REENTRANT ARRHYTHMIAS IN THE SUBACUTE INFARCTION PERIOD - THE PROARRHYTHMIC EFFECT OF FLECAINIDE ACETATE ON FUNCTIONAL REENTRANT CIRCUITS

Background The Cardiac Arrhythmia Suppression Trial has shown that fle cainide was associated with an increased incidence of sudden cardiac d eath in postinfarction patients. The exact mechanism(s) of the proarrh ythmic effects of flecainide remain unclear. We performed a detailed a nalysis of the electrophysiological and proarrhythmic effects of fleca inide in a well-characterized model of reentrant arrhythmias in the su bacute phase of myocardial infarction. Methods and Results Sixteen dog s were studied 4 days after ligation of the left anterior descending c oronary artery. Isochronal mapping of ventricular activation showed th at flecainide facilitated both the induction and sustenance of ventric ular tachycardia, especially at shorter basic cycle lengths. Flecainid e had negligible effect on the length of the are of functional conduct ion block but markedly depressed conduction of the common reentrant wa ve front that was usually oriented parallel to fiber axis. Whole heart mapping was analyzed in combination with basic measurements of the ef fects of flecainide on conduction and refractory properties of both no rmal and ischemic myocardia using a high-resolution cross electrode co nsisting of four orthogonal arms, each comprised of 16 poles with an i nterelectrode spacing of 500 mu m. The electrode was especially design ed to study the effects of the drug on anisotropic conduction as deter mined by a linear regression of activation time and distance in each d irection. Flecainide resulted preferentially in more marked rate-depen dent depression of conduction in ischemic compared with normal myocard ium. On the other hand, the effect of flecainide on refractoriness in both normal and ischemic myocardia was negligible. Conclusions Because flecainide caused no significant change in refractoriness in both nor mal and ischemic myocardia, there was no difference in the dimension o f the potential reentrant pathway, that is, the continuous line of fun ctional conduction block, around which the reentrant wave fronts circu late. Yet, flecainide resulted in significant rate-dependent slowing o f conduction preferentially in ischemic myocardium. The additional slo wing of conduction of the common reentrant wave front coupled with min imal 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 are of block. After flecainide, reentry could be induced in hearts in which reentry could not be induced during control. The sa me proarrhythmic mechanism explains the propensity of nonsustained fig ure-8 reentrant tachycardias to become sustained after flecainide.