The article is devoted to congenital and acquired ECG syndrome of long QT interval, as well as Amiodarone, as the most common drug cause of this condition.

Long QT syndrome is a combination of a prolonged QT interval on a standard ECG and life-threatening polymorphic ventricular tachycardias (torsade de pointes). 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, they use not the absolute, but the corrected value of the QT interval (QTc), which is calculated using the Bazett formula:

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

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

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

It has been established that both congenital and acquired forms of QT interval prolongation are predictors of fatal rhythm disturbances, which, in turn, lead to sudden death of patients.

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 increased dispersion of the QT interval is also a predictor of the development of a number of serious rhythm disturbances, including sudden death. QT interval dispersion is the difference between the maximum and minimum values ​​of the QT interval measured in 12 standard ECG leads: D QT = QTmax-QTmin.

Thus, there is no consensus on the upper limit of normal values ​​for the dispersion of the corrected QT interval. According to some authors, a predictor of ventricular tachyarrhythmia is a QTcd of more than 45; other researchers suggest that a QTcd of 70 ms and even 125 ms be considered the upper limit of normal.

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

The incidence of QT interval prolongation in individuals with mitral and/or tricuspid valve prolapse reaches 33%. According to most researchers, mitral valve prolapse is one of the manifestations of congenital connective tissue dysplasia. Other manifestations of “connective tissue weakness” include increased skin extensibility, asthenic body type, funnel chest deformity, scoliosis, flat feet, joint hypermobility syndrome, myopia, varicose veins, hernias. A number of researchers have identified a relationship between increased variability of the QT interval and the depth of prolapse and/or the presence of structural changes (myxomatous degeneration) of the mitral valve leaflets. One of the main reasons for the formation of prolongation of the QT interval in people with mitral valve prolapse is genetically predetermined or acquired magnesium deficiency

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

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

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

Prolongation of the QT interval can occur with electrolyte imbalance with hypokalemia, hypocalcemia, hypomagnesemia. Such conditions arise 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 is described against the background of prolongation of the QT interval with a fatal outcome in women who were on a low-protein diet to reduce body weight.

QT prolongation is well known in acute myocardial ischemia and myocardial infarction. A persistent (more than 5 days) increase in the QT interval, especially when combined with early ventricular extrasystoles, has an unfavorable prognosis. These patients showed a significant (5-6 times) increase in the risk of sudden death.

Hypersympathicotonia undoubtedly plays a role in the pathogenesis of QT prolongation in acute myocardial infarction, which is why many authors explain the high effectiveness of b-blockers in these patients. In addition, the development of this syndrome is also 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 between the level of magnesium in the blood (serum and erythrocytes) with the QT interval and its dispersion in patients with acute myocardial infarction was also revealed.

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 of the formation of QT interval prolongation syndrome, and “weakness” of connective tissue. In these individuals, after treatment with magnesium preparations, not only does the QT interval normalize, but also the depth of prolapse of the mitral valve leaflets, the frequency of ventricular extrasystoles, and the severity of clinical manifestations (vegetative dystonia syndrome, hemorrhagic symptoms, etc.) decrease. If treatment with oral magnesium supplements after 6 months has not had a complete effect, the addition of b-blockers is indicated.

Another important cause of prolongation of the QT interval is the use of special medications; one of the drugs most often used in clinical practice is Amiodarone (Cordarone).

Amiodarone belongs to class III antiarrhythmic drugs (class of repolarization inhibitors) and has a unique mechanism of antiarrhythmic action, since in addition to the properties of class III antiarrhythmics (potassium channel blockade), it has the effects of class I antiarrhythmics (sodium channel blockade), class IV antiarrhythmics (calcium channel blockade) ) and non-competitive beta-blocking action.
In addition to the antiarrhythmic effect, it has antianginal, coronary dilation, alpha and beta adrenergic blocking effects.

Antiarrhythmic properties:
- increasing the duration of the 3rd phase of the action potential of cardiomyocytes, mainly due to blocking the ion current in potassium channels (the effect of a class III antiarrhythmic according to the Williams classification);
- a decrease in the automaticity of the sinus node, leading to a decrease in heart rate;
- non-competitive blockade of alpha and beta adrenergic receptors;

Description
- slowing of sinoatrial, atrial and atrioventricular conduction, more pronounced with tachycardia;
- no changes in ventricular conductivity;
- an increase in refractory periods and a decrease in the excitability of the myocardium of the atria and ventricles, as well as an increase in the refractory period of the atrioventricular node;
- slowing down conduction and increasing the duration of the refractory period in additional atrioventricular conduction bundles.

Other effects:
- absence of negative inotropic effect when taken orally;
- reduction of oxygen consumption by the myocardium due to a moderate decrease in peripheral resistance and heart rate;
- increase coronary blood flow due to direct effects on the smooth muscles of the coronary arteries;
- maintaining cardiac output by reducing pressure in the aorta and reducing peripheral resistance;
- influence on the exchange of thyroid hormones: inhibition of the conversion of T3 to T4 (blockade of thyroxine-5-deiodinase) and blocking the uptake of these hormones by cardiocytes and hepatocytes, leading to a weakening of the stimulating effect of thyroid hormones on the myocardium.
Therapeutic effects are observed on average a week after starting to take the drug (from several days to two weeks). After stopping its use, amiodarone is detected in the blood plasma for 9 months. The possibility of maintaining the pharmacodynamic effect of amiodarone for 10-30 days after its discontinuation should be taken into account.

Each dose of amiodarone (200 mg) contains 75 mg of iodine.

Indications for use

Relapse Prevention

• Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation (treatment should be started in the hospital with careful cardiac monitoring).

• Supraventricular paroxysmal tachycardia:
  - documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with organic heart diseases;
  - documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients without organic heart disease, when antiarrhythmic drugs of other classes are not effective or there are contraindications to their use;
  - documented attacks of recurrent sustained supraventricular paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.

• Atrial fibrillation (atrial fibrillation) and atrial flutter

Prevention of sudden arrhythmic death in high-risk patients

• Patients after a recent myocardial infarction with more than 10 ventricular extrasystoles per hour, clinical manifestations of chronic heart failure and a reduced left ventricular ejection fraction (less than 40%).
  Amiodarone may be used in the treatment of arrhythmias in patients with coronary artery disease and/or left ventricular dysfunction

For patients with chronic heart failure, amiodarone is the only antiarrhythmic drug approved for use. This is due to the fact that other drugs in this category of patients either increase the risk of sudden cardiac death or depress hemodynamics.

In the presence of coronary heart disease, the drug of choice is sotalol, which, as is known, is 1/3 a beta-blocker. But given its ineffectiveness, we again have only amiodarone at our disposal. As for patients with arterial hypertension, from among them, in turn, there are patients with pronounced and unexpressed left ventricular hypertrophy. If the hypertrophy is small (in the 2001 Guidelines, the thickness of the left ventricular wall is less than 14 mm), the drug of choice is propafenone, but if it is ineffective, as always, amiodarone (along with sotalol). Finally, with severe left ventricular hypertrophy, as with chronic heart failure, amiodarone is the only possible drug.

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© Arsentyeva R.Kh., 2012 UDC 616.12-008.318

Long QT syndrome

ROZA KHADIEVNA ARSENTIEVA, functional diagnostics doctor 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, e-mail: [email protected]

Abstract. This article highlights the current state of the problem of congenital and acquired long QT syndrome. Information is presented on its prevalence, etiology, pathogenesis, diagnostic methods, clinical picture, and possible ways to prevent life-threatening complications.

Key words: long QT syndrome.

long QT siNDRoME

R.K.H. ARSENTYEVA

Abstract. This article describes the current state of congenital and acquired Long QT syndrome problem. Provided the information about its prevalence, etiology, pathogeny, diagnostic methods, clinical picture and possible prophylaxis ways.

Key words: long QT syndrome.

