Europace (2007) 9, 947950

doi:10.1093/europace/eum110

Clinical predictors of atrial brillation

in Brugada syndrome
Mohamad Ali Babai Bigi, Amir Aslani*, and Shahab Shahrzad
Cardiology Department, Namazee Hospital, Shiraz University of Medical Sciences, Zand Avenue,
PO Box 71935-1334, Shiraz, Iran
Received 9 March 2007; accepted after revision 27 April 2007; online publish-ahead-of-print 31 May 2007

KEYWORDS
Atrial brillation;
Brugada syndrome;
Ventricular brillation

Aims Atrial arrhythmias have been reported in patients with Brugada syndrome. The aim of this study
was to evaluate clinical predictors of atrial brillation (AF) in Brugada syndrome.
Methods and results Patients diagnosed with Brugada ECG pattern were enrolled in the study. Type 1, 2,
and 3 Brugada ECG pattern was found in 28, 56, and 31 patients, respectively. A total of 85 healthy age
and gender-matched subjects were selected as a control group. Mean age, maximum P-wave duration
(Pmax), P-wave dispersion (Pdisp), and left atrial dimension were not signicantly different between
patients and controls. There were no differences between Pmax, Pdisp, and left atrial dimension of the
type 1, 2, and 3 Brugada patients. Spontaneous paroxysmal AF was detected in 15 of 28 type 1
Brugada patients (53%) and none of the type 2 and 3 Brugada patients. All 15 patients with AF had at
least one episode of paroxysmal AF and none of the patients showed persistent or chronic AF. All 15
patients who had paroxysmal AF had previous life threatening cardiac events. In contrast, paroxysmal
AF did not occur in type 1 Brugada patients without previous life threatening cardiac events. In multiple
regression analysis, only the occurrence of previous life threatening cardiac events was a risk factor for
paroxysmal AF (P 0.0001).
Conclusion It is concluded that the most important predictor of AF in Brugada syndrome is the
occurrence of previous life threatening cardiac events.

Introduction
The Brugada syndrome is characterized by ST-segment
elevation in leads V1 to V3 with a right bundle branch
block pattern and nocturnal sudden cardiac death due to
ventricular brillation.16 Arrhythmias such as premature
ventricular contractions, monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular
brillation have been reported in this syndrome.79 In
addition, atrial arrhythmia has also been reported in
patients with Brugada syndrome.3,1014 The aim of this
prospective study was to evaluate clinical predictors of
atrial brillation (AF) in patients with Brugada syndrome.

Methods
Between September 2000 and October 2006, patients referred to the
Arrhythmia Clinic and diagnosed with Brugada ECG pattern were
enrolled in the study and were given informed written consent. A
12-lead ECG (at a paper speed of 25 mm/s and 10 mm per mV standard gain) was recorded from each subject. All ECG recordings
were evaluated by two cardiologists. Brugada type ECG pattern was
dened as type 1, 2, or 3. Type 1 pattern has coved ST-segment
elevation of 2 mm or greater, followed by an inverted T-wave, with

* Corresponding author. Tel: 98 711 2277181; fax: 98 711 2277182.

E-mail address: draslani@yahoo.com

little or no isoelectric separation. Type 2 pattern also has a hightakeoff ST-segment elevation of 2 mm or greater with gradually
descending ST-segment elevation (remaining 1 mm above the
baseline), followed by a positive or biphasic T-wave resulting in a saddleback conguration. Type 3 pattern has either coved or saddleback
appearance with right precordial ST-segment elevation of less than
1 mm.15 Type 1 pattern is diagnostic of the Brugada sign, whereas
type 2 and 3 patterns require conversion to the type 1 pattern
after challenge with a sodium channel blocking agent to be diagnostic.15 If the standard 12-lead ECG showed type 2 or 3 Brugada
pattern, 10 mg/kg of procainamide was intravenously administered
in 10 min, with the patient being continuously monitored in the intensive care unit. Maximum P-wave duration (Pmax) and P-wave dispersion (Pdisp) were measured with callipers and magnifying lens as
previously described.1618 Left atrial dimension was measured by
2D-guided M-mode echocardiography obtained in the parasternal
view according to American Society of Echocardiography recommendations.19 The endpoint of the study was the occurrence of spontaneous AF. The occurrence of AF was evaluated by clinical
follow-up, observing the patients symptoms, 24 h Holter ambulatory
ECG recording and ICD analysis data. Follow-up of patients with
Brugada ECG pattern consisted of every 2 months visit, during
which an ECG was performed and ICD was checked.

