• Users Online: 125
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 41-48

Risk stratification in Brugada syndrome


Department of Medicine II, Kansai Medical University, Moriguchi, Osaka, Japan

Date of Web Publication5-Feb-2019

Correspondence Address:
Dr. Masahiko Takagi
Division of Cardiac Arrhythmia, Department of Medicine II, Kansai Medical University, 10-15 Fumizono-Cho, Moriguchi 5708507, Osaka
Japan
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJHR.IJHR_3_18

Rights and Permissions
  Abstract 

Brugada syndrome is an arrhythmogenic disease associated with sudden cardiac death due to ventricular arrhythmias. The risk stratification of patients without previous cardiac arrest remains the most controversial issue, especially for asymptomatic individuals, in Brugada syndrome. We review the recent data of several clinical, electrocardiographic, and electrophysiological parameters proposed for risk stratification. A history of documented fatal ventricular arrhythmias or aborted sudden cardiac death and/or arrhythmogenic syncope is a predictor of arrhythmic events, whereas the prognostic value of a familial history of sudden cardiac death and the presence of an SCN5A mutation are not well defined. On the electrocardiographic features, the spontaneous type 1 electrocardiogram (ECG) is associated with the risk for arrhythmic events in most of the studies, whereas early repolarization and fragmented QRS increases the risk in some studies. Late potentials using signal-averaged ECG and microscopic T-wave alternans indicate some available results in small studies that should be validated. The prognostic value of programmed electrical stimulation during electrophysiological study as a risk marker also remains controversial. A less aggressive protocol of programmed electrical stimulation may be preferable for risk stratification in the Brugada syndrome patients without previous cardiac arrest. Multiparametric approaches evaluating specific clinical factors and ECG may improve risk stratification.

Keywords: Brugada syndrome, noninvasive marker, programmed electrical stimulation, review, risk stratification


How to cite this article:
Takagi M, Shiojima I. Risk stratification in Brugada syndrome. Int J Heart Rhythm 2018;3:41-8

How to cite this URL:
Takagi M, Shiojima I. Risk stratification in Brugada syndrome. Int J Heart Rhythm [serial online] 2018 [cited 2019 Feb 17];3:41-8. Available from: http://www.ijhronline.org/text.asp?2018/3/2/41/250861


  Introduction Top


Brugada syndrome (BrS) is an arrhythmogenic disease characterized by specific ST-segment elevation in the right precordial leads on the 12-lead electrocardiogram (ECG) without any structural heart disease and an increased risk of sudden cardiac death (SCD) due to fatal ventricular arrhythmia.[1],[2]

Currently, little controversy exists on the highest risk of recurrence of ventricular fibrillation (VF) or SCD among patients with spontaneous type 1 ECG and documented VF or aborted SCD, who are strongly advised to implant an implantable cardioverter-defibrillator (ICD).[3],[4] On the contrary, risk assessment in patients without previous documented VF or SCD, especially those for asymptomatic individuals, has not been fully established.

The current review aims to focus on the risk stratification in BrS patients based on available data mainly derived from registry studies.


  Diagnosis of Brugada Syndrome Top


According to the 2015 guidelines for the management of patients with ventricular arrhythmia and prevention of SCD,[3] and the J-wave syndromes expert consensus conference report,[4] the diagnosis of BrS is based on the specific ECG characteristics: J-point elevation ≥2 mm followed by coved-type ST-segment elevation and negative T wave (type 1 ECG) in at least one of the right precordial leads positioned in the 2nd to 4th intercostal space occurring either spontaneously or after pharmacologic challenge with a Class I antiarrhythmic agent (ajmaline, procainamide, flecainide, or pilsicainide) which can convert type 2 or type 3 ECG to type 1 ECG [Figure 1]A,[Figure 1]B,[Figure 1]C. Type 2 ECG is characterized by a high take-off of ≥2 mm and a saddleback-type ST-segment configuration ≥1 mm [Figure 1]B. Type 3 ECG displays a J-point elevation ≥2 mm and either a saddleback-type or coved-type ST-segment elevation of <1 mm.
Figure 1: Representative Brugada-type ECGs. (A) Type 1 ECG in leads V1 and V2. (B) Type 2 ECG in lead V2. (C) Type 2 ECG in lead V2 before pilsicainide administration (a) and type 1 ECG in lead V2 after pilsicainide administration (b). ECG=Electrocardiogram

Click here to view



  Prevalence of Brugada Type Electrocardiogram (Types 1–3) Top


The prevalence of Brugada type ECG (types 1–3) has been reported in several countries. However, it depends on regions and gender. According to some meta-analysis of the population-based studies,[5],[6],[7] the mean worldwide prevalence was about 0.4%, with the highest in Asia (0.9%) and lowest in North America (0.2%).[5] Pooled prevalence of types 1 and 2–3 ECG was 0.03%–0.05% and 0.42%–0.61%, respectively.[6],[7] The prevalence of type 1 ECG was higher in Asia (0.18%). The highest prevalence was found in Southeast Asia (0.37%), followed by the Middle Asia, East Asia, Europe, and North America. The prevalence of type 2 or 3 ECG was also higher in Asia (0.83%). The sex difference for the prevalence of Brugada type ECG was 0.9% in males, whereas 0.1% in females.[5]


  Prognosis of Brugada Syndrome Top


Definition of “arrhythmic events” in Brugada syndrome

In the majority of large-scale studies, appropriate ICD therapies or SCD was defined as the arrhythmic events, and most of them were appropriate ICD therapies rather than SCD.[8],[9] However, using “appropriate ICD therapies” as a surrogate for SCD tends to overestimate the actual risk of SCD among patients without ICD. This has been evaluated for BrS patients.[10]

However, in this review, “arrhythmic events” represent appropriate ICD therapies or SCD because of evaluation based on data mainly from previous registry studies.

