New electrocardiographic criteria to differentiate the Type-2B rugad a pattern from electrocardiogram of healthy athletes with r′-wave in leads V1/V2

●心電學(xué)英語

New electrocardiographic criteria to differentiate the Type-2B rugad a pattern from electrocardiogram of healthy athletes with r′-wave in leads V1/V2

TheType-2Brugada pattern presents characteristically an r′-wave thatmay be confused with other ECG patterns that also present an r′-wave in leads V1~V2including incomplete right bundle branch block(IRBBB), pectus exacavatum,arrhythmogenic right ventricular dysplasia(ARVD),and athletes′ECG.The differential diagnosisstill remains challenging.Majorefforts tohelp the clinician to distinguish these ECG morphologies have been pursued Chevallier et al.and Ohkubo etal. have described that the angle formed between the upslope of the S-wave and the downslope of the r′-wave(βangle)was the bestway to differentiate the Type-2 Brugada pattern from IRBBB.Aβ-angle cut-off of 58°yielded a positive predictive value of 73%and a negative predictive value of 87%in the Chevallier study.However,obtaining the proper β-anglemeasurementmay be difficult and noteasy to perform in clinical practice leading to misdiagnosis. Corrado et al.have also described an index based on the slope of the first80ms of the ST-segment in leads V1~V2that is of ascendant direction in athletes and of descendentdirection in Type-2 Brugada pattern,which may be also useful for differential diagnosis.However, recognition of the end of the QRS in leads V1~V2may not be easy in many cases of Type-2 Brugada pattern, and furthermore,sometimes the J point do not always coincide with the high take-off of the QRS in those leads1.

The aim of the present study was to assess the diagnostic accuracy of new ECG criteria to distinguish between the Type-2 Brugada pattern and healthy athletes with an r′-wave pattern in leads V1~V2.

Methods

A retrospective study was carried out comparing the surface ECG of 50 patients with confirmed Brugada syndrome(presenting with syncope and positive sodium blocker drug challenge)and Type-2 Brugada pattern vs. 58 healthy athletes with no family history of sudden death and no previous syncope or history of ventricular tachyarrhythmias,presenting with an r′-wave in leads V1~V2.

Surface12-lead electrocardiograms were recorded, placing leads V1~V2in the fourth intercostal space. Electrocardiograms were blindly analyzed by two different investigators.The characteristics of the r′-wave and the isoelectric line were measured in all QRS-T complexes in leads V1~V2in a 10 s ECG recording.We added for each beat with an r′-wave (Figure 1A part A)two segments that followed the up-slope and downslope of the r′-wave(Figure 1A part B)and one segment that followed the isoelectric line (Figure1A partC).

We measured the new three criteria(i)the duration of the base of the triangle between the upslope and the downslope of the r′-wave at 0.5 mV from the high take-off(Figure 1C,part A),(ii)the duration of the base of the triangle at the isoelectric line,and(iii)the ratio ofbase/height of the triangle formed by the upslope and the downslope of the r′-wave at the isoelectric line (Figure 1C,part B).We also measured theβangle,an angle formed between the r′-wave upslope and the downslope coined by Chevallier et al.(Figure1C,partC).

All measurements were calculated from both leads V1and V2.The mean value of the different measurements from the beats was computed for each lead and patient.

To improve the feasibility and reproducibility of the method,combinations of the same parameters in leads V1~V2were analyzed.It was considered that the test was positive for the Brugada pattern when the criterion was met for at least one of the two leads.The absence of r′-wave in a single lead was considered as a negative result in this lead.

Figure 1(A)Segment location performed by the observers.(A)Original signal.(B)Segment location at upslope and downslope of r′-wave.(C)Segment location at the isoelectric line.(B)Segment location for scale measurement from the original grid.(C)Measurements extracted from located segments by the analysts—(A) the duration of the base of the triangle at0.5mV from r′-wave high take-off,(B)Height and duration of the triangle at the isoelectric line,(C)angle from Swave upslope and r′downslope (βangle).

Figure 2 Two examples of healthy athletes ECG.(A)Healthy athlete with ST-T elevation and r′-wave but with a base of the triangle at 0.5mV measuring 40ms(1mm).(B)Electrocardiogram of a healthy athlete with similar ST-T morphology and the base of triangle measuring80ms(2mm).

