Genetic heart disease: Brugada syndrome

By Cristiano Antonino On Jun 13, 2023

Brugada syndrome is a disease that most commonly affects young males in adulthood. The genetic defect is in proteins that control the entry of sodium into the cardiac cell

The lack of sodium alters the cardiac electrical function resulting in arrhythmias that occur during sleep

The diagnosis is made by evaluating the electrocardiogram and by administering drugs that induce specific alterations in the electrocardiogram, as well as by genetic testing.

It was first described in 1992 by the Brugada brothers who immediately noticed an increased risk of sudden cardiac death in the absence of structural heart disease.

It is a genetic disorder that involves the structures on the surface of the heart cells, causing a malfunction and the resulting imbalances and irregularities in electrical activity, increasing the risk of fatal arrhythmias; arrhythmias, accelerated rhythm syncope, fainting and fainting spells, and even fatal cardiac arrest can also occur.

Genetics in Brugada syndrome

The alteration of ionic currents in Brugada syndrome has a genetic origin with autosomal dominant transmission: the first mutation in the syndrome is an alteration in the gene that codes for the protein that makes up the sodium channel.

A certain genetic mutation occurs in about 30% of affected patients, but with the development of genetic research, new mutations in this and other genes are being described.

The heart, in patients with Brugada Syndrome, does not see the presence of malformations but remains affected by pathologies that cause fibrillation and arrhythmias of the ventricle.

The diagnosis is made by excluding pathologies affecting the heart muscle that can be traced back to this syndrome.

Other tests useful for detecting Brugada syndrome are electrolyte tests

Calcium is administered intravenously in a situation controlled by special clinical instruments.

The test takes place in an outpatient setting in front of a team consisting of a cardiologist, anaesthetist and a nurse.

Characteristic of this disease, is an extreme variability of clinical and electrocardiographic presentation.

In fact, the electrocardiogram of the affected patient may vary even within the same day, going from times when the tracing is on the whole normal to others when it may be pathological.

For electrocardiographic monitoring, a 10-minute infusion is performed, followed by a further 10 minutes of observation.

If the test is positive, further investigations will be necessary and the hospital stay may be prolonged.

A drug will be administered that will reduce the function of the channel already suspected to be impaired, accentuating the imbalance with repolarising currents.

How to make the diagnosis

It is essential to undergo a cardiological examination and an electrocardiogram.

The latter, in subjects with Brugada syndrome, is not constant and therefore the diagnosis of the pathology may be more difficult.

If there is a suspicious trace, an ECG with Holter should be performed to follow the course of the electrocardiogram over 24 hours.

The echocardiogram would give a clearer picture than any other type of test, as it can examine the structure as a whole with particular attention to valves, ventricles, hypertrophy and wall thickening.

In order to arrive at a definition of the syndrome, one of the following symptoms must also be present: documented ventricular fibrillation, polymorphic ventricular tachycardia, family members of affected patients and sudden death under the age of 45, inducibility of ventricular tachycardia with programmed pacing on electrophysiological study, syncope, agonal nocturnal breathing.

Before establishing a diagnosis of Brugada, those causes that can lead to such an electrocardiographic appearance must be excluded: myocarditis, arrhythmogenic dysplasia of the right ventricle, chronic intake of certain drugs or simply intense sports activity.

The electrocardiographic alteration, in Brugada syndrome, is secondary to an imbalance between the incoming and outgoing ionic currents from the cardiac cells, usually caused by a reduced function of the channels conducting the incoming sodium current.

The electrocardiographic appearance is evident by the presence of a potassium outflow current, which is represented at the level of the right ventricular outflow tract and is not counterbalanced by the sodium outflow current.

The uneven distribution of the imbalance between the repolarising and depolarising currents causes arrhythmic risk due to the marked difference in the polarisation of neighbouring myocardial areas.

This makes it easier to manifest polymorphous ventricular arrhythmias that can lead to ventricular fibrillation and cardiac arrest.

Not everyone with Brugada syndrome experiences cardiac arrest and sudden death as a result.

An electrophysiological examination is performed to test for ventricular arrhythmia in those patients with a family history of sudden cardiac death.

Should there be positivity for dangerous ventricular arrhythmias, the placement of an implantable defibrillator will be recommended; placement being the only therapy considered effective.

Even ‘asymptomatic’ patients, after undergoing electrophysiological examinations and in case of positivity for malignant ventricular arrhythmias, will have an implantable defibrillator placed.

Should implantable defibrillator placement be inaccessible or should recurrent arrhythmias occur, drug therapy with quinidine, a blocker of both the outgoing potassium current and the sodium current, will be followed in order to reduce polarisation heterogeneity and reduce the arrhythmic risk.

Heart: What Is Brugada Syndrome And What Are The Symptoms