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Europace Advance Access published online on April 17, 2008

Europace, doi:10.1093/europace/eun092
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Pulmonary vein potentials in patients with and without atrial fibrillation

Eva Hertervig, Ole Kongstad, Erik Ljungstrom, Bertil Olsson and Shiwen Yuan*

Department of Cardiology, Lund University Hospital, SE-221 85 Lund, Sweden

Manuscript submitted 17 October 2007. Accepted after revision 28 February 2008.

* Corresponding author. Tel: +46 46 173648; fax: +46 46 157857. E-mail address: shiwen.yuan{at}med.lu.se


    Abstract
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 Abstract
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 Methods
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Background: Pulmonary vein (PV) potentials are invariably recordable at the PV ostia in patients with atrial fibrillation (AF) and delayed conduction around the PV ostia may play a role in the initiation and maintenance of AF.

Aims: To investigate the presence and extent of PV potentials in patients with and without AF.

Methods and results: Circumferential catheter recordings at the PV ostia were obtained from 10 patients with paroxysmal AF and 9 with concealed Wolff-Parkinson-White (WPW) syndrome without history of AF. Typical PV potential was defined as either rapid deflections that separated from atrial deflection with a time delay in-between, or multiphasic, continuous or fractionated potentials. The presence of PV potentials was verified during sinus rhythm and during atrial pacing at the distal coronary sinus for the left PVs or at the right atrial appendage for the right PVs. To quantify the extent in which the PV potentials were recordable, the number of PVs with typical PV potentials recordable was counted. The time interval from the onset to the end of the electrograms recordable at the PV ostium (A–PV interval) was measured, and the maximal and mean of this interval were obtained. Typical PV potentials were recorded in 31 of 34 PVs (91%) in patients with AF, but in 4 of 36 PVs (11%) in patients with concealed WPW. A narrow, biphsic or triphasic, potential was recorded in 3 of 34 PVs (9%) in patients with AF, but in 29 of 36 (81%) PVs in patients with concealed WPW. The maximal and mean A–PV intervals were significantly longer in patients with AF (71 ± 24 and 49 ± 13 ms) than in patients with concealed WPW syndrome (33 ± 14 and 25 ± 6 ms).

Conclusion: In patients with AF, typical PV potentials with marked conduction time delay were almost invariably recordable at the PV ostium, but in patients without a history of AF, merely simple, narrow potentials were found. These findings support the involvement of conduction delay and re-entrant activities around the PV ostia in the genesis and/or perpetuation of AF.

Key Words: Pulmonary vein potential, Atrial fibrillation, Concealed WPW syndrome


    Introduction
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 Abstract
 Introduction
 Methods
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 Discussion
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 References
 
Atrial fibrillation (AF) is currently the most challenging arrhythmia in clinical practice, which is associated with a 1.5- to 1.9-fold mortality risk.1Go There has been clear anatomical evidence that myocardial sleeves extend into the pulmonary veins (PVs)2Go,3Go and are capable of conducting electrical impulses4Go,5Go and generating ectopic beats as triggers for initiation of AF.6Go PVs may also play a role in the maintenance of AF, due to the complicated architecture of the myocardial sleeves surrounding the ostium of the PVs and their heterogeneity in conduction properties and refractoriness.7Go

In the clinical setting, it has become clear that typical PV potentials are almost invariably recordable at the PV ostium in patients with AF and ablation around the PV ostium leads to curative results.8Go–11Go These findings suggest that electrical activities around the ostia of PVs are of clinical importance. We know very little, however, about the prevalence of PV potentials in patients without AF. The current study was, therefore, conducted to investigate the presence and extent of PV potentials in patients with and without AF in order to achieve a better understanding of the importance of PV potential and the electrical activity around the PV ostium in the genesis and perpetuation of AF.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
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 References
 
Patients
The AF group consisted of 10 patients (8 males) with paroxysmal AF, aged 30–66 (median 49.5) years, who were scheduled for AF ablation. There was no detectable cardiovascular disease in these patients, except one of them with hypertension. Paroxysmal AF was clinically documented with ECG and/or Holter ECG recording. The history of AF in these patients was 2–28 (median 9.5) years.

The control group included nine patients (four males) with concealed WPW syndrome without history of AF, aged 25–65 (median 52) years, who were scheduled for ablation of accessory pathways.

Anti-arrhythmic drugs were discontinued for at least five half-lives before the study. There was no patient on amiodarone treatment. Informed consent was obtained from all patients. The study was approved by the local Ethics Committee of Lund University, and the electrophysiological procedure was in accordance with our institutional guidelines.

