Prolonged QT interval. ECG interpretation: QT interval Prolongation of the qt interval over 450 ms

Long Q-T interval syndrome attracts close attention as a factor in sudden cardiovascular death, first described by the French cardiologist Dessertin in 1966. It has been established that both congenital and acquired forms of Q-T interval prolongation are harbingers of fatal heart rhythm disturbances, which, in turn, turn, lead to sudden death.

Long QT syndrome is a combination of a long QT interval on a standard ECG with life-threatening ventricular tachycardias (torsade de pointes - French pirouette). Paroxysms of ventricular tachycardia of the “pirouette” type are clinically manifested by episodes of dizziness, loss of consciousness and can result in ventricular fibrillation and sudden death.

The Q-T interval is the distance from the beginning of the QRS complex to the end of the T wave on the ECG curve. 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. The duration of the QT interval depends on the heart rate and gender of the person. Normally, women have an average O-T interval slightly longer than men of the same age. In healthy people at rest there is only a slight variability in repolarization processes, so the change in the Q-T interval is minimal. QT prolongation is diagnosed if the average QT duration exceeds 0.44 seconds.

There are two most studied mechanisms of arrhythmias in long QT interval syndrome.

• The first is intracardiac disorders of myocardial repolarization, namely, increased sensitivity of the myocardium to the arrhythmogenic effect of adrenaline, norepinephrine and other synthetic adrenergic agonists. For example, the fact of QT prolongation in acute myocardial ischemia and myocardial infarction is well known.
• 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) and other genetic abnormalities, especially against the background of congenital deafness. The most dangerous thing is that a person may not realize the existence of such a pathology for a long time and use drugs and their combinations that affect the Q-T interval.

DRUGS THAT PROLONGE THE QT INTERVAL

Prolongation of the QT interval can occur with electrolyte disturbances such as hypokalemia, hypocalcemia, hypomagnesemia. Such conditions occur under the influence of many factors, for example, with long-term use of diuretics, especially loop diuretics (furosemide), as well as strong laxatives. The development of ventricular tachycardia of the “pirouette” type is described against the background of prolongation of the Q-T interval with a fatal outcome in women who were on a low-protein diet for the purpose of losing weight and taking furosemide. The QT interval can also be lengthened when therapeutic doses of a number of drugs are used, in particular quinidine, procainamide, phenothiazine derivatives, etc. (see table). 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 the processes of repolarization. For example, pachycarpine in toxic doses, a number of alkaloids that block the active transport of ions (K +, Mg 2+)

HEART AND MEDICINES

Recently, pharmacovigilance authorities in various countries, including the FDA (USA), Australia and Canada, as well as the domestic State Expert Center, have been drawing the attention of doctors and pharmacists to the danger of developing arrhythmias associated with taking well-known drugs, especially when they are prescribed in combination with other drugs. drugs that prolong the QT interval in the myocardial cell and have a ganglion-blocking effect. There are also cases of prolonged QT interval and fatal arrhythmias due to poisoning with barbiturates, organophosphate insecticides and mercury, and scorpion stings.

In case of arrhythmias or their threat, all drugs that can prolong the QT interval should be discontinued. Correction of serum electrolytes is necessary, especially potassium, calcium and magnesium. In some cases, this is sufficient to normalize the size and dispersion of the Q-T interval and prevent ventricular arrhythmias.

DOMPERIDONE AND SUDDEN CARDIAC DEATH

In December 2012, the Australian TGA published the results of pharmacoepidemiological studies indicating that the use of domperidone may be associated with a risk of serious ventricular premature beats or sudden cardiac death, particularly in patients taking the drug in daily doses. above 30 mg, and persons over 60 years of age. These findings confirmed the warnings of the Canadian pharmacovigilance authorities published in 2007. Therefore, domperidone should be avoided in the presence of cardiac arrhythmias, heart failure, coronary artery disease, myocardial infarction, heart defects, and in the absence of contraindications, start with the lowest dose. Domperidone, despite its over-the-counter status, should not be used in children. It is necessary to avoid joint use with CYP3A47 inhibitors that may increase its plasma level, such as itraconazole, amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, diltiazem, verapamil, aprepitant, etc. In addition, domperidone is contraindicated for simultaneous use use with other drugs that prolong the QT interval.

