Long qt interval syndrome treatment. What you need to know about the QT interval on the ECG, the norm of its length and deviations from it

Long QT syndrome (LQT) is a congenital or acquired cardiac pathology, which is characterized by lengthening of the corresponding interval by , the presence of repeated syncope and a high risk of sudden death due to the development of malignant arrhythmias. The congenital variant of the syndrome occurs in all ethnic groups with a frequency of 1:2000 to 1:2500. Females are somewhat more likely to suffer from it. The prevalence of the acquired syndrome ranges from 2.5 to 4 cases per 1 million people. In our article, we will look at why LQT occurs, what symptoms it causes, why it is dangerous, and how to treat it.

The disease has been known since the end of the 19th century, when the observation of a girl with congenital deafness and frequent fainting that occurs with strong excitement was first described in the medical literature (1856, Meissner). Later, his electrocardiographic picture was revealed (1953, Moller). Currently, the study of this syndrome and the search for effective methods his treatment is ongoing.

Causes of the congenital syndrome

The hereditary variant of the syndrome is based on mutations in genes encoding the functions of protein molecules of ion channels in the heart muscle. Currently, more than 180 such mutations are known in 7 genes, which are located on the 3rd, 7th, 11th and 21st chromosomes. In most cases, they disrupt the work of potassium and sodium channels, less often - calcium channels and specific building proteins. This leads to an increase in the duration of the action potential in cardiomyocytes, initiating the appearance ventricular tachycardia type "pirouette", which can turn into.

The processes of depolarization and repolarization, which occur as a result of the movement of electrolytes into the cell from the extracellular space and back, reflect the QT interval on the ECG, which is lengthened in this pathology.

AT clinical practice There are 3 main variants of the hereditary syndrome:

• Romano-Ward (characterized by isolated QT prolongation, transmitted from parents with dominant genes);
• Jervell-Lange-Nielsen (inherited in an autosomal recessive manner and associated with congenital deafness);
• autosomal dominant variant with extracardiac manifestations.

The last of them can manifest itself in the form:

• Andersen-Tavila syndrome (QT prolongation is combined with a pronounced U-wave, ventricular tachycardia, anomalies in the development of the skeletal system, hyper- or hypokalemic periodic paralysis);
• Timothy's syndrome (syndactyly, congenital heart anomalies, various conduction disorders, an extremely high risk of sudden death).

Acquired form

It was previously believed that the occurrence of acquired LQT syndrome is associated with a malfunction of ion channels, which is caused not by a mutation, but by the impact of any external or internal factors. This statement is true, but it has been proven that a genetic defect contributes to the development of the pathological process. At the same time, the acquired syndrome is difficult to distinguish from congenital pathology because they have a lot in common. This pathology is usually long time goes unnoticed and manifests itself in adverse conditions, for example, under the influence of stress or physical exertion. Factors contributing to QT interval prolongation include:

• reception medicines(we will consider which ones below);
• electrolyte disturbances (lack of potassium, sodium, magnesium);
• heart rhythm disturbances;
• diseases nervous system(injuries, infections, tumors);
• change in hormonal status (, pathology thyroid gland or adrenal glands)
• alcoholism;
• starvation, etc.

Of particular danger is the exposure of a susceptible organism to several risk factors.

Groups of drugs that can affect the length of the QT interval

Due to the fact that LQT syndrome can be caused by direct exposure medicines, and their cancellation often leads to the normalization of all indicators, let's take a closer look at which drugs can change the length of the QT interval:

• (amiodarone, novocainamide, sotalol, propafenone, disopyramide);
• antibiotics (erythromycin, spiramycin, clarithromycin, isoniazid);
• (ebastine, astemizole);
• anesthetics;
• antimycotics (fluconazole, ketoconazole);
• anticancer drugs;
• psychotropic drugs (droperidol, amitriptyline);
• (indapamide), etc.

They cannot be prescribed to persons who already have an extension of this interval. And with a late debut of the disease, their role as a provoking factor is necessarily excluded.

Clinical manifestations

The clinical picture of the syndrome is characterized by polymorphism of symptoms. Their severity can vary from mild dizziness to loss of consciousness and sudden death. Sometimes the latter can act as the first sign of the disease. Most typical manifestations This pathology is considered:

• bouts of loss of consciousness;
• congenital deafness;
• cases of sudden death in the family;
• changes on the electrocardiogram (QT more than 450 ms, T wave alternation, ventricular tachycardia of the "pirouette" type,).

With congenital variants of the syndrome, other symptoms characteristic only of it can be detected.

It should be noted that syncopal conditions in this pathology have their own characteristics:

• occur against the background of stress, under the influence of strong sound stimuli (alarm clock, phone call), physical activity, sports (swimming, diving), during a sharp awakening from a night's sleep, in women - after childbirth;
• the presence of symptoms preceding the loss of consciousness (, severe weakness, ringing in the ears, darkening in the eyes, feeling, heaviness behind the sternum);
• rapid recovery of consciousness with a favorable outcome;
• lack of amnesia and personality changes (as in epilepsy).

Sometimes loss of consciousness can be accompanied by convulsions and involuntary urination. In such cases, differential diagnosis with epileptic seizures is carried out.

The course of the pathological process in each patient may have certain differences. It depends both on the genotype and on the living conditions. The following options are considered the most common:

• syncope that occurs against the background of prolongation of the QT interval;
• isolated lengthening of this interval;
• syncope in the absence of ECG changes;
• complete absence of symptoms (high risk without phenotypic manifestations of the disease).

The most unfavorable course is complicated by the development of ventricular fibrillation and cardiac arrest.

In congenital variants of the disease, syncope appears in childhood(5-15 years). Moreover, their occurrence in preschool children is a prognostically unfavorable sign. A paroxysm of ventricular tachycardia, which required emergency care, increases the likelihood of a second cardiac arrest in the near future by 10 times.

Patients with asymptomatic long QT syndrome may be unaware of their diagnosis and have a normal life expectancy, but pass the mutation on to their children. This flow is observed very often.

