Atrial Fibrillation and Wolff‐Parkinson‐White Syndrome:

Atrial fibrillation (AF) and preexcitation may be deadly companions. A rapid preexcited ventricular response during AF may lead to ventricular fibrillation and sudden cardiac death in otherwise healthy and mostly young patients. Although rare, efforts have to be undertaken to identify patients with accessory pathways (AP) at risk of AF occurrence. This may be especially true when considering the additional implications of AF in patients at risk for thromboembolic events. Up to 38% of patients with APs may have episodes of AF. In some patients, recurrent AF after AP ablation may occur.1–10 This implies that AP-dependent and AP-independent (intrinsic) mechanisms are involved. Pulmonary vein (PV) triggers have been documented to be the initiators of paroxysms of idiopathic AF. In addition, an atrial substrate appears to be mandatory for ongoing AF. So, why is the incidence of AF relatively higher in patients with the Wolff-Parkinson-White syndrome (WPW) when compared with non-WPW patients? Do the mechanisms of trigger and substrate differ in these two populations? In this issue of the Journal, Derejko et al.11 for the first time give a conclusive analysis of the electrophysiology of the PVs in patients with APs in relation to a history of AF. In patients with idiopathic AF, the PVs play a crucial role in the initiation of AF episodes and electrical disconnection of the PVs may lead to freedom from AF. Derejko et al.11 investigated the role of the PVs in patients with WPW syndrome comparing patients with and without a history of AF. In 16 patients with WPW and a history of AF, the effective refractory periods (ERPs) of the PVs were significantly shorter than in 15 control patients without a history of AF. This finding is consistent over all 4 PVs and is similar to observations made in patients with paroxysmal AF who do not have a WPW. Jais et al.12 documented mean PV-ERPs in patients with paroxysmal AF to be significantly shorter than in control patients (185 milliseconds compared to 282 milliseconds). Derejko et al.11 documented even shorter PV-ERPs in patients who had a recurrence of AF after effective AP ablation, although the number of patients is limited (N = 3). It is of interest that the PV-ERPs in patients with idiopathic AF are shorter than the presented data by Derejko et al.11 in WPW patients. In addition, Jais et al.12 documented PV-ERPs as short as 60 milliseconds contrary to the data presented for WPW patients (shortest PV-ERP 130 milliseconds). Derejko et al.11 were able to evaluate only 3 patients with AF recurrences and these differences may be explained by the low number of patients. In addition, Derejko et al.11 documented that the conduction delay when pacing from within the left superior or right superior PV to the proximal coronary sinus is significantly longer in patients with a history of AF. These findings may imply that the electrophysiological properties of WPW patients with a history of AF are different from those without a history of AF, even though it may only be speculated whether this is a consequence of electrical remodeling or an intrinsic factor. It would have been interesting to know whether differences in electrophysiology are detected when comparing studies before and after AP ablation. The shorter PV-ERPs in patients with recurrences of AF appear to indicate that the PVs play a more enhanced role in the perpetuation of AF after effective AP ablation. Jais et al.12 identified a striking difference in patients with AF without WPW. The ERPs of the PVs were significantly shorter than those of the left atrial appendage. This gradient in refractory periods is a consistent and exclusive finding in patients with AF. A trend toward the same ERP gradient was seen in WPW patients with a history of AF but not in those without prior AF episodes. The gradient in both patient groups with AF is because of the shorter ERPs of the PVs. It would have been interesting to learn more about the subgroup of WPW patients with recurrence of AF after AP ablation. It may be speculated, that in these patients PV-ERPs would be shorter indicating the arrhythmogeneity of the PVs. Potentially, the documented short ERPs of the PVs in patients with a history of AF may be a consequence rather than an arrhythmia-independent finding. In the presented study by Derejko et al.,11 only patients without a history of tachycardia within 7 days before the electrophysiological study were included. A second phenomenon consistent with findings in idiopathic AF patients is the documented longer veno-atrial conduction delay. In the presented study by Derejko et al.,11 no basket catheters were used to identify the exact site of conduction delay. So, no analysis of intra-PV conduction disturbances and the occurrence of fractionated and long-duration potentials were possible. Changed circumferential activation sequences and PV breakthroughs have been documented in patients with AF when performing PV programmed stimulation. The presented electrophysiological properties of patients with WPW and AF compared with those without AF are similar to the findings in patients without WPW. The data favor an AF mechanism including a potential trigger area (indicated by the short ERPs in the PV region) and a changed electrophysiological atrial substrate (indicated by differences in conduction times). Specifically, shorter PV-ERPs than in the rest of the left atrium may lead to dispersion of refractoriness. It would have been interesting to see whether, at least in some patients with a history of AF, changes in ERPs comparing pre- to postablation data were identified. There are discrepant findings on atrial electrophysiological parameters when comparing before and after AP ablation data. Whereas atrial ERP appears to be prolonged after surgical cryo-ablation of APs, the ERP remained unchanged after catheter ablation.13 Atrial vulnerability defined mostly by maximum atrial conduction delay decreased after AP ablation in patients without a history of AF and remained unchanged in patients with a history of AF. Further studies are needed on the predictive value of electrophysiological parameters assessed in WPW patients