Brugada Syndrome was first described in 1992 and is characterized by ST-segment elevation in the right precordial leads and risk of sudden cardiac death. It is caused by mutations that result in loss of function of the cardiac sodium channel. Diagnosis requires a type 1 ECG pattern with coved ST elevation of ≥2 mm in ≥1 right precordial lead, either spontaneously or after sodium channel blocker administration. Implantable cardioverter defibrillator placement is the primary treatment for those who experience symptoms or induced arrhythmias due to high risk of sudden death. Lifestyle modifications and sodium channel blockers like quinidine may also be used for prevention and treatment of arrhythmias.

1. Brugada Syndrome
Dr Abhishek Rathore
Sri Jayadeva Institute of Cardiovascular Science and
research, Bangalore

2. History
 A case of a three year old boy in Poland presented in 1986
with multiple episodes of syncope, which was brought to
the attention of the Brugada Brothers. His ECG showed
ST elevation in leads V1-V3. His sister displayed a similar
clinical and ECG profile and she died at the age of two
years
 Six similar cases came to their attention in the succeeding
years.

3.  In 1992 – Brugada brothers
reported these eight cases as
the basis of a new and distinct
clinical entity

4.  In 1996, Yan and Antzelevitch et al, highlighted the
importance of ST segment elevation and apparent
RBBB described by Brugada & Brugada and named it
the BRUGADA SYNDROME

5. Clinical Features and Epidemiology
 first described in 1992
 characterized by an aberrant pattern of ST segment
elevation in right precordial leads and a high incidence of
sudden death in patients with structurally normal heart
 20% of sudden death in patients with structurally normal
heart
 Leading cause of death of men under age 40 in regions
where the inheritance is endemic
 Prevalence ranges from 1 in 1000 to 1 in 10 000

6. Clincial Features and Epidemiology
 True prevalence in general population is difficult
to estimate as ECG pattern can be dynamic and
concealed.
 Much higher in Asian, Southeast asian countries
especially Thailand, Philipines , and Japan
 In a Japanese study, Brugada syndrome ECG type 1
was observed in 12/10000 inhabitants; type 2 and 3
ECG (not diagnostic of BrS) in 58/10000.

7. Clinical Features and Epidemiology
 Age of onset at 30-40s (mean age of SCD 41+/-15 years)
 M:F ratio of 8:1
 Percentage of clinically affected patients with at least 1
cardiac arrest before age 60 is 10-15%
 Typically cardiac events (syncope and SCD) manifests at
rest, during sleep and may be triggered by hyperpyrexia,
large meals, excessive alcohol.
 Approximately 20% of BrS patients develop SVT (M.C.-
AF)

8. D/D of
BRUGADA
SYNDRO
ME

9. Genetic basis and pathophysiology
 Inheritance - Autosomal dominant with incomplete penetrance.
 The first gene linked to BrS is SCN5A on chromosome 3 which
encodes for the alpha subunit of the cardiac Na channel.
 13 different genetic variants of syndrome are known nowadays
with >300 mutations.
 Mutation in SCN5A result in loss of function of Na+ Channel
and reduce Na current
 Only less than 30% of clinically diagnosed BrS are
accountable by SCN5A mutations.
 Triggers for BrS ECG and SCD----Fever, cocaine, electrolyte
disturbance, Class I drugs, other non-cardiac drugs.

10. Mechanism of Arrhythmogenesis
During phase 1 of the normal action potential, the
inward Na+ current and transient outward K+ current,
ITo, cause a normal spike and dome morphology.
 In the presence of weak Na+ current, the unopposed
outward K+ current ITo and ICa, cause accentuation of
the action potential notch in the RV epicardium,
resulting in accentuated J wave and ST segment
elevation .
 As these changes occur in the epicardium but not in
the endocardium, they create a transmural voltage
gradient.
 This inhomogeneous repolarisation in different areas

11. TYPES OF
BRUGADA
SYNDROME

12. Brugada syndrome: Diagnosis
ECG patterns in the right precordial leads

13. Brugada pattern:ECG

14.  Only Type I ECG pattern is diagnostic of BrS
 Type II and Type III are suggestive of but not
diagnostic of BrS
 Almost every individual with Type I ECG show
normalisation during follow up.

15. Diagnostic Criteria of Brugada Syndrome
 Appearance of on a type 1 ST segment elevation (coved type)
≥2mm in >1 right precordial lead (V1-3)
 either spontaneously or after Na channel blocker exposure
AND
 One of the following:
 Documented VF
 (Self-terminating) polymorphic VT
 Inducibility of ventricular arrhythmias with programmed electrical
stimulation
 Family history of sudden death before age 45
 Presence of of a coved-type ECG in family members
 Syncope
 Nocturnal agonal respiration
 Other factors accounting for the ECG abnormality should be ruled
out

16. Brugada syndrome: Diagnosis
 Brs is diagnosed in patients with ST elevation with type 1
morphology ≥2 mm in one or more leads among the right
precordial leads V1 and/or V2 positioned in the second,
third, or fourth intercostal space, occurring either
spontaneously or after provocative drug test.
 Drug induced ST elevation to <2mm is considered
inconclusive
 Drug-induced conversion of type 3 to type 2 ECG pattern
is considered inconclusive.

