The aim of the present study was to investigate the effects of
almokalant on sustained reentrant
supraventricular tachycardias. Reentrant
tachycardias were induced, using transesophageal atrial stimulation, in 82 patients with
atrioventricular reentrant tachycardia (n = 54) or
AV nodal reentrant tachycardia (n = 28). After a baseline procedure during which the
tachycardia was induced and overdrive terminated, the
tachycardia was reinduced and studied during 12 minutes of infusion of either placebo or
almokalant, aiming at plasma concentrations of 20, 50, 100, and 150 nmol/l. Each patient was studied at two dose levels during the same procedure. There was an increase in the RR interval during
tachycardia of 6% at 100 nmol/l (p = 0.001 vs. baseline
tachycardia). The QT interval during
tachycardia increased by 5% (p = 0.001) at 50 nmol/l and by 10% (p = 0.001) at 100 nmol/l.
Bundle branch block during
tachycardia developed in 13% during
almokalant infusion, aiming at 20 nmol/l, in 25% at 50 nmol/l, in 50% at 100 nmol/l, and in 33% at 150 nmol/l. Rapid baseline
tachycardia, increasing
almokalant dose, and an increasing number of induced
tachycardias correlated with the appearance of
bundle branch block. In six patients with
AV nodal reentrant tachycardia, 2:1
AV block occurred, in all cases preceded by
bundle branch block. The QT prolongation during sustained
tachycardia was larger in patients who were noninducible at the same plasma concentration level than in the inducible patients.
Almokalant caused
bundle branch block and 2:1
AV block during sustained
supraventricular tachycardia. These findings emphasize the importance of studying
drug effects at rates in the range of clinical
tachycardias that expose the conduction system to the limits of its refractoriness.