AZITHROMYCIN AND OTHER MACROLIDE ANTIBIOTICS

Also, special care should be taken when prescribing macrolides, in particular azithromycin preparations, available in the form of tablets, capsules, powders for the preparation of oral suspensions and lyophilisate for injection solutions. The fact is that with regard to azithromycin, back in March 2013, the FDA informed about the risk of developing pathological changes in the electrical conductivity of the heart, which can lead to potentially fatal arrhythmias. It must be remembered that the risk group consists of patients with a history of QT interval prolongation, hypokalemia or hypomagnesemia, bradycardia, as well as patients using class IA (quinidine, procainamide) and class III antiarrhythmic drugs (dofetilide, amiodarone, sotalol). Therefore, it is necessary to avoid the combined use of these drugs with azithromycin and other macrolides in order to avoid the development of potentially dangerous arrhythmias. When choosing alternative antibiotic therapy for such patients, it should be remembered that other macrolide drugs, as well as fluoroquinolones, can cause QT prolongation.

Thus, when prescribing these drugs, it is necessary to determine the presence of contraindications and drug incompatibility. Patients taking these medications should stop taking all medications and seek immediate medical attention if they experience heart failure or abnormal heart rate or rhythm (particularly rapid heartbeat - tachycardia), dizziness, loss of consciousness, or seizures. .

Medicines that can prolong the QT interval

), characterized by prolongation of the QT interval on the electrocardiogram (ECG), attacks of loss of consciousness against the background of episodes of life-threatening ventricular arrhythmias (most often ventricular tachycardia of the “pirouette” type) and high mortality, which in the absence of treatment reaches 40 - 70% during the first year after clinical manifestation. In some cases, SCD may serve as the first manifestation of SUIQT. The frequency of the syndrome, according to various sources, ranges from 1:2000 to 1:3000.

The QT interval reflects the electrical systole of the ventricles (time in seconds from the beginning of the QRS complex to the end of the T wave). Its duration depends on gender (in women the QT is longer), age (with age the QT lengthens) and heart rate (HR) (inversely proportional). To objectively assess the QT interval, the corrected (heart rate-adjusted) QT interval (QTc), determined using the Bazett formulas (see below), is currently used.

Clinically, two main variants of SUIQT are identified: the most common in the population, Romano-Ward syndrome with an autosomal dominant type of inheritance and Jervell-Lange-Nielsen syndrome with an autosomal recessive type of inheritance. Since the first study proving the genetic nature of the syndrome in 1997, more than 400 mutations have been identified in 12 genes, responsible for the development of the syndrome, manifested by dysfunction of cardiac ion channels. Moreover, to date, in most countries, mutations in known genes are detected only in 50 - 75% of probands, which dictates the need for further study of the genetic mechanisms of the disease.

It should be remembered that SUIQT can be not only congenital, but also acquired syndrome, being a typical side effect of antiarrhythmic drugs (drugs) of classes I and III. Also, this pathology can be observed when using other, non-cardiological drugs, incl. antibiotics (clarithromycin, erythromycin, ciprofloxacin, spiromycin, bactrim, etc.), opioid analgesics (methadone), antihistamines (loratadine, diphenhydramine, etc.), antifungal drugs (ketoconazole, miconazole, fluconazole, etc.), antipsychotics (haloperidol, aminazine), etc. Acquired prolongation of the QT interval can occur with atherosclerotic or post-infarction cardiosclerosis, with cardiomyopathy, against the background and after suffering myo- or pericarditis; an increase in the dispersion (see below) of the QT interval (more than 47 ms) may also be a predictor of the development of arrhythmogenic syncope in patients with aortic heart defects.

Clinical manifestations of SUIQT are prolongation of the QT interval on the ECG, episodes of ventricular arrhythmia - most often ventricular fibrillation, less often ventricular polymorphic tachycardia, recorded by various methods, and syncope (which, as a rule, are associated with the development of ventricular fibrillation or flutter, less often - ventricular asystole) . The disease, as a rule, is detected either against the background of pronounced QT prolongation during preventive examinations, or during a targeted examination in connection with attacks of loss of consciousness.

To date, the diagnosis of SUIQT remains a difficult task, especially in relation to controversial subclinical and silent forms of the disease, as well as in the syncopal form due to overdiagnosis in these cases of epilepsy.

A standard 12-lead ECG allows you to identify prolongation of the QT interval of varying severity, assess the dispersion of the QT interval and changes in the morphology of the T wave. Bazett's formula (QTс = QT / (RR)0.5 at RR< 1000 мс) остается наиболее популярным инструментом коррекции интервала QT по отношению к частоте сердечных сокращений (ЧСС). Согласно рекомендациям 2008 г., приняты следующие значения для определения удлинения интервала QT: для лиц женского пола QTc460 мс, для лиц мужского пола - 450 мс.

