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2/28/2010 1 Brugada’s Syndrome and Sudden Brugada’s Syndrome and Sudden Cardiac Death Cardiac Death Nitish Badhwar, MD, FACC University of California, San Francisco 3 rd Asian Heart and Vascular Symposium February 27, 2009 1 1 Myerberg RJ, Castellanos A. Cardiac Arrest and Sudden Cardiac Death. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 5 th Ed. New York: WB Saunders. 1997: 742-779. 2 Circulation. 2001; 104: 2158-2163. 3 Vreede-Swagemakers JJ et al. J Am Coll Cardiol 1997; 30: 1500-1505. <5% 400,000 3 W. Europe 5% 450,000 2 U.S. <1% 3,000,000 1 Worldwide Survival Incidence (cases/year) Sudden Cardiac Death Sudden Cardiac Death Sudden Cardiac Death Sudden Cardiac Death 2 1 U.S. Census Bureau, Statistical Abstract of the United States: 2001. 2 American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001. 3 2002 Heart and Stroke Statistical Update, American Heart Association. 4 Circulation. 2001;104:2158-2163. SCD claims more lives each year than these other diseases combined. Magnitude of Sudden Cardiac Magnitude of Sudden Cardiac Death (SCD) in United States Death (SCD) in United States Magnitude of Sudden Cardiac Magnitude of Sudden Cardiac Death (SCD) in United States Death (SCD) in United States 3 80% Coronary Artery Disease Adapted from Heikki et al. N Engl J Med, Vol. 345, No. 20, 2001. * ion-channel abnormalities, valvular or congenital heart disease, other causes 15% Cardiomyopathy 5% Other* 4 Causes of Sudden Cardiac Death Causes of Sudden Cardiac Death Causes of Sudden Cardiac Death Causes of Sudden Cardiac Death

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  • 2/28/2010

    1

    Brugadas Syndrome and Sudden Brugadas Syndrome and Sudden Cardiac Death Cardiac Death

    Nitish Badhwar, MD, FACCUniversity of California, San Francisco

    3rd Asian Heart and Vascular SymposiumFebruary 27, 2009

    11

    1 Myerberg RJ, Castellanos A. Cardiac Arrest and Sudden Cardiac Death. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 5th Ed. New York: WB Saunders. 1997: 742-779.

    2 Circulation. 2001; 104: 2158-2163.3 Vreede-Swagemakers JJ et al. J Am Coll Cardiol 1997; 30: 1500-1505.

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    CardiomyopathyCardiomyopathyCardiomyopathyCardiomyopathy

    Dilated Cardiomyopathy

    Hypertrophic Cardiomyopathy (HCM)

    Arrhythmogenic Right Ventricular

    Cardiomyopathy (ARVC)

    Left Ventricular Non-compaction

    Restrictive Cardiomyopathy

    Dilated Cardiomyopathy

    Hypertrophic Cardiomyopathy (HCM)

    Arrhythmogenic Right Ventricular

    Cardiomyopathy (ARVC)

    Left Ventricular Non-compaction

    Restrictive Cardiomyopathy

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    Cardiac Cardiac ChannelopathiesChannelopathiesCardiac Cardiac ChannelopathiesChannelopathies

    Brugada Syndrome

    Long QT Syndrome (LQTS)

    Short QT Syndrome

    Catecholamine induced Polymorphic

    Ventricular Tachycardia (CPVT)

    Short coupled Short coupled TorsadesTorsades

    Idiopathic VFIdiopathic VF

    Brugada Syndrome

    Long QT Syndrome (LQTS)

    Short QT Syndrome

    Catecholamine induced Polymorphic

    Ventricular Tachycardia (CPVT)

    Short coupled Short coupled TorsadesTorsades

    Idiopathic VFIdiopathic VF66

    First described in 1992 in 8 patients with aborted sudden cardiac death

    Characterized by: ECG findings of RBBB and

    persistent ST segment elevation in V1-V3

    Structurally normal hearts Propensity for life threatening

    ventricular arrhythmias

    First described in 1992 in 8 patients with aborted sudden cardiac death

    Characterized by: ECG findings of RBBB and

    persistent ST segment elevation in V1-V3

    Structurally normal hearts Propensity for life threatening

    ventricular arrhythmias

    BrugadaBrugada SyndromeSyndromeBrugadaBrugada SyndromeSyndrome BrugadaBrugada Syndrome: ECGSyndrome: ECGBrugadaBrugada Syndrome: ECGSyndrome: ECG

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    BrugadaBrugada : Clinical Features: Clinical FeaturesIncidence and DistributionIncidence and Distribution

    BrugadaBrugada : Clinical Features: Clinical FeaturesIncidence and DistributionIncidence and Distribution

    Unexpected sudden death

    Syncope, seizures

    Agonal nocturnal respirations

    Affects male patients predominately (8:1)

    Cases reported worldwide

    Unexpected sudden death

    Syncope, seizures

    Agonal nocturnal respirations

    Affects male patients predominately (8:1)

