[SCD-FORUM] 际心脏猝死在线论坛 59E RE：询问评估一Brugada患者的风险 Dr. Perez Riera

[SCD Symposium]

Translator: NINGNING ZHUANG, Research Associate,University of Utah  
School of Medicine,CVRTI



国际心脏猝死在线论坛 [SCD-FORUM] 59E RE：询问评估一 
Brugada患者的风险

Dr. Perez Riera



★提问来自菲律宾马尼拉University of Santo Tomas的MARCELLUS  
FRANCIS RAMIREZ,

首先祝贺本次国际心脏猝死在线论坛非常成功地举 
办。我最近的一个病例：男性，三十五岁左右，心电 
图示I 型Brugada’s 表现，心内电生理检测未能诱发室 
速，无家族猝死史，现职是海员。请教各位专家评估 
一下该Brugada患者猝死的风险及能否从事目前工作。



★专家答复来自巴西圣保罗Dr. Andrés Ricardo Pérez Riera

该患者有心脏猝死（SCD）的高危因素。此病例来自 
Brugada病高发国家，在菲律宾，本病称为Bangungut(睡眠 
猝死时尖叫)。马尼拉的死亡证明中对于难以解释的 
夜间猝死综合征(SUDS)调整后，掩盖了发病率增加的事 
实。SUDS是东南亚地区性现象，可能由环境因素所 
至，因为死亡有季节性，死亡率随临床观测时段累计 
增长，马尼拉外来人口中SUDS比本地人口多，男性亚 
裔青年高发。这种死亡在日本称为Pokkuri（夜间意外 
猝死）,在菲律宾为Bangungut,在美国（疾病控制中心） 
称为SUDS(sudden unexplained death syndrome)。SUDS和 BRUGADA 是 
同一种病。http://www.cdc.gov/mmwr/preview/mmwrhtml/00001278.htm



本例患者为男性，有自发 I 型Brugada’s心电图表现,男 
性预示有恶性的倾向。无症状个体伴自发ECG I 型 
Brugada’s 表现一般在27-29个月的随访期内出现心律失 
常。Brugada综合征心电图的改变遵照首届欧洲共识报告 
1，即存在右胸前导联V1－V3伴有ST段抬高的复极异 
常，特征性的ST段抬高表现为穹窿样，抬高>2mm 
（0.2mV），伴随T波倒置。或（见如下提议的I 型分类） 
1A穹窿型或1B三角型：http://www.scd-symposium.org/files/ 
clasification.pdf



下列情形表明BrS患者预后差：

1)，患者有自发的“穹窿型“ECG特征性改变(IA 或IB型)；

2)，关于PES（Programmed Electrical Stimulation,程序电刺激） 
电生理检查中可诱导持续室速的患者：目前认为PES在 
鉴别自发室颤发作的高危患者，还没有统一意见。。 
BRUGADA兄弟认为这类患者应接受ICD2－3。Priori等人的一 
项研究中，用Kaplan-Meier总结了200例PES测试患者的无心 
脏事件时间，PES可诱导出室速或室颤的患者和其自发 
室颤发作的危险性无相关性，(4) 换句话说，PES可诱 
导出室速或室颤的患者与PES未能诱导出室速或室颤的 
患者比较，前者心脏事件的危险性并不增加。 Eckardt 
等人的一项随访(平均40个月)研究入选212例患者，皆有 
Brugada I型ECG表现，其中125例(59%)为自发性，其余是用I 
类抗心律失常药物试验后出现。作者证实58%无临床症 
状， 31%有过一次或以上的晕厥，11%为室颤经抢救复 
苏的病例。有晕厥或心脏骤停复苏的病史者提示预后 
不良。ST段抬高幅度在有症状患者为2.3mm，比无症状 
患者(1.9mm)要高，(个人认为这在本文中并不重要，因为 
Brugada I型ECG表现抬高为2mm)；无症状患者的心脏事件 
发生率很低，PES不能准确预测病情发展。该文章拟明 
确一个在Priori和Brugada两个研究组间一直有争议的问 
题，就是PES的预测价值如何。这篇文章与Priori意见一 
致，关于BrS患者心脏事件的危险性，数据中并不一 
致，取决于不同的受试患者人群。该文章描述了对一 
大样本明确诊断BrS的患者的长期随访，并分析了PES的 
预测价值。与既往的有关文章不同，这项研究没能显 
示PES的预测价值。无症状患者的心律失常事件危险度 
很低，说明这类患者比原来认为的风险要低。这项临 
床观察可能对BrS患者的诊断优先次序（优先治疗）和 
药物治疗手段有一定影响。