In recent years, in clinical cardiology, the problem of prolongation of the QT interval has attracted close attention of domestic and foreign researchers as a factor leading to sudden death. It has been established that both congenital and acquired forms of QT interval prolongation are predictors of fatal rhythm disturbances, which, in turn, lead to sudden death of patients. The QT interval is the distance from the beginning of the QRS complex to the end of the T wave. From the point of view of electrophysiology, it reflects the sum of the processes of depolarization (electrical excitation with a change in cell charge) and subsequent repolarization (restoration of electrical charge) of the ventricular myocardium.

This parameter is often called electrical systole of the heart (figure). The most important factor determining the duration of the QT interval is heart rate. The dependence is nonlinear and inversely proportional.

The history of the discovery of LQTS dates back to 1856, when T. Meissner described the sudden death of a young man during emotional stress, in whose family two other children died under similar circumstances. Only 100 years later, in 1957, A. Jervell and F. Lange-Nielsen presented a complete clinical description of LQTS in four members of one family, where all suffered from congenital deafness, frequent loss of consciousness and had persistent prolongation of the QT interval on the ECG. Soon C. Romano (1963) and

O. Ward (1964) presented an observation of a similar syndrome, but without congenital deafness. LQTS with high frequency

occurs in persons with paroxysmal conditions, and in children with congenital deafness - in 0.8%. When examining patients with cardiogenic syncope, LQTS was detected in 36% of cases. Bazett (1920), Fridericia (1920), Neddypn and Hotman (1937) were the first researchers of this phenomenon. NeddPp and Ho^tapp proposed a formula for calculating the proper value of the QT interval: QT=K/RR, where K is the coefficient

Electrical systole of the heart

0.37 for men and 0.40 for women. Since the duration of the QT interval depends on the heart rate (lengthening as it slows down), it must be corrected relative to the heart rate for evaluation. The duration of the QT interval is variable both within individuals and across populations. The factors that change its duration are (only the main ones): heart rate (HR); state of the autonomic nervous system; the effect of so-called sympathomimetics (adrenaline, for example); electrolyte balance (especially Ca2+); some medications; age; floor; Times of Day. Long QT syndrome (LQTS) is a prolongation of the QT interval on the ECG, against the background of which paroxysms of ventricular tachycardia of the “pirouette” type occur. In children, the duration of the interval is shorter than in adults. There are tables that present the standards for electrical ventricular systole for a given gender and rhythm frequency. If the patient's QT interval duration exceeds the intervals by more than 0.05 s, then they speak of prolongation of the electrical systole of the ventricles, which is a characteristic sign of cardiosclerosis. The main danger is the frequent transformation of tachycardia into ventricular fibrillation, which often leads to loss of consciousness, asystole and death of the patient.

The most commonly used formulas are Bazett QT QT

QTc(B) = - and Frederic QTc(B) = - ,

where QTc is the corrected (relative to heart rate) value of the QT interval, a relative value; RR is the distance between this QRS complex and the one preceding it, expressed in seconds.

Bazett's formula is not entirely correct. There was a tendency toward over-correction at high heart rates (with tachycardia) and under-correction at low heart rates (with bradycardia). The proper values ​​are in the range of 300-430 for men and 300-450 for women. One of the reliable predictors of SCD can also be an increase in the dispersion of the QT interval (AQT), which is the difference between the maximum and minimum values ​​of the duration of the QT interval in 12 standard ECG leads: AQT = QTmax - QTmin. This term was first proposed by S.R. Day et al. in 1990. If the QT interval reflects the duration of the overall electrical activity of the ventricles, including both depolarization and repolarization, then in the absence of changes in the duration of the ventricular QRS complex, AQT reflects regional heterogeneity of repolarization. The AQT value depends on the number of ECG leads included in the assessment, so excluding several leads from the analysis could potentially affect the result downward. To eliminate this factor, an indicator such as the normalized dispersion of the QT interval (AQT^, calculated by the formula AQ^ = AQ^ - the number of leads used was proposed. Normally, in healthy individuals in 12 ECG leads, this indicator does not exceed 20-50 ms.

Etiology of elongated syndrome

QT interval

The etiology of LQTS until recently remained unclear, although the presence of this syndrome in non-

how many members of one family allowed almost from the moment of the first description to consider it as a congenital pathology. There are several main hypotheses for the pathogenesis of LQTS. One of them is the hypothesis of a sympathetic imbalance of innervation (a decrease in right-sided sympathetic innervation due to weakness or underdevelopment of the right stellate ganglion and a predominance of left-sided sympathetic influences). The hypothesis of ion channel pathology is of interest. It is known that the processes of depolarization and repolarization in cardiomyocytes arise as a result of the movement of electrolytes into the cell from the extracellular space and back, controlled by the K+, Na+ and Ca2+ channels of the sarcolemma, the energy supply of which is carried out by the Md2+-dependent ATPase. It is believed that all LQTS variants are based on dysfunction of various ion channel proteins. Moreover, the causes of disruption of these processes leading to prolongation of the QT interval can be congenital and acquired. This is often preceded by a short-long-short sequence (SLS): alternation of supraventricular extrasystolia, post-extrasystolic pause and repeated ventricular extrasystoles. There are two most studied pathogenetic mechanisms of arrhythmias in long QT interval syndrome. The first mechanism of intracardiac disorders of myocardial repolarization, namely: increased sensitivity of the myocardium to the arrhythmogenic effect of catecholamines. The second pathophysiological mechanism is an imbalance of sympathetic innervation (decreased 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 refractory forms of QT interval prolongation. According to the mechanism of development of ventricular tachycardias, all congenital LQTS syndromes are classified into the adrenergic-dependent group (ventricular tachycardia in such patients develops against the background of increased sympathetic tone), while acquired LQTS constitutes a pause-dependent group (ventricular extrasystole, predominantly pirouette, occurs after a change in the R-R interval in the form of SLS -sequences). This division is rather arbitrary, since there is evidence of the presence, for example, of pause-dependent congenital LQTS. Cases have been reported where taking medications leads to the manifestation of previously asymptomatic LQTS.

While Romano-Ward syndrome can result from any of 6 types of mutations, Jervell-Lange-Nielsen syndrome occurs when a child receives mutant genes from both parents. Some mutations cause more severe forms of the disease, others less severe forms of the disease. It has been proven that Romano-Ward syndrome with the homozygous variant is more severe than with the heterozygous one. According to V.K. Gusak et al., of all cases of congenital LQTS, LQT1 accounts for 42%, LQT2 - 45%, LQT3 - 8%, LQT5 - 3%, LQT6 - 2%. It has been established that LQT1 is characterized by a widened T wave, LQT2 is characterized by a low-amplitude and double-humped wave, and LQT3 is characterized by a normal T wave. The longest QT duration s is observed in LQT3. Of interest is the difference in continuation

the duration of the QT interval at night: with LQT1, the QT interval is slightly shortened, with LQT2 it is slightly lengthened, with LQT3 it is significantly lengthened. The manifestation of clinical manifestations in LQT1 is most often observed at the age of 9 years, in LQT2 - at 12 years, in LQT3 - at 16 years. Of particular importance is measuring the interval after physical activity. With LQT1, syncope occurs more often during physical activity, and with LQT2 and LQT3 - at rest. Carriers of the LQT2 genes in 46% of cases have tachycardia and syncope induced by sharp sounds.

congenital forms

Congenital forms of long QT interval syndrome are becoming one of the causes of death in children. The mortality rate for untreated congenital forms of this syndrome reaches 75%, with 20% of children dying 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-Lange-Nielsen syndrome and Romano-Ward syndrome.

Gervell-Lange-Nielsen syndrome is a rare disease, has an autosomal recessive mode of inheritance and is a combination of congenital deaf-muteness with prolongation 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. It has a similar clinical picture: cardiac arrhythmias, in some cases with loss of consciousness against the background of an extended QT interval in children without hearing or speech impairment. The frequency of detection of a prolonged QT interval in school-age children with congenital deaf-muteness on a standard ECG reaches 44%, while almost half of them (about 43%) experienced episodes of loss of consciousness and paroxysms of tachycardia. During daily ECG monitoring, paroxysms of supraventricular tachycardia were recorded in almost 30% of them, and in approximately every fifth “jog” ventricular tachycardia of the “pirouette” type was registered. To diagnose congenital forms of long QT interval syndrome in the case of borderline prolongation and/or absence of symptoms, a set of diagnostic criteria has been proposed. “Large” criteria are prolongation of the QT interval by more than

0.44 ms, a history of episodes of loss of consciousness and the presence of long QT interval syndrome in family members. “Minor” criteria are congenital sensorineural hearing loss, episodes of T-wave alternans, slow heart rate (in children), and abnormal ventricular repolarization.

