Long QT syndrome
Long QT syndrome (LQTS) is a group of syndromes caused by mutations in the genes encoding cardiac ion channels. It presents with a normal cardiac structure, prolonged QT interval and abnormal T waves, typical torsade de pointes (TdP) during arrhythmic episodes, prone to syncope, convulsions and sudden death.
(i) Clinical presentation
Arrhythmic events and electrocardiographic abnormalities are classified. Patients with LQTS may have atrial arrhythmias, such as atrial fibrillation. The ECG changes are diverse, and prolonged QT interval is the characteristic change of LQTS.
(B) Diagnosis
(1) One or more of the following conditions are present for a definite diagnosis: (1) No secondary factors of QT interval prolongation and Schwartz diagnostic score ≥ 3.5. (2) The presence of a clear pathogenic mutation in at least one gene. (3) No secondary cause of QT interval prolongation and 12-lead ECG QTc ≥ 500 ms.
(2) The following conditions can be diagnosed: unexplained syncope, no secondary cause of QT interval prolongation, no pathogenic gene mutation identified, and 12-lead ECG QTc of 480-499 ms.
(C) Treatment
(1) Lifestyle changes include avoidance of drugs that prolong the QT interval, correction of diarrhea, vomiting, metabolic diseases, and diet imbalance due to weight loss, and prevention and treatment of electrolyte disturbances.
(2) High-risk patients should avoid competitive sports.
(3) β-blockers: those without syncope but with QTc ≥ 470 ms, with syncope or with documented VT or VF should use β-blockers. those with QTc ≤ 470 ms and without symptoms can be used.
(4) LCSD: ICD contraindication or refusal; β-blocker ineffective or intolerant; cardiac events occurring despite β-blocker and/or ICD therapy.
(5) ICD: cardiac arrest survivor; syncope still occurs during β-blocker therapy.
(6) Sodium channel blockers: LQT3 and QTc>500 ms, if a single oral dose can shorten the QTc by more than 40 ms, may be used.
(7) ICD is not recommended in asymptomatic patients with LQTS without a trial of beta-blockers.
Brugada syndrome
Brugada syndrome is a genetic disorder characterized by an elevated ST segment in the right thoracic lead of the ECG, often with varying degrees of heart block, a potential risk of malignant arrhythmias, and a family history of SCD.
(A) Clinical manifestations
Clinical manifestations include VF or SCD survival (more frequent at night than during the day), syncope, nocturnal near-death breathing, palpitations, and chest discomfort. These symptoms often occur at rest or during sleep and in febrile or otherwise vagally stressed states, and rarely during exercise. Symptoms appear mainly in adulthood, with a mean age at death of (41±15) years.
(ii) Diagnosis
The following ECG features are recommended for the diagnosis of Brugada syndrome type I: spontaneous or class I antiarrhythmic drug-induced type I ST-segment elevation ≥ 2 mm recorded in at least 1 of the right thoracic leads located at the 2nd, 3rd, or 4th intercostal space. Type I ST-segment elevation can be induced by a class I antiarrhythmic drug provocation test. (3) Clinical confirmation of Brugada syndrome: In addition to ECG features, VF or polymorphic VT or family history of sudden death should be recorded.
(C) Treatment
(1) Lifestyle changes: Avoid drugs that may induce or worsen ST-segment elevation in the right thoracic leads; avoid excessive alcohol consumption; treat fever with antipyretic drugs promptly.
(2) Survivors of cardiac arrest and/or patients with documented spontaneous sustained VT with or without syncope should have an ICD implanted.
(3) Patients with spontaneous type I ECG changes and a clear history of syncope due to ventricular arrhythmias may have an ICD implanted.
(4) Diagnosis of Brugada syndrome, where VF is induced by programmed electrical stimulation, may be considered for ICD implantation.
(5) Asymptomatic Brugada syndrome with a family history of sudden death and drug-induced type I ECG changes only should not be implanted with an ICD.