3)，男性一般预后差

4)，对于有症状的患者，如晕厥或心脏骤停复苏后， 
预示预后不良。

5)，自发的V1-V3导联ST段抬高伴晕厥史是Brugada患者心 
脏事件病发的一个最强预测标志。

6)，在I型ECG表现的Brugada患者，自发的ST段改变是一个 
很高危的因素对于日后心脏事件的发生。在有记录的 
晕厥史，家族猝死史，和/或晚电位检查等可增加其 
评估价值。6

7)，晕厥史或SCD史，有自发的Brugada-1型穹窿型ECG表 
现，男性，均预示有恶性的倾向。SCD家族史，SCN5A基 
因突变， EPS不能作为治疗Brugada患者的指导。7

8)，SCN5A基因缺陷与心脏事件危险性无相关性，基因 
检测可用于诊断但无助于危险性分层。

Brugada型ECG表现比出现临床症状的BrS更常见。虽然介 
入性电生理诊断被推荐用于危险性分层，其价值仍有 
争议，非介入技术不失为有用的方法。IKEDA6 用非介 
入技术对无心脏事件史的Brugada型ECG表现的患者长期 
随访。入选124例患者，预后指征有年龄，性别，SCD家 
族史，晕厥史，自发穹窿ST段升高，最大ST段升高幅 
度，自发ST段演化，平均QRSd， 最大QT间期，QT离散度， 
SA-ECG测LP, TWA。 在124名患者中，20例在参加随访前即有 
ICD。在40+/-19月的随访中，12例(9.7%)到达随访终点(SCD或 
VT)。上述12项指标中，SCD家族史、晕厥史、自发穹窿样 
ST段抬高、自发ST段演化，LP晚电位，有重要意义。多 
因素分析表明自发ST段演化有最重要意义(相对危险度 
9.2,P=0.036)。将自发ST段演化和其它有意义的指标结合 
使用会有更高的预测价值(43-71%)。作者得到的结论 
是: 在I型ECG表现的Brugada患者，自发的ST段改变是一个 
很高危的因素对于日后心脏事件的发生。在有记录的 
晕厥史，家族猝死史，和/或晚电位检查等可增加其 
评估价值。



References:

1) Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R,  
Brugada P, Corrado D, Hauer RNm Kass RS, Nademanee K, Priori SG,  
Towbin JA. Proposed diagnostic criteria for the Brugada syndrome Eur  
Heart J 2002; 23:1648-1654.

2) Brugada P, Brugada R, Mont L, Rivero M, Geelen P, Brugada J.  
Natural history of Brugada syndrome: the prognostic value of  
Programmed electrical stimulation of the heart. J Electrophysiol   
2003;  14: 455-457.

3) Brugada J, Brugada R, Brugada P. Right bundle-branch block and ST- 
segment elevation in leads V1 through V3: a marker for sudden death  
in patients without demonstrable structural heart disease.  
Circulation. 1998; 97: 457–460.

4) Priori SG, Napolitano C, Gasparini M, et al. Natural history of  
Brugada syndrome: insights for risk stratification and management.  
Circulation. 2002; 105: 1342-1347.

5) Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R,  
Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, Lemarec  
H, Bocker D, Wilde AA. Long-Term Prognosis of Individuals With Right  
Precordial ST-Segment-Elevation Brugada Syndrome.Circulation. 2005;  
111: 257-262; 111: 257-263.

