Introduction: syndromes in the cardiovascular circulatory system are very frequent; bring with them the death of millions of people, one of the least known and rare is the Brugada Syndrome that affects cardiac ion channels, characterized by clinical manifestations such as arrhythmias, tachycardia, syncope among others. This makes urgent the implementation of an outbreak to increase knowledge of this syndrome. Objective: to describe the Brugada Syndrome as a cardiac manifestation. Method: an information search was carried out in the SciELO , Scopus, PubMed, BASE and Redib databases in the period from March to April of the year 2022. Of 30 bibliographic references were cited 24 references. Development: Brugada Syndrome is a rare cardiac arrhythmia; the usefulness of clinical, electrocardiographic and electrophysiological parameters showing an ST segment elevation with type 1 morphology ≥2 mm between the right precordial leads V1 and/or V2 positioned in the second, third or fourth intercostal space, occurring spontaneously from the patient They are effective for a better diagnosis of this syndrome and thus its correct treatment. Conclusions: currently the total number of patients suffering from the syndrome is not known. It was found that the majority of appearances are in the male sex. Affect children, youth and adults over 60 years of age. In asymptomatic patients, clinical-echocardiographic follow-up is recommended to stratify the risk of complications.
Cardiac arrhythmia, Electrocardiograph, Brugada syndrome, Sudden death.
Brugada syndrome (BS) is part of a group of cardiac diseases known as channelopathies [1] and belongs to a group of diseases known as hereditary primary arrhythmia syndromes [1] . It is a non-structural cardiac disease that affects cardiac ion channels, characterized by clinical manifestations such as arrhythmias, tachycardia, syncope, among others [2] .
It was first described in 1992 by Pedro and Josep Brugada [3] , known as “right bundle branch block syndrome, persistent ST-segment elevation and sudden death”, in 1996 it was first named Brugada syndrome in Japan. A report was published on 8 individuals resuscitated from sudden cardiac death, caused by documented ventricular fibrillation (VF). These individuals had a characteristic ST-segment elevation in the right precordial leads of the electrocardiogram (ECG) in a structurally normal heart. In 1998, the first genetic alteration in the SCN5A gene associated with BS was identified within a family [4] .
The total number of patients with BS is difficult to determine due to the unknown true prevalence of asymptomatic patients and the dynamic variability of the ECG pattern in individuals. However, its prevalence is thought to range from 1 in 2000 to 1 in 5000. It has been considered responsible for 4% to 12% of all sudden deaths and up to 20% of sudden deaths in patients with structurally normal hearts, and is 8 to 10 times more prevalent in men than in women [5] .
In Western countries, the approximate prevalence is 1 to 5 cases per 10,000 inhabitants, while in Eastern countries, 1 in every 2,500 people present the syndrome. In the Americas, epidemiological studies on the subject have not been carried out, so the exact number of cases is unknown and further study is required. In its minority, some cases have been reported in countries such as the United States, Canada, Brazil, Argentina and Uruguay [3] .
It is objectively necessary to investigate the characteristics of Brugada syndrome because it is a rare disease, about which there is not enough literature. It has become a health problem, hence the need for a literature review, which aims to describe this syndrome as a cardiac manifestation.
A search was conducted in the SciELO, Scopus, PubMed, BASE, and Redib databases from March to April 2022. The terms "Brugada Syndrome"; "Cardiac Arrhythmia"; "Sudden Death"; "Electrocardiography" and their English translations were used to search for information; combined using Boolean operators to narrow down the database search results, the most commonly used being AND, OR, and NOT.
Articles published between 2017 and 2022 were used. Of the 30 bibliographic references, 26 were cited that met the validity criteria: approval by a recognized institution, support by scientific research theories or methods, and relevance and relevance of the articles.
BS occurs due to genetic mutations that produce a loss of function in the inward ionic currents, including the sodium channel (INa) and the Ca channel (ICa) or a stimulation in the outward ionic currents; also, the potassium ionic current (Ito) and the ATP-sensitive potassium ionic current (IK-ATP) [6] .