Statistical analysis
Categorical variables were compared using x2 test. Group differences were analysed by one-way ANOVA followed by Scheffe
s

& The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

948

M.A. Babai Bigi et al.

Table 1 Characteristics of patients with Brugada electrocardiographic pattern and control group

Age (years)
Female
Syncope
Polymorphic ventricular tachycardia
Ventricular brillation
Aborted sudden cardiac death
Type 1 Brugada ECG pattern
(Spontaneous or after procainamide)
Type 2 Brugada ECG pattern
Type 3 Brugada ECG pattern
Maximum P-wave duration (ms)
P-wave dispersion (ms)
Left atrial dimension (cm)

Patients
(n 115)

Control group
(n 85)

P-value

32.1 + 13.6
23 (20%)
8 (7%)
5 (4.3%)
2 (1.7%)
2 (1.7%)
28 (24%)

30.6 + 11.2
16 (19%)
0
0
0
0

NS
NS
,0.05
,0.05
,0.05
,0.05

56 (48%)
31 (27%)
119.3 + 14.5
38.9 + 10.6
3.22 + 0.45

121.1 + 13.7
39.6 + 11.1
3.11 + 0.48

NS
NS
NS

NS, non signicant.

Table 2 Characteristics of patients with type 1, 2, and 3 Brugada electrocardiographic Pattern

Syncope
Polymorphic VT
Ventricular brillation
Aborted sudden cardiac death
Maximum P-wave duration (ms)
P-wave dispersion (ms)
Left atrial dimension (cm)
Atrial brillation
Follow-up (months)

Type 1 (n 28)

Type 2 (n 56)

Type 3 (n 31)

P-value

8
5
2
2
117.1 + 15.2
39.7 + 11.4
3.21 + 0.44
15
47 + 14

0
0
0
0
120.3 + 14.3
38.3 + 10.5
3.24 + 0.51
0
49 + 18

0
0
0
0
119.4 + 11.8
38.1 + 12.3
3.19 + 0.63
0
51 + 14

,0.05
,0.05
,0.05
,0.05
NS
NS
NS
,0.05
NS

multiple comparison test. Numeric variables were compared using

dependent-samples t-test. To identify variables independently
associated with the occurrence of AF, univariate and multivariate
logistic regression analyses were performed. Data are expressed
as mean + SD. A value of P , 0.05 was considered statistically
signicant.

(3.23 + 0.45 vs. 3.11 + 0.48 cm, P NS) (Table 1). There
were no differences between Pmax, Pdisp, and left atrial dimension of the type 1, 2 and 3 Brugada patients (Table 2).

Predictors of atrial brillation

Results
Baseline characteristics
Type 1 Brugada ECG pattern was found in 28 patients
(24 spontaneous and 4 after procainamide challenge test).
Implantable cardioverter debrillator was implanted in
10 symptomatic patients. Type 2 and 3 ECG pattern was
found in 56 and 31 patients, respectively. A total of 85
healthy age and gender-matched subjects were selected
as a control group for the purpose of comparison of ECG
and echocardiographic parameters. Clinical and paraclinical
characteristics of the patients and controls are listed in
Table 1. Mean age was identical in the two groups (patients
vs. controls) (32.1 + 13.6 years vs. 30.6 + 11.2 years,
respectively), as might be expected from the matching.
Pmax and Pdisp were not signicantly different between
patients and controls (Pmax: 119.3 + 14.5 vs. 121.1 +
13.7 ms, respectively; P NS) (Pdisp: 38.9 + 10.6 vs.
39.6 + 11.1 ms, respectively; P NS). Left atrial dimension
was also identical between patients and controls

