The LQTS diagnosis is based on clinical history in combination with ECG abnormalities.6 Important historical elements include symptoms of palpitations, syncope, seizures, or cardiac arrest.3 In addition, a family history of unexplained syncope or sudden death, especially at a young age, should raise LQTS suspicion.5
A variety of ECG findings can be witnessed in LQTS patients.4,5 Although the majority of patients have a QTc >440 ms, approximately one-third have a QTc ≤460 ms, and about 10% have normal QTc intervals.5 Other ECG abnormalities include notched, biphasic, or prolonged T-waves, and the presence of U-waves.4,5 Schwartz et al used these elements to publish criteria (see Table 1, right) that physicians can use to assess the probability that a patient has LQTS.7
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Types of Long QT Syndromes
Because the risk of developing significant dysrhythmias with LQTS is dependent on both the actual QT interval, with risk for sudden cardiac death increased two to three times with QT >440 ms compared with QT <440 ms and the specific underlying genotype, it is important to have an understanding of congenital and acquired LQTS and the associated triggers for torsades de pointes.
Congenital LQTS
Congenital LQTS is caused by mutations in cardiac ion channel proteins, primarily sodium, and potassium channels.5,6 These defects either slow depolarization or lengthen repolarization, leading to heterogeneity of repolarization of the membrane.5 This, in turn, predisposes to ventricular dysrhythmias, including torsades de pointes and subsequent ventricular fibrillation and death.2 Currently, 12 genetic defects have been identified in LQTS. Hundreds of mutations have been described to cause these defects (see Table 2, right).8 Approximately 70% of congenital LQTS are caused by mutations in three genes and are classified as LQTS 1, LQTS 2, and LQTS 3.8 The other seven mutation types account for about 5% of cases; a quarter of LQTS cases have no identified genetic mutations.8
LQTS usually can be distinguished by clinical features and some ECG characteristics, but diagnosis of the specific type requires genetic testing.8,9 The most common types of LQTS are discussed below.
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- Long QT1 is the most common type, occurring in approximately 40% to 50% of patients diagnosed with LQTS. It is characterized by a defect in the potassium channel alpha subunit leading to IKs reduction.9 These patients typically present with syncope or adrenergic-induced torsades, might have wide, broad-based T-waves on ECG, and respond well to beta-blocker therapy.6 Triggers for these patients include physical exertion or emotional stressors, particularly exercise and swimming. These patients typically present in early childhood.1
- Long QT2 occurs in 35% to 40% of patients and is characterized by a different defect in the alpha subunit of the potassium channel, which leads to reduced IKr.9 ECGs in LQTS2 can demonstrate low-amplitude and notched T-waves. Sudden catecholamine surges related to emotional stress or loud noises and bradycardia can trigger dysrhythmias in Long QT2.6 Thus, beta blockers reduce overall cardiac events in LQTS2 but less effectively than in LQTS1.6 These patients also present in childhood but typically are older than patients with LQTS1.6
- Long QT3 is less common than LQTS1 or LQTS2, at 2% to 8% of LQTS patients, but carries a higher mortality and is not treated effectively with beta blockers. LQTS3 is characterized by a defect in a sodium channel, causing a gain-of-function in the INa.4,9 These patients are more likely to have a fatal dysrhythmia while sleeping, are less susceptible to exercise-induced events, and have increased morbidity and mortality associated with bradycardia.4,9 ECG frequently reveals a relatively long ST segment, followed by a peaked and tall T-wave. Beta-blocker therapy can predispose to dysrhythmias in these patients; therefore, many of these patients will have pacemakers implanted as first-line therapy.6