Adrenergic dependence

Introduction Adrenergic dependent torsade ventricular tachycardia (ADTdpVT) is a type of ion channel abnormality caused by genetic defects in multiple gene mutations, leading to prolonged QT interval and recurrent TDP Clinical syndrome with recurrent syncope and sudden death.

Cause

(1) Causes of the disease

In the past, ADTdp was divided into the following three types:

1. Jervell-Lange-Nielson syndrome (JLNS): characterized by congenital deafness, prolonged QT interval, T wave abnormalities, and torsades de pointes ventricular tachycardia (TDP) under stress and stress Ventricular fibrillation, even syncope, sudden death, is an autosomal recessive hereditary disease.

2. Romano-Ward syndrome (RWS): an autosomal dominant hereditary disease without deafness, the same as JLNS. Ganstorp syndrome is a subtype of RWS with no congenital deafness and a decrease in serum potassium.

3. Scattered hairstyle: no family history, normal hearing, the rest with JLNS.

(two) pathogenesis

In recent years, it has been recognized that genetic mutation is the basic cause of its genetic basis. ADTdp is genetically heterogeneous. It is known that at least six LQTS (LQT1~LQT6) mutation sites are autosomal dominant, five of which have been mapped on chromosomes, and four have established related mutations. JLNS belongs to LQT1 and the related mutation gene is KVLQT1. When the parental parents of JLNS patients both contain KVLQT1 and the abnormal gene is homozygous from parental inheritance, KVLQT1 makes the cardiac ion channel function abnormal, that is, the potassium channel regulation function is abnormal. The apparent delay of myocardial repolarization is characterized by a prolonged QT interval, which is autosomal dominant inheritance. Its gene carriers also have TDP only when conditions such as low potassium. KVLQT1 also produces congenital hearing abnormalities and deafness by encoding hearing elements, which are autosomal recessive. Since the conditions for forming JLNS are so special, JLNS is rare. Other types of LQT constitute RWS, so RWS is caused by a variety of genetic defects and is autosomal dominant. Known related genes are LQT2, LQT3 (HERG), LQT4 (SCN5A), LQT5, LQT6 (KCNE4).

Defective genes mediate cell membrane ion channel regulation dysfunction: SCN5A encodes a sodium channel to increase Na inward current, and its ion mediated may be related to Cl- abnormality. KVLQT1, KCNE1 and HERG encode potassium channels, which reduce K outward current. Therefore, no matter which one or more gene mutations can cause a decrease in K outflow, and/or an increase in Na influx, that is, an inward current increase. This causes the 2-phase and 3-phase time courses of the action potential to be prolonged and the membrane potential to increase. Repolarization delay and incompleteness are generated. The electrocardiogram showed an extension of the QT interval and an abnormal TU wave. Because of this electrical abnormality, the posterior depolarization (especially the early post-depolarization EAD) is easy to reach the threshold potential and cause atrial arrhythmia, which is manifested as TDP or ventricular fibrillation. The formation and maintenance of EAD and TDP are also associated with myocardial M cells. The maintenance of arrhythmia is related to the mechanism of reentry.

JLNS often develops TDP when emotional, mental stress, exercise and fatigue lead to increased heart rate, manifested as paroxysmal syncope or even sudden death. This is related to increased sympathetic tone, increased catecholamines, increased calcium channel opening, and increased Ca2 influx, which promotes the increase of inward current, which increases the imbalance of ion flux inside and outside the cell membrane, and is more prone to post-depolarization, especially EAD and triggered rhythm. Abnormal. Some ADTdp usually do not show QT interval prolongation, only when the sympathetic tone is increased and the inward current is more obvious. Therefore, JLNS and RWS and their associated TDP are called adrenergic-dependent TDP. However, there are also a small number of patients with ADTdp who are in sleep or quiet (as types of HERG and SCN5A gene defects), which are intermittently dependent; at the same time, adrenergic nerve stimulation can also promote the onset of TDP in patients with secondary LQTS caused by drugs. There are a few crossovers between the two types of mechanism.

an examination

Related inspection

Electrocardiogram

ADTdp is rare. About 3,000 children and adolescents die each year in the United States, and about 2/3 of the gene carriers have syncope, and the sudden death rate is about 15%. The age of onset is from a few days after birth to 50 years. The age of the first onset of TDP is mostly in infants and children. Mainly manifested as paroxysmal syncope and sudden death. Most of the syncope occurs when the sympathetic nerves are highly stressed or the tension is suddenly changed (the episodes are characterized by adrenergic dependence), such as strenuous exercise, fatigue, defecation, mental stress, pain, fear, anxiety, nightmares, sound and light stimulation. Wait. The heart rate gradually increases and ventricular premature contraction occurs, which induces TDP, sometimes converted to ventricular fibrillation and sudden death.

The symptoms are not lost, only black, dizziness, and blurred vision, anxiety, screaming, shouting, etc. Severe cases of syncope, loss of consciousness, convulsions, urinary incontinence, sudden death, easily misdiagnosed as epilepsy. There is often burnout or lethargy within 24 hours after the onset. The number of TDP or syncope episodes is as many as one, several times a year, or only one or two times in a lifetime. With the increase of age, the QT interval is gradually shortened, and the number of attacks is correspondingly reduced. JLNS is associated with congenital deafness and skeletal deformities. Family members may have prolonged QT interval, unexplained syncope or sudden death. Clinically, adrenergic-dependent TDP can be classified into the following three types:

1.Typical: The disease is initially in infants and children, and it can be seen that it is delayed to 30 years or adulthood. The main feature is paroxysmal syncope. The reason is caused by TDP. Often induced by sudden movement, fear, pain, shock or emotional agility, adrenergic dependence. Easy to mistake for epilepsy.

2. Atypicality: The incidence of this type is higher than typical. U wave increases and TDP occurs during exercise and mental stress. The clinical manifestations are lighter. It is often due to exercise test or IA class anti-heart rhythm due to ventricular premature contraction. TDP occurs in the treatment of abnormal drugs, and stimulation tests such as exercise tests and instillation of isoproterenol can be induced.

3. Intermediate LQTS Some patients develop TDP when adrenaline is excited, and TDP also occurs when there is a long heartbeat. The former is treated with a beta blocker, and the latter treatment can terminate TDP with isoproterenol. In other people, there is a significant U wave in the electrocardiogram. There is no long interval in the TDP episode, and there is no obvious relationship with physical exertion or emotional agitation.

Differential diagnosis

Distortion of torsade ventricular tachycardia and other polymorphic ventricular tachycardia is difficult, mainly based on its QT interval prolongation, U wave, often no serious organic heart disease, have a special cause, often recurrent and Can be terminated by itself.

In addition, it must be differentiated from general ventricular tachycardia or ventricular fibrillation. The general ventricular tachycardia is characterized by a series of wide QRS waves with almost fixed shape. The ST segment and the T wave can be recognized, and the occurrence often does not stop by itself; the general ventricular tachycardia can also be induced early by the RonT chamber, but the interval between the early compartments is short. The QRS wave and the ST segment and the T wave cannot be recognized during ventricular fibrillation, and the seizure persists and dies.

The disease should be differentiated from paroxysmal syncope and sudden death, such as intermittently dependent TDP, pre-excitation syndrome with extreme atrial fibrillation, idiopathic ventricular fibrillation, Brugada syndrome, sick sinus syndrome, and epilepsy. Identification. Secondary QT interval extension should be excluded.

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