**3. Electrocardiographic risk markers**

#### **3.1. Type 1 pattern**

#### *3.1.1. Spontaneous type 1 pattern*

The spontaneous nature of the ECG type 1 pattern (contrary to the drug-induced type 1) seems to indicate an increased risk of ventricular fibrillation. This was demonstrated in 2005 by Eckardt et al. [32] and has since been found in several large studies, particularly in the FINGER cohort [33] involving 1029 patients, where a spontaneous type 1 pattern was predictive of a greater risk of sudden death with a hazard ratio (HR) of 1.8 (CI 1.03– 3.33, p = 0.04).

A study by Cerrato et al. [34] has shown that the use of the 24-h holter ECG monitoring can help with spontaneous type 1 diagnosis, which is more common during the sleep. This method could be an alternative to avoid the risks related to the pharmacological challenge.

#### *3.1.2. Duration of type 1 pattern expression*

Similarly, Extramiana et al. [35] showed by holter ECG monitoring that permanent type 1 expression was associated with an increased risk of syncope and/or ventricular fibrillation.

The 24 or 48 h-holter ECG monitoring could therefore be an interesting tool in the stratification of patients' risk.

Two opposed theories [36] can explain the electrocardiographic and rhythmic abnormalities observed in the Brugada syndrome: a so-called depolarization theory and a so-called repolarization theory. The abnormalities of depolarization and repolarization explain a number of ECG changes that may indicate a poor prognosis.

#### **3.2. Depolarization and conduction disorders**

#### *3.2.1. Supraventricular level*

with right ventricle extension or anterior infarction [7–9], Tako-Tsubo cardiomyopathy [10], cardiac tumors [11], Chagas disease [12]), in pulmonary and mediastinal diseases (acute pulmonary embolism [13], pneumothorax [14], mediastinal tumors [15]), in metabolic and hydroelectrolytic disorders (hypokalemia [16, 17], hyperkalemia [18], hyponatremia [19], hypophosphatemia [20], keto-acidosis [21]), in intoxications (heroin and ethanol overdose [22], propofol [23], propafenone [24], yellow phosphorus [25], lamotrigine [26], phosphine [27]), and various diseases such intracranial hemorrhages [28], hypothermia [29], and elec-

According to Baranchuk and Anselm [6], the diagnosis of phenocopy is based on the context, on the normalization of the ECG with the resolution of the cause, and on the negativity of the

The spontaneous nature of the ECG type 1 pattern (contrary to the drug-induced type 1) seems to indicate an increased risk of ventricular fibrillation. This was demonstrated in 2005 by Eckardt et al. [32] and has since been found in several large studies, particularly in the FINGER cohort [33] involving 1029 patients, where a spontaneous type 1 pattern was predictive of a greater risk of sudden death with a hazard ratio (HR) of 1.8 (CI 1.03–

A study by Cerrato et al. [34] has shown that the use of the 24-h holter ECG monitoring can help with spontaneous type 1 diagnosis, which is more common during the sleep. This method could be an alternative to avoid the risks related to the pharmacological

Similarly, Extramiana et al. [35] showed by holter ECG monitoring that permanent type 1 expression was associated with an increased risk of syncope and/or ventricular

The 24 or 48 h-holter ECG monitoring could therefore be an interesting tool in the stratifica-

Two opposed theories [36] can explain the electrocardiographic and rhythmic abnormalities observed in the Brugada syndrome: a so-called depolarization theory and a so-called repolarization theory. The abnormalities of depolarization and repolarization explain a number of

trocution [30]. Pectus excavatum can also mimic a type 1 pattern [31].

The prognostic impact of phenocopies is poorly documented.

**3. Electrocardiographic risk markers**

pharmacological challenge.

*3.1.1. Spontaneous type 1 pattern*

*3.1.2. Duration of type 1 pattern expression*

ECG changes that may indicate a poor prognosis.

**3.1. Type 1 pattern**

106 Cardiac Arrhythmias

3.33, p = 0.04).

challenge.

fibrillation.

tion of patients' risk.