    Cases reported worldwide

    BrugadaBrugada : Clinical Features: Clinical FeaturesIncidence and DistributionIncidence and Distribution

    BrugadaBrugada : Clinical Features: Clinical FeaturesIncidence and DistributionIncidence and Distribution

    Responsible for up to 50% of sudden death in victims with structurally normal hearts in Thailand

    Recognized in Asia for decades: Bangungut: scream followed by

    sudden death during sleep (Philippines)

    Lai tai: death during sleep (Thailand) Pokkuri: unexpected death during

    sleep (Japan)

    Responsible for up to 50% of sudden death in victims with structurally normal hearts in Thailand

    Recognized in Asia for decades: Bangungut: scream followed by

    sudden death during sleep (Philippines)

    Lai tai: death during sleep (Thailand) Pokkuri: unexpected death during

    sleep (Japan)

    Type 1 Type 2 Type 3

    BrugadaBrugada Syndrome: ECGSyndrome: ECGBrugadaBrugada Syndrome: ECGSyndrome: ECGBrugadaBrugada Syndrome: Before (A) and Syndrome: Before (A) and

    After (B) After (B) ProcainamideProcainamideBrugadaBrugada Syndrome: Before (A) and Syndrome: Before (A) and

    After (B) After (B) ProcainamideProcainamide

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    Na+ channel blockersNa+ channel blockers Alpha agonists, Alpha agonists, VagotonicVagotonic agents,Betaagents,Beta--

    blockersblockers FeverFever TricyclicTricyclic antidepressants, antidepressants, antihistaminicsantihistaminics HypercalcemiaHypercalcemia, , HyperkalemiaHyperkalemia Alcohol, CocaineAlcohol, Cocaine Severe ischemiaSevere ischemia

    Na+ channel blockersNa+ channel blockers Alpha agonists, Alpha agonists, VagotonicVagotonic agents,Betaagents,Beta--

    blockersblockers FeverFever TricyclicTricyclic antidepressants, antidepressants, antihistaminicsantihistaminics HypercalcemiaHypercalcemia, , HyperkalemiaHyperkalemia Alcohol, CocaineAlcohol, Cocaine Severe ischemiaSevere ischemia

    Factors / Drugs that enhance ECG Factors / Drugs that enhance ECG PatternPattern

    Factors / Drugs that enhance ECG Factors / Drugs that enhance ECG PatternPattern

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    20% Atrial Fibrillation

    Prolonged PR interval (prolonged HV interval)

    AV nodal reentrant tachycardia

    WPW

    20% Atrial Fibrillation

    Prolonged PR interval (prolonged HV interval)

    AV nodal reentrant tachycardia

    WPW

    BrugadaBrugada Syndrome: Other Syndrome: Other ArrhythmiasArrhythmias

    BrugadaBrugada Syndrome: Other Syndrome: Other ArrhythmiasArrhythmias

    Autosomal dominant

    60 different mutations in the SCN5A (chromosome 3) gene have been linked to the syndrome.

    Failure of alpha subunit of Sodium channel to express

    Shift in voltage and time dependence of INA+ activation, inactivation or reactivation

    Autosomal dominant

    60 different mutations in the SCN5A (chromosome 3) gene have been linked to the syndrome.

    Failure of alpha subunit of Sodium channel to express

    Shift in voltage and time dependence of INA+ activation, inactivation or reactivation

    BrugadaBrugada Syndrome: GeneticsSyndrome: GeneticsBrugadaBrugada Syndrome: GeneticsSyndrome: Genetics

    More pronounced AP notch (red arrow) due to greater Ito mediated outward current in RVMore pronounced AP notch (red arrow) due to greater Ito mediated outward current in RV

    BrugadaBrugada: : PathophysiologyPathophysiologyVariation Between LV and RV Action Potentials Variation Between LV and RV Action Potentials

    BrugadaBrugada: : PathophysiologyPathophysiologyVariation Between LV and RV Action Potentials Variation Between LV and RV Action Potentials

    BrugadaBrugada: : PathophysiologyPathophysiologyHeterogeneous Loss of Action Potential DomeHeterogeneous Loss of Action Potential Dome

    BrugadaBrugada: : PathophysiologyPathophysiologyHeterogeneous Loss of Action Potential DomeHeterogeneous Loss of Action Potential Dome

    Transmural voltage gradient

    EndocardiumEpicardium

    Transmembrane dispersion of repolarization

    Epicardial dispersion of repolarization

    Normal

    Brugada

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    BrugadaBrugada: Diagnosis: DiagnosisBrugadaBrugada: Diagnosis: Diagnosis

    Symptoms: syncope, SCD (usually during sleep) Physical exam: normal Family history: strong history of SCD ECG: best test to identify Brugada patients