Electrophysiology protocol
In both groups, standard catheters were inserted via the right femoral vein: a bipolar catheter to the right ventricular apex for pacing, a 10-polar catheter to the coronary sinus for pacing and recording, and a 4-polar catheter to record the His bundle electrogram. Via a transseptal access, a 10- or 20-polar circumferential catheter (Lasso, 10-polar with 15 mm loop or 20-polar 15–25 mm expandable loop, Biosense-Webster, Waterloo, Belgium) was inserted into the left atrium and was placed at the PV ostium.

In order to obtain consistent placement of the circumferential catheter in all the patients, the following efforts were made: (i) Bi-plane PV angiography for identification of the left atrium–PV junction. (ii) Rotating or bending the ablation catheter, while withdrawing it from the PV under fluoroscopy to further verify the anterior, posterior, and inferior aspects of the left atrium–PV junction by observing the sudden dislocation of the catheter. (iii) Careful adjustment of the expandable loop of the circumferential catheter for good tissue contact, stable and parallel loop-PV ostium positioning. (iv) When angiography and/or three-dimensional CT/MR image showed a funnel shaped PV antrum, the circumferential catheter was placed at about the middle of the funnel. (v) Fine adjustment by rotating, expanding/reducing, and moving the catheter loop forth and back within a range of 5–10 mm to find a position where both the atrial deflection and the PV potentials were recordable, if possible. (vi) Catheter position was not accepted when it was clearly inside the PV or out in the atrium, even if the atrial deflection and PV potential were clearly separated at those positions.

The left PVs were explored during sinus rhythm and during atrial pacing from the distal coronary sinus at a pacing rate ~20 beats/min faster than during sinus rhythm (at a cycle length of 500, 600, or 700 ms), and the right PVs were explored during sinus rhythm and during pacing from the right atrial appendage using the His catheter with a pacing cycle length of 500, 600, or 700 ms. The recordings were performed before ablation in the AF group. In the control group, the recordings were performed after ablation of the accessory pathway.

All the recordings were recorded as bipolar electrograms using a multichannel electrophysiology recorder (Bard Lab System; Bard, NJ, USA) with a frequency response of 30–500 Hz and at a sampling rate of 1 kHz. Each recording lasted 30 s and was stored on optical disc for off-line analysis. All recordings were reviewed off-line on the screen of the Bard system and documented by printout at a paper speed of 100 mm/s.

Data analysis
Typical PV potentials were defined as rapid deflections (i) separated from the atrial deflection with a clear conduction delay in-between, or (ii) multiphasic, i.e. continuous or fractionated potentials wihtout separate atrial deflection and PV potential recognizable. Atypical PV potential was defined as (i) a sharp, distinct, biphasic or triphasic, potential without separate atrial deflection simultaneously recordable at the PV ostium and (ii) during atrial pacing as specified above, the distance from the potential to the atrial deflection that recorded by the pacing catheter did not become shorter than before pacing. In recording channels where no electrical activity was recordable or only low frequency and low amplitude (<0.1 mV) signals were recordable, we defined that channel as no PV potential.

To quantify the extent to which PV potentials were recordable, the number of recording channels with typical or atypical PV potentials was calculated for each PV and for all the PVs in each individual patient. In patients with a 10-polar Lasso catheter, the recordings were collected from channels 1-2, 2-3, 3-4, etc., whereas in patients in whom a 20-polar catheter was used, the recordings were collected from channels 1-2, 3-4, 5-6, etc. In this way, all patients would have totally 10 channels of recording for analysis.

To evaluate the conduction time delay across the PV ostium, the time interval between the onset of the atrial deflection (A) and the end of the PV potential, A–PV interval, was also measured. We did not use the onset of the PV potential because it was difficult to measure when the PV potential was fractionated or continuous. When there was no separate A and PV potential recordable at the PV ostium, the interval from the onset to the end of the recorded potential was measured as A–PV interval. The maximal and mean A–PV intervals for each PV and for all four PVs were calculated.


    Results
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 Abstract
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In the AF group, totally 34 of the 40 PVs were included in the data analysis, i.e. in three patients the right inferior PV was not catheterized due to clinical or technical reasons, in one patient the recording at the left inferior PV was performed during AF when it was not possible to analyse the PV potentials as during sinus rhythm, and in two additional patients recordings from one of the four PVs were missing due to technical errors. In three PVs, a simple, narrow, biphasic or triphasic, potential was recorded. Thus, typical PV potentials were recorded in the remaining 31 of the 34 PVs (91%) (Figure 1).


