OVERVIEW
有明显遗传倾向的原发性心脏病，常因伴发心室颤动导致猝死
临床表现为反复晕厥发作，心脏性猝死
由于编码心肌离子通道基因突变引起离子通道功能异常而发病
治疗主要包括植入型心脏复律除颤器、导管消融治疗、药物治疗
Definition
Brugada syndrome is a heart condition that can lead to a sudden death attack. Similar cases have been reported in the Philippines as early as 1917, mostly in males, who often suffered convulsions during sleep at night and then died, and were called “Bangungut (screaming in sleep)” at the time, “Lai Tai (death in sleep)”.
In 1986, Prof. Brugada was the first to discover and report its characteristic manifestations and electrocardiogram (ECG) changes, and named it Brugada syndrome.
Brugada syndrome is a hereditary cardiac ion channel disease that develops due to mutations in the gene encoding myocardial ion channels.
Clinically, it is characterized by ST-segment elevation or polymorphism in the right thoracic (V1-V3) leads on the electrocardiogram, no obvious abnormalities of the cardiac structure, polymorphic ventricular tachycardia or ventricular fibrillation and recurrent episodes of syncope, as well as sudden cardiac death [1].
Incidence
The incidence of Brugada syndrome is about 5/100,000 [2], but the exact incidence is difficult to calculate because Brugada waves are dynamic and often insidious.
Epidemiologic studies have found that the incidence of Brugada syndrome is significantly higher in Asian populations than in Western populations, especially in Southeast Asian countries.Brugada syndrome is most common in young men, with a male-to-female ratio of 8:1 to 10:1 [2], and the age of onset is between 30 and 40 years [2].
Classification
Brugada syndrome is categorized into three subtypes depending on the electrocardiographic presentation.
Type I
Right thoracic leads are characterized by ST-segment “dome-type” elevation (J-point) of ≥2 mm, accompanied by T-wave inversion.
Type II
A “saddle-type” elevation of the right thoracic lead, with an elevated J-point (≥2 mm) followed by a gradually decreasing elevated ST-segment (≥1 mm), accompanied by positive or bidirectional T-waves.
Type III
A “saddle-type” or “dome-type” ST-segment elevation of <1 mm in the right precordial leads.
In fact, only type I is directly diagnosed by the characteristic electrocardiogram, while types II and III require a sodium channel blocker provocation test.
Etiology
Causes
The etiology and pathogenesis of Brugada syndrome have not yet been clarified. Recent studies have suggested that Brugada syndrome is a genetically determined disease with autosomal dominant inheritance.
The lesion gene is located in multiple loci of the gene encoding the α-subunit of the sodium channel of the cardiomyocyte membrane, and the inactivation and deceleration of the sodium channel and the increase of the Ito current after the mutation lead to the disappearance of the plateau period of the right ventricular epicardial action potential, which leads to the increase of the myocardial repolarization discretization and the occurrence of 2-phase folding, which constitutes the ST-segment elevation in the leads of V1-V3 and ventricular arrhythmia, and it belongs to the group of abnormalities of the myocardial repolarization [3].
Symptoms
Main symptoms
Patients are mostly young men, usually with syncope or sudden death as the first manifestation, usually without angina attack, chest tightness, dyspnea and other symptoms.
The attack is often preceded by no aura symptoms, and most often occurs at night during sleep (higher frequency between 10:00 p.m. and 8:00 a.m.) or at rest, which may be accompanied by groaning and shallow, slow and difficult breathing [4].
The interictal period may be asymptomatic.
Routine investigations are usually unremarkable, and electrocardiographic monitoring of the attack is usually characterized by polymorphic ventricular tachycardia or ventricular fibrillation. 20% of patients with Brugada syndrome have supraventricular arrhythmias [5].
Consultation
Department of Medicine
Cardiovascular medicine
A routine physical examination reveals abnormal Brugada waves on the electrocardiogram, or symptoms such as recurrent episodes of syncope or nocturnal episodes of near-death respiration, and a family history of sudden cardiac death, prompt medical attention is recommended.
Emergency Department
If syncopal episodes, or nocturnal near-death respiratory episodes, dyspnea, sudden cardiac death occurs, timely consultation is recommended.
Preparation for medical treatment
Preparation for medical consultation: registration, preparation of documents, frequently asked questions
Tips for seeking medical treatment
Sudden cardiac death runs in families, so please collect the medical history of your close relatives, especially the electrocardiogram report, which may be an important reference for your doctor.
Preparation checklist
症状清单
Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.
When did the syncope occur? Is it recurrent? At what time of the day were each episodes?
Has sudden cardiac death occurred? What time of day did it occur?
Were there any episodes of near-death respiration or dyspnea at night?
病史清单
Is there a family history of sudden cardiac death?
Has anyone in the family had Brugada wave ECG changes?
检查清单
Results of tests in the last 6 months to bring to your doctor’s appointment
Electrocardiogram
Drug induced test
Cardiac electrophysiology
Imaging: cardiac-related ultrasound, CT, MRI
Diagnosis
Diagnosis is based on
Medical history
Sudden cardiac death in a relative, Brugada wave ECG changes.
