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Int J Clin Exp Med 2015;8(8):14520-14526
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Original Article
Clinical observations of supraventricular arrhythmias in
patients with brugada syndrome
Bing Liu, Chengjun Guo, Dongping Fang, Jinping Guo
Department of Cardiology, Beijng Anzhen Hospital, Capital University of Medical Sciences, Beijing, China
Received March 25, 2015; Accepted June 4, 2015; Epub August 15, 2015; Published August 30, 2015
Abstract: Objective: To study various types of supraventricular arrhythmias in patients with Brugada Syndrome.
Methods: Forty six patients with ECG of spontaneous type Brugada and with ventricular and/or supraventricular
tachyarrhythmia, without structural heart diseases which were excluded by echocardiography, underwent 24 hHolter recording, electrophysiological study and/or radiofrequency ablation. Results: There were thirty-nine male
and seven female (mean age 37.44 years) among total forty-six patients. Twenty one patients had family histories
of tachycardia, twentythree patients experienced episodes of syncope, and three patients were resuscitated from
cardiac arrest. One patient had ventricular fibrillation and third degree atrioventricular block, eleven patients had
polymorphic ventricular tachycardia and five patients had monomorphic ventricular tachycardia. Fourteen patients
had atrial tachyarrhythmia, paroxysmal supraventricular tachycardia was found in five patients including four WolfParkinson-White syndrome, two patients hadventricular tachycardia and third degree atrioventricular block, one of
them had atrial fibrillation, two patients had both supraventricular tachycardia and ventricular tachycardia, three
patients had both atrial tachyarrhythmia and supraventricular tachycardia, two third degree atrioventricular block
patients had atrial flutter, one patienthad both atrial tachyrhythmia and ventricular tachycardia. Radiofrequency blation was performed in thirty-nine patients and succeed in thirty-two, four patients were implanted with pacemakers,
and four patients had implantable cardioverter defibrillators. Conclusion: In addition to ventricular tachycardia and
ventricular fibrillation, patients with Brugada syndrome exhibit various supraventricular tachyarrhythmia and third
degree atrioventricular block. In patients with Brugada syndrome, the dysfunction of the cardiac ion channel, which
related to mutation of cardiac sodium channelgene, is not limited in His Purkinje system and ventricular myocardium, but also in the atrium and atrioventricular node, which may serves as a cause of dispersion of repolarization
and phase 2 reentry leading to various arrhythmias.
Keywords: Brugada syndrome, cardiac arrhythmia, conduction abnormality, atrioventricular block, supraventricular tachyarrhythmia
Introduction
Brugada syndrome (BS) is an autosomal dominant genetic disease characterized by dometyped or saddle-shaped ST segment elevation
in V1~V3 leads, with diagram in V1 lead resemblingthat of right bundle branch block [1, 2].
Patients suffer from paroxysmal palpitations,
syncope, or ventricular fibrillation (VF) which
leads to sudden unexplained nocturnaldeath
[3]. The current study found that BSis associated with dysfunction of the sodium channel
caused by mutation of the SCN5A gene which
encodes α subunit of cardiac sodium channel
[4]. Since BS is causedby mutation of cardiac
sodium channel gene, then the sodium channel
dysfunction should not be limited to ventricular
muscle, other parts of the myocardium should
also have this problem which will trigger a variety of arrhythmias. Current studies focuses
mostly on the mechanism of BS complicated
ventricular tachycardia (VT) and ventricular
fibrillation, not many reports on supraventricular arrhythmia. Here we reported the clinical
observation results of 46 cases of BS patients
complicated with various types of arrhythmias.
