Cohort of Patients Referred for Brugada Syndrome Investigation in an Electrophysiology Service – 19-Year Registry

Sarabanda, Alvaro Valentim Lima

doi:10.5935/abc.20180120

Keywords:
Brugada Syndrome; Bundle-Branch Block; Death, Sudden; Tachycardia, Ventricular; Syncope

Palavras-chave:
Síndrome de Brugada; Bloqueio de Ramo; Morte Súbita; Taquicardia Ventricular; Síncope

Keywords:
Brugada Syndrome; Bundle-Branch Block; Death, Sudden; Tachycardia, Ventricular; Syncope

Palavras-chave:
Síndrome de Brugada; Bloqueio de Ramo; Morte Súbita; Taquicardia Ventricular; Síncope

Brugada syndrome (BrS) was described by Pedro and Josep Brugada in 1992 as a new clinical entity characterized by specific electrocardiographic (ECG) changes, such as the patterns of right bundle-branch block and persistent ST-segment elevation in right precordial leads, associated with increased risk for sudden death.¹

Brugada syndrome is an autosomal dominant channelopathy, with clinical manifestation at the age of 30 to 40 years, affecting mainly men. Currently, BrS is estimated to account for 12% of all sudden cardiac deaths and up to 20% of the sudden cardiac deaths in individuals with no structural heart disease.² The real prevalence of BrS in the general population is difficult to establish, being estimated at 5 to 20 in every 10,000 individuals.² Several genetic mutations have been associated with BrS, most of them related to the encoding of sodium channel proteins (INa), calcium channel proteins (ICa) or potassium channel proteins (usually Ito) of the sarcoplasmatic membrane.²^-⁵

The usual clinical manifestation of BrS is arrhythmic syncope, nocturnal agonal respiration or sudden death secondary to polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). The symptoms usually occur during sleep, at rest during the day or in situations with increased vagal tone, such as binge drinking or heavy meals. In addition, fever is a common trigger, mainly among children.²^-⁵

The diagnosis and risk stratification of BrS are mainly based on clinical history and ECG pattern, which can generate controversy because of the incomplete penetrance of the channelopathy and the dynamic pattern of ECG manifestations.²^-⁵ Although three ECG patterns have been described, the diagnosis of BrS can only be established in patients with type 1 ECG pattern (coved-type), characterized by a concave ST-segment elevation ≥ 2 mm in at least two right precordial leads (V1, V2) positioned on the 2nd, 3rd and 4th intercostal spaces, occurring spontaneously or after provocative drug test with the intravenous administration of class I antiarrhythmic drugs (ajmaline, flecainide or procainamide). The other ECG patterns (types 2 and 3) do not establish the diagnosis of BrS.²^-⁵

In BrS risk stratification and treatment, individuals with history of resuscitated cardiac arrest (class I indication) and those with history of syncope and type 1 ECG pattern (class IIa indication) are at high risk for sudden death and have indication for implantable cardioverter-defibrillator (ICD) placement for secondary prevention. Several studies have reported that asymptomatic patients with type 1 ECG pattern only after infusion of class I antiarrhythmic drugs are at low risk for arrhythmic events during clinical follow-up.⁶^-⁸ Thus, in those patients, ICD placement should be avoided because of the risk of complications, such as inappropriate shocks.³^-⁵

The role of programmed ventricular stimulation (PVS) during invasive electrophysiological study for risk stratification and management of asymptomatic patients with BrS is controversial. While some studies have shown that the induction of ventricular tachyarrhythmias (polymorphic VT or VF) during PVS is an independent predictor of arrhythmic events during clinical follow-up, emphasizing their negative predictive value,⁹^,¹⁰ other studies have questioned those findings.⁶^,⁷ It is worth noting the results of a recent systematic review of eight observational prospective studies, including 1,312 patients with BrS and no history of cardiac arrest, in which the induction of polymorphic VT or VF during PVS could predict an increased risk for arrhythmic events (cardiac arrest or ICD shocks) during clinical follow-up, with an increased risk for events when VT/VF induction occurred with only one or two extra-stimuli. However, those authors have reported that the lack of VT/VF induction could not predict a lower risk of arrhythmic events, especially in the subgroup of patients with type 1 ECG pattern and history of syncope.⁸ Thus, the most recent expert consensus recommend caution when indicating ICD placement in asymptomatic patients with BrS when ventricular tachyarrhythmias were induced by PVS, emphasizing the need to consider an individualized approach for ICD implantation (class IIb indication) in those patients.³^-⁵

It is worth noting that, despite the description of BrS by the Brugada brothers more than 25 years ago,¹ its genetic changes, arrhythmogenic mechanisms and clinical management continue to be debated. This is attributed to the continuous report of new information on BrS and its constantly evolving understanding, driven by new clinical and basic research findings.²^-⁸^,¹⁰

In the present Arquivos Brasileiros de Cardiologia issue, Warpechowski Neto et al.¹¹ report the clinical characteristics, management and follow-up of patients with an ECG pattern suggestive of BrS, who had been referred to a tertiary center for risk stratification by use of invasive electrophysiological study. In the study, aligned with those previously reported in the literature, most patients were of the male gender, adults and had spontaneous type 1 ECG pattern. The study provides a timely and updated overview of the complexity of the BrS clinical management, discussing the controversies of using PVS for risk stratification of asymptomatic patients, as well as ICD placement to treat those at higher risk for fatal arrhythmias in the long-term clinical follow-up.

Short Editorial regarding the article: Cohort of Patients Referred for Brugada Syndrome Investigation in an Electrophysiology Service - 19-Year Registry

References

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(6):1391-6.
² Brugada R, Campuzano O, Sarquella-Brugada G, Brugada J, Brugada P. Brugada syndrome. Methodist Debakey Cardiovasc J. 2014;10(1):25-8.
³ Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013;10(12):1932-63.
⁴ Priori SG, Blomstrom-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(41):2793-867.
⁵ 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(4):665-94.
⁶ 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(5):635-43.
⁷ Priori SG, Gasparini M, Napolitano C, Della Bela 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(1):37-45.
⁸ 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(7):622-30.
⁹ 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(25):3092-6.
¹⁰ Sieira J, Conte G, Ciconte G, Chierchia GB, Casado-Arroyo R, Baltogiannis G, et al. A score model to predict risk of events in patients with Brugada Syndrome. Eur Heart J. 2017;38(22):1756-63.
¹¹ Warpechowski Neto S, Lima GG, Ley LL, Ley AL, Dutra LZ, Pires LM, et al. Coorte de pacientes encaminhados para investigação de síndrome de Brugada em um Serviço Terciário de Eletrofisiologia - Registro de 19 Anos. Arq Bras Cardiol. 2018; 111(1):13-18.

Publication Dates

Publication in this collection
July 2018

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[1] 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(6):1391-6.

[2] ² Brugada R, Campuzano O, Sarquella-Brugada G, Brugada J, Brugada P. Brugada syndrome. Methodist Debakey Cardiovasc J. 2014;10(1):25-8.

[3] ³ Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013;10(12):1932-63.

[4] ⁴ Priori SG, Blomstrom-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(41):2793-867.

[5] ⁵ 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(4):665-94.

[6] ⁶ 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(5):635-43.

[7] ⁷ Priori SG, Gasparini M, Napolitano C, Della Bela 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(1):37-45.

[8] ⁸ 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(7):622-30.

[9] ⁹ 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(25):3092-6.

[10] ¹⁰ Sieira J, Conte G, Ciconte G, Chierchia GB, Casado-Arroyo R, Baltogiannis G, et al. A score model to predict risk of events in patients with Brugada Syndrome. Eur Heart J. 2017;38(22):1756-63.

[11] ¹¹ Warpechowski Neto S, Lima GG, Ley LL, Ley AL, Dutra LZ, Pires LM, et al. Coorte de pacientes encaminhados para investigação de síndrome de Brugada em um Serviço Terciário de Eletrofisiologia - Registro de 19 Anos. Arq Bras Cardiol. 2018; 111(1):13-18.