Inherited Arrhythmia Syndromes

Essentials of Diagnosis

• Includes long QT syndrome, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia (VT)

• Genetic testing for patients with suspected congenital long QT syndrome based on family history, ECG or exercise testing, or severely prolonged QT interval (> 500 ms) on serial ECGs

• Patients with long QT syndrome or catecholaminergic polymorphic VT should be managed long-term with an oral beta-blocker (nadolol or propranolol)

• Implantable cardioverter defibrillator (ICD) is indicated for patients with ventricular arrhythmia or syncope despite medical treatment

General Considerations

• Inherited arrhythmia syndromes may result in life-threatening ventricular arrhythmias due to gene mutations in cardiac channels resulting in abnormal electrolyte regulation across the cardiac cell membrane

• Congenital long QT syndrome

  • Uncommon (1 in 2500 live births)

  • Characterized by a long QT interval (usually > 470 ms) and ventricular arrhythmia, typically polymorphic VT

• Acquired long QT syndrome is usually secondary to

  • Use of antiarrhythmic agents (sotalol, dofetilide), methadone, antidepressant medications, or certain antibiotics

  • Electrolyte abnormalities

  • Myocardial ischemia

  • Significant bradycardia

• Brugada syndrome

  • Accounts for up to 20% of sudden cardiac death in the absence of structural heart disease

  • Most often due to a defect in a sodium channel gene

• Arrhythmogenic right ventricular cardiomyopathy

  • Predominantly affects the right ventricle

  • Characterized by areas of myocardial replacement with fibrosis and adipose tissue that frequently causes ventricular arrhythmia

• Catecholaminergic polymorphic VT is a rare but important cause of sudden cardiac death associated with exercise

• Variable clinical presentation

• Patients may be asymptomatic or have palpitations, sustained tachyarrhythmia, syncope, or sudden cardiac arrest

• In young patients, syncopal episodes may be misdiagnosed as a primary seizure disorder

• Personal and family history should be thoroughly reviewed in all patients

• A 12-lead ECG should be performed with careful attention to any abnormality in the ST segment, T wave, and QT interval

• A corrected QT interval longer than 500 ms on serial ECGs in the absence of a secondary cause (medication or electrolyte abnormality) identifies a high-risk subset of patients with long QT syndrome

• Ambulatory ECG monitoring may be used to evaluate for ventricular arrhythmias as well as dynamic changes to the QT interval or T wave

• Exercise ECG testing may be performed in patients with suspected long QT syndrome to assess for lack of appropriate QT interval shortening with higher heart rates

Medications

• Inherited arrhythmia syndromes

  • Antiarrhythmic medications should be avoided, except when specific genetic abnormalities have been identified and under the direction of a specialist

  • Long-term management depends on the presence of high-risk features

• Long QT syndrome or catecholaminergic polymorphic VT

  • Use of beta-blockers (particularly propranolol or nadolol) is the mainstay of treatment

    • Intravenous beta-blockers may be effective in treating electrical storm due to long QT syndrome or catecholaminergic polymorphic VT

    • Increasing the heart rate, whether by infusion of beta-agonist (dopamine or isoproterenol) or temporary atrial or ventricular pacing, is an effective approach that can both break and prevent the rhythm

• Class Ia, Ic, or III antiarrhythmics

  • Prolong QT interval

  • Avoid or withdraw immediately if being used in patients with long QT syndrome

• Brugada syndrome

  • No reliable medication therapy

  • Focus is on preventing arrhythmias and promptly treating exacerbating triggers, particularly fever

Therapeutic Procedures

• Surgical cervicothoracic sympathectomy should be considered for patients who do not respond to or are intolerant of beta-blockers

• ICD implantation

  • Recommended for patients with an inherited arrhythmia syndrome in whom sudden cardiac arrest is the initial presentation

  • Should be considered in patients with recurrent sustained ventricular arrhythmias or syncope despite medical therapy

When to Refer

• Any patient with known or suspected inherited arrhythmia syndrome or with severe corrected QT interval prolongation (> 500 ms on serial ECGs) should be referred to a cardiologist or cardiac electrophysiologist

• Consultation with a genetic counselor and genetic testing is recommended for patients and family members with a high suspicion of an inherited arrhythmia syndrome