Spontaneous paroxysmal AF was detected in 15 of 28 type 1

Brugada patients (53%) and none of the type 2 and 3 Brugada
patients during 50 months of follow-up. All 15 patients with
AF had at least one episode of paroxysmal AF and none of
the patients showed persistent or chronic AF. All 15 patients
who had paroxysmal AF had previous life threatening cardiac
events (eight patients had syncope, two had ventricular
brillation, four had polymorphic ventricular tachycardia
based on ICD analysis data, and one had aborted
sudden cardiac death). In contrast, paroxysmal AF did not
occur in type 1 Brugada patients without previous life
threatening cardiac events. As mentioned earlier, none of
the type 2 and 3 Brugada patients have episodes of AF.
Characteristics of type 1 Brugada patients with and
without paroxysmal AF are listed in Table 3. In multiple
regression analysis, age, sex, Pmax, Pdisp, and left atrial
dimension did not bear a signicant univariate relation to
occurrence of paroxysmal AF. In contrast, the occurrence
of previous life threatening cardiac events was a signicant
risk factor for paroxysmal AF (P 0.0001) (Table 4).

Clinical predictors of AF in Brugada syndrome

949

Table 3 Characteristics of type 1 Brugada patients with and without paroxysmal atrial brillation

Age (years)
Male
Previous cardiac events
Syncope
Polymorphic ventricular tachycardia
Ventricular brillation
Aborted sudden cardiac death
Maximum P-wave duration (ms)
P-wave dispersion (ms)
Left atrial dimension (cm)

With paroxysmal
atrial brillation (n 15)

Without paroxysmal atrial

brillation (n 13)

P-value

29.3 + 7.6
12 (80%)

31.1 + 9.3
10 (76%)

NS
NS

6 (40%)
5 (13%)
2 (13%)
2 (13%)
117.3 + 12.5
39.9 + 11.6
3.19 + 0.53

2 (15%)
0
0
0
118.1 + 13.7
39.6 + 11.1
3.23 + 0.44

,0.05
,0.05
,0.05
,0.05
NS
NS
NS

NS, non signicant.

Table 4 Association between previous cardiac events in type 1

Brugada patients and atrial brillation

Previous events
No events
Total

AF

No AF

Total

15
0
15

2
11
13

17
11
28

Statistics: Fischer exact test (P 0.0001).

Discussion
Incidence of atrial brillation in Brugada syndrome
Recently, it has been shown that mutations in the cardiac
sodium channel gene, which result in slow recovery from
inactive states of the sodium channel or sodium channel
dysfunction, cause Brugada syndrome.2024 This functional
change in the mutational sodium channel will explain the
conduction abnormality of the ventricle, easy inducibility
of ventricular brillation,25 the late activation in the right
ventricular outow tract, and the abnormal late potentials.26 If a mutation in the cardiac sodium channel does in
fact cause Brugada syndrome,2022,25 a myocardial electrical
abnormality might exist not only in the ventricular myocytes
but also in the atrial myocytes. This hypothesis is supported
by previous studies that showed Brugada patients are prone
to AF,25,1114 but the exact incidence of AF in patients
with Brugada syndrome is not known. Antzelevitch et al. 3
reported that only 10% of patients with Brugada syndrome
exhibit paroxysmal AF. In one study, the incidence of spontaneous AF in patients with Brugada syndrome was 39%,
and the incidence of AF induced by electrical stimulation
was also high.27 In the present study, paroxysmal AF was
occurred in 53% of patients with type1 Brugada ECG
pattern. These results show that AF is not rare in patients
with Brugada syndrome.

Predictors of atrial brillation in Brugada syndrome

In the present study, we showed that only type 1 Brugada
ECG pattern (spontaneous or following procainamide) is
prone to AF. None of the type 2 or 3 Brugada patients
showed episodes of AF, whereas paroxysmal AF was occurred
in 53% of patients with type 1 Brugada ECG pattern during