#### *3.2.1.1. Sinus node dysfunction*

The sinus node dysfunction (**Figure 2**) frequently observed in Brugada syndrome is the conjunction of two phenomena secondary to the reduction of sodium current: an alteration of sinus tissue function and a sino-atrial functional block [37]. Sinus node dysfunction is more frequent in case of mutation on the SCN5A gene [38].

A study conducted on 400 patients by Siera et al. [39] showed that sinus dysfunction was a predictor of ventricular fibrillation risk. The same observation was also made on a cohort of children [40] and a cohort of women [41] with Brugada syndrome (**Table 1**).

#### *3.2.1.2. First degree atrioventricular block*

Maury et al. [42] showed in a study of 325 patients with Brugada type 1 that the presence of first-degree atrioventricular block (**Figure 3**) was significantly associated in multivariate analysis with increasing risk of ventricular fibrillation (OR 2.41, 95% CI 1.01–5.73, p = 0.046) (**Table 2**).

**Figure 2.** Sinus pause in a 54-year-old woman with Brugada type 1 syndrome and recurrence of syncopes.


**Table 1.** Criteria of sinus node dysfunction in Sieira et al. study [41].

Functional studies using surface ECG mapping [45], tissular Doppler imaging [46], and endoand epicardial electrophysiology [47, 48] show that there is an abnormally long conduction delay in the epicardium of the right ventricular outflow tract. This conduction delay is some-

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Several factors may explain these abnormalities of conduction. On the one hand, the decrease of the incoming sodium current reduces the intramyocardial conduction velocity [49], while on the other hand, histological and histochemical studies [50, 51] reveal the abnormally large presence of fibrosis deposits in the epicardium of the right ventricle outflow tract, these deposits are accompanied locally by a reduction in expression of gap-junctions. An experimental model in the mouse showed that these two abnormalities

The shift created between the depolarization (and thereby, secondarily, the repolarization) of the right ventricular outflow tract and the other segments of the ventricles could thus

Several studies show that the importance of these conduction abnormalities is highly variable between patients with Brugada syndrome and is correlated with the risk of ventricular fibril-

These findings are supported by several interventional studies highlighting the lower recurrence of ventricular rhythmic events after radiofrequency ablation in the right ventricular

It is therefore important to estimate the importance of impairment of right ventricular conduction in patients to determine their level of risk of sudden death. Several ECG markers can

could be the consequence of the decrease of SCN5A gene expression [52].

explain the ST segment elevation and the negativity of the T waves [36].

times accompanied by late ventricular potentials [48].

lation [53].

outflow tract [54].

help with a non-invasive evaluation.

In lead V2, width of QRS ≥ 120 ms

**Table 3.** Wide QRS criterion on Ohkubo et al. study [55].

**Figure 4.** Wide QRS in lead V2 in a patient with a Brugada type 1 pattern.

**Figure 3.** First-degree AVB in a woman with Brugada type 1 pattern.

In addition, Smits et al. [38] demonstrated that atrioventricular conduction abnormalities were significantly increased in the case of SCN5A gene mutation. A PR interval ≥ 210 ms would be a good predictor of a mutation in the SCN5A gene in Brugada syndrome. Previous observations [43, 44] have shown that sodium channels genes mutations are also implicated in conduction disturbances in Lev/Lenegre disease.

#### *3.2.2. Ventricular level*

#### *3.2.2.1. Pathophysiology*

Cardiac imaging tests (transthoracic echocardiography, angiography, MRI) are usually normal in Brugada syndrome, so it was long believed that this pathology did not lead to heart structural abnormalities. Several recent studies question this dogma.

PR interval ≥ 200 ms

**Table 2.** First-degree atrioventricular block criterion in Maury et al. study [42].

Functional studies using surface ECG mapping [45], tissular Doppler imaging [46], and endoand epicardial electrophysiology [47, 48] show that there is an abnormally long conduction delay in the epicardium of the right ventricular outflow tract. This conduction delay is sometimes accompanied by late ventricular potentials [48].