Diagnostic principles

Diagnosis of the syndrome is based on clinical data and electrocardiography results. Additional information Holter monitoring is provided to the doctor.

Considering that it is not always easy to make a diagnosis, major and minor diagnostic criteria have been developed. The latter include:

• hearing loss from birth
• variability of the T wave in different leads (on the electrocardiogram);
• violation of the processes of repolarization of the myocardium of the ventricles;
• low heart rate.

Major criteria include:

• prolongation of the corrected QT interval over 450 ms at rest;
• episodes of loss of consciousness;
• cases of illness in the family.

The diagnosis is considered reliable in the presence of two major or one major and two minor criteria.

Treatment

The main direction of treatment of such patients is the prevention of malignant arrhythmias and cardiac arrest.

All individuals with a long QT interval should avoid:

• stressful situations;
• doing sports;
• heavy physical exertion;
• taking drugs that increase the length of this interval.

Of the medications for this syndrome, the following are usually prescribed:

• β-blockers;
• preparations of magnesium and potassium;
• mexiletine or flecainide (low doses).

With the ineffectiveness of conservative therapy, sympathetic denervation or implantation of a cardioverter-defibrillator is resorted to. The latter is especially important in patients with a high risk of sudden cardiac death and undergoing resuscitation.

- a genetically heterogeneous hereditary condition characterized by a violation of the structure and functionality of some ion channels of cardiomyocytes. The severity of manifestations of pathology varies over a very wide range - from a practically asymptomatic course (only electrocardiological signs are detected) to severe deafness, fainting and arrhythmias. The definition of long QT syndrome is based on data from electrocardiological studies and molecular genetic analyzes. Treatment depends on the form of the pathology and may include continuous or course intake of beta-blockers, magnesium and potassium preparations, as well as the installation of a defibrillator-cardioverter.

General information

Long QT syndrome is a group of cardiac disorders of a genetic nature, in which the passage of ion currents in cardiomyocytes is disrupted, which can lead to arrhythmias, fainting and sudden cardiac death. For the first time, such a condition was identified in 1957 by Norwegian doctors A. Jervell and F. Lange-Nielsen, who described a combination of congenital deafness, syncopal attacks and prolongation of the QT interval in a patient. Somewhat later, in 1962-64, similar symptoms were found in patients with normal hearing - such cases were described independently by K. Romano and O. Ward.

This, as well as further discoveries, determined the division of long QT syndrome into two clinical variants - Romano-Ward and Jervell-Lange-Nielsen. The first is inherited by an autosomal dominant mechanism, its frequency in the population is 1 case per 5,000 population. The occurrence of Jervell-Lange-Nielsen-type long QT syndrome ranges from 1-6:1,000,000, it is characterized by an autosomal dominant inheritance and more pronounced manifestations. According to some reports, all forms of long QT syndrome are responsible for a third of cases of sudden cardiac death and about 20% of sudden infant death.

Causes and classification

Currently, 12 genes have been identified, mutations in which lead to the development of long QT syndrome, all of which encode certain proteins that are part of the ion channels of cardiomyocytes responsible for sodium or potassium ion current. It was also possible to find reasons for the differences in clinical course this disease. Autosomal dominant Romano-Ward syndrome is caused by a mutation in only one gene and therefore may be asymptomatic or at least without hearing loss. With the Jervell-Lange-Nielsen type, there is a defect in two genes - this variant, in addition to cardiac symptoms, is always accompanied by bilateral sensorineural deafness. To date, mutations of which genes are known to cause the development of long QT syndrome:

1. Long QT syndrome type 1 (LQT1) due to a mutation of the KCNQ1 gene located on the 11th chromosome. Defects in this gene are most often detected in the presence of this disease. It encodes the sequence of the alpha subunit of one of the varieties of potassium channels in cardiomyocytes (lKs)
2. Long QT syndrome type 2 (LQT2) is caused by defects in the KCNH2 gene, which is located on the 7th chromosome and encodes the amino acid sequence of the protein - the alpha subunit of another type of potassium channels (lKr).
3. Long QT syndrome type 3 (LQT3) due to a mutation of the SCN5A gene located on the 3rd chromosome. Unlike the previous variants of the pathology, this disrupts the work of the sodium channels of cardiomyocytes, since this gene encodes the sequence of the alpha subunit of the sodium channel (lNa).
4. Long QT syndrome type 4 (LQT4)- a rather rare variant of the condition caused by a mutation of the ANK2 gene, which is located on the 4th chromosome. The product of its expression is the ankyrin B protein, which in the human body is involved in the stabilization of the structure of myocyte microtubules, and is also released in neuroglia and retinal cells.
5. Long QT syndrome type 5 (LQT5)- a type of disease that is caused by a defect in the KCNE1 gene, localized on the 21st chromosome. It encodes one of the ion channel proteins, the beta subunit of potassium channels of the lKs type.
6. Long QT syndrome type 6 (LQT6) caused by a mutation in the KCNE2 gene, also located on the 21st chromosome. Its expression product is the beta subunit of potassium channels of the lKr type.
7. Long QT syndrome type 7(LQT7, another name - Andersen's syndrome, in honor of the pediatrician E. D. Andersen, who described this disease in the 70s) is caused by a defect in the KCNJ2 gene, which is localized on the 17th chromosome. As in the case of the previous variants of pathology, this gene encodes one of the protein chains of potassium channels.
8. Long QT syndrome type 8(LQT8, another name is Timothy's syndrome, in honor of K. Timothy, who described this disease) is caused by a mutation of the CACNA1C gene, which is located on the 12th chromosome. This gene encodes the alpha-1 subunit of the L-type calcium channel.
9. Long QT syndrome type 9 (LQT9) due to a defect in the CAV3 gene located on the 3rd chromosome. The product of its expression is the protein caveolin 3, which is involved in the formation of many structures on the surface of cardiomyocytes.
10. Long QT syndrome type 10 (LQT10)- the cause of this type of disease lies in the mutation of the SCN4B gene, which is located on the 11th chromosome and is responsible for the amino acid sequence of the beta subunit of sodium channels.
11. Long QT syndrome type 11 (LQT11) caused by defects in the AKAP9 gene located on chromosome 7. It encodes a specific protein - A-kinase of centrosomes and the Golgi complex. The functions of this protein are not yet well understood.
12. Long QT syndrome type 12 (LQT12) due to a mutation of the SNTA1 gene located on the 20th chromosome. It encodes the alpha-1 subunit of the syntrophin protein, which is involved in the regulation of the activity of sodium channels in cardiomyocytes.

