Brugada syndrome overview

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Overview
Historical Perspective
Classification
Pathophysiology
Differentiating Brugada syndrome from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Examples of Type I Brugada Syndrome
Chest X Ray
Echocardiography or Ultrasound
Electrophysiologic Studies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Brugada syndrome is a genetic disease that is characterized by abnormal electrocardiogram (EKG) findings and an increased risk of sudden cardiac death in young adults, and occasionally in children and infants. Brugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to uncoordinated electrical activity in the heart's lower chambers (ventricles), an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.

Historical Perspective

Brugada syndorme was potentially first seen on EKG in survivors of cardiac arrest in 1989, but it was not until 1992 that the Brugada brothers recognized it as a distinct clinical entity which could cause sudden death by ventricular fibrillation.

Classification

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide.

Pathophysiology

Approximately 20% of persons with Brugada syndome have a mutation in the gene SCN5A. This gene encodes for the sodium ion channel. The mutation is inherited in an autosomal dominant pattern, and is more commonly seen in males. Brugada syndrome has also been shown to result from defects in a calcium channel.

Differentiating Brugada syndrome from other Diseases

Brugada syndrome should be differentiated from other cardiac disorders, electrolyte disturbances, and drug intoxication syndromes. The condition which most similarly presents to Brugada syndrome is arrhythmogenic right ventricular dysplasia, as they both cause sudden cardiac death in children. Brugada syndrome can be differentiated from arrhythmogenic right ventricular dysplasia by the genetic counterpart of SCN5A, the lack of structural abnormalities within the heart, the association with polymorphic ventricular tachycardia during sleep, and EKG changes that are enhanced by vagotonic agents.

Epidemiology and Demographics

Insofar as Brugada syndrome is a relatively newly recognized syndrome, its incidence and prevalence continues to increase. Brugada syndrome is quite common in Southeast Asia where it is endemic, and affects 500 out of every 100,000 individuals. It is the second leading cause of death after car accidents among young people in these countries. It has been estimated that Brugada syndrome accounts for 4% of all sudden cardiac deaths and 20% of sudden cardiac deaths among patients with structurally normal hearts. It is 8-10 times more common in men.

Risk Factors

The EKG changes of Brugada syndrome can vary 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. During sleep, there is heightened vagal tone, and the pattern may be exacerbated at that time (as is the risk of sudden cardiac death at that time). The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever. The impact of exercise depends upon when the EKG is obtained: during exercise the ST segment elevation may decrease but may increase later after exercise when the body temperature has risen. Similar to early repolarization variant, when the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. While Brugada syndrome is often associated with polymorphic VT which may be self terminating, in the presence of autonomic imbalance, hypokalemia, fever or exacerbating drugs sustained ventricular fibrillation and sudden cardiac death may result.

Screening

Relatives of patients with Brugada syndrome can be screened for the syndrome by obtaining an EKG, although the diagnostic pattern may be concealed. Genetic testing can also be used to support the diagnosis of Brugada syndrome and to detect relatives at risk. Unfortunately, despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis.

Natural History, Complications and Prognosis

Brugada syndrome usually becomes apparent in adulthood, although it may present in infants and children as sudden cardiac death. The mean age of sudden death in patients with Brugada syndrome is 40 years old. The Brugada patient may develop atrial arrhythmias and abnormalities in atrial conduction, and these abnormalities are associated with inducibility of ventricular fibrillation. Implantation of a cardiac defibrillator AICD can improve prognosis for some.

Diagnosis

Diagnostic Criteria

The diagnosis of brugada syndrome is based upon electrocardiographic and clinical criteria. Only the Type I Brugada pattern qualifies as part of the diagnostic criteria for Brugada syndrome. Other rhythm abnormalities and family history are also taken into account when making the diagnosis of Brugada syndrome.

History and Symptoms

Patients with Brugada syndrome will sometimes have a family history of sudden cardiac death and a personal history of of arrhythmias. If patients are symptomatic they often have symptoms of syncope, seizures, agonal breathing, difficulty breathing, and patients may even present with sudden death. These symptoms most often come on either at rest or during sleep.

Physical Examination

Insofar as Brugada syndrome is not associated with any structural heart disease, there are generally no abnormalities on physical examination. Vagal maneuvers such as carotid sinus massage may increase vagal tone and may unmask the presence of a Type I Brugada pattern. In a patient who has experienced recent symptoms such as syncope, it is important to check the temperature in so far as fever may trigger a self terminating or sustained episode of ventricular tachycardia / ventricular fibrillation. The presence of fever is also a target of antipyretic therapy.

Laboratory Findings

Hypokalemia and hyperkalemia can both trigger either sustained or nonsustained episodes of ventricular tachycardia / ventricular fibrillation and serum electrolytes should therefore be checked. Both alcohol and cocaine intoxication can be associated with either sustained or nonsustained episodes of ventricular tachycardia/ventricular fibrillation and a toxicology screen should be ordered if there is a clinical suspicion. Likewise, tricyclic antidepressants can be associated with exacerbations of the syndrome, and levels of these agents should also be checked if there is a clinical suspicion.

Electrocardiogram

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide. Type 1 Brugada syndrome may always be present on the EKG, or it may be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels such as ajmaline, flecainide) or it may be unmasked by various triggers or risk factors.

Chest X Ray

Insofar as Brugada syndrome is not associated with structural abnormalities of the heart, there are no associated abnormalities on the chest x-ray.

Echocardiography or Ultrasound

There is ongoing controversy as to whether there are structural abnormalities among patients with Brugada syndrome. There was one small study of 11 patients with Brugada syndrome that demonstrated a rapid swinging motion shifting towards the right ventricle of the basal segment of the intraventricular septum and early systole in 73% (8/11) of patients with Brugada syndrome. None of the control patients demonstrated this abnormality.

Electrophysiologic Studies

Patients who are inducible at the time electrophysiologic study have an eightfold increased risk of aborted sudden cardiac death compared with those patients who are not inducible. Some groups have advocated that programmed electrical stimulation (PES) be performed to induce ventricular fibrillation for risk assessment in Brugada patients Other groups have not reproduced the predictive value of these tests, so the value of programmed electrical stimulation (PES) and inducibility remains controversial.

Genetic Testing

Despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis. Genetic testing can be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.

Treatment

Implantation of a cardiac defibrillator is the only proven method of treatment in Brugada syndrome.Patients with aborted sudden cardiac death are at high risk for recurrence and should undergo AICD implantation, and do not require an electrophysiologic study to assess inducibility. Patients with symptoms (either syncope, seizures or nocturnal agonal respirations) should undergo implantation of a defibrillator if no other cause of their symptoms can be identified. Asymptomatic patients should undergo electrophysiologic testing, and if VT / VF can be induced, they should undergo implantation of an ICD. Asymptomatic patients who cannot be induced should followed-up closely. Patients who are asymptomatic with no family history of Brugada syndrome can be followed-up closely.

Drugs to Avoid

There are certain drugs that should be avoided in patients with Brugada syndrome. These drugs include ajmaline, flecainide, pilsicainide, procainamide, and propafenone. These drugs are all sodium blocking antiarrhythmics which are either in the IA class or IC class.

Drugs to Preferably Avoid

Drugs which are not contraindicated in Brugada syndrome, but which should be avoided, are amiodarone, cibenzoline, disopyramide, lidocaine, propanolol, and verapamil. These agents are all antiarrhythmics. Topical lidocaine used for anesthesia is thought to be safe when used in persons with Brugada syndrome.