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Europace Advance Access originally published online on November 10, 2006
Europace 2006 8(12):1031-1037; doi:10.1093/europace/eul120
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


ELECTROPHYSIOLOGY

Pulmonary vein activation in atrial fibrillation and sinus rhythm

Xiao Sheng Hu1 and Stuart P. Thomas2,*

1 Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China; 2 Department of Cardiology and University of Sydney, Westmead Hospital, Sydney, Australia

Manuscript submitted 31 March 2006. Accepted after revision 28 August 2006.

* Corresponding author. Tel: +61 2 98456795; fax: +61 2 98458323. E-mail address: stuartth{at}westgate.wh.usyd.edu.au


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Aims The purpose of this study was to determine the relationship between pulmonary vein (PV) electrical activation during atrial fibrillation (AF) and after cardioversion into sinus rhythm.

Methods and results Electrograms were recorded using a circular mapping catheter during AF and after cardioversion in 53 PVs from 41 patients. Two activation patterns were observed in AF. Group 1 had fixed, consistent, uniform activation sequences most (>70%) of the recording time. Group 2 had no fixed activation sequence. In Group 1, a constant single activation sequence pattern was seen in 22 PVs (Group 1a). The earliest PV activation sites were the same during AF and after cardioversion to sinus rhythm in 17 (77%) PVs from Group 1a. Fourteen of these 17 (82%) cases also had a common site of electrogram polarity reversal. In Group 2, a relationship between PV activation before and after cardioversion was not found. Segmental radio frequency (RF) ablation was performed during sinus rhythm after cardioversion. There was no difference in the number of atriovenous breakthroughs between the two groups (1.9±0.7 vs. 2.0±0.6 breakthroughs, P=NS). PV disconnection was achieved in all PVs with a mean RF duration of 13.5±4.5 min per vein in Group 1 and 14.0±4.9 min per vein in Group 2 (P=NS).

Conclusion A uniform PV electrogram pattern recorded during AF usually predicts the activation sequence and/or the polarity reversal sites during sinus rhythm. This pattern does not necessarily suggest a single atriovenous breakthrough point.

Key Words: Atrial fibrillation, Catheter ablation, Pulmonary vein electrogram


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice.1Go Pulmonary vein (PV) isolation for treatment of drug-refractory paroxysmal or persistent AF can be achieved by elimination of PV triggers.2Go Haïssaguerre et al. described the technique for segmental isolation of the PVs with a circular mapping catheter. During sinus rhythm, delivery of radiofrequency (RF) energy was guided by mapping the earliest PV potentials (PVPs)3Go or the site of bipolar electrogram polarity reversal using a circular mapping catheter.4Go PV isolation has also been used to treat patients with persistent or permanent AF.5Go,6Go Previous studies described the PV electrogram patterns during sustained AF.7Go,8Go They demonstrated that PV isolation could be achieved by ablation during AF. However, the relationship between the PV electrogram pattern during AF and that during sinus rhythm is unknown. It was not clear from earlier studies whether the pattern of PV activation in sinus rhythm could be predicted by the pattern of activation during AF. The purpose of this study was to determine the relationship between PV electrical activation during AF and after electrical cardioversion to sinus rhythm.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Patient characteristics
Consecutive patients (n=117) with symptomatic AF who underwent segmental PV ablation were considered for the study. Electrical activation in a PV was studied if the following conditions were satisfied: (i) the episode of AF was present at the start of the procedure or occurred during the procedure, (ii) PV activation was able to be recorded before electrical cardioversion and after restoration of sinus rhythm for at least 60 s, (iii) no ablation had been performed at or near the PV ostium, and (iv) episodes of AF induced by rapid pacing were not included in the study. All patients provided written informed consent.

Electrophysiological study
Before the ablation procedure, transoesophageal echocardiography was performed to exclude intracardiac thrombi. The patients were in the fasting state and sedated with intravenous midazolam and fentanyl during the procedure. A 6 F decapolar electrode catheter (Biosense Webster, Cordis Corp., Diamond Bar, CA, USA) was positioned in the coronary sinus and used for atrial pacing and recording. Two transseptal punctures were performed using Multipurpose Preface sheaths (Biosense Webster). A Lasso circular decapolar catheter (Biosense Webster) was advanced sequentially into each PV and was used for PV ostial mapping. Angiograms of all PVs were performed before and after the ablation and were displayed during the procedure to show the venous anatomy and the location of left atrial (LA)-PV junction. The selection of Lasso catheter diameter was guided by the angiographically estimated size of the PVs. Ablation was performed with a 4 mm tip (Blazer, Boston Scientific, San Jose, CA, USA) or irrigated tip (Thermocool, Biosense Webster) catheter with the maximum temperature set at 50°C and the power set at 30 W.

