Brugada syndrome

Synonyms

1

Overview

Brugada syndrome (BrS) is a genetic disease that is characterised by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death. It is named by the Spanish cardiologists Pedro Brugada and Josep Brugada. It is the major cause of sudden unexplained death syndrome (SUDS), also known as sudden adult death syndrome (SADS), and is the most common cause of sudden death in young men without known underlying cardiac disease in Thailand and Laos.

Although the ECG findings of Brugada syndrome were first reported among survivors of cardiac arrest in 1989, it was only in 1992 that the Brugada brothers[5]recognized it as a distinct clinical entity, causing sudden death by causing ventricular fibrillation (a lethal arrhythmia) in the heart.

Symptoms

  • Ventricular arrhythmia
  • Abnormal heart rhythm
  • Fainting
  • Seizures
  • Breathing difficulty

Causes

In 20-30% of cases, a loss-of-function mutation in the SCN5A gene is found. Another locus on chromosome 3 has been reported, but thus far the gene is still unknown. The genetic cause or causes of the remaining cases of Brugada syndrome are still under investigation. Many clinical situations may unmask or exacerbate the ECG pattern of Brugada syndrome. Examples are use of sodium-channel blockers, a febrile state, use of vagotonic agents, use of alpha-adrenergic agonists, use of beta-adrenergic blockers, use of heterocyclic antidepressants, use of a combination of glucose and insulin, hyperkalemia, hypokalemia, hypercalcemia, and alcohol or cocaine intoxication (Antzelevitch, 2005).

Diagnosis

Genetic testing 

Genetic testing for Brugada syndrome is clinically available and may help confirm a diagnosis as well as differentiate between relatives who are at risk for the disease and those who are not. Some symptoms when pinpointing this disease include fainting, irregular heartbeats, and chaotic heartbeats. However, just detecting the irregular heartbeat may be a sign of another disease so the doctor must detect another symptom as wel.

Electrocardiography

In some cases, the disease can be detected by observing characteristic patterns on an electrocardiogram, which may be present all the time or might be elicited by the administration of particular drugs (e.g., Class IA (ajmaline, procainamide) or class 1C (flecainide, pilsicainide) antiarrhythmic drugs that block sodium channels and cause appearance of ECG abnormalities) or resurface spontaneously due to as yet unclarified triggers.

Brugada syndrome has three different ECG patterns.

  • Type 1 has a coved type ST elevation with at least 2 mm (0.2 mV) J-point elevation a gradually descending ST segment followed by a negative T-wave.
  • Type 2 has a saddle back pattern with a least 2 mm J-point elevation and at least 1 mm ST elevation with a positive or biphasic T-wave. Type 2 pattern can occasionally be seen in healthy subjects.
  • Type 3 has either a coved (type 1 like) or a saddle back (type 2 like) pattern with less than 2 mm J-point elevation and less than 1 mm ST elevation. Type 3 pattern is not rare in healthy subjects.

The pattern seen on the ECG is persistent ST elevations in the electrocardiographic leads V1-V3 with a right bundle branch block (RBBB) appearance with or without the terminal S waves in the lateral leads that are associated with a typical RBBB. A prolongation of the PR interval (a conduction disturbance in the heart) is also frequently seen. The ECG can fluctuate over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the ST segment elevation, while vagal stimulation worsens it. (There is a case report of a patient who died while shaving, presumed due to the vagal stimulation of the carotid sinus massage.)

The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever. Exercise decreases ST segment elevation in some patients but increases it in others (after exercise when the body temperature has risen). The changes in heart rate induced by atrial pacing are accompanied by changes in the degree of ST segment elevation. When the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. However, the contrary can also be observed.


Treatment

The cause of sudden death in Brugada syndrome is ventricular fibrillation (VF). The average age of death is 41. According to clinical reports, sudden death in people with Brugada syndrome most often happens during sleep.The episodes of syncope (fainting) and sudden death (aborted or not) are caused by fast polymorphic ventricular tachycardias or ventricular fibrillation. These arrhythmias appear with no warning. While there is no exact treatment modality that reliably and totally prevents ventricular fibrillation from occurring in this syndrome, treatment lies in termination of this lethal arrhythmia before it causes death. This is done via insertion of an implantable cardioverter-defibrillator (ICD), which continuously monitors the heart rhythm and will shock the wearer if ventricular fibrillation is sensed.

Recent studies have evaluated the role of quinidine, a Class Ia antiarrhythmic drug, for decreasing VF episodes occurring in this syndrome. Quinidine has been found to both decrease the number of VF episodes and correct spontaneous ECG changes, possibly via inhibiting Ito channels.  Some drugs have been reported to induce the type-1 ECG and/or (fatal) arrhythmias in Brugada syndrome patients. Patients with Brugada syndrome can prevent arrhythmias by avoiding these drugs or using them only in controlled conditions. Those with risk factors for coronary artery disease may require an angiogram before ICD implantation.