Brugada Syndrome

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Brugada Syndrome

• Morning Report
• June, 2008
• Jessie Stewart

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Why Present Brugada?

• 1. Lots of us missed it.
• 2. A new discovery- first described in 1992.
• 3. Drs. Josep, Pedro and Ramon Brugada.

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Where are we going?

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

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Goal

• Recognize Brugada I coved ST segment in V1-V3,
  gt2mm elevation, inverted T wave.

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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.

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Type I- Diagnostic

• V1-V3 (as least two leads) ST segment elevation
  gt2mm, coved shape, inverted T-wave.
• Coupled with
• Documented VFib
• Polymorphic VT
• FH of sudden cardiac death lt45 yo
• Type I EKG in family members
• VT inducable in EP lab
• Syncope
• Nocturnal agonal respiration

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Types II and III- Suggestive

• II V1-V3 ST segment elevation gt2mm, saddleback
  shape, pos or biphasic T.
• III lt1 mm elevation, either coved or saddleback.

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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.

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Priori, S. G. et al. Circulation 199999674-681
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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, 10341049 (December 2006) doi10.1038/nrd2112
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Where are we going?

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

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Prevalence

• In Thailand, estimated to be the second leading
  cause of death in men lt40, 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.

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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.

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Where are we going?

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

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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
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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 (95 CI) SVA Inducible, percent (95 CI)
Prior syncope Prior syncope Prior syncope
EKG EKG EKG
Spontaneously abnormal 4.1 (1.4-11.7) 27.2 (17.3-40.0)
Abnormal after drug challenge 1.2 (0.2-6.6) 9.7 (2.3-33.1)
No prior syncope No prior syncope No prior syncope
EKG EKG EKG
Spontaneously abnormal 1.8 (0.6-5.1) 14.0 (8.1-23.0)
Abnormal after drug challenge 0.5 (0.1-2.7) 4.5 (1.0-17.1)
Adapted from Brugada, J, Brugada, R, Brugada, P,
Circulation 2003 1083092
SCA- Sudden Cardiac Arrest SVA- Sustained
Ventricular Arrhythmia
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Where are we going?

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

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Treatment

• Implantable Cardiac Defibrillator

Prior History of SCA 69 recur within 5 years.
  SVA Noninducible, percent (95 CI) SVA Inducible, percent (95 CI)
Prior syncope Prior syncope Prior syncope
ECG ECG ECG
Spontaneously abnormal 4.1 (1.4-11.7) 27.2 (17.3-40.0)
Abnormal after drug challenge 1.2 (0.2-6.6) 9.7 (2.3-33.1)
No prior syncope No prior syncope No prior syncope
ECG ECG ECG
Spontaneously abnormal 1.8 (0.6-5.1) 14.0 (8.1-23.0)
Abnormal after drug challenge 0.5 (0.1-2.7) 4.5 (1.0-17.1)
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Drug Therapy?

• Quinidine (Class IA) may blunt Ito.
• Isoproterenol (Beta-adrenergic agonist) may
  augment L-type Ca current.

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Goal

• Recognize Brugada I coved ST segment in V1-V3,
  gt2mm elevation, inverted T wave.

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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
  1083092.
• 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 13911396.
• 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 199999674-681.