Long Q-T Syndrome

Introduction to long QT interval syndrome Long Q-Tsyndrome (LQTS), also known as delay repolarization syndrome, refers to prolongation of QT interval on electrocardiogram with T wave and / or u wave morphology abnormalities, clinical manifestations A group of syndromes of ventricular arrhythmia, syncope and sudden death. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific people Mode of infection: non-infectious Complications: syncope, sudden death

Causes of long QT syndrome

(1) Causes of the disease

There are many causes of long QT syndrome, including both congenital and acquired.

1. Congenital long QT syndrome includes the autosomal dominant Romano Ward syndrome and the autosomal recessive Jervell Lange-Nielsen syndrome, the former with normal hearing and the latter with congenital deafness.

There are many hypotheses about the causes of congenital long QT syndrome, including sympathetic dominance imbalance, myocardial repolarization abnormalities, intracardiac neurodegeneration and congenital myocardial enzyme deficiency. Currently, congenital long QT synthesis is considered. The sign is caused by a mutation in the gene that regulates the repolarization ion channel of the ventricular myocyte membrane.

In 1991, Keating et al. used DNA probe technology to find that 40 genes in a family with long QT syndrome are closely related to the IIarvey ras 1 gene, perhaps the disease gene of long QT syndrome, and this finding is in another 6 long QTs. In the family of the syndrome, the Harvey ras 1 gene is located on the short arm of chromosome 11, and the protein product is the guanine nucleotide-binding protein, G protein, which is distributed in the inner layer of the cell membrane, and receptors of various hormones. Effectors such as adenylate cyclase, phospholipase C and ion channels are involved. Codina et al. observed that G protein and Ras protein regulate cardiomyocytes affected by acetylcholine-activated K channels, but insufficiently, Moss did not find Harvey ras. 1 gene and long QT syndrome transformation relationship, in 1995, Wang et al confirmed that idiopathic long QT syndrome is associated with gene mutations encoding cardiomyocyte ion channel proteins, and confirmed that at least three pathogenic genes exist, namely the third , mutations in scN5A, HERG and KVLQT1 genes on chromosomes 7 and 11, SCN5A encodes sodium channels in cardiomyocytes, and HERG encodes potassium channels in cardiomyocytes. The function of KVLQTl is not well understood. Can be related to the synthesis of certain potassium channels.

2. Acquired long QT interval syndrome

(1) Drug effects: In recent years, in-depth study of clinical pharmacology and the wide application of ECG monitors, more and more drugs have been found to cause QT interval prolongation and Tdp tip torsade ventricular tachycardia, including:

1 anti-arrhythmia drugs: among the various drugs that cause long QT syndrome, anti-arrhythmia drugs are the most common, among them, class I anti-arrhythmia drugs are most likely to cause long QT interval syndrome, class Ia Antiarrhythmic drugs such as quinidine, propiamine, procainamide can moderately inhibit conduction, prolong ventricular repolarization, is the exact cause of Tdp, and class Ib antiarrhythmic drugs such as lidocaine Kaan, Mexilet does not prolong ventricular repolarization, whether it causes long QT syndrome is still controversial, Ic antiarrhythmic drugs such as flecainide, Encarni, etc. can slightly prolong ventricular repolarization, often can cause room Sexual tachycardia, but whether it causes Tdp, the understanding is still inconsistent. Among the class II antiarrhythmic drugs, blockers, only Sotolol can cause long QT syndrome, class III antiarrhythmic drugs and amiodarone. It is confirmed that long QT syndrome and Tdp can be caused, and only Bepridil can cause long QT syndrome and Tdp in the class IV antiarrhythmic drug.

2 phenothiazine drugs.

3 tricyclic and tetracyclic antidepressants, erythromycin injections and organophosphate insecticides can cause long QT syndrome.

(2) Electrolyte metabolism disorder: The literature reports that hypokalemia, hypomagnesemia, hypocalcemia, etc. can cause long QT syndrome, but hypokalemia is the most common. When mild hypokalemia is reduced, QT interval prolongation is not obvious. When the moderate to severe degree is lowered, the T wave and the u wave are fused, and a long QT syndrome occurs.

(3) slow arrhythmia: is a common cause of long QT syndrome, of which the most common is high atrioventricular block or complete atrioventricular block, the domestic segment reported Tdp accounted for 25.6%; Followed by severe sinus bradycardia, also seen in borderline rhythm, sinus block.

