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doi:10.1093/europace/eun031
KEYWORDS Background Paroxysmal atrial fibrillation (PAF) develops in up to one-third of patients with the Wolff-
Paroxysmal atrial fibrillation; Parkinson–White syndrome (WPW). The reason for this high incidence of PAF in the WPW syndrome is not
Wolff–Parkinson–White yet clearly understood. When PAF appears in patients with WPW syndrome who have anterograde con-
syndrome; duction via the accessory pathway (AP), it may be life-threatening if an extremely rapid ventricular
Atrial vulnerability; response develops degenerating into ventricular fibrillation.
Accessory pathway; Methods and results Several mechanisms responsible for the genesis of PAF in WPW patients were
Abnormal atrial electrograms hypothesized, namely, spontaneous degeneration of atrioventricular reciprocating tachycardia into
atrial fibrillation (AF), electrical properties of the APs, effects of APs on atrial architecture, and intrinsic
atrial muscle vulnerability. Focal activity, multiple reentrant wavelets, and macroreentry have all been
implicated in AF, perhaps under the further influence of the autonomic nervous system. AF can also be
initiated by ectopic beats originating from the pulmonary veins, and elsewhere. Several studies demon-
strated a decrease incidence of PAF after successful elimination of the AP, suggesting that the AP itself
may play an important role in the initiation of PAF. However, PAF still occurs in some patients with the
WPW syndrome even after successful elimination of the AP. There is an important evidence of an under-
lying atrial disease in patients with the WPW syndrome.
Conclusions Atrial vulnerability has been studied performing an atrial endocardial catheter mapping
and analysing abnormal atrial electrograms. Other studies evaluated atrial refractoriness and intraatrial
conduction times, suggesting an intrinsic atrial vulnerability as the mechanism of PAF and considering
the AP as an innocent bystander. It is our intention to analyse the available data on this particular
and interesting topic since AF has a singular prognostic significance in patients with the WPW syndrome,
and its incidence is unusually high in the absence of any clinical evidence of cardiac organic disease.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008.
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Mechanisms for the genesis of PAF in WPW syndrome 295
PAF in WPW patients were hypothesized, namely, spon- during AVRT. Chen et al.15 observed that the AVRT cycle
taneous degeneration of atrioventricular reciprocating length at the time of electrophysiological study was signifi-
tachycardia (AVRT) into atrial fibrillation (AF), electrical cantly shorter in WPW patients with than without AF. This
properties of the AP, effects of AP on atrial architecture, finding suggests that it is easier to develop PAF in a rapid
and intrinsic atrial muscle vulnerability.4–9 episode of sustained AVRT. Long-term follow-up studies
Spontaneous degeneration of AVRT into AF has been after successful surgical or catheter ablation of the AP
observed during electrophysiological studies in a minority have shown significantly reduced incidences of spontaneous
of patients with WPW syndrome. On the other hand, PAF is PAF. The recurrence rate of spontaneous PAF after successful
often observed in patients without AVRT. Several studies ablation of the AP is reported to be in the range of 6–10%.1–3
demonstrated a decrease incidence of PAF after successful In this respect, Hamada et al. observed that clinical epi-
elimination of the AP, suggesting that the AP itself may sodes of PAF recurred in 71% of their patients whose AF
play an important role in the initiation of PAF. Therefore, remained inducible post-ablation, however, in none of the
the existence of a functional AP and inducible AVRT has patients who remained uninducible post-ablation.16 There-
been found to play an important role in triggering AF in fore, there is a high incidence of AF recurrence in a subgroup
right atrial site regardless of AP location, with only 19% of AF available. Most of the histopathological studies in patients
episodes starting at the electrode site in the coronary sinus with WPW syndrome have dealt with the AP itself. It was
closest to the AP. Iesaka et al.20 found that the incidence of postulated that the AP is the result of an embryological
clinical PAF as well as induced AF was significantly greater fault in the formation of fibrous tissue separating the atria
in patients with multiple AP. However, the incidence of clini- and the ventricles.24 Therefore, developmental abnormal-
cal AVRTwas similar between multiple and single AP patients. ities may also be present in the atrial tissue adjacent to
The incidence of AF initiated during ventricular pacing and the AP, which may affect the functional electrical properties
AVRT was significantly greater in the multiple AP patients. A of the atrium close to the AP. Dispersion of the refractory
very interesting finding in this study20 was that AF inducibility periods and conduction disturbances apparently occur
during AVRT and ventricular pacing was eliminated by partial around the interconnection between different tissues such
ablation of multiple or multifibre AP. However, AVRT inducibil- as the atrium and the AP. Either anatomical or functional
ity remained in most patients with partial ablation of the mul- properties of the atrial tissue near the AP may play a role
tiple o multifibre AP. The incidence of induced AF after total in the genesis of AF and may contribute to the different inci-
ablation was similar between patients with multiple or dence of atrial vulnerability and AF in the WPW syndrome.