ECG signs of SUIQT:

Prolongation of the QT interval, exceeding the norm for a given heart rate by more than 50 ms, regardless of the reasons underlying it, is generally accepted as an unfavorable criterion for electrical instability of the myocardium (Committee on Patented Medicines of the European Agency for the Evaluation of Medicinal Products (European Agency for the Evaluation of Medicinal Products). Medical Products) offers the following interpretation duration of the QTc interval);
T wave alternans - a change in the shape, polarity, amplitude of the T wave (which indicates electrical instability of the myocardium);
QT interval dispersion - the difference between the maximum and minimum values ​​of the QT interval in 12 standard ECG leads (QTd = QTmax - QTmin, normally QTd = 20 - 50 ms; an increase in QT interval dispersion indicates the readiness of the myocardium for arrhythmogenesis).

Polymorphic ventricular tachycardia type " pirouette"(or ventricular flutter - TdP - torsade de pointes) is characterized by an unstable, constantly changing shape of the QRS complex and develops against the background of an extended QT interval. It is assumed that the mechanism of TdP may be triggered activity due to early afterdepolarizations, or a “reentry” mechanism due to pronounced transmural dispersion of repolarization. Ventricular tachycardia of the “pirouette” type in 45 - 65% of cases is preceded by a “short-long-short” sequence (“short-long-short” interval, including extrasystole).

The presence of SUIQT with a risk of transition to torsades de pointes should be suspected in all patients with sudden loss of consciousness, palpitations, convulsions, or cardiac arrest.

Optimizing the treatment of patients with SUIQT remains a difficult and not fully resolved problem. Recommendations for the treatment of SUIQT are based primarily on data from International Registers and specialized clinics; No prospective randomized studies have been conducted in this area. The main methods of treatment are beta-blocker therapy and left-sided sympathectomy (LSS), as well as implantation of a cardioverter-defibrillator. Development of gene-specific therapy is also underway.

Among the beta-blockers in the treatment of SUIQT, propranolol, nadolol and atenolol are most widely used; in addition, metoprolol and bisoprolol are prescribed in some clinics. Propranolol and nadolol are the most effective in the treatment of SUIQT. However, propranolol has a number of disadvantages associated with the need to take it four times, as well as the development of tolerance with long-term use. Nadolol does not have these disadvantages and is used twice a day at a dose of 1.0 mg/kg. Metoprolol is the least effective beta-blocker, the use of which is accompanied by a high risk of recurrence of syncope. For those patients who, despite taking the maximum allowable dose of beta-blockers, continue to have recurrent ventricular tachycardia, LSE is currently recommended.

Implantation of cardioverter defibrillators (ICDs) is one of the relatively new treatment methods for children with SUIQT. According to the recommendations of the American and European Societies of Cardiology from 2006, ICD therapy in combination with beta blockers, regardless of age, is indicated for: patients who have survived cardiac arrest (class I); those who have persistent syncope and/or ventricular tachycardia while taking beta blockers (class IIa); for the prevention of SCD in patients at high risk (SCD), for example, with a diagnosed second and third molecular genetic variant of the syndrome or with a QTc exceeding 500 ms (class IIb).

Studying the molecular basis of SUIQT has opened up opportunities for the use of gene-specific therapy. In all cases of the syndrome, there is an increase in the duration of the action potential, but the cellular mechanism underlying this is different. This is reflected not only in differences in the clinical picture of the disease, but also affects the effectiveness of therapy. In 1995, P. Schwartz et al. convincingly demonstrated the effectiveness of the class I drug mexiletine in patients with LQT3. Another Class IC drug that has been used in the treatment of LQT3 is flecainide. In the group of patients with the SCN5AD1790G mutation, there was an increase in heart rate, a decrease in the duration of the QT interval, and suppression of T wave alternans during flecainide therapy.

All patients diagnosed with SUIQT, regardless of the volume of therapy, should be under continuous monitoring with assessment of the dynamics of all individual SCD risk markers at least once a year. Increased concentrations of risk factors and markers, which, for example, are typical for adolescent males with LQT1, serve as a basis for intensifying therapy. Monitoring can significantly reduce the risk of SCD even in patients with severe syndrome.

The connection between an altered QT interval and SCD has been known for more than 50 years, but only recently has it become clear that not only prolongation of the QT interval, but also its shortening may be a predictor of SCD...

