Journal of Arrhythmia 29 (2013) 134–137

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Journal of Arrhythmia
journal homepage: www.elsevier.com/locate/joa

Review

Similarities and differences of clinical characteristics between Brugada

syndrome and early repolarization syndrome
Hiroshi Watanabe n, Tohru Minamino
Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-754 Asahimachidori, Niigata 951-8510, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Early repolarization (or J wave) is a common electrocardiographic finding that occurs in 1% to 10% of
Received 4 December 2012 healthy persons. It has been generally considered benign for decades. However, there is increasing
Received in revised form evidence showing that early repolarization is associated with the susceptibility to ventricular
18 January 2013
fibrillation and sudden cardiac death. Therefore, early repolarization syndrome, or J-wave syndrome,
Accepted 22 January 2013
Available online 20 March 2013
has recently been proposed as a new disease entity. Brugada syndrome is characterized by ST-segment
elevation in the right precordial leads (V1 to V3) of a 12-lead electrocardiogram, and is another form of
Keywords: idiopathic ventricular fibrillation associated with J-point elevation. Brugada syndrome and early
Arrhythmia repolarization syndrome share genetic, clinical, and electrophysiological characteristics, such as
Ventricular fibrillation
causative genes, male dominance, pause-dependent augmentation of J-point elevation, and response
Electrocardiogram
to drugs. However, these two diseases also have certain differences. This review focuses on the
Genetics
Treatment similarities and differences between Brugada syndrome and early repolarization syndrome, both of
which are associated with J-point elevation and sudden cardiac death.
& 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
2. Clinical characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
3. Electrophysiological characteristics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
4. Genetic basis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
5. Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

1. Introduction showing that early repolarization is associated with an increased

risk of ventricular fibrillation and sudden cardiac death [6–8].
Early repolarization or J-wave is characterized by an elevation In a number of case reports, early repolarization has been
at the junction between the end of the QRS complex and the associated with the pathogenesis of idiopathic ventricular fibrilla-
beginning of the ST-segment (J-point) in a 12-lead electrocardio- tion [9,10]. In 2008, Haissaguerre et al. [6] reported in a case-
gram (ECG). Early repolarization is a common electrocardio- control study that the early repolarization pattern is more frequent
graphic finding that occurs in 1% to 10% of healthy persons, and in patients with idiopathic ventricular fibrillation (31%) than in
it has been generally considered benign for decades [1]. However, matched controls (5%). After this report was published in the New
early repolarization can be observed under various biological England Journal of Medicine, idiopathic ventricular fibrillation
abnormalities, such as low body temperature, hypercalcemia, associated with early repolarization, the so-called early repolariza-
and ischemia [2–5]. Furthermore, there is increasing evidence tion or J-wave syndrome, started receiving increasing attention.
Brugada syndrome is characterized by ST-segment elevation in
the right precordial leads (V1 to V3) of a 12-lead ECG and
episodes of ventricular fibrillation [11]. Brugada syndrome is
n
Corresponding author. Tel.: þ81 25 227 2185; fax: þ 81 25 227 0774. another form of idiopathic ventricular fibrillation associated with
E-mail address: hiroshi7@med.niigata-u.ac.jp (H. Watanabe). J-point elevation, and this led Antzelevitch and Yan [12] to

