prognosis of brugada syndrome patients with icd in korea
TRANSCRIPT
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Prognosis of Brugada syndrome
patients with ICD in Korea
Young Keun On, MD, PhD, FHRS
Samsung Medical Center
Sungkyunkwan University School of Medicine
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• In 1992, Brugada brothers first reported a unique
electrocardiographic syndrome in which ventricular fibrillation
could occur without obvious structural heart disease.
• Brugada syndrome is electrocardiographically characterized
by ST-segment elevation in the right precordial leads.
• Sudden death is common and may be the first manifestation
of disease during its clinical course.
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67 year-old gentleman complained of recurrent syncope
for 5 years.
During work (agriculture) or walking
No prodromal symptom
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28 month-old grandson presented to the hospital for fever and sepsis.
Tachycardia of 212 bpm
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Lidocaine 13 mg
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28 month-old grandson
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< SCN5A Gene Mutation Analysis >
SCN5A Gene Mutation : Detected
Indentified Mutation : c.3911C>T (p.Thr1304Met)
GENETIC VARIATIONS OBSERVED
-------------------------------------------------------------------------------------------------------
Exon# NT# BaseChange Codon# AA Chage Designation Mutation Type/Effect
-------------------------------------------------------------------------------------------------------
2 87 A > G 29 Ala>Ala A29A (Het) Polymorphism(rs6599230)
16 2695 T > C 899 Trp>Arg W899R (Het) Unclassified
17 3183 A > G 1061 Glu>Glu E1061E (Hom) Polymorphism(rs7430407)
22 3911 C > T 1304 Thr>Met T1304M (Het) Mutation (Known)
28 5457 T > C 1819 Asp>Asp D1819D (Het) Polymorphism(rs1805126)
------------------------------------------------------------------------------------------------------
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Brugada syndrome
SCN5A Gene Mutation :
c.3911C>T (p.Thr1304Met)
67/M
38/M
2/M
Syncope
VT during fever
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• Introduction as a clinical entity in 1992
• Electrocardiographically characterized by a distinct ST-segment
elevation in the right precordial leads
• Association with high risk for sudden death in young and healthy adults
• Manifests during adulthood, with a mean age of sudden death of 41 ±
15 years. (2 days old to 84 years old)
• 4% of all sudden deaths and 20% of sudden deaths in patients with
structurally normal hearts.
• Second only to automobile accidents as a cause of death among
young adults
Brugada syndrome
Second Consensus Conference Circulation 2005;111;659
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Difference between epicardial and endocardial membrane
action potential (AP) morphology
Shu J, et al. J Electrocard 2005;38:26
• The epicardial AP showed “spike and dome” pattern.
• Loss of epicardial AP dome shortens AP duration.
• A difference in action potential plateau amplitude
generates a transmural voltage gradient that
manifests as ST-segment displacement in surface
ECG.
Accelerated inactivation of Na channels and
predominance of transient outward K current (Ito)
to generate a voltage gradient in the RV layers
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Phase-2 reentry in the epicardium of an isolated canine right ventricular outflow
tract preparation having Brugada type ECG
Morita H, et al. Heart Rhythm 2007;4:66
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Three ECG repolarization patterns in the right precordial leads
• Type I : diagnostic for Brugada syndrome
coved-type ST segment elevation greater than 2 mm, followed by a
negative T wave in at least one right precordial lead (V1 to V3).
• Type II and type III : saddleback-shaped patterns, with a high initial augmentation
followed by an ST elevation greater than 2 mm for type II and less than 2 mm for
type III. suggestive of but not diagnostic for Brugada syndrome.
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Brugada syndrome is definitively diagnosed when a type 1 ST-segment
elevation is observed in >1 right precordial lead (V1 to V3)
and in conjunction with one of the following
: documented ventricular fibrillation (VF),
polymorphic ventricular tachycardia (VT),
a family history of sudden cardiac death at < 45 years old,
coved-type ECGs in family members,
inducibility of VT with programmed electrical stimulation,
syncope,
or nocturnal agonal respiration.
Diagnostic Criteria
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15, May, 2001 22, May, 2001 24, Aug, 2001
Dynamic change of ECG pattern in a Brugada syndrome patient
Park DW, et al. Circ J 2003; 67: 934
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Drug challenge test in Brugada syndrome
Baseline After flecainide
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Precipitating Factors
The ECG manifestations of Brugada syndrome are often concealed
but can be unmasked by sodium channel blockers,
a febrile state,
vagotonic agents,
α-adrenergic agonists,
β-adrenergic blockers,
tricyclic or tetracyclic antidepressants,
a combination of glucose and insulin,
hyperkalemia, hypokalemia,
hypercalcemia,
and alcohol and cocaine toxicity.
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• VF and sudden death in Brugada syndrome usually occur at rest and at night.
• Circadian variation of sympathovagal balance, hormones, and metabolic factors are
likely to contribute to this circadian pattern.
Circadian pattern of VF episodes in Brugada syndrome.
Second Consensus Conference Circulation 2005;111;659
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• Syncope and sudden death are caused by fast polymorphic
ventricular tachycardia or ventricular fibrillation.
• These arrhythmias appear with no warning.
• Treatment for symptomatic patients with Brugada syndrome is
needed.
• Patients presenting with Brugada syndrome ECG at baseline
conditions have an increased risk for sudden death and need risk
stratification.
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• Brugada syndrome is a genetically transmissible disease manifesting
as an autosomal dominant and age-dependent trait.
• More than 100 causative gene mutations have been identified,
mostly located on the SCN5A gene of the cardiac sodium channel.
• Further studies are needed to establish the underlying mechanism of
Brugada syndrome.
• The role of EPS in risk stratification of asymptomatic patients with
Brugada syndrome remains controversial.