The frequency of negative cardiovascular effects of psychotropic therapy, according to large-scale clinical studies, reaches 75%. Mentally ill people have a significantly higher risk of sudden death. Thus, a comparative study (Herxheimer A. et Healy D., 2002) showed a 2-5-fold increase in the incidence of sudden death in patients with schizophrenia compared to two other groups (patients with glaucoma and psoriasis). The US Food and Drug Administration (USFDA) reported a 1.6- to 1.7-fold increase in the risk of sudden death with all modern antipsychotic drugs (both classical and atypical). Long QT syndrome (QTS) is considered one of the predictors of sudden death during therapy with psychotropic drugs.

The QT interval reflects the electrical systole of the ventricles (time in seconds from the beginning of the QRS complex to the end of the T wave). Its duration depends on gender (in women the QT is longer), age (with age the QT lengthens) and heart rate (hcc) (inversely proportional). To objectively assess the QT interval, the corrected (heart rate-adjusted) QT interval (QTc), determined using the Bazett and Frederick formulas, is currently used:

Normal QTc is 340-450 ms for women and 340-430 ms for men.

It is known that QT AIS is dangerous for the development of fatal ventricular arrhythmias and ventricular fibrillation. The risk of sudden death with congenital AIS QT in the absence of adequate treatment reaches 85%, with 20% of children dying within a year after the first loss of consciousness and more than half in the first decade of life.

In the etiopathogenesis of the disease, the leading role is played by mutations in the genes encoding potassium and sodium channels of the heart. Currently, 8 genes have been identified that are responsible for the development of clinical manifestations of QT AIS. In addition, it has been proven that patients with AIS QT have a congenital sympathetic imbalance (asymmetry of heart innervation) with a predominance of left-sided sympathetic innervation.

Genes responsible for the development of AIS QT

The clinical picture of the disease is dominated by attacks of loss of consciousness (syncope), the connection of which with emotional (anger, fear, sharp sound stimuli) and physical stress (physical activity, swimming, running) emphasizes the important role of the sympathetic nervous system in the pathogenesis of AIS QT.

The duration of loss of consciousness averages 1-2 minutes and in half of the cases is accompanied by epileptiform, tonic-clonic convulsions with involuntary urination and defecation. Since syncope can occur in other diseases, such patients are often interpreted as patients with epilepsy or hysteria.

Features of syncope in AIS QT:

As a rule, they occur at the height of psycho-emotional or physical stress
typical warning signs (sudden general weakness, darkening of the eyes, palpitations, heaviness in the chest)
rapid, without amnesia and drowsiness, restoration of consciousness
absence of personality changes characteristic of patients with epilepsy

Syncope in QT AIS is caused by the development of polymorphic ventricular tachycardia of the “torsades de pointes” type (TdP). TdP is also called “cardiac ballet”, “chaotic tachycardia”, “ventricular anarchy”, “cardiac storm”, which is essentially synonymous with circulatory arrest. TdP is an unstable tachycardia (the total number of QRS complexes during each attack ranges from 6 to 25-100), prone to relapses (within a few seconds or minutes the attack can recur) and transition to ventricular fibrillation (refers to life-threatening arrhythmias). Other electrophysiological mechanisms of sudden cardiogenic death in patients with QT AIS include electromechanical dissociation and asystole.
ECG signs of AIS QT.

1 Prolongation of the QT interval - exceeding the norm for a given heart rate by more than 50 ms, regardless of the reasons underlying it, is generally accepted as an unfavorable criterion for electrical instability of the myocardium.
The Committee on Proprietary Medicines of the European Agency for the Evaluation of Medical Products offers the following interpretation of the duration of the QTc interval

An increase in QTc of 30 to 60 ms in a patient taking new medications should raise concern for a possible drug relationship. An absolute QTc duration greater than 500 ms and a relative increase greater than 60 ms should be considered a risk for TdP.
2. Alternation of the T wave - a change in the shape, polarity, amplitude of the T wave indicates electrical instability of the myocardium.
3. QT interval dispersion – the difference between the maximum and minimum values ​​of the QT interval in 12 standard ECG leads. QTd = QTmax – QTmin, normally QTd = 20-50ms. An increase in QT interval dispersion indicates the readiness of the myocardium for arrhythmogenesis.
The growing interest in the study of acquired QT AIS, noted in the last 10-15 years, has expanded our understanding of external factors, such as various diseases, metabolic disorders, electrolyte imbalance, drug aggression, causing disturbances in the functioning of cardiac ion channels, similar to congenital mutations in idiopathic QT AIS.