History of recurrent syncope and sudden cardiac death.
Clinical manifestations
Repeated syncopal episodes, or nocturnal episodes of near-death respiration, dyspnea.
Sudden cardiac death occurs most often during nighttime sleep (more frequent between 10:00 p.m. and 8:00 a.m.) or at rest. The attack is often preceded by no aura and may be asymptomatic between attacks.
Some patients may be asymptomatic.
Electrocardiogram
The electrocardiogram in Brugada syndrome is typically characterized by Brugada waves, with type I Brugada waves being an important reference for physicians to diagnose the disease [6].
Drug provocation test
Some patients with Brugada syndrome do not have typical ECG changes and can be diagnosed with the aid of drug provocation test [7]. The test is noninvasive but dangerous, so it is important to have cardiac monitoring and be ready for electrical resuscitation at all times during the test.
Cardiac electrophysiologic examination
Electrophysiologic examination should be performed in all patients with the symptoms described above or in asymptomatic patients with a previous family history of sudden cardiac death, and polymorphic ventricular tachycardia or ventricular fibrillation can be induced by electrophysiologic examination in 50% to 70% of the patients in order to assist the physician in the diagnosis [8]. This test is a precise and invasive method of evaluating the electrophysiologic function of the heart.
Diagnostic criteria
Brugada syndrome can be diagnosed when a patient presents with typical type I Brugada wave ECG changes with one of the following six manifestations and excludes other factors causing ECG abnormalities [9-12]:
出现室颤
出现自行终止的多形性室性心动过速
心脏电生理检查诱发出室颤或室性心动过速
心脏猝死家族史（＜45岁）
家族成员有典型的Ⅰ型Brugada波心电图改变
晕厥或夜间濒死状的呼吸
Brugada syndrome can also be diagnosed in those with type II and III Brugada wave ECG manifestations who have a positive drug provocation test and one of the above six manifestations [9-12].
Differential diagnosis
The diagnosis of Brugada syndrome requires the exclusion of organic heart disease and other conditions that can cause ST-segment elevation in the right thoracic leads, so other diseases that have similar manifestations to the Brugada pattern on the electrocardiogram must be identified [9-12], and a differential diagnosis must be made, which mainly includes the following:
Acute anterior interstitial myocardial infarction
ST segments Vl to V3 are elevated upward in a bow-backed fashion, fusing with the T wave to form a unidirectional curve, and there is a ST-segment drop in the corresponding leads with pathologic Q waves. The electrocardiographic changes have a clear dynamic evolution and are accompanied by symptoms such as chest pain, chest tightness, and changes in myocardial enzymes.
Acute pericarditis
The ST segment is elevated in the universal leads and decreases in the aVR leads, and the ST segment morphology is often plateau-type, and the ST segment elevation is often accompanied by PR segment decrease. t-wave is low and flat, often accompanied by sinus tachycardia, and usually not accompanied by right bundle branch conduction block. At the onset of the disease, there are mostly infection, chest pain, fever and other prodromal symptoms, and some of them may have pericardial friction sound.
Early repolarization syndrome
It is characterized by multi-lead ST-segment elevation, T-wave elevation, and J-wave after QRS wave. ST-segment elevation in early repolarization syndrome is often seen in R-wave dominated leads. Moreover, ST-segment elevation in early repolarization syndrome is relatively fixed, and exercise can normalize it, and there is no right bundle branch block. No malignant ventricular arrhythmia occurs.
Right bundle branch block
The J wave in the Brugada pattern can be pseudo-like R’ wave, which is called right bundle branch block-like electrocardiographic manifestations, but pure right bundle branch block is not accompanied by ST segment Vl-V3 elevation, and right bundle branch block should have a significantly widened and coarsened S wave in the I, aVL and V5~V6 leads.
Pulmonary embolism
Pulmonary embolism can be characterized by right bundle branch block, T-wave inversion and ST-segment elevation in leads Vl-V3. However, pulmonary embolism is characterized by sinus tachycardia, rightward deviation of the electrical axis, paraclockwise transposition, and the characteristic “SIQIIITm”, and there are acute clinical symptoms such as chest pain, dyspnea, and hemoptysis.
Congenital long QT interval syndrome
The resting ECG is characterized by a prolonged QT interval (>0.44s). It is accompanied by T-wave tangential or T(u)-wave electrical alternans, which can lead to the occurrence of ventricular tachycardia, ventricular fibrillation and other malignant arrhythmias. It is more common in children and adolescents, more common in females than males, and has a family history. It may be accompanied by congenital deafness.
There is no right bundle branch block and ST segment elevation on ECG. Tip-twisting ventricular tachycardia is often induced by sympathetic excitation, increased heart rate, progressive prolongation of the QT interval, and premature ventricular beats with long inter-syllabic intervals. In contrast, Brugada syndrome has a normal or shortened QT interval and episodes of ventricular tachycardia or ventricular fibrillation.