Several factors may explain these abnormalities of conduction. On the one hand, the decrease of the incoming sodium current reduces the intramyocardial conduction velocity [49], while on the other hand, histological and histochemical studies [50, 51] reveal the abnormally large presence of fibrosis deposits in the epicardium of the right ventricle outflow tract, these deposits are accompanied locally by a reduction in expression of gap-junctions. An experimental model in the mouse showed that these two abnormalities could be the consequence of the decrease of SCN5A gene expression [52].

The shift created between the depolarization (and thereby, secondarily, the repolarization) of the right ventricular outflow tract and the other segments of the ventricles could thus explain the ST segment elevation and the negativity of the T waves [36].

Several studies show that the importance of these conduction abnormalities is highly variable between patients with Brugada syndrome and is correlated with the risk of ventricular fibrillation [53].

These findings are supported by several interventional studies highlighting the lower recurrence of ventricular rhythmic events after radiofrequency ablation in the right ventricular outflow tract [54].

It is therefore important to estimate the importance of impairment of right ventricular conduction in patients to determine their level of risk of sudden death. Several ECG markers can help with a non-invasive evaluation.

**Figure 4.** Wide QRS in lead V2 in a patient with a Brugada type 1 pattern.

In lead V2, width of QRS ≥ 120 ms

In addition, Smits et al. [38] demonstrated that atrioventricular conduction abnormalities were significantly increased in the case of SCN5A gene mutation. A PR interval ≥ 210 ms would be a good predictor of a mutation in the SCN5A gene in Brugada syndrome. Previous observations [43, 44] have shown that sodium channels genes mutations are also implicated

Cardiac imaging tests (transthoracic echocardiography, angiography, MRI) are usually normal in Brugada syndrome, so it was long believed that this pathology did not lead to heart

in conduction disturbances in Lev/Lenegre disease.

**Figure 3.** First-degree AVB in a woman with Brugada type 1 pattern.

structural abnormalities. Several recent studies question this dogma.

**Table 2.** First-degree atrioventricular block criterion in Maury et al. study [42].

*3.2.2. Ventricular level*

108 Cardiac Arrhythmias

*3.2.2.1. Pathophysiology*

PR interval ≥ 200 ms

**Table 3.** Wide QRS criterion on Ohkubo et al. study [55].

#### *3.2.2.2. Wide QRS in lead V2*

Wide QRS in lead V2 (**Figure 4**) is the most obvious marker of alteration of right ventricular conduction. The widening of the QRS in V2 classically demonstrates a slowdown of conduction in the right ventricle.

Ohkubo et al. [55] found, in a cohort of 35 patients with Brugada syndrome, a significant association between wide QRS in lead V2 and ventricular fibrillation and/or syncope (**Table 3**).

#### *3.2.2.3. S-waves in lead DI*

Based on the assumption that S-waves in lead DI are the translation of the third vector resulting from the depolarization of right ventricular outflow tract and the basal parts of the two ventricles, Calò et al. [56] demonstrated an electroanatomical correlation between the epicardial activation time of the right ventricular outflow tract and the importance of S-waves in DI.

The same team has shown in a multicentric study [56] of 347 patients with spontaneous type 1, that significant S-waves in lead DI (**Figure 5**) represent a strong marker of risk of sudden death, with a sensitivity of 90.6% and a specificity of 62.2% for the depth of the waves and a sensitivity of 96.9% and a specificity of 61.1% for the duration of the waves (**Table 4**).