Clinical conditions and diseases closely associated with QT prolongation

According to data provided in a report by the Centers for Disease Control and Prevention dated March 2, 2001, the incidence of sudden cardiac death among young people is increasing in the United States. Among the possible causes of this increase, it has been suggested that drugs play an important role. The volume of drug consumption in economically developed countries is constantly increasing. Pharmaceuticals have long become a business like any other. On average, pharmaceutical giants spend about $800 million on new product development alone, which is two orders of magnitude higher than in most other areas. There has been a clear negative trend in pharmaceutical companies introducing an increasing number of drugs as status or prestigious drugs (lifestyle drugs). Such drugs are taken not because they are needed for treatment, but because they correspond to a certain lifestyle. This is Viagra and its competitors Cialis and Levitra; "Xenical" (weight loss product), antidepressants, probiotics, antifungals and many other drugs.

Another alarming trend can be described as Disease Mongering. The largest pharmaceutical companies, in order to expand their sales market, convince completely healthy people that they are sick and need drug treatment. The number of imaginary illnesses, artificially inflated to the scale of serious diseases, is constantly increasing. Chronic fatigue syndrome (manager's syndrome), menopause as a disease, female sexual dysfunction, immunodeficiency conditions, iodine deficiency, restless legs syndrome, dysbiosis, “new” infectious diseases are becoming brands to increase sales of antidepressants, immunomodulators, probiotics, and hormones.
Independent and uncontrolled use of medications, polypharmacy, unfavorable combinations of drugs and the need for long-term medication use create the preconditions for the development of QT IMS. Thus, drug-induced prolongation of the QT interval as a predictor of sudden death has become a serious medical problem.

A variety of drugs from the widest pharmacological groups can lead to prolongation of the QT interval.

Drugs that prolong the QT interval

The list of drugs that prolong the QT interval is constantly growing.

All centrally acting drugs prolong the QT interval, often clinically significant, and this is why the problem of drug-induced QT interval in psychiatry is most acute.

A series of numerous publications have proven the connection between the prescription of antipsychotics (both old, classical, and new, atypical) and AIS QT, TdP and sudden death. In Europe and the United States, the licensing of several antipsychotic drugs was prevented or delayed, and others were withdrawn from production. Following reports of 13 cases of sudden unexplained death associated with pimozide, a decision was made in 1990 to limit its daily dose to 20 mg per day and treat with ECG monitoring. In 1998, following the publication of data linking sertindole to 13 cases of serious but non-fatal arrhythmia (36 deaths were suspected), Lundbeck voluntarily temporarily stopped selling the drug for 3 years. That same year, thioridazine, mesoridazine, and droperidol received a black box warning for QT prolongation, and ziprasidone received a bold warning. By the end of 2000, after the death of 21 people due to taking thioridazine prescribed by doctors, this drug became a second-line drug in the treatment of schizophrenia. Shortly thereafter, droperidol was withdrawn from the market by its manufacturers. In the United Kingdom, the release of the atypical antipsychotic drug ziprasidone was delayed because mild QT prolongation occurred in more than 10% of patients taking the drug.

Cases of sudden death, closely associated with AIS QT, have been described in patients receiving long-term tricyclic antidepressants, incl. with postmortem identification of the “slow-metabolizer” phenotype of CYP2D6 due to drug accumulation.

Newer cyclic and atypical antidepressants are safer with respect to cardiovascular complications, demonstrating QT prolongation and TdP only at higher therapeutic doses.

Most psychotropic drugs widely used in clinical practice belong to class B (according to W. Haverkamp 2001), i.e. their use carries a relatively high risk of TdP.

According to experiments in vitro, in vivo, sectional and clinical studies, anticonvulsants, antipsychotics, anxiolytics, mood stabilizers and antidepressants are able to block fast potassium HERG channels, sodium channels (due to a defect in the SCN5A gene) and L-type calcium channels, thus causing functional failure of all channels of the heart.

In addition, well-known cardiovascular side effects of psychotropic drugs are involved in the formation of AIS QT. Many tranquilizers, antipsychotics, lithium drugs, and TCAs reduce myocardial contractility, which in rare cases can lead to the development of congestive heart failure. Cyclic antidepressants can accumulate in the heart muscle, where their concentration is 100 times higher than the level in the blood plasma. Many psychotropic drugs are calmodulin inhibitors, which leads to dysregulation of myocardial protein synthesis, structural damage to the myocardium and the development of toxic cardiomyopathy and myocarditis.