(4) Central nervous system diseases: brain trauma, cerebrovascular accidents, brain tumors, etc. can cause long QT syndrome, especially in subarachnoid hemorrhage.

(5) Coronary heart disease: Although coronary heart disease is not a common cause of long QT syndrome, acute myocardial infarction, patients with variant angina can also have QT interval prolongation and Tdp.

(6) Other causes: myotonic dystrophy, mitral valve prolapse syndrome, primary cardiomyopathy, myocarditis can occur long QT syndrome.

(two) pathogenesis

The pathogenesis of long QT syndrome has not yet been fully elucidated. Many scholars have put forward some hypotheses, but there are two kinds of compelling ones:

1. Repolarization Discrete Hypothesis This theory suggests that the prolongation of Tdp in the QT interval is due to the inconsistent repolarization of different parts of the myocardium.

The ideological basis of this theory can be traced back to 1940, when Wigg et al. studied the pathogenesis of ventricular fibrillation and proposed that different parts of the myocardium are prone to reentry arrhythmia at different repolarization stages, and use "vulnerability". The term "Vulnerability" is used to indicate that when a strong stimulus is applied to different parts of the ventricle, the activation is first spread along the myocardium after repolarization, while the incompletely repolarized myocardial conduction is delayed or retarded, when these are not complete. After the repolarization of the repolarized myocardium, the myocardium was excited and turned back. As a result, a multi-site, unstable reentry channel was formed, resulting in polymorphic ventricular tachycardia and ventricular fibrillation. In 1963, Han et al developed this theory. And put forward the concept of "refractory discrete", that is considered to be prone to arrhythmia when the relative refractory period of different parts of the myocardium is obviously inconsistent.

According to the above hypothesis, many scholars have used repolarization discrete to explore the pathogenesis of long QT syndrome, and believe that QT interval prolongation and Tu wave may reflect a significant delay in the repolarization time of ventricular myocytes action potential in some areas. It shows that the repolarization discrete time of normal myocardium is 31-81ms, and the repolarization discrete time of patients with long QT syndrome can reach 100-270ms, especially in slow heart rhythm, the discrete time increases more obviously.

Tdp in patients with long QT syndrome often occurs in bradycardia, after long RR interval, can also be induced by R on T, and can be inhibited by rapid rhythm, hypokalemia can prolong the relative refractory period of ventricular muscle And increase the repolarization discrete time, some drugs that prolong the ventricular repolarization time, such as quinidine, procainamide, etc. can induce long QT syndrome, etc., which support the theory of repolarization discrete, but the theory Can not fully explain the occurrence of long QT syndrome, for example, this theory can not explain the triggering impulse of long QT syndrome, that is, the first ectopic beat of the reentry process that interrupts the sinus beat Tu wave, according to the discrete theory of refractory Stimulation is easy to induce supraventricular tachycardia during Tu waves, but clinical practice results are not the case.

2. Cardiac Sympathetic Innervation Disequilibrium Theory This theory was proposed by Schwartz in 1975. It is mainly for the adrenaline-dependent long QT syndrome. It is believed that this disease occurs due to excessive sympathetic nerve activity in the left heart. The function on the right side is reduced.

The theoretical basis of this theory comes from experimental and clinical research. As early as 1966, Yanowitz et al. found in the dog's experiment that stimulating the left stellate ganglion or resecting the right stellate ganglion can prolong the QT interval. The same results were obtained in pig experiments. In 1990, Malfatto et al. injected nerve growth factor into newborn rats to produce abnormal sympathetic innervation, which also caused QT interval prolongation. The most powerful support material is clinical observation, for example, Patients with this disease often have sinus rhythm slowing, which is associated with decreased activity of the right stellate ganglion. In 1971, Moss and McDonald first used left stellate ganglionectomy to treat this disease. Recently, Schwartz et al reported 85 In the case of QT syndrome, the arrhythmia was significantly reduced after the left stellate ganglion resection after treatment with blockers.

Although there are many support points in this theory, there are many results that are not consistent.

