The Brugada Syndrome

This article was written in collaboration with Paris’ center of reference for hereditary cardiac diseases (MD Philippe Charron and MD Isabelle Denjoy) and with Nantes’ center of reference for the care of rhythmic hereditary diseases (MD Vincent Probst).

The Pathology

The Brugada syndrome is one of the syndromes responsible for ventricular rhythm disorders. The Brugada brothers first described it in 1992.

The syndrome is characterized by an abnormal electrocardiogram (ECG) pattern associated with an increased risk of sudden death by ventricular fibrillation.

Typical ECG anomalies are characterized by a rise of the ST segment on at least two successive right precordial lead associated with an atypical right bundle-block branch pattern.

Three types are described (I, II and III) and only a type I ECG is considered as a diagnosis. This pathology occurs in a  structurally healthy heart. The dysfunction is purely electrical.

Frequency of the pathology

The Brugada syndrome is responsible for 4% to 12% of cardiac sudden deaths and almost 20% of these occur on a healthy heart.

It affects one individual out of 2000 approximately.

Every patient presenting an electrocardiographic anomaly will not necessarily experience symptoms, or sudden death.

The symptoms

Most patients who show the electrical anomaly do not experience any symptoms. When these are described, they are experienced as an acceleration of cardiac rhythm. The symptoms are intermittent and very rare. Sometimes they take the form of faintness, with or without loss of consciousness, occasionally with spasms. 

The first symptoms usually appear around the age of 40 on average, with a very heterogeneous distribution (from 2 days old to 84 years old).

Rhythm disorders occur at rest or during the night and sudden death affects men more frequently than women.

Fever encourages the occurrence of rhythm disorders.

Genetic transmission

The Brugada syndrome is a hereditary rhythm disorder. Its pattern of inheritance is a autosomal dominant pattern, which means that the mutated gene (abnormal) has a 50% likelihood of being inherited by each child, regardless of gender.

The main gene associated with this pathology is the gene SCN5A which codes for the cardiac sodium channel. This channel plays a major role in the heart’s electrical activity. The mutations of this gene cause an alteration of the functionality of the sodium channel and lead to an abnormal electrical activity which  can degenerate into a ventricular fibrillation.

The mutations of this gene are found in 15% to 25% of Brugada syndrome cases.

Clinical diagnosis

Basic ECG is sufficient to establish a diagnosis of the Brugada syndrome when it is typical (that is to say a “spontaneous type I”).

Electrical anomalies are variable in the course of time, which makes it difficult to diagnosis.

When there is suspicion of Brugada syndrome, a pharmacological test by intravenous injection of a drug such as Ajmaline or Flecainide may be proposed. This test allows to unmask the type I pattern and thus confirms or rules out the diagnosis. It is carried out during a short hospitalization in cardiology under constant ECG monitoring.

Of course, other cardiac pathologies will need to be eliminated as possible causes and an echography will be needed to ensure “normality” of the cardiac muscle.

Genetic test

It is prescribed in one of the reference centers or competence centers.

It consists of a blood test followed by DNA extraction. Initially, the analysis will seek a mutation in the gene SCN5A. Given that only 15% to 25% of people affected by the Brugada syndrome show a mutation of this gene, which means that if the test result is “negative” (without an identified mutation) then the mutation affects another gene not known to this day. Further analysis on other genes is sometimes offered, especially as part of research efforts. 

When the test result is “positive”, that is to say a mutation was identified, it is then simple to look for it among relatives in order to know if they carry the mutation or not. In this situation the genetic test makes for an important diagnosis input to guide cardiologic monitoring. However, in the case of an ill patient, the genetic test does not alter clinical care.  

It should be noted that in the future, genetics’ research should provide with discoveries of new genes implicated in the disease.

Rhythmic rhythm

Some patients may experience a complication of the disease such as ventricular arrhythmia with ventricular fibrillation (fast and anarchical cardiac rhythm) or  sudden death.

This rhythmic risk is difficult to assess. The elements taken into account for the rosk evaluation are the symptoms (blackout, syncope, recovered sudden death) and the existence of a spontaneous type I pattern.

A study showed that the likelihood of occurrence of an arrhythmia is of 7.7% with patients having already recovered from a sudden death, of 1.9% with patients showing a history of syncope and of 0.5% for symptomless patient.

Treatments

As of  today, no drug has shown complete efficacy in preventing sudden death associated with the Brugada syndrome. Nevertheless, some studies show that Quinidine or Hydroquinidine could lower the risk of ventricular fibrillation. However, drug therapies alone do not seem sufficiently effective and the insertion of an implantable cardioverter-defibrillator (ICD) is proposed to symptomatic patients (showing a history of syncope).

This device is implanted under the skin and is usually placed under the left clavicle (collarbone). Its goal is to monitor the heart’s electrical activity and to administer an electrical shock in case of a serious ventricular rhythm disorder. The device is connected to the heart by a probe.

Asymptomatic patients show a much lower risk of sudden death. In a majority of cases it will not be necessary to insert  an implantable cardioverter-defibrillator. An ECG will be carried out every year and any occurrence of a symptom should be brought to a cardiologist’s attention.

Patients carrying an ICD should be monitored in consultation every six months. They should quickly consult their cardiologist in case their device delivers a shock.

In any case fever should be lowered by an antipyretic treatment.

Intense physical activity is also limited in order to avoid brutal fainting attacks.

Pregnancy

Pregnancy is possible. Pregnant patients carrying an ICD should be monitored more closely.

The disease and children

With young children ECG is difficult to interpret. With some children it can be performed at a young age whereas for others at puberty (in the absence of symptoms). However, the electrocardiographic pattern being inconsistent it is necessary to repeat the examination on a regular basis.

The absence of a typical pattern does not permanently exclude the existence of the pathology. A pharmacological test is offered from the age of 15 in order to establish final diagnosis.

Contraindicated drugs

A certain number of drugs are contraindicated for patients with the Brugada syndrome. A list of these medicines is available  on www.brugadadrugs.org ; on www.cardiogen.aphp.fr ; or on the website http://www.chu-nantes.fr/le-syndrome-de-brugada-medicaments-contre-indiques-27110.kjsp.

Some drugs can sometimes be adapted in a patient’s particular situation and in any case should be discussed with the treating cardiologist.