Brugada SyndromeMorning ReportJune, 2008Jessie 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 GoalUnderstanding BrugadaPrevalencePresentationPrognosisTherapy

GoalRecognize Brugada I: coved ST segment in V1-V3, >2mm elevation, inverted T wave.

Brugada Syndrome isA 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- DiagnosticV1-V3 (as least two leads) ST segment elevation >2mm, coved shape, inverted T-wave.Coupled with Documented VFibPolymorphic VTFH of sudden cardiac death

Types II and III- SuggestiveII: V1-V3 ST segment elevation >2mm, saddleback shape, pos or biphasic T.III:

SCN5A geneCodes for cardiac sodium channel that opens during phase 2 of the action potential. In Brugada, it opens poorly in RV epicardial cells. Autosomal dominant inheritance20-30% of cases have anbl SCN5A gene.80+ mutations, differing prognosis. Priori, S. G. et al. Circulation 1999;99:674-681112340440mVolts-85mVolts

Nattel and Carlsson Nature Reviews Drug Discovery 5, 10341049 (December 2006) | doi:10.1038/nrd2112Defective 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.

PrevalenceIn Thailand, estimated to be the second leading cause of death in men

PresentationSudden cardiac arrest often the first symptom. More common at night, esp when sleeping.Ages 22-65- mean age of sudden death 41 +/- 15 years.

PrognosisRisk Stratification based on- 1. Prior History of SCA: 69% recur within 5 years. 2. History of syncope3. EKG abnormal at baseline or only after drug challenge?4. Is a SVA inducible in the EP lab?SCA- Sudden Cardiac ArrestSVA- Sustained Ventricular Arrhythmia

PrognosisIn 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. Adapted from Brugada, J, Brugada, R, Brugada, P, Circulation 2003; 108:3092 SCA- Sudden Cardiac ArrestSVA- Sustained Ventricular Arrhythmia

SVA Noninducible, percent (95% CI)SVA Inducible, percent (95% CI)Prior syncopeEKGSpontaneously abnormal 4.1 (1.4-11.7)27.2 (17.3-40.0)Abnormal after drug challenge1.2 (0.2-6.6)9.7 (2.3-33.1)No prior syncopeEKGSpontaneously abnormal 1.8 (0.6-5.1)14.0 (8.1-23.0)Abnormal after drug challenge0.5 (0.1-2.7)4.5 (1.0-17.1)

TreatmentImplantable Cardiac DefibrillatorPrior History of SCA: 69% recur within 5 years.

SVA Noninducible, percent (95% CI)SVA Inducible, percent (95% CI)Prior syncopeECGSpontaneously abnormal 4.1 (1.4-11.7)27.2 (17.3-40.0)Abnormal after drug challenge1.2 (0.2-6.6)9.7 (2.3-33.1)No prior syncopeECGSpontaneously abnormal 1.8 (0.6-5.1)14.0 (8.1-23.0)Abnormal after drug challenge0.5 (0.1-2.7)4.5 (1.0-17.1)

Drug Therapy?Quinidine (Class IA) may blunt Ito.Isoproterenol (Beta-adrenergic agonist) may augment L-type Ca++ current.

GoalRecognize Brugada I: coved ST segment in V1-V3, >2mm elevation, inverted T wave.

ReferencesAntelevitch 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: 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 1999;99:674-681.