Hereditary long QT interval syndrome: symptoms, diagnosis, treatment

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

[1], [2], [3], [4], [5], [6]

Epidemiology

The syndrome is met with a frequency of 1: 5000. Having a relatively low prevalence in the infant population, in the absence of adequate therapy, the syndrome is accompanied by a high mortality rate, reaching 70% in the first year after the onset of clinical symptoms. Characteristic features of the syndrome are lengthening of QT-interval by ECG [QT interval corrected (Q-Tc) more than 440 ms], abnormalities of ventricular repolarization morphology (alternative to T wave), syncopal conditions and family concentration of pathology and sudden cardiac death as a result of life-threatening ventricular arrhythmias.

[7], [8], [9], [10], [11], [12], [13], [14], [15], [16]

Causes of hereditary long QT interval syndrome

The autosomal recessive form of the long QT syndrome syndrome, the Jervell-Lange-Nielsen syndrome, was discovered in 1957, it is rarely seen. The prolongation of the QT interval and the risk of sudden cardiac death due to the development of life-threatening arrhythmias are associated with this syndrome with congenital deafness. More common is the autosomal dominant form - the Romano-Ward syndrome, it has an isolated "cardiac" phenotype. Currently, 10 molecular-genetic variants of the syndrome (LQ-T 1-10) are isolated. Along with general characteristics in the form of a significant elongation of the QT interval on the ECG, fits of loss of consciousness against life-threatening arrhythmias and sudden deaths in families, these variants have clinical and electrocardiographic features caused by specific electrolyte disorders caused by changes in genes that modulate the functional activity of cardiac ion channels. The most common is LQ-T1, accounting for up to 70% of cases of CYHQ-T. This is followed by LQ-T2 and LQ-T3. CYHQ-T may be due to mutations in genes that regulate the function of potassium or sodium channels, as well as membrane components. Mutations lead both to the loss of potassium channel functions with a delay in repolarization, and to the enhancement of the functions of the sodium or calcium channels responsible for delaying the repolarization currents. The genetic heterogeneity of the syndrome has not been fully studied to date. Patients with CYHQ-T can be long standing on the account of a neurologist with a diagnosis of "epilepsy". Until now, it is not unusual for a family variant of CYHQ-T to be identified only after the sudden death of one of the family members during the first loss of consciousness in life.

[17], [18], [19]

Symptoms and Diagnosis of Genetic Long QT Intermittent Syndrome

Attacks of loss of consciousness in patients with long QT interval syndrome are caused by malignant arrhythmia - tachycardia such as "pirouette" or ventricular fibrillation. Stressful effects, such as emotional arousal and high physical activity, become arrhythmogenic factors for patients with this syndrome. All patients, at least once in their lifetime had syncope, should be attributed to the group at increased risk of sudden cardiac death. The frequency of recurrences of life-threatening ventricular arrhythmias lies in the range of 3-5% per year. In children who have survived the adolescent period, the disease acquires a less malignant course: the frequency of syncope with age decreases. The duration of loss of consciousness during attacks in young patients is usually 1-2 min, but in some cases can reach 20 min. In 50% of patients with syncopal form of the attack accompanied by convulsions of tonic-clonic nature with involuntary urination, less often - defecation. The presence of convulsions is considered an unconditional criterion for the severity of syncope, since it is known that the unconscious state is accompanied by convulsions only with a sufficiently long and deep ischemia of the brain. The frequency and amount of syncope is a measure of the severity of the disease, but it is noteworthy that death may occur during the first attack of loss of consciousness. This dictates the need to determine the risk of sudden death in patients with both syncopal and non-syncopal form of the syndrome. Syncopal states with CYHQ-T due to the presence of the convulsive component should be differentiated from epileptic seizures. The main distinctive 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 interval syndrome

Treatment of patients with syncopal form of primary CYHQ-T consists in the maximum exclusion of triggers of life-threatening arrhythmias specific for each patient, as well as the exclusion of drugs that can prolong the QT interval (the list is given to patients on discharge from the hospital), and mandatory long-term (life-long) appointment antiarrhythmic drug. The drug of the first choice - beta-blocker (propranolol, atenolol, metoprolol or nadolol). When LQ-T3 beta-blockers should be used with caution under the control of heart rate, as a marked decrease in heart rate increases the dispersion of repolarization and can facilitate the occurrence of tachycardia such as "pirouette" with this version of the syndrome. LQ-T2 therapy was suggested to be strengthened by prescribing potassium preparations (the electrolyte content in the blood plasma should be kept at the maximum acceptable level) in combination with potassium-sparing diuretics. With LQ-T3, the appointment of mexiletine (antiarrhythmic drug IB class) - a blocker of sodium channels. In combination antiarrhythmic therapy, while preserving syncope against the background of antiarrhythmic drug monotherapy in children, the prescription of an anticonvulsant drug carbamazepine may be effective. The drug also affects the inactivation of sodium channels - the mechanism for the implementation of the third variant of the syndrome. In order to stabilize the emotional background with increased anxiety, provocation of syncopal conditions, emotional excitation involves aminophenylbutyric acid (phenybut).

The genotype, which has a large effect on the CYHQ-T prognosis, is an independent predictor of sudden arrhythmic death, along with a pronounced elongation of Q-Tc-2c (> 500 ms), recurrent syncopal conditions, and a clinical history of death.

Implantation of a cardioverter-defibrillator is indicated for patients with a high risk of sudden arrhythmic death (clinical history or repeated syncope against antiarrhythmic therapy). As a rule, when implanting a modern antiarrhythmic device, functions of the pacemaker are used along with defibrillator functions.