It should be recognized that clinically significant prolongation of the QT interval is a serious but rare complication of psychotropic therapy (8-10% during treatment with antipsychotics). Apparently, we are talking about a latent, hidden form of congenital QT AIS with clinical manifestation due to drug aggression. An interesting hypothesis is about the dose-dependent nature of the drug’s effect on the cardiovascular system, according to which each antipsychotic has its own threshold dose, exceeding which leads to a prolongation of the QT interval. It is believed that for thioridazine it is 10 mg/day, for pimozide - 20 mg/day, for haloperidol - 30 mg/day, for droperidol - 50 mg/day, for chlorpromazine - 2000 mg/day. It has been suggested that QT prolongation may also be associated with electrolyte abnormalities (hypokalemia).

Cytochrome P450: drugs metabolized by certain isomers (according to Pollock B.G. et al., 1999)

There are 4 statuses of genetically determined metabolic phenotype:

o extensive (fast) metabolizers (Extensive Metabolizers or fast) – having two active forms of microsomal oxidation enzymes; in therapeutic terms, these are patients with standard therapeutic doses.
o intermediate metabolizers (Intermediate Metabolizers) - having one active form of the enzyme and, as a result, slightly reduced drug metabolism
o low metabolizers or slow (Poor Metabolizers or slow) – do not have active forms of enzymes, as a result of which the concentration of the drug in the blood plasma can increase 5-10 times
o Ultra-extensive Metabolizers – having three or more active forms of enzymes and accelerated drug metabolism

Many psychotropic drugs (especially neuroleptics, phenothiazine derivatives) have a hepatotoxic effect (up to the development of cholestatic jaundice), due to a complex (physico-chemical, autoimmune and direct toxic) effect on the liver, which in some cases can transform into chronic liver damage with enzyme impairment metabolism according to the “poor metabolizing” type (“poor” metabolism).

In addition, many neurotropic drugs (sedatives, anticonvulsants, neuroleptics and antidepressants) are inhibitors of microsomal oxidation of the cytochrome P450 system, mainly enzymes 2C9, 2C19, 2D6, 1A2, 3A4, 5, 7.

Medicines that block the CYP3A4 isoenzyme of the cytochrome P450 system. (A. John Camm, 2002).

1A inhibitors

2C9 inhibitors

2C19 inhibitors

2D6 inhibitors

Thus, the preconditions are created for cardiovascular complications with a constant dose of a psychotropic drug and with unfavorable drug combinations.
There is a group of high individual risk of cardiovascular complications when treated with psychotropic drugs.

These are elderly and children's patients, with concomitant cardiovascular pathology (heart disease, arrhythmias, bradycardia less than 50 beats per minute), with genetic damage to the ion channels of the heart (congenital, including latent, and acquired QT AIS), with electrolyte imbalance (hypokalemia, hypocalcemia, hypomagnesemia, hypozincemia), with a low level of metabolism (“poor”,”slow”-metabolizers), with dysfunction of the autonomic nervous system, with severe impairment of liver and kidney function, simultaneously receiving drugs that prolong the QT interval, and/or inhibiting cytochrome P450. In a study by Reilly (2000), risk factors for prolongation of the QT interval were recognized:

A modern doctor faces the difficult task of choosing the right drug from a huge number of drugs (in Russia there are 17,000 names!) according to the criteria of effectiveness and safety.

Proper monitoring of the QT interval will help avoid serious cardiovascular complications of psychotropic therapy.

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LONG QT INTERVAL SYNDROME AND PROBLEMS OF PSYCHOPHARMACOTHERAPY SAFETY
© Limankina, I. N.
St. Petersburg Psychiatric Hospital No. 1 named after. P.P. Kashchenko

Long QT syndrome is a heart condition that causes uncontrolled arrhythmias. It is the most common cause of unexplained deaths, affecting approximately 1 in every 2,000 people.

People with long QT syndrome have a structural defect in the ion channels of the heart muscle. A defect in these ion channels causes abnormalities in the electrical conduction system of the heart. This heart defect makes them prone to uncontrollable, rapid and chaotic heartbeats (arrhythmias).

With each heartbeat, an electrical signal is transmitted from the top to the bottom. An electrical signal causes the heart to contract and pump blood. This pattern for each heart rhythm can be seen on the ECG as five separate waves: P, Q, R, S, T.

The QT interval is a measurement of the time between the onset of the Q wave and the T wave and represents the time it takes for the heart muscles to relax after contracting to pump blood.

In people with long QT syndrome, this interval is longer than usual and disrupts the heart rhythm causing arrhythmias.

At least 17 genes are known to cause long QT syndrome. Mutations of these genes are associated with the structure and functioning of ion channels. There are 17 types of long QT syndrome, each associated with a single gene.

They are numbered sequentially as LQT1 (type 1), LQT2 (type 2) and so on.

