, Toulouse, France; 6 Division of Cardiology, Lahti Central Hospital,
Lahti, Finland; and 7 Hopital Cardiologique du Haut-Leveque, Bordeaux-Pessac, France
Received 7 February 2006; revised 4 July 2006; accepted 20 July 2006; online publish-ahead-of-print 22 August 2006

KEYWORDS
Short QT syndrome;
Sudden death;
Ion channelopathies;
SIDS

Aims Clinical presentation, occurrence of sudden infant death, and results of the available therapies in
the largest group of patients with short QT syndrome (SQTS), studied so far, are reported.
Methods and results Clinical history, physical examination, electrocardiogram (ECG), exercise stress
testing, electrophysiological study, morphological evaluation, genetic analysis and therapy results in
29 patients with SQTS and personal and/or familial history of cardiac arrest are reported. The
median age at diagnosis was 30 years (range 480). In all subjects, structural heart disease was
excluded. Eighteen patients were symptomatic (62%): 10 had cardiac arrest (34%) and in 8 (28%) this
was the rst clinical presentation. Cardiac arrest had occurred in the rst months of life in two patients.
Seven patients had syncope (24%); 9 (31%) had palpitations with atrial brillation documented even in
young subjects. At ECG, patients exhibited a QT interval
320 ms and QTc
340 ms. Fourteen patients
received an implantable cardioverter-debrillator (ICD) and 10 hydroquinidine prophylaxis. At a median
follow-up of 23 months (range 949), one patient received an appropriate shock from the ICD; no
patient on hydroquinidine had sudden death or syncope.
Conclusion SQTS carries a high risk of sudden death and may be a cause of death in early infancy. ICD is
the rst choice therapy; hydroquinidine may be proposed in children and in the patients who refuse the
implant.

Introduction
Although the association between QT prolongation and
sudden death has been known since the 1950s,13 it has
become necessary to wait until recent years to understand
that short QT may also be related to an increased risk of
sudden death. In fact, only recently the association
between a familial history of sudden death4 or atrial brillation (AF)5 with a short QT interval has been recognized and
short QT syndrome (SQTS) identied as a genetic disorder.68
Only one case of aborted sudden infant death has been
reported to date,4 but, in general little is known about the
clinical presentation of SQTS, because the published data
includes only a small number of patients.4,5,710
The aim of this study was to evaluate the clinical presentation, the occurrence of sudden infant death, the electrocardiographic (ECG) morphology, the prevalence of the
known genetic mutations, and the results of the available

* Corresponding author. Tel: 39 0141 487121; fax: 39 0141 487134.

E-mail address: [email protected]

therapies at a mid-term follow-up in a relatively large

group of patients with SQTS.

Methods
Inclusion criteria
This is an observational study designed to be partly prospective and
partly retrospective. A total of 29 patients, 25 belonging to eight
families and four sporadic cases (Figure 1), who had personal
and/or a family history of sudden death or aborted sudden death
and ECG documentation of short QT interval, were included in the
study. Three out the these 29 patients were included after sudden
death, having ECG documentation of short QT. The number of
patients initially assessed was 14. After the screening of their
family members, this number increased to 29. All patients gave
their consent to the study protocol.
In the families, there were another 12 cases of sudden death
without available ECG (Figure 1). For this reason, these subjects
were not included in the study group. However, because all of
them were apparently healthy people, who died suddenly, most
,40 years of age, the association with SQTS may be hypothesized
(Figure 1).

& The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: [email protected]

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See page 2382 for the editorial comment on this article (doi:10.1093/eurheartj/ehl223)

SQTS: clinical ndings and diagnostictherapeutic implications

2441

A value of QT/QTp 80% (where QTp is the predicted QT value

following Rautaharjus formula),11 as previously reported,12 was
chosen as the upper limit for short QT. These patients, all
Caucasian, were referred to our institution from different countries.
Familial and personal medical histories, paying particular attention
to the cases of sudden infant death, were collected from each
patient. The patients underwent an extensive evaluation, including
physical examination, exercise stress testing, ECG, and cardiac
magnetic resonance (MR), in order to rule out structural heart
disease. Blood samples were taken to exclude any electrolyte
abnormalities and to perform a genetic analysis.

stimulation was performed at a pacing cycle length of 600 ms in

the high lateral right atrium.