Prognosis of symptomatic patients with Brugada syndrome

Most of the studies consistently indicate that the risk of arrhythmic events is the highest for patients with previously documented VF or SCD, intermediate for those with arrhythmic syncope, and the lowest for asymptomatic individuals at enrollment. Therefore, the risk of recurrence of arrhythmic event is the highest for patients who previously experienced VF or SCD with an event rate of about 35% at 4 years,[8],[11] 44% at 7 years,[12] and 48% at 10 years.[12] The risk of arrhythmic events for patients with syncope is 4 times higher than that of originally asymptomatic individuals but 4 times lower compared with that of patients with previously documented VF or SCD.[8] Approximately 30% of BrS patients experience syncope.[13],[14] However, patients with syncope derived from most registries were divided into two groups: the arrhythmic syncope with bad prognosis and the nonarrhythmic syncope such as vagal syncope with good prognosis. A significant percentage of patients with nonarrhythmic syncope repeat some episodes of nonarrhythmic syncope and those with nonarrhythmic syncope are at a very low risk for SCD (0%–0.3% per year) compared with arrhythmic syncope (2.2% per year).[15]

Prognosis of asymptomatic patients with Brugada syndrome

Although some initial studies showed a relatively high rate of fatal arrhythmic events in individuals without symptoms,[16],[17],[18],[19] recent studies reported much lower rate of cardiac events (VF or SCD). In the France, Italy, Netherlands, and Germany (FINGER) registry, the largest series of BrS, the incidence of the arrhythmic events in individuals without symptoms was 0.5% per year. In a substudy of the FINGER registry with a 66-month follow-up period, 4.5% of the individuals without symptom had a newly arrhythmic event (0.8% per year).[8] Similarly, in the PRogrammed Electrical stimUlation preDictive valuE (PRELUDE) registry, an annual rate of arrhythmic events in asymptomatic individuals with type 1 ECG was about 1%.[9] Recently, we reported data on 267 asymptomatic BrS individuals with a mean follow-up of 50 ± 30 months and the annual rate of cardiac events was 0.3%.[20] In a recent meta-analysis including 2743 individuals, the annual rate of cardiac event for individuals without symptom was 1%.[21] Until now, similar results of the low incidence of arrhythmic events in asymptomatic individuals have been reported in some studies.[22],[23],[24],[25],[26],[27],[28],[29],[30]

In about 50% of BrS patients, arrhythmic events will suddenly occur as VF without any premonition.[31] It is difficult to predict the progression of the arrhythmic risk. Sacher et al. revealed that the rate of arrhythmic event is easily fixed over time in BrS patients with an ICD. The rate of appropriate therapy for 10 years after ICD implantation was 12% in asymptomatic individuals.[13] Raju et al.[32] have recently reported that most of SCD occur in previously asymptomatic individuals. These data reveal the necessity to establish a more precise risk marker for asymptomatic individuals.


  Risk Stratification in Brugada Syndrome Top


The majority of the clinical, electrocardiographic, and electrophysiological variables have been evaluated in symptomatic patients with syncope or aborted SCD.[3],[4],[8] Most of these factors have not been evaluated in a prospective study. Therefore, their utility in risk stratification for asymptomatic individuals is still unknown.

Clinical parameters

Age and sex

Different registries have shown the male dominance of BrS.[8],[9] Male gender increases the 3-fold risk of a spontaneous type I ECG and of inducibility of ventricular tachycardia (VT)/VF by programmed electrical stimulation (PES).[33] Moreover, male gender increases a 7-fold risk of arrhythmic events.[33] In large registries, male gender was 64%,[12] 89%,[8] and up to 94%[13] of patients with SCD. A recent pooled analysis from 24 clinical studies also showed that male gender is associated with a higher risk of arrhythmic events. In male patients, symptomatic patients have a higher risk of arrhythmic events compared to asymptomatic individuals, but not within the female patients.[34] However, because most of the asymptomatic individuals are also male, gender is not an independent predictor of arrhythmic events.[8],[33] Recently, Sieira et al.[35] have reported that female individuals tended to be asymptomatic and less displayed the type 1 ECG. The prognosis and clinical presentation in female are more benign with an annual rate of arrhythmic event (0.25% per year).[33]

Although the genetic trait is present from birth, the mean age at the onset of cardiac arrest was 39–48 years in different large series.[8],[11],[12] Most patients with arrhythmic events were between 20 and 65 years.[8],[11],[12],[36] In a recent survey, the majority (94.2%) of the patients were 16–70 years at the time of arrhythmic event, whereas elderly (>70 years) and pediatric (<16 years) patients were 1.5% and 4.3%, respectively. Arrhythmic event most frequently occurred at 38–48 years (mean, 42 ± 15; range, 0.3–84 years).[37]

Familial and genetic background

Physicians tend to pay attention to genetic tests and their values on risk assessment because BrS is classified as a genetic arrhythmic syndrome. However, results from some studies are still controversial. Kamakura et al.[11] have shown that a family history of SCD occurring at <45 years old is an independent risk marker for poor prognosis. Delise et al.[24] have demonstrated that family history of SCD may have prognostic value only in combination with other risk markers. On the contrary, in other studies including a meta-analysis, a family history of SCD was not confirmed to have predictive value for future arrhythmic events.[8],[29] Moreover, a family history of SCD was not associated with the increase of SCD in patients with family history of SCD in a first-degree relative, or in those with CD in a young (<35 years old) relative or multiple SCD in the same family.[38]

In 19 genes, mutations have been identified in individuals with Brugada type ECG until now.[39] Most of the mutation are SCN5A gene mutation encoding for the cardiac sodium channel. However, screening of gene abnormality identifies this mutation only in approximately 15%–20% of BrS patients.[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50] Furthermore, risk stratification of other rare genes mutations associated with BrS is still lacking. Some large-scale registries had not found an association between the SCN5A gene mutations with the risk of cardiac events.[8],[12],[26],[42] On the contrary, a recent multicenter registry demonstrated an association between the SCN5A gene mutations with the cardiac events. The individuals with SCN5A mutations in the pore region were associated with significantly poorer outcomes compared to those without the SCN5A mutation, among probands with prior syncope and probands without symptoms, as well as in the entire cohort. Multivariate analysis revealed that only BrS patients with SCN5A mutation showed more conduction delay and had a higher risk for future cardiac events.[43] Moreover, a recent systemic review and meta-analysis from seven studies reported a significant association between SCN5A mutations and major arrhythmic events in the Asian population.[51] Whether the detailed genetic analysis is a promising tool in risk assessment of BrS patients or not is needed to validate in future studies.