Recording of the PV electrograms
In each patient, the Lasso catheter was first inserted into the left superior (LS) PV during AF and withdrawn gradually to achieve a position as close to the PV ostium as possible. Electrograms were recorded in bipolar mode from 10 dipoles using a Cardiolab electrophysiological recording system (Prucka Cardiolab, GE Marquette, Milwaukee, WI, USA) at gains of 2500–5000 and a sweep speed of 200 mm/s. After at least 30 s of recording of electrograms from the PVs during AF, transthoracic cardioversion was performed. When sinus rhythm was restored after cardioversion, the PV electrograms were recorded for at least 30 s during sinus rhythm for the right PVs or during steady-state coronary sinus stimulation with a cycle length of 500—600 ms for the left PVs. If AF did not recur, the PVs were isolated during sinus rhythm. Induction of AF was not performed, and electrograms of the remaining PVs during sinus rhythm were not used for analysis. If AF recurred after a recording or was still persistent after isolation of one vein, then other PV electrograms were recorded during AF and during sinus rhythm. The Lasso was, thus, sequentially inserted into LS, right superior (RS), left inferior (LI), and right inferior (RI) PVs to record PV electrograms. Specific care was taken to maintain the position of the mapping catheter before and after cardioversion. Pulmonary vein muscle potentials during AF and sinus rhythm were defined as high-frequency sharp potentials recorded within veins.3Go,7Go

The electrogram patterns recorded during AF were divided into two types according to the uniformity of PVP activation sequence. Those PVPs that had fixed consistent activation sequences for >70% of recording sequences were regarded as uniform (Group 1). An irregular pattern (Group 2) was defined as recordings from mapping catheters with no fixed or clear activation sequence.

Ablation procedure
The ablation was performed during sinus rhythm after cardioversion, and RF energy was delivered at the PV ostium with individual 30–60 s applications. Ostial sites of the PV perimeter were targeted on the basis of the bipole(s) from the Lasso catheter showing the earliest activation and/or demonstrating polarity reversal during sinus rhythm or pacing of the distal coronary sinus. Sites of electrical breakthrough were defined as ablation sites at which the PVP activation sequence changed as a result of localized RF delivery.4Go Elimination or dissociation of all distal PVPs during sinus or paced rhythm was the endpoint of ablation.

Pulmonary vein angiography was repeated after the procedure, with PV stenosis defined as a diameter reduction of >50%. Patients were discharged after day 2 on oral anticoagulants. Anticoagulants were interrupted 6 months after successful elimination of AF, unless there were other risk factors.

Statistical analysis
Continuous variables are expressed as mean±SD. Continuous variables were compared using Student's t-test. Categorical variables were compared using the {chi}2 test. A P<0.05 was considered statistically significant.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Fifty-three (35LS, 9LI, 8RS, and 1RI) PVs electrograms were recorded before and after cardioversion in 41 patients (34 males). The mean age was 55.9±11.5 years. The mean duration of symptomatic AF before the ablation procedure was 6.4±6.3 months and a mean of 2.1±1.3 antiarrhythmic drugs had failed to suppress AF. Atrial fibrillation was associated with structural heart disease in nine patients. Ablation was performed during sinus rhythm in 30LS, 9LI, 7RS, and 1RI PVs. The other PVs were ablated during AF because AF recurred shortly after recording or during ablation.

PV electrogram pattern during AF
During AF, a uniform pattern (Group 1) of PVP activation was recorded in 26 PVs (17LS, 4LI, 4RS, and 1RI) from 22 patients. An irregular pattern (Group 2) was seen in 27 PVs (18LS, 5LI, and 4RS) from 23 patients (Figures 1A and 2A). The clinical characteristics of the two groups are shown in Table 1.


Figure 1201
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Figure 1 Examples of electrograms recorded during AF and during sinus rhythm with a uniform activation pattern (Group 1a). (A) The intracardiac electrograms during AF recorded from the circular mapping catheter and distal coronary sinus catheters are shown. The electrogram pattern recorded in the LSPV was uniform with the earliest PVPs (asterisk) at electrodes 5 and 6 and electrodes 6 and 7. (B) Electrogram recording from the same LSPV during distal coronary sinus pacing after cardioversion with the earliest PVPs (asterisk) at electrodes 5 and 6 and electrodes 6 and 7. Note that the PVP activation sequence was the same before and after cardioversion. Ostial ablation of the above LSPV revealed three distinctive breakthroughs. (C) Local ablation at LSPV ostium corresponding to electrodes 5 and 6 and electrodes 6 and 7 eliminated breakthroughs at this site and revealed a secondary breakthrough (asterisk). (D) Another RF delivery at this site abolished PVPs in all but five electrodes (asterisk). (E) Further RF application at this remaining PVP abolished conduction into the vein. I, II, V1, and V6 represent recordings from 12-lead surface ECG.

