The heterogeneous spectrum of the long QT syndrome.

摘要

The long QT syndrome affects predominantly younger people who demonstrate structurally normal hearts. The underlying defect in the long QT syndrome seems to be genetic mutations in the cardiac ionic channels responsible for generating action potentials. Genetic linkage mapping has identified six genes (designated LQT1-6) associated with the Romano-Ward syndrome; two of these genes (LQT1, LQT5) are associated with the Jervell and Lange-Nielsen syndrome. All of these genes encode potassium channels with the exception of LQT3, which encodes a sodium channel. Mutations affecting these channels will lead to a derangement in ionic flows across the cytoplasmic membranes of cardiac cells, thereby leading to prolongation of the cardiac action potential and lengthening of the QT interval on the surface electrocardiogram. Long QT syndrome is a cause of death in young, otherwise healthy individuals. The heterogeneity of the long QT syndrome also makes prognosis and risk stratification difficult. In patients with long QT syndrome genotypes 1 and 2, as well as during slower heart rates, men exhibited shorter mean QTc interval durations than did women; thus, women possess a predilection for developing torsades de pointes. In female probands with the congenital long QT syndrome, the postpartum period appears to confer a significant risk for experiencing a cardiac event. The study determined that certain combinations, such as exhibiting a QTc of 500ms or more, along with the presence of LQT1, LQT2, and LQT3 (with male gender), conferred a 50% or greater risk of a first cardiac event. Based on the observation that physical exertion and emotional stress are significant triggers for cardiac events in the setting of congenital long QT syndrome (specifically the LQT1 and LQT2 genotypes), avoidance of competitive sports seems to be a prudent lifestyle modification. This heterogeneity stems from the presence of different mutations in the genes that encode cardiac ion channels. The triggering events, prognosis, and risk stratification of the patient with long QT syndrome appear to be influenced by the underlying genotype. The primary treatment of congenital long QT syndrome, i.e., beta-blockade therapy with internal cardioverter defibrillator therapy, appears to be useful in a subset of patients.