Syncope

The risk of arrhythmic events in patients with syncope is intermediate. One of the reasons for this intermediate-risk prognosis is that the syncope population derived from most studies consists of patients with arrhythmic and nonarrhythmic syncope. One study showed that VF occurred in 22% of patients with presumably arrhythmic syncope but in none of the patients with nonarrhythmic syncope during follow-up.[14] Similarly, in another study,[15] 12% of patients with presumed arrhythmic syncope but none of those with nonarrhythmic syncope documented VF episodes during follow-up of 4.5 years. These data show that the discrimination of syncope is important by taking a detailed clinical history at the time of syncope. Some studies revealed prodromes with blurred vision suggests nonarrhythmic syncope and abnormal respiration is observed with arrhythmic syncope.[14],[15] Recently, some studies showed the presence of fragmented QRS and a spontaneous type 1 ECG correlate with a high arrhythmic risk in patients with arrhythmic syncope.[9],[44]

Electrocardiogram parameters

Several ECG parameters have been proposed for the risk assessment in BrS patients [Table 1].
Table 1: ECG parameters proposed for the risk stratification in Brugada syndrome

Click here to view


Spontaneous type 1 electrocardiogram

General consensus exists that patients with spontaneous type 1 ECG have a higher risk than those with drug-induced type 1 ECG for arrhythmic events.[8],[9],[24],[26] A meta-analysis also demonstrated that individuals with spontaneous type 1 ECG had a threefold to 4-fold increased risk of arrhythmic events compared to those with a drug-induced type 1 ECG.[45] This observation applies for asymptomatic individuals[8] and for patients with syncope.[8],[9],[24] In addition to place the recording electrodes on the standard fourth intercostal space, electrodes on the right precordial upper intercostal spaces increase the sensitivity for detecting the type 1 ECG.[46],[47] The value of spontaneous type 1 ECG for predicting VF was similar on ECG recorded on the right precordial upper intercostal spaces.[48],[49]

Fragmented QRS

Several studies indicated the fragmented QRS (f-QRS; multiple spikes in the QRS in leads V1 to V3) was associated with increased risk of arrhythmic events[9],[44],[50],[51],[52] but another study did not support the result.[53] Take et al.[44] reported that, in patients with syncope, those with f-QRS had 2-fold risk of fatal ventricular arrhythmia compared to the risk in those without. A prospective study of patients without previous cardiac arrest revealed patients with f-QRS had 9-fold risk for fatal ventricular arrhythmia.[9] Recent meta-analysis also showed an association between f-QRS and arrhythmic event in BrS. Rattanawong et al.[54] reported that patients with baseline f-QRS had up to 3-fold arrhythmic events (VF, sustained VT, SCD, or sudden cardiac arrest). Moreover, a meta-analysis of f-QRS from eight studies showed f-QRS predicted future cardiac events in BrS.[55] However, we need to pay attention to the definitions of f-QRS, which was different among studies, and ECG filter settings because it is still unclear how different filter settings would have an influence on f-QRS.

aVR sign and S wave in lead I

One study reported that the aVR sign defined R/q ≥0.75 or R wave ≥0.3 mV in lead aVR may be a risk factor for the development of fatal arrhythmic events.[56] Recently, another study revealed the presence of a large and/or wide S-wave in lead I may be a predictive marker of ventricular tachyarrhythmias.[57] These parameters have been speculated to be related to the conduction abnormality in the right ventricular outflow tract (RVOT).[56],[57] However, this relationship with fatal ventricular tachyarrhythmias was not confirmed in a larger study.[42]

Wide QRS width

A wide QRS duration in leads II, V2, and V6 has been proposed as a noninvasive risk factor of fatal VT/VF in BrS patients.[30],[58] Recent reports indicated that a wide QRS duration in lead V1 or V2 predicted ventricular tachyarrhythmias or syncope in BrS.[20],[29],[59],[60]

Inferolateral early repolarization

The early repolarization (ER) pattern in inferior and/or lateral leads is seen in 12%–15% of BrS.[20],[61],[62] Several studies have demonstrated that the ER pattern predicts future arrhythmic events.[20],[61],[62] In particular, it have been shown that patients with inferolateral J waves and/or horizontal ST-segment morphology following the J wave [Figure 2] display a higher incidence of cardiac events than those without.[20] The inferolateral ER is associated not only with VF episodes but with VF storms.[63] A recent meta-analysis on the prognostic value of ER pattern in BrS revealed that patients with ER showed a higher risk of arrhythmic events compared to those without ER (odds ratio 3.29).[64] Based on these findings, the inferolateral ER pattern in BrS appears to be highly arrhythmogenic.
Figure 2: Inferolateral ER in patients with Brugada syndrome. (a) Horizontal ST segment in the leads deploying notching type of J wave (J waves are marked with solid arrows). Dotted arrow indicates slurring type of J wave. (b) Rapidly ascending (dotted arrow) ST segment in the leads deploying notching type of J wave (solid arrows). ER=Early repolarization

Click here to view


Type 1 electrocardiogram in peripheral leads

One study reported that 10% of patients with a positive ajmaline challenge test developed type 1 ECG not only in the right precordial leads but in peripheral leads.[65] In another study, 9% of the patients showed type 1 ECG in at least one peripheral lead either spontaneously or after ajmaline challenge test. In this study, spontaneous VF was documented in 8 of the 30 patients with peripheral type 1 ECG but in 18 of 293 patients who showed type 1 ECG only in the right precordial leads.[66] Furthermore, in the series of 234 initially asymptomatic individuals, it has been reported that 13% of those with right precordial and peripheral type 1 ECG but 3% with only right precordial type 1 ECG developed spontaneous VF within 4 years.[67]

Intervals between T peak and T end (T p-e) and T p-e dispersion

A QTc interval >460 ms in lead V2 as well as an increased T peak-T end interval (T p-e), and T p-e dispersion in the precordial leads have been reported to be associated with fatal arrhythmic events in BrS.[67] Another study also showed that the T p-e and T p-e dispersion significantly increased in patients with SCD and appropriate ICD therapies and that the T p-e is associated with arrhythmic events in BrS.[68] Recent meta-analysis demonstrated that increased T p-e was related to up to 5.7-fold risk of VT/VF and/or SCD in BrS patients.[69]