Figure 1
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Figure 1 Recordings at the ostium of the left superior PV during distal coronary sinus pacing from patients 15 (A), 16 (B), and 14 (C) with AF, showing separate, distinct PV potentials, e.g. Patient 14, channels PV 3-4, 4-5 and 5-6, or multiphasic, fractionated potentials that is not clearly separated from the atrial deflection, e.g. Patient 16, channels PV 1–2, 2–3, 8–9, and 9–10. Note in Patient 16, channels PV 3-4, 4-5, and 5-6 and in patient 14, channels PV 7-8, 8-9, 9-10, and 10-1 were counted as no PV potential.

 
In the nine patients with concealed WPW syndrome, all the 36 PVs were explored. Typical PV potentials were recorded in 4 of the 36 PVs (11%) (Figure 2C), i.e. in 2 of the 10 recording channels in the left superior PV in 2 patients and in 2 and 5 recording channels, respectively, in the left inferior PV in 2 other patients. In 3 PVs no electrical signal was recordable (8%). Thus, in 29 of the 36 PVs (81%), only a simple, biphasic or triphasic, narrow potential was recorded, i.e. no separate atrial deflection and PV potential were recordable at the PV ostium (Figure 2A and B).


Figure 2
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Figure 2 Recordings at the ostium of the left superior PV during distal coronary sinus pacing from patients 1 (A), 3 (B), and 4 (C) with concealed WPW syndrome, showing in majority of the recording channels merely simple, narrow potentials were recordable, with rare exceptions where separate PV potentials were recorded in limited number of channels [e.g. in channels PV 13-14 and 15-16 (C)]. Note in Patient 1, channels PV 9-10 and 11-12 and in Patient 3, channels PV 3-4, 5-6, 17-18, and 19-20 were counted as no PV potential.

 
The time interval between the onset of the atrial deflection and the end of the PV potential, A–PV interval, was significantly longer in patients with AF than in patients with concealed WPW syndrome, not only for each of the PV, but also for all the four PVs, and not only for the maximal A–PV interval, but also for the mean A–PV interval between the two groups (Table 1).


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Table 1 Maximal and mean A–PV intervals recorded at the ostia of the PVs

 

    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 References
 
PV potentials are almost invariably recordable at the PV ostium in patients with AF. Although the role of PV potentials in the genesis and/or perpetuation of AF is still not very clear, PV isolation and thereby elimination of the PV potentials is an important component in most of the strategies of AF ablation that lead to curative results in patients with paroxysmal, persistent, or even permanent AF, e. g. segmental PV ablation,12Go,13Go circumferential ablation,8Go,14Go the double Lasso technique,11Go and the stepwise strategy.10Go With the accumulation of clinical experience, the AF ablation technique has been modified continuously. However, electrical isolation of the PVs remains the cornerstone of AF ablation procedures. In the recent HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of AF, complete electrical PV isolation is recommended as the goal if the PVs are targeted.15Go These facts may suggest that the electrical activities around the PV ostium, as manifested by the PV potential, are of clinical importance.

PV potentials typically appear as rapid local potentials following an atrial deflection with a clear time delay in-between. Sometimes they are rapid, continuous, fractionated potentials without separate atrial deflection and PV potential recognizable.16Go It is generally accepted that PV potentials are generated from electrical activities of the myocardial sleeves within the PV. The time interval from the atrial deflection to the PV potential may represent conduction time across the PV ostium. There are also occasions that only a rapid but simple, biphasic or triphasic, potential is recorded at the PV ostium, without clear simultaneously recordable atrial deflection. Although referencing to the atrial deflection in other simultaneously recorded channels of electrograms and pacing from neighbouring area can help to verify if it is a PV potential or electrogram from atrial muscles nearby, it is sometimes difficult to identify the nature of the signal. It could be a merged signal from both the atrial deflection and the PV potential, but we cannot exclude the possibility that it is purely generated from myocardial tissue outside or inside the PV. However, recent results of catheter ablation have shown that electrically complete PV isolation is invariably accompanied by sudden disappearance of all the PV potentials, including this kind of simple, narrow potentials,11Go suggesting that these signals are also generated from myocardial tissue within the PV ostium or at least at the nearest vicinity of the PV ostium.

Thus, in the current study, we took this kind of signals as atypical PV potentials and calculated their interval to compare them with the A–PV intervals measured from recordings with typical PV potentials. Further study is certainly required to clarify whether this narrow potential reflects only electrical activity of the muscle sleeves within the PV, or more likely, it generates from myocardial tissues both within and outside the PV. However, it is obvious that the signal clearly differs from the typical PV potentials that represent marked conduction delay across the PV ostium. It should therefore be understandable to refer the simple, narrow potential as representing less conduction delay than the wide, typical PV potentials.