Treatment
Aims of treatment: To prevent sudden cardiac death and improve the quality of life.
Principles of treatment: Current treatment methods include implantable cardioverter-defibrillator (ICD), catheter ablation, and drug therapy. ICDs are preferred for high-risk groups, while other treatments may be chosen if they are not suitable.
Implantable Cardioverter Defibrillator (ICD)
The ICD is the only treatment that has been shown to be effective in preventing sudden cardiac death. A past history of sudden cardiac death or evidence of ventricular tachycardia/ventricular fibrillation on ECG, with or without syncope, makes ICD implantation a Class I recommendation.
Syncope may be caused by ventricular tachycardia/ventricular fibrillation when the patient is symptomatic and type I Brugada wave ECG changes are documented, and ICD implantation is a class IIa recommendation.
In patients who are asymptomatic but in whom ventricular fibrillation can be induced by cardiac programmed electrical stimulation, implantation of an ICD is a Class IIb recommendation.
In asymptomatic patients with spontaneous type I Brugada wave electrocardiographic changes, cardiac electrophysiology should be performed, and if ventricular tachycardia/ventricular fibrillation can be induced, an ICD should be administered. However, ICD implantation in asymptomatic patients without these features is not recommended [13].
Catheter ablation therapy
Catheter ablation therapy may be considered in patients whose episodes of malignant arrhythmia cannot be controlled by other measures or who cannot be fitted with an ICD.
Catheter ablation therapy is also recommended for patients with frequent ICD discharges due to repeated episodes of electrical storms.
Quinidine medication and catheter ablation are class I recommendations for patients who are not candidates for an ICD or who have recurrent discharges after ICD implantation.
Medication
Quinidine.
Significantly inhibits Ito and is an effective drug in the treatment of Brugada syndrome. It can normalize the ST segment and prevent 2-phase refractoriness and polymorphic ventricular tachycardia, and is effective in preventing electrophysiological examination-induced ventricular fibrillation by 76% to 90%. Quinidine should be considered for recurrent discharges after electrical storm or ICD implantation [14].
Quinidine may also be used in asymptomatic patients with spontaneous type I Brugada wave ECG changes who refuse or have contraindications to ICD implantation despite indications for an ICD (class IIa recommendation).
Drugs that increase L-type calcium currents
e.g., beta-adrenergic agonists (isoprenaline, dinopamine, mesylate isoprenaline) are effective in treatment. In combination with electrical storms, isoprenaline is a class IIa recommendation. Isoprenaline in combination with quinidine is effective in controlling ventricular fibrillation storms and normalizing elevated ST segments.
Phosphodiesterase III inhibitors
such as cilostazol, may play a role in preventing ventricular fibrillation by increasing cyclic adenosine monophosphate (cAMP) and heart rate increasing calcium current (ICa), decreasing Ito, and correcting ST-segment elevation.
Heart Stabilizing Granules
a traditional Chinese medicine, inhibits Ito, and is effective in combination with low concentrations of quinidine to suppress episodes of polymorphic ventricular tachycardia [13-15].
Prognosis
Cure.
The disease is currently incurable and has a poor prognosis.
If untreated sudden cardiac death may occur at any time, resulting in death.
Implantable cardioverter-defibrillator is the only treatment that has been shown to be effective in preventing sudden cardiac death, while catheter ablation therapy and medication are only used as a means of relieving the symptoms and preventing the occurrence of sudden cardiac death, and are not able to cure the disease.
Hazards
Daily life
Recurrent syncopal episodes may occur without any aura, and the episodes may seriously affect daily work and life.
Mental health
This disease may lead to sudden cardiac death episodes, and there may be no symptoms before and between episodes, so it is impossible to prevent, and the prognosis of this disease is poor, the patient is prone to depression, anxiety and other negative emotions, which seriously affects mental health.
Daily
Daily Management
Diet management
Balanced diet, reasonable combination. Eat fish, poultry, eggs and lean meat in moderation to supplement high-quality protein, and eat more fresh vegetables and fruits to supplement the required vitamins.
Avoid intake of stimulating food containing alcohol, coffee, etc., so as not to induce malignant arrhythmia.
Life management
Prevent colds and flu, and actively use antipyretic drugs and closely monitor the ECG changes when you have a cold or fever. Because the fever caused by cold may induce Brugada wave ECG changes [16].
Reasonable and moderate exercise, not to participate in strenuous physical activities, to avoid aggravating the burden on the heart.
Actively understand the knowledge related to the disease, pay attention to the physical state, reduce psychological pressure, avoid depression, anxiety and other adverse emotions.
Prevention
ICD is the only therapeutic measure proved to be effective in preventing sudden cardiac death. Patients who meet the indications should be treated as early as possible to prevent the occurrence of sudden death and improve the quality of life.
Monitor the sleep status at night, and seek medical attention when syncopal episodes, dyspnea and other manifestations occur.
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