the follow-up. This results show that ECG can be a suitable

predictor of AF in Brugada syndrome. On the other hand,
among type 1 Brugada patients, AF was occurred only in
patients who have previous life-threatening cardiac
events. Patients who have no history of previous cardiac
events never experienced episodes of paroxysmal AF.
Other clinical and paraclinical covariates (e.g. age, sex,
left atrial dimension, Pmax, and Pdisp) were not signicantly
associated with occurrence of AF. In our study, with amalgamation of the above data and considering the results of multiple regression analysis, history of previous cardiac events
(e.g. syncope, aborted sudden cardiac death, and VT/VF)
was the strongest predictor of AF in Brugada syndrome. It
is well known that history of previous life threatening
cardiac events is the strongest predictor of ventricular brillation in Brugada syndrome. We hypothesized that Brugada
patients with previous cardiac events might have a more
severe cardiac sodium channelopathy when compared with
asymptomatic Brugada patients. As mentioned earlier,
sodium channelopathy might exist not only in the ventricular
myocytes but also in the atrial myocytes and it is possible
that similar genetic defects alter both atrial and ventricular
electrophysiology in patients who experienced previous life
threatening cardiac events. Therefore, the more severe
defects in atrial sodium channels may be present in
Brugada patients with previous cardiac events and the
most powerful predictor of both AF and VF is history of
previous cardiac events.

Prognostic value of atrial brillation

in Brugada syndrome
Bordachar et al. 28 showed that in patients with an indication
for ICD, the incidence of atrial arrhythmias was 27 vs. 13% in
patients without an indication for an ICD (P , 0.05), which
suggests a more advanced disease process in patients with
Brugada syndrome and spontaneous atrial arrhythmias.
They also found that ventricular inducibility is positively
correlated with a history of atrial arrhythmias.28 In the
present study, we showed a highly signicant relationship
between AF and a history of previous life threatening
cardiac events. We suggest that BS patients with paroxysmal
AF may present with a more advanced level in the disease
process and AF may be an important indicator in risk
stratication of BS patients.

950

Signicance of atrial brillation in treatment

of Brugada syndrome
The present study showed that the occurrence of paroxysmal AF was frequent in patients with Brugada syndrome.
ICD can detect AF as ventricular brillation and would
start inappropriate cardioversion. Inappropriate shocks
from atrial arrhythmia episodes were observed in 14% of
cases, highlighting the need for careful programming of
the ICD.29 The fth generation implantable cardioverter
debrillator should be preferred for patients with Brugada
syndrome who experienced previous life threatening
cardiac events, even those who have not experienced an
attack of AF, because AF is common in this subgroup of
Brugada patients and AF may occur during the follow-up
period.

Conclusion
It is concluded that the history of previous life threatening
cardiac events is the strongest predictor of AF in Brugada
syndrome.
Conict of interest: none declared.

References
1. Babaee Bigi MA, Aslani A, Shahrzad S. Prevalence of Brugada sign in
patients presenting with palpitation in southern Iran. Europace 2007;
9:2525.
2. Brugada P, Brugada J. Right bundle branch block, persistent ST segment
elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol 1992;20:13916.
3. Antzelevitch C, Brugada P, Brugada J, Brugada R, Nademanee K,
Towbin J. The Brugada syndrome. In: Camm AJ, ed. Clinical Approaches
to Tachyarrhythmias. Armonk, NY: Futura, 1999.
4. Gussak I, Antzelevitch C. Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanism. J Electrocardiol
2000;33:299309.
5. Takenaka S, Kusano KF, Hisamatsu K, Nagase S, Nakamura K, Morita H
et al. Relatively benign clinical course in asymptomatic patients with
Brugada-type electrocardiogram without family history of sudden
death. J Cardiovasc Electrophysiol 2001;12:26.
6. Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R et al. The
idiopathic ventricular brillation induced with vagal activity in patients
without obvious heart disease. Circulation 1997;95:227785.
7. Shimada M, Miyazaki T, Miyoshi S, Soejima K, Hori S, Mitamura H et al.
Sustained monomorphic ventricular tachycardia in a patient with
Brugada syndrome. Jpn Circ J 1996;60:36470.
8. Brembilla-Perrot B, Beurrier D, Jacquemin L, Jacquemin L, Kubler L,
Brouant B et al. Incomplete bundle branch block and ST-segment
elevation: syndrome associated with sustained monomorphic ventricular
tachycardia in patients with apparently normal heart. Clin Cardiol
1997;20:40710.
9. Boersma L, Jaarsma W, Jessurun ER, Van Hemel N, Wever E. Brugada syndrome: a case report of monomorphic ventricular tachycardia. Pacing
Clin Electrophysiol 2001;24:1125.

M.A. Babai Bigi et al.

