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.