Brugada Syndrome

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Brugada syndrome\: rare autosomal-dominant inherited cardiac sodium channelopathy with ST-segment elevation in at
least one of the anterior precordial leads (V1-V3), but a structurally normal heart. Patients are at risk of sudden cardiac
death (SCD)\: high risk due to polymorphic ventricular tachycardia (VT) or ventricular
Aetiology\: complex genotype-phenotype relationship; primarily mutations in S C N 5 A gene encoding Nav1.5 sodium
channel; other genes also implicated; S C N 5 A mutations also linked to other cardiac conditions.
Pathophysiology\: defective Nav1.5 channels cause slower conduction in the heart, increasing risk of ventricular
arrhythmias; theories involve right ventricular out
Risk factors\: more common in males, middle-aged (30-50), Southeast Asian ancestry, positive family history.
Clinical features\: two-thirds asymptomatic; cardiogenic syncope, unexplained cardiac arrest (usually during sleep or rest),
documented polymorphic VT or VF, atrial
Triggers\: febrile illness, medications with sodium channel blockage, excessive alcohol intake, illicit drugs (cannabis,
cocaine).
ECG
elevation, positive or biphasic T wave; Type 3 with right precordial ST elevation not meeting criteria.
Diagnosis\: based on spontaneous Type 1 ECG pattern in right precordial leads, absence of other heart diseases; use of
Shanghai Score System for additional factors (clinical history, family history, ECG, genetic testing).
Management\: no cure; aims to prevent SCD with ICD implantation.
Lifestyle advice\: avoid Brugada-aggravating drugs, treat fever promptly, avoid excessive alcohol, illicit drugs.
Family screening\: ECG, drug provocation test for 1st-degree relatives; speci
Pharmacological\: Quinidine to suppress ventricular arrhythmia in selected cases.
Interventional\: ICD implantation for prior aborted cardiac arrest, documented sustained VT; catheter ablation for recurrent
ICD shocks or contraindications.
Complications\: arrhythmia-related (polymorphic VT, VF, SCD, cardiogenic syncope, atrial arrhythmias); ICD-device related
(procedure-related complications, infection, inappropriate shocks).
Article 🔍
A comprehensive topic overview

Introduction

Brugada syndrome is a rare autosomal-dominant inherited cardiac sodium channelopathy, characterised by ST-segment
elevation in at least one of the anterior precordial leads (V1-V3) in the context of a structurally normal heart.
1
Patients are at high risk of sudden cardiac death (SCD) secondary to polymorphic ventricular tachycardia (VT) or ventricular

1
This is a relatively new syndrome that was
had recurrent episodes of aborted cardiac arrest secondary to polymorphic VT that could not be explained by known
diseases.
2Aetiology
Traditionally, Brugada syndrome has been described as having an autosomal-dominant inheritance pattern. However, it is
worth noting that a recent paper published in B M J H e a r t stated that “ w h i l e B r u g a d a s y n d r o m e w a s i n i t i a l l y t h o u g h t t o b e
i n h e r i t e d a s a m o n o g e n i c , a u t o s o m a l d o m i n a n t d i s e a s e r e q u i r i n g o n l y o n e m u t a t i o n , i t i s n o w c o n s i d e r e d m o r e l i k e l y t o
e n c o m p a s s a n o l i g o g e n i c o r p o l y g e n i c i n h e r i t a n c e , i n w h i c h m u l t i p l e ‘ g e n e t i c m o d i
p h e n o t y p i c a l e x p r e s s i o n o f t h e p r i m a r y g e n e t i c d e f e c t .
”
3
The genotype-phenotype relationship of Brugada syndrome is highly complex and is yet to be fully understood.
Multiple gene mutations have been implicated in Brugada syndrome, but only variants of the S C N 5 A gene are considered
pathogenic. 4,5 6
S C N 5 A gene encodes the alpha subunit of the cardiac voltage-gated sodium channel (Nav1.5). Over 300
mutations of the S C N 5 A gene have been discovered so far.
7
It is now known that other genes apart from S C N 5 A play a role in Brugada syndrome. Only ~20% of patients with Brugada
syndrome were found to have mutations in S C N 5 A .
4,8
Furthermore, S C N 5 A mutations are also known to be implicated in other cardiac conditions, including long QT syndrome
type III, sick sinus syndrome, progressive cardiac conduction diseases, dilated cardiomyopathy etc.
1
Pathophysiology
Mutations in the S C N 5 A gene result in defective Nav1.5 channels in the cardiac cell membrane, which play a crucial role in
the initial depolarisation phase (phase zero) of the cardiac action potential. This loss of function leads to a delayed phase
zero, causing slower conduction in the heart and increasing the risk of developing ventricular arrhythmias.
Although the precise mechanism is not fully understood, two main hypotheses have been proposed\: the repolarisation
and the depolarisation disorder models. Both theories emphasise the involvement of the right ventricle, particularly the
right ventricular out
(V1-V3).
1,3,5,9