Results

The duration of the base of the triangle at0.5mV from the high take-off,the duration of the base of the triangle at the isoelectric line,and the ratio of the base/height of the triangle formed by the upslope and the downslope of the r′-wave at the isoelectric line were significantly higher in patients with confirmed Brugada Syndrome and Type-2 Brugada ECG pattern than in the healthy athlete group.Figures 2 and 3 show how the base of the triangle of r′-wave at0.5mV from the high take-off differs between Type-2 Brugada pattern(＞160ms,4mm)and healthy athletes(＜160 ms,4 mm)even presenting similar ST-T morphology. Receiver-operating characteristic curves showed that the AUC for the duration of the base of the triangle of r′-wave at 0.5 mV from the high take-off for lead V1was 0.955 and for lead V20.944;the duration of the base of the triangle at the isoelectric line for lead V1was 0.907 and for lead V20.938;the triangle base/height ratio for lead V1was 0.940 and for lead V20.944;and theβangle for lead V1was 0.957 and for lead V20.952.

Discussion

Brugada syndrome is an inherited heart disease produced by inactivation of the sodium channels in the right ventricle,which can present polymorphic ventricular tachycardia and ventricular fibrillation.

Figure 3 Two examples of Type-2 Brugada ECG pattern.(A)Type-2 Brugada pattern with the base of the triangle at0.5mV,measuring 184ms(4.6mm).(B)Type-2 Brugad a pattern with base of the triangle at 0.5mV measuring 188 ms(4.7mm).

The importance of electrocardiogram for the diagnosis of Brugada syndrome

The ECG is the hallmark diagnostic test in Brugada syndrome.Proper interpretation of the r′-wave characteristics in leads V1~V2may be crucial for differentiating benign ECG patterns from Type-2 Brugada pattern.

Other inherited diseases such as arrhythmogenic right ventricular dysplasia have also been considered in the differential diagnosis,but usually the ECG characteristics in leads V1~V2do not depicta clear r′-wave(epsilon wave is usually separated from the QRS), no clear ST-segment elevation and symmetric negative T-waves are usually seen in leads V1~V3.

The differential diagnosis of Type-2 Brugada pattern and electrocardiogram of athletes

It is of utmost importance to distinguish the Type-2 Brugada pattern from r′-wave patterns in healthy athletes.The Type-2 Brugada ECG pattern is characterized by a positive r′-wave deflection at the QRS-ST junction in leads V1~V2with a shallow down slope of descendent arm,with minimal or no reciprocal changes in other leads.On the contrary,the r′-wave seen in incomplete RBBB presents a fast down slope due to early conduction delay in the right bundle.For some authors,the coved QRS-ST pattern in Type-1 or the r′-wave in Type-2 Brugada patterns may not indicate only delayed RV activation,but also early repolarization and J-point elevation.The downsloping ST-segment in the′coved′type is followed by a negative T-wave due to voltage gradient at the end of repolarization,as a consequence of delayed action potential duration that overcomes the duration of the endocardium action potential.On the contrary,an inverted voltage gradient in Type-2 Brugada pattern explains the positivity of the T-wave that is seen frequently in the Type-2 Brugada pattern.

The importance of new electrocardiogram criteria to diagnose Type-2 Brugada pattern

In this study,we described new electrocardiographic criteria to discriminate the Type-2 Brugada pattern from healthy athletes with r′-wave in leads V1~V2.All three new criteria demonstrated high diagnostic yield to identify patients with true Brugada syndrome which are not superior to theβ-angle criterion described by Chevallier et al.,and therefore may be used in addition or as an alternative to it.Furthermore,its real value should be also tested in a prospective study.This author found that theβangle at58°cut-offyielded a positive predictive value of73%and a negative predictive value of 87%.Our findings suggest that theβ-angle best cut-off value is lower than that in the Chevalier series (≥36.8°).One of the reasons for the discrepancy could be related to the fact that obtaining the properβ-angle measurement is not easy and inter-intrapersonal variation may be high.