Conclusions
Atrial fibrillation has a particular prognostic significance in
patients with the WPW syndrome, and its incidence is unu-
sually high in the absence of any clinical evidence of organic
heart disease. It may be life-threatening if an extremely
rapid ventricular response develops degenerating into ventri-
cular fibrillation.50 The existence of a retrograde multiple or
multifibre AP is strongly related to AF inducibility, and the
complex excitation inputs into the atrium over the retrograde
multiple or multifibre AP facilitate the development of AF in
WPW patients. The decrease incidence of PAF after successful
elimination of the AP suggests that the AP itself may play an
important role in the initiation of PAF.
Figure 5 (A) Normal atrial endocardial electrograms. Examples of On the other hand, there is an important evidence of an
measurement of the duration (top), and the number of deflections underlying atrial disease in patients with the WPW syn-
(bottom) of the intraatrial electrogram. Surface electrocardio- drome. Abnormally prolonged and fractionated atrial endo-
graphic lead V1 is shown together with the right atrial electrogram cardial electrograms are observed with a significantly higher
(RA). In the top panel, the arrows show the onset and the end of the incidence in WPW patients with documented episodes of AF.
intraatrial electrogram. In the bottom panel, the arrows show the Furthermore, the electrophysiological findings of altered
deflections of the intraatrial electrograms. Reprinted with per-
atrial refractoriness, increased induction of repetitive
mission from Konoe A, Fukatani M, Tanigawa M, et al. Electrophysio-
logical abnormalities of the atrial muscle in patients with manifest
atrial firing and increased intra-atrial conduction delay
Wolff–Parkinson–White syndrome associated with paroxysmal atrial suggest an intrinsic atrial vulnerability as the mechanism
fibrillation. PACE 1992;15:1040–1052. (B) Abnormally prolonged and of PAF in certain patients with the WPW syndrome. The
fractionated atrial endocardial electrogram. Example of an ‘abnor- atrial vulnerability in the WPW syndrome seems to be
mal atrial electrogram’. This abnormal atrial electrogram was either reversible and AP-dependent, or intrinsic and
recorded from high lateral right atrium (RA). Abnormal atrial elec- AP-independent atrial vulnerability.
trogram as defined in the text. Reprinted with permission from Therefore, it is concluded that the available evidence
Konoe et al.4 suggests the presence of different mechanisms of AF devel-
opment in different patients with the WPW syndrome. A
evident, diffuse, and extensive alteration in the atrial his- detailed electrophysiological examination before and after
tology compared with those who do not develop AF.47 The AP ablation could shed insight into the understanding of
histological studies of the atrial tissue that had electro- the mechanism for the genesis of AF in individual patients
physiological alteration consist of widely separated atrial with the WPW syndrome.
Mechanisms for the genesis of PAF in WPW syndrome 301
Conflict of interest: none declared. 22. Frame LH, Page RL, Hoffman BF. Atrial reentry around an anatomic
barrier with a partially refractory excitable gap. Circ Res 1986;58:
495–511.
23. Inoue H, Zipes DP. Conduction over an isthmus of atrial myocardium in
vivo: a possible model of Wolff-Parkinson-White syndrome. Circulation
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