Despite the wide genetic diversity of long QT syndrome, the general links of its pathogenesis are generally the same for each of the forms. This disease belongs to the group of channelopathies due to the fact that it is caused by disturbances in the structure of certain ion channels. As a result, the processes of myocardial repolarization occur unevenly and not simultaneously in different parts of the ventricles, which causes a prolongation of the QT interval. In addition, the sensitivity of the myocardium to the influences of the sympathetic nervous system increases significantly, which causes frequent tachyarrhythmias that can lead to life-threatening ventricular fibrillation. At the same time, different genetic types of long QT syndrome have different sensitivity to certain influences. For example, LQT1 is characterized by syncopal seizures and arrhythmia during exercise, with LQT2, similar manifestations are observed with loud and sharp sounds, for LQT3, on the contrary, the development of arrhythmias and fibrillations in a calm state (for example, in sleep) is more characteristic.

Long QT symptoms

The manifestations of long QT syndrome are quite diverse. With a more severe clinical type of Jervell-Lange-Nielsen, patients have deafness, frequent fainting, dizziness, and weakness. In addition, in some cases, epileptoid-like convulsive seizures are recorded in this condition, which often leads to incorrect diagnosis and treatment. According to some geneticists, from 10 to 25% of patients with long QT syndrome receive the wrong treatment, and they develop sudden cardiac or infantile death. The occurrence of tachyarrhythmias and syncopal conditions depends on external influences - for example, with LQT1 this can occur against the background of physical activity, with LQT2, loss of consciousness and ventricular fibrillation can occur from sharp and loud sounds.

More mild form long QT syndrome (Romano-Ward type) is characterized by transient syncope (fainting) and rare attacks of tachyarrhythmia, but there are no hearing impairments. In some cases, this form of the disease does not manifest itself in any way, with the exception of electrocardiographic data, and is an accidental finding during medical examination. However, even with this course of long QT syndrome, the risk of sudden cardiac death due to ventricular fibrillation is many times higher than in a healthy person. Therefore, this type of pathology requires careful study and preventive treatment.

Diagnostics

Diagnosis of long QT syndrome is made on the basis of a study of the patient's history, electrocardiological and molecular genetic studies. When questioning the patient, episodes of fainting, dizziness, palpitations are often found, but in mild forms of pathology they may not be. Sometimes similar manifestations occur in one of the patient's relatives, which indicates the family nature of the disease.

With any form of long QT syndrome, ECG changes will be detected - an increase in the QT interval to 0.6 seconds or more, an increase in the amplitude of the T wave is possible. The combination of such ECG signs with congenital deafness indicates the presence of Jervell-Lange-Nielsen syndrome. In addition, Holter monitoring of the work of the heart throughout the day is often necessary to identify possible attacks of tachyarrhythmias. The definition of long QT syndrome using the methods of modern genetics is currently possible for almost all genetic types of this disease.

Treatment of long QT syndrome

Therapy for long QT syndrome is quite complicated, many experts recommend some schemes for this disease and reject others, but there is no single protocol for the treatment of this pathology. Beta-blockers are considered universal drugs, which reduce the risk of developing tachyarrhythmias and fibrillations, as well as reduce the degree of sympathetic effects on the myocardium, but they are ineffective in LQT3. In the case of long QT syndrome type 3, it is more reasonable to use class B1 antiarrhythmic drugs. These features of the treatment of the disease increase the need for molecular genetic diagnostics to determine the type of pathology. In the case of frequent attacks of tachyarrhythmias and a high risk of developing fibrillation, implantation of a pacemaker or cardioverter defibrillator is recommended.

Forecast

The prognosis of long QT syndrome, according to most experts, is uncertain, since this disease is characterized by a wide range of symptoms. In addition, the absence of pathological manifestations, with the exception of electrocardiographic data, does not guarantee the sudden development of fatal ventricular fibrillation under the influence of external or internal factors. If long QT syndrome is identified, a thorough cardiac examination and genetic determination of the type of disease is necessary. Based on the data obtained, a treatment regimen is developed to reduce the likelihood of sudden cardiac death, or a decision is made to implant a pacemaker.

AT last years In clinical cardiology, the problem of QT prolongation attracts close attention of domestic and foreign researchers as a factor leading to sudden death. Determined that both congenital and acquired forms of QT interval prolongation are predictors of fatal arrhythmias which, in turn, lead to sudden death of patients.

Long QT syndrome is a combination of a long QT interval on a standard ECG and life threatening polymorphic ventricular tachycardias (torsade de pointes - "pirouette"). Paroxysms of ventricular tachycardia of the "pirouette" type are clinically manifested by episodes of loss of consciousness and often end in ventricular fibrillation, which is the direct cause of sudden death.

The duration of the QT interval depends on the heart rate and gender of the patient. Therefore, not the absolute, but the corrected value of the QT interval (QTc), which is calculated according to the Bazett formula, is used.

where: RR is the distance between adjacent R waves on the ECG in seconds;

K = 0.37 for men and K = 0.40 for women.

Prolongation of the QT interval is diagnosed if the duration of QTc exceeds 0.44 s.

In recent years, much attention has been paid to the study of the variability (dispersion) of the QT interval, a marker of the inhomogeneity of repolarization processes, since an increased dispersion of the QT interval is also a predictor of the development of a number of serious arrhythmias, including sudden death. The dispersion of the QT interval is the difference between the maximum and minimum values ​​of the QT interval measured in 12 standard ECG leads: D QT = QT max - QT min .