*3.2.2.5. Fragmented QRS*

In lead aVR, R-wave ≥0.3 mV and/or R/q ratio ≥ 0.75

**Table 5.** Criterion of aVR sign in Babai Bigi et al. study [57].

**Figure 6.** aVR sign.

Fragmented QRS (**Figure 7**) were first described in ischemic cardiomyopathies [58], where they are a sign of significant fibrotic scars and lead to a risk of malignant ventricular arrhythmias by macro-reentry. They could also testify of the importance of right ventricular fibrosis in Brugada syndrome. Morita et al. [49] also showed the existence of a dynamic part to this

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The same team showed [49], with a cohort of 115 patients with Brugada syndrome, that fragment QRS were significantly more frequent in the ventricular fibrillation group (**Table 6**).

pattern, varying according to the conditions of conduction.

**Figure 7.** Fragmented QRS in a patient with a Brugada type 1 pattern.

The right ventricular outflow tract is notably the last structure responsible to eject the blood to the pulmonary artery. This is notably ensured by a delay in action potentials. While such delay constitutes a physiological need, it also creates a first-degree heterogeneity between this specific structure and the right ventricle. In the background of a SCN5A mutation, such heterogeneity would be even more pronounced, making the right ventricular outflow tract a pro-arrhythmogenic area.

#### *3.2.2.4. The aVR sign*

The positivity of the QRS complexes in lead aVR (**Figure 6**) may reflect a right ventricular conduction delay responsible for a right axial deviation of the QRS.

Babai Bigi et al. [57] found in a prospective cohort of 24 patients with a Brugada type 1 pattern a significant association between the presence of significant R-waves in aVR and the risk of syncope and/or ventricular fibrillation (**Table 5**).

**Figure 5.** Significant S-waves in lead DI.

In lead DI, S-waves with a depth of at least 0.1 mV and/or a width of at least 40 ms

**Table 4.** Criteria of S-waves in Calò et al. study [56].

**Figure 6.** aVR sign.

*3.2.2.2. Wide QRS in lead V2*

110 Cardiac Arrhythmias

tion in the right ventricle.

*3.2.2.3. S-waves in lead DI*

pro-arrhythmogenic area.

**Figure 5.** Significant S-waves in lead DI.

**Table 4.** Criteria of S-waves in Calò et al. study [56].

*3.2.2.4. The aVR sign*

Wide QRS in lead V2 (**Figure 4**) is the most obvious marker of alteration of right ventricular conduction. The widening of the QRS in V2 classically demonstrates a slowdown of conduc-

Ohkubo et al. [55] found, in a cohort of 35 patients with Brugada syndrome, a significant association between wide QRS in lead V2 and ventricular fibrillation and/or syncope (**Table 3**).

Based on the assumption that S-waves in lead DI are the translation of the third vector resulting from the depolarization of right ventricular outflow tract and the basal parts of the two ventricles, Calò et al. [56] demonstrated an electroanatomical correlation between the epicardial activation time of the right ventricular outflow tract and the importance of S-waves in DI. The same team has shown in a multicentric study [56] of 347 patients with spontaneous type 1, that significant S-waves in lead DI (**Figure 5**) represent a strong marker of risk of sudden death, with a sensitivity of 90.6% and a specificity of 62.2% for the depth of the waves and a

sensitivity of 96.9% and a specificity of 61.1% for the duration of the waves (**Table 4**).

The right ventricular outflow tract is notably the last structure responsible to eject the blood to the pulmonary artery. This is notably ensured by a delay in action potentials. While such delay constitutes a physiological need, it also creates a first-degree heterogeneity between this specific structure and the right ventricle. In the background of a SCN5A mutation, such heterogeneity would be even more pronounced, making the right ventricular outflow tract a

The positivity of the QRS complexes in lead aVR (**Figure 6**) may reflect a right ventricular

Babai Bigi et al. [57] found in a prospective cohort of 24 patients with a Brugada type 1 pattern a significant association between the presence of significant R-waves in aVR and the risk of

conduction delay responsible for a right axial deviation of the QRS.

In lead DI, S-waves with a depth of at least 0.1 mV and/or a width of at least 40 ms

syncope and/or ventricular fibrillation (**Table 5**).