LQT1 to LQT15 are known as Romano-Ward syndrome and are inherited in an autosomal dominant manner. In autosomal dominant inheritance, a mutation in one copy of the gene is sufficient to cause the disorder.

A rare form of long qt syndrome, known as Jervell and Lange-Nielsen syndrome, is associated with congenital deafness. It has two types: JLN1 and JLN2, depending on the gene involved.

Jervell and Lange-Nielsen syndrome is inherited in an autosomal recessive manner, meaning both copies of the gene must be mutated to cause the condition.

Causes and risk factors

Long QT syndrome is often inherited, which means it is caused by a mutation in one of 17 genes. Sometimes it is caused by a medicine.

More than 17 drugs, including some common ones, can prolong the QT interval in healthy people. Some of these include:

• antiarrhythmic drugs: Sotalol, Amiodarone, Dofetilide, quinidine, procainamide, disopyramide;
• Antibiotics: erythromycin, clarithromycin, levofloxacin;
• : Amitriptyline, Doxepin, desipramine, clomipramine, imipramine;
• Antipsychotic drugs: thioridazine, chlorpromazine, haloperidol, Prochlorpherazine, Fluphenazine;
• Antihistamines: terfenadine, astemizole;
• Diuretics, cholesterol medications, and some diabetes medications.

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Risk factors

There are various factors that determine a person's risk of having long QT syndrome.

You are at risk if:

• You or a family member have a history of unexplained fainting or seizures, drowning or near drowning incidents, unexplained accidents or deaths, or cardiac arrest at a young age.
• Your close relative has been diagnosed with long QT syndrome.
• You are taking medications that cause it.
• If you have low levels of calcium, potassium or magnesium in your blood.

People suffering from this condition often go undiagnosed or are misdiagnosed. Therefore, it is important to consider key risk factors to ensure accurate diagnosis.

Symptoms

Symptoms of long QT syndrome are common in children. However, they can begin at any time in a person's life from birth to old age or never at all. These symptoms include:

• Fainting: Loss of consciousness is the most common symptom. It occurs when there is a limited supply of blood to the brain due to a temporary irregular heartbeat.
• Seizures: When the heart continues to beat erratically for a long period of time, the brain becomes deprived of oxygen, leading to seizures.
• Sudden death: If the heart does not return to normal rhythm immediately after an arrhythmic attack, sudden death may result.
• Arrhythmia during sleep: People who have long QT syndrome type 3 may experience irregular heartbeats during sleep.

Diagnostics

Not all people show symptoms of the condition, making diagnosis difficult. Therefore, it is important to use a combination of methods to identify individuals suffering from long qt syndrome.

Some methods used for diagnosis:

• Electrocardiogram (ECG);
• Medical and family history;
• Genetic test result.

Electrocardiogram

An ECG analyzes the electrical activity of the heart and helps determine the interval. This is done while the person is resting or while performing a stationary exercise. This test is performed several times as electrical activity may vary over time.

Some doctors attach a wearable heart monitor to the body to monitor heart activity for 24 to 48 hours.

Medical and family history

Medical history and family history of symptoms and signs of long QT syndrome can help determine the chances of having the condition. Therefore, the doctor examines a detailed family history of three generations to assess the risk.

Genetic results

A genetic test is done to check if there is a mutation in the gene associated with long-qt syndrome.

Treatment

The goal of treatment is to prevent arrhythmias and syncope. It may vary among individuals, depending on previous history of syncope and sudden cardiac arrest, type of QT syndrome, and family history.
Treatment options:

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Drugs

Beta blockers, medications that prevent the heart from beating at a high rate, are prescribed to prevent arrhythmias. In some cases, potassium and fish oil supplements are prescribed to help maintain a regular heart rate.

Implantable devices

Pacemakers or implantable cardioverter defibrillator (ICD) are small devices that help control your heart rhythm. They are implanted under the skin of the chest or stomach through a minor procedure.

If they detect any abnormalities in the heart rhythm, they send electrical impulses to teach the heart to correct its rhythm.

Surgery

In some people, the nerves that send messages to the heart to beat faster are surgically removed. This prevents the risk of sudden death.

How to prevent

Long QT syndrome is a lifelong condition and the risk of fainting or sudden cardiac arrest never goes away. However, there are several preventative options that people can incorporate into their lives to reduce the risk of complications associated with the syndrome.

