Brugada syndrome

Generality

Brugada syndrome is a heart disease that alters the heart rhythm, causing palpitations, syncope, ventricular arrhythmias and, in the most severe, cardiac arrest.

The triggering causes can be of different nature: some patients inherit this disorder from one of the parents; others, instead, develop it around 30-40 years in a totally inexplicable way.

Brugada syndrome is difficult to diagnose, because, very often, it is latent and asymptomatic. However, cardiologists, thanks also to the study of pathophysiological mechanisms, have developed an electrocardiographic examination particularly suitable for the identification of the disease.

The only effective and adoptable therapeutic treatment is the implantation, near the heart, of a small defibrillator.

Brief reminder of cardiac arrhythmias: what are they?

Before proceeding with the description of Brugada syndrome, it is advisable to review what heart arrhythmias are.

A cardiac arrhythmia is an alteration of the normal heart rhythm, or sinus rhythm, which originates from the atrial sinus node. In fact, this atrial sinus node is a generator of electrical impulses, which contract the heart and scan the heart rate. It is not by chance and for this reason, the atrial sinus node is defined as the dominant pedestal center, to distinguish it from other secondary marker centers.

The measurement of heart rate (or heart rate ) is based on the activity of the ventricle and is expressed in beats per minute . The sinus rhythm involves between 60 and 100 beats per minute in resting conditions.

There are three possible alterations and it is sufficient if one is present only because an arrhythmia occurs. They are:

• Changes in the frequency and regularity of sinus rhythm. Heart rate can become faster (over 100 beats per minute → tachycardia) or slower (less than 60 beats per minute → bradycardia).
• Variation of the dominant marker center. The marker centers are more than one in the heart, but the main one, which determines the normality of the heartbeat, is the atrial sinus node.
• Disorders of the propagation (or conduction) of the contraction pulse, which modify the heart rhythm.

HISTORY

Brugada syndrome owes its name to two cardiologist brothers, Pedro and Josep Brugada, who described it accurately in 1992. In reality, however, its discovery dates back to a few years earlier, exactly to 1988, when a group of Italian researchers traced the main features on the Italian Journal of Cardiology.

Epidemiology

Brugada syndrome is much more common in adult men (between 30-40 years) than in adult women; consequently, even sudden cardiac death, caused by this disease, is much more common among males than among females.

It mainly affects the populations of Asian origin (in particular, those who come from Thailand and Laos).

Although it rarely occurs among young people (males and females without distinction), even for them, as for male adults, it represents one of the main causes of sudden cardiac death ( sudden cardiac death in young people ).

Causes

Individuals with Brugada syndrome usually have a structurally sound heart, but unable to adequately transmit impulses for cardiac contraction. Remembering that contractile impulses are electrical in nature, this is why Brugada syndrome is considered a disorder caused by an abnormal heart electrical activity.

But what determines this anomaly?

For a certain number of patients, the cause is certainly linked to an inherited genetic mutation, that is transmitted by the parents; for the remaining part of the patients, however, the origin of the disease is unknown, or rather it is not clear.

What is a genetic mutation?

Genes are short stretches, or sequences, of DNA with a fundamental biological meaning: in fact, proteins are derived from them, or biological molecules indispensable for life.

A genetic mutation is an alteration, or an error, within the sequence that makes up a gene. Because of this error, the resulting protein is defective or completely absent. In both cases, the effects can be deleterious both for the life of the cell, in which the mutation occurs, and for that of the organism in its totality. Congenital diseases and neoplasms (or tumors) are responsible for one or more genetic mutations.

BRUGADA SYNDROME WITH HEREDITARY GENETIC ORIGIN

Researchers have identified several genes responsible for Brugada syndrome: the one most studied and known best is known as SCN5A and is located on chromosome 3.

SCN5A produces special proteins, very similar to channels, which, lying in the plasma membranes of cardiac muscle cells, allow the passage of sodium ions .

Thanks to a fine mechanism, the passage of sodium ions in these cells allows the transmission of electrical impulses for the contraction of the heart.

Patients with Brugada syndrome of genetic origin produce, through SCN5A, defective channels, which do not guarantee an adequate heartbeat. The SCN5A mutation, in these subjects, is transmitted by one of the parents, who was suffering from the same disorder.

BRUGADA SYNDROME OF UNKNOWN ORIGIN (FORM ACQUIRED)

Part of the patients diagnosed with Brugada syndrome have an altered electrical activity of the sodium channels contained in the heart muscle cells, but no related genetic mutation. In other words, the muscle cells of the heart, while being genetically normal, do not transmit the electrical impulses correctly.

The efforts to identify an alternative cause were mostly in vain, as the hypotheses considered so far have not been ascertained in any way.

In the list of hypothetical reasons, appear:

• Drug use, especially cocaine
• High blood pressure
• Angina pectoris
• An imbalance of electrolytes in the blood. In other words, the levels of calcium, potassium, etc. they are unusually high or low
• Taking certain medications

RISK FACTORS

Based on the statistical data collected around the world, you are more exposed to the Brugada syndrome if:

• There is a family history behind it. If a parent carries Brugada syndrome, his children are more at risk of getting the same heart disease.
• It is male . The disease is much less common among women.
• It is of Asian race . The most exposed population is the Asian one.
• One is struck by a feverish state . A fever of any kind, in those suffering from Brugada syndrome, can trigger all the symptoms.

Symptoms and Complications

To learn more: Symptoms Brugada syndrome

Brugada syndrome is a disease, very often latent and asymptomatic, and therefore difficult to diagnose. In fact, the characteristic symptoms and signs, which consist of fainting (or syncope ), epileptic seizures, ventricular arrhythmias, palpitations and cardiac arrest, occur alternately, suddenly and sometimes even deadly.

THE SIGN OF BRUGADA

As will be seen in the chapter on diagnosis, patients with Brugada syndrome show a particular electrocardiographic pattern (ECG), known as the Brugada sign, which is not accompanied by obvious disorders. In other words, the sign of Brugada does not manifest itself in any way and the only way to realize its presence is to do a specific cardiological examination. This contributes to the deceptive nature of which we spoke earlier.

Very important note : all Brugada syndrome patients have the homonymous sign, but not all those who have such a sign are sick with Brugada syndrome.

This means that, once the sign of Brugada has been diagnosed by ECG, it is necessary to undergo further checks to understand the origin of the heart disorder.

COMPLICATIONS: WHEN AND WHY IS IT LETHAL?

Brugada syndrome, when it emerges from its latent state and manifests itself from a symptomatic point of view, can be lethal, as it triggers a ventricular fibrillation .

Ventricular fibrillation is an arrhythmia with a rapid and mostly fatal course, as it causes severe cardiac arrest.

WHEN TO REFER TO THE DOCTOR?

When suffering from sudden palpitations, arrhythmias and fainting, it is advisable to undergo cardiac tests immediately. Only these will be able to say what is at the origin of the disorders and whether one is suffering from severe heart disease or not.

It is also strongly recommended to undergo genetic testing if you are aware that a direct member of your family has suffered (or is suffering) from Brugada syndrome.

Diagnosis

Diagnosing Brugada syndrome, which tends to be latent and asymptomatic, is not at all easy.

Physical examination can provide useful information, especially if there is a family history of Brugada syndrome, but very often it is not enough. To dispel any doubt, in fact, you need an electrocardiogram and an echocardiogram.

Genetic tests have value and are carried out only if the hypothesis of a family origin of the disorders is concrete.

EXAMINATION OBJECTIVE

The objective examination consists of the analysis of the symptoms and the clinical history of the patient.

In the case of Brugada syndrome, it serves to confirm cardiac disorders, but little is said about their origin, as the disease resembles other heart diseases.

It becomes very important, instead, if there is a family history of Brugada syndrome on the shoulders: in these situations, the path of diagnosis takes a precise direction immediately.

Some information on the ECG

The ECG is not an invasive exam. It is used to measure the rhythm and electrical activity of the heart, through the application, on the chest, on the arms and on the legs, of different electrodes, which are connected, in turn, to an electrocardiographic machine.

All beat irregularities, if they are in progress during the examination, are readily recognized.

ECHOCARDIOGRAM

The echocardiogram shows cardiac anatomy and serves the purpose of differential diagnosis. In fact, if the heart has some structural anomaly (heart valve problems, ventricular hypertrophy, etc.), it is conceivable that the heart problems are due to one of these malformations and not to the Brugada syndrome (which, as we will remember, is characterized from a structurally normal heart).

NB: the differential diagnosis consists in the exclusion of all those pathologies capable of causing symptoms and signs similar to the suspected one.

GENETIC TESTS

Genetic tests are performed only when, from physical examination, a family history of Brugada syndrome emerges. Otherwise, in fact, DNA tests may be completely useless for diagnostic purposes.

Treatment

The only viable therapeutic treatment in patients with Brugada syndrome is to install an implantable defibrillator (also called an implantable cardioverter defibrillator or ICD ).

This instrument, which is housed in the left side of the thorax, is connected to the heart by means of electrocatheters, which emit an electric discharge whenever an abnormal increase in cardiac rhythm occurs. The discharge, if successful, brings the electrical activity of the heart back to normal.

All the most important features, related to the implantable defibrillator:

It's a computer . The implantable cardioverter defibrillator (ICD) is, in fact, a small, battery-powered computer capable of monitoring the heart rate and noticing when the latter rises above the normal threshold.

Figure: the implantable cardioverter defibrillator. Leads can be seen, which are nothing more than thin metal wires connected to the heart.

Duration . It lasts an average of 7-8 years, after which it must be replaced.

Size and weight . It has the size of a pocket watch and weighs about 70 grams.

How do you adjust it? Once implanted, the defibrillator must be adjusted so that it can "notice" when the heart rate is exceeding the limits of normality. The adjustment is made via a computer programmer, located in any specialized hospital (or clinic) center.

Device malfunction . It can sometimes happen that the defibrillator emits unwanted electrical discharges.

Does it prevent ventricular fibrillation or cardiac arrest? ICD prevents cardiac arrest, but not ventricular fibrillation. The latter, in fact, especially in those who suffer from diseases such as Brugada syndrome, is unpredictable.

In what other cases can it be applied? The implantable defibrillator can be used in many situations. The classic circumstances are those in which the individual has a personal history of severe cardiac arrhythmias, repeated syncopes or cardiac arrest, to which he fortunately survived.

PHARMACOLOGICAL TREATMENT: WHEN APPLIES?

There is no drug therapy that replaces the role of the implantable defibrillator.

The only medicines that are administered to a patient with Brugada syndrome are quinidine and hydroquinidine and serve to strengthen the action of the ICD when a ventricular arrhythmia is in progress.

Prognosis

Establishing a prognosis, for a patient with Brugada syndrome, is not at all easy, as the disease, as we have said, manifests itself suddenly and with sometimes mild and sometimes decidedly more serious, if not lethal effects.

IMPORTANCE OF DIAGNOSIS

Diagnosing the disease is already a big step towards a positive prognosis or, at least, not a negative one. In fact, being aware of which heart condition you suffer, allows you to take the necessary precautions (the implantable defibrillator).

PERIODICAL CHECKS

Once the diagnosis is established and the ICD is applied, it is advisable to carry out periodic cardiological checks, in order to monitor the progress of the Brugada syndrome and prevent any complications.