Risk factors

Brugada syndrome is found to be more common in\:
5,10
Male (~8-10 times more prevalent than female)
Middle age (30-50 y/o)
Asian ancestry, especially Southeast Asia (leading cause of death in male \<40 in Southeast Asia)
Positive family history

Clinical features

Two-thirds of patients are asymptomatic at the time of diagnosis, making the diagnosis of Brugada syndrome challenging.
5
No speci
The following selected points of clinical history and family history are based on the Shanghai Score System for diagnosing
Brugada syndrome. See the diagnosis paragraph for more details.
History
There are three main clinical manifestations of symptomatic Brugada syndrome\:
4,5
Cardiogenic syncope
Unexplained cardiac arrest (usually during sleep or at rest, unlike in hypertrophic cardiomyopathy where cardiac arrest
usually happens during physical activity)
Documented polymorphic VT or VF
Some other clinical features associated with Brugada syndrome\:
4,5
Atrial or atrial
Nocturnal agonal respirationsIn patients who present with syncope, detailed clinical assessment is necessary to di
mimics like vasovagal syncope.
As mentioned, most patients are asymptomatic. The Brugada syndrome phenotype may only manifest when induced by
certain triggers. It is important to screen for the following\:
4,5
Febrile illness (cardiac action potential is further shortened at high temperatures, thus further slowing conduction in the
RVOT)
Use of medications with sodium channel blockage – antiarrhythmics, anaesthetics, antipsychotics
Excessive alcohol intake
Use of illicit drugs like cannabis and cocaine
A detailed family history should be explored in cases of suspected Brugada syndrome. It is important to ask if any of the
following is present in
4,5
De
Unexplained SCD in \<45 y/o with negative autopsy
Suspicious SCD (febrile induced, nocturnal death, Brugada-aggravating drug)
Clinical examination
Physical examination of patients with Brugada syndrome is usually normal. In the context of suspected Brugada syndrome,
it is important to check one’s temperature to exclude febrile illness.
A full cardiovascular examination should always be performed in all patients to exclude other potential underlying
cardiovascular pathologies and pectus excavatum, a potential cause of type I Brugada ECG pattern.

Investigations

Bedside investigations
ECG
There are three recognised ECG patterns in Brugada syndrome. Type I is the only diagnostic ECG change. 1,5,11
following ECG changes must be observed in at least one lead in V1-V3 (right precordial leads).
11
Type 1 Brugada ECG pattern\:
ST-T con
J wave amplitude ≥ 2mm
Negative T wave
Type 2 Brugada ECG pattern\:
ST-T con
J wave amplitude ≥ 2mm
Positive or biphasic T wave
Type 3 Brugada ECG pattern\:
Right precordial ST-segment elevation
Coved type, saddle-back type, or both
Not meeting the above criteria
TheFigure 1. Types of Brugada Syndrome ECG pattern.
High precordial lead ECG positions
High precordial leads increase the sensitivity of detecting the Brugada ECG changes due to individual variations in
the RVOT anatomical position. It is thought to increase the diagnostic yield by ~1.5 times compared with standard lead
positions.
5
High precordial lead positions are as follows\:
hV1 and hV2 at 2 nd
intercostal space
hV3 and hV4 at 3 rd
intercostal space
hV5 and hV6 at 4 th
intercostal space
As such, hV5 and hV6 are equivalent to V1 and V2 in a standard ECG lead placement.
Drug provocation testing
Drug provocation testing can unmask Brugada syndrome. Authors of a review paper on Brugada syndrome published in
J A C C \: C l i n i c a l E l e c t r o p h y s i o l o g y recommends drug provocation testing in patients with\:
5
Baseline type 2 or 3 Brugada ECG
Suspected Brugada syndrome based on clinical or family history
Note that drug provocation testing is not recommended in patients with spontaneous type 1 Brugada ECG at baseline, as
it has no additional diagnostic value.
5
The drug class of choice is sodium channel blockers (SCBs). Four SCBs are routinely used for provocation testing. 5
have a predominant action on inhibiting the Nav1.5\:
They all
Ajmaline (class Ia antiarrhythmic) – mainly used in Europe
Flecainide (class Ic antiarrhythmic) – mainly used in Europe
Procainamide (class Ia antiarrhythmic) – mainly used in North America
Pilsicainide (class Ic antiarrhythmic) – mainly used in Japan
The administration of SCBs may exaggerate or unmask Brugada ECG changes. During the drug provocation testing,
a series of ECGs should be taken\:
4,5,11
Baseline – before the infusion
During the infusion
After the infusion
Laboratory investigations
Genetic testing
Currently, only genetic testing for variants in the S C N 5 A gene is performed. It is important to note that the yield of genetic
testing in diagnosing Brugada syndrome is only ~20%.
4,8The sole presence of a probable pathogenic S C N 5 A mutation is not diagnostic of Brugada syndrome, it only scores 0.5 in
the Shanghai Score System. Genetic testing is not routinely o
screening.
5
Imaging
Baseline echocardiogram
An echocardiogram should be performed in all patients as part of their work-up for Brugada syndrome to exclude
underlying structural heart disease that may have caused their presentation.
5,12
Expected echocardiogram
right ventricle or RVOT.
5,12
Cardiac CT or MRI
Advanced cardiac imaging like CT or MRI are not routinely performed nor required to diagnose Brugada syndrome.
It is usually used to help di
cardiomyopathy.
12
Other investigations
Electrophysiological study (EPS) with programmed electrical stimulation (PES)
The main indication of performing EPS in Brugada syndrome is risk strati
recommendations regarding the use of EPS remain controversial\:
Authors of a consensus report on the proposed diagnostic criteria for Brugada syndrome published in C i r c u l a t i o n
recommends EPS in all symptomatic patients.
11
Authors of a review paper on Brugada syndrome published in J A C C \: C l i n i c a l E l e c t r o p h y s i o l o g y do not recommend the
routine use of EPS with PES for risk strati
5
The latter recommendation is because of results from two recent large prospective multicentre registries, FINGER (France,
Italy, Netherlands, Germany) and PRELUDE (Programmed Electrical stimulation predictive value), who failed to validate the
role of EPS with PES in Brugada syndrome.
5