The normal action potential in BS shows alterations, which is why two hypotheses have been described: impaired repolarization and depolarization theory. The impaired repolarization explains that the imbalance of positive charges due to altered ionic currents leads to a loss of the plateau, shortening it by 40-70% in the epicardium. This causes a transmural dispersion of repolarization and refractoriness, which gives rise to the typical ECG pattern, with ST segment elevation observed in right precordial leads, as well as the inscription of the J wave [3], [6] .
The inscription of the J wave, with an amplitude of ≥2 mm, is mainly due to the development of a transmural voltage gradient during the early phases of the action potential caused by the predominance of the outgoing currents, especially the potassium current (Ito) that mediates the appearance of the notch, spike or dome morphology of the action potential in the epicardium but not in the endocardium [6] .
According to Puga-Bravo MV [7] , the diagnosis of BS is based on an ECG showing ST-segment elevation with type 1 morphology≥2 mm in 1 or more leads between the right precordial leads V1 and/or V2 positioned in the second, third or fourth intercostal space, occurring spontaneously or after a drug challenge, with intravenous administration of sodium channel blockers (such as ajmaline, flecainide, procainamide, or pilsicainide) [7] .
The presence of all other known causes of ST-segment elevation in the right precordial leads must be excluded before making the diagnosis of BS, e.g. , convex superior elevation of acute myocardial infarction, in which completely occlusive thrombi produce ischemia-necrosis of the ventricular wall in the area where the myocardium is supplied by the affected coronary artery and usually elevate the ST segment greater than 1 mm in two or more leads V2 and V3 greater than 2 mm. In pericarditis, generalized, concave ST-segment elevation is present; ST depression in aVR and PR depression are frequently present [8], [9] .
There are three electrocardiogram patterns in Brugada syndrome, even in the same patient at different times, only type I is considered diagnostic of the disease [10] :
a) Type I pattern: downward elevation of the ST segment ≥ 2 mm in more than one right precordial lead (V1-V3), followed by negative T waves.
b) Type II pattern: characterized by ST segment elevation ≥ 2 mm in the right precordial leads followed by positive or isobiphasic T waves, giving the electrocardiogram a saddle-shaped appearance.
c) Type III pattern: defined as either of the two above if the ST segment elevation is ≤ 1 mm.
The diagnosis is purely electrocardiographic, with a highly suggestive but not pathognomonic pattern, so there are differential diagnoses from an electrocardiographic perspective. Some research suggests that asymptomatic patients are at greater risk of sudden death due to the lack of a timely diagnosis.
According to Brugada J [5] , patients with SB may present syncope, seizures and nocturnal agonal breathing due to polymorphic ventricular tachycardia (PVT) [5] . Most asymptomatic patients are never diagnosed, therefore they are at risk of obtaining serious manifestations.
Symptoms usually first appear during adulthood, with a mean age of onset of MSC of 41 ± 15 years, although the onset of the first symptoms can also occur in children and the elderly [5] .
Fever, alcohol intake, and medications may increase the occurrence of arrhythmias; these triggers may unmask an ECG pattern of BS in asymptomatic patients [11] .
Fever decreases the activation and accelerates the inactivation of sodium channels present on the surface of the right ventricle that are basally reduced and dysfunctional in patients with BS, this facilitates the appearance of the type I pattern with the generation of malignant ventricular arrhythmias [12] .
Multiple genes have been linked to the presentation of this syndrome, among which the SCN5A gene stands out, the most described in the literature, which is the main one involved in the sodium channel [13] , in addition there are others in a smaller percentage.
Dissimilar potentially pathogenic variants associated with SB have been reported in other genes for example (CACNA1C, GPD1L, HEY2, PKP2, RANGRF, SCN10A, SCN1B, SCN2B, SCN3 B, SLMAP and TRPM4) . In recent years, (ABCC9, CACNA2D1, KCND2, KCND3, KCNE3, KCNE5, KCNH2, CACNB2, FGF12, HCN4KCNJ8, LRRC10 and SEMA3A) have been suggested [14] , however, no clinical and cellular study has confirmed the association of these genes with the syndrome.
