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

●心电学英语

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.

词汇

arrhythmogenic n.致心律失常的

dysp lasia n.发育不全，发育不良

pursue v.追,追赶,继续,追求,追随

misdiagnosis n.错误的诊断

feasibility n.可行性

reproducibility n.再生产,重复性

hallmark n.纯度印记,标志

interpretation n.解释,表现,口译,表演,翻译

crucial adj.决定性的,十字形的,严酷的

endocardium n.心内膜

discrim inate adj.&v.有区别的,著名的;区别,区分

depict v.描画,描绘,描写

注释

1.take-off医学文献中多指“起点，起始”，如The take-off of the right coronary artery is quite variable.右冠状动脉的起始变化很大。Tissue isolated from the sinoatrial node center shows spontaneous activity and the action potential has a low take-off potential.从窦房结中心分离的组织显示自发激动，动作电位有一低起始电位。

参考译文

第67课II型Brugada综合征图形与健康运动员心电图V1/V2r′波的鉴别新标准

Ⅱ型Brugada综合征特征表现为心电图V1~V2上r′波，易与其他情况如不完全性右束支传导阻滞（IRBBB）、漏斗胸、致心律失常右心室发育不良和运动员在该导联上的r′波相混绕。这种鉴别诊断仍然是一种挑战。帮助医生鉴别这些心电图形态的巨大努力一直不断付出。Chevallier和Ohkubo等报道指出由S波的上升支和r′波的下降支构成的β夹角是区分Ⅱ型Brugada图形与IRBBB的最佳方法。Chevallier的研究表明以β夹角58°作为切点的阳性预测值为73%、阴性预测值为87%。然而，临床实践中难以准确测定β夹角，且不易实施，导致误诊。Corrado等也基于V1~V2上ST段最初80ms的斜坡，描绘了一索引特征，即该处斜坡在运动员是向上的，而Ⅱ型Brugada是向下的，这有助于鉴别诊断。不过，对于许多Ⅱ型Brugada图形，V1~V2识别QRS波群终点并非易事，而且，有时在那些导联上J点不总是与QRS的高起点（take-off）相一致。

本研究的目的是分析新的心电图标准在鉴别Ⅱ型Brugada图形和健康运动员V1~V2上r′波的诊断准确性。

方法

进行回顾性研究，比较确诊Brugada综合征（有晕厥，且钠通道阻滞剂激发试验阳性）并呈Ⅱ型Brugada图形的50例患者的体表心电图与58例无猝死家族史、没有晕厥和室性心律失常病史、V1~V2呈r′波的健康运动员的体表心电图。

记录体表12导联心电图，V1~V2电极置于第4肋间。由两位独立的研究者单盲分析心电图。在记录10s的心电图片上测定V1~V2上QRS-T波的r′波和等电位线。在每一r′波（Figure1A partA）上添加两段直线,沿着r′波的上升支和下降支（Figure 1A partB），在等电位线（Figure 1A partC）上添加一段直线。

测定三个新标准（1）高起点下0.5mV处r′波上升支和下降支构成的三角形底边间期（Figure1C,partA），（2）等电位线水平该三角形底边间期,和（3）r′波上升支和下降支构成的三角形基线水平底边与高的比值（Figure 1C,partB）。同时测定Chevallier等提出的由r′波上升支和下降支构成的β夹角（Figure1C,partC）。

所有数值由V1和V2计算而得。计算每例患者每个导联数次搏动测值的均值。

为提高这一方法的可行性和重复性，对V1和V2的同一参数作联合分析。只要两个导联中至少一个导联符合标准即为Brugada阳性。单一导联缺乏r′波判为该导联阴性。

结果

高起点下0.5mV处三角形底边间期、等电位线处三角形底边间期及等电位线处r′波上升支和下降支构成的三角形底边与高比值，呈Ⅱ型Brugada心电图图形的Brugada综合征患者均显著高于健康运动员组。图2和图3显示r′波高起点下0.5mV处三角形底边在Ⅱ型Brugada图形（＞160ms, 4mm）和健康运动员（＜160ms,4mm）之间是如何不同的，即使ST-T形态相似。ROC曲线显示，r′波高起点下0.5mV处三角形底边间期的曲线下面积（AUC）V1为0.955，V2为0.944，而等电位线水平三角形底边间期的AUC V1为0.907，V2为0.938；三角形底边/高比值的AUC V1为0.94，V2为0.944；βangleV1为0.957，V2为0.952。