The greatest diagnostic significance is a significant prolongation of the QT interval, paroxysms of tachycardia torsade de pointes and episodes of syncope. Congenital long QT syndrome is a genetically heterogeneous disease that involves more

5 different chromosome 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 people is a combination of this syndrome with mitral valve prolapse. The incidence of QT interval prolongation in individuals with mitral and/or tricuspid valve prolapse reaches 33%.

According to most researchers, mitral valve prolapse is one of the manifestations of congenital connective tissue dysplasia. Other manifestations include weakness of connective tissue, increased skin extensibility, asthenic body type, funnel chest deformity, scoliosis, flat feet, joint hypermobility syndrome, myopia, varicose veins, hernias. A number of researchers have identified a relationship between increased variability of the OT interval and the depth of prolapse and/or the presence of structural changes (myxomatous degeneration) of the mitral valve leaflets. One of the main reasons for the formation of prolongation of the OT interval in persons with mitral valve prolapse is genetically predetermined or acquired magnesium deficiency.

Acquired forms

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

There is no consensus on the prognostic significance of an increase in the dispersion of the OT interval in patients with post-infarction cardiosclerosis: some authors have identified in these patients a clear relationship between the increase in the duration and dispersion of the OT interval (on the ECG) and the risk of developing paroxysms of ventricular tachycardia, other researchers have not found a similar pattern. In cases where in patients with post-infarction cardiosclerosis at rest the dispersion of the WC interval is not increased, this parameter should be assessed during an exercise test. In patients with post-infarction cardiosclerosis, many researchers consider the assessment of WC dispersion against the background of stress tests to be more informative for verifying the risk of ventricular arrhythmias.

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

Autonomic neuropathy also increases the value of the OT interval and its dispersion, therefore these syndromes occur in patients with diabetes mellitus types I and II. Prolongation of the OT interval can occur in case of electrolyte imbalance with hypokalemia, hypocalcemia, hypomagnesemia. Such conditions arise 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 is described against the background of prolongation of the OT interval with a fatal outcome in women who were on a low-protein diet to reduce body weight. The OT interval can be prolonged when using therapeutic doses of a number of drugs, in particular quinidine, procainamide, and phenothiazine derivatives. Prolongation 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

repolarization processes. For example, pachycarpine in toxic doses, a number of alkaloids that block the active transport of ions into the myocardial cell and also have a ganglion-blocking effect. There are also cases of prolongation of the OT interval due to poisoning with barbiturates, organophosphorus insecticides, and mercury.

Prolongation of WC in acute myocardial ischemia and myocardial infarction is well known. A persistent (more than 5 days) increase in the OT interval, especially when combined with early ventricular extrasystoles, has an unfavorable prognosis. These patients showed a significant (56-fold) increase in the risk of sudden death. With the development of acute myocardial ischemia, the dispersion of the OT interval also significantly increases. It has been established that the dispersion of the OT interval increases already in the first hours of acute myocardial infarction. There is no consensus on the magnitude of the dispersion of the WC interval, which is a clear predictor of sudden death in patients with acute myocardial infarction. It has been established that if during anterior myocardial infarction the dispersion is more than 125 ms, then this is a prognostically unfavorable factor, indicating a high risk of death. In patients with acute myocardial infarction, the circadian rhythm of OT dispersion is also disrupted: 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 prolongation of OT in acute myocardial infarction, hypersympathicotonia undoubtedly plays a role, which is why many authors explain the high effectiveness of beta-blockers in these patients. In addition, the development of this syndrome is also 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 between the level of magnesium in the blood (serum and red blood cells) with the value of the WC interval and its dispersion in patients with acute myocardial infarction was also revealed. Of interest are data on the daily rhythms of OT dispersion obtained from Holter ECG monitoring. A significant increase in the dispersion of the WC interval was found at night and in the early morning hours, which may increase the risk of sudden death at this time in patients with various cardiovascular diseases (myocardial ischemia and infarction, heart failure, etc.). It is believed that the increase in the dispersion of the OT interval at night and in the morning is associated with increased sympathetic activity at this time of day. When it is carried out, along with a permanent or transient prolongation of the OT interval, patients may experience bradycardia during the day and a relative increase in heart rate at night, and a decrease in the circadian index (CI).

Characteristic signs are also prolongation of all parameters of the OT interval; identification of ventricular tachyarrhythmias or short paroxysms of ventricular tachycardia, which are not always manifested by fainting; T wave alternans; rigid circadian heart rate rhythm, often CI less than 1.2; identification of SLS sequence; decreased rhythm concentration function (increased rMSSD); signs of paroxysmal readiness of the heart rhythm (increase by more than 50% in periods of increased dispersion during sleep).

With Holter ECG monitoring, various conduction rhythm disturbances are much more common

are detected in systole-diastolic myocardial dysfunction, and the frequency of their detection is almost 2 times higher than the detection of rhythm disturbances in patients with isolated diastolic myocardial dysfunction. This indicates that rhythm disturbance and QT indicator are one of the criteria for the severity of myocardial dysfunction. Holter ECG monitoring in combination with VEM and everyday physical activity makes it possible to assess coronary reserve in patients with coronary artery disease - a relationship has been identified between prolongation of the QT interval, the degree of damage to the coronary arteries and a decrease in coronary reserve. In patients with less tolerance to physical activity and a more severe form of coronary artery disease, a significant prolongation of the corrected QT interval is observed, especially pronounced against the background of ischemic shift of the ST segment, which may indicate a high risk of fatal arrhythmias. According to modern approaches to assessing Holter ECG monitoring data, the duration of the QT interval should not exceed 400 ms in young children, 460 ms in preschool children, 480 ms in older children, 500 ms in adults.

In 1985, Schwarts proposed the following set of diagnostic criteria for LQTS syndrome, which are still used today:

1. “Large” diagnostic criteria for LQTS: prolongation of the QT interval (QT with more than 0.44 s); history of syncope; presence of LQTS in family members.

2. “Minor” diagnostic criteria for LQTS: congenital sensorineural deafness; episodes of T wave alternans; bradycardia (in children); pathological ventricular repolarization.

The diagnosis can be made if two “major” or one “major” and two “minor” criteria are present. Prolongation of the QT interval can lead to acute arrhythmias and sudden death in alcohol abusers. It is also possible that there may be early nonspecific changes in the ECG of the final part of the ventricular complex with negative dynamics of these changes with the “ethanol” test and the absence of positive dynamics when using a test with nitroglycerin and obsidan. The greatest diagnostic value has the measurement of the duration of the QT interval after the end of physical activity (and not during its implementation).

To date, there is no treatment method that would eliminate the risk of unfavorable outcome in patients with LQTS. At the same time, existing approaches to patient management can eliminate or significantly reduce the frequency of paroxysms of tachycardia and syncope, and reduce mortality by more than 10 times.

Drug treatments can be divided into acute and long-term therapy. The latter is based primarily on the use of p-blockers. The choice of these drugs is based on the theory of specific sympathetic imbalance, which plays a leading role in the pathogenesis of the disease. The preventive effect when using them reaches 80%. First of all, the etiological factors that led to prolongation of the QT interval should be eliminated where possible. For example, you should stop or reduce the dose of medications

(diuretics, barbiturates, etc.), which may increase the duration or dispersion of the QT interval. Adequate treatment of heart failure according to international recommendations and successful surgical treatment of 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 size 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: beta-blockers and magnesium drugs.

Clinical and etiological classification

prolongation of the QT interval ECG

According to clinical manifestations: 1. With attacks of loss of consciousness (dizziness, etc.). 2. Asymptomatic.

By origin: I. Congenital: 1. Gervell-Lange-Nielsen syndrome. 2. Romano-Ward syndrome.