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FINGER (France, Italy, Netherlands, Germany)
Brugada Syndrome Registry
• to evaluate the prognosis and risk factors of SCD in Brugada syndrome
patients
• 11 tertiary centers in 4 European countries
• 1,029 consecutive individuals (men; 72%), median age of 45 (35~55) years
• aborted SCD (6%); unexplained syncope (30%); asymptomatic (64%)
• median follow-up of 32 months, 51 cardiac events (5%, appropriate shock
44 patients, SCD 7 patients)
• Cardiac event rate per year; 7.7% in patients with aborted SCD,
1.9% in patients with syncope,
0.5% in asymptomatic patients
• Symptoms and spontaneous type 1 ECG were predictors of arrhythmic
events
FINGER Brugada Syndrome Registry Circulation. 2010;121:635
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FINGER Brugada Syndrome Registry Circulation. 2010;121:635
The presence of symptoms and a spontaneous type 1 ECG are the only independent
predictors of arrhythmic events.
FINGER (France, Italy, Netherlands, Germany) Brugada Syndrome Registry
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FINGER Brugada Syndrome Registry Circulation. 2010;121:635
Gender, family history of SCD, inducibility of ventricular tachyarrhythmias during EPS,
and presence of a mutation in the SCN5A gene have no predictive value.
FINGER (France, Italy, Netherlands, Germany) Brugada Syndrome Registry
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Absolute and annual event rate in the major Brugada syndrome registries
Napolitano C, Priori SG. Circulation. 2012;125:2027
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Devices
ICD - only established effective therapy
? Ablation or cryosurgery
? Pacemaker
Drugs
Amiodarone: does not protect
β-Blockers: do not protect
α-Adrenergic agonists (isoproterenol)
Phosphodiesterase inhibitors (cilostazol)
Class IC antiarrhythmics (flecainide, propafenone):contraindicated
Class IA antiarrhythmics
Procainamide: contraindicated
? Disopyramide
Quinidine (nonspecific Ito blocker)
? Tedisamil
Ito blockers: cardioselective and ion channel–specific
Therapy in Brugada Syndrome
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• No drug has been definitely proven effective in reducing the cardiac
arrest burden.
• Risk assessment is a key issue to tailor the use of ICD therapy.
• Annual incidence of cardiac arrest was between 1%/y and 2%/y.
• The event rate is time dependent with events peaking in the third to
fourth decade of life.
• The presence of a spontaneous type 1 ECG with history of
syncope could identify subjects who warrant an ICD.
• Genotype-phenotype correlation is scanty in Brugada syndrome.
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Second Consensus Conference Circulation 2005;111:659
FINGER Brugada Syndrome Registry Circulation. 2010;121:635
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• Risk stratification and treatment strategy for asymptomatic patients
with Brugada syndrome remain to be defined.
• Studies for follow-up of ICD therapy and risk stratification for sudden
cardiac death in Korean patients with Brugada syndrome are limited.
• Korea Survey of Brugada syndrome patients with ICD
• The objective of the Survey was
to evaluate the prognosis of Korean patients with Brugada
syndrome after implantation of ICD
and to search for predictor of adverse cardiac outcomes.
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• N=69 patients of Brugada syndrome with ICD implantation
• Jan 1998 ~ Apr 2012
• Male : 68, Female : 1
• 4 university hospitals
Asan Medical Center,
Chunnam National University Hospital,
Korea University Anam Hospital,
Samsung Medical Center
• Follow up duration: mean 59 ± 46 months
median 4.1 years (IQR 2.0-7.7)
Korea Survey of Brugada syndrome patients with ICD
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N (%)
n 69
Male gender 68 (99%)
Age 46 ± 14
FHx. of Brugada syndrome 4 (6%)
FHx. of SCD 13 (19%)
ECG ST elevation type
Type 1 44 (64%)
Type 2 18 (26%)
Type 3 3 (4%)
Clinical presentation
Cardiac arrest 38 (55%)
Syncope 17 (25%)
Presyncope 3
Palpitation 10
Chest pain 7
Nocturnal agonal respiration 6
Dyspnea 4
Baseline characteristics
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Cardiac arrest
Syncope
Asymptomatic17 명 (25%)
14 명 (20%)
38 명 (55%)
Indication for ICD implantation
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Clinical outcome
Cardiac event N (%)
Composite cardiac event 30 (44%)
Annual event rate 8.8%
Appropriate shock 19 (28%)
Annual event rate 5.6%
Inappropriate shock 14 (20%)
Hospitalization for cardiac cause 6 ( 9%)
Cardiac death 0
Follow up duration: mean 59 ± 46 months
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Appropriate shock : 19 (28%)
Inappropriate shock : 14 (20%)
Hospitalization for cardiac cause : 6 (9%)
Cardiac death : 0
Composite cardiac event free survival
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Appropriate shock free survival
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Composite cardiac event free survival
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Appropriate shock free survival
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Appropriate shock free survival
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Inappropriate shock
• 73 events in 14 patients (20%)
Cause of
inappropriate shock
Number of patients
AF, AFL 4
SVT 3
Abnormal sensing 2
Lead failure 2
NA 3
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• Brugada syndrome is electrocardiographically characterized by a distinct
ST-segment elevation in the right precordial leads.
• Manifests during adulthood, with a mean age of sudden death of 41 yrs
• Korean Brugada syndrome patients with ICD implantation : 69 patients
Composite cardiac events during mean follow up of 59 mo: 44%
Appropriate shock : 28%
Inappropriate shock : 20%
Hospitalization for cardiac cause : 9%
Cardiac death : 0
• Predictor of cardiac events : history of aborted cardiac arrest
• The presence of spontaneous type 1 ECG demonstrated no statistical
differences in cardiac event.
Summary