The most common method for detecting QT variance is to record a standard ECG for 3-5 minutes at a recording speed of 25 mm/hour. Holter ECG monitoring is also used, which allows analyzing fluctuations in QTc dispersion (QTcd) during the day. However, a number of methodological aspects of this method are under development. Thus, there is no consensus on the upper limit of the normal values ​​of the dispersion of the corrected QT interval. According to some authors, a QTcd of more than 45 is a predictor of ventricular tachyarrhythymia, other researchers suggest that the upper limit of the normal QTcd is 70 ms and even 125 ms.

There are two most studied pathogenetic mechanism arrhythmias in long QT syndrome. The first - mechanism of "intracardiac disorders" of myocardial repolarization , namely, hypersensitivity myocardium to the arrhythmogenic effect of catecholamines. The second pathophysiological mechanism is imbalance of sympathetic innervation (decrease in right-sided sympathetic innervation due to weakness or underdevelopment of the right stellate ganglion). This concept is supported by animal models (QT interval prolongation after right-sided stellectomy) and the results of left-sided stellectomy in the treatment of resistant forms of QT interval prolongation.

Etiology of long QT syndrome

At healthy people at rest, there is only a slight variability in repolarization processes, so the dispersion of the QT interval is minimal. Causes of prolongation of the QT interval are conditionally divided into 2 groups - congenital and acquired.

congenital forms

Congenital forms of QT prolongation syndrome are becoming one of the causes of death in children. Mortality in untreated congenital forms of this syndrome reaches 75%, while 20% of children die within a year after the first loss of consciousness and about 50% in the first decade of life. Congenital forms of long QT syndrome include Gervell and Lange-Nielsen syndrome and Romano-Ward syndrome. Gervell and Lange-Nielsen Syndrome - a rare disease, has an autosomal recessive type of inheritance and is a combination of congenital deaf-mutism with lengthening of the QT interval on the ECG, episodes of loss of consciousness and often ends in the sudden death of children in the first decade of life. Romano-Ward syndrome has an autosomal dominant pattern of inheritance with a population frequency of 1:10,000-1:15,000 and a gene penetrance of 0.9. It has a similar clinical picture: cardiac arrhythmias, in some cases with loss of consciousness against the background of a prolonged QT interval in children without hearing and speech impairment.

The frequency of detecting a prolonged QT interval in school-age children with congenital deaf-mutism on a standard ECG reaches 44%, while almost half of them (about 43%) had episodes of loss of consciousness and paroxysms of tachycardia. With 24-hour ECG monitoring, almost 30% of them had paroxysms of supraventricular tachycardia, approximately one in five had "runs" of ventricular tachycardia of the "pirouette" type.

A set of diagnostic criteria. "Large" criteria are QT prolongation of more than 0.44 ms, a history of episodes of loss of consciousness, and the presence of long QT interval syndrome in family members. "Small" criteria are congenital sensorineural hearing loss, episodes of T-wave alternation, slow heartbeat(in children) and abnormal ventricular repolarization. Significant prolongation of the QT interval, paroxysms of tachycardia torsade de pointes and episodes of syncope are of the greatest diagnostic value.

Congenital long QT syndrome is a genetically heterogeneous disorder involving more than 5 different chromosomal loci. At least 4 genes have been identified that determine the development of congenital prolongation of the QT interval.

The most common form of long QT syndrome in young adults is combination of this syndrome with prolapse mitral valve . The frequency of detection of prolongation of the QT interval in individuals with prolapse of the mitral and / or tricuspid valves reaches 33%. According to most researchers, mitral valve prolapse is one of the manifestations of congenital connective tissue dysplasia. Among other manifestations of "weakness of the connective tissue" - increased extensibility of the skin, asthenic body type, funnel-shaped deformity chest, scoliosis, flat feet, joint hypermobility syndrome, myopia, varicose veins veins, hernias. A number of researchers have identified a relationship between increased variability in the QT interval and the depth of prolapse and/or the presence of structural changes (myxomatous degeneration) of the mitral valve cusps. One of the main reasons for the formation of QT prolongation in individuals with mitral valve prolapse is a genetically predetermined or acquired magnesium deficiency.

Acquired Forms

Acquired prolongation of the QT interval can occur with atherosclerotic or post-infarction cardiosclerosis, with cardiomyopathy, against and after myo- or pericarditis. An increase in the dispersion of the QT interval (more than 47 ms) may also be a predictor of the development of arrhythmogenic syncope in patients with aortic heart disease.

There is no consensus on the prognostic value of an increase in the dispersion of the QT interval in patients with postinfarction cardiosclerosis: some authors have revealed in these patients a clear relationship between an increase in the duration and dispersion of the QT interval (on the ECG) and the risk of developing paroxysms of ventricular tachycardia, other researchers have not found such a pattern. In cases where the magnitude of the dispersion of the QT interval is not increased in patients with postinfarction cardiosclerosis at rest, this parameter should be assessed when conducting a test with physical activity. In patients with postinfarction cardiosclerosis, the assessment of QT dispersion against the background of exercise tests is considered by many researchers to be more informative for verifying the risk of ventricular arrhythmias.

Prolongation of the QT interval can also be observed in sinus bradycardia, atrioventricular block, chronic cerebrovascular insufficiency and brain tumors. Acute cases of QT prolongation can also occur with trauma (chest, craniocerebral).

Autonomic neuropathy also increases the QT interval and its dispersion, so these syndromes occur in patients with type I and type II diabetes mellitus.

Prolongation of the QT interval can occur with electrolyte imbalance with hypokalemia, hypocalcemia, hypomagnesemia. Such conditions occur under the influence of many reasons, for example, with long-term use of diuretics, especially loop diuretics (furosemide). The development of ventricular tachycardia of the "pirouette" type against the background of prolongation of the QT interval with a fatal outcome in women who were on a low-protein diet in order to reduce body weight is described.