To prevent abnormal heart rhythms, you should:

• Avoid activities that may cause irregular heart rhythm. For example, strenuous exercise such as swimming should be avoided as it causes arrhythmias.
• Medicines that cause arrhythmias should not be prescribed to persons with long QT syndrome. Ask your doctor for a list of medications to avoid.
• If you have an implanted pacemaker or ICD device, be careful when playing sports not to move the device from its location.
• Let people you see regularly about your condition so they can help you if an emergency arises.
• Visit your cardiologist regularly.

• Know your body: Keep checking for symptoms and see your doctor if you notice anything unusual.
• Visit your doctor regularly: follow the advice carefully.
• Maintain a healthy lifestyle, avoid smoking, drinking alcohol to avoid the risk of heart disease.
• Reduce sports activities: Avoid or reduce sports activities that cause your heart rate to fluctuate constantly.
• Medications: Be very careful to avoid drugs that cause long QT syndrome. You should tell all doctors you see about your condition so that they do not prescribe medications that may cause arrhythmia.

If I have a heartbeat, what does it mean?

Palpitation is the feeling that the heart is beating quickly. It is not necessarily a symptom of arrhythmia. If you feel this sensation, get checked by a cardiologist.

Long QT syndrome (LQT) is a congenital or acquired cardiac pathology, which is characterized by prolongation 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 suffer from it somewhat more often. 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 conditions that occurred with severe 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 of treating it continue.

Causes of 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 chromosomes 3, 7, 11 and 21. In most cases, they disrupt the functioning 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 of ventricular tachycardia of the “pirouette” type, which can develop into.

The processes of depolarization and repolarization that occur as a result of the movement of electrolytes into the cell from the extracellular space and back are reflected on the ECG by the QT interval, which lengthens with this pathology.

In clinical practice, there are 3 main variants of 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 combined with congenital deafness);
• autosomal dominant variant with extracardiac manifestations.

The last of them can manifest itself in the form:

• Andersen-Tawil syndrome (QT prolongation combined with pronounced U-wave, ventricular tachycardia, abnormalities of the skeletal system, hyper- or hypokalemic periodic paralysis);
• Timothy syndrome (syndactyly, congenital cardiac anomalies, various conduction disorders, extremely high risk of sudden death).

Acquired form

Previously, it was believed that the occurrence of acquired LQT syndrome is associated with a disruption in the functioning of ion channels, which is caused not by a mutation, but by the influence of some 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, it is difficult to distinguish the acquired syndrome from congenital pathology, since they have much in common. Typically, this pathology goes undetected for a long time and manifests itself under unfavorable conditions, for example under stress or physical exertion. Factors that contribute to prolongation of the QT interval include:

• taking medications (we’ll look at which ones below);
• electrolyte disturbances (lack of potassium, sodium, magnesium);
• heart rhythm disturbances;
• diseases of the nervous system (trauma, infection, tumor);
• changes in hormonal status (pathology of the thyroid gland or adrenal glands);
• alcoholism;
• fasting, 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 the direct effects of drugs, and their withdrawal often leads to normalization of all indicators, we will take a closer look at which drugs can change the length of the QT interval:

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

They should not be prescribed to persons who already have a prolongation of this interval. And with a late onset 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 illness. The most typical manifestations of this pathology are:

• attacks of loss of consciousness;
• congenital deafness;
• cases of sudden death in the family;
• changes in the electrocardiogram (QT more than 450 ms, T wave alternans, ventricular tachycardia of the “pirouette” type).

With congenital variants of the syndrome, other symptoms characteristic only of it may appear.

It should be noted that syncope with this pathology has its own characteristics:

• occur against a 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 loss of consciousness (severe weakness, ringing in the ears, darkening of the eyes, feeling of heaviness in the chest);
• rapid restoration of consciousness with a favorable outcome;
• absence of amnesia and personality changes (as with epilepsy).

Sometimes loss of consciousness may 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 living conditions. The following options are considered the most common:

• syncope occurring against the background of prolongation of the QT interval;
• isolated prolongation of this interval;
• syncope in the absence of changes on the ECG;
• 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.

With congenital variants of the disease, fainting appears in childhood (5-15 years). Moreover, their occurrence in preschool children is a prognostically unfavorable sign. And paroxysm of ventricular tachycardia, which requires emergency care, increases the likelihood of repeated 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 trend is observed very often.

Diagnostic principles

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

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

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

Among the major criteria are:

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

The diagnosis is considered reliable if two major or one major and two minor criteria are present.

Treatment

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

All persons with prolonged QT interval should avoid:

• stressful situations;
• playing sports;
• heavy physical activity;
• taking medications that increase the length of this interval.

Medications for this syndrome are usually prescribed:

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

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