Therapeutic approach
The implant of an automatic implantable cardioverter-debrillator
(ICD) was proposed to all the patients, except the young children.
In these latter patients, the decision to implant an ICD was considered after taking into account the weight and the age as well.
The young children and the patients who refused the implant
were treated with hydroquinidine, which had already been proved
to prolong the QT interval in a previous study.12

QT measurement
The QT interval was evaluated in all 12-lead ECGs. The QT interval
was measured at a speed of 25 or 50 mm/s and with a 200% magnication, usually in V2, by two independent examiners. The QT was
manually measured as the time interval between QRS onset and
the point at which the isoelectric line intersected a tangential
line drawn at the maximum downslope of the T-wave. The QT interval was corrected for the heart rate using Bazetts formula (QTc).13
The QT interval at different heart rates during the stress test was
compared with the expected QT intervals using the Framingham
linear regression formula,14 as Bazetts formula may not be appropriate for correcting the QT interval for short cardiac cycle lengths.

Electrophysiological study
After informed written consent was obtained, a detailed electrophysiological study was carried out. Ventricular programmed stimulation was performed at two ventricular sites (right ventricular apex
and outow tract) at two or three different pacing cycle lengths,
with two to three extrastimuli up to refractoriness, without any
limits for the shortest coupling interval. Atrial programmed

Follow-up
The patients underwent regular outpatient visits at the reference
centre.

Statistical analysis
Quantitative data was expressed as a mean + SD or as a median,
range, and interquartile range (IQR) as appropriate. Statistical
analysis was performed using STATAw software (8.0). The probability of survival free from cardiac arrest, from birth and before
the age of 40 years or before pharmacological therapy, was assessed
using the KaplanMeier product-limit estimates. To assess the presence of predictors of the occurrence of cardiac arrest before
therapy and accounting for possible within-group correlation, a
shared frailty Cox proportional hazard regression model (latent
familiar-level random effect) based on 12 clusters (eight families
and one group for each sporadic patient) was tted. The Cox
model was used to estimate hazard ratios (HR) and corresponding
95% CI according to the potential prognostic variables sex and QTc.

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Figure 1 Family trees of the eight affected families and of the four sporadic patients. Circles indicate female; squares indicate male; symbols with a slash
indicate deceased subjects. The age reported in subjects with sudden death or aborted sudden death indicates the age at the event, whereas in those with diagnosis of short QT and without cardiac arrest it indicates the age at the time of diagnosis.

2442

C. Giustetto et al.

All tests performed were two-sided and statistical signicance

level was set at 0.05.

Results
Clinical characteristics

Electrocardiography
The number of analysed ECGs for each patient was 18
with a median of 3 (IQR 25). In all the available ECGs,
the QT/QTp interval was always ,80%, with an absolute
QT interval
320 ms, ranging from 210 to 320 ms, and a
QTc
340 ms, varying from 250 to 338 ms. In most
cases, the T-wave showed a narrow, peaked, high
voltage, and symmetrical appearance and an ST-segment
was almost absent (Figure 3). No relationship was observed
between the T-wave amplitude and the prognosis, as
cardiac arrest was observed both in subjects with high
peaked T-waves and in the few subjects without high
peaked T-waves.
The QTc interval was 300 + 20 ms in the 10 patients with
cardiac arrest and 309 + 19 ms in the other 19 patients.
The sex and the QTc interval were evaluated in a multivariable analysis to assess the presence of predictors of
the occurrence of cardiac arrest. Neither the sex
(P 0.275), nor the QTc interval (P 0.319) resulted to
be signicantly related to cardiac arrest. Syncope was not
evaluated as a possible predictor of cardiac arrest,
because the patients who presented syncope were subsequently treated.
Thirteen patients underwent an exercise stress test. A
physiological heart rate increase was observed in all
patients. Heart rate at rest was 71 + 9 b.p.m., with a QT
interval of 273 + 19 ms. The maximum heart rate was
148 + 32 b.p.m., with a mean QT interval of 233 + 27 ms.
With increasing heart rate, only a slight further reduction
of the QT interval was observed and its values tended to
be closer to the expected values.

Figure 2 KaplanMeier estimate of cumulative survival free from cardiac

arrest from birth to the age of 40 years or before pharmacological therapy
in the 29 patients with SQTS. The CIs are reported.

