Toward a Mechanism‐Based Understanding of Atrial Fibrillation

In light of recent knowledge, it is becoming evident that atrial  brillation is a syndrome with different mechanisms. This shift of perspective in pathophysiologic terms has been spurred on by recognition of the pulmonary veins (PV) as the main source of triggers initiating atrial  brillation and, therefore, the chief anatomic target site for curative ablation therapy.1 A tachyarrhythmia (as an abnormal deviation from sinus rhythm) develops because of an initiating mechanism, is sustained by a maintaining substrate, and is ended by a terminating mechanism, whether natural or exogenous. This undoubtedly also is true for paroxysmal atrial  brillation, whereas chronic atrial  brillation may be considered the prolonged maintenance of a paroxysm that does not terminate. Spontaneous initiations have not been documented in the various animal models used; therefore, only data from the maintenance phase of atrial  brillation can be extrapolated to human atrial  brillation. The irregularly irregular atrial activation characteristic of atrial  brillation, resulting from the presence of multiple changing wavefronts, invalidates the use of sequential site-by-site (point-by-point)mapping and restricts activation analysis to simultaneous multisite mapping. Nevertheless, mapping studies during sustained atrial  brillation in the available models essentially corroborate the results of the early computer simulations of Moe et al.2: multiple drifting reentrant loops (or rotors) produce the typical rapid and irregular beat-to-beat activation observed during sustained atrial  brillation. Data from canine models suggested that 4 to 6 wavelets are required to sustain ongoing atrial  brillation.3 Variations in tissue properties and/or “sources” of high-frequency discharges (originating from outside the  eld) responsible for maintaining the arrhythmia may modify the local wavelet frequency and number. Recent studies focusing on patients with frequent and therefore short-lasting self-terminating paroxysmal atrial  brillation have provided new insights into the evolution of these paroxysms. As exempli ed by the aconitine model of atrial  brillation,4 a burst of short-coupled discharges from consistent anatomic locations typically initiates each paroxysm of atrial  brillation. In the clinical setting, paroxysms are frequently (although not always) preceded by isolated extrasystoles from the same source as the initiating trigger of atrial  brillation. In instances where these extrasystoles are not evident, they may be blocked in the AV node and masked by the previous ST-T segment; or the extrasystolic activity may not capture the atrium or each discharge(s) may directly trigger atrial  brillation. Whereas the mechanism of this arrhythmia and its pathophysiology remain unclear, observations gleaned from clinical work may be able to contribute useful insights.1 ,5 When studied by endocardial activation mapping, initiation of atrial  brillation from within the most common sources (the PVs) begins with near- eld PV activity, which precedes atrial activity and is linked to it with a 1:1 or Wenckebach-type relationship, followed by a second phase of completely irregular and chaotic activity. Sometimes an intermediate period of near- eld continuous activity can be observed. Although successful elimination of arrhythmia by a single or few radiofrequency applications simply indicates the spatial restriction of critical mechanisms (including reentry), the sudden unheralded appearance of PV activation without mappable activity in the interval following the previous sinus P wave suggests either abnormal automaticity or triggered activity as opposed to reentry. Provocation by postpacing pauses with or without supplemental isoprenaline as well as a  xed coupling interval in individual patients (and individual veins) indicates a link to a speci c phase of local repolarization and is concordant with triggered activity. Ectopic activity may be con ned to the veins by conduction block in the region of the venoatrial junction, but the atria may be captured under the in uence of isoprenaline or if the coupling interval is prolonged by as little as 5 msec. These observations further support a relationship of spontaneous PV activity with the end of local or adjacent left atrial repolarization. The not uncommon documentation of simultaneous activity from . 1 PV points to the role of circulatory-hemodynamic factors or diffuse neural autonomic in uences. Decremental conduction to the atria and the documentation of long-duration fractionated electrograms in close juxtaposition to sharp dV/dt spikes within the PVs suggests the presence of signi cant anisotropic conduction. Taken together with the short refractory periods in the PVs, the stage may be set for reentry to occur within or around the PVs (in relatively con ned spatial restriction) when triggered by short-coupled “automatic” discharges. Whether PV anatomy plays a role is not clear, although there may be an association of arrhythmogenicity with aneurysmal dilation.6 Similarly, the role of branching sites (which may affect  ber direction and/or act as anchors for reentry) is not clear. Anisotropy with or without age and hemodynmic related  brotic changes may contribute to the observed association of long PV activation times with arrhythmogenicity.7 The near ubiquity of PV arrhythmogenicity as opposed to the much less common role of the superior vena cava or coronary sinus (all being venous structures connecting to the atria and covered by an extension of atrial myocardium) requires explanation and may be related to left heart hemodynamics and/or a direct connection to the left atrium. The relative paucity of automatic activity con ned to the PVs after proximal (ostial) disconnection may favor triggered activity insomuch as a driving rhythm is required for arrhythmogenesis. When observed after ablation, dissoJ Cardiovasc Electrophysiol, Vol. 12, pp. 600-601, May 2001.