The QT interval can be lengthened with the use of therapeutic doses of a number of drugs, in particular, quinidine, novocainamide, phenothiazine derivatives. Elongation of the electrical systole of the ventricles can be observed in case of poisoning with drugs and substances that have a cardiotoxic effect and slow down the repolarization processes. For example, pachycarpine toxic doses, a number of alkaloids that block the active transport of ions into the myocardial cell, and also have a ganglioblocking effect. There are also cases of prolongation of the QT interval in case of poisoning with barbiturates, organophosphorus insecticides, mercury.

Of interest are the data on circadian rhythms of QT variance obtained from ECG Holter monitoring. A significant increase in the dispersion of the QT interval at night and early morning hours was found, which may increase the risk of sudden death at this time in patients with various cardiovascular diseases (ischemia and myocardial infarction, heart failure, etc.). It is believed that an increase in the dispersion of the QT interval during the night and morning hours is associated with increased sympathetic activity in given time days.

It's common knowledge QT prolongation in acute myocardial ischemia and myocardial infarction . Persistent (more than 5 days) increase in the QT interval, especially when combined with early ventricular extrasystoles, is unfavorable prognostically. These patients showed a significant (5-6 times) increased risk of sudden death.

With the development of acute myocardial ischemia, the dispersion of the QT interval also significantly increases. It has been established that the dispersion of the QT interval increases already in the first hours of acute myocardial infarction. There is no consensus on the magnitude of the dispersion of the QT interval, which is a clear predictor of sudden death in patients with acute myocardial infarction. It has been established that in case of anterior myocardial infarction, a dispersion of more than 125 ms is a prognostically unfavorable factor, indicating a high risk of death. A number of authors have revealed an even more significant increase in QT dispersion during reperfusion (after coronary angioplasty). However, other researchers, on the contrary, found a decrease in QT variance during reperfusion in patients with acute myocardial infarction, and an increase in QT variance was noted in cases where reperfusion was not achieved. Therefore, some authors recommend using a decrease in QT variance as a marker of successful reperfusion. In patients with acute myocardial infarction, the circadian rhythm of QT dispersion is also disturbed: it is increased at night and in the morning, which increases the risk of sudden death at this time of day.

In the pathogenesis of QT prolongation in acute myocardial infarction, hypersympathicotonia undoubtedly plays a role, and this is precisely what many authors explain the high effectiveness of b-blockers in these patients. In addition, the development of this syndrome is based on electrolyte disturbances, in particular, magnesium deficiency. The results of many studies indicate that up to 90% of patients with acute myocardial infarction have magnesium deficiency . An inverse correlation was also found between the level of magnesium in the blood (serum and erythrocytes) and the QT interval and its dispersion in patients with acute myocardial infarction.

Treatment

First of all, the etiological factors that led to the lengthening of the QT interval should be eliminated in cases where this is possible. For example, medications (diuretics, barbiturates, etc.) that may increase the duration or variance of the QT interval should be discontinued or reduced. Adequate treatment of heart failure, according to international guidelines, and successful surgery heart defects will also lead to normalization of the QT interval. It is known that in patients with acute myocardial infarction, fibrinolytic therapy reduces the magnitude and dispersion of the QT interval (although not to normal values). Among the groups of drugs that can influence the pathogenesis of this syndrome, two groups should be especially noted - b-blockers and magnesium preparations .

Congenital long QT syndrome

Patients with Romano-Ward and Gervell and Lange-Nielsen syndromes require continuous use of b-blockers in combination with oral magnesium preparations ( Magnesium orotate 2 tab. 3 times a day). Left-sided stellectomy and removal of the 4th and 5th thoracic ganglia may be recommended in patients in whom pharmacological therapy has failed. positive result. There are reports of the successful combination of treatment with b-blockers with the implantation of an artificial pacemaker.

For patients requiring emergency treatment, the drug of choice is propranolol intravenously (at a rate of 1 mg / min, the maximum dose is 20 mg, the average dose is 5-10 mg under the control of blood pressure and heart rate) or bolus intravenous administration 5 mg propranolol against the background of intravenous drip of magnesium sulfate (Kormagnezina) (at the rate of 1-2 g of magnesium sulfate (200-400 mg of magnesium) depending on body weight (in 100 ml of 5% glucose solution for 30 minutes).

In patients with idiopathic mitral valve prolapse, treatment should begin with the use of oral magnesium preparations (Magnerot 2 tablets 3 times a day for at least 6 months), since tissue magnesium deficiency is considered one of the main pathophysiological mechanisms for the formation of both the syndrome of lengthening the QT interval, and "weakness" of the connective tissue. In these individuals, after treatment with magnesium preparations, not only the QT interval normalizes, but also the depth of prolapse of the mitral valve cusps decreases, the frequency ventricular extrasystoles, severity clinical manifestations(vegetative dystonia syndrome, hemorrhagic symptoms, etc.). If treatment with oral magnesium preparations after 6 months has not had a full effect, the addition of b-blockers is indicated.

Acquired Long QT Syndrome

All drugs that can prolong the QT interval should be discontinued. Correction of electrolytes of blood serum is necessary, especially potassium, calcium, magnesium. In some cases, this is sufficient to normalize the magnitude and dispersion of the QT interval and prevent ventricular arrhythmias.

In acute myocardial infarction, fibrinolytic therapy and b-blockers reduce the magnitude of the dispersion of the QT interval. These appointments, according to international recommendations, are mandatory in all patients with acute myocardial infarction, taking into account standard indications and contraindications.

However, even with adequate management of patients with acute myocardial infarction, in a considerable part of them, the magnitude and dispersion of the QT interval do not reach normal values, therefore, the risk of sudden death remains. Therefore, the question of the effectiveness of the use of magnesium preparations in acute stage myocardial infarction. Duration, dosages and methods of administration of magnesium preparations in these patients have not been finally established. The following schemes are available: intravenous administration Kormagnezina-400 at the rate of 0.5-0.6 g of magnesium per hour for the first 1-3 days, followed by the transition to oral administration of Magnerot (Table 2, 3 times for at least 4-12 weeks). There is evidence that in patients with acute myocardial infarction who received such therapy, normalization of the magnitude and dispersion of the QT interval and the frequency of ventricular arrhythmias was noted.