In our study,the three new electrocardiographic criteria are based on the characteristics of the r′-wave. The duration of the base of the triangle formed by ascendant and descendent arms of r′-wave at0.5mV from the high take-off was the easiest to measure andmay be useful in clinical practice.The duration equal or greater than 160ms(4mm)in V1and/or V2identifies patients with Brugada patterns.The other two parameters,duration of the base of the triangle at the isoelectric line≥60ms and the ratio of duration/height of those triangle at the isoelectric line≥0.8,also demonstrated high sensitivity and specificity,similar to or higher than thatobtained with theβangle.

In this study,we have demonstrated the value of these criteria for the differential diagnosis between Type-2 Brugada pattern and healthy athletes with r′wave in leads V1~V2.This remains a challenge to demonstrate whether these new parameters are useful to distinguish the Type-2 Brugada pattern from other entities depicting r′-wave in leads V1~V2.

It is very important to bear in mind that the surface ECG recording,discovered more than 100 years ago by Einthoven,may still provide such interesting information 20 years after the discovery of the syndrome.It may be useful in the stratification of risk,a very important advantage from a clinical and patient management point of view.

詞匯

arrhythmogenic n.致心律失常的

dysp lasia n.發(fā)育不全，發(fā)育不良

pursue v.追,追趕,繼續(xù),追求,追隨

misdiagnosis n.錯(cuò)誤的診斷

feasibility n.可行性

reproducibility n.再生產(chǎn),重復(fù)性

hallmark n.純度印記,標(biāo)志

interpretation n.解釋,表現(xiàn),口譯,表演,翻譯

crucial adj.決定性的,十字形的,嚴(yán)酷的

endocardium n.心內(nèi)膜

discrim inate adj.&v.有區(qū)別的,著名的;區(qū)別,區(qū)分

depict v.描畫,描繪,描寫

注釋

1.take-off醫(yī)學(xué)文獻(xiàn)中多指“起點(diǎn)，起始”，如The take-off of the right coronary artery is quite variable.右冠狀動(dòng)脈的起始變化很大。Tissue isolated from the sinoatrial node center shows spontaneous activity and the action potential has a low take-off potential.從竇房結(jié)中心分離的組織顯示自發(fā)激動(dòng)，動(dòng)作電位有一低起始電位。

參考譯文

第67課II型Brugada綜合征圖形與健康運(yùn)動(dòng)員心電圖V1/V2r′波的鑒別新標(biāo)準(zhǔn)

Ⅱ型Brugada綜合征特征表現(xiàn)為心電圖V1~V2上r′波，易與其他情況如不完全性右束支傳導(dǎo)阻滯（IRBBB）、漏斗胸、致心律失常右心室發(fā)育不良和運(yùn)動(dòng)員在該導(dǎo)聯(lián)上的r′波相混繞。這種鑒別診斷仍然是一種挑戰(zhàn)。幫助醫(yī)生鑒別這些心電圖形態(tài)的巨大努力一直不斷付出。Chevallier和Ohkubo等報(bào)道指出由S波的上升支和r′波的下降支構(gòu)成的β夾角是區(qū)分Ⅱ型Brugada圖形與IRBBB的最佳方法。Chevallier的研究表明以β夾角58°作為切點(diǎn)的陽性預(yù)測(cè)值為73%、陰性預(yù)測(cè)值為87%。然而，臨床實(shí)踐中難以準(zhǔn)確測(cè)定β夾角，且不易實(shí)施，導(dǎo)致誤診。Corrado等也基于V1~V2上ST段最初80ms的斜坡，描繪了一索引特征，即該處斜坡在運(yùn)動(dòng)員是向上的，而Ⅱ型Brugada是向下的，這有助于鑒別診斷。不過，對(duì)于許多Ⅱ型Brugada圖形，V1~V2識(shí)別QRS波群終點(diǎn)并非易事，而且，有時(shí)在那些導(dǎo)聯(lián)上J點(diǎn)不總是與QRS的高起點(diǎn)（take-off）相一致。

本研究的目的是分析新的心電圖標(biāo)準(zhǔn)在鑒別Ⅱ型Brugada圖形和健康運(yùn)動(dòng)員V1~V2上r′波的診斷準(zhǔn)確性。

方法

進(jìn)行回顧性研究，比較確診Brugada綜合征（有暈厥，且鈉通道阻滯劑激發(fā)試驗(yàn)陽性）并呈Ⅱ型Brugada圖形的50例患者的體表心電圖與58例無猝死家族史、沒有暈厥和室性心律失常病史、V1~V2呈r′波的健康運(yùn)動(dòng)員的體表心電圖。