3. ^radical. II. Acquired: caused by drugs.

congenital elongation syndrome

QT interval

Patients with Romano-Ward and Ger-vell-Lange-Nielsen syndromes require constant use of β-blockers in combination with oral magnesium supplements (magnesium orotate, 2 tablets 3 times a day). Left-sided stellectomy and removal of the 4th and 5th thoracic ganglia may be recommended in patients who have failed pharmacological therapy. There are reports of successful combination of p-blocker treatment with implantation of an artificial cardiac pacemaker. 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 of the formation of QT prolongation syndrome -interval, and “weakness” of connective tissue. In these individuals, after treatment with magnesium preparations, not only does the QT interval normalize, but also the depth of prolapse of the mitral valve leaflets, the frequency of ventricular extrasystoles, and the severity of clinical manifestations (vegetative dystonia syndrome, hemorrhagic symptoms, etc.) decrease. If treatment with oral magnesium supplements after

6 months did not have a complete effect; the addition of β-blockers is indicated.

Acquired elongation syndrome

QT interval

All drugs that can prolong the QT interval should be discontinued. Correction of serum electrolytes is necessary, especially potassium, calcium, magnesium. In some cases, this is sufficient to normalize the size and dispersion of the QT interval and prevent ventricular arrhythmias. In acute myocardial infarction, fibrinolytic therapy and p-blockers reduce the amount of QT interval dispersion. These appointments, according to international recommendations, are mandatory for

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 value 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 the acute stage of myocardial infarction is being actively studied. The duration, dosage and methods of administration of magnesium preparations in these patients have not been fully established.

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 of QT prolongation and its dispersion, including with Holter ECG monitoring and stress testing, will allow us to identify a group of patients with an increased risk of developing ventricular arrhythmias, syncope and sudden death. Effective means of preventing and treating ventricular cardiac arrhythmias in patients with congenital and acquired forms of long QT interval syndrome are p-blockers in combination with magnesium preparations.

The relevance of long QT syndrome is determined primarily by the proven association with syncope and sudden cardiac death, as indicated by the results of numerous studies, including the recommendations of the European Association of Cardiology. Awareness of this syndrome among pediatricians, cardiologists, neurologists, and family doctors, and the mandatory exclusion of LQTS as one of the causes of syncope will facilitate the diagnosis of the pathology under discussion and the prescription of adequate therapy to prevent an unfavorable outcome.

literature

1. Shilov, A.M. Diagnosis, prevention and treatment of long QT interval syndrome: method. rec. / A.M. Shilov, M.V. Melnik, I.D. Sanodze. - M., 2001. - 28 p. Shilov, A.M. Diagnostika, profilaktika i lechenie sindroma udlineniya QT-intervala: method. recom. / A.M. Shilov, M.V. Mel "nik, I.D. Sanodze. - M., 2001. - 28 s.

2. Stepura, O.B. Results of the use of magnesium salt of orotic acid “Magnerot” in the treatment of patients with idiopathic mitral valve prolapse / O.B. Stepura O.O. Melnik, A.B. Shekhter, L.S. Pak, A.I. Martynov // Russian medical news. - 1999. - No. 2. - P.74-76.

Stepura, O.B. Rezul"taty primeneniya magnievoi soli orotovoi kisloty "Magnerot" pri lechenii bol"nyh s idiopaticheskim prolapsom mitral"nogo klapana / O.B. Stepura O.O. Mel"nik, A.B. SHehter, L.S. Pak, A.I. Martynov // Rossiiskie medicinskie vesti. - 1999. - No. 2. - S.74-76.

3. Makarycheva, O.V. Dynamics of QT dispersion in acute myocardial infarction and its prognostic significance / O.V. Makarycheva, E.Yu. Vasilyeva, A.E. Radzevich, A.V. Spektor // Cardiology. - 1998. - No. 7. - P.43-46.

Makarycheva, O.V. Dinamika dispersii QT pri ostrom infarkte miocarda i ee prognosticheskoe znachenie / O.V. Makarycheva, E. Yu. Vasil"eva, A.E. Radzevich, A.V. Shpektor // Kardiologiya. - 1998. - No. 7. - S.43-46.

– a genetically heterogeneous hereditary condition characterized by a violation of the structure and functionality of some ion channels of cardiomyocytes. The severity of the manifestations of the 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 interval syndrome is based on data from electrocardiological studies and molecular genetic tests. Treatment depends on the form of the pathology and may include constant or course use of beta-blockers, magnesium and potassium supplements, 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 ionic currents in cardiomyocytes is disrupted, which can lead to arrhythmias, fainting and sudden cardiac death. A similar condition was first identified in 1957 by Norwegian doctors A. Jervell and F. Lange-Nielsen, who described a patient’s combination of congenital deafness, syncope, and prolongation of the QT interval. Somewhat later, in 1962-64, similar symptoms were identified 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 incidence of long QT syndrome of the Jervell-Lange-Nielsen type ranges from 1-6:1,000,000, it is characterized by an autosomal dominant mode of inheritance and more pronounced manifestations. According to some data, 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, it has been possible to identify 12 genes in which mutations lead to the development of long QT interval syndrome; all of them 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 the reasons for the differences in the clinical course of this disease. Autosomal dominant Romano-Ward syndrome is caused by a mutation in only one gene and therefore can be asymptomatic or, at a minimum, without hearing impairment. With the Jervell-Lange-Nielsen type, there is a defect in two genes - this option, in addition to cardiac symptoms, is always accompanied by bilateral sensorineural deafness. Today it is known which gene mutations cause the development of long QT syndrome:

1. Long QT syndrome type 1 (LQT1) caused by a mutation in the KCNQ1 gene located on chromosome 11. 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 cardiomyocyte potassium channels (lKs)
2. Long QT syndrome type 2 (LQT2) is caused by defects in the KCNH2 gene, which is localized on chromosome 7 and encodes the amino acid sequence of a protein - the alpha subunit of another type of potassium channel (lKr).
3. Long QT syndrome type 3 (LQT3) caused by a mutation in the SCN5A gene located on chromosome 3. Unlike previous variants of the pathology, the functioning of sodium channels in cardiomyocytes is disrupted, 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 stabilizing the structure of myocyte microtubules, and is also secreted in neuroglial 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 chromosome 21. 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) is caused by a mutation in the KCNE2 gene, also located on chromosome 21. The product of its expression is the beta subunit of potassium channels of the lKr type.
7. Long QT syndrome type 7(LQT7, another name is Andersen 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 previous variants of the pathology, this gene encodes one of the protein chains of potassium channels.
8. Long QT syndrome type 8(LQT8, another name is Timothy 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) caused by a defect in the CAV3 gene, localized on chromosome 3. The product of its expression is the caveolin 3 protein, 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 a mutation in the SCN4B gene, which is located on chromosome 11 and is responsible for the amino acid sequence of the beta subunit of sodium channels.
11. Long QT syndrome type 11 (LQT11) is caused by defects in the AKAP9 gene, located on chromosome 7. It encodes a specific protein - A-kinase of the centrosome and Golgi complex. The functions of this protein have not been sufficiently studied to date.
12. Long QT syndrome type 12 (LQT12) caused by a mutation in the SNTA1 gene, located on chromosome 20. 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 interval syndrome, the general links of its pathogenesis are generally the same for each of the forms. This disease is classified as a channelopathy 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 prolongation of the QT interval. In addition, the sensitivity of the myocardium to the influences of the sympathetic nervous system increases significantly, which becomes the cause of frequent tachyarrhythmias that can lead to life-threatening ventricular fibrillation. At the same time, different genetic types of long QT interval syndrome have different sensitivity to certain influences. For example, LQT1 is characterized by syncope attacks and arrhythmia during physical activity, 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 typical.

Symptoms of a Long QT Interval

The manifestations of long QT syndrome are quite varied. With the more severe clinical type of Jervell-Lange-Nielsen, patients experience deafness, frequent fainting, dizziness, and weakness. In addition, in some cases, epilepsy-like seizures are recorded in this condition, which often leads to incorrect diagnosis and treatment. According to some geneticists, 10 to 25% of patients with long QT syndrome are treated incorrectly and experience sudden cardiac or infant death. The occurrence of tachyarrhythmias and syncope 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.