Electrophysiological study
Eighteen patients underwent an electrophysiological study.
The ventricular effective refractory period (ERP) at the
right ventricular apex at a cycle length of 600500 ms
varied between 140 and 180 ms (mean 155 + 12 ms) and at
a pacing cycle of 430400 ms varied between 130 and
180 ms (mean 150 + 13 ms). Programmed ventricular stimulation was performed with two to three premature stimuli
up to refractoriness, except in two patients in which extrastimuli ,180 ms were not used. Ventricular brillation was
induced in 11 out of the 18 patients (61%): three had a
history of aborted sudden death, four had syncope, two
experienced palpitations, and two were asymptomatic. In
seven patients, ventricular brillation was not induced:
four were asymptomatic; two had a previous resuscitated
cardiac arrest (in these two patients, two extrastimuli on
two pacing cycle lengths up to 180 ms were used) and one
patient was symptomatic for syncope, but later had a ventricular brillation interrupted by the ICD (this patient was
studied using three extrastimuli on three pacing cycle
lengths up to refractoriness).
As only three patients out of six with documented ventricular brillation were induced, the sensitivity of electrophysiological study was 50%.
Atrial ERPs were measured in the high lateral right atrium
in 12 patients and at a cycle length of 600 ms varied
between 120 and 180 ms, with a mean of 157 + 22 ms.

Genetics and other diagnostic tests

Genetic screening was performed in all the eight families
and in the sporadic patient I and III; HERG mutation (encoding for IKr) was found in two families (A and B, Figure 1),
whereas none of the known mutations were found in six
families and in the two sporadic patients. Concerning the
other patients, the parents of the sporadic patient II have
refused it and the sporadic patient IV died before genetic
screening could be performed (Table 1).
The ECG was normal in all the patients. Eight patients
underwent cardiac MR, which was normal in all of them.

Therapeutic approach
Of the 29 patients, three died before clinical evaluation, 14
received an ICD and 12 patients did not receive an implant

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Of the 29 patients, 21 were males and eight females. The

median age at diagnosis was 30 years (IQR: 1849 years;
range 480). At the time of inclusion in the study, 18 out
of 29 patients (62%) were symptomatic. Nine patients had
a history of cardiac arrest (31%), resuscitated in six, two
of whom had serious neurological damage. In eight of
these nine patients cardiac arrest was the rst clinical presentation. It occurred in patients from 4 months to 62 years
of age. One more case of cardiac arrest was observed
during the follow-up (patient IV, family B). The survival
probability free from a rst cardiac arrest is reported in
Figure 2.
Six of the 29 patients had syncope and one patient presyncope (24%). In four (14%), this was the rst clinical presentation. In three patients syncope was prolonged and
resuscitation attempts were performed by bystanders; one
episode occurred in an infant at 8 months of age (Table 1).
Nine patients (31%) had palpitations, with AF or utter
documented in seven (24%). In ve patients (17%), AF was
the rst clinical manifestation. Two subjects had AF before
20 years of age, whereas in the other ve AF occurred
after 40 years of age. Frequent ventricular extrasystoles
were documented in ve patients.

Patients

Sex

Family A
I
F
II
M
III
M
Family B
I
F
II
F
III
F
IV
M
Family C
I
M
II
M
III
M
IV
M
Family D
I
M
II
M
III
M
Family E
I
F
II
M
III
F
Family F
I
M
II
M
Family G
I
M
II
M
III
M
Family H
I
F
II
M
III
M
Sporadic patients
I
M
II
F
III
M
IV
M

Symptoms

Family
history
of SD

Mutation

Syncope

Cardiac
arrest

Age at
symptom

Circumstances
of symptom

Comments

31
35
6

Yes
Yes

Yes

30 years
18 years
8 months

At rest
During effort
Loud noise

Vaso-vagal
Running
Resuscitated

Yes

HERG

62
67
40
15

Yes

Yes

62 years

8 months

Unknown

During sleep

Sudden death

Yes

49
39
50
21

Yes
Yes

29 years
50 years

During sleep
Daily activities

80
53
18

Yes

18 years

35
14
16

Yes

43
17

16
19
21

ECG
QT (ms)

