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26/06/2019
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National Cerebral and Cardiovascular Center
Brugada syndrome – nothing, Quinidine, ICD, or AblationWhat to do in the storm
6/13/2016Kenichiro Yamagata
National Cerebral and Cardiovascular Center, Japan
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
National Cerebral and Cardiovascular Center
Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation
with type 1 morphology ≥2 mm in ≥1 lead among the right precordial leads V1, V2,
positioned in the 2nd, 3rd or 4th intercostal space occurring either spontaneously
or after provocative drug test with intravenous administration of Class I
antiarrhythmic drugs.
2013, Heart Rhythm
National Cerebral and Cardiovascular Center
(Europace, 2017, 19, 665–694)
National Cerebral and Cardiovascular Center
Shanghai Score System for diagnosis of Brugada syndrome
ECG
Spontaneous type 1 Brugada ECG pattern at nominal or high leads 3.5
Fever-induced type 1 Brugada ECG pattern at nominal or high leads 3
Type 2 or 3 Brugada ECG pattern that converts with provocative drug
challenge
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Clinical History
Unexplained cardiac arrest or documented VF/polymorphic VT 3
Nocturnal agonal respirations 2
Suspected arrhythmic syncope 2
Syncope of unclear mechanism/unclear etiology 1
Atrial flutter/fibrillation in patients, 30 years without alternative etiology 0.5
Family History
First- or second- degree relative with definite BrS 2
Suspicious SCD (fever, nocturnal, Brugada aggravating drugs) in a first-
or second-degree relative
1
Unexplained SCD, 45 years in first- or second- degree relative with
negative autopsy
0.5
Genetic Test Result
Probable pathogenic mutation in BrS susceptibility gene 0.5
≥3.5 points: Probable/definite BrS2–3 points: Possible BrS2 points: Nondiagnostic
Score(requires at least 1 ECG finding)
J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge
(Europace, 2017, 19, 665–694)
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National Cerebral and Cardiovascular Center
Shanghai Score System for Diagnosis of Brugada SyndromeValidation of the Score System and Reclassification of the Patients
(Kawada et al., JACC CE 2018)
The Shanghai Score System for the diagnosis and risk stratification of patients with BrS
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
National Cerebral and Cardiovascular Center
Ⅰ
Ⅱ
Ⅲ
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
Brugada syndrome
Ⅰ
Ⅱ
Ⅲ
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
ICD is highly recommended
National Cerebral and Cardiovascular Center
Are we always happy with ICD when it saves life?
VF storm…
Brugada syndrome
National Cerebral and Cardiovascular Center
Pharmacological Treatment
Evaluate the precipitating factors• Fever• Hypokalemia
• Ishchemia• Drug
Catheter Ablation
How to treat Brugada Syndrome Storms
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National Cerebral and Cardiovascular Center
Pharmacological Treatment of BrS
• Quinidine →Ito block
• Isoproterenol →PKA activate→Increase Ica-L
• Cilostazol →PDE block→cAMP increase→Increase Ica-L
Quinidine or isoproterenol should be considered inpatients with Brugada syndrome to treat electrical storms(IIa)
Quinidine should be considered in patients who qualifyfor an ICD but present a contraindication or refuse it andin patients who require treatment for supraventricular
arrhythmias (IIa)(EHJ(2015) 36, 2793–2867)
National Cerebral and Cardiovascular Center
Pharmacological Treatment• Isoproterenol• Quinidine
• Cilostazole
Evaluate the precipitating factors• Fever• Hypokalemia
• Ishchemia• Drug
Catheter Ablation• Trigger• Substrate
How to treat Brugada Syndrome Storms
National Cerebral and Cardiovascular Center
Purkinje potentials
First report to succeeded eliminating PVCs and no recurrence of VF
Mapping and Ablation of Ventricular Fibrillation Associated
With Long-QT and Brugada Syndromes
Most BrS patients don’t have frequent PVCs
(Haissaguerre, Circulation. 2003;108:925-928.)
National Cerebral and Cardiovascular Center
Prevention of Ventricular Fibrillation Episodes in Brugada Syndrome by Catheter
Ablation Over the Anterior Right Ventricular Outflow Tract Epicardium
purple represents the longest duration (160 ms) during
sinus rhythm
• 8 out of 9 patients had normalized BrS type ECG• 9 out of 9 patients had no recurrence of VF events
(Nademanee et al., Circulation. 2011;123:1270-1279.)
National Cerebral and Cardiovascular Center
4ICS
43y.o. maleDiagnosed as BrS at 29 y.o.Implanted ICD for secondary prevention
Experienced VF storm and prescribed Quinidine
VF storm reccured 3 years after
Case
National Cerebral and Cardiovascular Center
Fragmented / delayed potential
Voltage map
RAO LAO
RAO LAO
<Epi>
<Endo>
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National Cerebral and Cardiovascular Center
Bordeline of FP area
Ablation site
Ablation site
Pre Post
No recurrence after 5years of f/u
National Cerebral and Cardiovascular Center
Electrical Substrate Elimination in 135 Consecutive
Patients With Brugada Syndrome
(Pappone et al., Circ Arrhythm Electrophysiol. 2017;10:e005053.)