 


Figure 1202
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Figure 2 Example of electrograms recorded during AF and sinus rhythm with an irregular activation pattern (Group 2). (A) Electrogram of PVP recording from LSPV during AF. The electrogram pattern was irregular with a variable PVP activation sequence. (B) The same PV after cardioversion with consistent PVP activation sequence (asterisk) during distal coronary sinus pacing.

 


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Table 1 Comparison of clinical characteristics between two pattern groups

 
Comparison of PV electrogram pattern before and after cardioversion
In Group 1, a constant single activation sequence was seen in 22 PVs (14LS, 4LI, 3RS, and 1RI), although two or three consistent alternating activation sequences were recorded during AF in the same PV in the other 4 PVs (3LS and 1RS).

In the subgroup with a single activation sequence (Group 1a), the earliest sites of PV activation were the same during AF and after cardioversion to sinus rhythm in 17 (77%) of 22 PVs (Figure 1A and B). In the remaining five PVs, similarity of the electrogram polarity reversal site was observed in two PVs (Figure 3A and B). A consistent bipolar electrogram polarity reversal was also documented before and after cardioversion in 14 (82%) of 17 first activation sites, whereas the other three veins did not have a clear site of polarity reversal.


Figure 1203
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Figure 3 Example of similarity of electrogram polarity reversal site during AF and sinus rhythm. (A) The electrogram pattern recording from LSPV during AF was uniform with the first activation site at electrodes 1 and 2, electrodes 2 and 3, and electrodes 3 and 4. A reversal of the electrogram polarity was observed at electrodes 2 and 3 and electrodes 8 and 9 (asterisk). (B) Electrogram recorded during coronary sinus pacing. The earliest activation site was at electrodes 8 and 9, whereas polarity reversal was seen at electrodes 2 and 3 and electrodes 8 and 9 (asterisk).

 
In the subgroup with an alternating sequence of PVP activation (Group 1b), the PVPs sequence during sinus rhythm resembled one of the activation sequences pattern during AF in two of four PVs.

In Group 2, a relationship between the PVP activation sequences, earliest activation sites, or polarity reversal sites before and after cardioversion could not be identified (Figure 2A and B).

Location of atriovenous breakthrough points
In Group 1, 21 PVs were ablated during sinus rhythm. Radio frequency application at the earliest activation site (one breakthrough) eliminated all PVPs in 5 PVs, whereas in the other 16 PVs two or more breakthroughs were present (Figure 1CE). In Group 2, a single breakthrough was seen in 4 PVs, whereas multiple breakthroughs were ablated in 19 PVs (Figure 4AC). There was no significant difference in the number of breakthroughs in Groups 1 and 2 (1.9±0.7 vs. 2.0±0.6 breakthroughs, P=NS). PV disconnection was achieved in all PVs with a mean RF duration of 13.5±4.5 min per vein in Group 1 and 14.0±4.9 min per vein in Group 2 (P=NS). No acute PV stenosis or other complications were observed among the 41 patients in this study.


Figure 1204
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Figure 4 Ostial ablation of LSPV with a single breakthrough in which there was an irregular electrogram pattern during AF. (A) Pulmonary vein potentials recording from LSPV during AF. The electrogram pattern was irregular with a variable PVP activation sequence. (B) The same PV after cardioversion with sequential activation from the site of the earliest breakthrough (asterisk). (C) Radio frequency application at this site (electrodes 7 and 8) eliminated all PVPs.

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
The electrogram pattern recorded during AF can generally be divided into two types as described by Macle et al.7Go The major finding of this study was that in most cases the baseline uniform pattern observed in some PVs during AF was the same as the first activation site and/or polarity reversal site recorded during sinus rhythm or atrial pacing. The irregular pattern did not allow identification of these breakthrough sites.

The cause of two different baseline PVP electrogram patterns during AF is not known. Macle et al. described how disorganized patterns of PV activation could become organized after initial application of RF energy at the atriovenous junction. This was attributed to a reduction in LA to PV electrical connections. In the present study, ablation was performed in both groups during sinus rhythm (right PV) or atrial pacing (left PV). Breakthroughs were confirmed by ablation producing local elimination or prolongation of conduction or distinct alteration in the activation sequence. However, no difference in the number of breakthroughs was found between the two patterns in this study. This indicates that the uniform pattern of PV activation during AF does not necessarily suggest a single breakthrough, whereas multiple breakthroughs can manifest as a uniform pattern of PV electrogram during AF.