When stopping ventricular tachyarrhythmias in patients with acquired forms of QT interval prolongation, it is also recommended to add an intravenous drip of Kormagnesin to the treatment regimen at the rate of 2-4 g of magnesium sulfate (400-800 mg of magnesium) in 100 ml of 5% glucose solution for 30 minutes. If necessary, it can be reintroduced.

Conclusion

Thus, prolongation of the QT interval is a predictor of fatal arrhythmias and sudden cardiogenic death both in patients with cardiovascular diseases (including acute myocardial infarction) and in individuals with idiopathic ventricular tachyarrhythmias. Timely diagnosis QT prolongation and its dispersion, including during ECG Holter monitoring and during exercise tests, will make it possible to identify a group of patients with an increased risk of developing ventricular arrhythmias, syncope, and sudden death. effective means prevention and treatment of ventricular arrhythmias in patients with congenital and acquired forms of QT interval prolongation syndrome are b-blockers in combination with magnesium preparations.

Magnesium Orotate -

Magnerot (trade name)

(Worwag Pharma)

The genes responsible for the development of the disease have been identified, the function of cardiomyocytes at the molecular level and clinical manifestations have been studied. The deciphering of mutations in the genes encoding the protein structural elements of some ion channels made it possible to establish a clear relationship between the genotype and the phenotype.

Pathophysiology

Long OT interval syndrome develops due to the prolongation of the period of repolarization of ventricular cardiomyocytes, which is manifested by a prolongation of the OT interval on the ECG, predisposes to the occurrence of ventricular arrhythmias in the form of tachycardia of the "pirouette" type, ventricular fibrillation, sudden cardiac death. The action potential of a cardiomyocyte is generated by the coordinated work of at least 10 ion channels (which mainly transport sodium, calcium and potassium ions through the cell membrane). Functional disorders any of these mechanisms (acquired or genetically determined), leading to an increase in depolarization currents or a weakening of the repolarization process, can cause the development of the syndrome.

Congenital form of the syndrome

Two hereditary forms of this pathology are well studied. The most common is Romano-Ward syndrome (an autosomal dominant disorder with varying penetrance that has no other phenotypic features) and the less common Jervell-Lange-Nielsen syndrome, an autosomal recessive disorder that is associated with deafness. Modern gene classification has now replaced these eponyms. Six chromosomal loci (LQTS1-6) have been identified, encoding six genes responsible for the occurrence of pathology. Each of the genetic syndromes also has characteristic clinical manifestations.

There is a connection between congenital and acquired forms. Carriers of the genetic abnormality may not show characteristic electrocardiographic signs, but when taking drugs that prolong the QT interval, such as erythromycin, such people may develop torsades de pointes and cause sudden death.

Acquired form of the syndrome

Clinical manifestations

A characteristic sign of the syndrome of prolongation of the OT interval is repeated fainting, provoked by emotional or physical stress. At the same time, pirouette-type arrhythmia is observed, which is often preceded by "short-long-short" cardiac cycles. Such bradycardia-related phenomena are more common in the acquired form of the disease. Clinical signs congenital forms are due to individual genetic mutations. Unfortunately, the first clinical manifestation of the disease can be sudden cardiac death.

ECG. The duration of the corrected OT interval is more than 460 ms and can reach 600 ms. By the nature of the changes in the T wave, it is possible to determine the specific gene mutation. The normal WC interval in the presence of the disease in family members does not exclude the possibility of carriage. The degree of prolongation of the OT interval varies, so the variance of the OT interval is also increased in these patients.

Normal corrected QT - EXL/(RR interval) = 0.38-0.46 s (9-11 small squares).

Long QT syndrome: treatment

Usually episodes of arrhythmia such as "pirouette" are short-lived and disappear on their own. Long-term episodes that cause hemodynamic disturbances should be immediately eliminated with the help of cardioversion. In case of recurrent seizures or after cardiac arrest, a solution of magnesium sulfate is administered intravenously and then drip, and then, if necessary, temporary pacing is performed (frequency 90-110). As a preparatory therapy, an isoprenaline infusion is started before stimulation.

Acquired form

The causes of the development of the syndrome should be identified and eliminated. It is necessary to stop taking drugs that cause lengthening of the OT. Before receiving the results of blood tests, magnesium sulfate should be administered. It is necessary to quickly determine the level of potassium in the blood serum, the gas composition of the blood. With a decrease in the level of potassium less than 4 mmol / l, a correction of its level to the upper limit of the norm is necessary. Long-term treatment is usually not required, but if the cause pathological condition is an unrecoverable heart block, a permanent pacemaker is required.

congenital form

Most episodes are provoked by a sharp increase in the activity of the sympathetic nervous system, so treatment should be aimed at preventing such situations. The most preferred drugs are β-blockers. Propranolol reduces the relapse rate in symptomatic patients. In the absence of effect or intolerance to β-blockers, surgical denervation of the heart is an alternative.

Cardiac stimulation reduces symptoms in bradycardia induced by taking β-blockers, as well as in situations where pauses in the work of the heart provoke clinical manifestations (LOT3). In the congenital form, pacemakers are never considered as monotherapy. Defibrillator implantation should only be considered if there is a high risk of sudden cardiac death or if the first manifestation of the disease was sudden cardiac death followed by successful resuscitation. Installing a defibrillator prevents sudden cardiac death, but does not prevent recurrence of torsades de pointes. Repetitive shocks for short episodes may
significantly reduce the quality of life of patients. Careful selection of patients, the simultaneous appointment of β-blockers, the choice of the mode of operation of defibrillators help to achieve success in the treatment of such patients.

Asymptomatic patients

Screening among family members of the patient allows you to identify individuals with long QT syndrome who have never had clinical symptoms. Most patients do not die from long QT syndrome, but are at risk of death (lifetime risk is 13% if untreated). It is necessary to evaluate the ratio of efficiency lifelong treatment with possible development side effects and the risk of sudden cardiac death in each case.