QTc (ms)

QT/QTp (%)

86
66
76

250
270
260

299
283
293

71
68
70

HERG

85
72
75
80

210
270
240
260

250
296
268
300

59
71
64
71

Yes

Not found

73
69
75
64

275
290
280
300

303
311
313
310

73
75
75
75

No

Not found

At rest

Resuscitated

70
66
78

280
300
270

302
315
308

73
76
73

14 years

During effort

After intensive training

Yes

Not found

59
83
74

320
240
300

317
282
333

78
67
80

Yes

17 years

Unknown

Resuscitated

No

Not found

82
115

290
210

338
291

80
69

Yes

16 years

At rest

Resuscitated

No

Not found

77
73
65

280
294
320

317
324
333

76
78
80

52
30
25

Yes

30 years

During sleep

Sudden death

Yes

On going

67
55
63

310
315
315

327
302
323

79
74
78

21
4
69
28

Yes

Yes
Yes

Yes

19 years
4 months
62 years
28 years

During effort
While awake
Unknown
Unknown

Resuscitated
Resuscitated

Yes
Yes
Yes
Unknown

Not
Not
Not
Not

67
128
90
65

300
210
240
300

317
307
294
312

76
73
70
75

H.R. (b.p.m.)

found
done
found
done

2443

Cardiac arrest during the follow-up, at the age of 17 years, during sleep, debrillated by ICD.

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Age at
observation
(years)

SQTS: clinical ndings and diagnostictherapeutic implications

Table 1 Clinical characteristics of the 29 patients with SQTS

2444

C. Giustetto et al.

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Figure 3 Twelve-lead ECG (25 mm/s paper speed) of four patients with SQTS. (A) Patient III, family C (50 years): sinus rhythm, heart rate 75 b.p.m., QT 280 ms,
QTc 313 ms. (B) Patient II, family C (39 years): sinus rhythm, heart rate 69 b.p.m., QT 290 ms, QTc 311 ms. (C) Patient III, family A (6 years): sinus rhythm, heart
rate 76 b.p.m., QT 260 ms, QTc 293 ms. (D) sporadic patient II (35 months): sinus rhythm, heart rate 143 b.p.m., QT 210 ms, QTc 324 ms. Note the deep negative
T waves in leads V1V3, which are the equivalent of the high peaked T-waves in adult patients.

SQTS: clinical ndings and diagnostictherapeutic implications

with a change score of 45 + 25 ms. In this latter group,

only the two patients with the higher QTc increase underwent an electrophysiological study during therapy: the ventricular ERP increased, respectively, from 160 to 200 ms and
from 150 to 190 ms. Also in these patients ventricular brillation was not induced any more.

Children
Three children had aborted sudden death or syncope during
infancy: patient III, family A; sporadic patient II and patient
IV, family B.
Patient III, family A was observed at the age of 6 years. He
had severe neurological damage as a consequence of
aborted sudden death at the age of 8 months. An ECG
recorded at the age of 35 months showed, at HR 120 b.p.m.,
a QT interval of 240 ms (QTc 339 ms, QT/QTp 80%). When
he was 6 years old, he had, at HR 76 b.p.m., a QT interval
of 260 ms (QTc 293 ms, QT/QTp 70%). He did not undergo
an electrophysiological study because of the severe neurological damage; he was genotyped (HERG mutation).

Figure 4 Twelve-lead ECG recordings of a short QT patient, showing hydroquinidine effect. From left to right: (A) basal ECG (sinus rhythm, heart rate 52 b.p.m.,
QT 280 ms, QTc 261 ms); (B) ECG during hydroquinidine administration (sinus rhythm, heart rate 60 b.p.m., QT 380 ms, QTc 380 ms). ST-segment appearance,
T-wave duration increase, and T-wave amplitude reduction can be observed; (C) electrophysiologic study during hydroquinidine treatment shows a ventricular
ERP of 200 ms.