6) Ikeda T, Takami M, Sugi K, Noninvasive risk stratification of  
subjects with a Brugada-type electrocardiogram and no history of  
cardiac arrest. Ann Noninvasive Electrocardiol. 2005; 10:396-403.

7) Gehi AK, Duong TD, Metz LD, et al. Risk stratification of  
individuals with the brugada electrocardiogram: a meta-analysis. J  
Cardiovasc Electrophysiol. 2006; 17:577-583.

8) Priori SG, Napolitano C, Gasparini M, et al. Natural history of  
Brugada syndrome: insights for risk stratification and  management.  
Circulation. 2002; 105: 1342-1347.





[SCD-FORUM] 59E RE: Brugada patient. Can he work? Dr. Perez Riera



Dear Marcellus Francis Ramirez from Mannila Philippines: Here Andrés  
Ricardo Pérez Riera from Sao Paulo Brazil answer.  I think that your  
patient has high risk of SCD.

First dear colleague you live in a Country were the disease is  
endemic. In Philippines, the entity is known as Bangungut (wailing  
followed by SCD during sleep)   The death  certificate classification  
of sudden unexplained nocturnal deaths (SUDS) in Manila has changed  
considerably, obscuring an increase in incidence. SUDS appears to be  
a regional phenomenon in Southeast Asia and environmental causes are  
likely because the deaths are seasonal, increased over the timespan  
studied, and are more common among migrants to Manila than among  
those born there. A high incidence of SUDS has been reported among  
young Asian males. These deaths are known as Pokkuri in Japan,  
Bangungut in the Philippines and SUDS in the USA. SUDS AND BRUGADA  
DISEASE ARE THE SAME DISEASE.

You say that the patient has spontaneous ECG type 1 pattern and  
additionally he belongs to male gender. Male gender predicts a more  
malignant natural history.

Asymptomatic individuals with a spontaneous abnormal type 1 ECG  
developed an arrhythmic event during a mean follow-up period of only  
27±29 months. A "spontaneous pattern" is defined as an ECG showing  
the patterns established for the first European Consensus about the  
syndrome (1): presence of  repolarization disorders occurred in the  
right precordial leads (V1 and V2) or in the anteroseptal wall (V1 to  
V3) with ST-segment elevation coved to the top  “coved type” or  
type 1A of my classification or rectilinear (type 1B of my  
classification) equal or mayor than 2mm (0.2mV), and followed by  
negative T wave (Brugada phenotype).

See the classification

http://www.scd-symposium.org/files/clasification.pdf

The following are markers of a poor prognosis in BrS patients:

1) Patients with an a spontaneously abnormal ECG type 1 pattern  
(Types 1A or 1B);

2) Patients with inducibility of sustained ventricular arrhythmias at  
PES: concensus does not exist on the value of PES to identify the  
subjects with risk of spontaneous occurrence of VF.  Brugada brothers  
think that theses patients should receive an ICD.(2-3) On the other  
hand,  Priori et al from 200 patients using the life-table method of  
Kaplan-Meier used to define the cardiac arrest-free interval in  
patients undergoing PES failed to demonstrate an association between  
PES inducibility and spontaneous occurrence of VF(4) ; Eckardt et al  
studied during a mean follow-up of 40 months a numerous universe of a  
collaborative large cohort 212 individuals who presented Brugada type  
1 electrocardiographic pattern, from which 125 (59%) was spontaneous,  
and the rest only after pharmacological test with a class I drug. The  
authors verified that 58% were asymptomatic; 31% had suffered >/=  
1episodes of syncope with unknown origin and 11% had been  
resuscitated from a VF episode (aborted sudden death).  A history of  
syncope or aborted sudden death was predictor of adverse outcome. The  
degree of elevation of the T segment was greater between symptomatic  
individuals: 2.3 mm higher than asymptomatic ones (mean 1.9 mm ???: I  
think that this is a byes of the manuscript because type 1 is 2mm).  
In the latter, it was observed that the incidence of events was very  
low, and PES had a very low accuracy in predicting evolution. This  
paper attempts to clarify the controversial issue, which still  
persists, between Priori's group and Brugada's group, regarding the  
predictive value of PES, agreeing with the former. The data regarding  
the risk of events in patients with BrS are controversial and depend  
on the cohort of patients studied. This collaborative paper describes  
long-term follow up of a large cohort of well-identified BrS patients  
as well as explores predictive value of PES. In contrary to some  
previous papers on the topic, in this study the authors could not  
demonstrate significant prognostic value of PES testing. The risk of  
arrhythmic events in asymptomatic patients is very low indicating  
that they could be considered as patients of much lesser risk than it  
was previously considered. This observation might have impact on both  
diagnostic triage and therapy approach in BrS patients  
(pharmacological approach).

