Brugada syndrome (BrS)

1. Brugada Syndrome (BrS).
B Y S I M O N M A R K D A L E Y ( 2 0 1 8 )
A presentation.

2. SOME HISTORY...
Although ECG changes were reported in 1989, amongst survivors
of cardiac arrest, not recognised until 1992 (by the Brugada
brothers) as a distinct clinical entity.
Exponential rise in the number of cases reported since then.
Second Consensus Conference (2005) reported it as the second
biggest killer in males <40 years (non-traumatic).
Incidence higher in SE Asia than Europe and the US where it was
previously known as Sudden Unexplained Nocturnal Death
Syndrome (SUNDS).
Mean age of sudden death is 41 years.
Age at diagnosis ranging from 2 days to 84 years.
More common in males due to higher penetrance of the
responsible gene.

3. WHAT IS IT?
Brugada syndrome (BrS) is a genetic disorder characterised by abnormal
ECG findings (incomplete right bundle-branch block and ST-segment
elevations in the anterior precordial leads). There is an increased risk of
sudden cardiac death associated with this disorder.
- Dizon and Nazif (2015)
BrS is an ECG abnormality with a high incidence of sudden death in
patients with structurally normal hearts.
- Lifeinthefastlane.com

4. IN MORE DETAIL PLEASE...
BrS is a channelopathy; a disorder caused by an alteration in the
transmembrane ion currents that together constitute the cardiac action
potential.
- Dizon and Nazif (2015)

5. Approximately 20% of cases of BrS have been shown to be associated with mutations in a gene that
encodes for a sodium ion channel in the cell membranes of myocytes. The gene, named SCN5A is
located on the short arm of the third chromosome (3p21). Over 160 mutations in this gene have been
discovered to date, each having varying mechanisms and effects on function.
Loss-of-function mutations in this gene lead to a loss of the action potential dome of some
epicardial areas of the right ventricle. This results in transmural and epicardial dispersion of
repolarisation. The transdermal dispersion underlies ST-segment elevation and the development of a
vulnerable window across the ventricular wall, whereas the epicardial dispersion of repolarisation
facilitates the development of phase 2 reentry,, which generates a phase 2 re-entrant extrasystole
that captures the vulnerable window to precipitate VT and/or VF.
EVEN MORE DETAIL...
(TOO MUCH DETAIL)

6. - Dizon and Nazif (2015)
VISUAL
REPRESENTATION
OF THIS;

7. The majority of patients affected by BrS are not found to have
known genetic mutations to explain the disease, as of 2015.
(Sarquella-Brugada, Campuzano, Arbelo, Brugada and Brugada, 2015).
Over 60 different mutations have been described so far and at least
50% are spontaneous mutations, but familial clustering and
autosomal dominant inheritance has been demonstrated.
GO ON...
(SOMEWHAT SIMPLIFIED)

8. It is important to understand that ECG changes may be transient and can be
unmasked or augmented by multiple factors;
Fever – very common, particularly in children
Ischaemia
Multiple drugs; sodium channel blockers, calcium channel blockers, alpha
agonists, beta blockers, nitrates, cholinergic stimulation, cocaine, alcohol.
Hypokalaemia
Hypothermia
Post DC Cardioversion
Typical presentation is syncope or aborted sudden cardiac death (SCD) secondary
to VF (less commonly VT) and symptoms typically occur at night or at rest,
particularly after a large/heavy meal.
WHAT ARE WE LOOKING FOR?
(CLINICAL PRACTICE)

9. Type 1 has a coved type ST elevation with at least 2 mm J-
point elevation a gradually descending ST segment followed
by a negative T-wave.
Type 2 has a saddle back pattern with a least 2 mm J-point
elevation and at least 1 mm ST elevation with a positive or
biphasic T-wave. Type 2 pattern can occasionally be seen in
healthy subjects.
Type 3 has either a coved (type 1 like) or a saddle back (type
2 like) pattern with less than 2 mm J-point elevation and less
than 1 mm ST elevation. Type 3 pattern is not rare in healthy
subjects.
An incomplete RBBB pattern can be observed, and prolongation
of the PR-interval is also frequently seen.
ECG PATTERNS IN BSR;
(WHEN UNMASKED)

