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Publicaciones > Revista > 12V41N4

Brugada syndrome

 

Paola Berne*, Luis Enrique Aguinaga†, Josep Brugada*

 

*Sección de Arritmias, Servicio de Cardiología, Instituto Del Tórax,
Hospital Clínic, Instituto de Investigación Biomédica August Pi i Sunyer (IDIBAPS) Universidad de Barcelona, Cataluña, España.
† Centro Privado de Cardiología, Tucumán, Argentina.
E-Mail

Recibido 24-AGO-12 – ACEPTADO 31-AGOSTO-2012.

The authors declare not having a conflict of interest.

 


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SUMMARY

Brugada syndrome is a primary electric cardiac disease (it does not produce structural abnormalities of the heart). It has a genetic basis, and it is characterized by distinctive electrocardiographic abnormalities and an increased risk of sudden cardiac death secondary to polymorphic ventricular tachycardia / ventricular fibrillation, mainly affecting individuals during the fourth decade of life. Two consensus documents on the syndrome have been published (2002 and 2005), in order to establish its diagnostic criteria, risk stratification and therapeutic indications. In spite of the increasing amount of information generated by multiple research groups worldwide, controversy remains in some areas, especially regarding the pathophysiological basis of the disease or risk stratification in asymptomatic patients. This article provides a review of the recent advances in knowledge regarding genetic and molecular basis of Brugada syndrome, its arrhythmogenic mechanisms, clinical course and tools for risk stratification and treatment of the condition.

Key words: Brugada syndrome. Cardiac channelopathies. Sudden cardiac death. Ventricular fibrillation.
Rev Fed Arg Cardiol. 2012; 41(4):

 


INTRODUCTION
Brugada syndrome (BrS), described for the first time in 1992 by Pedro and Josep Brugada [1], is a primary electrical disease or cardiac channelopathy that is not accompanied by structural alterations, with a genetic basis with variable penetrance, the diagnosis of which is based on the presence of characteristic repolarization alterations located in the right precordial leads and that entails the risk of sudden cardiac death (SCD) secondary to polymorphic ventricular tachycardia (PVT) and/or ventricular fibrillation (VF). This paper offers a review on the recent advancements on the knowledge on the genetic and molecular basis of Brugada syndrome, its arrhythmogenic mechanisms, its clinical evolution, and an update on the tools used for risk stratification and the management of this pathology.

Epidemiology and general characteristics.
The estimated world prevalence of BrS is approximately 0.05% or 1 in 2,000 individuals [2], and it presents a marked geographical and ethnical variability, lower prevalence in Europe [3-5] and higher in Southeast Asia [6], where it is considered endemic, and it has been acknowledged as the same phenotypical, genetic and functional entity as sudden unexplained nocturnal death syndrome (SUNDS) in Japan and Thailand [7]. There is also evidence that connects BrS to the sudden infant death syndrome (SIDS) [8]. BrS is responsible for 4% of all sudden cardiac deaths and of up to 20% of SCD that occur in patients without structural heart disease [9].

The average age at the moment of the diagnosis in most of the series is around 40 years old (although Brugada syndrome has been identified in patients with ages ranging from 2 days of life to 84 years of age)[9]. Most arrhythmic events also occur during the third or fourth decades of life [10-15]; generally during sleep, rest or after abundant meals.

The series published to the present, show a clear prevalence of the male gender between adult patients (representing approximately 80% of patients) [10,11,13-15], while in patients in a pediatric age, there had been no differences observed in prevalence according to gender [16]. These differences seem to have hormonal causes, as well as differences of expression of determined cardiac ion currents between men and women (see “Pathophysiology of Brugada syndrome”).

Electrocardiographic pattern diagnostic of Brugada syndrome
The diagnosis of BrS requires the objectification of a characteristic repolarization pattern called “Type 1 BrS” in at least 2 right precordial leads (V1 though V3) [9,17] and less frequently in the inferior side leads (DII, DIII and aVF)[18], characterized by prominent ST segment elevation of convex morphology, with J point width or ST segment elevation equal or greater than 2 mm, followed by negative T wave (Figure A). Another two repolarization patterns, respectively called “Type 2 BrS” (J point elevation ≥2 mm, ST segment elevation ≥1 mm of concave morphology, followed by positive or biphasic T wave), and “Type 3 BrS” (concave or convex morphology, with ST segment elevation <1 mm) are considered suggestive, although not diagnostic of the pathology, when observed in the previously mentioned locations (Figures B and C). The repolarization disorders characteristic of BrS have a dynamic character [19,20]. The patient himself could present the 3 electrocardiographic patterns associated to the syndrome at different times, as well as normal ECGs in the baseline, with appearance of type 1 BrS pattern being observed with different stimuli such as fever, vagotonic agents or class I antiarrhythmic agents.

