Journal of Interventional Cardiac Electrophysiology

, Volume 22, Issue 1, pp 31–37

Clinical outcome of left atrial ablation for paroxysmal atrial fibrillation is related to the extent of radiofrequency ablation

Authors

    • Department of CardiologyAthens Euroclinic
  • Kenneth A. Ellenbogen
    • Division of CardiologyMedical College of Virginia
  • Eleftherios Giazitzoglou
    • Department of CardiologyAthens Euroclinic
  • Dimitrios Sougiannis
    • Department of CardiologyAthens Euroclinic
  • George Paxinos
    • Department of CardiologyAthens Euroclinic
  • Nicolaos Fragakis
    • Department of CardiologyAthens Euroclinic
  • A. John Camm
    • Cardiac and Vascular SciencesSt George’s, University of London
Article

DOI: 10.1007/s10840-008-9247-9

Cite this article as:
Katritsis, D., Ellenbogen, K.A., Giazitzoglou, E. et al. J Interv Card Electrophysiol (2008) 22: 31. doi:10.1007/s10840-008-9247-9

Abstract

Background

The exact mechanism of eliminating atrial fibrillation (AF) by catheter ablation techniques is not known. We investigated whether the extent of atrial damage conferred by radiofrequency lesions is a predictor of success after ablation, regardless of the method employed for ablation.

Methods

Ninety consecutive patients with paroxysmal AF subjected to ostial–antral pulmonary vein isolation (n = 41) or circumferential (n = 49) catheter ablation were studied.

Results

At 1 year follow-up, 16 out of 41 patients (39%) with ostial–antral ablation and 16 out of 49 patients (32.6%) with circumferential ablation had AF recurrences (p = 0.5). The mean duration of radiofrequency ablation lesions was statistically significantly shorter in patients with recurrence of AF compared to those with sinus rhythm 1 year after ablation (22.3 ± 4.2 min vs. 27.2 ± 4.5 min, respectively, p value < 0.001). Radiofrequency ablation time was inversely associated with the risk of recurrence of AF 1 year after ablation and this relationship remained even after adjustment for potential confounding factors such as age, sex, left atrial size, and type of ablation technique (ostial–antral or circumferential; HR  =  0.80, 95% CI: 0.72–0.87, p < 0.001).

Conclusions

Duration of radiofrequency energy delivery is an independent predictor of clinical outcome at 1 year follow-up both among patients undergoing circumferential as well as ostial–antral ablation.

Keywords

Atrial fibrillationAblationCircumferentialOstialAntral

The exact mechanism of eliminating atrial fibrillation (AF) by catheter ablation techniques is not known. Although re-emergence of AF following pulmonary vein (PV) disconnection procedures is usually due to recurrence of PV conduction, [13] complete electrical isolation of the PVs may not be necessary for a successful outcome. [2, 48] Nonencircling left atrial lesions created by catheter ablation have been found equally effective with circumferential ablation in eliminating permanent AF [9], and tailored catheter approaches that either target triggers and drivers of AF [10] or aim at non-inducibility of the arrhythmia can produce favourable long-term results with [11, 12] or without [12, 13] verification of PV isolation. Electrogram-guided ablation may also produce favorable clinical results [14] although the mechanism of eliminating AF appears to be different than that of circumferential ablation [15]. It has been suggested that the extent of left atrial ablation (average 30%) is a marker of success rather than PV isolation [16], but no specific data relating clinical efficacy of various ablation techniques with the duration of radiofrequency lesions exists.

The present study investigated the relationship between clinical efficacy of various ablation techniques with the extent of left atrial lesions performed in patients with paroxysmal atrial fibrillation.

1 Methods

Patients

Consecutive patients with symptomatic, paroxysmal atrial fibrillation subjected to catheter ablation according to different techniques and in whom no second ablation attempt was performed throughout a 1-year follow-up period were included in the study. Patients who underwent a repeat ablation attempt for AF recurrence or ablation-induced atrial flutter or focal tachycardia were excluded from this analysis. Detailed data regarding radiofrequency energy delivery (number of lesions, and energy delivery time) were kept for all patients. The trial was approved by our Institutional Review Board and all patients had provided a written, informed consent.