Late potentials

A prospective study evaluating signal-averaged ECG reported that positive late potentials may have good predictive value for fatal ventricular arrhythmias in BrS.[19] In another study, the positive predictive value, the predictive accuracy, and the negative predictive value of the late potentials were 92.0%, 86.4%, and 78.9%, respectively.[70] We reported that daily fluctuations in specific 12-lead ECG and signal-averaged ECG characteristics were useful for distinguishing high-risk and low-risk patients in BrS,[71] and that patients with previously VF episodes more frequently have late potentials after a pilsicainide challenge test.[72] The limitation of late potentials for clinical use is the high prevalence in both symptomatic and asymptomatic cases. The late potentials might be helpful for risk assessment in the setting of multiparametric approach.

T-wave alternans

Whether T-wave alternans (TWA) is a predictor for fatal arrhythmic event in BrS is still controversial.[73],[74] In our recent study, a higher level of TWA was more frequently observed at night in BrS patients with prior VF.[56] Moreover, the increased nocturnal TWA was one of the independent predictors of cardiac events during the follow-up. Furthermore, in another study, we reported the prognostic significance of the seasonal variations of TWA in BrS. The patients with prior VF episodes showed the greatest max-TWA value in lead V2 at the third intercostal space during morning and had higher the max-TWA value in summer than in the other seasons.[75]

Programmed electrical stimulation

The prognostic role of PES during electrophysiologic study remains to be debated because of conflicting evidence in BrS.[76],[77] Some studies suggest that inducibility of VT/VF during electrophysiologic testing predicts the future arrhythmic events,[24],[78],[79] whereas large recent studies show the opposite result.[8],[11],[20]

The prognostic value of PES for patients without previous cardiac arrest is limited and not enough for risk stratification and clinical decision-making. The recent large-scale studies,[8],[14],[80],[81] including approximately 500 patients with syncope and studies with 3–5 years' follow-up, show the occurrence of arrhythmic events tends to be higher in patients with inducible VT/VF, but the risk for noninducible patients is also high. As mentioned earlier, the discrimination of syncope as arrhythmic or nonarrhythmic based on clinical history, is more important than the results of PES for risk stratification. For asymptomatic individuals at presentation, several meta-analysis of previous studies evaluating the prognostic significance of PES has been reported and the results remain controversial. The initial two meta-analysis demonstrated VT/VF inducibility was not associated with fatal arrhythmic events,[45],[82] whereas recent other meta-analysis showed that inducibility of VT/VF at PES definitely predicted the future arrhythmic events.[21],[83],[84]

There are several possible reasons for the conflicting evidence regarding the prognostic value of PES in BrS. First, the differences in the stimulation protocols, including basic cycle lengths, the number of extrastimuli, the minimum coupling intervals used (up to 200 ms or refractoriness), and the pacing site (right ventricular apex [RVA] and/or RVOT), impact on the results of the inducibility at PES.[85] Second, a few number of asymptomatic individuals experience fatal ventricular arrhythmias during follow-up. Therefore, the statistical analysis for the prognostic significance of several parameters including the value of PES becomes challenging. The stimulation protocol differs in each study. The PRELUDE registry used a fixed stimulation protocol. RV was stimulated from RVA and RVOT.[9] Basic cycle lengths were 600 and 400 ms, and minimal coupling intervals were effective refractory period ≥200 ms by up to 2 extrastimuli or effective refractory period by 3 extrastimuli. The order of pacing sites and the number of extrastimuli at both basic cycle lengths were up to 3 extrastimuli at one site then moved to another site. In this registry, inducibility of VT/VF was not confirmed to be a significant risk factor in all patients as well as those induced by up to 2 ventricular extrastimuli. On the other hand, Brugada group stimulated RV only from RVA. Basic cycle lengths were 600, 500, and 430 ms, and minimal coupling intervals were effective refractory period ≥200 ms by up to 3 extrastimuli. Using the same protocol, Sieira et al.[79] indicated inducibility of VT/VF is only significant risk factor in 363 asymptomatic individuals at multivariate analysis. Recent two Japanese studies reported a utility of a uniform less aggressive protocol of PES for risk stratification in patients without previous cardiac arrest.[86],[87] In these studies, RV was stimulated from RVA and RVOT. The order of pacing sites and the number of extrastimuli were single and double stimulus from RVA, single and double from RVOT, triple from RVA, and then triple stimuli from RVOT. These studies revealed the PES inducibility by up to 2 extrastimuli had significant predictive value for future cardiac events. A less aggressive stimulation protocol at PES for VT/VF induction is preferable for risk assessment in patients without previous cardiac arrest.

Combinations of risk factors

Several studies showed the presence of several independent risk markers may improve risk stratification of patients without previous cardiac arrest.[24],[48],[59],[88],[89],[90],[91] Most of them have shown the combination of spontaneous type 1 ECG and at least one other proposed risk marker is useful to identify high-risk patients for cardiac events.[24],[48],[88] Two studies reported that combination of spontaneous type 1 ECG, syncope and inducible VT/VF at PES was predictive of later arrhythmic events.[48],[88] Delise et al.[24] recently demonstrated that patients with spontaneous type 1 ECG and at least two other proposed risk factors (family history of SCD, syncope, or inducibility of VT/VF) are at higher risk of cardiac events. Furthermore, other studies exhibited that the combination of ER pattern and f-QRS is an independent risk marker of further arrhythmic events.[89],[90] Kawazoe et al.[59] reported the combination of syncope, r-J interval in lead V1, QRS duration in lead V6 and T p-e dispersion was a useful marker to identify high-risk patients for cardiac events. Moreover, Sieira et al.[91] revealed the combination of specific risk markers such as aborted SCD, syncope, spontaneous type 1 ECG, familial SCD at young age, inducible VT/VF, and sinus node dysfunction predicts more precisely risk of future arrhythmic events.