In lead aVR, R-wave ≥0.3 mV and/or R/q ratio ≥ 0.75

**Table 5.** Criterion of aVR sign in Babai Bigi et al. study [57].

#### *3.2.2.5. Fragmented QRS*

Fragmented QRS (**Figure 7**) were first described in ischemic cardiomyopathies [58], where they are a sign of significant fibrotic scars and lead to a risk of malignant ventricular arrhythmias by macro-reentry. They could also testify of the importance of right ventricular fibrosis in Brugada syndrome. Morita et al. [49] also showed the existence of a dynamic part to this pattern, varying according to the conditions of conduction.

The same team showed [49], with a cohort of 115 patients with Brugada syndrome, that fragment QRS were significantly more frequent in the ventricular fibrillation group (**Table 6**).

**Figure 7.** Fragmented QRS in a patient with a Brugada type 1 pattern.


**Table 6.** Criteria of fragmented QRS in Morita et al. study [49].

#### **3.3. Repolarization disorders**

#### *3.3.1. Pathophysiology*

The repolarization theory was mainly developed in the works of Antzelevitch [59–61].

The right ventricular outflow tract epicardial cells hold more Ito potassium channels than other myocardial cells. In the Brugada syndrome, the reduction of the sodium current accentuates locally in the right ventricular outflow tract the shortening duration of the action potentials induced by the important activity of the Ito channels. A voltage gradient is thus created between the endocardium and the epicardium, resulting in the dome-shaped ST elevation observed on the ECG. Brugada syndrome thus carries a risk of ventricular fibrillation by Phase 2 reentry mechanism.

arrhythmia. Antzelevitch and Yan [67] have shown that the pathophysiology of this syndrome is close to the repolarization theory of Brugada syndrome: a large repolarization heterogeneity in the left ventricle could lead to a risk of ventricular fibrillation by Phase 2 reentry. The association of both syndromes would result in repolarization heterogeneity in both the right ventricle and the inferior lateral parts of the left ventricle with a high risk of

• Measurement of the interval between the peak of the T wave and the tangent between the downward slope of

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Kawata et al. [68] showed, in a cohort of 49 patients with Brugada type 1 syndrome and a history of ventricular fibrillation, that the presence of a permanent early repolarization pattern (HR 4.88, 95% CI 2.02–12.7) or intermittent (HR 2.50, 95% CI 1.03–6.43) was significantly (p = 0.043) associated with a higher risk of recurrence of a fatal rhythmic event (**Table 8**).

Calò et al. [56] showed through a multivariate analysis of 347 patients that the occurrence of atrial fibrillation (**Figure 9**) episodes in Brugada type 1 patients was a significant and indepen-

ventricular fibrillation [67, 68].

Tpeak-Tend measurement method: • From lead V1 to lead V4

the T wave and the isoelectric line

• Average of three consecutive complexes by derivation

*3.4.1. Atrial fibrillation*

**3.4. Other electrocardiographic markers**

Maximum Tpeak-Tend adjusted to heart rate among leads V1–V4 ≥ 100 ms

• Correction of the heart rate according to the Bazett method (Tp-e corrected = Tp-e/√RR)

**Table 7.** Criteria of prolonged maximum Tpeak-Tend interval in Maury et al. study [64].

dent risk marker for ventricular fibrillation.

**Figure 8.** Early repolarization pattern (notching).

This theory is usually opposed to the theory of conduction described earlier [62].

#### *3.3.2. Tpeak-Tend interval, QT*

The three types of ventricular myocardial cells have different repolarization durations [61]. The epicardial cells are the most rapidly repolarized, then the endocardial cells, and finally the M-cells. Thus, the peak of the T waves corresponds with the moment when the epicardial cells are completely repolarized and the end of the T waves coincides with the end of the repolarization of the M-cells. Therefore, the Tp-e, corresponding with the interval between the vertex and the end of the T waves, is considered by many authors [63] as proportional to the importance of the transmural dispersion of repolarization in the ventricular myocardium. A wide dispersion of repolarization increases myocardial vulnerability and therefore the risk of arrhythmia. An elongated Tp-e would thus translate into a high risk of sudden death by ventricular arrhythmia.

