Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome.

Abstract

BACKGROUND Several recent experimental and clinical studies have shown that early afterdepolarizations (EADs) are important in the genesis of QTU prolongation and ventricular tachyarrhythmias (VTs) in patients with long QT syndrome. On the other hand, sympathetic stimulation is well known to contribute to the genesis of QTU prolongation and VTs in patients with congenital long QT syndrome. The present study was performed to examine the influence of isoproterenol on the genesis of EADs and on the action potential durations and QTU intervals in patients with congenital long QT syndrome. METHODS AND RESULTS We recorded monophasic action potentials (MAPs) with a contact electrode during right atrial pacing at a constant cycle length of 500 msec before and after continuous isoproterenol infusion (1 microgram/min). MAPs were obtained from the right and left ventricular endocardium in six patients with congenital long QT syndrome (LQT group, 18 recording sites) and in eight control patients (control group, 19 recording sites). Although no EADs were recorded from either group during the control state, MAP duration at 90% repolarization (MAPD90) was significantly longer in the LQT group (n = 18) than in the control group (n = 19) (275 +/- 36 versus 231 +/- 22 msec; p less than 0.0005). Isoproterenol induced EADs in four of the six LQT patients (five of 18 recording sites) but not in the eight control patients (zero of 19 recording sites). The appearance of EADs in the LQT group was associated with an increased amplitude of the late component of the TU complex, and the corrected QT (QTc) interval was prolonged by isoproterenol from 543 +/- 53 to 600 +/- 30 msec 1/2 (n = 6; p less than 0.05). Isoproterenol also prolonged the MAPD90 from 275 +/- 36 to 304 +/- 50 msec in the LQT group (n = 18; p less than 0.005), whereas it shortened the MAPD90 from 231 +/- 22 to 224 +/- 25 msec in the control group (n = 19; p less than 0.05). Moreover, isoproterenol increased the dispersion of MAPD90 (difference between the longest MAPD90 and the shortest MAPD90 in each patient) from 30 +/- 5 to 62 +/- 35 msec in the LQT group (n = 6; p = 0.08), whereas it did not change the dispersion of MAPD90 in the control group (n = 8; 25 +/- 14 versus 27 +/- 14 msec). CONCLUSIONS These results suggest that patients with congenital long QT syndrome have primary repolarization abnormalities and that EADs induced by isoproterenol play an important role in the exaggeration of these repolarization abnormalities.