Materials and methods
Patients who visited our hospital between
March 1998 to March 2007 suffering from
heart palpitations, syncope and nocturnal dys-
Supraventricular arrhythmias of brugada syndromepatients
Table 1. Clinical characteristics of patients with Brugada
Syndrome
Clinical characteristics
Number of cases
Total number of patients
46
Male
39
Female
7
History of illness
Palpitation
43
Syncope
23
Cardiopulmonary resuscitation
3
Family history
21
Treatments
Electrophysiology exam + RFA
35
Electrophysiology exam + RFA + pace maker
3
Electrophysiology exam + ICD
3
Electrophysiology exam + RFA + ICD
1
Electrophysiology exam
1
Pace maker
1
Follow-up
2
Follow-up time
(5.25±2.37) years
who could afford the cost. In this study,
the term supraventricular arrhythmia
means atrial arrhythmia or arrhythmia
caused by atrioventricular bypass and
dual atrioventricular node pathways, and
paroxysmal supraventricular tachycardia
(PSVT) means supraventricular tachycardiacaused by atrioventricular bypass
and dual atrioventricular node pathways.
Results
Total forty-six cases who met the BS
diagnostic criteria were treated during
the nine-year periods as above mentioned, with thirty-nine males and seven
females, and ages ranging from twelve to
sixty-six years old (37.44 ± 14.52).
Twenty-one cases have a family history,
and twenty-three cases have history of
syncope, including three cases undergoing cardiopulmonary resuscitation (Table
Note: ICD=implantable cardioverter defibrillators; RFA=radiofrequency
1). Among the total forty-six cases, there
ablation.
arefive cases complicated with paroxysmal supraventricular tachycardia (PSVT,
pnea were selected for routine ECG study. If
with four cases of dominant WPW syndrome,
found to have ST segment elevationin leads
Figure 1); two cases of PSVT coexisting withVT;
V1~V3, excluded organic heart disease and electhree cases of PSVT coexisting with atrial flutter
trolyte imbalance by physical examina(AFL); fourteen cases of atrial tachycardia (AT)
tion, blood biochemical tests, echocardiogracoexisting withAFL and atrial fibrillation (AF);
phy and coronary angiography, diagnosed with
two cases of AT coexisting with third-degree
the “Expert Consensus Recommendations”
atrioventricular block; one case of AT coexisting
about BS diagnosis and treatment revised in
with VT; eleven cases of polymorphic VT; five2005 as a diagnostic criterion [5]. Spontaneous
cases of monomorphic VT; one case of ventrictype I Brugada syndrome was diagnosed directular fibrillation (VF) electrical storm coexisting
ly by the combination of ECG changes with hiswith third-degree atrioventricular block; onetory of illness and familyhistory; Type II and
case of VT coexisting withthird-degree atriovenIIIBrugada syndrome was diagnosed with initial
tricular block; one case of VTcoexisting with
ECG with induced ECG changes in the precorthird degree atrioventricular block and AF.
dial leads inPropafenone stimulation test;
There are total ten cases (21.74%, Table 2)
Induced type I Brugada syndrome was diagcoexisting withPSVT (with/without other types
nosed with the combination of ECG changes
of arrthymia) among the forty-six BS cases, six
with history of illness and family history. For all
of which wereconfirmed as paroxysmal atrioBS patients, routine ECG and Holter were perventricular reentrant tachycardia (AVRT,
formed to observe the types of arrhythmia, and
13.04%), and the rest fourwere confirmed as
for some patients,conventional electrophysiolparoxysmal atrioventricular nodal reentrant
ogy and radiofrequency ablation were pertachycardia (AVNRT, 8.70%. Figure 2 by electroformed following the protocol described in the
physiological examination. There are twentyliterature [6]. Permanent cardiac pacemakers
two cases concurrent with rapid atrial arrhythwere implanted in patient with symptomatic
mia (47.83%, Figure 3), including eighteen
third-degree atrioventricular block, and implantcases of atrial flutter and atrial fibrillation
able cardioverter defibrillators (ICD) were
(39.13%, Figure 4), seventeen cases of which
implanted in patients with cardiac arrest and
were treated with radiofrequency ablation with
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Int J Clin Exp Med 2015;8(8):14520-14526
Supraventricular arrhythmias of brugada syndromepatients
Figure 1. ECG in a patient with Brugada syndrome coexisting within intermittent WPW syndrome. Patient is a 37-yearold male, with arrows indicating the oblique ST segment in V1lead, and ST segment elevation in V2leads inversely
down during pre-excitation.