Maury et al. [64] showed in 2015 with a large retrospective cohort of 325 patients, that a maximum Tp-e in precordial leads greater than or equal to 100 ms was significantly and independently associated with an increased risk of ventricular fibrillation in Brugada syndrome (**Table 7**).

Similarly, a study by Castro Hevia et al. [65] highlighted a correlation between a Tpeak-Tend dispersion (difference between Tpeak-Tend maximum and minimum in precordial shunt) > 20 ms and a risk of ventricular fibrillation.

QT interval prolongation may also means a worse prognosis in Brugada syndrome [65].

#### *3.3.3. Early repolarization*

Haïssaguerre et al. [66] have recently individualized the early repolarization syndrome, which associates an early repolarization pattern (**Figure 8**) with malignant ventricular Maximum Tpeak-Tend adjusted to heart rate among leads V1–V4 ≥ 100 ms

Tpeak-Tend measurement method:

• From lead V1 to lead V4

**3.3. Repolarization disorders**

**Table 6.** Criteria of fragmented QRS in Morita et al. study [49].

*3.3.2. Tpeak-Tend interval, QT*

ventricular arrhythmia.

*3.3.3. Early repolarization*

shunt) > 20 ms and a risk of ventricular fibrillation.

The repolarization theory was mainly developed in the works of Antzelevitch [59–61].

• The filters must be kept to a minimum so that they do not erase the spikes, especially with a high frequency cut-

off (around 150 Hz). This explains why fragmented QRS are often missing on standard ECG.

• In leads V1, V2, and V3: ≥4 spikes in a derivation and/or ≥8 spikes in these 3 leads

syndrome thus carries a risk of ventricular fibrillation by Phase 2 reentry mechanism. This theory is usually opposed to the theory of conduction described earlier [62].

The right ventricular outflow tract epicardial cells hold more Ito potassium channels than other myocardial cells. In the Brugada syndrome, the reduction of the sodium current accentuates locally in the right ventricular outflow tract the shortening duration of the action potentials induced by the important activity of the Ito channels. A voltage gradient is thus created between the endocardium and the epicardium, resulting in the dome-shaped ST elevation observed on the ECG. Brugada

The three types of ventricular myocardial cells have different repolarization durations [61]. The epicardial cells are the most rapidly repolarized, then the endocardial cells, and finally the M-cells. Thus, the peak of the T waves corresponds with the moment when the epicardial cells are completely repolarized and the end of the T waves coincides with the end of the repolarization of the M-cells. Therefore, the Tp-e, corresponding with the interval between the vertex and the end of the T waves, is considered by many authors [63] as proportional to the importance of the transmural dispersion of repolarization in the ventricular myocardium. A wide dispersion of repolarization increases myocardial vulnerability and therefore the risk of arrhythmia. An elongated Tp-e would thus translate into a high risk of sudden death by

Maury et al. [64] showed in 2015 with a large retrospective cohort of 325 patients, that a maximum Tp-e in precordial leads greater than or equal to 100 ms was significantly and independently asso-

Similarly, a study by Castro Hevia et al. [65] highlighted a correlation between a Tpeak-Tend dispersion (difference between Tpeak-Tend maximum and minimum in precordial

Haïssaguerre et al. [66] have recently individualized the early repolarization syndrome, which associates an early repolarization pattern (**Figure 8**) with malignant ventricular

ciated with an increased risk of ventricular fibrillation in Brugada syndrome (**Table 7**).

QT interval prolongation may also means a worse prognosis in Brugada syndrome [65].

*3.3.1. Pathophysiology*

112 Cardiac Arrhythmias


**Table 7.** Criteria of prolonged maximum Tpeak-Tend interval in Maury et al. study [64].

arrhythmia. Antzelevitch and Yan [67] have shown that the pathophysiology of this syndrome is close to the repolarization theory of Brugada syndrome: a large repolarization heterogeneity in the left ventricle could lead to a risk of ventricular fibrillation by Phase 2 reentry. The association of both syndromes would result in repolarization heterogeneity in both the right ventricle and the inferior lateral parts of the left ventricle with a high risk of ventricular fibrillation [67, 68].

