**2. Positive and differential diagnoses**

#### **2.1. Definition of Brugada type 1 pattern**

The diagnosis of Brugada type 1 pattern is based exclusively on the analysis of the electrocardiogram. The panel of experts who elaborated the 2015 ESC recommendations on sudden death prevention [1] has reached a consensus on the diagnosis criteria.

Type 1 pattern is defined by a coved ST segment elevation with a rise of the J-point ≥2 mm in at least one derivation between V1 and V2 on a resting surface electrocardiogram (**Figure 1**). It is often accepted [2] that the T waves must be negative in the same lead(s), although this criterion is not included in the guidelines.

**Figure 1.** Brugada type 1 pattern.

Several methods can help in case of borderline aspects.

Beyond the diagnosis based on an accurate analysis of right precordial leads, the ECG phenotype of patients with Brugada syndrome is not unique. Many recent studies have shown that several electrocardiographic markers may indicate a more severe disease with an increased

A simple electrocardiographic approach to the risk of sudden death in Brugada syndrome

In this chapter, we propose to review the main ECG markers and the pathophysiological

The diagnosis of Brugada type 1 pattern is based exclusively on the analysis of the electrocardiogram. The panel of experts who elaborated the 2015 ESC recommendations on sudden

Type 1 pattern is defined by a coved ST segment elevation with a rise of the J-point ≥2 mm in at least one derivation between V1 and V2 on a resting surface electrocardiogram (**Figure 1**). It is often accepted [2] that the T waves must be negative in the same lead(s), although this

may be worthwhile at a time when risk stratification is being questioned.

death prevention [1] has reached a consensus on the diagnosis criteria.

risk of sudden death.

104 Cardiac Arrhythmias

hypotheses underlying them.

**2. Positive and differential diagnoses**

**2.1. Definition of Brugada type 1 pattern**

criterion is not included in the guidelines.

**Figure 1.** Brugada type 1 pattern.

First, refitting the electrodes to the second or third intercostal spaces can reveal a type 1 pattern. Secondly, when type 1 pattern is not spontaneous but it remains a clinical suspicion of Brugada syndrome (e.g., ventricular fibrillation on an apparently healthy heart, unexplained syncope, family history of Brugada syndrome) or an electrocardiographic suspicion (Brugada types 2 and 3 patterns), it is possible to carry out a pharmacological challenge by blocker of the sodium channels to unmask a type 1 pattern [1]. This pharmacological challenge must be carried out in a specialized cardiological environment under strict supervision. Febrile episodes can also unmask a type 1 pattern and increase the risk of ventricular fibrillation.

Around 40% of Brugada syndrome cases are familial forms, thus linked to genetic mutations [3]. With 20–30% of familial forms, mutations of the SCN5A gene are the most common mutations identified. SCN5A gene encodes the cardiac voltage-gated sodium channel (Nav1.5). These proteins ensure the rapid sodium upstroke, resulting in cellular depolarization [4, 5]. Studies of mutations linked to the development of Brugada syndrome revealed loss of Nav1.5 function, thus indicating a decreased amount of sodium going through the cardiomyocyte membrane. The loss of function appears to be shared by all SCN5A mutations but the molecular underlying mechanism can slightly vary from a trafficking defect to alterations in the biophysical properties. While this does not affect the final result, this is an important characteristic that could in the future determine the appropriate pharmacology.

The loss of sodium channel function is expected to cause an imbalance between depolarizing and hyperpolarizing currents in cardiomyocytes. Furthermore, as shown in the next sections, epicardium and endocardium present different levels of repolarizing currents such as Ito currents. This difference would increase the depolarizing/hyperpolarizing imbalance underlying the ST elevation and promote an arrhythmogenic substrate.

The rational to the use of Nav blockers to unmask Brugada ECG phenotypes is thus notably supported by the high occurrence of SNC5A mutations. Consequently, in case of SCN5A mutation, the use of a Nav blocker will rapidly unmask the phenotype. In case where a SCN5A mutation is not involved, larger doses of Nav blocker could mimic a SCN5A mutation and thus reveal the phenotype.

The old types 2 and 3, with saddle-back ST segment elevation, no longer allow to make the diagnosis.

The diagnosis of Brugada syndrome remains context-dependent, as illustrated in the next section.

#### **2.2. Phenocopies**

A number of pathological conditions can mimic a Brugada type 1 pattern on the electrocardiogram. The works of Baranchuk and Anselm has improved knowledge in this area [6]. These observations are rare and no large series has allowed studying it yet.

Several clinical cases highlight many underlying conditions. Type 1 Brugada phenocopies have been observed in various cardiac diseases (myocardial ischemia such inferior infarction 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 electrocution [30]. Pectus excavatum can also mimic a type 1 pattern [31].

**3.2. Depolarization and conduction disorders**

frequent in case of mutation on the SCN5A gene [38].

*3.2.1.2. First degree atrioventricular block*

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

Brugada Type 1 Pattern and Risk Stratification for Sudden Death: Does the Key Hide in the ECG…

http://dx.doi.org/10.5772/intechopen.75488

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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

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.

among sinus bradycardia, sinus arrest, sick sinus syndrome, and chronotropic incompetence; • A Holter ECG was practiced in case of doubt to correlate electrical events and symptoms; and

• electrophysiological exploration of the sinus node was also performed.

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

• clinical-electrical criterion with correlation between symptoms (faintness, syncope) and a documented event

children [40] and a cohort of women [41] with Brugada syndrome (**Table 1**).

*3.2.1. Supraventricular level*

*3.2.1.1. Sinus node dysfunction*

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 pharmacological challenge.

The prognostic impact of phenocopies is poorly documented.