Table 2. Clinical characteristics of PSVT in patients with Brugada syndrome
ID Age/gender Palpitation Syncope CPR Family history Arrthymia SVT type/VT and AF origin
1
2
3
4
5
6
7
8
9
10
34/F
59/M
45/M
42/M
48/M
47/F
37/F
42/M
25/M
36/M
+
+
+
+
+
+
+
+
+
+
+
+
-
-
+
+
+
-
PSVT
PSVT/AF
PSVT/VT
PSVT/AF
PSVT/AFL
PSVT
PSVT/VT
PSVT
PSVT
PSVT
AVRT
AVNRT/PV
AVNRT/RVOT
AVNRT/PV
LAVRT
AVNRT
AVRT/RT, His B.
AVRT
AVRT
AVRT
Treatment/followup (years)
RFA/4
RFA/7
RFA/4.5
RFA/7
RFA/7
RFA/3.5
RFA/4
RFA/5
RFA/4.5
RFA/5
Note: F=female; M=male; AFL=Atrial flutter; AF=Atrial fibrillation; RFA=radiofrequencyablation; AVRT=atrioventricular reentrant
tachycardia; AVNRT=atrioventricular nodal reentrant tachycardia; RVOT=Right ventricular outflow tract; RV=Right ventricle;
PV=Pulmonary vein; PSVT=paroxysmal supraventricular tachycardia; VT=Ventricular tachycardia; CPR=Cardiopulmonary resuscitation; His B.=His bundle.
success in eleven cases, and three cases had
recurrence of the arrhythmia during follow-ups.
There are five cases concurrent with threedegree atrioventricular block (10.87%). There
are twenty-two cases (47.83%) concurrent with
rapid ventricular arrhythmias (with or without
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other types ofarrhythmia). There are different
degrees ofintraventricular block in all forty-six
cases. Thirty-nine cases underwent radiofrequency ablation with success in thirty-two
cases, four cases were implanted with implantable cardiac pacemakers, one case underwent
Int J Clin Exp Med 2015;8(8):14520-14526
Supraventricular arrhythmias of brugada syndromepatients
Figure 2. ECG in a patient with Brugada syndrome coexisting withatrioventricular nodal reentrant tachycardia.Patient is a 42-year-old male, with sinus rhythm (left) and atrioventricular nodal reentrant tachycardia at onset (Right).
Figure 3. ECG in a patient with Brugada syndrome coexisting withatrial tachycardia. Patient is 36-year-old male.
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Supraventricular arrhythmias of brugada syndromepatients
Figure 4. ECG in a patient with Brugada syndrome coexisting withatrial flutter. Patient is a 50-year-old male.
electrophysiological examination alone, and
four cases were implanted with ICDs. There is
one case of paroxysmal atrial tachycardia
showing concurrence of BS and short QT syndrome (SQTS) (Figure 5).
Discussion
Clinically, BS usually coexists with malignant
ventricular arrhythmias, with sudden cardiac
death as the initial presentation in some cases,
and has become the focus of clinical studies
recently. In our study, among total forty-six BS
cases, there are thirty-two cases complicated
by rapid atrial arrhythmia and/orparoxysmal
supraventricular tachycardia and atrioventricular block, few such studies have been reported
in the literature.
Our data confirm that, besides ventricular
tachycardia and ventricular fibrillation, BS
patients can also be complicated by non-ventricular arrhythmias, including atrial flutter and
atrial fibrillation (39.13%), AVRT (13.04%) and
AVNRT (8.70%). Two or more types of arrhythmias can coexist. In 1999, Anzelevitchet al
reported only 10% of BS patients were compli-
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cated with paroxysmal atrial fibrillation, but
recent studies have shown that the concurrence rate can be as high as 39%, which is similar to the results inour study [7].