3)Male gender predict a more malignant natural history;

4)Symptomatic patients: A history of syncope or aborted sudden death  
is predictor of adverse outcome.

5)Spontaneous ST-segment elevation in leads V1 through V3 combined  
with the history of syncope is a powerful marker to identify  
individuals who had cardiac arrest.

6)A spontaneous change in ST segment is associated with the highest  
risk for subsequent events in subjects with a Brugada-type 1 ECG. The  
presence of syncopal episodes, a history of familial sudden death,  
and/or LP may increase its value (6).

7)A history of syncope or SCD, the presence of a spontaneous Type 1  
Brugada ECG, and male gender predict a more malignant natural  
history. The use of a family history of SCD, the presence of an SCN5A  
gene mutation, or EPS to guide the management of patients with a  
Brugada ECG is not supported(7);

8)A genetic defect on the SCN5A gene is not associated with a higher  
risk of events, suggesting that genetic analysis is a most useful  
diagnostic parameter but it is not helpful for risk stratification(8).

The Brugada phenotype ECG) is much more prevalent than the manifest  
BrS. Although invasive electrophysiologic investigations have been  
proposed as a risk stratifier, their value is controversial, and  
alternative noninvasive techniques may be preferred.

Ikeda et al (6) sought a noninvasive strategy to detect a high-risk  
group in a long-term follow-up study of subjects with a Brugada-type  
ECG, and no history of cardiac arrest. The study enrolled 124  
consecutive subjects with a Brugada-type ECG. Prognostic indices  
included: age; sex, a family history of SCD, syncopal episodes, a  
spontaneous coved-type ST-segment elevation, maximal magnitude of ST- 
segment elevation, a spontaneous change in ST segment, a mean QRSd,  
maximal QT interval, QT dispersion, LPs by SA-ECG, and TWAs. Of the  
124 subjects, 20 consenting subjects had an ICD before follow-up.  
During a 40 +/- 19-month follow-up, 12 subjects (9.7%) reached one of  
the endpoints (SCD or VT). Of the 12 risk indices, a family history  
of SCD, syncopal episodes, a spontaneous coved-type ST-segment  
elevation, a spontaneous change in ST segment, and LP had significant  
values. In multivariate analysis, a spontaneous change in ST segment  
had the most significance (a relative hazard, 9.2; P = 0.036).  
Combined assessment of this index and other significant indices  
obtained higher positive predictive values (43-71%). The authors  
concluded that a spontaneous change in ST segment is associated with  
the highest risk for subsequent events in subjects with a Brugada- 
type ECG. The presence of syncopal episodes, a history of familial  
sudden death, and/or LP may increase its value.



All the best

Andrés Ricardo Pérez Riera.

Chief of Electro-Vectocardiology Sector of the Discipline of   
Cardiology, ABC Faculty of Medicine (FMABC), Foundation of ABC  
(FUABC) - Santo André -  Sao Paulo - Brazil. Rua Sebastiao Afonso   
885 - Zip Code: 044417-100- Jardim Miriam   S.P  Brazil- Phone:
--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee