Brugad's syndrome – genetically caused cardiological state which is characterized by various violations of work of heart which lead to sharp increase in risk of development of sudden warm death. Symptoms of this state are attacks of paroksizmalny tachycardia, faints, the fibrillations of auricles and zhizneugrozhayushchy fibrillations of ventricles most often arising during sleep. Diagnostics of a syndrome of Brugad is made on the basis of characteristic simptomokompleks, electrocardiographic data and studying of the hereditary anamnesis, some forms of pathology are defined by molecular and genetic methods. Specific treatment of a disease does not exist, apply antiarrhytmic therapy, use various pacemakers.
Brugad's syndrome – group of the genetic disorders leading to change of ionic permeability of membranes of kardiomiotsit owing to what there are pathologies of a rhythm and conductivity creating the increased risk of sudden warm death. For the first time such state was described in 1992 by two brothers – the Belgian cardiologists of the Spanish origin of José and Pedro Brugad who paid attention to interrelation of certain electrocardiological manifestations and violations of a warm rhythm. Now it is established that Brugad's syndrome is a hereditary state with presumably autosomno-prepotent mechanism of transfer, it was succeeded to reveal several genes which mutations are capable to cause this disease. According to some information, nearly a half of all cases of sudden warm death in the world are caused by this pathology. Prevalence of a syndrome of Brugad differs in different regions of the planet – in the countries of America and Europe it makes about 1:10 000 whereas in the African and Asian states this disease meets more often – 5-8 cases on 10 000 population. The syndrome about 8 times more often than Brugad strikes men, than women, displays of pathology arise at different age, but the symptomatology most often expressed is observed in 30-45 years.
Reasons and classification of a syndrome of Brugad
The reason of development of violations at Brugad's syndrome consists in pathological work of ion channels of kardiomiotsit, generally sodium and calcic. Their defect, in turn, is caused by mutations of the genes coding proteins of ion channels. Methods of modern genetics succeeded to identify authentically 6 main genes which defeat leads to development of a syndrome of Brugad, concerning several more there is a suspicion, but there is no necessary evidential base. On this basis the classification of this state including 6 forms of a disease (BrS) is constructed:
- BrS-1 – the most widespread and well studied option of a syndrome of Brugad. It is caused by a mutation of a gene of SCN5A located on the 3rd chromosome. A product of an expression of this gene is alpha sodium channel 5 of the type which is widely presented in a myocardium. Besides Brugad's syndrome of a mutation of this gene become the reason of a large number of hereditary cardiological pathologies – family fibrillation of auricles, a syndrome of weakness of sinusovy knot of 1 type and some others.
- BrS-2 – this kind of a syndrome of Brugad is caused by defects of a gene of GPD1L which is localized on the 3rd chromosome. It codes one of components glitserol-3-phosphate of the degidrogenaza taking active part in operation of sodium channels of kardiomiotsit.
- BrS-3 – this type of a syndrome of Brugad is caused by defect of a gene of CACNA1C located on the 12th chromosome. A product of its expression is alpha the calcic channel of the L-type which is also present at kardiomiotsita.
- BrS-4 – as well as in the previous case, 4 types is the reason of development of a syndrome of Brugad defeat potential - dependent calcic channels of L-type. It is caused by a mutation of the gene of CACNB2 located on the 10th chromosome and coding beta 2 - the above-stated ion channels.
- BrS-5 – the widespread kind of a syndrome of Brugad caused by a mutation of a gene of SCN4B localized on the 11th chromosome. It codes protein of one of small sodium channels of kardiomiotsit.
- BrS-6 – is caused by defect of a gene of SCN1B located on the 19th chromosome. In many respects this option of a syndrome of Brugad is similar to the first type of a disease as in this case sodium channels 5 of type are surprised too. The gene of SCN1B codes beta 1 - this ion channel.
Besides, mutations of genes of KCNE3, SCN10A, HEY2 and some other are suspected of development of a syndrome of Brugad. However today it is reliable it is not possible to prove their role in developing of this disease therefore so far the quantity of genetic options of a syndrome of Brugad is limited by six. Inheritance of all forms of this pathology is not clear, only at 25% of patients signs of autosomno-prepotent transfer are defined. Presumably the prepotent type of inheritance with an incomplete penetrantnost or influence of spontaneous mutations takes place. The reasons of why Brugad's syndrome to a bowl strikes men are also unclear, than women – it is possible, expressiveness of displays of a disease is depending on a hormonal background of the patient.
The pathogenesis of violations at any form of a syndrome of Brugad is approximately identical – because of change of permeability of a membrane of kardiomiotsit for ions of sodium there is a violation of transmembrane potential and the characteristics of excitable fabrics interconnected with it: excitabilities, sokratimost, excitement transfers to surrounding cages. Blockade of the carrying-out ways of heart (Gis's bunches), the takhiaritmiya amplifying at increase in vagusny influences (during sleep) result. Degree of expressiveness of symptoms at Brugad's syndrome depends on a share of the struck sodium channels. Some medicinal substances can strengthen displays of a disease, are capable to inhibit ion channels of heart.
