prognosis of brugada syndrome patients with icd in korea
TRANSCRIPT
Prognosis of Brugada syndrome
patients with ICD in Korea
Young Keun On, MD, PhD, FHRS
Samsung Medical Center
Sungkyunkwan University School of Medicine
• 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.
67 year-old gentleman complained of recurrent syncope
for 5 years.
During work (agriculture) or walking
No prodromal symptom
28 month-old grandson presented to the hospital for fever and sepsis.
Tachycardia of 212 bpm
Lidocaine 13 mg
28 month-old grandson
< 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)
------------------------------------------------------------------------------------------------------
Brugada syndrome
SCN5A Gene Mutation :
c.3911C>T (p.Thr1304Met)
67/M
38/M
2/M
Syncope
VT during fever
• 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
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
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
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.
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
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
Drug challenge test in Brugada syndrome
Baseline After flecainide
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.
• 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
• 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.
• 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.
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
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
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
Absolute and annual event rate in the major Brugada syndrome registries
Napolitano C, Priori SG. Circulation. 2012;125:2027
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
• 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.
Second Consensus Conference Circulation 2005;111:659
FINGER Brugada Syndrome Registry Circulation. 2010;121:635
• 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.
• 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
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
Cardiac arrest
Syncope
Asymptomatic17 명 (25%)
14 명 (20%)
38 명 (55%)
Indication for ICD implantation
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
Appropriate shock : 19 (28%)
Inappropriate shock : 14 (20%)
Hospitalization for cardiac cause : 6 (9%)
Cardiac death : 0
Composite cardiac event free survival
Appropriate shock free survival
Composite cardiac event free survival
Appropriate shock free survival
Appropriate shock free survival
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
• 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