記錄體表12導(dǎo)聯(lián)心電圖，V1~V2電極置于第4肋間。由兩位獨(dú)立的研究者單盲分析心電圖。在記錄10s的心電圖片上測(cè)定V1~V2上QRS-T波的r′波和等電位線。在每一r′波（Figure1A partA）上添加兩段直線,沿著r′波的上升支和下降支（Figure 1A partB），在等電位線（Figure 1A partC）上添加一段直線。

測(cè)定三個(gè)新標(biāo)準(zhǔn)（1）高起點(diǎn)下0.5mV處r′波上升支和下降支構(gòu)成的三角形底邊間期（Figure1C,partA），（2）等電位線水平該三角形底邊間期,和（3）r′波上升支和下降支構(gòu)成的三角形基線水平底邊與高的比值（Figure 1C,partB）。同時(shí)測(cè)定Chevallier等提出的由r′波上升支和下降支構(gòu)成的β夾角（Figure1C,partC）。

所有數(shù)值由V1和V2計(jì)算而得。計(jì)算每例患者每個(gè)導(dǎo)聯(lián)數(shù)次搏動(dòng)測(cè)值的均值。

為提高這一方法的可行性和重復(fù)性，對(duì)V1和V2的同一參數(shù)作聯(lián)合分析。只要兩個(gè)導(dǎo)聯(lián)中至少一個(gè)導(dǎo)聯(lián)符合標(biāo)準(zhǔn)即為Brugada陽性。單一導(dǎo)聯(lián)缺乏r′波判為該導(dǎo)聯(lián)陰性。

結(jié)果

高起點(diǎn)下0.5mV處三角形底邊間期、等電位線處三角形底邊間期及等電位線處r′波上升支和下降支構(gòu)成的三角形底邊與高比值，呈Ⅱ型Brugada心電圖圖形的Brugada綜合征患者均顯著高于健康運(yùn)動(dòng)員組。圖2和圖3顯示r′波高起點(diǎn)下0.5mV處三角形底邊在Ⅱ型Brugada圖形（＞160ms, 4mm）和健康運(yùn)動(dòng)員（＜160ms,4mm）之間是如何不同的，即使ST-T形態(tài)相似。ROC曲線顯示，r′波高起點(diǎn)下0.5mV處三角形底邊間期的曲線下面積（AUC）V1為0.955，V2為0.944，而等電位線水平三角形底邊間期的AUC V1為0.907，V2為0.938；三角形底邊/高比值的AUC V1為0.94，V2為0.944；βangleV1為0.957，V2為0.952。

討論

Brugada綜合征是一種遺傳性心臟疾病，由右心室鈉通道失活所致，可表現(xiàn)為多形性室性心動(dòng)過速和心室顫動(dòng)。Brugada綜合征診斷中心電圖的重要性

心電圖是Brugada綜合征的標(biāo)志性診斷性檢查。合理解釋V1~V2上的r′波特性對(duì)于區(qū)分良性心電圖圖形與Ⅱ型Brugada圖形至關(guān)重要。

其他遺傳性疾病如致心律失常右心室發(fā)育不良也是鑒別診斷之一，但心電圖V1~V2通常不出現(xiàn)清晰的r′波（epsilon波通常與QRS波群分），無清晰的ST-段抬高，V1~V3上通常T波對(duì)稱性倒置。

II型Brugada圖形與運(yùn)動(dòng)員心電圖的鑒別診斷

鑒別Ⅱ型Brugada圖形與健康運(yùn)動(dòng)員r′波極為重要。Ⅱ型Brugada心電圖圖形特征表現(xiàn)為V1~V2上正向r′波于QRS-ST連接處發(fā)生偏轉(zhuǎn)，伴隨降支的淺降斜坡，其他導(dǎo)聯(lián)伴或不伴細(xì)微的對(duì)應(yīng)變化。相反，不完全性RBBB中見到的r′波呈現(xiàn)速降斜坡，這由右束支早期傳導(dǎo)延緩所致。有些學(xué)者認(rèn)為Ⅰ型Brugada的穹形QRS-ST圖形或Ⅱ型Brugada圖形的r′波不僅表明右心室激動(dòng)延遲，而且提示早復(fù)極和J點(diǎn)抬高。穹形的下斜型ST段后隨倒置的T波，這源于復(fù)極結(jié)束時(shí)的電壓梯度，是延遲的動(dòng)作電位時(shí)程超過心內(nèi)膜動(dòng)作電位時(shí)程的結(jié)果。相反，Ⅱ型Brugada圖形中的反向電壓梯度可以解釋直立T波，這常見于Ⅱ型Brugada圖形中。