Diagnosis

According to both the E S C (European Society of Cardiology) guidelines and the Shanghai Score System, Brugada
syndrome can be diagnosed in the presence of spontaneous type 1 Brugada ECG pattern (observed in standard ECG lead
positioning or high precordial lead positioning) in the absence of other heart diseases, regardless of symptoms.
4,5
If the above criteria are not ful
conference report published in 2017 developed the Shanghai Score System for Diagnosis of Brugada Syndrome for such
13
purposes.
The Shanghai Score System considers four aspects\:
Clinical history
Family history
ECG
Genetic testing result

Di

Conditions that can give rise to a similar type 1 Brugada ECG pattern include\:
11,12,14
Acute coronary syndrome (ACS) (right coronary artery or left anterior descending artery infarction)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Incomplete right bundle branch block (RBBB)
Left ventricular hypertrophy (LVH)
Mechanical compression of RVOT (e.g., pectus excavatum, mediastinal tumour)Electrolyte disturbances (e.g., hyperkalaemia, hypokalaemia, hypercalcaemia)
Conditions that can give rise to a similar type 2/3 Brugada ECG pattern include\:
11,12,14
Early repolarisation syndrome (ERS)
Athlete’s heart

Management

There is currently no cure for Brugada syndrome. Current management aims to prevent SCD with ICD implantation.
Conservative management
Lifestyle advice
The following advice should be communicated to all patients\:
4,5,12
Avoidance of Brugada-aggravating drugs, important drug classes include antiarrhythmics, anaesthetics and
antipsychotic drugs
Prompt treatment of fever with antipyretic drugs
Avoidance of cocaine, cannabis, and excessive alcohol intake
Avoid sleeping immediately after eating big meals
Family screening
Screening should be o
unexplained SCD.
4,5,12
Family screening for Brugada syndrome should entail\:
4,5
Adults\: standard and high precordial lead ECG and consider drug provocation test.
Children\: standard and high precordial lead ECG at 3 y/o, every three years until 15 y/o. Drug provocation test should not
be o
If the drug provocation test is negative, there is no need for additional testing and follow-up.
Pharmacological management
Quinidine
Quinidine is a class 1a antiarrhythmic that inhibits cardiac voltage-gated sodium channels to decrease phase zero of rapid
depolarisation. Its most important antiarrhythmic e
period.
5
Quinidine is useful in suppressing ventricular arrhythmia, it should be considered in the following patients\:
4,12
ICD indicated but not implanted due to contraindications or patient preferences
ICD implanted but experiencing recurrent shocks
Asymptomatic spontaneous type 1 Brugada ECG
History of electrical storm (>2 episodes of VT or VF within 24 hours)
History of asymptomatic ventricular arrhythmia
Interventional management
Implantable cardioverter de
The implantation of an ICD is the only current intervention that reduces the risk of SCD in Brugada syndrome. 4
ESC Guidelines regarding ICD implantation for SCD prevention are summarised below.
4
The 2022
ICD implantation is recommended in the presence of (class I indication)\:
Prior aborted cardiac arrest
Documented spontaneous sustained VT
ICD implantation should be considered in the presence of (class IIa indication)\:
History of cardiogenic syncope with type 1 Brugada ECG
ICD implantation may be considered in the presence of (class IIb indication)\:Inducible VF during EPS with PES using up to two extra stimuli
Catheter ablation
Ablation of abnormal areas with
normalise the ECG in >75% of patients. 4,5
Prior EP mapping could help identify these areas.
Selected points regarding the recommendation of catheter ablation in patients with Brugada syndrome\:
Consider in patients with recurrent ICD shocks that is refractory to pharmacological therapy.
4
Consider in patients where an ICD is indicated but not implanted due to contraindications or patient preferences.
5
Not recommended in asymptomatic patients.
4

