Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome.

AIMS: Differences in the sensitivity of the genotype of the congenital long QT syndrome to sympathetic stimulation have been suggested. This study compared the influence of sympathetic stimulation on continuous corrected QT (QTc) intervals between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome. METHODS AND RESULTS: We recorded a 12-lead electrocardiogram continuously before and after bolus injection (0.1 microg x kg(-1)) of epinephrine followed by continuous infusion (0.1 microg x kg(-1) min(-1)) in 12 LQT1, 10 LQT2, 6 LQT3, and 13 control patients. The QT intervals and previous RR intervals of all beats were measured semi-automatically, and the QTc intervals of all beats were calculated by Bazett's method. The dynamic response of the RR interval to epinephrine was no different between the four groups. The QTc was prolonged remarkably (477+/-42 to 631+/- 59 ms; P<0.0005, % delta prolongation =+32%) as the RR was maximally decreased (at peak of epinephrine), and remained prolonged at steady state conditions of epinephrine (556+/-56 ms; P<0.0005 vs baseline, +17%) in LQT1 patients. Epinephrine also prolonged the QTc dramatically (502+/-23 to 620+/-39 ms; P<0.0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened to baseline levels at steady state (531+/-25 ms; P=ns vs baseline, +6%). The QTc was much less prolonged at peak of epinephrine in LQT3 (478+/-44 to 532+/-41 ms; P<0.05, +11%) and controls (394+/-21 to 456+/-18 ms; P<0.0005, +16%) than in LQT1 and LQT2 patients, and shortened to the baseline levels (LQT3; 466+/-49 ms, -3%, controls; 397+/-16 ms, +1%; P=ns vs baseline) at steady state. CONCLUSION: Our data suggest that the dynamic response of ventricular repolarization to sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may explain why the trigger of cardiac events differs between the genotypes.