We found in the current study that typical PV potentials were almost invariably recordable in all the PVs (91%) in patients with AF, but they were only found in a few recording channels in 11% of PVs in patients without AF. Quantitatively, we found that the A–PV interval, the time interval between the onset of the atrial deflection and the end of the PV potential, was clearly longer in patients with AF than in patients with concealed WPW syndrome (Table 1 and Figures 1 and 2). In other words, in our patients with concealed WPW syndrome, the local potentials recorded at the PV ostium were merely simple, biphasic or triphasic, narrow signals without clear separation from the atrial activation. This may suggest that conduction delay between the left atrial tissue surrounding the PV ostium and the myocardium within the PV does not exist or is minimal in patients without AF, while it is obvious and extensive in patients with AF. These findings suggest that conduction delay around and/or across the PV ostium may be an important electrophysiological substrate for the development and/or maintenance of AF, and strongly support the involvement of re-entrant activities around the PV ostium in the genesis/perpetuation of AF. Our postulation is also supported by a similar study by Boersma et al.17Go that published in abstract form simultaneously with our abstract.18Go They recorded PV potentials in 88% of the PVs in four patients with AF, but only in 25% of the PVs in six of nine patients with WPW. The time delay between the atrium and the PV potential was also greater in the AF than in the WPW patients. Moreover, Jais et al.16Go have reported earlier that patients with AF were associated with longer PV–left atrium conduction time and shorter venous refractory period when compared with patients without AF, which favours re-entry within and around the ostium of the PVs. The anatomical variations of the atrial myocardium extending into the PVs were found to be more complex in patients with AF than in patients without, which also facilitates the re-entrant activities around the ostium of the PVs.19Go Thus, the ostia of PVs may be important both for the initiation and maintenance of AF, as evidenced by the fact that PV potentials are present in almost all patients with AF, and radiofrequency ablations to the ostial region of the PVs can eliminate AF.12Go,20Go–22Go

Limitations
Patients with WPW syndrome have a tendency to get paroxysmal AF, which is observed in about one-third of all patients.23Go Little is known about the incidence of AF in concealed WPW syndrome, but according to Della Bella et al.,24Go it may be ~3%. The control group in our study had no clinical history of AF, but this does not exclude asymptomatic episodes of AF and the tendency of AF to occur later in these patients. In this sense, patients with concealed WPW syndrome are not ideal as controls for AF. However, a significant difference in PV potential recordings was found between the groups. Besides, it is clear that pathological and pathophysiological changes can be found in the atrium of patients with AF, whereas patients with concealed WPW syndrome have an otherwise healthy heart. This gives us good reason to regard concealed WPW syndrome patients as a valid control group in this particular study.

Conclusion
Patients without AF merely have simple, narrow potentials recordable at the PV ostium when compared with patients with AF, in whom excessive, separate or continuous, PV potentials invariably exist. The time interval between the onset of atrial deflection and the end of the PV potential was significantly longer in patients with AF than in patients with concealed WPW syndrome. These findings support the involvement of conduction delay and re-entrant activities around the PV ostium in the genesis and/or perpetuation of AF.

Conflict of interest: none declared.


    Funding
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 References
 
This study was supported by research grants from The Swedish Heart-Lung Foundation, Lund University Hospital Donation Funds, The Franke and Margareta Bergqvist Foundation, and Governmental funding of clinical research within the NHS (ALF medel).


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 References
 
[1] Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation (1998) 98:946–52.[Abstract/Free Full Text]

[2] Wang K, Ho SY, Gibson DG, Anderson RH. Architecture of atrial musculature in humans. Br Heart J (1995) 73:559–65.[Abstract/Free Full Text]

[3] Ho SY, Anderson RH, Sanchez-Quintana D. Atrial structure and fibres: morphologic bases of atrial conduction. Cardiovasc Res (2002) 54:325–36.[Abstract/Free Full Text]

[4] Chen YJ, Chen SA, Chang MS, Lin CI. Arrhythmogenic activity of cardiac muscle in pulmonary veins of the dog: implication for the genesis of atrial fibrillation. Cardiovasc Res (2000) 48:265–73.[Abstract/Free Full Text]

[5] Hocini M, Ho SY, Kawara T, Linnenbank AC, Potse M, Shah D, et al. Electrical conduction in canine pulmonary veins: electrophysiological and anatomic correlation. Circulation (2002) 105:2442–8.[Abstract/Free Full Text]

