Gene mutations associated with atrioventricular block complicated by long QT syndrome.

he congenital long QT syndrome (LQTS) is characterized by abnormally prolonged ventricular repolarization, leading to QT prolongation on the ECG, with frequent development of the polymorphic ventricular tachycardia known as torsades de pointes (Tdp), syncope or sudden cardiac death.1,2 Most cases of congenital LQTS are caused by gene mutations in several ion channels and their interacting proteins. Among these ion channel genes, KCNQ1 (LQTS1), HERG or KCNH2 (LQTS2) and SCN5A (LQTS3) are the most prevalent in the incidence.1,2 Gene mutations are identified in approximately 70% of patients with LQTS, which suggests the presence of unidentified genetic factors in the remaining 30%. On the other hand, all the gene carriers among LQTS family members do not necessarily show clinical signs of QT prolongation and ventricular tachyarrhythmias, including Tdp, suggesting the presence of factors modifying the clinical phenotypes.3 Acquired forms of LQTS are more frequently seen in clinical practice than the congenital forms, and comprise a leading cause of Tdp, indicating a need for careful attention to their genesis. Acquired forms of QT prolongation are supposed not to be caused by gene mutations as a major factor, but can be induced by multiple clinical conditions, including drugs, bradycardia, hypokalemia, congestive heart failure etc.2,4,5 Moreover, the QT interval and abnormal ST-T waves seen in LQTS are variously affected by changes in physiological factors, including serum electrolyte and catecholamine levels, which underlines both the different phenotypes and the time-dependent fluctuations in QT prolongation. Among the inciting conditions, bradycardia is a frequent cause not only of QT prolongation but also the development of Tdp. Kurita et al have demonstrated that patients with atrioventricular (AV) block-induced Tdp display abnormally prolonged QT intervals at slower heart rates (<60 beats/min), compared with those without Tdp.6