10. Type 1 either spontaneously present or induced with the
sodium-channel blocker challenge test is considered
diagnostic.
Type 2 and 3 may lead to suspicion but the drug challenge is
required for diagnosis.
The ECGs in the right and left panels are from the same patient
before (right panel, type 3) and after (left panel, type 1)
administration of 1 mg/kg of Ajmaline.
ECG PATTERNS IN BSR;
(WHEN UNMASKED)

11. 2 REAL LIFE EXAMPLES;

12. Resuscitated cardiac arrest and cardiac syncope are Class 1 indications for
implantation of an ICD.
All family members should be screened and those with normal or non-diagnostic
ECGs should be offered ajmaline or flecainide testing.
ICD implantation has a significant complication rate in BsR however, therefore
this should be avoided in asymptomatic patients. Family history of sudden
cardiac death (SCD) is NOT an indication for ICD implantation.
Asymptomatic individuals should be advised of lifestyle measures such as
avoidance of ‘Brugada drugs’*, prompt treatment of fever, avoiding excess of
alcohol, particularly hot baths and big/carbohydrate rich meals at night.
*So-called ‘Brugada drugs’ can be found listed at brugadadrugs.org and are not
necessarily the same as QTc prolongation drugs
MANAGEMENT;

13. Event rate in those with spontaneous type 1 ECG has been reported as 0.24-1.7%
per year. Drug induced BrS pattern ECG patients are at minimal risk.
Fragmentation of QRS on ECG (RSR/notched S/notched R), RV effective
refractory period (ERP) of <200msecs, a history of syncope or AF with
spontaneous type 1 pattern put the patient in a higher risk category.
RISK ASSESSMENT OF
ASYMPTOMATIC BRS PATIENTS;
TREATMENT OF
ARRHYTHMIC STORMS;
Isoprenaline infusion is effective in acute situations, whilst quinidine is the only
effective long-term agent.

14. A NOTE ON
MISDIAGNOSIS OF BRS;
Spurious BrS type ECG changes can be seen in patients
following cardioversion, may last for several hours and may
lead to a misdiagnosis of BrS. Misdiagnosis can occur with
ECG changes of early repolarisation, athlete’s heart, RBBB,
acute pericarditis, MI, prinzmetal angina, ARVC, myocarditis,
Duchenne muscular dystrophy, electrolyte disturbances and
hypothermia.
Basically, (as always) don’t make any assumptions based on
ECGs without context.

15. Dizon, JM and Nazif, TM. (2015) Brugada Sydrome; http://emedicine.medscape.com/article/163751-overview
http://lifeinthefastlane.com/ecg-library/brugada-syndrome/
Napolitano C, Priori SG. Brugada syndrome. Orphanet J Rare Dis. 1, 35. 2006
Sarquella-Brugada, G. Campuzano, O., Arbelo, E., Brugada, J., and Brugada, R. (2015) Brugada Syndrome: Clincal and
Genetic Findings. Genetics in Medicine (2016) 18, 3-12.
Postema et al. (2009) Heart Rhythm;6:1335-41
Priori, SG., Wilde, AA., Horie, M., Cho, Y., Behr, ER., Berul, C., Blom, N., Brugada, J., Chiang, C., Huikuri, H.,
Kannankeril, P., Krahn, A., Leenhardt, A., Moss, A., Schwartz, PJ., Shimizu, W., Tomaselli, G. and Tracy, T. (2013)
HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited
Primary Arrhythmia Syndromes. Available online at http://dx.doi.org/10.1016/j.hrthm.2013.05.014
Vohra, J. and Rajagopalan, S. (2015) Update on the Diagnosis and Management of Brugada Syndrome. Heart, Lung
and Circulation. Vol 24, Iss 12 p1141-1148.
REFERENCES