Pedro Brugada and his two brothers Josep and Ramon described this syndrome in 1992. The syndrome is characterized by a very peculiar featureelectrocardiogramand patients experience syncope, life-threatening ventricular arrhythmias, cardiac arrest, or even sudden cardiac death. The Brugada brothers also discovered that the syndrome - which was nicknameddas Brugada-Syndrom– appeared to be hereditary, as many patients reported a family history of the same symptoms and events. Perhaps the most distinctive feature was the characteristicST segment elevationson lines V1-V3.
Prevalence and genetics of Brugada syndrome
The prevalence of Brugada syndrome is still largely unknown. Available data suggest that it is more common in Asia, particularly in Thailand. The prevalence in the Caucasian population is believed to be about one in ten thousand individuals. Men are affected about ten times more often than women, and men also have the highest risk of developing malignant ventricular arrhythmias.
Brugada syndrome is hereditary with an autosomal dominant inheritance pattern, which means that only one mutated gene is needed for the disorder to develop. To date (2016), more than 12 genetic mutations have been associated with Brugada syndrome. These mutations are in genes that code for potassium and calcium channels in the cell's outer membrane.
Clinical picture of Brugada syndrome
Most patients are asymptomatic in the age group of 20 to 55 years. The disorder may manifest with any of the following symptoms:
- Syncope, pre-syncope
- ventricular tachycardia
- ventricular fibrillation
- cardiac arrestwith or without sudden cardiac death
Therefore, Brugada syndrome is a highly malignant condition that should be recognized by any healthcare professional. A family history of any of the symptoms and manifestations listed above should always raise suspicion of serious hereditary arrhythmias. Although clinicians are increasingly aware of Brugada syndrome, the diagnosis is still overlooked despite its obvious clinical presentation.
It should be noted that the ECG features of Brugada syndrome are quite specific for the disorder as long as the clinical features are consistent with the disorder. However, there are other disorders that can produce similar electrocardiographic changes and they are as follows:
- Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC/ARVD)-AVC also tends to manifest in young adults and the most common symptoms are palpitations (prevalence 40%), syncope (30%), sudden cardiac death (15%), atypical chest pain (30%) and dyspnea (10% ) . The main ECG findings in VAD/C areT wave inversionin V1–V3 (in the absence ofright bundle branch block); virtually all patients have it. OEpsilon-Welle,which is much less common (one third of patients), is defined as a wave that occurs in the first part of theST segment.
- hyperkalemiacan cause ST-segment elevations in V1-V3 similar to Brugada syndrome. This disorder is easily diagnosed with a simple blood test, and ST-segment elevations disappear once potassium levels return to normal.
- Brugada-like ECG changes may appear transiently thereafterelectrical cardioversion.
- early repolarizationit also has J-spot elevation (as does Brugada syndrome, see below) and can also result in syncope, ventricular arrhythmias, and even sudden cardiac death. However, ECG changes in early repolarization are easily distinguishable from those in Brugada syndrome, and the risk of ventricular arrhythmias and sudden cardiac death is significantly lower than the risk in patients with Brugada syndrome.
It follows that Brugada syndrome is a likely diagnosis in patients with these symptoms and typical ST-segment elevations in V1–V3 (see below).
Characteristic ECG changes may be intermittent, which is why the diagnosis may be missed. For unknown reasons, ECG changes, as well as arrhythmias and deaths, are more common during rest, sleep, fever, and situations of high vagal tone. Interestingly, exercise does not seem to induce arrhythmias, distinguishing Brugada syndrome from other channelopathies (eg, long QT syndrome (LQTS) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (up to 80% may experience ventricular arrhythmias during exercise).
If Brugada syndrome is suspected, ECG changes can be pharmacologically induced under controlled circumstances. Sodium channel blockers (Ajmaline, Flecainide) are given intravenously, with defibrillator and resuscitation functions set to produce the ECG changes. It should be noted that the list of drugs and disorders that can induce a Brugada ECG (and therefore the risk of arrhythmia) is much longer and includesbeta blockers, cocaine, hypercalcemia, etc. This list is continuously updated and maintained inwww.brugadrugs.org.
The ECG in Brugada syndrome
Brugada syndrome ECG: criteria and definitions
Brugada syndrome can present with three different electrocardiogram patterns, called Brugada syndrome type 1, type 2, and type 2 ECG. The most typical and diagnostic is Brugada syndrome type 1. It presents with large bulging ST-segment elevations and T-wave inversions in leads V1–V3. Arched elevations of the ST segment can resemble a shark's tailFigure 1, Panel A. These ECG changes should not be confused with right bundle branch block, as this error can be devastating for the patient. Prospective studies show that type 1 Brugada syndrome has the strongest correlation with future risk of ventricular arrhythmias and cardiac arrest.