Complications

Arrhythmia-related complications include\:
12
Polymorphic VT
VF
Sudden cardiac death
Cardiogenic syncope
Atrial arrhythmias (e.g., new-onset atrial )
ICD-device related complications include\:
15
Procedure-related complications – pneumothorax, haematoma
Physiological and physical impact
Lead malfunction
Infection
Inappropriate shocks

References

Mizusawa Y, Wilde AAM. Brugada Syndrome. C i r c u l a t i o n \: A r r h y t h m i a a n d E l e c t r o p h y s i o l o g y 2012 Jun;5\:606-616.
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 o u r n a l o f t h e A m e r i c a n C o l l e g e o f C a r d i o l o gy 1992
Nov;20(6)\:1391-1396.
Marsman EMJ, Postema PG, Remme CA. Brugada syndrome\: update and future perspectives. H e a r t 2022 Apr;108\:668-675.
Zeppenfeld K, e t a l . 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of
sudden cardiac death\: Developed by 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 the Association for European
Paediatric and Congenital Cardiology (AEPC). E u r o p e a n H e a r t J o u r n a l 2022 Oct;43(40)\:3997-4126.
Krahn AD, e t a l . Brugada Syndrome. J o u r n a l o f t h e A m e r i c a n C o l l e g e o f C a r d i o l o gy \: C l i n i c a l E l e c t r o p h y s i o l o gy 2022
Mar;8(3)\:386-405.
Brugada R, e t BRUGADA SYNDROME. M e t h o d i s t D e b a k e y C a r d i o v a s c u l a r J o u r n a l 2014 Jan-Mar;10(1)\:25-28.
Attard A, e t a l . Brugada syndrome\: should we be screening patients before prescribing psychotropic medication?
Therapeutic Advances in Psychopharmacology 2022 Jan;12\: 20451253211067017.
Kapplinger JD, e t a l . An international compendium of mutations in the S C N 5 A -encoded cardiac sodium channel in patients
referred for Brugada syndrome genetic testing. H e a r t R h y t h m 2010 Jan;7(1)\:33-46.
Meregalli PG, Wilde AAM, Tan HL. Pathophysiological mechanisms of Brugada syndrome\: depolarization disorder,
repolarization disorder, or more? C a r d i o v a s c u l a r R e s e a r c h 2005 Aug;67(3)\:367-378.
Bayés de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern\: a
consensus report. J Electrocardiol. 2012;45(5)\:433-42.
Wilde AAM, et al. Proposed Diagnostic Criteria for the Brugada Syndrome. Circulation 2022 Nov;106(19)\:2514-2519.BMJ Best Practice. Brugada syndrome. Reviewed 2024 Feb; updated 2023 Aug. Available from\:
https\:/ /bestpractice.bmj.com/topics/en-gb/3000313
Antzelevitch C, e t a l . J-Wave syndromes expert consensus conference report\: Emerging concepts and gaps in knowledge.
E P E u r o p a c e 2017 Apr;19(4)\:665-694.
Snir AD, Raju Hariharan. Current Controversies and Challenges in Brugada Syndrome. E u r o p e a n C a r d i o l o g y R e v i e w 2019
Dec;14(3)\:169-174.
Ezzat VA, e t a l . A systematic review of ICD complications in randomised controlled trials versus registries\: is our ‘real-world’
data an underestimation? O p e n H e a r t 2015 Feb;2(1)\:e000198.
Image references
Figure 1. Life in the fast lane. Brugada Syndrome. License\: [CC-BY-NC-SA]

Reviewer

Dr John Bonello
Specialist in Cardiology

Related notes

Acute Coronary Syndrome (ACS)
Acute Heart Failure
Atrial Fibrillation (AF)
Atrioventricular Block
Bundle Branch Block

Test yourself

Contents

Source\: geekymedics.com