(6) Application of quinidine: (1) Diagnosis of Brugada syndrome with a history of arrhythmic storm (more than 2 episodes of VT or VF within 24 h) should be used. Patients with a diagnosis of Brugada syndrome and one of the following conditions should be used: patients who meet the indications for ICD implantation but have a contraindication to ICD implantation or refuse to implant an ICD; patients with a clear history of supraventricular arrhythmias requiring treatment.
(7) Isoprenaline: for suppression of arrhythmic storms in patients with Brugada syndrome.
(8) Catheter radiofrequency ablation: diagnosis of Brugada syndrome with a history of arrhythmic episodes or recurrent ICD with inappropriate electrical shocks.
Catecholamine-sensitive polymorphic ventricular tachycardia
Catecholamine-sensitive polymorphic ventricular tachycardia (CPVT) is a genetic disorder in which the heart is structurally normal and sensitive to catecholamines. It is characterized by biphasic ventricular tachycardia (bVT), often manifested as syncope, cardiac arrest and SCD, and occurs in young people.
(i) Clinical presentation
The first onset of CPVT is usually between 10 and 20 years of age, and typically presents with syncope or sudden death induced by exercise or emotional stress, mostly in early childhood. The diagnosis of CPVT is often delayed by misdiagnosis of syncope as epilepsy. 30% of CPVT patients have a family history of exercise-related syncope, convulsions, and sudden death, and family history can help diagnose CPVT.
(ii) Diagnosis
The diagnosis is made when any 1 of the following is met: (1) age <40 years, cardiac structure, no abnormal resting ECG, bVT or polymorphic premature ventricular beats or polymorphic ventricular tachycardia (pVT) induced by exercise or catecholamines that cannot be explained by other causes. (2) Patients carrying a pathogenic genetic mutation (prevalent or family members). (3) A family member of a CPVT presentee who has exercise-induced ventricular premature contractions or bVT or pVT when organic heart disease is excluded.
2. The diagnosis can be made by meeting the following criteria: age > 40 years, no abnormalities in cardiac structure and coronary arteries, normal resting ECG, and exercise or catecholamine-induced bVT or polymorphic premature ventricular contractions or pVT that cannot be explained by other causes.
(iii) Treatment
Recommendations for the treatment of CPVT
1. All patients with CPVT should follow the following lifestyle: (1) Limit or avoid competitive sports. (2) Limit or avoid vigorous activity. (3) Avoid mental stress.
2. All patients with symptomatic CPVT should use beta-blockers.
3. β-blockers can be used in carriers of disease-causing mutations without clinical manifestations (patients with recessive positive mutations).
4. β-blockers combined with flecainide: recurrent syncope or bVT/pVT in patients with confirmed CPVT despite taking β-blockers alone.
5. Implanted ICD: Patients with diagnosed CPVT with cardiac arrest, recurrent syncope, or bVT/pVT despite optimal drug therapy and/or LCSD.
6. ICD is not recommended as a stand-alone treatment for asymptomatic CPVT patients.
7. LSCD: Confirmed CPVT with recurrent syncope or bVT/pVT despite beta blockers alone or several documented appropriate ICD discharges; intolerance of beta blockers or contraindications to beta blockers.
Short QT syndrome
Short QT syndrome (SQTS) is a rare ion channel disorder with QTc < 330 ms, hyperacute T waves, and a very short T-wave peak to T-wave end time frame. SQTS is a rare ion channel disease with QTc < 330 ms, hyperacute T waves, and a very short T-wave peak to T-wave end time. The first clinical symptoms are early, with onset in childhood, and may be a cause of SCD in infants.
(a) Clinical diagnosis
1. If QTc ≤ 330 ms, SQTS is diagnosed.
2. SQTS is diagnosed if QTc < 360 ms and one or more of the following conditions are present: family history of sudden death with a causative mutation, family history of SQTS, age ≤ 40, and survivor of VT/VF without organic heart disease. The panel recommends QTc ≤ 330 ms as a diagnostic criterion.