1880-4276/$ - see front matter & 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.joa.2013.01.007
 H. Watanabe, T. Minamino / Journal of Arrhythmia 29 (2013) 134–137
hypothesize about ‘‘J-wave syndromes.’’ This review presents the
available evidence about the similarities and differences between
Brugada syndrome and early repolarization syndrome.
2. Clinical characteristics
Brugada syndrome is more common in Southeast Asia, including
Japan, with an estimated prevalence of 12 in 10,000 individuals,
compared with Western countries where the estimated prevalence
is 1 to 5 in 10,000 individuals. However, the incidence of early
repolarization syndrome and the regional variation in incidence are
not known [13]. In both Brugada and early repolarization syn-
dromes, the age at diagnosis is around 40 years, and 70% to 80% of
patients are men (Table 1).[14–17] A family history of unexplained
sudden death is present in 20% to 30% of patients with Brugada
syndrome and in 10% to 20% of patients with early repolarization
syndrome [14–17]. In Brugada syndrome, arrhythmia events result-
ing from ventricular fibrillation mainly occur during sleep, while
resting, or after meals [18]. However, cardiac arrest occurs during
sleep in only 19% and 26% of patients with early repolarization
syndrome in the reports by Haissaguerre et al. [6] and us, [17]
respectively, and also occurs during physical exertion in 9% to 19% of
patients. The frequency of arrhythmia recurrences in survivors of
ventricular fibrillation or cardiac arrest seems similar; the annual
incidence of ventricular fibrillation is 7% to 8% in patients with
Brugada syndrome and 6% to 7% in those with early repolarization
syndrome [14–17]. In addition to their susceptibility to ventricular
fibrillation, atrial fibrillation has also been found in 10% to 20% of
patients with Brugada syndrome and in 23% of patients with early
repolarization syndrome [17,19].
3. Electrophysiological characteristics
In the 12-lead ECG, Brugada syndrome is characterized by a
unique ‘‘coved-type’’ J-point and ST-segment elevation in the
right precordial leads V1 to V3, whereas early repolarization
syndrome is characterized by an elevation of the J-point, either
as QRS slurring or notching of Z0.1 mV in Z2 consecutive
inferior leads (II, III, and aVF) or lateral leads (I, aVL, V5, and
V6). However, the diagnostic criteria for early repolarization
syndrome, such as the morphology and amplitude of J-point
elevation, are still controversial [6]. However, in early
Table 1
Clinical characteristics.
Eary repolarization
syndrome
Male sex 87%
Age, years 44 717
Family history of sudden death 13%
Activity at initial cardiac arrest 26%
Sleeping 23%
Rest 19%
Physical effort 32%
Other activities 48%
Inducible ventricular fibrillation 23%
Atrial fibrillation
Location of early repolarization/J-point
elevation
Inferior 70%
Lateral 70%
Right precordial 21%
Multiple locations of early 53%
repolarization
Modified from Watanabe et al. [17] and Kamakura et al. [15] with permission.
135
repolarization syndrome, J-point elevation in the right precordial
leads can also be found in up to 20% of patients (Table 2),
[17,20] and early repolarization appearing globally in the inferior,
lateral, and right precordial leads has been associated with the
highest risk of ventricular fibrillation [12,20]. Similarly, the
presence of inferolateral early repolarization is associated with
an increased risk of arrhythmia events in patients with Brugada
syndrome.
In both Brugada and early repolarization syndromes, the
characteristic electrocardiographic changes are dynamic, and the
amplitude and the existence of the characteristic J-point/ST-
segment or early repolarization varies. J-point elevation becomes
most prominent just before the development of ventricular
fibrillation, supporting the arrhythmogenicity of J-point abnorm-
alities [6,11]. Both syndromes share pause- and bradycardia-
dependent augmentation of the J-point amplitude (Figure), which
has been suggested useful in distinguishing persons with an
increased risk of arrhythmia events from those with benign early
repolarization [21]. Because the electrocardiographic changes can
occasionally disappear, efforts to provoke electrocardiographic
changes have been attempted. In Brugada syndrome, sodium
channel blockers are used to detect the diagnostic Brugada
electrocardiographic pattern. However, sodium channel blockers
attenuate J-point elevation in early repolarization syndrome, and
to date, there is no established test for the diagnosis [22].
Fig. 1 Conduction abnormalities at the His–Purkinje system
and the right ventricular outflow tract are sometimes evident in
Brugada syndrome. In our recent report, the PR interval and QRS
duration are also longer in patients with early repolarization
syndrome than in matched controls (Table 2) [23]. Table 3 shows
a comparison of the electrocardiographic parameters between
patients with early repolarization syndrome and those with
Brugada syndrome. The incidence of late potential in signal-
averaged ECG is higher in patients with Brugada syndrome
(60%) than in those with early repolarization syndrome (7%)
[22]. The QT interval is relatively short in patients with early
repolarization syndrome [6,23]. The QT interval is unusually short
in patients with Brugada syndrome who are affected by specific
genetic defects (mutations in calcium channel genes), as
described below [24]. The early repolarization pattern is fre-
quently found and is associated with an increased risk of
arrhythmia events in patients with short QT syndrome [25].
4. Genetic basis
Similar to other arrhythmia syndromes, Brugada and early
Brugada repolarization syndromes are inherited diseases that are usually
syndrome transmitted in an autosomal-dominant manner [26]. To date, 13
genes have been associated with Brugada syndrome. Loss-of-
76–96%
41–50
function mutations in SCN5A, encoding the cardiac predominant
19–34%
Table 2
82% Electrocardiographic parameters in Japanese patents with early repolarization
syndrome.
63–73% ERS patients Matched controls P value
19% N ¼44 N ¼220
Male sex, N (%) 39 (89) 95 (89) –
Age, years 47 718 47 717 –
Heart rate (beats/ 63 710 707 14 o 0.001
Inferolateral, min)
8% PR interval (ms) 173 735 148 722 o 0.001
100% QRS interval (ms) 94 716 907 8 0.008
 QTc (ms) 391 730 397 722 0.07
ERS denotes early repolarization syndrome; QTc, corrected QT interval;modified
from Watanabe et al., [23] with permission.
136 H. Watanabe, T. Minamino / Journal of Arrhythmia 29 (2013) 134–137