[6] Hwang C, Karagueuzian HS, Chen PS. Idiopathic paroxysmal atrial fibrillation induced by a focal discharge mechanism in the left superior pulmonary vein: possible roles of the ligament of Marshall. J Cardiovasc Electrophysiol (1999) 10:636–48.[Web of Science][Medline]

[7] Tada H, Oral H, Ozaydin M, Greenstein R, Pelosi F Jr, Knight BP, et al. Response of pulmonary vein potentials to premature stimulation. J Cardiovasc Electrophysiol (2002) 13:33–7.[CrossRef][Web of Science][Medline]

[8] Pappone C, Oreto G, Lamberti F, Vicedomini G, Loricchio ML, Shpun S, et al. Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system. Circulation (1999) 100:1203–8.[Abstract/Free Full Text]

[9] Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, et al. Circumferential radiofrequency ablation of pulmonary vein ostia: a new anatomic approach for curing atrial fibrillation. Circulation (2000) 102:2619–28.[Abstract/Free Full Text]

[10] Haissaguerre M, Sanders P, Hocini M, Takahashi Y, Rotter M, Sacher F, et al. Catheter ablation of long-lasting persistent atrial fibrillation: critical structures for termination. J Cardiovasc Electrophysiol (2005) 16:1125–37.[CrossRef][Web of Science][Medline]

[11] Ouyang F, Bansch D, Ernst S, Schaumann A, Hachiya H, Chen M, et al. Complete isolation of left atrium surrounding the pulmonary veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation. Circulation (2004) 110:2090–6.[Abstract/Free Full Text]

[12] Haissaguerre M, Shah DC, Jais P, Hocini M, Yamane T, Deisenhofer I, et al. Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation (2000) 102:2463–5.[Abstract/Free Full Text]

[13] Haissaguerre M, Hocini M, Sanders P, Sacher F, Rotter M, Takahashi Y, et al. Catheter ablation of long-lasting persistent atrial fibrillation: clinical outcome and mechanisms of subsequent arrhythmias. J Cardiovasc Electrophysiol (2005) 16:1138–47.[CrossRef][Web of Science][Medline]

[14] Pappone C, Santinelli V, Manguso F, Vicedomini G, Gugliotta F, Augello G, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation (2004) 109:327–34.[Abstract/Free Full Text]

[15] Calkins H, et al, EHRA, ECAS, ACC, AHA, STS. HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm (2007) 4:816–61.[CrossRef][Web of Science][Medline]

[16] Jais P, Hocini M, Macle L, Choi KJ, Deisenhofer I, Weerasooriya R, et al. Distinctive electrophysiological properties of pulmonary veins in patients with atrial fibrillation. Circulation (2002) 106:2479–85.[Abstract/Free Full Text]

[17] Boersma L, Wittkampf F, Khan M, Wever E. Electrophysiological properties of the pulmonary veins in patients with an accessory pathway without atrial fibrillation. Heart Rhythm (2006) 3:S319.

[18] Hertervig E, Kongstad O, Ljungström E, Olsson S, Yuan S. Pulmonary vein potential recordings using a circumferential catheter in patients with and without atrial fibrillation. Heart Rythm (2006) 3:S276.

[19] Hassink RJ, Aretz HT, Ruskin J, Keane D. Morphology of atrial myocardium in human pulmonary veins: a postmortem analysis in patients with and without atrial fibrillation. J Am Coll Cardiol (2003) 42:1108–14.[Abstract/Free Full Text]

[20] Jais P, Haissaguerre M, Shah DC, Chouairi S, Gencel L, Hocini M, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation (1997) 95:572–6.[Abstract/Free Full Text]

[21] Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, et al. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation (2001) 104:2539–44.[Abstract/Free Full Text]

[22] Oral H, Knight BP, Tada H, Ozaydin M, Chugh A, Hassan S, et al. Pulmonary veins isolation for paroxysmal and persistent atrial fibrillation. Circulation (2002) 105:1077–81.[Abstract/Free Full Text]

[23] Campbell RW, Smith RA, Gallagher JJ, Pritchett EL, Wallace AG. Atrial fibrillation in the preexcitation syndrome. Am J Cardiol (1977) 40:514–20.[CrossRef][Web of Science][Medline]

[24] Della Bella P, Brugada P, Talajic M, Lemery R, Torner P, Lezaun R, et al. Atrial fibrillation in patients with an accessory pathway: importance of the conduction properties of the accessory pathway. J Am Coll Cardiol (1991) 17:1352–6.[Abstract]


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