Pilsicainide

Observational studies

In 40 patients with paroxysmal atrial fibrillation pilsicainide was given either as 75 or 150 mg tds ( n = 25) or as a single oral dose of 100 mg ( n = 15) [ ]. There was conversion to sinus rhythm in 15 of the former and 12 of the latter. There were no significant differences in QT interval duration, but PQ intervals were significantly prolonged. A pacemaker was needed in one patient because of excessive sinus bradycardia; two patients had presyncopal episodes of atrial flutter with 2:1 atrioventricular conduction and wide QRS complexes; and one patient died suddenly during treatment.

In 18 patients with supraventricular tachycardias, the sinoatrial conduction time, the AH and HV intervals, and the effective refractory period of the right ventricle were prolonged 1 h after administration of a single oral dose of pilsicainide [ ]. Ventriculoatrial conduction was blocked in 11 patients (nine via an accessory pathway and two via the atrioventricular node), resulting in suppression of supraventricular tachycardia induction in nine. Pilsicainide increased the heart rate and mean pulmonary arterial pressure and reduced the stroke volume index. PQ interval, QRS width, and QT _c interval were significantly prolonged, and the prolongation of the PQ interval correlated with the plasma pilsicainide concentration. The minimum effective plasma concentration for suppression of supraventricular tachycardia was 0.5 mg/l.

In 22 patients with paroxysmal atrial fibrillation, pilsicainide increased atrial refractoriness and the wavelength index in a tachycardia-dependent manner but did not affect the maximal interatrial conduction delay [ ].

In 34 patients, mean age 66 years, who had 42 episodes of supraventricular dysrhythmias after coronary artery bypass grafting (paroxysmal atrial fibrillation in 34, paroxysmal atrial flutter in six, and sinus tachycardia in two), mostly 2–4 days postoperatively, sinus rhythm was restored in 32 episodes (78%) by a single oral dose of pilsicainide 50 or 100 mg [ ]. Conversion was obtained within 90 min in 44% of episodes and within 3 h in 56%, with a mean conversion time of 119 min. There were no significant changes in blood pressure and no significant adverse reactions.

Cardiovascular

The electrophysiological mechanisms of adverse reactions to class I antiarrhythmic drugs (cibenzoline, pilsicainide, disopyramide, procainamide) in causing orthodromic atrioventricular re-entrant tachycardia have been studied in 14 patients, mean age 37, whose dysrhythmia was inducible despite the use of class I drugs [ ]. In four of six patients with an accessory pathway, class I drugs caused unidirectional conduction block of the accessory pathway (anterograde conduction block associated with preserved retrograde conduction) and enhanced the induction of atrioventricular re-entrant tachycardia with atrial extrastimulation. In eight patients with a concealed accessory pathway, there was outward or inward expansion of the tachycardia induction zone in those who had greater prolongation of the conduction time than the refractory period of the retrograde accessory pathway after class I drugs. During ventricular extrastimulation, induction of bundle branch re-entry after class I drugs initiated the tachycardia in those with accessory pathways.

In a 38-year-old man, who had no apparent baseline electrocardiographic abnormality and who had been resuscitated from ventricular fibrillation, pilsicainide 1 mg/kg was followed by short coupled ventricular extra beats followed by a repetitive polymorphic ventricular tachycardia without apparent J waves, ST elevation, or changes in QRS duration or QT interval; his father had a history of ventricular fibrillation and his brother had multiple episodes of syncope, so a genetic mechanism was likely [ ].

Dysrhythmias due to pilsicainide are likely to be tachydysrhythmias, but in one case of pilsicainide toxicity in the presence of renal impairment there were sinus pauses with marked prolongation of the PQ interval and QRS duration, which resolved on drug withdrawal [ ].

In 12 patients with dual-chamber pacemakers, six of whom had paroxysmal atrial fibrillation, a single oral dose of pilsicainide 150 mg increased pacing thresholds significantly, in line with the plasma pilsicainide concentration [ ]. The atrial pacing thresholds in those with atrial fibrillation were significantly higher than in those without. The authors suggested caution in patients with pacemakers, particularly those with paroxysmal atrial fibrillation. In one case there was ventricular pacing failure immediately after a single oral dose of pilsicainide [ ].

Pilsicainide toxicity can also cause left ventricular dyssynchrony [ ].