New Insights into the Arrhythmogenic Substrate of the Long QT Syndrome
A lot has transpired in our understanding of the inherited Long QT syndrome (LQTS) since the first description of a family with prolonged QT interval, deafness, and sudden death by Jervell and Lange-Nielsen in 19571 and a similar family reported in 1958 by Levine, et al.2 Several children with LQTS and sudden death without deafness were reported by Romano, et al. in 19633 and Ward in 1964.4 Numerous LQTS case reports were published during the next several years, and the first specific therapy for this disorder involving antiadrenergic left cervico-thoracic sympathetic ganglionectomy was reported in 1971,5 with beta-blocker therapy introduced a few years thereafter. The Rochester-based International LQTS Registry was initiated in 1979. Using some patients from the LQTS Registry, Keating, et al., reported linkage of LQTS to the Harvey ras-1 locus on chromosome 11 in 1991,6 and within a few years Keating and associates identified the genes for LQT1, 2, and 3 that ushered in the extensive LQTS genotype-phenotype studies during the last 20 years. Various clinical studies identified the duration of the QT interval corrected for heart rate (QTc) as a major risk factor for syncope, aborted cardiac arrest, and sudden death,7-10 and several recent studies highlighted the cardiac risk associated with mutation type and location on the cardiac ion channel membranes.11, 12 Various electrophysiologic studies have suggested the role of action potential prolongation, early after depolarizations, and spatial dispersion of repolarization as the substrate for ventricular tachyarrhythmias and torsade de pointes in this disorder.
- Received September 24, 2014.
- Accepted October 3, 2014.