Brugada Syndrome is a genetic condition characterized by abnormal ECG patterns and risk of sudden cardiac death. It is caused by mutations in the SCN5A gene which result in arrhythmogenesis. Key features include ST segment elevation in leads V1-V3, increased risk in males, and episodes of polymorphic ventricular tachycardia or ventricular fibrillation. Diagnosis involves family history, ECG findings, and provocation of ECG changes with sodium channel blockers. Treatment involves lifestyle modifications and implantation of an ICD for high-risk individuals.

1. Brugada Syndrome

2. Definition
“ Syncopal episodes and/or sudden death in patients
with a structurally normal heart and a
characteristic electrocardiogram displaying a
pattern resembling right bundle branch block
with ST segment elevation in leads V1 to V3 ”
Brugada et al. Circulation

3. What is Brugada Syndrome?
• Descibed 10 years ago by Ramon Brugada
• Inherited arrhythmia - Genetic
• Episodes of fast polymorphic VT – VF
• Usually effects men in their mid – late 30’s but
can affect all ages
• Differs from LQT in that there is no prolongation
of QT interval during sinus rhythm
• No preceding acceleration in heart rate

4. Other Forms of
Presentation
• Symptomatic with normal ECG during control
• Asymptomatic with abnormal ECG
• Asymptomatic family members with an abnormal
ECG either during, or after flecainide challenge

5. Epidemiology
• First reported in Poland
• Incidence & distribution difficult to ascertain
• Geographic distribution – worldwide but common in
S.E. Asia
– Philippines - Bangungut (Scream followed by
sudden death at night)
– Japan - Pokkuri (Unexpected sudden death at
night)
– Thailand - Lai Tai (Death during sleep)

6. Presentation
• Sudden cardiac death survivor (SCD)
• Approximately 10% of patients experience
paroxysmal AF
• Unexplained syncope

7. Genetic Considerations
• Link to gene SCN5A located in chromosome 3
• Approximately 60% of patients with aborted SCD
with the typical ECG, have family members with
the same ECG abnormalities or a family history of
SCD.
• The defect may be due to anomalies in the cellular
conduction channels, which may be inherited.
• Predominance of affected males
• Different from LQT and ARVD

9. Mechanism of
arrhythmogenesis
• Loss of AP dome in epicardial tissue
• Dispersion of refractories
• Phase II re-entry
• Rapid polymorphic VT
• VF
• Changes enhanced by Sodium channel
blockers (class Ia/Ic agents)

10. Genetics
• 50% familial
• 2/3 autosomal
dominant
• 1/3 genetics unclear
• 50% sporadic
• 15% have documented abnormalities on
SCN5A chromosome 3
• SCN5A also implicated in LQT3

11. Clinical features
• Male 8:1
• Caucasian or Asian
• Normal Physical examination or PMH
• Family history of sudden death/
syncope /VF in 22%

12. Diagnosis
• FH of sudden cardiac death or PMVT
• Brugada Shift pattern on ECG
• Normal structural heart
• Accentuation of ECG changes with
class Ia/Ic agents
• Demonstration of defects on SCN5A

13. Differential diagnosis 1
• Arrhythmogenic right ventricular
dysplasia
• Idiopathic ventricular fibrillation
• Polymorphic ventricular tachycardia
(inherited or acquired prolonged QT)
• Asymptomatic variants

14. Differential diagnosis 2
• Brugada vs idiopathic VF
40-60 % Chen et al
3-24% Remmne et al
• Brugada vs ARVD
No structural or histopathological similarities
Different genetic loci
Morphological abnormalities on MRI

15. Differential diagnosis 3
• Brugada vs MI
Similar to Right ventricular infarction
Younger age group

16. Asmyptomatic individuals
with Brugada ECG
• 0.05-0.14% general population
• No symptoms over 2-3 year follow up
• Variable response to Na blockers
• Brugada reported 27% event rate in
patients picked up with family
screening over a 3 year follow up

17. Treatment
• Brugada recommends/ESC advisory
board
• ICD for symptomatic individuals
• Extensive investigation of asymptomatic
individuals to exclude structural heart
disease
• ICD in patients with inducible VT/VF on EPS

18. Unanswered Questions
• Risk to asymtomatic individuals ?
• Interplay of pathological,
physiological and pharmacological
factors ?
• The predictive role of
electrophysiological studies

