almokalant and Atrial-Fibrillation

To assess the efficacy of the Ikr-blocker almokalant attempting to convert chronic atrial tachyarrhythmias, and to find predictors of conversion, to sinus rhythm.. 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).. The conversion rate was 32%. The time to conversion was 3.5 +/- 2.2 hours. During infusion increases in QTtop (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.. 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.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Electrocardiography; Female; Heart Rate; Humans; Male; Propanolamines; Time Factors; Torsades de Pointes

This study assesses the occurrence of and identifies clinical characteristics associated with the development of aberrant conduction during infusion of the I(kr)-blocker almokalant. Class III drugs may induce aberrant conduction by prolongation of cardiac repolarization, especially during atrial fibrillation (AF). Ninety-two patients with AF received a 6-hour almokalant infusion, aiming at conversion to sinus rhythm (SR). Fiftyfive of the patients received an identical infusion during SR. During almokalant infusion, the number of patients with intermittent QRS aberration during AF increased, from 21% to 80% at rest, and was further increased to 89% during exercise, with predominantly left, and sequential bilateral, bundle branch aberrancy. Patients with aberrant conduction showed signs of more advanced myocardial disease. Predictors of the development of QRS aberration were female gender, arrhythmia duration, and decreased left ventricular ejection fraction, while use of calcium antagonists decreased the probability. No patient showed aberration during regular SR. Twenty-one patients experienced aberrantly conducted supraventricular premature beats. In conclusion, aberrant conduction is common during infusion of the I(kr)-blocker almokalant during AF, and seems to be more frequent in females and in patients with more advanced myocardial disease.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Echocardiography; Electrocardiography; Exercise; Exercise Test; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Potassium Channel Blockers; Propanolamines; Rest; Sex Factors; Torsades de Pointes

Drug-induced increase in QT dispersion has been associated with increased risk of ventricular proarrhythmia. The aim of the present study was to compare QT dispersion during atrial fibrillation and sinus rhythm in the same patients at normal and prolonged ventricular repolarization.. Sixty-one patients who had had chronic atrial fibrillation for 8 +/- 14 months received a 6 h infusion of the Ikr-blocker almokalant, the first 90 min of which are used for this analysis. The following day, after conversion to sinus rhythm, by almokalant (n = 19) or direct current cardioversion (n=42), an identical 90 min infusion was administered. Prior to infusion, there was no difference in precordial QT dispersion between atrial fibrillation and sinus rhythm (29 +/- 12 vs 36 +/- 17 ms, P=ns). During infusion, at prolonged repolarization, the increase in QT dispersion was greater during sinus rhythm than during atrial fibrillation (58 +/- 49 vs 30 +/- 15 ms, P=0.0011, after 30 min infusion). No correlation was found between QT dispersion and the QT or RR interval.. QT dispersion during atrial fibrillation does not differ from QT dispersion during sinus rhythm during normal repolarization. while measurement of QT dispersion during prolonged repolarization, induced by an Ikr-blocker, yielded larger values during sinus rhythm than during atrial fibrillation.

Topics: Action Potentials; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Pacing, Artificial; Electrocardiography; Esophagus; Female; Heart Rate; Heart Ventricles; Humans; Infusions, Intravenous; Male; Propanolamines

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443 +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74 vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24 +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs 40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.

Topics: Aged; Analysis of Variance; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Diuretics; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Odds Ratio; Predictive Value of Tests; Propanolamines; Proportional Hazards Models; Prospective Studies; Torsades de Pointes