Spectrum of ST-T-wave patterns and repolarization parameters in congenitallong-QT syndrome - ECG findings identify genotypes

Background-Congenital long-QT syndrome (LQTS) is caused by mutations of gen es encoding the slow component of the delayed rectifier current (LQT1, LQT5 ), the rapid component of the delayed rectifier current (LQT2, LQT6), or th e Na+ current (LQT3), resulting in ST-T-wave abnormalities on the EGG. This study evaluated the spectrum of ST-T-wave patterns and repolarization para meters by genotype and determined whether genotype could be identified by E GG. Methods and Results-ECGs of 284 gene carriers were studied to determine ST- T-wave patterns, and repolarization parameters were quantified. Genotypes w ere identified by individual ECG versus family-grouped ECG analysis in sepa rate studies using ECGs of 146 gene carriers from 29 families and 233 membe rs of 127 families undergoing molecular genotyping, respectively. Ten typic al ST-T patterns (4 LQT1, 4 LQT2, and 2 LQT3) were present in 88% of LQT1 a nd LQT2 carriers and in 65% of LQT3 carriers. Repolarization parameters als o differed by genotype. A combination of quantified repolarization paramete rs identified genotype with sensitivity/specificity of 85%/70% for LQT1, 83 %/94% for LQT2, and 47%/63% for LQT3. Typical patterns in family-grouped EC Gs best identified the genotype, being correct in 56 of 56 (21 LQT1, 33 LQT 2, and 2 LQT3) families with mutation results. Conclusions-Typical ST-T-wave patterns are present in the majority of genot yped LQTS patients and can be used to identify LQT1, LQT2, and possibly LQT 3 genotypes. Family-grouped ECG analysis improves genotype identification a ccuracy. This approach can simplify genetic screening by targeting the gene for initial study. The multiple ST-T patterns in each genotype raise quest ions regarding the pathophysiology and regulation of repolarization in LQTS .