17. Drugs used to unmask Brugada syndrome
Ajmaline 1mg/kg over 5min. IV (BEST DRUG)
Flecainide 2mg/kg over 10 min. IV (max 150mg)
Procainamide 10mg/kg over 10min. IV
Pilsicainide 1mg/kg over 10min. IV
Sensitivity and Specificity of the test remains undefined.
Flecainide : Sens 77%, Spec 80%, PPV 96%, NPV 36%
(Meregalli et al. J Cardiovas Electrophysiol 2006; 17:857-864)
Ajmaline: Sens 80%, Spec 94.4%, PPV 93.3%, NPV 82.9%
(Hong et al. Circulation 2004; 110:3203-7)

18. Termination of test
• Test should be terminated when:
Type 1 ECG develops
ST segment in Type 2 pattern ↑ses by >2mm
Premature ventricular beats or other arrhythmias develop
QRS widens by ≥30% of baseline

19. Induction of diagnostic Coved type (type 1) ECG by Na channel blocking.

20. Treatment for Brugada syndrome
 ICD is the only proven effective treatment of BrS.
 Pharmacologic Treatment in BrS
Isoproterenol (Increase IcaL current)--- for electrical storm
Quinidine (Ikr and Ito blocking effects)
1.supress ventricular arrythmias
2.prevent induction of VF
3.Patients with ICD and multiple shocks
4. When ICD is contraindicated.
5. Supraventricular arrythmias
6.Children with BrS as a bridge or alternative to ICD
 Radiofrequency Ablation
For ventricular ectopy which triggered VF

21. Prevention
 Drugs reported to exacerbate the ECG pattern
of ST segment elevation and trigger
arrhythmias in BrS should be avoided.
(Brugadadrugs.org)
 Antiarrhythmics (class Ia Ic betablockers), CCB,
nitrates, TCA, phenothiazines, SSRI like fluoxetine,
bupivacaine, propoxyphene, propofol, pinacidil,
nicorandil (K channel activators), Li, cociane,
methxamine (alpha- agonists)
 Avoid excessive alcohol, large carbohydrate
meal, very hot baths, hypokalemia
 Hyperpyrexia should be treated promptly.

22.  In all the analysis of Dr. Brugada’s series (1998, 2002,
2003), several clinical variables predict a worst
outcome:
 Presence of symptoms before diagnosis
 Spontaneous type 1 ECG at baseline
 Inducibility of ventricular arrhythmia by programmed
stimulation (EPS)
 Male gender

23. Risk Assesment of Asymptomatic
BrS
 Event rate with spontaneous type 1 ECG - 0.24
to 1.7% per year.
 Drug induced BrS pattern ECG patients are at
minimal risk.
 Programmed electrical stimulation is not helpful in
risk stratification.
 Fragmentation of QRS on the ECG, RV ERP of
200msec, history of syncope, atrial fibrillation and
spontaneous type 1 Brugada pattern on the ECG,
put the patient in the higher risk category.

24. ESC 2015
Recommendations on BrS therapeutic interventions
Class I
 lifestyle changes like:
 a. Avoidance of drugs that may induce or aggravate
ST-segment elevation in right precordial leads (e.g.,
Brugadadrugs.org)
 b. Avoidance of excessive alcohol and large meals.
 c. Immediate treatment of fever with antipyretic drugs.
 ICD implantation:
 a. Are survivors of a cardiac arrest and/or
 b. Have documented spontaneous sustained VT

25. Class IIa
 ICD in patients with spontaneous diagnostic type I ECG who
have a H/O syncope.
 Quinidine and Isoproterenol infusion to treat arrythmic
storms.
 Quinidine :
 a. who qualify for an ICD but present a contraindication to
the ICD or refuse it and/or
 b. Have a history of documented supraventricular
arrhythmias that require treatment.
ESC 2015
Recommendations on BrS therapeutic interventions

26. Class IIb
 ICD in those who develop VF during programmed
electrical stimulation (inducible patients).
 Quinidine in asymptomatic patients with a diagnosis of
BrS with a spontaneous type I ECG.
 Catheter ablation may be considered in patients with a
diagnosis of BrS and history of arrhythmic storms or
repeated appropriate ICD shocks
ESC 2015
Recommendations on BrS therapeutic interventions

27. Class III
 ICD in asymptomatic BrS patients with a drug-
induced type I ECG and family history of SCD
alone