Determining the risk of developing sudden death is a difficult task, but with an accurate knowledge of the nature of the genetic anomaly, it becomes easier. Recent studies have shown the need for initiation of treatment in LOT1 with a lengthening of the corrected OT interval of more than 500 ms (for both men and women); with LQT2 - in all men and women with an increase in the QT interval of more than 500 ms; at LQT3 - in all patients. In each case, an individual approach is required.

Relevance. Lack of awareness of pediatricians, therapists and neurologists about this disease often leads to tragic outcomes - sudden death of patients with long QT syndrome (Long-QT syndrome - LQTS). Also, such patients often have an overdiagnosis of epilepsy due to the clinical similarity of syncopal conditions (complicated by "convulsive syndrome"), which are incorrectly interpreted as classic epileptic seizures.

Definition. LQTS - is a prolongation of the QT interval on the ECG (more than 440 ms), against which there are paroxysms of ventricular tachycardia of the "pirouette" type. The main danger lies in the frequent transformation of this tachycardia into ventricular fibrillation, which often leads to loss of consciousness (fainting), asystole and death of the patient (sudden cardiac death [SCD]). Currently, LQTS is classified as a common rhythm disorder.

reference Information. QT interval - the time interval of the electrocardiogram (ECG) from the beginning of the Q wave to the return of the descending knee of the T wave to the isoline, reflecting the processes of depolarization and repolarization of the ventricular myocardium. The QT interval is a generally accepted, and, at the same time, widely discussed indicator that reflects the electrical systole of the ventricles of the heart. It includes the QRS complex (rapid depolarization and initial repolarization of the myocardium of the interventricular septum, the walls of the left and right ventricles), the ST segment (repolarization plateau), the T wave (final repolarization).

The most important factor in determining the length of the QT interval is HR (heart rate). The dependence is non-linear and inversely proportional. The length of the QT interval is variable both in the individual and in populations. Normally, the QT interval is at least 0.36 seconds and not more than 0.44 seconds. Factors that change its duration are: [ 1 ] HR; [ 2 ] state of the autonomic nervous system; [ 3 ] the action of the so-called sympathomimetics (adrenaline); [ 4 ] electrolyte balance (especially Ca2+); [ 5 ] some drugs; [ 6 ] age; [ 7 ] floor; [ 8 ] Times of Day.

Remember! The determination of QT prolongation is based on the correct measurement and interpretation of the QT interval relative to heart rate values. The duration of the QT interval normally varies with heart rate. To calculate (correct) the magnitude of the QT interval, taking into account heart rate (= QTc) use various formulas (Bazett, Fridericia, Hodges, Framingham formula), tables and nomograms.

The prolongation of the QT interval reflects an increase in the time of conduction of excitation through the ventricles, but such a delay in the impulse leads to the formation of the prerequisites for the formation of the re-entry mechanism (the mechanism for re-entry of the excitation wave), that is, for the repeated circulation of the impulse in the same pathological focus. Such a center of impulse circulation (hyper-impulsation) can provoke a paroxysm of ventricular tachycardia (VT).

Pathogenesis. There are several main hypotheses for the pathogenesis of LQTS. One of them is the hypothesis of a sympathetic imbalance of innervation (decrease in right-sided sympathetic innervation due to weakness or underdevelopment of the right stellate ganglion and the predominance of left-sided sympathetic influences). The hypothesis of pathology of ion channels is of interest. It is known that the processes of depolarization and repolarization in cardiomyocytes arise due to the movement of electrolytes into the cell from the extracellular space and back, controlled by K+-, Na+- and Ca2+-channels of the sarcolemma, the energy supply of which is carried out by Mg2+-dependent ATPase. All LQTS variants are thought to be based on dysfunction of various ion channel proteins. At the same time, the reasons for the violation of these processes, leading to a lengthening of the QT interval, can be congenital and acquired (see below).

Etiology. It is customary to distinguish between congenital and acquired variants of the LQTS syndrome. The congenital variant is a genetically determined disease that occurs in one case per 3-5 thousand of the population, and from 60 to 70% of all patients are women. According to the International Registry, in about 85% of cases the disease is hereditary, while about 15% of cases are the result of new spontaneous mutations. To date, more than ten genotypes have been identified that determine the presence of different options LQTS syndrome (all of them are associated with mutations in the genes encoding the structural units of the membrane channels of cardiomyocytes) and designated as LQT, but the most frequent and clinically significant are three of them: LQT1, LQT2 and LQT3.

Secondary etiological factors for LQTS may include drugs (see below), electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia); CNS disorders(subarachnoid hemorrhage, trauma, tumor, thrombosis, embolism, infection); heart disease (slow heart rhythms [sinus bradycardia], myocarditis, ischemia [especially Prinzmetal's angina], myocardial infarction, cardiopathy, mitral valve prolapse - MVP [the most common form of LQTS in young people is the combination of this syndrome with MVP; frequency of detection of prolongation of the QT interval in persons with MVP and / or tricuspid valves reaches 33%]); and other various reasons (low-protein diet, consumption of fatty animal foods, chronic alcoholism, osteogenic sarcoma, lung carcinoma, Kohn's syndrome, pheochromocytoma, diabetes, hypothermia, neck surgery, vagotomy, familial periodic paralysis, scorpion venom, psycho-emotional stress). Acquired elongation Q-T interval 3 times more common in men and is typical for older people with diseases in which coronarogenic myocardial damage predominates.