(ii) Treatment
SQTS with persistent VT/VF should be treated with ICD implantation. quinidine can prolong the QT interval and may be effective. Other antiarrhythmic drugs, including class III antiarrhythmic drugs such as sotalol, are less effective in prolonging QTc in patients with type I SQTS, but may be effective in other subtypes.
Premature repolarization syndrome
Premature repolarization syndrome is characterized by two or more adjacent J points and ST-segment elevation on the electrocardiogram. Premature repolarization ECG changes are also seen in young adults who are physically active, athletes, and African-Americans. In addition, early repolarization ECG changes are associated with high vagal tone, hypothermia, hypercalcemia, bradycardia, prolonged QRS time limit, short QT intervals, and left ventricular hypertrophy.
(A) Diagnosis
(1) J-point elevation ≥ 1 mm on 2 or more consecutive inferior and lateral leads on standard 12-lead ECG in patients recovering from unexplained VF polymorphic VT.(2) J-point elevation ≥ 1 mm on 2 or more consecutive inferior and/or lateral leads on standard 12-lead ECG at chest in patients with SCD without positive autopsy findings.(3) J-point elevation ≥ 2 mm on 2 or more consecutive inferior and/or lateral leads on standard 12-lead ECG. J-point elevation ≥ 2 mm on 12-lead ECG.
(ii) Treatment
1. ICD implantation is recommended for patients with a history of previous cardiac arrest with premature repolarization syndrome.
Isoproterenol is effective in suppressing electrical storms in patients with prodromal syndrome.
3. In patients with prodromal syndrome who have had an ICD implanted, quinidine can be used as a secondary prevention measure to suppress VF.
4. Consider ICD implantation in family members of patients with prodromal syndrome with syncope who have at least 2 inferior or lateral leads with ST-segment elevation ≥ 1 mm on the ECG.
5. ICD implantation may be considered in asymptomatic patients with a clear family history of sudden death, with or without the causative genetic mutation, who have a high-risk ECG presentation (high J-wave amplitude, horizontal or downward-sloping ST-segment elevation).
ICD implantation is not recommended in asymptomatic patients with only early repolarization ECG manifestations.
For patients with confirmed early repolarization syndrome, ICD implantation is recommended, and if ICD cannot be performed, long-term oral quinidine is recommended. In patients with early repolarization syndrome combined with electrical storm, intravenous isoproterenol is very effective.
Progressive cardiac conduction disorders
Progressive cardiac conduction disorder (PCCD) is a disease of unknown etiology characterized by abnormalities in the atrial and intraventricular conduction systems.
(i) Clinical manifestations
PCCD is predominantly inherited in an autosomal dominant fashion. Patients who already have bifascicular block and other ECG abnormalities may be asymptomatic, while some may develop high and third degree AV block with significant symptoms. There are 3 risk stages: neonatal, adolescence and middle age. The earlier the onset of the disease, the more severe the conduction dysfunction, and the onset of the disease in the newborn can cause sudden neonatal death. The disease is more common in males than females.
(ii) Diagnosis
Diagnostic criteria: Progressive cardiac conduction abnormalities without a clear cause in patients < 50 years of age, normal heart structure and absence of skeletal muscle myopathy, and a family history of PCCD are helpful.
(iii) Treatment
In the initial or early stages of the disease, there may be only right bundle branch block or combined left anterior branch block, which does not cause significant hemodynamic abnormalities, and no specific pharmacological treatment is required. When the patient is combined with other types of arrhythmias and needs to apply antiarrhythmic drugs, attention should be paid to the effect of the drugs on the cardiac conduction system, and it is advisable to start with small doses and give pacing protection if necessary. Patients with rapidly progressing disease may be treated with hormone therapy.
Unexplained cardiac arrest: idiopathic VF
A survivor of cardiac arrest without a clear cause, which cannot be identified by known methods, is called idiopathic VF.