3. After the depolarization hypothesis is late, many scholars believe that the mechanism of long QT syndrome is after depolarization according to the results of cell electrophysiological research and clinical research. The post-depolarization refers to the spike of action potential. The membrane potential does not immediately return to the resting state, but continues to show some potential fluctuations that are lower in amplitude and last longer. Depending on the time of occurrence, the post-depolarization can be divided into early post-depolarization and delayed post-depolarization. Early post-depolarization (EAD) is an oscillating potential that occurs in the early stage of ventricular repolarization, ie, action potential 2 and 3 phases. The amplitude of this potential can increase when the bradycardia is slow, and the mechanism is still unclear. It is related to the decrease of potassium conductance, the decrease of K outward current or Na inward current, and the increase of Ca2 inward current. All of the above factors can cause the repolarization process to slow down, the action potential duration is prolonged, and the late after depolarization (DAD) is Occurs in the late stage of ventricular repolarization, that is, the potential at the end of the action potential 3 phase. When the heart rate increases, the amplitude of the potential increases, and the mechanism is the abnormal increase of intracellular calcium. After initiation by the inward oscillatory transient current (ITi) induced potential.

Initially, due to post-delay depolarization-dependent epinephrine stimulation, it is speculated that it may be the basis of congenital long QT syndrome, and early post-depolarization has bradycardia dependence or (pacing) cycle length dependence, presumably The basis for acquired long QT syndrome is that the reason for delayed depolarization is the basis of the onset of congenital long QT syndrome. Under the stimulation of adrenaline, the amplitude of depolarization increases after delay, and many experimental and clinical findings are also Prompt for this, for example, in early years, it was found that the canine heart corpus, the coronary sinus and the mitral mitral valve, which are immersed in catecholamines, can produce delayed depolarization. In 1984, Schechter et al. confirmed in vitro experiments. Canine ventricular myocytes can produce delayed depolarization under the action of adrenaline alone. However, recent studies have shown that the pathophysiological mechanisms of congenital long QT syndrome and acquired long QT syndrome are early post-depolarization. .

In the study of congenital long QT syndrome, Levine Bailey and El sherif found that blocking potassium channels and increasing calcium influx induced early post-depolarization, thereby prolonging myocardial repolarization time and triggering activity. Ventricular tachyarrhythmia, in 1981, Hartzler Osborn et al. used conventional bipolar electrode technique to record early posterior depolarization in the right ventricular muscle of patients with Jerye II and Lange Nielsen syndrome, and found that after blocking of the left stellate ganglion, The amplitude was significantly reduced, followed by Bonatti et al. Reporting 10 cases of long QT syndrome, 8 of which were acquired long QT syndrome and 2 were congenital long QT syndrome. All cases were recorded in the early stage by single-phase action potential recording technique. After depolarization, and found that there is no significant difference between congenital and acquired. Recently, EggeLing et al. used signal-average electrocardiography to record the early depolarization of patients with Romano Ward long QT syndrome and found the use of beta blockers. After disappearing, Vincent and Eggeling further speculated that the production of the Harlleg ras 1 gene changed the function of the G protein and caused the potassium ion of the cell membrane. Damage to the channel and beta-adrenergic receptors leads to early post-depolarization and arrhythmias.

The mechanism of acquired long QT syndrome has been well understood, that is, caused by early post-depolarization. This conclusion has been confirmed by many experimental and clinical studies. For example, in 1983, Brachmann et al. used chlorination.Intravenous injection of dogs, resulting in transient sinus rhythm slowing and prolongation of QT interval, T wave morphology changes, followed by polymorphic ventricular tachycardia, characterized by intermittent and long-term QT syndrome patients The performance is exactly the same, because the ruthenium can block the potassium ion flow in the repolarization and the repolarization is delayed. If the Purkinje fiber is immersed in the strontium chloride solution, it can cause early post-depolarization and trigger activity, and the dog is in the body. The internal single-phase action potential recording confirmed that under the action of barium chloride, the waveform similar to the early post-depolarization can cause Tdp. Therefore, many scholars believe that the early post-depolarization is the basis of abnormal Tu waves and arrhythmia. In addition, in vitro experiments In the middle, the Purkinje fiber was immersed in a low-concentration potassium solution and a therapeutic concentration of quinidine. The single-phase action potential recording technique was used to record the early post-depolarization of bradycardia-dependent, further confirming the relationship between the two. Clinical findings have further supported this hypothesis. Bonatli et al. used adsorptive electrodes to record waveforms similar to early post-depolarization in patients with acquired long QT syndrome. Coraboeuf et al. inhibited repolarization potassium ion outward current in acidosis. The Purkinje fiber, recorded in the early post-depolarization, and noted the phenomenon observed by Bonatu, further speculated that the early post-depolarization can be suppressed when the heart rate increases.