Although multiparametric approaches appear to be promising in risk stratification in BrS, the approaches should be validated in prospective studies including a larger number of patients, particularly for asymptomatic individuals.


  Conclusions Top


Risk stratification in BrS patients is still a big challenge for physicians. Despite limited and conflicting evidence for risk assessment, especially in individuals without previous cardiac arrest, multiparametric approaches evaluating specific clinical, electrocardiographic, and electrophysiologic parameters may improve risk stratification, as individual risk factors show limited prognostic values. Prospective large-scale multicenter studies on risk stratification with longer follow-up more than 10 years will be needed to clarify this unsolved issue within the next decade.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391-6.  Back to cited text no. 1
    
2.
Sieira J, Brugada P. The definition of the Brugada syndrome. Eur Heart J 2017;38:3029-34.  Back to cited text no. 2
    
3.
Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015;36:2793-867.  Back to cited text no. 3
    
4.
Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, et al. J-wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Europace 2017;19:665-94.  Back to cited text no. 4
    
5.
Quan XQ, Li S, Liu R, Zheng K, Wu XF, Tang Q, et al. Ameta-analytic review of prevalence for Brugada ECG patterns and the risk for death. Medicine (Baltimore) 2016;95:e5643.  Back to cited text no. 5
    
6.
Vutthikraivit W, Rattanawong P, Putthapiban P, Sukhumthammarat W, Vathesatogkit P, Ngarmukos T, et al. Worldwide prevalence of Brugada syndrome: A systematic review and meta-analysis. Acta Cardiol Sin 2018;34:267-77.  Back to cited text no. 6
    
7.
Shi S, Barajas-Martinez H, Liu T, Sun Y, Yang B, Huang C, et al. Prevalence of spontaneous Brugada ECG pattern recorded at standard intercostal leads: A meta-analysis. Int J Cardiol 2018;254:151-6.  Back to cited text no. 7
    
8.
Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, et al. Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada syndrome registry. Circulation 2010;121:635-43.  Back to cited text no. 8
    
9.
Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, et al. Risk stratification in Brugada syndrome: Results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol 2012;59:37-45.  Back to cited text no. 9
    
10.
Delise P, Allocca G, Sitta N, DiStefano P. Event rates and risk factors in patients with Brugada syndrome and no prior cardiac arrest: A cumulative analysis of the largest available studies distinguishing ICD-recorded fast ventricular arrhythmias and sudden death. Heart Rhythm 2014;11:252-8.  Back to cited text no. 10
    
11.
Kamakura S, Ohe T, Nakazawa K, Aizawa Y, Shimizu A, Horie M, et al. Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3. Circ Arrhythm Electrophysiol 2009;2:495-503.  Back to cited text no. 11
    
12.
Conte G, Sieira J, Ciconte G, de Asmundis C, Chierchia GB, Baltogiannis G, et al. Implantable cardioverter-defibrillator therapy in Brugada syndrome: A 20-year single-center experience. J Am Coll Cardiol 2015;65:879-88.  Back to cited text no. 12
    
13.
Sacher F, Probst V, Maury P, Babuty D, Mansourati J, Komatsu Y, et al. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: A multicenter study-part 2. Circulation 2013;128:1739-47.  Back to cited text no. 13
    
14.
Sacher F, Arsac F, Wilton SB, Derval N, Denis A, de Guillebon M, et al. Syncope in Brugada syndrome patients: Prevalence, characteristics, and outcome. Heart Rhythm 2012;9:1272-9.  Back to cited text no. 14
    
15.
Olde Nordkamp LR, Vink AS, Wilde AA, de Lange FJ, de Jong JS, Wieling W, et al. Syncope in Brugada syndrome: Prevalence, clinical significance, and clues from history taking to distinguish arrhythmic from nonarrhythmic causes. Heart Rhythm 2015;12:367-75.  Back to cited text no. 15
    
16.
Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P, et al. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 2002;105:73-8.  Back to cited text no. 16
    
17.
Brugada P, Brugada R, Brugada J. Patients with an asymptomatic Brugada electrocardiogram should undergo pharmacological and electrophysical testing. Circulation 2005;112:279-85.  Back to cited text no. 17
    
18.
Sarkozy A, Boussy T, Kourgiannides G, Chierchia GB, Richter S, De Potter T, et al. Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome. Eur Heart J 2007;28:334-44.  Back to cited text no. 18
    
19.
Huang Z, Patel C, Li W, Xie Q, Wu R, Zhang L, et al. Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: A prospective study. Heart Rhythm 2009;6:1156-62.  Back to cited text no. 19
    
20.
Takagi M, Aonuma K, Sekiguchi Y, Yokoyama Y, Aihara N, Hiraoka M, et al. The prognostic value of early repolarization (J wave) and ST-segment morphology after J wave in Brugada syndrome: Multicenter study in Japan. Heart Rhythm 2013;10:533-9.  Back to cited text no. 20
    
21.
Fauchier L, Isorni MA, Clementy N, Pierre B, Simeon E, Babuty D, et al. Prognostic value of programmed ventricular stimulation in Brugada syndrome according to clinical presentation: An updated meta-analysis of worldwide published data. Int J Cardiol 2013;168:3027-9.  Back to cited text no. 21
    
22.
Sacher F, Probst V, Iesaka Y, Jacon P, Laborderie J, Mizon-Gérard F, et al. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: A multicenter study. Circulation 2006;114:2317-24.  Back to cited text no. 22
    
23.
Makimoto H, Nakagawa E, Takaki H, Yamada Y, Okamura H, Noda T, et al. Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. J Am Coll Cardiol 2010;56:1576-84.  Back to cited text no. 23
    
24.
Delise P, Allocca G, Marras E, Giustetto C, Gaita F, Sciarra L, et al. Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: Usefulness of a combined clinical and electrophysiologic approach. Eur Heart J 2011;32:169-76.  Back to cited text no. 24
    
25.
Hiraoka M, Takagi M, Yokoyama Y, Sekiguchi Y, Aihara N, Aonuma K, et al. Prognosis and risk stratification of young adults with Brugada syndrome. J Electrocardiol 2013;46:279-83.  Back to cited text no. 25
    