Myocardial sleeve connections from LA to PV are the anatomical basis for electrical breakthroughs.9Go The electrophysiological character of breakthroughs has not been specifically elucidated in the literature. The presence of a uniform pattern of PV activation in patients with multiple breakthroughs is probably due to variations in the conduction time of the breakthrough tracts. In these cases, a single breakthrough has a shorter conduction time compared with the other breakthroughs that only became apparent after the elimination of the first. The irregular pattern may be the result of fusion of activation from two or more breakthrough tracts with similar but temporally varying conduction times. Other possible causes of an irregular pattern of activation within the vein include fibrillatory conduction within the musculature of the vein itself and fusion of wave fronts conducted into the vein via the breakthrough tracts with those generated by the vein either by abnormal automaticity or by re-entry. Regular PV activation during AF is likely to be due to passive vein activation via atriovenous breakthroughs, whereas an irregular pattern may be due to passive activation of the vein or may involve impulse generation within the vein.

The findings of this study have clinical implications. Nearly half of the PVPs recorded during AF had a consistent activation sequence in our study. During sinus rhythm or atrial pacing, PV isolation can usually be performed by ablating at the first activation site and/or the site showing polarity reversal. Since the PVP electrogram is generally the same during AF in patients with a uniform PV activation sequence, ablation during AF can be map guided, based on the activation sequence and polarity reversal. This may reduce the required duration of the ablation and minimize the risk of PV stenosis.

In the earlier study by Macle et al., longer ablation times were required to isolate the veins with an irregular pattern of activation during AF. An important finding of the present study was that when similar patients were converted to sinus rhythm the ablation time was identical in patients with and without a consistent PV activation sequence and PV electrogram morphology. Thus, where electrical cardioversion is possible, it may reduce the required ablation time to achieve PV isolation in this group.

Limitations
Isolation of the PVs in a standardized order resulted in an unequal distribution of the veins studied. Most of the sampled veins were from the LS position and only one was an RI vein. Therefore, it is not possible to conclude that the properties of the RIPV were adequately explored in this study. Further, there may be subtle differences in each PV, which this study was not sensitive enough to detect.

Following restoration of sinus rhythm, PV activation was recorded during sinus rhythm for the right-sided PVs or during steady-state pacing for the left-sided veins. This reflected the protocol described by Yamane et al.4Go Pacing assists with delineation of the PV activation sequence for the left-sided veins. The relationship between the paced activation sequence and that during sinus rhythm was not addressed in the current study.

Only spontaneous AF or episodes of AF occurring apparently spontaneously during the study were included for analysis. This represents a small proportion of the total number of patients undergoing PV isolation and, therefore, the general principles regarding vein activation in AF may not apply to all patients. However, the study group consists of patients for whom the operator may need to make a decision about whether or not to isolate a vein in sinus rhythm or AF. Therefore, in this group, our findings have practical importance.

Some of the apparently spontaneous episodes of AF may have been induced by catheter manipulation or have been procedure related. The characteristics of AF induced in this way may be different from those of spontaneous AF.


    Conclusion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
We concluded that the PV activation sequence recorded during AF can be divided into uniform and irregular patterns. Nearly half of the electrograms manifest as a uniform pattern. Veins with the uniform pattern in AF had similar earliest PV activation sites or polarity reversal sites when compared with those recorded during sinus rhythm. However, the regular pattern does not always indicate a single atriovenous electrical breakthrough. Isolation of PVs can be performed during AF guided by the first activation site or polarity reversal site in patients with a uniform pattern of activation during AF.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
[1] Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of the patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995; 155: 469–73.[Abstract/Free Full Text]

[2] Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659–66.[Abstract/Free Full Text]

[3] Haïssaguerre M, Shah DC, Jaïs P, et al. Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation 2000; 102: 2463–5.

[4] Yamane T, Shah DC, Jaïs P, et al. Electrogram polarity reversal as an additional indicator of breakthroughs from the left atrium to the pulmonary veins. J Am Coll Cardiol 2002; 39: 1337–44.[Abstract/Free Full Text]

[5] Haïssaguerre M, Jaïs P, Shah DC, et al. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation 2000; 101: 1409–17.

[6] Oral H, Knight BP, Özaydm M, et al. Segmental ostial ablation to isolate the pulmonary veins during atrial fibrillation: feasibility and mechanistic insights. Circulation 2002; 106: 1256–62.

[7] Macle L, Jaïs P, Scavée C, et al. Electrophysiologically guided pulmonary vein isolation during sustained atrial fibrillation. J Cardiovasc Electrophysiol 2003; 14: 255–60.[Web of Science][Medline]

[8] Oral H, Özaydm M, Tada H, et al. Mechanistic significance of intermittent pulmonary vein tachycardia in patients with atrial fibrillation. J Cardiovasc Electrophysiol 2002; 13: 645–50.[CrossRef][Web of Science][Medline]

[9] Pappone C, Oreto G, Rosanio S, 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.


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