Sex. Since SB transmission is observed with an autosomal mode of inheritance, the prevalence is expected to be similar between men and women. However, SB clearly has a high predominance in men, and a threefold increased risk of a type 1 ECG pattern and/or cardiac event [11] .
Males are more vulnerable to this syndrome than females. The higher prevalence in males than in females, found in a ratio of 8:1, is probably due to the regulatory action of sex hormones, which allow greater expression of genes sensitive to steroid hormones, especially testosterone, which favors greater expression of sodium channels in the heart [15] .
Age. The risk may be significant, particularly in children with previous symptoms and a spontaneous ECG pattern. However, the risk of arrhythmia appears to decrease significantly after age 60 [16] .
The prevalence and clinical implications of SB in children and young populations remain unclear, but malignant infections have been reported, which is a topic requiring further investigation. Current diagnosis in children is based on ECG patterns similar to those in adults [17] .
Treatment options for BS have been limited to medications. Fever should be treated promptly with antipyretics and/or physical measures, and any contraindicated substances should be avoided [16] .
Radiofrequency ablation is a procedure that scars heart tissue to block abnormal electrical signals. Ablation of abnormal potentials resulted in elimination of the Brugada pattern on the surface electrocardiogram and prevention of spontaneous ventricular arrhythmias and has been suggested as a possible therapeutic option . Initial work in patients with electrical storm has shown to be effective in controlling ventricular arrhythmias [20] .
The ability to use ajmaline or other class I drugs and three-dimensional electroanatomical mapping to perform ablation and persistently normalize the ECG pattern and prevent VF inducibility holds great promise for the long-term value of epicardial ablation [19] .
Keushkerian J [20] expressed that the only treatment that has proven effective is the implantation of a defibrillator, but it is accompanied by a high risk of complications in this population, the evaluation of rhythmic risk is essential for the management of these patients [20] . It is advisable to use another type of treatment to preserve health.
Currently, BS is treated with certain drugs or with the use of an implantable cardioverter-defibrillator (ICD) in symptomatic patients. However, in asymptomatic patients, deciding on a therapeutic approach is very difficult. Available drugs include quinidine, which has proven useful in the treatment of patients who develop electrical storms, as well as isoproterenol, disopyramide, and orciprenaline [21] .
Treatment of electrical storm aims to increase calcium current (depolarizing) to normalize ST segment elevation and reduce phase 2 reentry. Isoproterenol, as a beta-adrenergic agonist, may be effective, preferably in association with quinidine [18] . Quinidine, an important Ito channel blocker, has been shown to be safe and to reduce arrhythmic events in clinical follow-up of high-risk patients [22] .
Counseling in daily living for patients is very effective, this includes: avoiding excessive alcohol intake, treating fever aggressively and progressively decreasing physical activity [23] and performing family screening to achieve early identification of affected family members who could be at risk.
Before the If this syndrome is suspected in the patient, it is recommended to avoid some risk factors that increase ST segment elevation, such as cocaine and alcohol intake and the use of antiarrhythmic drugs (procainamide, propafenone), psychotropic drugs (amitriptyline, lithium) and anesthetics/analgesics (procaine and propofol), among others [24] .
Some authors [25], [26] consider that the drugs that should be avoided in Brugada syndrome include class IA and class IC antiarrhythmics, tricyclic antidepressants, oxcarbazepine, acetylcholine, ergonovine, cocaine, marijuana, although there are reports of isolated cases with the use of beta blockers and calcium channel inhibitors.
The total number of patients suffering from the syndrome is currently unknown. It has been found that the majority of cases are in males. It affects children, young adults, and adults over 60 years of age. Clinical and echocardiographic monitoring is recommended for asymptomatic patients to stratify the risk of complications. Pharmacological treatment is among the most widely used, although the only one that has proven effective is the implantation of a defibrillator.
DMH: conceptualization , research , administration of the project , supervision , writing from the original draft, writing , revision .
EAHG: conceptualization , research , writing from the original draft, writing , review and editing .
The authors declare that there was no conflict of interest.
The authors declare that there was no funding for the production of this article.
Copyright 2024 Deborah Mitjans Hernández et al.
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