Hereditary syndrome of prolonged Q-T interval: symptoms, diagnosis, treatment

Hereditary long QT syndrome is a genetically heterogeneous pathology with a high risk of sudden cardiac death.

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Epidemiology

The syndrome occurs with a frequency of 1:5000. Having a relatively low prevalence in the pediatric population, in the absence of adequate therapy, the syndrome is accompanied by a high mortality rate, reaching 70% in the first year from the onset of clinical symptoms. Characteristic signs of the syndrome are prolongation of the QT interval on the ECG [corrected QT interval (Q-Tc) more than 440 ms], abnormalities in the morphology of ventricular repolarization (alternation of the T wave), syncope, and a familial concentration of pathology and cases of sudden cardiac death as a result of life-threatening ventricular arrhythmias.

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Causes of hereditary long QT syndrome

The autosomal recessive form of long QT syndrome, Jervell-Lange-Nielsen syndrome, was discovered in 1957 and is rare. Prolongation of the QT interval and the risk of sudden cardiac death due to the development of life-threatening arrhythmias are associated with congenital deafness in this syndrome. The autosomal dominant form, Romano-Ward syndrome, is more common; it has an isolated "cardiac" phenotype. Currently, 10 molecular genetic variants of the syndrome (LQ-T 1-10) have been identified. Along with common characteristics such as significant prolongation of the QT interval on the ECG, attacks of loss of consciousness against the background of life-threatening arrhythmias and cases of sudden death in families, these variants have clinical and electrocardiographic features due to the specificity of electrolyte disturbances caused by changes in the genes that modulate the functional activity of cardiac ion channels. LQ-T1 is the most common, accounting for up to 70% of CYHQ-T cases. It is followed by LQ-T2 and LQ-T3. CYHQ-T can be caused by mutations in genes that regulate the functions of potassium or sodium channels, as well as membrane components. Mutations lead to both loss of function of potassium channels with delayed repolarization and to enhancement of function of sodium or calcium channels responsible for delayed repolarization currents. The genetic heterogeneity of the syndrome has not yet been fully studied. Patients with CYHQ-T may be registered with a neurologist for a long time with a diagnosis of epilepsy. Until now, it is not uncommon for a familial variant of CYHQ-T to be detected only after the sudden death of one of the family members during the first episode of loss of consciousness in life.

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Symptoms and diagnosis of hereditary long QT syndrome

Attacks of loss of consciousness in patients with long QT syndrome are caused by malignant arrhythmia - tachycardia of the "pirouette" type or ventricular fibrillation. Stressful effects, such as emotional excitement and high physical activity, become arrhythmogenic factors for patients with this syndrome. All patients who have had syncope at least once in their life should be classified as a high-risk group for sudden cardiac death. The recurrence rate of life-threatening ventricular arrhythmias is within 3-5% per year. In children who have survived adolescence, the disease takes a less malignant course: the frequency of syncope decreases with age. The duration of loss of consciousness during attacks in young patients is usually 1-2 minutes, but in some cases it can reach 20 minutes. In 50% of patients with the syncopal form, the attack is accompanied by tonic-clonic convulsions with involuntary urination, less often - defecation. The presence of seizures is considered an absolute criterion of syncope severity, since it is known that the unconscious state is accompanied by seizures only with sufficiently prolonged and deep cerebral ischemia. The frequency and number of syncopes are criteria for the severity of the disease, but it is noteworthy that death can occur during the 1st attack of loss of consciousness. This dictates the need to determine the degree of risk of sudden death in patients with both syncopal and non-syncopal forms of the syndrome. Syncopal states in CYHQ-T due to the presence of a convulsive component should be differentiated from epileptic seizures. The main distinguishing feature should be considered a rapid recovery of consciousness and a good degree of orientation after the end of the attack.

Treatment of hereditary long QT syndrome

Treatment of patients with syncopal form of primary CYHQ-T consists of maximum exclusion of triggers of life-threatening arrhythmias specific for each patient, as well as exclusion of drugs capable of prolonging the QT interval (a list is given to patients upon discharge from the hospital), as well as mandatory long-term (lifelong) administration of an antiarrhythmic drug. The drug of first choice is a beta-blocker (propranolol, atenolol, metoprolol or nadolol). In LQ-T3, beta-blockers should be used with caution under heart rate monitoring, since a marked decrease in heart rate increases repolarization dispersion and can facilitate the development of pirouette-type tachycardia in this variant of the syndrome. It was proposed to enhance LQ-T2 therapy by prescribing potassium preparations (it is desirable to maintain the electrolyte content in the blood plasma at the maximum permissible level) in combination with potassium-sparing diuretics. In LQ-T3, mexiletine (an IB class antiarrhythmic drug) is indicated - a sodium channel blocker. In combination antiarrhythmic therapy, if syncope persists against the background of monotherapy with an antiarrhythmic drug in children, the anticonvulsant drug carbamazepine may be effective. The drug also affects the inactivation of sodium channels - the mechanism for the implementation of the 3rd variant of the syndrome. In order to stabilize the emotional background in case of increased anxiety, provocation of syncopal states by emotional excitement, aminophenylbutyric acid (phenibut) is added.

The genotype that has a major impact on the prognosis of CYHQ-T is an independent predictor of sudden arrhythmic death along with a marked prolongation of Q-Tc-2s (more than 500 ms), repeated syncope and a history of clinical death.

Implantation of a cardioverter-defibrillator is indicated for patients with a high risk of sudden arrhythmic death (clinical death in the anamnesis or repeated syncope during antiarrhythmic therapy). As a rule, when implanting a modern antiarrhythmic device, along with the functions of a defibrillator, the functions of an electrical cardiac stimulation are used.