    May require Flecainide or Procainamide to bring out typical findings

    ST elevation more predictive of SCD than RBBB

    Imaging tests: usually no underlying structural disease

    Stress tests: symptoms and ECG findings not usually reproducible with exercise

    SAECG: can show late potentials in 80%

    Symptoms: syncope, SCD (usually during sleep) Physical exam: normal Family history: strong history of SCD ECG: best test to identify Brugada patients

    May require Flecainide or Procainamide to bring out typical findings

    ST elevation more predictive of SCD than RBBB

    Imaging tests: usually no underlying structural disease

    Stress tests: symptoms and ECG findings not usually reproducible with exercise

    SAECG: can show late potentials in 80%

    Major criteria

    1. Presence of the ECG marker of Brugada syndrome in patients with structurally normal heart

    2. Appearance of the ECG marker of Brugada syndrome after administration of sodium channel blockers

    Minor criteria

    1. Family history of sudden cardiac death

    2. Syncope of unknown origin

    3. Documented episodes of ventricular tachycardia/ventricular fibrillation

    4. Positive programmed electrocardiostimulation test on ventricular tachycardia/ventricular fibrillation

    5. Genetic mutations of ion channels

    BrugadaBrugada Syndrome: Diagnostic Syndrome: Diagnostic CriteriaCriteria

    BrugadaBrugada Syndrome: Diagnostic Syndrome: Diagnostic CriteriaCriteria

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    BrugadaBrugada: Prognosis: PrognosisRecurrence of VF or SCD in Asymptomatic vs. Recurrence of VF or SCD in Asymptomatic vs.

    Symptomatic PatientsSymptomatic Patients

    BrugadaBrugada: Prognosis: PrognosisRecurrence of VF or SCD in Asymptomatic vs. Recurrence of VF or SCD in Asymptomatic vs.

    Symptomatic PatientsSymptomatic PatientsRisk StratificationRisk StratificationRisk StratificationRisk Stratification

    Risk factors for asymptomatic individuals Male - 5.5 fold Spontaneous positive ECG - 7.7 fold Inducible VT/VF 8 fold

    Asymptomatic, drug induced type 1 Brugada ECG pattern and no inducible VT during Electrophysiology study - 0.5% probability of event

    Asymptomatic, Spontaneous type 1 Brugada ECG pattern and inducible sustained VT during EP study - 14% probability of event

    Syncope, Spontaneous type 1 Brugada ECG pattern , and inducible sustained VT during EP study- 27% probability of event

    Risk factors for asymptomatic individuals Male - 5.5 fold Spontaneous positive ECG - 7.7 fold Inducible VT/VF 8 fold

    Asymptomatic, drug induced type 1 Brugada ECG pattern and no inducible VT during Electrophysiology study - 0.5% probability of event

    Asymptomatic, Spontaneous type 1 Brugada ECG pattern and inducible sustained VT during EP study - 14% probability of event

    Syncope, Spontaneous type 1 Brugada ECG pattern , and inducible sustained VT during EP study- 27% probability of event

    Brugada et al. Circulation. 2003;108. 3092-3096.

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    BrugadaBrugada: Treatment: TreatmentBrugadaBrugada: Treatment: Treatment

    Symptomatic patients with the disease: Symptomatic patients with the disease: ICDICD

    Asymptomatic patients with a family Asymptomatic patients with a family history of SCD: with normal ECG and history of SCD: with normal ECG and negative EP study negative EP study OBSERVEOBSERVE

    Asymptomatic pt with prolonged HAsymptomatic pt with prolonged H--V V interval, and inducible VT/VF: interval, and inducible VT/VF: controversial controversial ICDICD

    Symptomatic patients with the disease: Symptomatic patients with the disease: ICDICD

    Asymptomatic patients with a family Asymptomatic patients with a family history of SCD: with normal ECG and history of SCD: with normal ECG and negative EP study negative EP study OBSERVEOBSERVE

    Asymptomatic pt with prolonged HAsymptomatic pt with prolonged H--V V interval, and inducible VT/VF: interval, and inducible VT/VF: controversial controversial ICDICD

    Potential Potential antiarrhythmicantiarrhythmic drugs in drugs in BrugadaBrugada SyndromeSyndrome

    Potential Potential antiarrhythmicantiarrhythmic drugs in drugs in BrugadaBrugada SyndromeSyndrome

    Quinidine (non specific Ito blocker)

    Isoproterenol (open L typecalcium channel)

    Cilostazol (augment Ica )

    Tedisamil (Ito blocker)

    Quinidine (non specific Ito blocker)

    Isoproterenol (open L typecalcium channel)

    Cilostazol (augment Ica )

    Tedisamil (Ito blocker)

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    Sudden Cardiac Death in Southeast Asia

    Characteristic ECG pattern

    ICD implantation in symptomatic patients

    Sudden Cardiac Death in Southeast Asia

    Characteristic ECG pattern

    ICD implantation in symptomatic patients

    BrugadaBrugada Syndrome: SummarySyndrome: SummaryBrugadaBrugada Syndrome: SummarySyndrome: Summary

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