Effects of the Ikr-Blocker Almokalant and Predictors of Conversion of Chronic Atrial Tachyarrhythmias to Sinus Rhythm. A Prospective Study

Purpose: To assess the efficacy of the I_kr-blocker almokalant attempting to convert chronic atrial tachyarrhythmias, and to find predictors of conversion, to sinus rhythm.Methods: The electrophysiological effects of a 6-hour infusion of almokalant, to a total dose of 25 ± 4 mg, were assessed by ECG and transesophageal atrial electrograms (TAE) in 100 consecutive patients with atrial fibrillation / flutter (n = 95 / 5) of 8 ± 12 months' duration (range 1 to 99 months).Results: The conversion rate was 32%. The time to conversion was 3.5 ± 2.2 hours. During infusion increases in QT_top (292 ± 35 to 335 ± 44 ms, p < 0.001, after 30 minutes), QT (387 ± 40 to 446 ± 60 ms, p < 0.001), corrected QT (425 ± 30 to 487 ± 44 ms, p < 0.001), and QT dispersion (21 ± 12 to 29 ± 31 ms, p = 0.02), were paralleled by decreases in T wave amplitude (0.31 ± 0.19 to 0.23 ± 0.16 mV, p < 0.001), and atrial rate (425 ± 78 to 284 ± 44 beats per minute (bpm) on ECG, and 396 ± 72 to 309 ± 44 bpm on TAE), with no differences between converters to sinus rhythm and non-converters. Patients with aberrantly conducted beats, and T wave variation, also increased. Calcium antagonists were more common among converters. A decreasing T wave amplitude predicted conversion. Four patients developed torsades de pointes.Conclusions: This study demonstrates class III action of almokalant, with a conversion rate of 32% of long-standing, chronic atrial tachyarrhytmias. An early decrease in T wave amplitude was associated with conversion to sinus rhythm.