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as two patients were very young children and 10 patients

refused the implant. The ICD was implanted in nine patients
who had ventricular brillation induced at electrophysiological study. Of the other ve patients, two had a previous
resuscitated cardiac arrest, one had a history of syncope and
two were asymptomatic. Seven patients who did not receive
the ICD were started on hydroquinidine, as well as another
three patients implanted with an ICD, who were symptomatic for episodes of AF. Of the 10 patients who received
hydroquinidine, ve had HERG mutation; these patients
had an increase in the QTc from 289 + 14 to 405 + 26 ms,
with a change score of 116 + 18 ms. Moreover, in these
patients an ST-segment became more evident and the
T-waves increased in duration and decreased in amplitude
(Figure 4). An electrophysiological study performed during
therapy showed a mean ventricular ERP increase from
150 + 12 ms to a mean of 200 + 21 ms, with a change
score of 66 + 11 ms. In these patients ventricular brillation
was not induced any more. In the other ve patients without
HERG mutation, the QTc increment was lower and less
homogeneous, varying from 307 + 22 ms to 352 + 41 ms,

2445

2446

Follow-up
For the 26 surviving patients included in the study, the
median follow-up was 23 months (IQR: 2035 months;
range: 949). No patient died. Patient IV, family B, with a
history of syncope and not inducible ventricular brillation,
had an appropriate ICD intervention. In three patients, drug
therapy was discontinued due to enteric side effects: two
patients with an ICD did not receive any further antiarrhythmic therapy; the other one was a child (patient III,
family A) with severe neurological sequelae due to a previous cardiac arrest and he was treated with ecainide
and nadolol. The median follow-up of the seven patients
in hydroquinidine was 29 months (IQR: 2236 months;
range 2136).
None of the patients on hydroquinidine had documented
or symptomatic AF episodes.

Discussion
Only in recent years an inherited short QT interval has been
identied as a cause of familial sudden death.4 As only a few
families with different clinical histories are available, many
questions remain unanswered. Little is known about what is
the symptom prevalence associated with SQTS, what is the
rst clinical manifestation and at what age it can occur,
what are the QT interval limits in the affected subjects,
the role of the electrophysiological study in the

stratication of the risk of sudden death, and the efcacy

of the available therapies. This study analyses the clinical
characteristics of 29 patients with SQTS, which up to now
has been the largest group of patients reported.
Cardiac arrest was the most frequent symptom and the
most frequent rst clinical presentation. It was also
observed in the rst year of life, suggesting that this new
ion channel disease may be one of the causes of the
sudden infant death syndrome (SIDS). Syncope was observed
less frequently and it occurred at any age. The most likely
mechanism of syncope in SQTS, as in other channelopathies,
is self-terminating VT/VF episodes.
Patients often presented palpitations, which were not
only related to AF, but also to ventricular extrasystoles. AF
was also observed in young patients and should presumably
be related to the presence of short ERPs in the atria.
Concerning the ECG, in the rst publication relating a
short QT interval to familial sudden death, two families
were described with QT and QTc
300 ms.4 In this larger
cohort of patients, the QT interval ranges from values as
short as 210 ms to values of 320 ms; similarly the QTc
varies from 250 to 340 ms. The multivariable analysis did
not indicate the QTc interval as a signicant risk factor for
the occurrence of cardiac arrest, although it would be
reasonable to suppose that a shorter QTc could predispose
to a higher risk of ventricular arrhythmias. However, the
absence of statistical signicance might depend on the low
number of patients.
A short QT interval is easier to recognize at low heart
rates, whereas with increasing heart rates it tends to be
closer to the normal values, as was observed, for example,
during the exercise stress test. However, the QT values are
still always below the normal values also at higher rates
and this also makes possible the diagnosis in infants, who
typically show high heart rates. This is particularly important considering that sudden death occurs also in the rst
months of life. It is likely that infants affected by SQTS
could be identied by an ECG performed in the rst
months of life, as can be seen for those with long QT syndrome.15 Besides the QT interval, also the T-wave morphology appears to be very important in order to identify
short QT patients. High, peaked, and narrow T-waves particularly in the precordial leads appear to be the typical
morphology of T-waves in congenital SQTS.
The electrophysiological study showed extremely short
ERPs at both atrial and ventricular level. It is well known
that short refractory periods cause a reduction in the
wavelength (the product of refractory period and conduction velocity) and this might in itself explain atrial and
ventricular vulnerability to arrhythmias. A heterogeneous
shortening of the action potential duration among the
different cell types spanning the ventricular wall has
been proposed as an additional mechanism for re-entry
responsible for tachycardia/brillation in SQTS.17
Ventricular brillation was induced in most patients,
however, the sensitivity of the electrophysiological study
appears low and thus its value in dening the risk of
sudden death in this population remains uncertain as the
lack of ventricular brillation induction does not allow us
to predict a good prognosis.
As far as genetics is concerned, mutations in three different genes have been linked to the SQTS until now: two
different missense mutations in KCNH2 (HERG), the gene

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The sporadic patient II was observed at the age of 4 years.