26.
Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, et al. Natural history of Brugada syndrome: Insights for risk stratification and management. Circulation 2002;105:1342-7.  Back to cited text no. 26
    
27.
Giustetto C, Drago S, Demarchi PG, Dalmasso P, Bianchi F, Masi AS, et al. Risk stratification of the patients with Brugada type electrocardiogram: A community-based prospective study. Europace 2009;11:507-13.  Back to cited text no. 27
    
28.
Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, et al. Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 2005;111:257-63.  Back to cited text no. 28
    
29.
Takagi M, Yokoyama Y, Aonuma K, Aihara N, Hiraoka M; Japan Idiopathic Ventricular Fibrillation Study (J-IVFS) Investigators, et al. Clinical characteristics and risk stratification in symptomatic and asymptomatic patients with Brugada syndrome: Multicenter study in Japan. J Cardiovasc Electrophysiol 2007;18:1244-51.  Back to cited text no. 29
    
30.
Letsas KP, Weber R, Efremidis M, Korantzopoulos P, Astheimer K, Charalampous C, et al. Long-term prognosis of asymptomatic individuals with spontaneous or drug-induced type 1 electrocardiographic phenotype of Brugada syndrome. J Electrocardiol 2011;44:346-9.  Back to cited text no. 30
    
31.
Viskin S, Rogowski O. Asymptomatic Brugada syndrome: A cardiac ticking time-bomb? Europace 2007;9:707-10.  Back to cited text no. 31
    
32.
Raju H, Papadakis M, Govindan M, Bastiaenen R, Chandra N, O'Sullivan A, et al. Low prevalence of risk markers in cases of sudden death due to Brugada syndrome relevance to risk stratification in Brugada syndrome. J Am Coll Cardiol 2011;57:2340-5.  Back to cited text no. 32
    
33.
Benito B, Sarkozy A, Mont L, Henkens S, Berruezo A, Tamborero D, et al. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol 2008;52:1567-73.  Back to cited text no. 33
    
34.
Yuan M, Tian C, Li X, Yang X, Wang X, Yang Y, et al. Gender differences in prognosis and risk stratification of Brugada syndrome: A pooled analysis of 4,140 patients from 24 clinical trials. Front Physiol 2018;9:1127.  Back to cited text no. 34
    
35.
Sieira J, Conte G, Ciconte G, de Asmundis C, Chierchia GB, Baltogiannis G, et al. Clinical characterisation and long-term prognosis of women with Brugada syndrome. Heart 2016;102:452-8.  Back to cited text no. 35
    
36.
Kamakura T, Wada M, Nakajima I, Ishibashi K, Miyamoto K, Okamura H, et al. Evaluation of the necessity for cardioverter-defibrillator implantation in elderly patients with Brugada syndrome. Circ Arrhythm Electrophysiol 2015;8:785-91.  Back to cited text no. 36
    
37.
Milman A, Andorin A, Gourraud JB, Sacher F, Mabo P, Kim SH, et al. Age of first arrhythmic event in Brugada syndrome: Data from the SABRUS (Survey on arrhythmic events in Brugada syndrome) in 678 patients. Circ Arrhythm Electrophysiol 2017;10. pii: e005222.  Back to cited text no. 37
    
38.
Sarkozy A, Sorgente A, Boussy T, Casado R, Paparella G, Capulzini L, et al. The value of a family history of sudden death in patients with diagnostic type I Brugada ECG pattern. Eur Heart J 2011;32:2153-60.  Back to cited text no. 38
    
39.
Antzelevitch C, Patocskai B. Brugada syndrome: Clinical, genetic, molecular, cellular, and ionic aspects. Curr Probl Cardiol 2016;41:7-57.  Back to cited text no. 39
    
40.
Crotti L, Marcou CA, Tester DJ, Castelletti S, Giudicessi JR, Torchio M, et al. Spectrum and prevalence of mutations involving brS1-through brS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: Implications for genetic testing. J Am Coll Cardiol 2012;60:1410-8.  Back to cited text no. 40
    
41.
Smits JP, Eckardt L, Probst V, Bezzina CR, Schott JJ, Remme CA, et al. Genotype-phenotype relationship in Brugada syndrome: Electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J Am Coll Cardiol 2002;40:350-6.  Back to cited text no. 41
    
42.
Maury P, Rollin A, Sacher F, Gourraud JB, Raczka F, Pasquié JL, et al. Prevalence and prognostic role of various conduction disturbances in patients with the Brugada syndrome. Am J Cardiol 2013;112:1384-9.  Back to cited text no. 42
    
43.
Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, et al. Genotype-phenotype correlation of SCN5A mutation for the clinical and electrocardiographic characteristics of probands with Brugada syndrome: A Japanese multicenter registry. Circulation 2017;135:2255-70.  Back to cited text no. 43
    
44.
Take Y, Morita H, Toh N, Nishii N, Nagase S, Nakamura K, et al. Identification of high-risk syncope related to ventricular fibrillation in patients with Brugada syndrome. Heart Rhythm 2012;9:752-9.  Back to cited text no. 44
    
45.
Gehi AK, Duong TD, Metz LD, Gomes JA, Mehta D. Risk stratification of individuals with the Brugada electrocardiogram: A meta-analysis. J Cardiovasc Electrophysiol 2006;17:577-83.  Back to cited text no. 45
    
46.
Veltmann C, Papavassiliu T, Konrad T, Doesch C, Kuschyk J, Streitner F, et al. Insights into the location of type I ECG in patients with Brugada syndrome: Correlation of ECG and cardiovascular magnetic resonance imaging. Heart Rhythm 2012;9:414-21.  Back to cited text no. 46
    
47.
Shimeno K, Takagi M, Maeda K, Tatsumi H, Doi A, Yoshiyama M, et al. Usefulness of multichannel holter ECG recording in the third intercostal space for detecting type 1 Brugada ECG: Comparison with repeated 12-lead ECGs. J Cardiovasc Electrophysiol 2009;20:1026-31.  Back to cited text no. 47
    
48.
Miyamoto K, Yokokawa M, Tanaka K, Nagai T, Okamura H, Noda T, et al. Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada syndrome. Am J Cardiol 2007;99:53-7.  Back to cited text no. 48
    