19. Prognosis & Treatment
• Poor prognosis when left untreated
• Antiarrhythmic therapy does not protect against
SCD
• Only available treatment is the Implantable
Cardioverter Defibrillator (ICD)

20. Considerations
• Genetic screening
• Exclude conditions where the ECG may mimic
Brugada
– Pectus excavatum
– Mediastinal tumours
– Steinert’s disease

21. The Flecainide Challenge
• IV flecainide is the standard test used to identify
individuals with concealed forms of the disease
• May reveal the characteristic ECG changes
• Conducted at the request of the attending
consultant cardiologist and with the approval of
the consultant electrophysiologist
N.B.The flecainide challenge is a significant moment
for the patient & their family, as it may represent the
confirmation of a lifelong and potentially life threatening
condition

22. Patient Education
• Discuss why the flecainide challenge is necessary,
the side effects & the need for continuous cardiac
monitoring
• The treatment options available must be discussed
should the flecainide challenge prove positive
• Full informed consent must be obtained by the
doctor administrating the dose.
• If the patient declines the flecainide challenge
then the associated risks must be discussed with
them

23. Medical Considerations
• Only medical personnel trained to administer
flecainide for this study may instigate therapy
• Raise awareness of the potential for ventricular
arrhythmias as in 0.5% of cases Ventricular
Fibrillation may be induced
• Additional counselling and support may be required
to help the patient cope with the associated
psychological, social and medical problems

24. Pre-Procedural Considerations
• Full explanation must be given and treatment
options outlined
• Informed consent must be obtained and
documented in the patients’ notes
• Serum electrolytes should be checked & corrected
• Record baseline observations
• Record a 12 lead ECG on admission
• Ensure cannula is sited and patent

25. Pre-Procedural Considerations
2
• The patient should be nil by mouth for at least 4
hours preceding the test
• The use of a pre-med sedation (eg. Midazolam)
may be required
• Ensure full resuscitation facilities, equipment and
drugs are available
N.B. - For paediatric cases the correct doses of
resuscitation drugs should be calculated and
prepared beforehand

26. Prescribed Drug Dosage
• The intravenous flecainide must be prescribed and
signed by the doctor administrating the dose,
clearly marked “For Flecainide challenge only”
• Confirm the correct dose of Flecainide is
prescribed according to the patients weight
• The recommended IV dose is 2mg/kg
N.B.The maximum dose licensed for Flecainide is 150mg = 75kg

27. The Clinical Setting
• The flecainide challenge should only be carried out
in a high dependency setting
• For paediatric cases:
- PICU should be informed with the bed space
booked and agreed in advance
- The medical team must liaise with the consultant
intensivist & PICU registrar
- A senior paediatric nurse to accompany & assist
- PICU staff will not be directly involved other
than in the event of a resuscitation

28. The Procedure
• Establish continuous 12 lead ECG monitoring for
duration of the challenge
• Monitor and record the patients BP, HR & Oxygen
saturations at 5 minute intervals
• The prescribing doctor must administer the IV
flecainide slowly over 10 minutes
• During administration, 12 lead ECGs should be
recorded at 5 minute intervals or with any
observed ECG changes on the monitor
• If, at any time, there are changes suggestive of
Brugada the remaining infusion must be
discontinued
• Twelve lead ECG monitoring should continue for 30
minutes on completion of the infusion

29. Study Interpretation
• The flecainide challenge is considered positive if
there is a 1mm ST elevation in leads V1, V2 & V3

30. Follow up Care
• The patient should be closely monitored until the
results of the test are known & the effects of
sedation have worn off
• If the test is positive the doctor should confirm
this with the consultant electrophysiologist, prior
to informing the patient and/or parents
• The discharging doctor should check with the
consultant electrophysiologist & cardiologist
regarding follow-up & arrange this prior to
discharge
• A discharge summary should be completed prior to
the patient leaving the ward

31. Case Report
• PC - 52 yr male
• 3 yr history of palpitations
• Usually on exertion
• 15 times in last 3 yrs
• Associated with pre syncope
• Previously fit and well
• Examination normal
• ECG
• Echo normal

36. Flecainide infusion

37. Investigations
• Multiple ambulatory monitoring
normal
• ETT
• Coronary angio normal
• EPS – VF with S4

38. Outcome
• Dual chamber ICD
• Currently well
– NSVT
– No therapy