10. Eckardt L, Kirchhof P, Loh P, Schulze-Bahr E, Johna R, Wichter T et al.
Brugada syndrome and supraventricular tachyarrhythmias: a novel
association? J Cardiovasc Electrophysiol 2001;12:6805.
11. Lee KT, Lau CP, Tse HF, Wan SH, Fan K. Prevention of ventricular brillation by pacing in a man with Brugada syndrome. J Cardiovasc
Electrophysiol 2000;11:9357.
12. Fujiki A, Usui M, Nagasawa H, Mizumaki K, Hayashi H, Inoue H. ST
segment elevation in the right precordial leads induced with class Ic
antiarrhythmic drugs: insight into the mechanism of Brugada syndrome.
J Cardiovasc Electrophysiol 1999;10:2148.
13. Matsuo K, Shimizu W, Kurita T, Inagaki M, Aihara N, Kamakura S. Dynamic
changes of 12-lead electrocardiograms in a patient with Brugada
syndrome. J Cardiovasc Electrophysiol 1998;9:50812.
14. Nakazato Y, Nakata Y, Yasuda M, Nakazato K, Sumiyoshi M, Ogura S et al.
Safety and efcacy of oral ecainide acetate in patients with cardiac
arrhythmias. Jpn Heart J 1997;38:37985.
15. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D
et al. Brugada syndrome: report of the second consensus conference.
Circulation 2005;111:65970.
16. Dilaveris PE, Gialafos EJ, Sideris SK, Theopistou AM, Andrikopoulos GK,
Kyriakidis M et al. Simple electrocardiographic markers for the prediction
of paroxysmal idiopathic atrial brillation. Am Heart J 1998;135:7338.
17. Aytemir K, Ozer N, Atalar E, Sade E, Aksoyek S, Ovunc K et al. P-wave
dispersion on 12-lead electrocardiogram in patients with paroxysmal
atrial brillation. Pacing Clin Electrophysiol 2000;23:110912.
18. Steinberg JS, Zelenkofske S, Wong SC, Gelernt M, Sciacca R, Menchavez E.
Value of P wave signal-averaged ECG for predicting atrial brillation after
cardiac surgery. Circulation 1993;88:161822.
19. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding
quantitation in M-mode echocardiography: results of a survey of echocardiographic measurement. Circulation 1978;58:10724.
20. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P et al.
Genetic basis and molecular mechanisms for idiopathic ventricular brillation. Nature 1998;392:2936.
21. Rook MB, Bezzina Alshinawi C, Groenewegen WA, van Gelder IC, van
Ginneken AC, Jongsma HJ et al. Human SCN5A gene mutations alter
cardiac sodium channel kinetics and are associated with the Brugada
syndrome. Cardiovasc Res 1999;44:50717.
22. Balser JR. Sodium channelopathies and sudden death: must you be so
sensitive? Circ Res 1999;85:8724.
23. Bezzina CR, Rook MB, Wilde AAM. Cardiac sodium channel and inherited
arrhythmia syndromes. Cardiovasc Res 2001;49:25771.
24. Antzelevitch C. Electrical heterogeneity, cardiac arrhythmias and the
sodium channel. Circ Res 2000;87:9645.
25. Towbin JA. Ventricular tachycardia or conduction disease: what is the
mechanism of death associated with SCN5A? J Cardiovasc Electrophysiol
2001;12:63788.
26. Ikeda T, Sakurada H, Sakabe K, Sakata T, Takami M, Tezuka N et al.
Assessment of noninvasive markers in identifying patients at risk in the
Brugada syndrome: insight into risk stratication. J Am Coll Cardiol
2001;37:162834.
27. Morita H, Kusano-Fukushima K, Nagase S, Fujimoto Y, Hisamatsu K, Fujio H
et al. Atrial brillation and atrial vulnerability in patients with Brugada
syndrome. J Am Coll Cardiol 2002;40:143744.
28. Bordachar P, Reuter S, Garrigue S, Cai X, Hocini M, Jais P et al. Incidence,
clinical implications and prognosis of atrial arrhythmias in Brugada
syndrome. Eur Heart J 2004;25:87984.
29. Takehara N, Makita N, Kawabe J, Sato N, Kawamura Y, Kitabatake A,
Kikuchi K. A cardiac sodium channel mutation identied in Brugada
syndrome associated with atrial standstill. J Intern Med 2004;255:
13742.