Symptoms of a syndrome of Brugad
The age of emergence of the first signs of a syndrome of Brugad strongly differs at different patients – cases of this pathology both at children of 3-4 years, and at persons of senile age were registered. Changes on the electrocardiogram at total absence of other clinical symptoms therefore this disease quite often comes to light incidentally become one of the first displays of pathology. In most cases the expressed clinic of a syndrome of Brugad arises at the age of 30-45 years, it is preceded by the asymptomatic period lasting 10-12 years during which the only symptom of pathology are changes on the ECG.
Usually sick with Brugad's syndrome complain of causeless dizziness, faints, frequent attacks of tachycardia, especially at night or during day rest. Abnormal reaction to reception of some medicines – antihistaminic medicines of the first generation, beta , vagotonichesky means is sometimes noted. Their application at Brugad's syndrome can be followed by strengthening of by-effects, and also serdtsebiyeniye, faints, falling of arterial pressure and other negative manifestations. No other symptoms at this disease come to light, than the rare address of patients to the cardiologist or other experts – in some cases manifestations of a syndrome of Brugad rather rare and ill-defined speaks. Nevertheless, it does not reduce risk of the sudden warm death caused by this pathology.
Diagnostics of a syndrome of Brugad
For definition of a syndrome of Brugad use electrocardiographic techniques, studying of the hereditary anamnesis of the patient, the molecular and genetic analysis. It is possible to suspect existence of this disease in the presence of the sinkopalny phenomena (dizzinesses, faints) of not clear origin, complaints to sudden attacks of takhiaritmiya. Changes on the electrocardiogram at Brugad's syndrome can be defined against the background of total absence of clinical symptoms of a disease. At the same time cardiologists allocate three main types of changes for the ECG slightly different among themselves. The typical picture of the electrocardiogram at Brugad's syndrome comes down to an elevation (rise) of a segment of ST over the isoelectric line and to a negative tooth of T on the right chest assignments (V1-V3). Also signs of blockade of the right leg of a bunch of Gis can be defined, at holterovsky monitoring attacks of paroksizmalny tachycardia or fibrillation of auricles come to light.
As a rule, the hereditary anamnesis of patients with Brugad's syndrome is burdened – among relatives or ancestors there are cases of lethal outcomes from heart failure, death in a dream or sudden warm death. This fact, and also existence of above-mentioned symptoms and changes on the ECG gives the grounds for performing molecular and genetic diagnostics. Now doctors geneticists in the majority of clinics and laboratories make definition of a syndrome of Brugad called only by mutations of genes of SCN5A and SCN4B (the 1 and 5 types of pathology), concerning other forms methods of genetic diagnostics are not developed yet. It is necessary to differentiate this state with reaction of an organism to reception of some medicines, chronic myocarditis and other cardiological pathologies.
Treatment and prevention of a syndrome of Brugad
Specific methods of treatment of a syndrome of Brugad do not exist for today therefore are limited only to fight against displays of this disease, and also prevention of zhizneugrozhayushchy attacks of a takhiaritmiya and fibrillations. Most widely at this state it is applied , are slightly less often used and . However medicamentous therapy at Brugad's syndrome in some cases is ineffective, implantation of a kardiovertera-defibrillator becomes the only well-tried remedy of prevention of arrhythmia and sudden warm death in this case. Only this device is capable to estimate work of a myocardium of the patient and at pathological and zhizneugrozhayushchy changes of a warm rhythm to normalize it by means of electric discharge.
Many traditional antiarrhytmic medicines at Brugad's syndrome are contraindicated as they oppress activity of sodium channels of kardiomiotsit and strengthen displays of pathology. Carry to the means forbidden at this disease , , procaineamide. Therefore a sick syndrome of Brugad it is necessary to report surely to experts about the available diagnosis to avoid purpose of incorrect antiarrhytmic means. In the presence of a similar disease at relatives or cases of sudden warm death in a sort it is necessary to make an ECG research for earlier diagnostics of this state regularly.
Forecast of a syndrome of Brugad
The forecast of a syndrome of Brugad uncertain as degree of expressiveness of symptoms of a disease is very variable and is depending on a number of factors. In the presence of only electrocardiographic displays of pathology without the expressed clinical symptoms the forecast rather favorable. If Brugad's syndrome is followed by losses of consciousness and attacks of arrhythmia – without installation of a kardiovertera-defibrillator the risk of sudden warm death increases many times over. At use of this device the forecast improves a little as the device can correct pathological changes of a warm rhythm round the clock.