Why does ablation work?
National Cerebral and Cardiovascular Center
Fibrosis, Connexin-43, and Conduction Abnormalitiesin the Brugada Syndrome
(Nademanee et al, JACC, VOL. 66, NO. 18, 2015)
Control BrS (BrS)In Vivo
BrS is associated with epicardial surface and interstitial fibrosis and reduced Connexin 43 gap junction
National Cerebral and Cardiovascular Center
Pharmacological Treatment• Isoproterenol• Quinidine
• Cilostazole
Evaluate the precipitating factors• Fever• Hypokalemia
• Ishchemia• Drug
Catheter Ablation• Trigger• Substrate
How to treat Brugada Syndrome Storms
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
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National Cerebral and Cardiovascular Center
How should we perform risk stratification for BrS?
Most supported risk factor
Other risk factors
Fragmented QRSEffective refractory period <200ms during EPSMale gender
Documented AFEPS
SCN5A mutation
Spontaneous type 1 ECG
HRS/EHRA/APHRS expert consensus statement
National Cerebral and Cardiovascular Center
NaV1.5 (SCN5A)
Nature Reviews Neuroscience 7, 548-562 (July 2006)
S5
S6
National Cerebral and Cardiovascular Center
BrS and SCN5A mutation
HRS, EHRA, and APHRS (2011)Expert consensus Statement on the State of Genetic Testing for the Channelopathises and Cardiomyopathies
Mutation-specific genetic testing is recommended for family members andappropriate relatives following the identification of the BrS-causative mutation in an
index case (Class I).
Comprehensive or BrS1 (SCN5A) targeted BrS genetic testing can be useful forany patient in whom a cardiologist has established a clinical index of suspicion forBrS based on examination of the patient’s clinical history, family history, and
expressed electrocardiographic phenotype (Class II).
Genetic testing is not indicated in the setting of an isolated type 2 or type 3Brugada ECG pattern (Class III).
The presence of a BrS-associated mutation does not impact the treatment ofan index case with BrS.
National Cerebral and Cardiovascular Center
BrS and SCN5A mutation
HRS, EHRA, APHRS (2013)Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia
Syndromes
SCN5A mutation has not been proven to be a risk marker in large studies. However, some specific types of mutations, such as those that result in atruncated protein, or some common SNPs, might have prognostic
significance.
National Cerebral and Cardiovascular Center
All SCN5A (+) SCN5A (-) P value
(n) 415 60 (14%) 355 (86%)
Age (years) 46 ± 14 44 ± 16 47 ± 13 0.210
Male Gender 403 (97%) 58 (97%) 345 (97%) 0.687
History of syncope
(without ACA) 99 (24%) 15 (25%) 84 (24%) 0.822
History of ACA 88 (21%) 15 (25%) 73 (21%) 0.437
Age of first syncopal
episode or ACA (years) 41 ± 16 34 ± 17 42 ± 15 0.013
Pore mutation of SCN5A 25 (42%)
FH of SCD 64 (15%) 11 (18%) 53 (15%) 0.500
ICD implantation 240 (58%) 37 (62%) 203 (57%) 0.515
Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada SyndromeA Japanese Multicenter Registry
(Yamagata et al., Circulation. 2017;135:2255–2270)
National Cerebral and Cardiovascular Center
Follow up (months)
20
40
60
80
100
0
20
40
60
80
100
0
0 100 200 300 0 100 200 300
nonpore-SCN5A (+)
P=0.110
SCN5A (-)
pore-SCN5A (+)
P=0.002
Pro
bability o
f Surv
ival (%
)
Overall Survival among All cases
SCN5A (-)
SCN5A (+)
P=0.017
SCN5A (-)
SCN5A (+)
P=0.017
SCN5A (-)
pore-SCN5A (+)
P=0.002
(Yamagata et al., Circulation. 2017;135:2255–2270)
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National Cerebral and Cardiovascular Center
SCN5A Mutations in Brugada Syndrome Are Associated with Increased Cardiac Dimensions and Reduced Contractility
(van Hoorn et al., 2012 | Volume 7 | Issue 8 | e42037)
SCN5A mutation in BrS
National Cerebral and Cardiovascular Center
Comparison of Long-Term Follow-Up of Electrocardiographic
Features in Brugada Syndrome Between the SCN5A-Positive
Probands and the SCN5A-Negative Probands
(Yokokawa et al., Am J Cardiol 2007; 100:649–655)
SCN5A mutation in BrS
National Cerebral and Cardiovascular Center
✓Diagnosing Brugada syndrome
✓Treating Brugada syndrome
✓SCN5A mutation in Brugada syndrome
Today’s Talk
National Cerebral and Cardiovascular Center
• Managing BrS VF storm is important
• Ablation can be a curable therapy for BrS
• BrS with SCN5A mutation can be a risk for cardiac event
Conclusion
National Cerebral and Cardiovascular Center
Thank you for your attention!!!
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