Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the Long-QT syndrome

Background-Experimental studies suggest that the interval between peak and end of T wave (Tpe) in transmural ECGs reflects transmural dispersion of repolarization (TDR), which is amplified by beta-adrenergic stimulation in the LQT1 model. In 82 patients with genetically identified long-QT syndrome (LQTS) and 33 control subjects, we examined T-wave morphology and various parameters for repolarization in 12-lead ECGs including corrected QT (QTc; QT/R-R-1/2) and corrected Tpe (Tpec; Tpe/R-R-1/2) before and during exercise stress tests. Methods and Results-Under baseline conditions, LQT1 (n=51) showed 3 cardinal T-wave patterns (broad-based, normal-appearing, late-onset) and LQT2 (n=31) 3 patterns (broad-based, bifid with a small or large notch). The QTc and Tpec were 510+/-68 ms and 143+/-53 ms in LQT1 and 520+/-61 ms and 195+/-69 ms in LQT2, respectively, which were both significantly larger than those in control subjects (402+/-36 ms and 99+/-36 ms). Both QTc and Tpec were significantly prolonged during exercise in LQT1 (599+/-54 ms and 215+/-46 ms) with morphological change into a broad-based T-wave pattern. In contrast, exercise produced a prominent notch on the descending limb of the T wave, with no significant changes in the QTc and Tpec (502+/-82 ms and 163+/-86 ms: n=19) in LQT2. Conclusions-Tpe interval increases during exercise in LQT1 but not in LQT2, which may partially account for the finding that fatal cardiac events in LQT1 are more often associated with exercise.