Congenital Long QT Syndrome

Background

• Selected genetic mutations are associated with abnormalities in cardiac repolarization resulting in prolongation of the QT interval, also known as congenital long QT syndrome.
• Patients with congenital long QT syndrome are at increased risk for ventricular arrhythmias and sudden death.
• The most frequent mutations occur in genes encoding potassium and sodium ion channels in the heart.
• Patients with congenital long QT syndrome may be asymptomatic or present with palpitations, syncope, or cardiac arrest.

Evaluation

• Suspect the diagnosis with an abnormal electrocardiogram (ECG) obtained at rest showing heart rate-corrected QT interval (QTc):
  • > 0.46 seconds in females
  • > 0.45 seconds in males
• Further support for diagnosis may be obtained from patient and family history.
• About 25% of genotype-positive patients have a normal QT interval and clinical diagnosis may require further confirmation via:
  • Schwartz score
  • genetic testing to identify causative mutations

Management

• General approach to treatment is based on risk for first cardiac event before age 40 years.
• Treatment is not necessary in very low-risk patients (such as elderly mutation carriers with normal QT intervals) but these patients should avoid medications known to prolong QT interval (Strong recommendation).
• Intermediate- or low-risk patients may be managed medically and observed over time for persistent symptoms.
• Treat high-risk patients (such as patients who are post cardiac arrest or with numerous arrhythmic syncopal episodes) aggressively with implantable cardioverter defibrillator placement and beta blockers to prevent future episodes (Strong recommendation).
• Lifestyle modifications:
  • Advise all patients to avoid QT-prolonging drugs (Strong recommendation).
  • Refer patients to a clinical expert for risk evaluation of engaging in competitive sports or advise patient to avoid genotype-specific triggers for arrhythmias (Strong recommendation).
  • Patients with long QT syndrome 1 (LQTS1) should avoid strenuous swimming (Strong recommendation).
  • Patients with LQTS2 should avoid exposure to loud noises (Strong recommendation).
• Beta blockers:
  • Use for all patients with clinical diagnosis of LQTS, asymptomatic patients with corrected QT (QTc) ≥ 470 milliseconds, and symptomatic patients with syncope or documented ventricular tachycardia/ventricular fibrillation (Strong recommendation).
  • Consider for patients with molecular diagnosis of LQTS and normal QT interval and asymptomatic patients with QTc ≤ 470 milliseconds (Weak recommendation).
  • Suggested dosing includes propranolol 2-3 mg/kg/day or nadolol 1-1.5 mg/kg/day.
  • Beta blockers are reported to reduce cardiac events in patients with LQTS.
  • Propranolol and nadolol may each be more effective than metoprolol in patients with LQT1 and LQT2 subtypes.
• Sodium channel blockers:
  • Consider the use of sodium channel blockers with caution. While they may normalize QTc interval in patients with LQT3 they may also increase risk of sudden death in patients with overlapping Brugada syndrome.
  • Consider the addition of a potassium-sparing agent in patients with LQT2 if serum potassium levels are not maintained by diet or oral potassium supplements.
• Implantable cardioverter defibrillator (ICD):
  • Use in patients with LQTS that survived cardiac arrest (Strong recommendation).
  • Do not use in asymptomatic patients with LQTS who have not tried beta blocker therapy (Strong recommendation).
  • Consider in patients with LQTS having syncope and/or ventricular tachycardia while on adequate dose of beta blockers (Weak recommendation).
  • Consider for sudden cardiac death (SCD) prophylaxis in patients with LQTS with factors possibly associated with higher risk of cardiac arrest such as LQT2 and LQT3 genotypes (Weak recommendation).
• Left cardiac sympathetic denervation (LCSD):
  • Use for high-risk patients with diagnosed LQTS in whom:
    • ICD therapy is contraindicated or refused (Strong recommendation), or
    • beta blockers are not effective, tolerated, accepted, or are contraindicated (Strong recommendation)
  • Consider in patients who experience either breakthrough events (such as syncope, torsades de pointes, or cardiac arrest) while receiving beta blockers or multiple ICD shocks while taking beta blockers (Weak recommendation).
• A pacemaker is sometimes used in conjunction with an ICD to facilitate titration of beta blockers to more effective doses.
• Follow-up:
  • Monitor QTc interval periodically.
  • For asymptomatic family members:
    • If they have a long QT interval, particularly younger patients, treat them the same as someone who already presented with syncope.
    • If they have a normal QT interval and no symptoms, but have a positive genetic diagnosis, the need for treatment is uncertain, but may be beneficial for patients with a LQT1 genotype or a family history of adrenergic-induced cardiac events.