I V1

II V2

III V3

aVR V4

aVL V5

aVF V6

Fig. 1. Electrocardiogram of a patient with Brugada syndrome. The electrocardiogram was recorded just after an episode of ventricular fibrillation. Early repolarization is
present in leads I, aVL, V4, V5, and V6. Note that the amplitude of the J-point of the Brugada-type electrocardiogram and the early repolarization pattern was increased
after a pause.

Table 3 Table 4
Comparisons of electrocardiographic parameters between ERS and Brugada Genetic basis.
syndrome.
Gene Frequency Function
ERS patients N ¼ 14 Brugada patients N ¼12 P value
Brugada syndrome
Heart rate (beats/min) 63 77 657 8 NS Na þ channel
PR interval (ms) 179 734 1917 33 NS SCN5A 10–30% INa þ k
QRS interval (ms) 90 713 977 18 NS SCN1B Rare INa þ k
QTc (ms) 387 723 3847 2 NS SCN3B Rare INa þ k
GPD1L Rare INa þ k
Modified from Kawata et al., [22] with permission. MOG1 Rare INa þ k
SLMAP1 Rare INa þ k
sodium channel a-subunit, are the most frequent genotype and Ca2 þ channel
CACNA1C  5% ICa2 þ k
account for  20% of patients with Brugada syndrome (Table 4)
CACNB2  5% ICa2 þ k
[13,27]. Other genes, including SCN1B [28], SCN3B [29], GPD1L CACNA2D1 Rare ICa2 þ k
[30], MOG1 [31], and SLMAP [32], encoding proteins that modify K þ channel
the sodium channel function, are also causative genes of Brugada HCN4 Rare IK þ m
syndrome. The importance of sodium channel genes in the KCNE3 Rare IK þ m
KCNE5 Rare IK þ m
pathogenesis of Brugada syndrome and the similarities of early KCND3 Rare IK þ m
repolarization syndrome to Brugada syndrome led us to find KCNJ8 Rare IK þ m
SCN5A mutations in patients with early repolarization syndrome Early repolarization syndrome
(Table 4) [23]. These two diseases have further common genetic Na þ channel
SCN5A Unknown INa þ k
backgrounds, including calcium channel genes such as CACNA1C,
Ca2 þ channel
CACNB2b, and CACNA2D1, as well as KCNJ8, which encodes the CACNA1C Unknown ICa2 þ k
ATP-sensitive potassium channel [24,33–35]. In fact, all of the five CACNB2 Unknown ICa2 þ k
causative genes reported for early repolarization syndrome are CACNA2D1 Unknown ICa2 þ k
also causative genes of Brugada syndrome. In early repolarization K þ channel
KCNJ8 Unknown IK þ m
syndrome, an ion channel dysfunction of a pathogenic genetic
background results in either the decrease of inward currents
(Na þ and Ca2 þ currents) or the increase of outward currents Brugada syndrome and those with early repolarization syndrome.
(K þ currents), both of which can cause shortening of the action The arrhythmogenicity of vagal stimulation has been reported,
potential duration, consistent with a relatively short QT interval. and the b-adrenergic agonist isoproterenol has been found
effective for treating electrical storm in both diseases. To date,
quinidine has been the only drug to show efficacy in preventing
5. Treatment recurrent episodes of ventricular fibrillation in patients with
Brugada syndrome [36]. Quinidine has been also effective in
Implantable cardioverter defibrillator is the only proven effec- patients with early repolarization syndrome [16]. These simila-
tive treatment to prevent sudden cardiac death in patients with rities in responses to drugs between patients with Brugada
 H. Watanabe, T. Minamino / Journal of Arrhythmia 29 (2013) 134–137
syndrome and those with early repolarization syndrome suggest
the presence of common electrophysiological abnormalities that
have a critical role in the formation of arrhythmogenic substrates.
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