For type 1 BrS pattern to be considered diagnostic of the pathology, it should be observed in at least 2 right precordial leads (V1 to V3) [9,17]; however, there is evidence that patients with type 1 ECG pattern in V1 or V2 in an isolated fashion, present a clinical and arrhythmic risk profile similar to that of patients with diagnostic ECG pattern in more than one lead; the same publication showed that lead V3 in general does not contribute diagnostic information in these patients [22]. These results may lead to the review of the current diagnostic criteria, accepting as diagnostic the finding of type 1 BrS pattern in a single right precordial lead.

A
 
B
 
C
 

Figure 1: The three ECG patterns associated to Brugada syndrome. A:  type 1 ECG (diagnostic); B: type 2 ECG (suggestive); C: type 3 ECG (suggestive).


 

Pharmacological tests for the diagnosis of Brugada syndrome
Given the dynamic character of the ECG in BrS, and the capacity of class I antiarrhythmic drugs to reproduce the diagnostic ECG pattern, the administrationof such drugs is used to unmask the pathology in those patients in whom the pathology is suspected, but the baseline ECG is normal (example: in cases of family study) or suggestive although not diagnostic (types 2 or 3 ECG patterns). The drugs that are used most frequently for this goal, are ajmaline, flecainide and procainamide. Table 1 shows the current recommendations as to drugs, doses and administration ways. A recent publication suggests performing the ajmaline test over 10 minutes (instead of the 5 minutes recommended in the 2nd consensus[9]), since no significant differences were observed between the slow and the rapid tests in terms of diagnostic performance, and the risk of potentially deadly arrhythmias was lower with the slow infusion protocol (10 minutes) [23]. The development of a type 1 ECG pattern of BrS during the test is a criterion to stop it, as well as the appearance of type 2 BrS pattern with ST segment elevation equal or greater than 5 mm, QRS widening ≥130% of its initial value, or the development of any arrhythmia. The patient should remain monitored until the full normalization of the ECG after the test. The pharmacological test was considered positive only when a conversion to the type 1 ECG pattern occurs in at least 2 right precordial leads.

In patients carriers of mutations in the SCN5A gene, ajmaline proved to be better to flecainide in terms of sensibility, specificity, positive predictive value, and mostly negative predictive value (NPV: 83% in the ajmaline test vs. 36% in the flecainide test) [24,25]. The low negative predictive value of the flecainide test, along with the short half life of ajmaline make this drug the favorite for diagnosis in the case of suspicion of BrS.

Both at the beginning and at the end of the pharmacological test, it is advised to make a recording of V1 and V2 in the 2nd and 3rd intercostal spaces, since the sensibility of ECG is increased to diagnose BrS [26-28].

Differential diagnosis and factors modulating the ECG in Brugada syndrome
There is a series of pathologies that may be accompanied by electrocardiographic changes similar to BrS pattern, and that should be carefully ruled out before confirming the diagnosis of this pathology (Table 2).

Certain circumstances, such as expositionto drugs or medications, and alterations in the internal milieu among others, may cause ST segment elevation similar to that found in patients carriers of BrS; it is believed that the individuals that show these alterations present a genetic predisposition to BrS [29].

Fever also modulates the phenotype, manifesting the diagnostic ECG pattern of BrS, as well as the risk of arrhythmias, acting as trigger for arrhythmic events in some patients [30-34].

Confirmation of the diagnosis of Brugada syndrome
BrS is diagnosed in a definitive manner in patients in whom, having ruled out the differential diagnoses mentioned previously, a type 1 ECG pattern is evident, whether spontaneously or unmasked by class I antiarrhythmic agents, along with at least one of the following clinical diagnostic criteria:

A)- Data of family history:
 
-
SCD in a relative before 45 years of age.
 
-
    Type 1 ECG in relatives.
 
 
B)- Symptoms related to ventricular arrhythmias .
 
-
Síncope.
 
-
Seizures
 
-
Nocturnal agonal respiration
 
 
C)- Documented ventricular arrhythmias: :
 
-

Polymorphic ventricular tachycardia (PVT)

 
-
Ventricular fibrillation (VF).