She had an aborted sudden death at the age of 4 months.
The child had two episodes of cardiac arrest treated with
resuscitation manoeuvres; one of these occurred in the hospital and ventricular brillation was documented at ECG.
When she was 8 months old an ECG showed, at HR
128 b.p.m., a QT interval of 210 ms (QTc 307 ms, QT/QTp
73%). An ECG recorded at the age of 35 months showed
the following values: HR of 143 b.p.m., QT interval of
210 ms (QTc 324 ms, QT/QTp 78%). An electrophysiological
study was tried when the child was 6 months old. The
study had to be interrupted because ventricular brillation
was induced twice by mechanical stimulation during catheter positioning. The genetic screening was not performed
because of the parents refusal.
The values of QT and QTc of these two children are below
the minimum value for children of the same age reported in
literature.11,15
Patient IV, family B experienced a syncope at the age of 8
months. SQTS was diagnosed at the age of 15 years; at this
age, an ECG showed, at HR 80 b.p.m., a QT of 260 ms (QTc
300 ms, QT/QTp 71%). At the electrophysiological study
there was no induction of ventricular arrhythmias. He
received an ICD due to the short QT interval and the
family history of sudden death over three generations.
One year later he had an appropriate ICD discharge at
night.16 He has HERG mutation.
In the families studied there were two other babies
which died suddenly: the infant which died at 3 months in
family A and the one which died at 4 months in family
C. These babies are shown in the family trees in Figure 1,
but were not included in the study as they had no investigations performed during life, including ECG, as they were
healthy.

C. Giustetto et al.

SQTS: clinical ndings and diagnostictherapeutic implications

Conclusions
SQTS is a genetic arrhythmogenic disorder with a high incidence of sudden death during life including the rst
months of life, and therefore should be considered as a possible cause of SIDS. The inheritance is autosomal dominant,
with genetic heterogeneity. The diagnosis of short QT can
be made with an ECG and it should always be considered
in the presence of a family history of sudden death, particularly a history of sudden death in infants. It should also be
considered in patients with idiopathic AF at a young age
and in patients with syncope and a structurally normal
heart. The outcome of SQTS patients becomes relatively
safe when they are identied and treated. Unfortunately,
without therapy the outcome is not so good. For this
reason today, subjects with SQTS and family history of
sudden death must be treated with ICD in primary prevention. At the moment there is no information on the prevalence of short QT in the general population. Further

studies should also clarify whether subjects with short QT

identied in a community-based survey have the same risk.
Conict of interest: none declared.