A milder form of long QT syndrome (Romano-Ward type) is characterized by transient syncope (fainting) and rare attacks of tachyarrhythmia, but there is no hearing impairment. In some cases, this form of the disease does not manifest itself at all, with the exception of electrocardiographic data, and is an accidental finding during a 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 interval syndrome is made based on a study of the patient's medical history, electrocardiological and molecular genetic studies. When questioning the patient, episodes of fainting, dizziness, and palpitations are often detected, but in mild forms of the pathology they may not be present. 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 interval syndrome, changes will be detected on the ECG - an increase in the QT interval to 0.6 seconds or more, possibly an increase in the amplitude of the T wave. The combination of such ECG signs with congenital deafness indicates the presence of Jervell-Lange-Nielsen syndrome. In addition, Holter monitoring of heart function throughout the day is often necessary to identify possible attacks of tachyarrhythmias. Determination of long QT interval syndrome using modern genetic methods is now possible for almost all genetic types of this disease.

Treatment of long QT syndrome

Therapy for long QT syndrome is quite complex; many experts recommend some regimens for this disease and reject others, but there is no single protocol for the treatment of this pathology. Beta-blockers are considered universal drugs, they reduce the risk of developing tachyarrhythmias and fibrillations, and also reduce the degree of sympathetic effects on the myocardium, but in LQT3 they are ineffective. 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 case of frequent attacks of tachyarrhythmias and a high risk of fibrillation, implantation of a pacemaker or defibrillator-cardioverter 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 manifestations of pathology, with the exception of electrocardiographic data, does not guarantee the sudden development of fatal ventricular fibrillation under the influence of external or internal factors. When long QT interval syndrome is detected, it is necessary to perform a thorough cardiac examination and genetic determination of the type of disease. 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.

Long QT syndrome(QT SID) is a genetically determined disease with a high risk of sudden cardiac death (SCD), characterized by persistent or transient prolongation of the QT interval on the electrocardiogram (ECG), episodes of loss of consciousness due to ventricular tachycardia (VT) and/or ventricular fibrillation (VF) .

IMS QT, as is known, can be congenital or acquired. The first of these usually appears at a young age (average age 14 years). The annual incidence of SCD in the absence of treatment ranges from 0.9% to 5% (in the presence of syncope), and in some genetic forms reaches 40-70% during the first year after clinical manifestation. SCD may be the first manifestation of the disease. In the pathogenesis of AIS QT, two main hypotheses are considered: the early one - autonomic imbalance in the direction of increasing sympathetic influences, the more modern one - dysfunction of transmembrane ion-selective channels due to various mutations in genes encoding structural or regulatory proteins. Impaired functioning of potassium, sodium, or calcium voltage-gated ion channels leads to an increase in the duration of the action potential in the cardiomyocyte, which, under concomitant conditions, can facilitate the appearance of early or late afterdepolarizations and the development of VT/VF. To date, more than 700 mutations are known in 13 genes, and according to some sources - in 16.

In 1985, P.J. Schwartz proposed diagnostic criteria for congenital QT AIS, which were subsequently modified. Currently, the diagnostic criteria presented in Table 1 are recommended for diagnosing congenital AIS QT. 1 and 2.

Because QT prolongation may be transient and episodes of syncope due to VT/VF are rare, long-term ECG recording (24-hour ECG monitoring or implantable devices) and provocative tests (for example, exercise testing or alpha infusion testing) are important in the diagnosis of the disease. - and beta-agonists). Normal QTc duration values ​​that are valid for 24-hour ECG recordings are under development. The maximum values ​​of the average daily QTc in healthy individuals when automatically calculated in different Holter monitoring systems usually do not exceed 450 ms. Molecular genetic analysis methods are of great importance in diagnosing QT AIS and determining the prognosis of patients. According to the International Registry, in approximately 85% of cases the disease is hereditary, while about 15% of cases are the result of new spontaneous mutations. In approximately 10% of patients with QT AIS, genotyping revealed at least two mutations associated with the genesis of this condition, which determines the variability of its clinical manifestations and pattern of inheritance. The results of molecular genetic analysis made it possible to create a classification of IMS QT depending on the mutant gene. Most patients with an established diagnosis of AIS QT belong to the first three variants of the syndrome: AIS QT type 1 (35-50% of cases), AIS QT type 2 (25-40% of cases) and AIS QT type 3 (5-10% of cases) - see table . 3.

The remaining genotypes of AIS QT occur in less than 1.5% of cases. Various types of hereditary QT AIS are characterized by changes in repolarization on the ECG: a wide smooth T wave with QT AIS type 1; biphasic T-wave with QT type 2 AIS; low-amplitude and shortened T-wave with an elongated, horizontal ST-segment with QT type 3 AIS. However, at present, the phenotypic classification of IMS QT has not lost its relevance. The most common phenotypic variant is Romano-Ward syndrome with an autosomal dominant type of inheritance (prevalence 1 case per 2500 people), which includes genotypes QT AIS from type 1 to type 6 and QT AIS from type 9 to type 13 and is characterized by isolated prolongation of the interval QT. The second most common phenotype with an autosomal recessive mode of inheritance is Jervell-Lange-Nielsen syndrome (QT-JLN1 AIS and QT-JLN2 AIS with mutations in the KCNQ1 and KCNE1 genes, respectively), which is characterized by a very pronounced prolongation of the QT interval and congenital deafness. The third phenotype, characterized by extracardiac manifestations (for example, abnormal development of the skeletal system) and an autosomal dominant type of inheritance, is extremely rare. It is divided into the following subtypes: Andersen-Tawil syndrome (ASI QT 7 genotype with a mutation in the KCNJ gene) and Timothy syndrome (ASI QT 8 genotype with a mutation in the CACNA1c gene). In Timothy syndrome, the most pronounced prolongation of the QT and QTc intervals (up to 700 ms) is noted, accompanied by an extremely high risk of SCD (average life expectancy is 2.5 years). About 50% of cases of Andersen-Tawil syndrome and Timothy syndrome are caused by a de novo mutation. When conducting comprehensive genetic tests, mutations can be detected in approximately 75% of patients with QT AIS, so a negative result of a genetic analysis does not completely exclude the diagnosis of QT AIS. Acquired AIS QT is caused by a violation of the electrical homogeneity of the myocardium or its innervation due to acute conditions, chronic diseases, or under the influence of drugs (antiarrhythmic, psychotropic, antihistamines, antibiotics, prokinetics, cytostatics, etc.).

Factors provoking the development of life-threatening arrhythmias, may be physical activity, emotional states, swimming, loud, sharp sound signals (for example, an alarm clock), the postpartum period. Less commonly, arrhythmias occur during sleep or at rest. In approximately 20% of patients with secondary QT prolongation, QT mutations specific to AIS are detected. There is an opinion that patients with the acquired form of QT AIS are latent carriers of such genotypes, which clinically manifest themselves under the influence of external provoking factors. Stratification of individual risk is carried out taking into account clinical, electrocardiographic and genetic parameters. To date, there is no data indicating the prognostic value of invasive electrophysiological testing with programmed ventricular stimulation in patients with QT AIS. Molecular genetic diagnostics help to develop gene-specific therapy for QT AIS. In particular, it was found that β-blockers are most effective in QT1 AIS, less effective in QT2 AIS, and ineffective in QT3 AIS. At the same time, it is known that potassium preparations are more effective for QT2 AIS, and sodium channel blockers (for example, mexiletine) are more effective for QT3 AIS. Lifestyle recommendations such as avoiding active swimming, especially in QT1 AIS, and avoiding exposure to loud noises in QT2 AIS may help prevent life-threatening arrhythmias. The persistence of syncope or episodes of SCD during β-blocker therapy is an absolute indication for implantation of a cardioverter-defibrillator. Considering the role of increased sympathetic activity in the pathogenesis of QT AIS, left-sided sympathetic denervation is considered as one of the additional treatment resources in patients with severe disease.