49.
Okamura H, Kamakura T, Morita H, Tokioka K, Nakajima I, Wada M, et al. Risk stratification in patients with Brugada syndrome without previous cardiac arrest – prognostic value of combined risk factors. Circ J 2015;79:310-7.  Back to cited text no. 49
    
50.
Morita H, Kusano KF, Miura D, Nagase S, Nakamura K, Morita ST, et al. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation 2008;118:1697-704.  Back to cited text no. 50
    
51.
Rattanawong P, Chenbhanich J, Mekraksakit P, Vutthikraivit W, Chongsathidkiet P, Limpruttidham N, et al. SCN5A mutation status increases the risk of major arrhythmic events in Asian populations with Brugada syndrome: Systematic review and meta-analysis. Ann Noninvasive Electrocardiol 2018:e12589. doi: 10.1111/anec.12589.   Back to cited text no. 51
    
52.
Tokioka K, Kusano KF, Morita H, Miura D, Nishii N, Nagase S, et al. Electrocardiographic parameters and fatal arrhythmic events in patients with Brugada syndrome: Combination of depolarization and repolarization abnormalities. J Am Coll Cardiol 2014;63:2131-8.  Back to cited text no. 52
    
53.
Sakamoto S, Takagi M, Tatsumi H, Doi A, Sugioka K, Hanatani A, et al. Utility of T-wave alternans during night time as a predictor for ventricular fibrillation in patients with Brugada syndrome. Heart Vessels 2016;31:947-56.  Back to cited text no. 53
    
54.
Rattanawong P, Riangwiwat T, Prasitlumkum N, Limpruttidham N, Kanjanahattakij N, Chongsathidkiet P, et al. Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta-analysis. Ann Noninvasive Electrocardiol 2018;23:e12507.  Back to cited text no. 54
    
55.
Meng L, Letsas KP, Baranchuk A, Shao Q, Tse G, Zhang N, et al. Meta-analysis of fragmented QRS as an electrocardiographic predictor for arrhythmic events in patients with Brugada syndrome. Front Physiol 2017;8:678.  Back to cited text no. 55
    
56.
Babai Bigi MA, Aslani A, Shahrzad S. AVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome. Heart Rhythm 2007;4:1009-12.  Back to cited text no. 56
    
57.
Calò L, Giustetto C, Martino A, Sciarra L, Cerrato N, Marziali M, et al. Anew electrocardiographic marker of sudden death in Brugada syndrome: The S-wave in lead I. J Am Coll Cardiol 2016;67:1427-40.  Back to cited text no. 57
    
58.
Junttila MJ, Brugada P, Hong K, Lizotte E, DE Zutter M, Sarkozy A, et al. Differences in 12-lead electrocardiogram between symptomatic and asymptomatic Brugada syndrome patients. J Cardiovasc Electrophysiol 2008;19:380-3.  Back to cited text no. 58
    
59.
Kawazoe H, Nakano Y, Ochi H, Takagi M, Hayashi Y, Uchimura Y, et al. Risk stratification of ventricular fibrillation in Brugada syndrome using noninvasive scoring methods. Heart Rhythm 2016;13:1947-54.  Back to cited text no. 59
    
60.
Ohkubo K, Watanabe I, Okumura Y, Ashino S, Kofune M, Nagashima K, et al. Prolonged QRS duration in lead V2 and risk of life-threatening ventricular arrhythmia in patients with Brugada syndrome. Int Heart J 2011;52:98-102.  Back to cited text no. 60
    
61.
Kawata H, Morita H, Yamada Y, Noda T, Satomi K, Aiba T, et al. Prognostic significance of early repolarization in inferolateral leads in Brugada patients with documented ventricular fibrillation: A novel risk factor for Brugada syndrome with ventricular fibrillation. Heart Rhythm 2013;10:1161-8.  Back to cited text no. 61
    
62.
Sarkozy A, Chierchia GB, Paparella G, Boussy T, De Asmundis C, Roos M, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009;2:154-61.  Back to cited text no. 62
    
63.
Kaneko Y, Horie M, Niwano S, Kusano KF, Takatsuki S, Kurita T, et al. Electrical storm in patients with Brugada syndrome is associated with early repolarization. Circ Arrhythm Electrophysiol 2014;7:1122-8.  Back to cited text no. 63
    
64.
Georgopoulos S, Letsas KP, Liu T, Kalafateli M, Korantzopoulos P, Bürkle G, et al. Ameta-analysis on the prognostic significance of inferolateral early repolarization pattern in Brugada syndrome. Europace 2018;20:134-9.  Back to cited text no. 64
    
65.
Batchvarov VN, Govindan M, Camm AJ, Behr ER. Brugada-like changes in the peripheral leads during diagnostic ajmaline test in patients with suspected Brugada syndrome. Pacing Clin Electrophysiol 2009;32:695-703.  Back to cited text no. 65
    
66.
Rollin A, Sacher F, Gourraud JB, Pasquié JL, Raczka F, Duparc A, et al. Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome. Heart Rhythm 2013;10:1012-8.  Back to cited text no. 66
    
67.
Castro Hevia J, Antzelevitch C, Tornés Bárzaga F, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina R, et al. Tpeak-tend and tpeak-tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol 2006;47:1828-34.  Back to cited text no. 67
    
68.
Maury P, Sacher F, Gourraud JB, Pasquié JL, Raczka F, Bongard V, et al. Increased tpeak-tend interval is highly and independently related to arrhythmic events in Brugada syndrome. Heart Rhythm 2015;12:2469-76.  Back to cited text no. 68
    
69.
Tse G, Gong M, Wong WT, Georgopoulos S, Letsas KP, Vassiliou VS, et al. TheT peak-T end interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: A systematic review and meta-analysis. Heart Rhythm 2017;14:1131-7.  Back to cited text no. 69
    
70.
Ajiro Y, Hagiwara N, Kasanuki H. Assessment of markers for identifying patients at risk for life-threatening arrhythmic events in Brugada syndrome. J Cardiovasc Electrophysiol 2005;16:45-51.  Back to cited text no. 70
    