References
1. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart
disease with prolongation of the QT interval and sudden death. Am
Heart J 1957;54:5968.
2. Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare delleta
`
pediatrica. Clin Pediatr 1963;45:656615.
3. Ward OC. A new familial cardiac syndrome in children. J Irish Med Assoc
1964;54:103106.
4. Gaita F, Giustetto C, Bianchi F, Wolpert C, Schimpf R, Riccardi R, Grossi S,
Richiardi E, Borggrefe M. Short QT syndrome. A familial cause of sudden
death. Circulation 2003;108:965970.
5. Gussak I, Brugada P, Brugada J, Wright RS, Kopecky SL, Chaltman BR,
Bjerregaard P. Idiopathic short QT interval: a new clinical syndrome?
Cardiology 2000;94:99102.
6. Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M,
Menendez TM, Brugada J, Pollevick GD, Wolpert C, Burashnikov E,
Matsuo K, Sheng Wu Y, Guerchicoff A, Bianchi F, Giustetto C, Schimpf
R, Brugada P, Antzelevitch C. Sudden death associated with short QT syndrome linked to mutations in HERG. Circulation 2004;109:3035.
7. Bellocq C, van Ginneken AC, Bezzina CR, Alders M, Escande D, Mannens
MM, Baro
` I, Wilde AA. Mutation in the KCNQ1 gene leading to the short
QT-interval syndrome. Circulation 2004;109:23942397.
8. Priori GS, Pandit SV, Rivolta I, Barenfeld O, Ronchetti E, Dhamoon A,
Napoletano C, Anumowo J, Raffaele di Barletta M, Gaudapakkam S,
Bosi G, Stramba-Badiale M, Jalife J. A novel form of short QT syndrome
(SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005;
96:800807.
9. Schimpf R, Wolpert C, Gaita F, Giustetto C, Borggrefe M. Short QT syndrome. Cardiovasc Res 2005;67:357366.
10. Wolpert C, Schimpf R, Giustetto C, Antzelevitch C, Cordeiro J, Dumaine
R, Brugada R, Hong K, Gaita F, Borggrefe M. Further insights into the
effect of quinidine in short QT syndrome caused by a mutation in
HERG. J Cardiovasc Electrophysiol 2005;16:15.
11. Rautaharju PM, Zhou SH, Wong S, Calhoun H, Berenson GS, Prineas R,
Davignon A. Sex differences in the evolution of the electrocardiographic
QT interval with age. Can J Cardiol 1992;8:690695.
12. Gaita F, Giustetto C, Bianchi F, Schimpf R, Haissaguerre M, Calo
` L,
Brugada R, Antzelevitch C, Borggrefe M. Short QT syndrome: pharmacological treatment. J Am Coll Cardiol 2004;43:12941299.
13. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart
1920;7:3570.
14. Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D. An improved
method for adjusting the QT interval for heart rate (the Framingham
Heart Study). Am J Cardiol 1992;70:797801.
15. Mc Cammon RW. A longitudinal study of electrocardiographic intervals in
healthy children. Acta Pediatrica 1961;50:252.
16. Schimpf R, Bauersfeld U, Gaita F, Wolpert C. Short QT-syndrome: successful prevention of sudden cardiac death in an adolescent by implantable
cardioverter-debrillator treatment for primary prophylaxis. Heart
Rhythm 2005;2:416417.
17. Extramiana F, Antzelevitch C. Amplied transmural dispersion of repolarization as the basis for arrhythmogenesis in a canine ventricular-wedge
model of short-QT syndrome. Circulation 2004;110:36613666.
18. Hong K, Piper DR, Diaz-Valdecantos A, Brugada J, Oliva A, Burashnikov E,
Santos-de-Soto J, Grueso-Montero J, Diaz-Enfante E, Brugada P, Sachse F,
Sanguinetti MC, Brugada R. De novo KCNQ1 mutation responsible for
atrial brillation and short QT syndrome in utero. Cardiovasc Res
Published online ahead of print August 16, 2005.

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encoding for IKr, the rapidly activating delayed rectier potassium channel, causing a gain of function in the channel,6
two mutations in KCNQ1 (KvLQT1), causing a gain of function
in IKs, the slowly activating delayed rectier potassium
channel7,18 and a mutation in KCNJ2 (Kir2.1), causing a
gain of function in I8K1. However, the prevalence of these
mutations does not seem high, as a mutation in HERG was
found in only two of the families described in this study
and neither a mutation in KCNQ1 nor in KCNJ2 was present
in any of them. It is thus reasonable to suppose that
mutations involving other genes will be identied in the
future, similarly to what happened in long QT syndrome.
The small number of genotyped families and the presence
of a history of sudden death in all families does not allow
us, up to now, to conclude that the genetic screening may
help in identifying high-risk patients.
Because of the high incidence of sudden cardiac death, at
the present time the implant of an ICD is the rst choice
therapy in patients with SQTS.4 However, an ICD implant in
very young children is technically difcult and is associated
to a higher risk of complications through life compared with
adults and, moreover, some patients refuse the implant. In
these cases, hydroquinidine has been proposed, as it prolongs the QT interval and the ventricular ERPs and prevents
ventricular arrhythmias induction in patients with HERG
mutation.12 However, in this study it was observed that
patients without HERG mutation show a lower and less
homogeneous QTc increment. In these patients, the effectiveness of hydroquinidine should be evaluated on the
basis of individual cases. A quinidine test showing a
marked QT interval prolongation could suggest a high probability of HERG mutation and could be useful in identifying
potential responders to the drug.

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