(i) Diagnosis
Recommendations for the diagnosis of idiopathic VF: after resuscitation from cardiac arrest, especially in patients in whom VF has been documented and in whom cardiac, respiratory, metabolic, and toxic etiologies have been excluded by clinical evaluation.
Recommendations for evaluation of idiopathic VF: (1) Genetic testing can be helpful in the diagnosis of idiopathic VF when there is clinical suspicion of a genetic disorder in the patient and/or family members. (2) Genetic screening is not necessary for those patients with idiopathic VF whose clinical evaluation has ruled out hereditary arrhythmia disease.
(ii) Treatment
(1) ICD implantation is recommended for patients with a diagnosis of idiopathic VF. (2) In patients with a diagnosis of idiopathic VF who have an ICD implanted, or who have a contraindication to ICD implantation or who refuse ICD implantation, quinidine may be considered as an antiarrhythmic agent under the guidance of electrophysiological examination or based on experience. (3) In patients with a diagnosis of idiopathic VF with monomorphic ventricular premature beats, implantation of an ICD may be accompanied by consideration of Purkinje potential ablation of the ventricular premature beats that induce VF. (4) If a first-degree relative of a patient with idiopathic VF presents with unexplained syncope and no corresponding disease is detected by examination, ICD implantation may be considered after adequate communication with the patient.
Unexplained SCD
Unexplained SCD includes SUCS and sudden unexplained death in infancy (SUDI), which is often caused by acquired heart disease, such as acute myocardial ischemia and dilated cardiomyopathy with heart failure, in which case the etiology is clear.
Sudden arrhythmic death syndrome (SADS) is SCD in which a non-cardiac cause has been ruled out and the morphology of the heart is completely normal after autopsy and toxicological examination.
(i) Diagnosis
(1) Sudden unexplained death occurs in patients >1 year of age and is referred to as SUDS. (2) SUDS deaths with negative pathology and toxicology are referred to as SADS.
(2) Sudden unexplained death in patients <1 year of age with negative pathology and toxicology is referred to as SUDI.
(ii) Treatment
1. Recommendations for therapeutic intervention for members of the SUDS family.
(1) Genetic screening of first-degree relatives of patients with SUDS is recommended when mutations in pathogenic genes that increase the risk of sudden death are identified in molecular autopsies of SUDS patients.
(2) All first-degree relatives related to a patient with SUDS should be screened for resting ECG, high-grade right heart lead ECG, exercise stress test, and echocardiography. Relatives who are carriers of gene mutations and have a history of palpitations, arrhythmias, and syncope should be evaluated as a priority.
(3) Family members of younger patients with SUDS may present with signs and/or symptoms at an older age. Therefore, younger family members of patients with SUDS should be evaluated on a follow-up basis and all family members should be reevaluated clinically if a recurrence of SUDS or SUDI events occurs.
(4) First-degree relatives with SUDS should be examined for ambulatory ECG, signal-averaged ECG, cardiac MRI, and lc class antiarrhythmic drug provocation test.
(5) Infusion of epinephrine may be considered for the evaluation of first-degree relatives of patients with SUDS.
2. Recommendations for therapeutic intervention for members of the SUDI family.
(1) Genetic screening of first-degree relatives of patients with SUDI is recommended when pathogenic gene mutations are identified on molecular autopsy in SUDI patients, regardless of whether they are associated with a high risk of sudden death.
(2) First-degree relatives of SUDI patients with a history of inherited heart disease or a family history of SUDS or SUDI death should be evaluated by resting ECG and exercise stress test. First-degree relatives with a history of cardiac arrhythmia or syncope should be evaluated first.
(3) Younger family members of patients with SUDI who have a family history of inherited heart disease or death from SUDS or SUDI may present with signs and/or symptoms of the disease at an older age. Therefore, younger members of the family of a patient with SUDS are evaluated on a follow-up basis. All family members should be reevaluated if there is a recurrence of SUDS or SUDI events in the family.
(4) First-degree relatives of patients with SUDI may be evaluated with resting ECG and exercise stress test.