讨论

Brugada综合征是一种遗传性心脏疾病，由右心室钠通道失活所致，可表现为多形性室性心动过速和心室颤动。Brugada综合征诊断中心电图的重要性

心电图是Brugada综合征的标志性诊断性检查。合理解释V1~V2上的r′波特性对于区分良性心电图图形与Ⅱ型Brugada图形至关重要。

其他遗传性疾病如致心律失常右心室发育不良也是鉴别诊断之一，但心电图V1~V2通常不出现清晰的r′波（epsilon波通常与QRS波群分），无清晰的ST-段抬高，V1~V3上通常T波对称性倒置。

II型Brugada图形与运动员心电图的鉴别诊断

鉴别Ⅱ型Brugada图形与健康运动员r′波极为重要。Ⅱ型Brugada心电图图形特征表现为V1~V2上正向r′波于QRS-ST连接处发生偏转，伴随降支的浅降斜坡，其他导联伴或不伴细微的对应变化。相反，不完全性RBBB中见到的r′波呈现速降斜坡，这由右束支早期传导延缓所致。有些学者认为Ⅰ型Brugada的穹形QRS-ST图形或Ⅱ型Brugada图形的r′波不仅表明右心室激动延迟，而且提示早复极和J点抬高。穹形的下斜型ST段后随倒置的T波，这源于复极结束时的电压梯度，是延迟的动作电位时程超过心内膜动作电位时程的结果。相反，Ⅱ型Brugada图形中的反向电压梯度可以解释直立T波，这常见于Ⅱ型Brugada图形中。

新的心电图标准在II型Brugada图形诊断中的意义

本研究中，我们描述了鉴别Ⅱ型Brugada图形与健康运动员V1~V2上r′波的新的心电图标准。所有3条新标准证实了在鉴别真正Brugada综合征患者时的高诊断率，但并不优于Chevallier等描述的β夹角标准，因此，可以作为补充或替代选择。此外，这一标准的真实价值有待于前瞻性研究检验。该作者发现以β夹角58°为切点，阳性预测值为73%，阴性预测值为87%。我们的发现提示β夹角切点低于Chevalier系列（≥36.8°）。这种差异的理由之一是不易获取恰当的β夹角测值，不同次和不同测定人之间差异大。

我们的研究中，3个新的心电图标准基于特征性的r′波。于高起点下0.5mV处测定r′波升支和降支形成的三角形底边间期最为容易，有助于临床实践应用。V1和（或）V2这一间期≥160ms（4mm）确定患者为Brugada图形。另两个参数，即等电位线上三角形底边间期≥60ms和等电位线上三角形底边/高的比值≥0.8,也具有高敏感度和特异度,类似或高于β夹角获得的相应值。

本研究中，我们已证实这些标准在鉴别Ⅱ型Brugada图形和健康运动员V1~V2上r′波的价值。这些新参数能否鉴别Ⅱ型Brugada图形与其他病症在V1~V2上出现的r′波仍然是一种挑战。

极为重要的是切记100年前由Einthoven所发现的体表心电图记录，在发现这一综合征20年后仍然可提供如此有益的信息。这将有助于危险分层，从临床和患者处理的角度看是非常有利的。

图1（A）观察者所作的节段定位：（A）原始信号，（B）r′波上升支和下降支节段定位，（C）等电位线节段定位；（B）由原始格栅对节段定位作标尺测定；（C）分析者从定位节段提取测值—（A）r′波高起点下0.5mV处三角形底边间期,（B）等电位线处三角形间期与高,（C）S波上升支与r′波下降支形成的β角度。

图2两份健康运动员心电图。（A）健康运动员ST-T抬高和r′波，0.5mV处三角形底边40ms（1mm）；（B）健康运动员心电图有着相似的ST-T形态，三角形底边80ms（2mm）。

图3两例Ⅱ型Brugada心电图图形。（A）Ⅱ型Brugada图形，0.5mV处三角形底边184ms（4.6mm）；（B）Ⅱ型Brugada图形，0.5mV处三角形底边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.

（童鸿）