Although not included in the clinical diagnosis criteria, it is important to point out that patients carriers of BrS usually report palpitations associated to a greater incidence of supraventricular tachycardias, mostly atrial fibrillation (up to 30% of cases [35,36]).

The isolated finding of type 1 ECG pattern without clinical criteria was called “idiopathic Brugada ECG pattern” in the first consensus document, but there are data [37,38] suggesting that this subset of patients also present an increased risk of sudden death. This fact, as well as the increasing role of the genetic test in the diagnosis of the disease, underscore the need of a review of the diagnostic criteria of BrS.

Genetic basis for Brugada syndrome
BrS is a pathology of a genetic basis that is transmitted by a pattern of dominant autosomal inheritance, with variable penetrance. Mutations in different genes that encode cardiac sodium (Na+), calcium (Ca+2) and potassium (K+) channels and that lead to a decrease in positive ion inward current (Na+, Ca+2) or increase in positive ion outward currents (K+) have been associated to this pathology.

The most frequent mutations found in patients with BrS (11-28% of cases) affect the SCN5A gene [39], which encodes the αsubunit of the cardiac Na+ channel and leads to a loss in function of the mentioned channel by different mechanisms, with up to 300 mutations described to this date [40]. Other genes associated to BrS by mutations that lead to a decrease in the voltage-gated Na+ current (INa) are: GPD1L (glycerol-3-phosphate dehydrogenase 1-like) [41], SCN1B [42] (that encodes the ß1- and ß1b- subunits, subunits modifiers of the auxiliary function of the cardiac Na+ channel, which in normal conditions increase INa); SCN3B [43] (that encodes the ß3 subunit of the cardiac Na+ channel) and MOG1 [44] (the mutations in this gene cause reduction of INaby interference in the traffic of the sodium channel toward the cell membrane). Mutations in the genes that encode the α-1 subunits (CACNA1C) and β- subunits (CACNB2b) of the L-type cardiac Ca2+ channel, and that cause a decrease in the inward Ca2+ current (ICaL) are responsible for a combined phenotype of BrS and short QT syndrome [45]. Mutations in the CACNA2D1 gene (that encodes the transmembrane δ1 subunit of the L-type calcium channel) also play a possible pathogenic role [46]. Mutations in genes that lead to an increase in outward K+ currents have been associated to BrS: KCNE3 [47] and KCNE5 cause an increase in the transient outward K+ current (Ito) to BrS [48]; and mutations in KCNJ8 (which encodes the α- subunit of the ATP-sensitive K+ channel (KATP Kir6.1 channel) that presents a preferential distribution in the epicardium) [49]. Finally, the mutations in the HCN4 gene and that lead to a decrease in the pacemaker current (If) have been associated to BrS [50].

The causal relationship is clearly established for mutations in the SCN5A and GPD1L genes (analysis of genetic ligation), while it is very likely in the cases of mutations in the CACNA1C, CACNB2b, SCN1B [42], KCNE3, SCN3B and HCN4 genes (co-segregation of BrS with mutations identified in small lineages) and it is not defined yet for the remaining subtypes (that should be considered as genes susceptible to cause BrS, since they have been identified in isolated patients). All this information confirms that BrS has a heterogeneous genetic basis, and it is suspected that the number of genes responsible for it will continue to increase.

Pathophysiology of Brugada syndrome
One of the greatest current controversies on BrS is that about the pathophysiological basis of that pathology. There are to date, two theories about it, the repolarization and depolarization theories.

There is evidence in animal models, as well as in human models that support the theory of repolarization [51-55]. The authors that advocate this theory state that the electrocardiographic manifestations and the increased risk of ventricular arrhythmias in patients with BrS are the direct consequence of an imbalance in active ion currents during the end of phase 1 of cardiac action potential (AP): a decrease in positive inward currents and/or an increase in positive outward currents lead to an enhancement of the notch at the end of AP phase 1, which causes an ST segment elevation in “saddleback” as a consequence of the repolarization of epicardial cells preceding that of M and endocardial cells, followed by positive T wave. Finally, the exaggeration of these ion changes causes a loss in the AP plateau, especially in the right ventricular (RV) epicardium. At this time, ST segment elevation will be greater, and its morphology will be convex, being followed by negative T wave secondary to reversion of the direction of repolarization from the endocardium to the epicardium, a consequence of AP prolongation in epicardial cells. All these changes generate a marked repolarization dispersion within the epicardium and transmurally. The propagation of the current from the sites where the AP plateau is maintained to sites of the myocardium where it has disappeared and/or is very decreased, causes a local re-excitation (a phenomenon called “reentry in phase 2”) that determines the appearance of premature ventricular contractions of epicardial origin, that may trigger PVT and/or VF episodes.

