Inherited Arrhythmia Syndromes

Background

• Inherited arrhythmias are caused by genetic mutations that disrupt the function of proteins regulating cardiac ion channels.
• Arrhythmias can also result from cardiac structural abnormalities associated with certain types of familial heart disease.
• Types of inherited arrhythmia syndromes include:
  • Congenital long QT syndrome (LQTS)
  • Brugada syndrome
  • catecholaminergic polymorphic ventricular tachycardia (CPVT)
  • short QT syndrome (SQTS)
  • progressive cardiac conduction disease (PCCD)

Evaluation

• Suspect inherited arrhythmias in patients with symptoms consistent with electrophysiological abnormalities, including palpitations, presyncope, syncope, or cardiac arrest, after ruling out potentially reversible causes.
• Diagnosis is made by cardiac monitoring with electrocardiogram (ECG) , Holter monitors, or implantable loop recorders
  • Congenital long QT syndrome (LQTS) is diagnosed by the presence of heart rate-corrected QT interval (QTc) > 460 milliseconds in women and > 450 milliseconds in men.
  • Brugada syndrome is diagnosed by an ECG showing Brugada type I pattern (coved ST-segment elevation ≥ 2 mm) on ≥ 1 right precordial lead (V1 to V3).
  • Catecholaminergic polymorphic ventricular tachycardia (CPVT) is diagnosed by the presence of bidirectional ventricular tachycardia during exercise or as induced by catecholamine administration.
  • Short QT syndrome (SQTS) is diagnosed by the presence of QTc ≤ 330 milliseconds or QTc < 360 milliseconds with clinical features (such as pathogenic mutation, sudden cardiac death, or family history of SQTS).
  • Progressive cardiac conduction disease (PCCD) is diagnosed by the presence of prolonged P-wave duration, prolonged PR interval, and QRS widening with axis deviation.

Management

• See Congenital long QT syndrome (LQTS) and Brugada syndrome for management of these syndromes.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

• Avoid or limit competitive sports, strenuous exercise, and exposure to stressful environments (Strong recommendation).
• Beta blockers
  • Use in symptomatic patients (Strong recommendation).
  • Consider in asymptomatic patients with confirmed pathogenic CPVT mutation (Weak recommendation).
  • Nadolol 1-2 mg/kg/day orally is the preferred beta blocker.
• Consider treatment intensification with combination medication therapy (such as beta blocker plus flecainide), left cardiac sympathetic denervation, and/or implantable cardioverter-defibrillator (ICD) for patients with recurrent sustained ventricular tachycardia or syncope while receiving adequate or maximally tolerated beta blockers (Weak recommendation).
• Other medications in addition to beta blockers
  • Consider flecainide in addition to beta blockers in patients with recurrent syncope or polymorphic/bidirectional ventricular tachycardia unresolved by beta blockers alone (Weak recommendation).
  • A combination of beta blockers plus verapamil is reported to inhibit ventricular arrhythmias in patients with CPVT.
  • Verapamil in addition to beta blockers may decrease premature ventricular contractions better than magnesium sulfate in patients with CPVT.
• Implantable cardioverter-defibrillator (ICD)
  • Use in symptomatic patients who have cardiac arrest, recurrent syncope, or polymorphic/bidirectional ventricular tachycardia unresolved by medications and/or left cardiac sympathetic denervation (LCSD) (Strong recommendation).
  • Do not use in asymptomatic patients (Strong recommendation).
• Do not use programmed electrical stimulation (Strong recommendation).
• Consider left cardiac sympathetic denervation (LCSD) for:
  • patients with recurrent syncope or polymorphic/bidirectional ventricular tachycardia/several appropriate ICD shocks while taking beta blockers (Weak recommendation)
  • patients with contraindications to or who are intolerant of beta blockers (Weak recommendation)
• LCSD is reported to reduce arrhythmic and cardiac events in patients with CPVT.

Short QT Syndrome (SQTS)

• Use observation without treatment for asymptomatic patients (Strong recommendation).
• Implantable cardioverter-defibrillator (ICD)
  • Use in survivors of cardiac arrest, patients with spontaneous persistent ventricular tachycardia with or without syncope, or patients with sustained ventricular arrhythmias if meaningful survival > 1 year expected (Strong recommendation).
  • Consider for asymptomatic patients (Weak recommendation).
• For asymptomatic patients with a diagnosis of SQTS and a family history of sudden cardiac death, consider ICD, quinidine, or sotalol (Weak recommendation).
• Quinidine may be more effective in patients with SQTS and KCNH2 mutations than without KCNH2 mutations.

Progressive Cardiac Conduction Disease (PCCD)

• Use permanent pacemaker (PPM) implantation for patients with:
  • intermittent or permanent third-degree or high-grade atrioventricular block (Strong recommendation)
  • symptomatic Mobitz I or II second-degree atrioventricular block (Strong recommendation)
• Consider PPM for patients with bifascicular block with or without first-degree atrioventricular block (Weak recommendation).
• Consider an implantable cardioverter-defibrillator (ICD) for adult patients with lamin A/C (LMNA) gene mutations and left ventricular dysfunction and/or nonsustained ventricular tachycardia (Weak recommendation).