Ablation Techniques

Details of ablation techniques performed in our laboratory have been published elsewhere [12, 17, 18]. In brief, segmental ostial–antral ablation of PVs was accomplished with a Lasso™ circular electrode catheter (Biosense Cordis-Webster, Diamond Bar, CA, USA). The PV isolation end-point was elimination of PV muscle conduction distal to the ablation site based on abolition or dissociation of distal PV potentials and demonstration of entrance and exit block [17]. Initially a purely ostial approach was adopted for PV disconnection. Later, lesions were delivered at the antrum just outside the ostium of the PV as indicated in Fig. 1, using the Lasso and the same end-points. Circumferential ablation was performed with the aid of electroanatomical mapping (Carto, Biosence-Webster) at a distance of approximately 1–2 cm from the ostia of the left and right PVs (Fig. 2), aimed at a voltage reduction by >80% or a peak to peak bipolar electrogram <0.1 mV [12, 18]. If these end-points were not achieved after 30 s of radiofrequency current application, the catheter was moved to the next site until completion of the circumferential lesions around the PV ostia was achieved.
https://static-content.springer.com/image/art%3A10.1007%2Fs10840-008-9247-9/MediaObjects/10840_2008_9247_Fig1_HTML.gif
Fig. 1

Diagram of lesions delivered for ostial or antral ablation. End-points for PV disconnection were the same as described in the text

https://static-content.springer.com/image/art%3A10.1007%2Fs10840-008-9247-9/MediaObjects/10840_2008_9247_Fig2_HTML.gif
Fig. 2

Circumferential ablation around the right PVs. Please note that lesions are delivered away from the ostium

Ablation procedures were performed following IV enoxaparin (1 mg/Kg) with a conventional 4 mm catheter tip and 2.5 mm interelectrode spacing (Cordis-Webster), at a preset electrical power of 40 Watts, aiming at a target temperature of 52°C (for ostial–antral ablation), and an irrigated-tip ablation catheter (infusion rate of 17 ml/min) with a 4 mm tip and 2.5 mm interelectrode spacing (Cordis-Webster) electrical power of 30 W and aiming at a target temperature of 46°C (for circumferential ablation).

1.1 Follow-up

As part of our routine AF ablation protocol, all but two patients with chronic obstructive pulmonary disease were receiving beta blockers, whereas all patients were kept on amiodarone and warfarin for 6 weeks post-ablation. Patients were subjected to monthly clinical assessment and ambulatory electrocardiographic monitoring up to 1 year. All patients were instructed to maintain personal records with descriptions of every episode of symptomatic palpitations and, in case of persistent arrhythmia episodes, to obtain trans-telephonic or electrocardiographic documentation of the underlying rhythm. A successful outcome over the follow-up period was defined as the lack of electrocardiographically recorded AF, and no PAF on Holter, and subjective symptomatic improvement after a 6-week blanking period. Patients we reviewed both by fellows who were blinded to treatment and at least two members of the ablation team. Final decisions regarding clinical outcome was made by consensus among the ablation team. Trans-esophageal echocardiography and magnetic resonance imaging of the PVs were also performed in all patients at completion of follow-up to exclude PV stenosis.

1.2 Statistical analysis

Shapiro–Wilk test was used to evaluate the normality of continuous variables (i.e. age, left atrial size, radiofrequency time) and because no variable was skewed, all of them are presented as mean±SD while categorical variables are summarized as absolute and relative (%) frequencies. Associations between categorical variables were tested with the chi square test, and associations between continuous and categorical variables were tested with Student's t test. Freedom from recurrent AF was determined using Kaplan–Meier analysis and differences in AF-free survival were evaluated using the log-rank test. Cox proportional hazard model was used to evaluate the association between the extent of left atrial ablation (extent of radiofrequency time in minutes) and the recurrence of AF 1 year post-ablation, after controlling for potential confounders such as type of ablation technique and ablation catheter type, age, sex, and left atrial size. Separate models were fitted using radiofrequency time as continuous and as binary variable (short vs. long time). Appropriate plot used to assess the proportional hazards assumption revealed that this was valid. All reported p values were based on two-sided tests and were compared to a significant level of 5%.