Kawata et al. [68] showed, in a cohort of 49 patients with Brugada type 1 syndrome and a history of ventricular fibrillation, that the presence of a permanent early repolarization pattern (HR 4.88, 95% CI 2.02–12.7) or intermittent (HR 2.50, 95% CI 1.03–6.43) was significantly (p = 0.043) associated with a higher risk of recurrence of a fatal rhythmic event (**Table 8**).

#### **3.4. Other electrocardiographic markers**

#### *3.4.1. Atrial fibrillation*

Calò et al. [56] showed through a multivariate analysis of 347 patients that the occurrence of atrial fibrillation (**Figure 9**) episodes in Brugada type 1 patients was a significant and independent risk marker for ventricular fibrillation.

**Figure 8.** Early repolarization pattern (notching).

J-point elevation at least 1 mm in at least two inferior or lateral leads (either notching or slurring pattern)

ventricular arrhythmia, compared to 6% for other patients. The multivariate analysis con-

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The surface electrocardiogram is the key examination in Brugada syndrome. It is currently the only means to allow diagnosis and it could help stratification of the ventricular fibrillation risk. In the last few years, numerous publications highlighted several electrocardiographic markers testifying to a more severe disease and a potentially unfavorable prognosis. These markers also contributed to the improvement of knowledge of the physiopathology of this

syndrome. However, studies are still needed to determine their use in daily practice.

Antoine Deliniere, Francis Bessiere, Adrien Moreau, Alexandre Janin, Gilles Millat and

[1] Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). European Heart Journal. 2015;**36**(41):2793-2867 [2] Sieira J, Brugada P. The definition of the Brugada syndrome. European Heart Journal.

[3] Watanabe H, Minamino T. Genetics of Brugada syndrome. Journal of Human Genetics.

[4] Amin AS, Tan HL, Wilde AAM. Cardiac ion channels in health and disease. Heart

[5] Ruan Y, Liu N, Priori SG. Sodium channel mutations and arrhythmias. Nature Reviews.

[6] Anselm DD, Evans JM, Baranchuk A. Brugada phenocopy: A new electrocardiogram

phenomenon. World Journal of Cardiology. 2014;**6**(3):81-86

firms a strong correlation (OR 4.58, 95% CI 1.7–12.32, p = 0.025).

\*Address all correspondence to: philippe.chevalier@chu-lyon.fr

**4. Conclusion**

**Author details**

Philippe Chevalier\*

**References**

Hôpital Louis Pradel, Lyon, France

2017;**38**(40):3029-3034

Rhythm. 2010;**7**(1):117-126

Cardiology. 2009;**6**(5):337-348

2016;**61**(1):57-60

The pathophysiological significance of this aspect still needs to be clarified.

**Table 8.** Early repolarization criteria in Kawata et al. study [68].

In at least one peripheral derivation (aVR included):


**Table 9.** Criteria of type 1 in peripheral lead pattern in Rollin et al. study [69].

**Figure 9.** Atrial fibrillation in a patient with Brugada type 1 pattern.

**Figure 10.** Type 1 pattern in peripheral lead (aVR).

#### *3.4.2. Type 1 in peripheral leads*

In a study by Rollin et al. [69] conducted on 323 patients, a type 1 pattern in peripheral leads (**Figure 10**) appears to be an independent marker of high risk of ventricular fibrillation (**Table 9**). In total, 27% of patients with type 1 in peripheral leads showed malignant ventricular arrhythmia, compared to 6% for other patients. The multivariate analysis confirms a strong correlation (OR 4.58, 95% CI 1.7–12.32, p = 0.025).

The pathophysiological significance of this aspect still needs to be clarified.
