Europace Advance Access originally published online on May 31, 2007
Europace 2007 9(10):947-950; doi:10.1093/europace/eum110
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MISCELLANEOUS
Clinical predictors of atrial fibrillation in Brugada syndrome
Cardiology Department, Namazee Hospital, Shiraz University of Medical Sciences, Zand Avenue, PO Box 71935-1334, Shiraz, Iran
Manuscript submitted 9 March 2007. Accepted after revision 27 April 2007.
* Corresponding author. Tel: +98 711 2277181; fax: +98 711 2277182. E-mail address: draslani{at}yahoo.com
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Abstract |
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Aims Atrial arrhythmias have been reported in patients with Brugada syndrome. The aim of this study was to evaluate clinical predictors of atrial fibrillation (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 significantly 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.
Key Words: Atrial fibrillation, Brugada syndrome, Ventricular fibrillation
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Introduction |
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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 fibrillation.1
–6 Arrhythmias such as premature ventricular contractions, monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular fibrillation have been reported in this syndrome.7–9 In addition, atrial arrhythmia has also been reported in patients with Brugada syndrome.3,10–14 The aim of this prospective study was to evaluate clinical predictors of atrial fibrillation (AF) in patients with Brugada syndrome. |
Methods |
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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 defined 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 little or no isoelectric separation. Type 2 pattern also has a high-takeoff 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 configuration. 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.16–18 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 patient's 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 |
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Categorical variables were compared using
2 test. Group differences were analysed by one-way ANOVA followed by Scheffé's 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 significant. |
Results |
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Baseline characteristics
Type 1 Brugada ECG pattern was found in 28 patients (24 spontaneous and 4 after procainamide challenge test). Implantable cardioverter defibrillator 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 significantly 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 (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).
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Predictors of atrial fibrillation
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 fibrillation, 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 significant univariate relation to occurrence of paroxysmal AF. In contrast, the occurrence of previous life threatening cardiac events was a significant risk factor for paroxysmal AF (P = 0.0001) (Table 4).
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Discussion |
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Incidence of atrial fibrillation 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.20
–24 This functional change in the mutational sodium channel will explain the conduction abnormality of the ventricle, easy inducibility of ventricular fibrillation,25 the late activation in the right ventricular outflow tract, and the abnormal late potentials.26 If a mutation in the cardiac sodium channel does in fact cause Brugada syndrome,20–22,25 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,2–5,11–14 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 fibrillation 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 significantly 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 fibrillation 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 fibrillation 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 significant 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 stratification of BS patients.
Significance of atrial fibrillation 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 fibrillation 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 fifth generation implantable cardioverter defibrillator 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.
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Conclusion |
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It is concluded that the history of previous life threatening cardiac events is the strongest predictor of AF in Brugada syndrome.
Conflict of interest: none declared.
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References |
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