in regard to AF recurrence after AP ablation. The high incidence of AF in 10–38% of patients with APs is well known but mostly unexplained.1,2,4,14 Many studies have tried to evaluate factors predictive of AF in patients with APs and data is somewhat conflicting. Patients with multiple APs compared with single APs,14,15 preexcitation versus concealed APs,9 and patients with AP-dependent circus movement tachycardia (AVRT) versus no AVRT have a higher incidence of AF.8 Atrial wavefront collision during AF with retrograde AP conduction may perpetuate AF.16 Shorter antegrade effective AP refractory periods have been documented in AF patients whereas the retrograde conduction properties of a single AP appear to be not a critical determinant of AF.4 AVRT may degenerate into AF in between 16% and 26%.8 In addition, ongoing AVRT increases atrial stretch, sympathetic tone, and atrial vulnerability predisposing for AF occurrence.8 Also, one could speculate that accessory pathways—as developmental pathology—may involve developmental differences in atrial tissue close to the AP and therefore lead to enhanced structural atrial abnormalities. Histopathological data on this hypothesis are missing. Most of these determinants change after successful AP ablation but AF inducibility seems to change after AP ablation—at least in some patients. Hamada et al.9 identified 2 distinct patient groups studying atrial vulnerability parameters. In one group, these parameters normalized after AP ablation (AP-dependent, reversible mechanism of AF) and in the other group atrial vulnerability remained high (AP-independent, intrinsic, and nonreversible mechanism).5,7,9 As a limitation, reversibility of electrophysiological changes may need more time and may not be properly studied directly after AP ablation. Although in most cases effective AP ablation prevents recurrence of AF, 6–24% of patients may have AF in the absence of prior ablated APs.1,2,5,6,7 In these patients, an AP-independent mechanism—comparable to mechanisms identified in patients with idiopathic AF—is proposed to generate episodes of AF. Derejko et al.11 identified electrophysiological differences in WPW patients comparable to the changes documented in idiopathic AF patients. A conclusive finding is that only patients with a prior history of AF or inducible AF during the procedure had recurrent AF episodes after AP ablation. Also, Dagres et al.6 have documented a clear age-related component in AF recurrences after AP ablation. Patients older than 50 years had a significantly higher recurrence rate (35%) compared with younger patients (12%) in a large cohort of WPW-patients. Another striking difference, although not statistically significant in a multivariate model, was the higher prevalence of coronary artery disease in patients with recurrent AF compared with no AF recurrence. An interesting finding was documented by Szumowski et al.4 identifying 2 peaks in timing of AF occurrence in patients with APs but without documented AVRT, one at an early stage (<35 years of patient age) and one in older patients (>50 years). Whether these two peaks represent two different mechanisms has not been evaluated. In their study, though, male gender was also associated with a higher incidence of AF, again comparable to the gender differences present in the general population with AF. In the presented study by Derejko et al.,11 ablation of the AP prevented recurrence from AF in 13 of 16 patients (81%). In 3 patients, AF recurred despite the absence of the ablated AP (in 2) and PV isolation in all 3 patients lead to freedom from recurrent AF. PV-triggered AF appeared to be the mechanism in these patients. The presented clinical data allow the conclusion that—comparable to patients with idiopathic AF—the mechanism of AF may be the same PV-focus triggered mechanism. Of interest, recurrence of AF after ablation of the AP occurred in 38% of patients with inducible AF after successful AP ablation. Therefore, patients inducible after AP ablation (especially those with a history of AF) should undergo close follow-up for recurrent AF especially if anticoagulation may be indicated in these patients. Recurrences of AF after AP ablation appear to be nearly exclusive to patients with prior history of AF. In addition, recurrent AF is more common in older patients, male gender, and those with AF inducible after AP ablation. This subgroup of WPW patients may have comparable distribution of predictors as identified in the general population.9,11 The current study by Derejko et al.11 allows further insights into the mechanisms involved in the occurrence of AF in patients with APs. The PV electrophysiology in these patients differs from patients without a history of AF and changes are comparable to those identified in idiopathic AF patients. Short PV-ERPs, increased dispersion of refractoriness, and delayed left atrial conduction times appear to be involved in the electrophysiological conditions initiating and perpetuating AF in WPW patients. It remains unclear, though, whether these changes in electrophysiology are at least in part remodeling of the atria because of prior episodes of AF or may be the primary cause of AF. The authors are to be commended on their decisive analysis of left atrial electrophysiology and it would have been very interesting to also have insights into the atrial structural substrate of these patients. Performing delayed enhancement cardiac magnetic resonance imaging to identify the percentage of atrial fibrosis would have helped to further stage the AF disease.17 Recurrence of AF after AP ablation may also be related to the amount of atrial substrate alterations. Recurrent AF after AP ablation appears to be related to primary AF mechanisms with specific electrophysiological properties of the PV area. Parameters associated with the occurrence of AF in the general population appear to be related to recurrence of AF. Although, recurrent AF appears to be nearly exclusive to patients with a history of AF, and AF induced during an AP ablation procedure. These patients need close follow-up for recurrent arrhythmia especially when considering potential implications for interventional AF treatment and anticoagulation regimens.