日本のBrugada症候群患者の予後予測因子

a：突然死の家族歴
b：早期再分極
出典
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1: Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3.
著者: Kamakura S, Ohe T, Nakazawa K, Aizawa Y, Shimizu A, Horie M, Ogawa S, Okumura K, Tsuchihashi K, Sugi K, Makita N, Hagiwara N, Inoue H, Atarashi H, Aihara N, Shimizu W, Kurita T, Suyama K, Noda T, Satomi K, Okamura H, Tomoike H; Brugada Syndrome Investigators in Japan.
雑誌名: Circ Arrhythm Electrophysiol. 2009 Oct;2(5):495-503. doi: 10.1161/CIRCEP.108.816892. Epub 2009 Aug 2.
Abstract/Text: BACKGROUND: The prognosis of patients with saddleback or noncoved type (non-type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non-type 1 ECG and those with coved (type 1) Brugada-pattern ECG.
METHODS AND RESULTS: A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation > or = 1 mm in leads V(1)-V(3) were divided into 2 ECG groups-type 1 (245 probands) and non-type 1 (85 probands)-and were prospectively followed for 48.7+/-15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non-type 1: 10.6%, probands with syncope; type 1: 0.6%, non-type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non-type 1: 0%). Family history of sudden cardiac death at age <45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters.
CONCLUSIONS: The long-term prognosis of probands in non-type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation.
Circ Arrhythm Electrophysiol. 2009 Oct;2(5):495-503. doi: 10.1161/CIRC...

Brugada症候群（特発性心室細動）

a：12誘導心電図　V2誘導でtype 1心電図（coved型ST上昇）を呈する。
b：心室細動
出典
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1: 著者提供

Brugada症候群の原因遺伝子とイオンチャネル機能

Brugada型心電図（V1-V6誘導心電図）

  1. a：安静時から、V2誘導でtype 1心電図（coved型ST上昇）を呈する。
  1. b：ピルジカイニド 30mg静注後、V2誘導でtype 1心電図を呈している。
  1. c：高位（第3）肋間のV2誘導で、type 1心電図を呈している。
出典
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1: 著者提供

Brugada症候群の薬物療法

参考文献：
Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013 Dec;10(12):1932-63. doi: 10.1016/j.hrthm.2013.05.014. Epub 2013 Aug 30. Review. PubMed PMID: 24011539.
出典
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1: 著者提供

Brugada様ST上昇を来す病態

[ID0621]:Brugada様ST上昇作用のある薬剤（薬剤誘発性Brugada症候群）

Brugada症候群発端者の全症例における生存曲線

A：SCN5A変異群（SCN5A(+)）と非SCN5A変異群（SCN5A(-)）の比較
SCN5A(+)でSCN5A(-)に比べ、有意に多くの致死性イベントを認めた。
B：SCN5A変異群において中心孔領域にSCN5A変異を有する群（pore-SCN5A(+)）、それ以外の部位に変異を有する群（nonpore-SCN5A(+)）、非SCN5A変異群（SCN5A(-)）の比較
SCN5A(+)の中でも、特にpore-SCN5A(+)で有意に致死性イベントを多く認めた。
出典
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1: Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.
著者: Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, Yamagishi M, Makita N, Sakurada H, Tanaka T, Shimizu A, Hagiwara N, Kishi R, Nakano Y, Takagi M, Makiyama T, Ohno S, Fukuda K, Watanabe H, Morita H, Hayashi K, Kusano K, Kamakura S, Yasuda S, Ogawa H, Miyamoto Y, Kapplinger JD, Ackerman MJ, Shimizu W.
雑誌名: Circulation. 2017 Jun 6;135(23):2255-2270. doi: 10.1161/CIRCULATIONAHA.117.027983. Epub 2017 Mar 24.
Abstract/Text: BACKGROUND: The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias.
METHODS: This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations.
RESULTS: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (SCN5A (-), n=355), probands with SCN5A mutations (SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P=0.013), had a higher positive rate of late potentials (89% versus 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A (+) versus SCN5A (-): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P<0.001).
CONCLUSIONS: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

© 2017 American Heart Association, Inc.
Circulation. 2017 Jun 6;135(23):2255-2270. doi: 10.1161/CIRCULATIONAHA...

Brugada症候群の心電図（Wildeの分類）

参考文献：
Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA; Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. 2002 Nov 5;106(19):2514-9. doi: 10.1161/01.cir.0000034169.45752.4a. PMID: 12417552.（Figure 1）

Brugada様ST上昇作用のある薬剤（薬剤誘発性Brugada症候群）

内向きNa+・Ca2+電流を減少または外向きK+電流を拡張させる薬剤は、Brugada様ST上昇を増強または顕性化する。
出典
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1: 著者提供

Brugada症候群のVF発作時のプロタノールの有効性

a：心室細動
b：Coved型ST上昇
c：プロタノール（0.002 μg/kg/分）
d：プロタノール（0.004 μg/kg/分）
出典
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1: 著者提供

欧州4カ国11施設のBrugada症候群患者の自然予後

年間心事故発生率は、心室細動・心肺停止既往例で7.7％、失神既往例で1.9％、無症候例で0.5％である。
出典
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1: Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.
著者: Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, Babuty D, Sacher F, Giustetto C, Schulze-Bahr E, Borggrefe M, Haissaguerre M, Mabo P, Le Marec H, Wolpert C, Wilde AA.
雑誌名: Circulation. 2010 Feb 9;121(5):635-43. doi: 10.1161/CIRCULATIONAHA.109.887026. Epub 2010 Jan 25.
Abstract/Text: BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry.
METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events.
CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.
Circulation. 2010 Feb 9;121(5):635-43. doi: 10.1161/CIRCULATIONAHA.109...

日本のBrugada症候群患者の予後予測因子

a：突然死の家族歴
b：早期再分極
出典
imgimg
1: Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3.
著者: Kamakura S, Ohe T, Nakazawa K, Aizawa Y, Shimizu A, Horie M, Ogawa S, Okumura K, Tsuchihashi K, Sugi K, Makita N, Hagiwara N, Inoue H, Atarashi H, Aihara N, Shimizu W, Kurita T, Suyama K, Noda T, Satomi K, Okamura H, Tomoike H; Brugada Syndrome Investigators in Japan.
雑誌名: Circ Arrhythm Electrophysiol. 2009 Oct;2(5):495-503. doi: 10.1161/CIRCEP.108.816892. Epub 2009 Aug 2.
Abstract/Text: BACKGROUND: The prognosis of patients with saddleback or noncoved type (non-type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non-type 1 ECG and those with coved (type 1) Brugada-pattern ECG.
METHODS AND RESULTS: A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation > or = 1 mm in leads V(1)-V(3) were divided into 2 ECG groups-type 1 (245 probands) and non-type 1 (85 probands)-and were prospectively followed for 48.7+/-15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non-type 1: 10.6%, probands with syncope; type 1: 0.6%, non-type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non-type 1: 0%). Family history of sudden cardiac death at age <45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters.
CONCLUSIONS: The long-term prognosis of probands in non-type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation.
Circ Arrhythm Electrophysiol. 2009 Oct;2(5):495-503. doi: 10.1161/CIRC...

Brugada症候群（特発性心室細動）

a：12誘導心電図　V2誘導でtype 1心電図（coved型ST上昇）を呈する。
b：心室細動
出典
img
1: 著者提供