新的心電圖標(biāo)準(zhǔn)在II型Brugada圖形診斷中的意義

本研究中，我們描述了鑒別Ⅱ型Brugada圖形與健康運(yùn)動(dòng)員V1~V2上r′波的新的心電圖標(biāo)準(zhǔn)。所有3條新標(biāo)準(zhǔn)證實(shí)了在鑒別真正Brugada綜合征患者時(shí)的高診斷率，但并不優(yōu)于Chevallier等描述的β夾角標(biāo)準(zhǔn)，因此，可以作為補(bǔ)充或替代選擇。此外，這一標(biāo)準(zhǔn)的真實(shí)價(jià)值有待于前瞻性研究檢驗(yàn)。該作者發(fā)現(xiàn)以β夾角58°為切點(diǎn)，陽性預(yù)測(cè)值為73%，陰性預(yù)測(cè)值為87%。我們的發(fā)現(xiàn)提示β夾角切點(diǎn)低于Chevalier系列（≥36.8°）。這種差異的理由之一是不易獲取恰當(dāng)?shù)摩聤A角測(cè)值，不同次和不同測(cè)定人之間差異大。

我們的研究中，3個(gè)新的心電圖標(biāo)準(zhǔn)基于特征性的r′波。于高起點(diǎn)下0.5mV處測(cè)定r′波升支和降支形成的三角形底邊間期最為容易，有助于臨床實(shí)踐應(yīng)用。V1和（或）V2這一間期≥160ms（4mm）確定患者為Brugada圖形。另兩個(gè)參數(shù)，即等電位線上三角形底邊間期≥60ms和等電位線上三角形底邊/高的比值≥0.8,也具有高敏感度和特異度,類似或高于β夾角獲得的相應(yīng)值。

本研究中，我們已證實(shí)這些標(biāo)準(zhǔn)在鑒別Ⅱ型Brugada圖形和健康運(yùn)動(dòng)員V1~V2上r′波的價(jià)值。這些新參數(shù)能否鑒別Ⅱ型Brugada圖形與其他病癥在V1~V2上出現(xiàn)的r′波仍然是一種挑戰(zhàn)。

極為重要的是切記100年前由Einthoven所發(fā)現(xiàn)的體表心電圖記錄，在發(fā)現(xiàn)這一綜合征20年后仍然可提供如此有益的信息。這將有助于危險(xiǎn)分層，從臨床和患者處理的角度看是非常有利的。

圖1（A）觀察者所作的節(jié)段定位：（A）原始信號(hào)，（B）r′波上升支和下降支節(jié)段定位，（C）等電位線節(jié)段定位；（B）由原始格柵對(duì)節(jié)段定位作標(biāo)尺測(cè)定；（C）分析者從定位節(jié)段提取測(cè)值—（A）r′波高起點(diǎn)下0.5mV處三角形底邊間期,（B）等電位線處三角形間期與高,（C）S波上升支與r′波下降支形成的β角度。

圖2兩份健康運(yùn)動(dòng)員心電圖。（A）健康運(yùn)動(dòng)員ST-T抬高和r′波，0.5mV處三角形底邊40ms（1mm）；（B）健康運(yùn)動(dòng)員心電圖有著相似的ST-T形態(tài)，三角形底邊80ms（2mm）。

圖3兩例Ⅱ型Brugada心電圖圖形。（A）Ⅱ型Brugada圖形，0.5mV處三角形底邊184ms（4.6mm）；（B）Ⅱ型Brugada圖形，0.5mV處三角形底邊188ms（4.7mm）。

[1]Serra G,Baranchuk A,Baye′s-De-Luna A,et al.New electrocardio graphic criteria to differentiate the Type-2 Brugada pattern from electrocardiogram of healthy athletes with r′-wave in leads V1/V2[J].Europace，2014，16∶1639-1645.

（童鴻）