Reentrant arrhythmias in the subacute infarction period. The proarrhythmic effect of flecainide acetate on functional...

The Cardiac Arrhythmia Suppression Trial has shown that flecainide was associated with an increased incidence of sudden cardiac death in postinfarction patients. The exact mechanism(s) of the proarrhythmic effects of flecainide remain unclear. We performed a detailed analysis of the electrophysiological and proarrhythmic effects of flecainide in a well-characterized model of reentrant arrhythmias in the subacute phase of myocardial infarction.

Sixteen dogs were studied 4 days after ligation of the left anterior descending coronary artery. Isochronal mapping of ventricular activation showed that flecainide facilitated both the induction and sustenance of ventricular tachycardia, especially at shorter basic cycle lengths. Flecainide had negligible effect on the length of the arc of functional conduction block but markedly depressed conduction of the common reentrant wave front that was usually oriented parallel to fiber axis. Whole heart mapping was analyzed in combination with basic measurements of the effects of flecainide on conduction and refractory properties of both normal and ischemic myocardia using a high-resolution cross electrode consisting of four orthogonal arms, each comprised of 16 poles with an interelectrode spacing of 500 microns. The electrode was especially designed to study the effects of the drug on anisotropic conduction as determined by a linear regression of activation time and distance in each direction. Flecainide resulted preferentially in more marked rate-dependent depression of conduction in ischemic compared with normal myocardium. On the other hand, the effect of flecainide on refractoriness in both normal and ischemic myocardia was negligible.

Because flecainide caused no significant change in refractoriness in both normal and ischemic myocardia, there was no difference in the dimension of the potential reentrant pathway, that is, the continuous line of functional conduction block, around which the reentrant wave fronts circulate. Yet, flecainide resulted in significant rate-dependent slowing of conduction preferentially in ischemic myocardium. The additional slowing of conduction of the common reentrant wave front coupled with minimal changes in the length of the reentrant pathway allowed additional time for the wave front to reexcite normal myocardium on the proximal side of the arc of block. After flecainide, reentry could be induced in hearts in which reentry could not be induced during control. The same proarrhythmic mechanism explains the propensity of nonsustained figure-8 reentrant tachycardias to become sustained after flecainide.