2 Results

2.1 Clinical characteristics

In total, 90 patients were analysed. Forty one patients were subjected to ostial–antral PV isolation (32 patients had purely ostial and 9 patients antral ablation) while 49 patients underwent circumferential ablation. Among all patients, 75 (83%) were men and the rest 15 (17%) were women with mean age 56 ± 8 and 55 ± 9 years, respectively. Demographic and clinical characteristics of patients according to the amount of ablation which they received (short-less than median- and long—more than median—radiofrequency time) are presented in Table 1. No difference was observed in age, cause and left atrial size distribution between the two groups, while patients who received more ablation were more likely to be men compared to those who received less ablation. Table 2 shows patients characteristics according to type of ablation technique.
Table 1

Characteristics of patients with respect to radiofrequency time of ablation

 

Short radiofrequency time (<median)

Long radiofrequency time (≥median)

p value

Age (years)

54.7 ± 8.2

54.8 ± 9.5

0.972

Males (n, %)

34 (76%)

41 (91%)

0.048

Cause of atrial fibrillation

Hypertension

25 (55%)

25 (56%)

0.812

Coronary Artery Disease

7 (16%)

9 (20%)

 

Lone AF

13 (29%)

11 (24%)

 

Left atrial size

40.5 ± 4.8

40.9 ± 4.08

0.655

Ablation technique

Ostial–antral

18 (40%)

23 (51%)

0.290

Circumferential

27 (60%)

22 (49%)

 
Table 2

Characteristics of patients by type of ablation technique

 

Ostial–antral Ablation (n = 41)

Circumferential Ablation (n = 49)

p value

Age (years)

52 ± 10

57 ± 7

0.005

Males (n, %)

36 (89%)

39 (80%)

0.298

Cause of atrial fibrillation

Hypertension

21 (51%)

29 (59%)

0.751

Coronary artery disease

8 (20%)

8 (16%)

 

Lone AF

12 (29%)

12 (24%)

 

Left atrial size

40.1 ± 2.3

41.2 ± 5.6

0.283

2.2 Procedural characteristics

Procedural characteristics are presented in Table 2. The mean±SD of radiofrequency time among all patients recruited in the study was 25.4 ± 4.9 min (range: 14.5–37.5 min, median: 25.4 min). No statistical difference was observed in radiofrequency time between patients who underwent ostial–antral ablation and those in whom circumferential ablation was performed (Table 3).

Procedures were uneventful in all but two patients who experienced tamponade immediately after the procedure. One was treated with pericardiocentesis without sequellae, whereas the other required surgical exploration and drainage during which perforation of the right atrial appendage was diagnosed. This was attributed to the transeptal puncture. No cases of PV stenosis or oesophageal fistula were encountered.
Table 3

Cumulative radiofrequency current delivery, procedure and fluoroscopy times

 

Ostial–antral Ablation (n = 41)

Circumferential Ablation (n = 49)

p value

RF time (minutes)

25.9 ± 3.6

25.1 ± 5.8

0.456

Fluoroscopy time (minutes)

56.3 ± 7.9

28.2 ± 6.1

<0.001

Procedure time (minutes)

208.8 ± 26.9

180.1 ± 18.4

<0.001

2.3 Clinical outcome and radiofrequency time

At 1 year follow-up, 16 out of 41 patients (39%) with ostial–antral ablation and 16 out of 49 patients (32.6%) with circumferential ablation had AF recurrences (p = 0.5). AF recurrence was statistically significantly higher among patients with short ablation times (51.1%) compared to those with long ablation times (20%, p = 0.002). Radiofrequency mean±SD time was statistically significantly shorter among patients with AF recurrence (22.3 ± 4.2 min) compared to those with sinus rhythm after 1 year of follow-up (27.2 ± 4.5 min, p < 0.001). Stratified analysis by sex, cause of AF and type of ablation technique showed that the radiofrequency time was statistically significantly shorter among patients with AF recurrence compared to those with SR independent of cause and type of ablation technique, while with respect to the sex, no significant relationship was observed between amount of ablation and clinical outcome among female patients (Table 4).
Table 4

Radiofrequency time for patients with sinus rhythm and those with AF recurrence, stratified by sex, cause of AF and type of ablation technique In brackets we present the number of patients for each group

 

Sinus rhythm (n = 58)

AF recurrence (n = 32)

p value

All (90)