4. Mechanism of tachycardia morphological torsion In the early years, Dessertenee believed that two ectopic rhythm points competed with each other and alternately obtained the dominant heart rhythm. Obviously, the tachycardia of two origins can produce specificity if the frequency is not much different. Reverse the shape.

According to the refractory period theory, the refractory period of the ventricular muscles will form two different reentry channels, and the two reentry tachycardia competition dominates the heart rhythm. According to the post-depolarization theory, the arrhythmia may be a continuous QRS complex. The origin of the part gradually moves in the myocardium, and it is assumed that the generation of the posterior depolarization is extensive, but a certain part may be more sensitive to adrenaline or other factors. If the whole ventricular muscle has a post potential, then each may The dominant part has a slowing internal tendency and gives the dominant position to the adjacent part, which causes the origin of the arrhythmia to move throughout the heart. It may also be that the two parts compete for the dominant heart rhythm. The self-terminating of Tdp may be high frequency. Ventricular tachycardia acts as a short burst of impulses that suppresses the potential of the post-depolarization.

It has been demonstrated that patients with long QT syndrome, whether intermittent or specific, develop a torsade-type ventricular tachycardia. In the case of torsades de pointes, the ventricular rate is generally For 160 ~ 280 times / min, and the ventricle almost lost contraction, causing a sudden decrease in cardiac output, blood pressure decreased, patients with loss of consciousness and syncope, some patients can further develop into ventricular fibrillation, and sudden death.

Long QT interval syndrome prevention

1. The prevention of LQTS is mainly to prevent syncope and sudden death caused by arrhythmia.

2. Try to avoid or actively treat the factors that cause the prolongation of QT interval. It is necessary to know the medication situation and the disease condition in time, and find out the situation in time to prevent it from happening.

Long QT interval syndrome complications Complications

This disease can cause serious complications such as syncope and sudden death due to repeated torsades de pointes.

Long QT syndrome symptoms common symptoms arrhythmia nervous sudden death conduction block atrioventricular block syncope

The clinical manifestations of long QT syndrome are mainly recurrent syncope and sudden death caused by torsades ventricular tachycardia. The symptoms of most patients occur during exercise, emotional stress, and when they are excited, syncope usually lasts for 1 to 2 minutes, and some patients die suddenly during sleep. Time.

Long QT interval syndrome examination

ECG diagnosis:

1. QT interval measurement selects the starting point and the end point clearer lead, generally chooses the standard II lead. In recent years, it is recommended to use V3 or V4 lead measurement as the best, measuring the QRS wave starting point to the T wave end point, the average adult does not More than 0.40s, but in judging whether the QT interval is prolonged, the heart rate factor must be considered, because the heart rate is the main determinant of the length of repolarization. The most common heart rate correction formula is the 1926 Bazett formula: QTc=QT/RR QT interval extension is considered when QT>0.44s.

2. Observe the ST and T wave changes.

3. Look for u waves.

4. Diagnosis of tachycardia In the long QT syndrome, various forms of ventricular tachycardia can occur when tachycardia occurs.

Diagnosis and differentiation of long QT interval syndrome

Diagnostic criteria

1. History of patients with episodic syncope and sudden death should be suspected of long QT syndrome, especially by exercise, emotional evoked syncope, suggesting that there may be long QT syndrome, the history of the disease asked about the age of onset, pre-injury, Whether you have emotional excitement, or use anti-arrhythmia drugs such as quinidine, propiamine or a history of heart disease such as atrioventricular block should be understood in detail.

2. The main diagnosis of electrocardiogram is based on male QTc0.47s, and female QTc0.48s can make independent diagnosis. If QTc is between 0.41~0.46s, it should be further combined with medical history and other diagnostic indicators.

3. For the idiopathic long QT syndrome, the diagnostic criteria proposed by Schwartz in 1985 are diagnostic criteria for idiopathic long QT syndrome with greater clinical significance.

Patients with two major criteria or one primary criterion + two secondary criteria can be diagnosed as idiopathic long QT syndrome.

Differential diagnosis

1. It is necessary to identify congenital or secondary long QT syndrome except for prolonged QT interval caused by antiarrhythmic drugs such as amiodarone, -blockers and electrolyte disorders, and intracranial lesions.

2. Must be differentiated from other causes of syncope, such as other malignant arrhythmias, cervical spondylosis, epilepsy, hypotension, hypoglycemia, etc.

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