The present studies suggest that the mechanism of arrhythmia in BS patients is dysfunction of the sodium channel in the cell membranecaused by gene mutation, such as accelerated inactivation or decelerated reactivation,
which results in loss of the action potential (AP)
dome. This loss is, however, heterogeneous,
generating epicardial dispersion of repolarization. This dispersion creates a vulnerable window, which allows phase 2 reentry to cause a
premature impulse, which triggers VT/VF based
on reentry between transmural layers [8, 9].
Since BS is caused by mutation of the cardiac
sodium channelgene, then the above mentioned mechanisms of increase of repolarization dispersion and reentry can also existin
atrial and atrioventricular node cells, which perhaps help to explain the pathogenesis of atrial
tachy-arrhythmias and AVNRT in BS patients
[10]. Increases in tension of Vagus nerve and
hemodynamic changes caused by supraven-
Int J Clin Exp Med 2015;8(8):14520-14526
Supraventricular arrhythmias of brugada syndromepatients
tricular tachy-arrhythmias can be inducing factors forventricular tachycardia and ventricular
fibrillation in BS patients.
The mechanism for concurrence of BS with AVRT
is currently unknown [11],
and it is suggested that
electrophysiological examination and drug provocation test should be performed in WPW syndrome
patients with history of
sudden death in order to
detect BS. In our study,
there areforty-six cases
(100%) coexisting with
intraventricular
block,
and five cases coexisting
with third degree atrioventricular block, indicating that conduction delays exist in atrium, atrioventricular junction and
ventricle, and conduction
delay may be associated
with tachy-arrhythmias,
which provides a new
idea for pathogenesis of
concurrent tachyarrhythmia in BS patients.
Figure 5. ECG in a patient with Brugada syndrome coexisting with short QT syndrome. Patient is a 19-year-old male. A. Standard lead ECG. The heart rate is 85
beats/min, QT interval is 280 mS, with ST segment almost completely lost, and
high and sharp symmetrical T waves on the right chest leads. B. Dynamic ECG
showing atrial tachycardia.
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There are few studies
published for non-ventricular arrhythmias in BS
patients, thus it is possible that a large number of
concurrent supraventricular arrhythmias in BS
patients have long been
neglected. In clinical, in
addition to ventricular
tachy-arrhythmias, nonventricular arrhythmias
such as atrial flutter, atrial fibrillation, AVNRT or
even AVRT and third
degree atrioventricular
block should also be considered as reasons to
cause palpitations and
syncope in BS patients.
In BS patients with syncope likely caused by
Int J Clin Exp Med 2015;8(8):14520-14526
Supraventricular arrhythmias of brugada syndromepatients
supraventricular tachy-arrhythmia, atrial stimulation should be performed during electrophysiological examination to induce such arrhythmia. Incases of BS concurrent with supraventricular tachycardia, radiofrequency ablation
should be the preferred treatment; the use of IC
antiarrhythmic drugsshould be avoided. In BS
patients with syncope, an ICD with supraventricular tachycardia recognition function should
be chosen to avoid false discharge [12].
Studies have found that BS can coexist with
SQTS suggesting that BS is possibly a polygenic
disease. The currently known three causative
genes for SQTS, KCNH2, KCNQ1 and KCNJ2
can all encode cardiac potassium channels
[13], the abnormalities of which can causeshortening of QT interval. But BS and SQTS
coexistence case was not found in our study.
[5]
[6]
[7]
Disclosure of conflict of interest
None.
Address correspondence to: Chengjun Guo, Department of Cardiology, Beijng Anzhen Hospital, Capital
University of Medical Sciences, No.2, Anzhen Road,
Chaoyang District, Beijing 100029, China. Tel:
86-010-64456132; E-mail: guochengjun@medmail.
com.cn
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