Brugada Syndrome

Morning Report
June, 2008
Jessie Stewart
 Why Present Brugada?
1. Lots of us missed it.
2. A new discovery- first described in 1992.
3. Drs. Josep, Pedro and Ramon Brugada.
 Where are we going?

• Primary Goal
• Understanding Brugada
• Prevalence
• Presentation
• Prognosis
• Therapy
 Goal
Recognize Brugada I: coved ST segment in
V1-V3, >2mm elevation, inverted T wave.
 Brugada Syndrome is…
• A sodium channel abnormality that
predisposes to sudden cardiac death.
• Characterized by specific EKG patterns:
– Type I is diagnostic when combined with the
right clinical picture.
– Types II and III raise suspicion for Brugada
but they are only diagnositic if they can be
converted to Type I during challenge with a
sodium channel blocker.
– These patterns are dynamic and inducible.
 Type I- Diagnostic
• V1-V3 (as least two leads)
ST segment elevation
>2mm, “coved” shape,
inverted T-wave.
• Coupled with
– Documented VFib
– Polymorphic VT
– FH of sudden cardiac death
<45 yo
– Type I EKG in family
members
– VT inducable in EP lab
– Syncope
– Nocturnal agonal respiration
 Types II and III- Suggestive
• II: V1-V3 ST segment
elevation >2mm,
“saddleback” shape, pos
or biphasic T.
• III: <1 mm elevation,
either coved or
saddleback.
 SCN5A gene
• Codes for cardiac sodium channel that opens during phase 2 of the action
potential. In Brugada, it opens poorly in RV epicardial cells.
• Autosomal dominant inheritance
• 20-30% of cases have anbl SCN5A gene.
• 80+ mutations, differing prognosis.
1
0mVolts 2

0 3
1 -85mVolts
4 4
4

Priori, S. G. et al. Circulation 1999;99:674-681

 Defective sodium
channels: shorter AP
(phase 0), deeper
notch (phase I), and
shorter phase 2.
Creates juxtaposition
of depolarized and
repolarized cells,
setting up possibility
of PHASE 2 RENTRY,
closely grouped
PVCs, and VT or V
Fib.
On EKG, ST segment
not at baseline
because no longer
have uniform
depolarization of the
entire ventricle.
Nattel and Carlsson Nature Reviews Drug Discovery 5, 1034–1049 (December 2006) | doi:10.1038/nrd2112
 Where are we going?

• Primary Goal
• Understanding Brugada
• Prevalence
• Presentation
• Prognosis
• Therapy
 Prevalence
• In Thailand, estimated to be the second
leading cause of death in men <40, after
accidents.
• In the Philippines, known as Bangungut-
scream followed by sudden death during
sleep- and in Japan as Pokkuri-
unexpected sudden death at night.
• At the Carolinas Medical Center, Charlotte,
found in 0.4% of all EKGs.
 Presentation
• Sudden cardiac arrest often the first
symptom.
• More common at night, esp when
sleeping.
• Ages 22-65- mean age of sudden death
41 +/- 15 years.
 Where are we going?

• Primary Goal
• Understanding Brugada
• Prevalence
• Presentation
• Prognosis
• Therapy
 Prognosis

Risk Stratification based on-

1. Prior History of SCA: 69% recur
within 5 years.
2. History of syncope
3. EKG abnormal at baseline or only
after drug challenge?
4. Is a SVA inducible in the EP lab?

SCA- Sudden Cardiac Arrest

SVA- Sustained Ventricular Arrhythmia
 Prognosis
In 547 patients with type 1 Brugada syndrome with no prior history of SCD, the
probability of SCA or VF during follow-up (average 2 years)
- Overall 8.2% with SCA or VFib.

SVA Noninducible, percent SVA Inducible, percent (95%

(95% CI) CI)
Prior syncope
EKG
Spontaneously abnormal 4.1 (1.4-11.7) 27.2 (17.3-40.0)
Abnormal after drug
1.2 (0.2-6.6) 9.7 (2.3-33.1)
challenge
No prior syncope
EKG
Spontaneously abnormal 1.8 (0.6-5.1) 14.0 (8.1-23.0)
Abnormal after drug
0.5 (0.1-2.7) 4.5 (1.0-17.1)
challenge

Adapted from Brugada, J, Brugada, R, Brugada, P, Circulation 2003; 108:3092

SCA- Sudden Cardiac Arrest
SVA- Sustained Ventricular Arrhythmia
 Where are we going?

• Primary Goal
• Understanding Brugada
• Prevalence
• Presentation
• Prognosis
• Therapy
 Treatment
• Implantable Cardiac Defibrillator
Prior History of SCA: 69% recur within 5 years.

SVA Noninducible, percent SVA Inducible, percent (95%

(95% CI) CI)
Prior syncope

ECG

Spontaneously abnormal 4.1 (1.4-11.7) 27.2 (17.3-40.0)

Abnormal after drug

1.2 (0.2-6.6) 9.7 (2.3-33.1)
challenge

No prior syncope

ECG

Spontaneously abnormal 1.8 (0.6-5.1) 14.0 (8.1-23.0)

Abnormal after drug

0.5 (0.1-2.7) 4.5 (1.0-17.1)
challenge
 Drug Therapy?
•Quinidine (Class IA) may blunt Ito.
•Isoproterenol (Beta-adrenergic agonist) may augment L-type Ca++
current.
 Goal
Recognize Brugada I: coved ST segment in
V1-V3, >2mm elevation, inverted T wave.
 References
• Antelevitch C et al. Brugada Syndrome: Report of the Second
Consensus Conference. Heart Rhythm 2005. 2(4):429-440.
• Benito and Brugada. Recurrent syncope: an unusual presentation of
Brugada syndrome. Nature Clinical Practice 2006. 3(10): 573-577.
• 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; 108:3092.
• 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: 1391–1396.
• UpToDate. Brugada Syndrome and Sudden Cardiac Arrest.
• Priori, S. G. et al. Genetic and Molecular Basis of Cardiac
Arrhythmias: Impact on Clinical Management Part III. Circulation
1999;99:674-681.