Congenital Long-QT Syndrome (LQTS)

Definition, Etiology, PathogenesisTop

Congenital long-QT syndrome (LQTS) refers to genetic abnormalities of ion channels (channelopathies) characterized by a long QT interval with an increased risk of polymorphic ventricular tachycardia (VT) (torsades de pointes) and sudden cardiac death (SCD). Overall, 16 types of LQTS caused by >600 mutations have been identified. The most common clinical types are types 1, 2, and 3 (LQT1, LQT2, LQT3).

Clinical Features and Natural HistoryTop

Most patients are asymptomatic. Syncope can occur, commonly caused by ventricular tachyarrhythmia or ventricular fibrillation (VF). Episodes may be triggered by emotions, exercise, or noise. Family history includes syncope or SCD, particularly at a young age. The condition is associated with an elevated risk of SCD, especially in patients with a history of syncope, QTc >500 milliseconds, documented polymorphic VT, prior cardiac arrest, and when combined with syndactyly or deafness syndromes.

DiagnosisTop

Diagnostic Criteria

Diagnosis is based on clinical symptoms, history, genetic studies, and electrocardiography (ECG) results: The normal upper limit for QTc is 470 milliseconds in adult men and 480 milliseconds in adult women, with a significant overlap between the normal spectrum and genetically affected individuals with no or only mild QT prolongation. Concealed long QT may be unmasked by either an exercise test or epinephrine challenge. The occurrence of torsades de pointes depends on the degree of QT prolongation and most of the time is triggered by a short—long—short sequence (ventricular premature beat [VPB]—pause after the VPB—another VPB following the next QRS and tachycardia).

Genetic studies play an important role in the diagnosis of LQTS as well as in prognosis assessment and therapeutic decision-making.

Differential Diagnosis

Acquired LQTS may present with syncope, SCD, or polymorphic VT (torsades de pointes). Causes include electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia) or drugs such as antiarrhythmic agents (amiodarone, sotalol), antihistamines (hydroxyzine, loratadine, terfenadine), antimicrobial agents (erythromycin, clarithromycin, moxifloxacin, trimethoprim), antimalarial drugs (chloroquine), or psychiatric drugs; a complete list of agents can be found at crediblemeds.org. Symptoms of acquired LQTS are very similar to those of congenital LQTS, with ECG also showing prolonged QT intervals. A thorough history including all drugs taken by the patient and measurements of serum potassium, magnesium, and calcium are crucial for diagnosis.

TreatmentTop

Classification of antiarrhythmic drugs: see Table 1 in Cardiac Arrhythmias.

Antiarrhythmic agents: see Table 2 in Cardiac Arrhythmias.

1. Avoid drugs causing QT prolongation.

2. Correct electrolyte disturbances.

3. Eliminate triggers (strenuous activity in patients with LQT1).

4. Beta-blocker treatment at the maximum tolerated doses is indicated, particularly in patients with LQT1 and LQT2. The preferred agents are nadolol and propranolol. In patients with LQT3, flecainide may be effective.

5. Placement of an implantable cardioverter-defibrillator (ICD) is indicated after seeking expert advice for secondary prevention of SCD in patients with a history of cardiac arrest as well as malignant syncope, VT, or both despite beta–blocker therapy. Prophylactic implantation of an ICD may be advisable in patients at high risk of SCD (eg, with extremely long QT, congenital deafness, double mutations, or mutations associated with a particularly high risk of SCD). In patients in whom beta-blockers are contraindicated, poorly tolerated, or ineffective, surgical removal of the left stellate (sympathetic) ganglion is an option.

6. Pacemaker implantation may be useful in patients with congenital or acquired LQTS where ventricular arrhythmias are related to pauses or bradyarrhythmia.