71.
Tatsumi H, Takagi M, Nakagawa E, Yamashita H, Yoshiyama M. Risk stratification in patients with Brugada syndrome: Analysis of daily fluctuations in 12-lead electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG). J Cardiovasc Electrophysiol 2006;17:705-11.  Back to cited text no. 71
    
72.
Kakihara J, Takagi M, Hayashi Y, Tatsumi H, Doi A, Yoshiyama M, et al. Utility of 12-lead and signal-averaged holter electrocardiograms after pilsicainide provocation for risk stratification in Brugada syndrome. Heart Vessels 2017;32:1151-9.  Back to cited text no. 72
    
73.
Ikeda T, Takami M, Sugi K, Mizusawa Y, Sakurada H, Yoshino H, et al. Noninvasive risk stratification of subjects with a Brugada-type electrocardiogram and no history of cardiac arrest. Ann Noninvasive Electrocardiol 2005;10:396-403.  Back to cited text no. 73
    
74.
Uchimura-Makita Y, Nakano Y, Tokuyama T, Fujiwara M, Watanabe Y, Sairaku A, et al. Time-domain T-wave alternans is strongly associated with a history of ventricular fibrillation in patients with Brugada syndrome. J Cardiovasc Electrophysiol 2014;25:1021-7.  Back to cited text no. 74
    
75.
Sakamoto S, Takagi M, Kakihara J, Hayashi Y, Doi A, Sugioka K, et al. The utility of T-wave alternans during the morning in the summer for the risk stratification of patients with Brugada syndrome. Heart Vessels 2017;32:341-51.  Back to cited text no. 75
    
76.
Wilde AA, Viskin S. EP testing does not predict cardiac events in Brugada syndrome. Heart Rhythm 2011;8:1598-600.  Back to cited text no. 76
    
77.
Brugada J, Brugada R, Brugada P. Electrophysiologic testing predicts events in Brugada syndrome patients. Heart Rhythm 2011;8:1595-7.  Back to cited text no. 77
    
78.
Brugada P, Brugada R, Brugada J. Should patients with an asymptomatic Brugada electrocardiogram undergo pharmacological and electrophysiological testing? Circulation 2005;112:279-92.  Back to cited text no. 78
    
79.
Sieira J, Ciconte G, Conte G, Chierchia GB, de Asmundis C, Baltogiannis G, et al. Asymptomatic Brugada syndrome: Clinical characterization and long-term prognosis. Circ Arrhythm Electrophysiol 2015;8:1144-50.  Back to cited text no. 79
    
80.
Brugada P, Brugada R, Mont L, Rivero M, Geelen P, Brugada J, et al. Natural history of Brugada syndrome: The prognostic value of programmed electrical stimulation of the heart. J Cardiovasc Electrophysiol 2003;14:455-7.  Back to cited text no. 80
    
81.
Takagi M, Sekiguchi Y, Yokoyama Y, Aihara N, Hiraoka M, Aonuma K, et al. Long-term prognosis in patients with Brugada syndrome based on class II indication for implantable cardioverter-defibrillator in the HRS/EHRA/APHRS expert consensus statement: Multicenter study in Japan. Heart Rhythm 2014;11:1716-20.  Back to cited text no. 81
    
82.
Paul M, Gerss J, Schulze-Bahr E, Wichter T, Vahlhaus C, Wilde AA, et al. Role of programmed ventricular stimulation in patients with Brugada syndrome: A meta-analysis of worldwide published data. Eur Heart J 2007;28:2126-33.  Back to cited text no. 82
    
83.
Letsas KP, Liu T, Shao Q, Korantzopoulos P, Giannopoulos G, Vlachos K, et al. Meta-analysis on risk stratification of asymptomatic individuals with the Brugada phenotype. Am J Cardiol 2015;116:98-103.  Back to cited text no. 83
    
84.
Sroubek J, Probst V, Mazzanti A, Delise P, Hevia JC, Ohkubo K, et al. Programmed ventricular stimulation for risk stratification in the Brugada syndrome: A pooled analysis. Circulation 2016;133:622-30.  Back to cited text no. 84
    
85.
Eckardt L, Kirchhof P, Schulze-Bahr E, Rolf S, Ribbing M, Loh P, et al. Electrophysiologic investigation in Brugada syndrome; yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats. Eur Heart J 2002;23:1394-401.  Back to cited text no. 85
    
86.
Makimoto H, Kamakura S, Aihara N, Noda T, Nakajima I, Yokoyama T, et al. Clinical impact of the number of extrastimuli in programmed electrical stimulation in patients with Brugada type 1 electrocardiogram. Heart Rhythm 2012;9:242-8.  Back to cited text no. 86
    
87.
Takagi M, Sekiguchi Y, Yokoyama Y, Aihara N, Hiraoka M, Aonuma K, et al. The prognostic impact of single extra-stimulus on programmed ventricular stimulation in Brugada patients without previous cardiac arrest: Multi-centre study in Japan. Europace 2018;20:1194-200.  Back to cited text no. 87
    
88.
Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation 2003;108:3092-6.  Back to cited text no. 88
    
89.
Amin AS, de Groot EA, Ruijter JM, Wilde AA, Tan HL. Exercise-induced ECG changes in Brugada syndrome. Circ Arrhythm Electrophysiol 2009;2:531-9.  Back to cited text no. 89
    
90.
Conte G, de Asmundis C, Sieira J, Ciconte G, Di Giovanni G, Chierchia GB, et al. Prevalence and clinical impact of early repolarization pattern and QRS-fragmentation in high-risk patients with Brugada syndrome. Circ J 2016;80:2109-16.  Back to cited text no. 90
    
91.
Sieira J, Conte G, Ciconte G, Chierchia GB, Casado-Arroyo R, Baltogiannis G, et al. Ascore model to predict risk of events in patients with Brugada syndrome. Eur Heart J 2017;38:1756-63.  Back to cited text no. 91
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Diagnosis of Bru...
Prevalence of Br...
Prognosis of Bru...
Risk Stratificat...
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed136    
    Printed9    
    Emailed0    
    PDF Downloaded20    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]