Clinic. The most striking clinical manifestations of LQTS, which in most cases are the root cause of contacting a doctor, should include attacks of loss of consciousness, or syncope, which are caused by a life-threatening polymorphic VT specific for LQTS, known as "torsades de pointes" (ventricular tachycardia of the "pirouette" type), or ventricular fibrillation (VF). With the help of ECG research methods, most often during an attack, special form VT with a chaotic change in the electrical axis of ectopic complexes. This fusiform ventricular tachycardia, turning into VF and cardiac arrest, was first described in 1966 by F. Dessertene in a patient with LQTS during syncope, who gave it the name "pirouette" ("torsades de pointes"). Often, paroxysms (VT) are short-lived, usually end spontaneously, and may not even be felt (LQTS may not be accompanied by loss of consciousness). However, there is a tendency for arrhythmic episodes to recur in the near future, which can cause syncope and death.

read also the article "Diagnosis of ventricular arrhythmias" by A.V. Strutynsky, A.P. Baranov, A.G. Elderberry; Department of Propaedeutics of Internal Diseases of the Medical Faculty of the Russian State Medical University (magazine "General Medicine" No. 4, 2005) [read]

In the literature, there is a stable relationship of provoking factors with syncopal episodes. When analyzing the factors involved in syncope, it was found that in almost 40% of patients, syncopal conditions are recorded against the background of strong emotional arousal (anger, fear). Approximately in 50% of cases, seizures are provoked by physical activity (excluding swimming), in 20% - by swimming, in 15% of cases they occur during awakening from a night's sleep, in 5% of cases - as a reaction to sharp sound stimuli (phone call, call in door, etc.). If syncope is accompanied by convulsions of a tonic-clonic nature with involuntary urination, sometimes with defecation, differential diagnosis between syncope with a convulsive component and a major epileptic seizure is difficult due to the similarity of clinical manifestations. However, a careful study will reveal significant differences in the post-attack period in patients with LQTS - a quick recovery of consciousness and a good degree of orientation without amnestic disturbances and drowsiness after the attack. LQTS does not exhibit personality changes typical of epilepsy patients. Main hallmark LQTS should be considered to be associated with established precipitating factors, as well as pre-syncope states of cases of this pathology.

Diagnostics. The ECG is often of decisive importance in the diagnosis of the main clinical variants of the syndrome (the duration of the QT interval is determined on the basis of an assessment of 3-5 cycles). An increase in the duration of the QT interval by more than 50 ms in relation to normal values for a given heart rate (HR) should alert the investigator to rule out LQTS. In addition to the actual lengthening of the QT interval, ECG also reveals other signs of electrical instability of the myocardium, such as alternation of the T wave (change in the shape, amplitude, duration or polarity of the T wave that occurs with a certain regularity, usually in every second QRST complex), an increase in the dispersion of the interval QT (reflects the heterogeneity of the duration of the repolarization process in the ventricular myocardium), as well as concomitant rhythm and conduction disturbances. Holter monitoring (HM) allows you to set the maximum duration of the QT interval.

Remember! The measurement of the QT interval is of great clinical importance, mainly because its prolongation may be associated with an increased risk of death, including SCD due to the development of fatal ventricular arrhythmias, in particular polymorphic ventricular tachycardia [ventricular tachycardia of the "pirouette" type - torsade de pointes , (TdP)]. Many factors contribute to QT interval prolongation, including special attention deserves the irrational use of drugs that can increase it.

Drugs that can cause LQTS: [1 ] antiarrhythmic drugs: class IA: quinidine, procainamide, disopyramide, giluritmal; Class IC: encainide, flecainide, propafenone; Class III: amiodarone, sotalol, bretilium, dofetilide, sematilide; IV class: bepridil; other antiarrhythmic drugs: adenosine; [ 2 ] cardiovascular drugs: adrenaline, ephedrine, cavinton; [ 3 ] antihistamines: astemizole, terfenadine, diphenhydramine, ebastine, hydroxyzine; [ 4 ] antibiotics and sulfonamides: erythromycin, clarithromycin, azithromycin, spiramycin, clindamycin, anthramycin, troleandomycin, pentamidine, sulfamethaxosole-trimethoprim; [ 5 ] antimalarial drugs: nalofantrine; [ 6 ] antifungal drugs: ketoconazole, fluconazole, itraconazole; [ 7 ] tricyclic and tetracyclic antidepressants: amitriptyline, norttriptyline, imipramine, desipramine, doxepin, maprotiline, phenothiazine, chlorpromazine, fluvoxamine; [ 8 ] neuroleptics: haloperidol, chloral hydrate, droperidol; [ 9 ] serotonin antagonists: ketanserin, zimeldin; [ 10 ] gastroenterological preparations: cisapride; [ 11 ] diuretics: indapamide and other drugs that cause hypokalemia; [ 12 ] other drugs: cocaine, probucol, papaverine, prenylamine, lidoflazin, terodilin, vasopressin, lithium preparations.

Read more about LQTS in the following sources:

lecture "Long QT Syndrome" N.Yu. Kirkina, A.S. Volnyagin; Tula State University, medical institute, Tula (journal "Clinical Medicine and Pharmacology" No. 1, 2018 ; pp. 2 - 10) [read ];

article "The clinical significance of prolongation of QT and QTC intervals while taking medications" N.V. Furman, S.S. Shmatova; Saratov Research Institute of Cardiology, Saratov (journal "Rational pharmacotherapy in cardiology" No. 3, 2013) [read];

article "Long QT syndrome - main clinical and pathophysiological aspects" N.A. Tsibulkin, Kazan State medical Academy(Journal "Practical Medicine" No. 5, 2012) [read]

article "Long QT Syndrome" Roza Khadiyevna Arsentieva, doctor of functional diagnostics at the Center for Psychophysiological Diagnostics of the Medical and Sanitary Unit of the Ministry of Internal Affairs of the Russian Federation for the Republic of Tatarstan (journal Bulletin of Modern clinical medicine No. 3, 2012) [read];

article "Long QT syndrome" heading - "Medicinal safety" (Zemsky doctor magazine No. 1, 2011) [read]

article “Acquired Long QT Syndrome” E.V. Mironchik, V.M. Pyrochkin; Chair hospital therapy Educational Establishment "Grodno State Medical University" (Journal of GrGMU No. 4, 2006) [read];

article "Long QT syndrome - clinic, diagnosis and treatment" L.A. Bokeria, A.Sh. Revishvili, I.V. Pronicheva Scientific Center for Cardiovascular Surgery. A.N. Bakuleva RAMS, Moscow (magazine "Annals of Arrhythmology" No. 4, 2005) [read]

© Laesus De Liro