Congenital and acquired long QT syndrome. Current concepts and management

Abstract

Congenital long QT syndrome (LQTS) is a rare but potentially lethal disease, characterized by prolongation of QT interval, recurrent syncope, and sudden death. In the pregenomic era (1959-1991), sympathetic imbalance was thought to be responsible for this disease. Since 1991 (postgenomic era), 7 LQTS genes have been discovered and more than 300 mutations have been identified to account for approximately 70% of patients affected. Despite the advancement in molecular genetic knowledge, diagnosis of congenital LQTS is still based on electrocardiographic and clinical characteristics. Beta-blockers remain the mainstay treatment. For high-risk patients, the implantable cardioverter-defibrillator (ICD) offer an effective therapeutic option to reduce mortality. Gene-based specific therapy is still preliminary. Further studies are required to investigate new strategies for targeting the defective genes or mutant channels. For acquired LQTS, it is generally believed that the main issue is the blockade of the slow component of the delayed rectifier K+ current (IKr). These IKr blockers have a "reverse frequency-dependent" effect on the QTc interval and increase the dispersion in repolarization. In the presence of risk factors such as female gender, slow heart rate, and hypokalemia, these IKr blockers have a high propensity to induce torsades de pointes. For patients with a history of drug-induced LQTS, care must be taken to avoid further exposure to QT-prolonging drugs or conditions. Molecular genetic analysis could be useful to unravel subclinical mutations or polymorphisms. Physicians not only need to be aware of the pharmacodynamic and pharmacokinetic interactions of various important drugs, but also need to update their knowledge.