The authors that support the theory of depolarization, say that conduction disorders are the main pathophysiological event in BrS, which has been verified in ECG (prolonged PR interval, complete right bundle branch block, etc.) and also in different clinical tests, such as the electrophysiology study (prolonged H-V interval and endocardial and epicardial activation maps), body surface mapping, determination of late potentials, among others [1,56,57]. These authors also state that these patients may present minimal structural alterations, that would justify the finding of late potentials and of conduction disorders. Such conduction disorders are more marked at the level of the RV outflow tract (RVOT), which activates very late in relation to other RV areas. When depolarization has started in the RV but not in the RVOT, there is current circulation toward the latter, which is recorded as J point and ST segment elevation in the right precordial leads. When depolarization starts in the RVOT, the AP of the RV is in phase 3, so potential gradients intervene and the current circulation occurs from the RVOT to the RV, moving away from the right precordial leads, and being recorded in these negative T waves [58,59].

Although this theory could not be reproduced in animal models, there is increasing evidence in favor of its pathophysiological significance from clinical studies [60]. A recent publication showed that a small group of patients with BrS, symptomatic and carriers of implantable cardioverter defibrillator (ICD) and multiple appropriate shocks, with spontaneous type 1 BrS pattern and PVT/VF inducible in EPS, presented abnormally low voltages in the endo/epicardial electroanatomic map, and fractionated potentials of prolonged duration in the epicardium of the anterior side of RVOT. Radiofrequency ablation (RFA) of the mentioned sites rendered PVT/VF not inducible in the EPS in 78% of patients, and normalized the ECG pattern in 89%, with no recurrences of sustained ventricular arrhythmias in follow-up (20±6 months) [61]. Since there is evidence of the participation of both mechanisms in the genesis of BrS, and both theories are not mutually exclusive, the debate on the pathophysiological basis of BrS remains, and more studies will be necessary to clarify this point.

About the different prevalence of BrS according to gender in adults, it is believed that estrogens causes a decrease in the magnitude of the Ito current; while testosterone increases the slow K+ currents [62-66]. It has been observed as well, that there is a different expression and density of the Ito current according to gender (less density of it in women) [66,67].

Prognosis and risk stratification
The second great current controversy in BrS is the one about arrhythmic risk stratification, especially in the subset of asymptomatic patients. It has as its object the unequivocal identification of those patients in high risk of presenting a deadly or almost deadly arrhythmic event, and its subsequent protection by the implantation of an ICD. All the series agree in that symptomatic patients with BrS present a high arrhythmic risk:

-
SCD survivors present a high risk of SCD or fatal or near fatal ventricular arrhythmias recurrence (17-62% at 48-84 months of follow-up, according to different series) and therefore have a class I indication for the implantation of ICD (secondary prevention) [10-15,68].
-
Syncope of cardiac origin is also a high risk marker for arrhythmias (rate of recurrence between 6 and 19% at 24-39 months of follow-up in different series), and these patients also have a class I indication of ICD implantation [10-15, 68,69].
-
It is reasonable to implant ICDs in patients carriers of BrS and that presented documented VT, although it may not have led to SCD or symptoms (class IIa indication) [68].
-
Spontaneous type 1 ECG pattern has been identified as an independent predictor for ventricular arrhythmias in most series [10,15,69,70]. It is recommended to perform clinical monitoring by ECG, with the goal of detecting a spontaneous type 1 ECG pattern in patients with BrS, the diagnosis of which was made by pharmacological test, with or without prior symptoms (class IIa indication) [68].
-
Men present a higher tendency to develop arrhythmic events than women in some series, although the difference did not reach a statistical significance [15,37]
-
The risk of arrhythmic episodes in previously asymptomatic patients carriers of BrS varies according to the series: while the group of Brugada et al, reported a rate of events of 8% in 33±39 months of follow-up (HR: 2.5; CI=1.2-5-3; p=0.017) [12], the rest of the groups reported much lower rates of events in this subpopulation of patients (of 6-1% in follow-up of between 34-40 months [10,13,14,15, 69]).
-
The value of inducibility of sustained ventricular arrhythmias during electrophysiology study (EPS) as a tool to evaluate the arrhythmic risk in BrS is still the topic about which there is more debate. The results published by Brugada et al, indicated that inducibility during EPS is an independent predictor of risk of cardiac events (HR: 8.33; 95% CI=2.8-25; p=0.0001) [12], and a recent publication by Giustetto et al [14] presented similar results (none of the patients with negative EPS presented arrhythmic eventsagainst15% of patients who had positive EPS at 30±21 months of follow-up) although the rest of the registries did not show the same [10,13,15,69].
Numerous reasons have been proposed for the disparity in results between the different registries, including differences in inclusion criteria, stimulation protocols and statistical analysis methods. In situations in which low rates of events are observed, and times of follow-up are short in patients suffering a pathology that presents a prolonged time of arrhythmic risk, it is difficult to draw definitive conclusions on the prognostic value of a given test. Current guidelines consider that the use of EPS in risk stratification in asymptomatic patients with BrS with spontaneous type 1 ECG is a class IIb indication [68].
-
Data from the PRELUDE study [69], indicated that the presence of short ventricular refractory period (VRP) in patients with BrS, defined as VRP below 200 ms of cycle, was an independent arrhythmic risk predictor in this cohort of patients (sensibility 78.6%, specificity 62.9%). However, additional information is necessary, about the predictive value of this determination coming from this cohort and of other prospective studies, before recommending its use to stratify risk in BrS.
-
In none of the series published, differences were observed in the arrhythmic events when dividing the population of patients according to their carrying or not mutations identified with the SCN5A gene.
-
The finding of common polymorphisms in the SCN5A gene that may modulate the effect of mutations associated to BrS [71,72], causing an improvement in the BrS phenotype, suggests that the identification of polymorphisms would be useful as risk stratification tools, and that polymorphisms could transform into possible targets for future therapeutic interventions.