Patient S., 22 years old, was admitted as planned to the cardiology department of the clinic of the Northwestern State Medical University named after. I.I. Mechnikov for endovascular treatment of stenosis of the right renal artery. Upon admission, she complained of episodes of increased blood pressure (BP), recently up to 170/100 mm Hg, accompanied by headaches in the occipital region and temples. The usual blood pressure values ​​are 110-130/70-80 mmHg. When interviewing organ systems, it turned out that since childhood, the patient has experienced sudden loss of consciousness with a frequency of 1-2 times a year, for which she was examined several times; the cause of syncope was not established. In addition, the patient has had almost constant nasal congestion for a long time during the day, worsening in a horizontal position, for which she uses naphthyzin intranasal drops daily. Over the past 3 years, there has been an increase in the number of psycho-emotional stresses (university studies) and disruption of the sleep-wake regime: restriction of night sleep, shift in sleep phase (departure from sleep).I sleep from the second half of the night followed by a late awakening).

History of the disease. For the first time, episodes of increased blood pressure began to be noted about 2 years ago with a maximum value of 190/110 mm Hg. Examined on an outpatient basis. Echocardiography revealed no abnormalities. According to 24-hour blood pressure monitoring: the dynamics are characteristic of stable systolic-diastolic arterial hypertension, mainly at night. No significant increase in the level of thyroid and adrenal hormones was detected. According to the duplex study, the right renal artery is diffusely changed along its length with hemodynamically significant stenosis - linear blood flow velocity is up to 600 cm/s, the left renal artery is diffusely changed with uneven thickening of the walls and acceleration of blood flow, but without hemodynamically significant stenosis. According to multislice computed tomography of the abdominal cavity with contrast, signs of stenosis of the right renal artery up to 83% were revealed (the right renal artery with a diameter of 0.6 cm, narrowed at a distance of 0.6 cm from the orifice); signs of stenosis of the inferior mesenteric artery up to 50%; CT picture of the developmental anomaly - independent departure from the aorta of the hepatic artery. The patient was prescribed treatment with amlodipine 2.5 mg per day, against which there was a decrease in the frequency of episodes of increased blood pressure (up to 1-2 times a week) and a decrease in blood pressure levels (150-170/90-100 mm Hg). When blood pressure rises, he takes a captopril tablet under the tongue with a positive effect. Considering the presence of stenosis of the right renal artery and persistent arterial hypertension, the patient was sent to the clinic for surgical treatment: angioplasty with possible stenting of the right renal artery.

The following facts were noteworthy in the anamnesis. From the age of 15, the patient began to notice syncope with a frequency of 1-2 times a year. Two types of fainting were observed. The first developed absolutely suddenly, against the background of complete well-being, without warning signs, lasted from 2 to 5 minutes, followed by a rapid restoration of consciousness; At the same time, the patient fell, convulsions, urination and tongue biting were not observed. The second occurred against a background of dizziness and general weakness, with a gradual restoration of consciousness: first hearing, and then vision. Regarding loss of consciousness, she was observed and examined by a neurologist. However, during the examination, which included magnetic resonance brain tomography, electroencephalography, ultrasound diagnostics of the brachiocephalic arteries, it was not possible to find out the cause of syncope. As a child, I often suffered from inflammatory diseases of the upper respiratory tract (rhinitis, sinusitis, otitis). At the age of 12, I noticed hearing loss. Examined by an audiologist and diagnosed with leftthird-party chronic sensorineural hearing loss of the 3rd degree, dysfunction of the auditory tubes, chronic vasomotor rhinitis. For many years he has been using intranasal drops, most often “naphthyzin” (uses 1 bottle for 1-2 days). Over the past 7 years, the patient has repeatedly undergone 24-hour ECG monitoring (CM-ECG). When analyzing the annual conclusions of the CM-ECG over the past 3 years, attention was drawn to the long-term registration of an extended corrected QT interval over 450 ms: from 64% to 87%monitoring time. One of the ECG monitors recorded episodes of pacemaker migration through the atria, replacing the atrial rhythm. In particular, according to the results of the last FM-ECG performed on an outpatient basis, sinus rhythm was recorded with an average heart rate of 83 per minute, episodes of atrial rhythm, ventricleextrasystole 3 gradations according to M. Ryan. During the day, there was an increase in the corrected QT interval over 450 ms (up to 556 ms) for 14 hours 49 minutes - 87% of the time (Fig. 1).

The QTc interval for the entire observation period took values ​​from 355 ms to 556 ms (average 474 ms), during wakefulness from 355 ms to 556 ms (average 468 ms), during physical activity from 431 ms to 470 ms (average 446 ms) , during sleep from 372 ms to 550 ms (average 480 ms). In addition, a change in repolarization was recorded in the form of negative or biphasic T waves in the chest leads from V1 to V5 at rest and positive T waves in the same leads when performing physical activity (Fig. 2).

Epidemiological and allergological anamnesis is unremarkable. Hereditary history on the part of the mother is not burdened, but her obstetric and gynecological history was noteworthy: first pregnancy ended in stillbirth, and the second - in the birth of a girl with Down syndrome, the cause of death of which in infancy remains unknown. Our patient was born as a result of the delivery of her third pregnancy. The hereditary history on the father’s side is not burdened (according to the patient’s mother). The patient never smoked and did not use alcohol or drugs. Objective status: satisfactory condition, clear consciousness, active position. The physique is normosthenic. Height 164 cm, weight 60 kg, body mass index 22.3. Skin of physiological color. Dystopia of the anterior teeth and enamel dysplasia attracted attention. There is no peripheral edema. The pulse is rhythmic, of satisfactory filling and tension, with a frequency of 110 per minute. The boundaries of relative cardiac dullness are not expanded. Heart sounds are clear, rhythmic, murmursNo. Blood pressure 135/80 mm Hg. on both sides. The respiratory rate is 16 per minute. When percussing the lungs, a clear pulmonary sound is detected. Breathing is vesicular, no wheezing. The tongue is moist and clean. The abdomen is soft and painless. The liver and spleen are not enlarged. The kidneys are not palpable. Tapping on the lower back is painless. There were no pathological changes in clinical and biochemical blood tests and general urine analysis performed in the hospital. ECG on admission to our clinic: sinus rhythm with heart rate 64 per minute, P = 100 ms, PQ = 130 ms, QRS = 90 ms, QT = 420 ms, RR = 940 ms, QTc = 433 ms, partial right bundle branch block (Fig. 3).

Noteworthy was the change in repolarization processes in leads V2-V4 in the form of “-” or “+/-” T waves. A week later in the hospital, a resting ECG recorded an atrial rhythm with a heart rate of 53 per minute (QTc = 450 ms ). When compared with the ECG upon admission, repolarization is unchanged. Episodes of atrial rhythm were recorded in the patient earlier, before hospitalization, both on a regular ECG and with a SM-ECG. According to the CM-ECG (without therapy), performed in the hospital: sinus rhythm during the observation period, with a heart rate from 48 to 156 (average 74) per minute. The following arrhythmias were recorded: single supraventricular extrasystoles with a pre-ectopic interval of 541 ms, 1 during the day, none at night. Pauses due to sinus arrhythmia lasting from 778 to 1588 (average 1070) ms, total - 12 (1 per hour), 9 during the day, 3 (1 per hour) at night. Ischemic ECG changes were not detected. During the day, QTc prolongation was observed over 450 ms for 13 hours 57 minutes (64% of the time). The QTc interval during the entire observation period took values ​​from 424 ms to 541 ms (average 498 ms), during wakefulness from 424 ms to 533 ms (average 486 ms), during exercise from 455 ms to 518 ms (average 486 ms), during sleep from 475 ms to 541 ms ( average 506 ms). Heart rate variability: the ratio of high-frequency and low-frequency components is balanced, there is no nighttime increase in the high-frequency component of variability. According to echocardiography performed in the hospital, no pathological changes were detected. According to duplex scanning of the renal vessels, performed in the hospital: the diameter of the aorta at the level of the renal arteries is 16 mm; in the infrarenal region 15 mm, the walls are smooth, not thickened, the lumen is not narrowed; on the left, the diameter of the renal artery at the mouth is 4.2 mm, blood flow is not accelerated (V = 105 cm/m); on the right, in the distal part of the renal artery, the lumen is unevenly narrowed, blood flow accelerates with Vmax≈540 cm/s.

