Termination of atrial fibrillation by flecainide: mechanistic insights from spectral analysis

Abstract

This editorial refers to ‘Increase in organization index predicts atrial fibrillation termination with flecainide post-ablation: spectral analysis of intracardiac electrograms’ by J. Tuan et al ., on page 488. The pathophysiology of atrial fibrillation (AF) is complex and remains incompletely understood. Atrial fibrillation is usually initiated by rapidly discharging foci, often from within the pulmonary veins, which is then maintained by an abnormal left atrial substrate. Experimental evidence suggests that AF is driven by rapidly discharging foci and waves rotating around fixed structures (mother rotors).1 These drivers give rise to daughter wavelets which propagate around the atria giving the appearance of ‘fibrillatory conduction’. Recurrent paroxysms of AF cause structural and electrophysiological remodelling of the left atrium eventually allowing it to persist.2 Within hours, there are changes in ion channel expression which shorten action potential duration (APD) and effective refractory period (ERP).2 Ultrastructural changes beginning within days of onset of AF include left atrial fibrosis, accumulation of extracellular matrix, and reduced expression of connexin 40 reducing conduction velocity.2 Heterogeneity of refractory periods and zones of slow conduction promote re-entry and support wavelets propagating around the atria. Flecainide exerts its effect through blockade of sodium channels ( I Na) and potassium channels ( I K1 and I KAch), which reduces conduction velocity and increases APD and ERP, respectively.3 These changes have opposing effects on wavelength, which is a product of conduction velocity and ERP. An increase in ERP and AF cycle length was demonstrated in response to flecainide in a canine model of AF.4 A concomitant increase in size and decrease in the number of re-entry wavelets was observed on high-density epicardial mapping. The authors assumed that the prolongation of ERP was the predominant effect, and that re-entry was … *Corresponding author. Tel: +44 207 601 8639; fax: +44 207 601 8627, Email: r.schilling{at}qmul.ac.uk