Noninvasive markers for arrhythmic risk proposed in Brugada syndrome
In an effort to solve the complex topic of risk stratification in BrS, numerous noninvasive methods have been proposed as risk markers for arrhythmic events in this population of patients:the decrease in the standard deviation of the NN interval in 5 minutes of analysis (SDANN) measured in Holter recordings [73]; S wave ≥ 80 milliseconds (ms) in V1 and ST segment elevation ≥ 0.18 mV in V2 [74], spontaneous changes in the ST segment [75], QT interval corrected (QTc) superior to 460 ms in V2, prolonged interval between the peak and the end of the T wave (Tp-e) and a dispersion of such Tp-e interval[76], the “aVR” sign (R wave ≥0.3 mV or R/q ≥0.75 in the aVR lead) [77]; a prolonged duration of the QRS complex in the precordial leads (r-J interval in V2 ≥90 ms and QRS ≥90 ms in V6; QRS ≥120 ms in V2) [78]; even an indicator of interventricular mechanical asynchrony has been associated to high risk of fatal or nearly fatal arrhythmic events in BrS [79]. The usefulness of late potentials evaluated by signal-averaged ECG (SAECG) as high risk markers has been evaluated by different groups in an extensive manner [20,75,80,81]. A recent publication identified the presence of QRS fragmentation (QRS-f), defined as 2 or more spikes in the QRS complex in the right precordial leads, as an independent risk predictor in a cohort of 308 patients studied in a prospective manner.

The usefulness of these noninvasive markers in the scheme of risk stratification for arrhythmias in patients with BrS should be proven in prospective studies that include a higher number of patients and a longer follow-up term.

Therapeutic options and recommendations for patients carriers of Brugada syndrome
- Implantable cardioverter defibrillator (ICD):
To this moment, the only therapeutic strategy that has shown to be effective to prevent SCD in patients with BrS is the implantation of an ICD. High rates of inappropriate shocks have been reported in this population of patients (20-36% at 21-47 months of follow-up), jointly with low rates of appropriate shocks (8-15% in an average follow-up of 45 months, annual rate of appropriate shocks of 2.6%). In fact, most series report that inappropriate shocks exceed 2 to 2.5 times the rate of appropriate shocks[82,83]. Between the recommendations to prevent inappropriate shocks, we find making a careful programming of the device, programming a single zone for VF therapy with a high cut-off rate (250 bpm minus the age of the patient in years, or a heart rate above 210-220 bpm)[84] increasing the window of detection, increasing the number of intervals to detect VF to 18 from 24, or 30 from 40[85,86], with the aim of preventing a shock on a nonsustained ventricular tachycardia. It is also recommended to emphasize the absolute contraindication to practice competitive sports and the limitations in the recreational practice of sports[87], especially those sports like rowing, swimming or weightlifting (that are associated to a greater risk of lead rupture), favoring the use of single-chamber devices (that have a lower rate of complications) and treating supraventricular arrhythmias.