Conclusion: stenosis of the right renal artery in the distal part of 80%. According to an ultrasound scan of the kidneys performed in the hospital: signs of a simple small cyst of the left kidney, diffuse changes in the right kidney. The sizes of both kidneys are normal. Thus, the patient had arterial hypertension, the genesis of which could not be ruled out by a vasorenal mechanism, most likely caused by fibromuscular dysplasia. The patient was prescribed metoprolol tartrate 12.5 mg 2 times a day; it was recommended to adhere to a physiological sleep-wake regimen and gradually reduce intranasal adrenergic agonists until discontinuation. During hospitalization, it was not possible to achieve a significant change in the dosage regimen of intranasal vasoconstrictor drugs, but the physiological sleep-wake regime was observed with great success. Increase in blood pressure to 140-150/80-90 mm Hg. Art. observed only at the beginning of hospitalization. With the selected dose of β-blocker, blood pressure levels of 110-120/70-80 mmHg were achieved. Art. and heart rate 55-75 per minute. The patient was consulted by a nephrologist: given her age, the absence of risk factors for atherosclerosis, and the identified structural anomalies of other vessels, stenosis of the right renal artery was regarded as fibromuscular dysplasia of the renal artery. Due to stable blood pressure during monotherapy, normal size of the right kidney and normal renal function (creatinine = 79 µmol/l, glomerular filtration rate = 92 ml/min/1.73 m2), it was decided to refrain from endovascular treatment of renal stenosis at this time. arteries. Taking into account the presence of syncope in the anamnesis, the prolongation of the corrected QT interval according to the SM-ECG data and the disturbance of repolarization processes according to the ECG data, a diagnosis of AIS QT was made. The patient's condition in the hospital remained stable, no episodes of loss of consciousness were observed, and no ventricular arrhythmias were registered. After discharge from the hospital, for further examination and treatment, the patient was referred to a consultation with an arrhythmologist at the North-Western Center for the Diagnosis and Treatment of Arrhythmias of the Scientific, Clinical and Educational Center "Cardiology" of St. Petersburg State University. To confirm hereditary QT IRS, the patient underwent testing at the international genetic laboratory “Health in Code” (La Coruña, Spain), specializing in the molecular genetic diagnosis of hereditary heart diseases, which included a search for mutations in 13 known genes associated with the syndrome long QT (CACNA1C, KCNE1, KCNE2, KCNH2,KCNJ2, KCNQ1, RYR2, SCN5A, etc.). However, the genetic variant of familial QT AIS could not be identified. Using next generation genomic sequencing (NGS), a mutation in the MYBPC3 gene was identified in the patient, which is associated with the development of hypertrophic cardiomyopathy. The patient was offered an implantation of a subcutaneous “event recorder” for long-term follow-up, which she refused. The patient was given recommendations after discharge from the hospital to continue taking β-blockers in the maximum tolerated doses in combination with magnesium supplements, control blood pressure, and avoid taking intranasal drops with a sympathomimetic effect. Against the background of the listed treatment and preventive measures, syncope did not recur for 1 year, the patient was not bothered by an increase in blood pressure, the QTc interval decreased, but did not normalize. Monitoring of the patient continues.

Discussion
The diagnosis of AIS QT in a young 22-year-old female patient was made during a planned hospitalization for arterial hypertension. Stenosis of the right renal artery was confirmed and most likely caused by a congenital anomaly, fibromuscular dysplasia. However, no relationship was found between increased blood pressure and renal artery stenosis. When observing the patient, emotional lability was noted, and a clear relationship between increased blood pressure and psycho-emotional stress was noted. It was also impossible to exclude the effect on blood pressure of uncontrolled daily long-term intranasal use of sympathomimetics (“naphthyzin”) in large doses. In addition, the angiotensin-converting enzyme inhibitor captopril reduced blood pressure well and a positive effect was obtained with minimal antihypertensive therapy with beta-blockers. Therefore, the patient did not undergo surgical correction of renal artery stenosis, but was recommended to monitor renal function and blood pressure levels, adhere to a physiological sleep-wake regimen, discontinue intranasal drops that have a sympathomimetic effect, and select antihypertensive therapy. Prognostically, a more serious diagnosis was the identified AIS QT: on the modified P.J. Schwartz scale, a total of at least 4 points (QTc more than 480 ms - 3 points, syncope outside of exercise - 1 point). In addition, it is not possible to unambiguously interpret the presence of hearing loss (a relationship with previous otitis media cannot be ruled out), and the cause of death of the patient’s sister in infancy is unknown. Due to existing syncope conditions that arose in childhood, the patient was observed and examined by doctors, including neurologists. A comprehensive diagnosis was carried out, which made it possible to exclude neurological causes of fainting. The patient was repeatedly recorded with an ECG and underwent SM-ECG for 7 years, during the analysis of which the fact of an extended QT interval and changes in repolarization processes in standard and, especially, chest leads V1-V4 remained underestimated. A noteworthy fact in the patient’s medical history is the long-term use of α-adrenergic agonists in large doses. There is limited information in the literature about their possible effect on myocardial repolarization and the development of arrhythmias. It is not possible to completely exclude the participation of α-adrenergic agonists in the manifestation of QT AIS. From a clinical and electrocardiographic point of view, the nature of the change in the T wave in the precordial leads corresponded to the second type of QT AIS, but the conditions for the occurrence of syncope were more consistent with the third. Despite the fact that the patient did not have any of the known genetic variants of QT AIS, this does not deny the possible presence of other, as yet unknown gene mutations. The identified combination with a mutation in the MYBPC3 gene, associated with the development of hypertrophic cardiomyopathy, is very interesting. There are isolated descriptions of such associations in the literature.

Literature
1. Bockeria, O.L., Sanakoev M.K. Long QT interval syndrome. Non-invasive arrhythmology. - 2015. - T12. - N2. - pp. 114-127.
2. Priori S.G., Blomström-Lundqvist C., Mazzanti A. et al. ESC 2015 guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal. - 2015. - Vol. 36, N 41. - P. 2793-2867. doi: 10.1093/eurheartj/ehv316.
3. Ildarova R.A., Shkolnikova M.A. Modern tactics for managing young patients with long QT syndrome: from early diagnosis to implantation of a cardioverter defibrillator and monitoring of sudden death risk markers. Siberian Medical Journal. - 2015. - T30. - N1. - P. 28-35.
4. Liu J.F., Jons C., Moss A.J. et al. International Long QT Syndrome Registry. Risk factors for recurrent syncope and subsequent fatal or near-fatal events in children and adolescents with long QT syndrome. JACC. - 2011. - No. 57. - R. 941-950. doi: 10.1016/j.jacc.2010.10.025.
5. Gordeeva M.V., Veleslavova O.E., Baturova M.A. and others. Sudden non-violent death of young people (retrospective analysis). Bulletin of Arrhythmology. - 2011. - T65. - P.25-32.
6. Gordeeva M.V., Mitrofanova L.B., Pakhomov A.V. and others. Sudden cardiac death of young people. Bulletin of Arrhythmology. - 2012. - T68. - P.34-44.
7. Baranov A.A., Shkolnikova M.A., Ildarova R.A. and others. Long QT syndrome. Clinical recommendations. - M., 2016. - 25 p.
8. Bezzina C.R., Lahrouchi N., Priori S.G. Genetics of Sudden Cardiac Death // Circ. Res. - 2015. - Vol. 12, No. 116. - P. 1919-1936. doi: 10.1161/CIRCRESAHA.116.304030.
9. Priori S.G., Wilde A.A., Horie M. et al. HRS/EHRA/ APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes //Heart Rhythm. - 2013. - Vol. 10, No. 12. - R. 1932-1963. doi: 10.1016/j.hrthm.2013.05.014.
10. Bockeria L.A., Bockeria O.L., Golukhova E.Z. and others. Ventricular arrhythmias. Clinical recommendations. - M.: “FSBI NNPCSSKh im. A.N.Bakulev" Ministry of Health of the Russian Federation, 2017. - 50 p.
11. Makarov L.M., Ryabykina G.V., Tikhonenko V.M. and others. National Russian recommendations for the use of Holter monitoring techniques in clinical practice. Russian Journal of Cardiology - 2014 - N2 (106) - P. 6-71.
12. Revishvili A.Sh., Neminushchiy N.M., Batalov R.E. and others. All-Russian clinical recommendations for controlling the risk of sudden cardiac arrest and sudden cardiac death, prevention and first aid. Bulletin of Arrhythmology - 2017 - T89 - P. 2-104.
13. Golitsyn S.P., Kropacheva E.S., Maikov E.B. etc. Hereditary (congenital) long QT syndrome. Diagnosis and treatment of heart rhythm and conduction disorders. Clinical recommendations. Society of Emergency Cardiology Specialists. - M., 2013. - P. 154-170.
14. Urrutia, J., Alday A., Gallego M. et al. Mechanisms of IhERG/IKr Modulation by α1-Adrenoceptors in HEK293 Cells and Cardiac Myocytes. Cell. Physiol. Biochem. - 2016. - Vol. 40, No. 6. - P. 1261-1273. doi: 10.1159/000453180.
15. Vilsendorf D.M., Strunk-Mueller C., Gietzen F.H., Kuhn H. Simultaneous hypertrophic obstructive cardiomyopathy and long QT syndrome: a potentially malignant association. Z Cardiol. 2002 Jul;91(7):575-80.
16. Boczek N.J., Ye D., Jin F. et al. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals With Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death. Circ Arrhythm Electrophysiol. 2015 Oct;8(5):1122-32. doi: 10.1161/CIRCEP. 115.002745.

