What are the causes and management of arrhythmias in adolescents with Long QT syndrome or Brugada syndrome?

Arrhythmias in Adolescents with Long QT Syndrome and Brugada Syndrome

Causes of Arrhythmias

Both Long QT syndrome (LQTS) and Brugada syndrome are inherited cardiac ion channelopathies that cause life-threatening ventricular arrhythmias in structurally normal hearts, with LQTS primarily involving potassium and sodium channel mutations and Brugada syndrome predominantly caused by loss-of-function mutations in the SCN5A cardiac sodium channel gene. 1, 2, 3

Long QT Syndrome Mechanisms

• Genetic basis: Over 250 different mutations in seven genes have been identified, with the most common being KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3), causing prolonged ventricular repolarization 2, 3
• Arrhythmia mechanism: The prolonged QT interval creates electrical instability that predisposes to torsades de pointes and ventricular fibrillation 4, 3
• Trigger-specific patterns: LQT1 patients experience events during exercise (especially swimming), LQT2 during emotional stress or auditory stimuli, and LQT3 during rest or sleep 1, 5

Brugada Syndrome Mechanisms

• Genetic basis: SCN5A mutations (loss-of-function) are the only definitively identified genetic cause, though 9 different genes have been associated with familial Brugada syndrome 1, 3, 6
• Arrhythmia mechanism: Abnormal sodium channel function creates a substrate for polymorphic ventricular tachycardia and ventricular fibrillation, typically occurring at rest or during sleep 4, 3
• ECG phenotype: Spontaneous ST-segment elevation in right precordial leads (V1-V3) indicates higher risk compared to drug-induced patterns 1

Environmental Triggers That Precipitate Arrhythmias

• Fever: Particularly dangerous in Brugada syndrome, as elevated temperature can unmask the ECG pattern and trigger arrhythmias; aggressive antipyretic therapy is mandatory 5, 6
• Medications: QT-prolonging drugs (certain antibiotics, antihistamines, antipsychotics, antidepressants) can precipitate torsades de pointes in LQTS patients 5, 7
• Electrolyte abnormalities: Hypokalemia and hypomagnesemia potentiate QT prolongation and increase arrhythmia risk in LQTS 5, 7
• Acidosis and ischemia: Can trigger arrhythmias in both conditions by altering ion channel function 6

Management Approach

Long QT Syndrome Management

Beta-blockers are the cornerstone of LQTS therapy and must be initiated in all patients with clinical diagnosis (QTc >470 ms), with nadolol being the preferred agent showing superior efficacy over other beta-blockers. 1, 5

First-Line Pharmacotherapy

• Nadolol is preferred; propranolol and atenolol are acceptable alternatives if nadolol unavailable 5
• Avoid metoprolol as it appears less effective 5
• Beta-blockers reduce adverse cardiac events by >75% 5
• Dosing must be adequate to prevent exercise-induced QT prolongation, verified by exercise stress testing 5

Risk Stratification for Therapy Intensification

• Very high risk (requires intensified therapy): QTc >500 ms, prior cardiac arrest, recurrent syncope despite beta-blockers 1, 5
• High risk: Male adolescents, family history of sudden death before age 40, QTc >500 ms on therapy 1, 5
• Mutation-specific risk: LQT1 and LQT2 have gender-specific and trigger-specific risk profiles that inform management 1

Therapy Escalation Algorithm

1. If syncope or cardiac events occur on adequate beta-blocker therapy: Add left cardiac sympathetic denervation or ICD implantation 1, 5
2. Asymptomatic patients with QTc >500 ms on beta-blockers: Consider therapy intensification 5
3. Prior cardiac arrest: ICD implantation plus beta-blockers is mandatory (Class I recommendation) 1

Critical Lifestyle Modifications

• Strict avoidance of all QT-prolonging medications using resources like CredibleMeds 5, 7
• Maintain normal potassium and magnesium levels at all times; aggressively treat hypokalemia from diuretics or gastrointestinal illness 5
• Aggressive fever management with antipyretics 5
• Exercise stress testing before clearing any physical activity to assess QTc response and beta-blocker adequacy 5
• Avoid competitive sports in high-risk patients 1

Brugada Syndrome Management

No effective pharmacological therapy exists for Brugada syndrome, making ICD implantation the only life-saving option for symptomatic patients or those at high risk, with therapy decisions based primarily on symptom history and ECG phenotype. 1, 4, 3

ICD Indications

• Class I (mandatory): Prior cardiac arrest or documented ventricular fibrillation 1, 4
• Consider ICD: Spontaneous type 1 Brugada ECG pattern with syncope of suspected arrhythmic origin 1
• Asymptomatic patients: Risk stratification is critical; drug-induced ECG patterns alone do not mandate ICD 1, 8

Risk Stratification

• Highest risk: Spontaneous ST-segment elevation in right precordial leads (not drug-induced) 1
• Lower risk: Drug-induced Brugada pattern in asymptomatic patients may not require ICD 8
• Electrophysiology study: May help risk stratify asymptomatic patients, though controversial 4

Pharmacological Considerations

• Quinidine: May be considered as adjunctive therapy to reduce arrhythmic events, though evidence is limited 3
• Avoid sodium channel blockers (flecainide, ajmaline) except for diagnostic purposes, as they can unmask or worsen the ECG pattern 6, 8
• Aggressive fever management is critical as fever can trigger arrhythmias 6

Genetic Testing and Family Screening

Genetic counseling and testing are Class I recommendations for all clinically diagnosed patients with LQTS or Brugada syndrome, with mandatory screening of first-degree relatives using ECG and genetic testing for identified mutations. 1, 5

• Genetic testing identifies causative mutations in up to 60% of young cardiac arrest survivors 1
• LQTS, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome are the most common genotypes identified 1
• Family screening can identify at-risk relatives before symptoms develop 1

Special Considerations for Adolescents

• Young age (<18 years) significantly increases cardiac event risk, with male adolescents having the highest risk during childhood 5
• Drowning/near-drowning events are particularly associated with LQT1 and should prompt evaluation for channelopathies 1
• Exertion-related cardiac arrest in children may indicate LQTS or catecholaminergic polymorphic ventricular tachycardia 1
• Subcutaneous ICD may not be optimal for idiopathic VF due to higher risk of T-wave oversensing 1

Critical Pitfalls to Avoid

• Never use metoprolol as primary beta-blocker in LQTS due to inferior efficacy 5
• Do not discharge patients with drug-induced Brugada pattern without thorough risk assessment; unlike acquired LQTS, these patients may require ICD 8
• Avoid all QT-prolonging medications in LQTS, including ADHD medications which increase syncope/cardiac arrest risk 5
• Never ignore fever in Brugada patients; it can be life-threatening 6
• Do not rely on family history of sudden death alone for risk stratification; it has not proven useful in affected patients 1

Post-Cardiac Arrest Arrhythmia Management

• Many antiarrhythmic drugs are contraindicated in patients with LQTS and Brugada syndrome 1
• Any drug that prolongs QT interval should be avoided in suspected LQTS 1
• Bradycardia during targeted temperature management usually does not require treatment 1
• Pediatric cardiac electrophysiology consultation is often necessary for ongoing arrhythmias after resuscitation 1