Note that ECG changes in patients with Brugada syndrome are dynamic. Most patients actually have a normal EKG most of the time, but they spontaneously convert to Brugada EKG patterns. As mentioned above, certain medications (www.brugadrugs.org) and situations (sleep, rest, fever) can also produce changes in the ECG. The patient can view all three Brugada ECG types, even during the same ECG recording.
- Brugada syndrome type 1:Curved ST-segment elevation ≥ 2 mm continuing in T-wave inversion in leads V1 and/or V2. This pattern establishes the diagnosis of Brugada syndrome (ie, no further investigation is required). Note that the electrodes in leads V1 and V2 can be placed in the second, third, or fourth intercostal space to monitor these ECG changes. Refer toillustration 1.
- Brugada syndrome type 2:Saddle-shaped ST-segment elevation with elevated J-spot ≥2 mm in leads V1 and/or V2. The final segment of the ST segment is elevated ≥1 mm.
- Brugada syndrome type 3:Similar to type 2 criteria, but the terminal part of the ST segment is < 1 mm elevated.
Note that it is permissible to record 12-lead ECG if electrodes from leads V1 and V2 are placed in the second, thirdorfourth intercostal space to maximize the likelihood of detecting ECG changes. This maneuver is recommended in available consensus documents.
Regarding type 2 and type 3 ECG patterns, the diagnosis of Brugada syndrome is only made if the patient converts to a type 1 ECG pattern after administration of class I antiarrhythmics (this is discussed in the electrophysiology laboratory under conditions controlled).
Screening for Brugada syndrome
It is motivated to examine family members of patients with Brugada syndrome. It is also motivated to perform an ECG in all patients whose clinical characteristics suggest the suspicion of Brugada syndrome. There are currently no other indications for screening.
The risk of syncope, life-threatening ventricular arrhythmias, cardiac arrest and/or sudden cardiac death is very high in patients with Brugada syndrome. The risk is greatest during sleep, rest, fever, and situations of high vagal tone. OVentricular tachycardia is polymorphic. Furthermore, the risk is higher in patients with a type 1 ECG pattern. For unknown reasons, up to 20% of patients with Brugada syndrome develop supraventricular tachyarrhythmias such as atrial fibrillation (AVNRT and WPW have also been described).
Treatment and management of Brugada syndrome
Some small lifestyle changes are needed. Excessive alcohol consumption is considered proarrhythmic and therefore should be avoided. The patient should not take medications that may cause arrhythmias; The list of these drugs is extensive and a constantly updated list is available atwww.brugadrugs.org/drug-lists/.
ICD (implantable cardioverter defibrillator) for Brugada syndrome
Prospective studies show that the use of an ICD can be of great benefit in selected cases of Brugada syndrome. The ICD prevents sudden cardiac death and thus increases the survival rate. However, the ICD is not indicated in individuals with asymptomatic Brugada syndrome (regardless of the ECG pattern) because the risk of sudden cardiac arrest is very low.
An ICD should be considered in the following situations:
- Patients who survive cardiac arrest should have an ICD.
- Patients with documented sustained ventricular tachycardia should receive an ICD.
- Patients with Brugada ECG type 1 and a history of syncope may benefit from an ICD. Therefore, an ICD should be considered.
- Patients with reducible ventricular fibrillation during invasive challenge (pacing during an electrophysiological study) may benefit from an ICD. Therefore, an ICD should be considered.
Therefore, the ICD is not indicated in asymptomatic individuals, regardless of the electrocardiographic pattern. ICD is also not indicated based on a family history of events. However, if ICD is being considered, family history should be included in risk stratification.
Quinidine (class I antiarrhythmic drug)
Quinidine reduces the occurrence of ventricular arrhythmias in patients with Brugada syndrome. This medication may be considered in patients with 3 or more episodes of ventricular fibrillation or ventricular tachycardia in 24 hours. Quinidine should also be considered in patients who do not wish to have an ICD or who have a contraindication for ICD use.
prior and others: Abstract: HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Hereditary Primary Arrhythmia Syndromes.
Antzelevitch and others: Brugada Syndrome: Report of the Second Consensus Conference.