"Bulletin of Arrhythmology", No. 94, 2018

The QT interval doesn't tell the average person much, but it can tell a doctor a lot about the patient's heart condition. Compliance with the norm of the specified interval is determined based on the analysis of the electrocardiogram (ECG).

Basic elements of an electrical cardiogram

An electrocardiogram is a recording of the electrical activity of the heart. This method of assessing the condition of the heart muscle has been known for a long time and is widespread due to its safety, accessibility, and information content.

The electrocardiograph records the cardiogram on special paper, divided into cells 1 mm wide and 1 mm high. At a paper speed of 25 mm/s, the side of each square corresponds to 0.04 seconds. A paper speed of 50 mm/s is also often found.

An electrical cardiogram consists of three basic elements:

• teeth;
• segments;
• intervals.

QT interval on ECG: the norm is in the range of 0.35-0.44 seconds

A spike is a kind of peak that goes either up or down on a line graph. The ECG records six waves (P, Q, R, S, T, U). The first wave refers to the contraction of the atria, the last wave is not always present on the ECG, so it is called intermittent. The Q, R, S waves show how the heart ventricles contract. The T wave characterizes their relaxation.

A segment is a straight line segment between adjacent teeth. The intervals are a tooth with a segment.

To characterize the electrical activity of the heart, the PQ and QT intervals are of greatest importance.

1. The first interval is the time it takes for excitation to travel through the atria and the atrioventricular node (the conduction system of the heart located in the interatrial septum) to the ventricular myocardium.

1. The QT interval reflects the combination of processes of electrical excitation of cells (depolarization) and return to a resting state (repolarization). Therefore, the QT interval is called electrical ventricular systole.

Why is the length of the QT interval so significant in ECG analysis? Deviation from the norm of this interval indicates a disruption in the processes of repolarization of the ventricles of the heart, which in turn can result in serious disturbances of the heart rhythm, for example, polymorphic ventricular tachycardia. This is the name for malignant ventricular arrhythmia, which can lead to sudden death of the patient.

Normal interval durationQTis in the range of 0.35-0.44 seconds.

The length of the QT interval can vary depending on many factors. The main ones:

• age;
• heart rate;
• state of the nervous system;
• electrolyte balance in the body;
• Times of Day;
• the presence of certain medications in the blood.

If the duration of the electrical systole of the ventricles exceeds 0.35-0.44 seconds, the doctor has reason to talk about the occurrence of pathological processes in the heart.

Long QT syndrome

There are two forms of the disease: congenital and acquired.

ECG for paroxysmal ventricular tachycardia

Congenital form of pathology

It is inherited in an autosomal dominant manner (one of the parents passes the defective gene to the child) and an autosomal recessive type (both parents have the defective gene). Defective genes disrupt the functioning of ion channels. Experts classify four types of this congenital pathology.

1. Romano-Ward syndrome. The most common occurrence is approximately one child in 2000 births. It is characterized by frequent attacks of torsades de pointes with an unpredictable rate of ventricular contraction.

The paroxysm may go away on its own, or it may develop into ventricular fibrillation with sudden death.

The following symptoms are typical for an attack:

• pale skin;
• rapid breathing;
• convulsions;
• loss of consciousness.

Physical activity is contraindicated for the patient. For example, children are exempt from physical education lessons.

Romano-Ward syndrome is treated with medication and surgery. With the medication method, the doctor prescribes the maximum acceptable dose of beta-blockers. Surgical intervention is performed to correct the conduction system of the heart or install a cardioverter-defibrillator.

1. Jervell-Lange-Nielsen syndrome. Not as common as the previous syndrome. In this case we observe:

• more noticeable prolongation of the QT interval;
• increased frequency of attacks of ventricular tachycardia, fraught with death;
• congenital deafness.

Surgical treatment methods are mainly used.

1. Andersen-Tawil syndrome. This is a rare form of a genetic, inherited disease. The patient is susceptible to attacks of polymorphic ventricular tachycardia and bidirectional ventricular tachycardia. Pathology clearly makes itself known by the appearance of patients:

• short stature;
• curvature of the spine;
• low position of the ears;
• abnormally large distance between the eyes;
• underdevelopment of the upper jaw;
• deviations in the development of fingers.

The disease can occur with varying degrees of severity. The most effective method of therapy is the installation of a cardioverter-defibrillator.

1. Timothy syndrome. It is extremely rare. With this disease, maximum prolongation of the QT interval is observed. Every six out of ten patients with Timothy syndrome have various congenital heart defects (tetralogy of Fallot, patent ductus arteriosus, ventricular septal defects). A variety of physical and mental abnormalities are present. The average life expectancy is two and a half years.

The clinical picture is similar in manifestations to that observed with the congenital form. In particular, attacks of ventricular tachycardia and fainting are characteristic.

Acquired prolonged QT interval on the ECG can be recorded for various reasons.

1. Taking antiarrhythmic drugs: quinidine, sotalol, ajmaline and others.
2. Electrolyte imbalance in the body.
3. Alcohol abuse often causes paroxysm of ventricular tachycardia.
4. A number of cardiovascular diseases cause prolongation of the electrical systole of the ventricles.

Treatment of the acquired form primarily comes down to eliminating the causes that caused it.

Short QT syndrome

It can also be either congenital or acquired.

Congenital form of pathology

It is caused by a rather rare genetic disease that is transmitted in an autosomal dominant manner. Shortening of the QT interval is caused by mutations in the genes of potassium channels, which ensure the flow of potassium ions through cell membranes.

Symptoms of the disease:

• attacks of atrial fibrillation;
• attacks of ventricular tachycardia.

Study of families of patients with short interval syndromeQTshows that sudden deaths of relatives at a young and even infancy occurred in them due to atrial and ventricular fibrillation.

The most effective treatment for congenital short QT syndrome is the installation of a cardioverter-defibrillator.

Acquired form of pathology

1. The cardiograph may reflect on the ECG a shortening of the QT interval during treatment with cardiac glycosides in case of overdose.
2. Short QT syndrome can be caused by hypercalcemia (increased calcium levels in the blood), hyperkalemia (increased potassium levels in the blood), acidosis (a shift in the acid-base balance towards acidity) and some other diseases.

Therapy in both cases comes down to eliminating the causes of the short QT interval.

More:

How to decipher an ECG analysis, norms and deviations, pathologies and diagnostic principles