- Pharmacological treatment of Brugada syndrome
With the aim of correcting the alterations in the ion currents involved in BrS, drugs have been tried that inhibit the Ito current or increase the Na+ and Ca2+ currents:

  • Isoproterenol (that increases the ICaL current) has proven to be useful to treat electrical storms in the context of BrS (class IIa indication) [68].
  • Quinidine, a class IA antiarrhythmic that has a blocking effect on the Ito and IKr currents, has been shown to prevent VF inducibility during EPS and to suppress spontaneous ventricular arrhythmias in a clinical scenario, currently being used in patients carriers of ICD that have presented multiple appropriate discharges; in cases in which the implantation of ICD is contraindicated or as an alternative to it, when the patient refuses the implant, or for the treatment of supraventricular arrhythmias. A high rate of gastrointestinal secondary effects have been reported in patients taking quinidine[88-91]. Quinidine has proven to be useful in the treatment of electrical storms in carriers of BrS [92,93] and its use in this context constitutes a class IIb indication[68].
  • Disopyramide[94] and orciprenaline [93,93] have also shown their usefulness in cases of electrical storm in some reports.

Radiofrequency ablation in Brugada syndrome, does it have a real clinical application?
Some publications have shown the usefulness of radiofrequency ablation (RFA) in patients with BrS of high risk and that presented frequent episodes of VF triggered by monomorphic premature ventricular contractions (PVC)[96-99], with the removal of arrhythmic events in follow-up. The following are good candidates for this approach: very symptomatic patients (multiple VF episodes/appropriate shocks), with very frequent monomorphic PVCs susceptible to be mapped, and refractory to pharmacological treatment. The reports published coincide in that the optimal time for RFA is immediately after the electrical storm, when the PVCs are more frequent.

In year 2011, the group by Dr. Nademanee reported the finding of abnormally low voltages in the electroanatomical endo/epicardial mapping, and fractionated potentials and of prolonged duration in the epicardium of the anterior side of RVOT in 9 patients with BrS of high risk: spontaneous and persistent type 1 ECG pattern of BrS, very symptomatic, with multiple appropriate ICD shocks and PVT/VF inducible in EPS. RFA in such areas rendered PVT/VF not inducible in the EPS in 78% of patients, normalizing the ECG pattern in 89%, with no recurrences of sustained ventricular arrhythmias in the follow-up (20±6 months)[61].

These reports indicate that both the ablation of frequent premature contractions and the ablation of the substrate may potentially have a role in the prevention of deadly or potentially deadly arrhythmias that affect a percentage of patients with BrS. More studies will be required to establish its real usefulness and limitations.

Other recommendations

  • It is recommended for the patients with BrS to prevent the use of drugs that unmask type 1 ECG and may potentially trigger ventricular arrhythmias, as well as preventing the unnecessary use of drugs, since the fact that a drug has not yet been identified as potentially dangerous for these patients, does not make its use safe. A Web page has been created (www.brugadadrugs.org) where there is updated information about the drugs and medications that should be prevented in this pathology and information about diagnostic tests and pharmacological treatment [100].
  • It is recommended to conduct ECG monitoring and an aggressive treatment during fever episodes, since fever can unmask the type 1 ECG pattern and has been acknowledged as a trigger for ventricular arrhythmias in patients with BrS.
  • The patients should consult urgently in case of presenting syncope.
  • A clinical evaluation is recommended in all 1st degree relatives of a patient carrier of BrS.
  • All patients should be followed regularly as outpatients, so as to identify the development of symptoms.
  • It is recommended to perform the genetic analysis, in case of being available (to confirm the clinical diagnosis, for the detection of affected relatives, and with investigation purposes).

 

CONCLUSIONS
After 20 years of having been described, the scientific knowledge on Brugada syndrome has increased exponentially in relation to its genetic and molecular bases, arrhythmogenic mechanisms, clinical evolution and treatment. A controversy still persists about the pathophysiologic mechanisms that determine the syndrome, as well as the risk stratification strategy of asymptomatic patients. Given the huge amount of valuable information gathered by numberless groups of investigators since the publication of the second consensus, we believe it is necessary to make a review of the current diagnostic criteria, prognostic tools and treatment recommendations. The data springing from prospective trials will help to refine our diagnostic and therapeutic approach in relation to patients with Brugada syndrome.

 

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