27.2 ± 4.5

22.3 ± 4.2

<0.001

Sex

   

 Female (15)

24.5 ± 3.8 (11)

23.3 ± 4.0 (4)

0.597

 Male (75)

27.8 ± 4.4 (47)

22.1 ± 4.2 (28)

<0.001

Cause of AF

   

 Hypertension (50)

26.8 ± 4.3 (31)

22.6 ± 4.7 (19)

0.002

 Coronary artery disease (16)

29.3 ± 4.8 (8)

22.9 ± 3.2 (8)

0.007

 Lone AF (24)

26.8 ± 4.6 (19)

20.1 ± 2.7 (5)

0.005

Type of ablation technique

   

 Ostial–antral (41)

27.6 ± 2.9 (25)

23.1 ± 2.9 (16)

<0.001

 Circumferential (49)

26.8 ± 5.4 (33)

21.5 ± 5.1 (16)

0.002

p value: for comparison of radiofrequency time between patients with SR and those with AF recurrence

Mean time of first recurrence was 3.2 ± 0.9 months. Log-rank test revealed that the AF-free survival was higher among patients who received higher amount of ablation compared to those who received lower amount of ablation (p = 0.001, Fig. 3). In particular, we observed that 48.9% and 80% of patients with short and long ablation time, respectively, had no AF recurrence after 1 year follow-up. Cox proportional hazard model showed that for one minute increase in radiofrequency energy delivery there was a 16% reduction in the risk for recurrence of AF (HR = 0.84, 95% CI: 0.77–0.90, p < 0.001). This inverse relationship between radiofrequency energy delivery time and recurrence of AF remained (HR: 0.80, 95% CI: 0.72–0.87, p < 0.001), even after adjustment for potential confounders such as age, sex, cause of AF, left atrial size and type of ablation technique (ostial–antral or circumferential). Further analysis revealed that the risk for AF recurrence among patients whose ablation procedure lasted more than 25.4 min (median of radiofrequency time) was almost 65% lower compared to those whose radiofrequency time was less than 25.4 min (HR: 0.34, 95% CI: 0.16–0.73).
https://static-content.springer.com/image/art%3A10.1007%2Fs10840-008-9247-9/MediaObjects/10840_2008_9247_Fig3_HTML.gif
Fig. 3

AF-free survival curves for patients with short ablation time (time < median) and those with long ablation time (time > median)

Since sex distribution among patients who received low and high amount of ablation was different (Table 1), remained confounding may exists. Therefore, we performed stratified analysis by gender. Cox proportional hazard models showed that among men the one minute increase in radiofrequency time is associated with 16% reduction in risk for AF recurrence (HR = 0.84, 95% CI: 0.77–0.90), while no association was observed among female patients (HR = 0.91, 95% CI: 0.66–1.25). The small number of women among the total study population may account for this finding.

3 Discussion

Our results suggest that elimination of the electrical activity of the left atrium is a powerful predictor of AF-free survival in patients subjected to catheter ablation, regardless of the ablation technique employed. This is in keeping with the observations of Pappone and colleagues in the setting of circumferential ablation [16]. Our study indicates that the amount of ablated atrial myocardium is also critical in the ostial–antral ablation approach.

Our results can be interpreted within the context of the multi-factorial aetiology of AF [19, 20]. There is now substantial evidence that apart from the PVs, other parts of the left atrium such as the PV-left atrial junction [21], the posterior left atrial wall [22], and areas rich in sympathetic [23] or parasympathetic [24] innervation may also contribute to triggering and maintaining of AF through various mechanisms [21, 22, 25, 26]. One might therefore speculate that the more extensive the ablation-induced damage, the higher the possibility of intervening with one of these mechanisms. An effect on rotors and AF nests as probably happens with real-time frequency analysis- and complex fractionated electrogram-guided ablation [14, 27] cannot be ruled out with extensive left atrial ablation. Nevertheless, mere elimination of the left atrial tissue below the critical amount required for reentry [24] may also theoretically affect clinical outcomes. Perhaps it is not surprising that in a recent report, single ablation end-points such as PV disconnection or voltage abatement did not to persist over time and did not predict clinical outcome [28].

However, our results should be considered with caution. The effect of ablation on left atrial transport function is still debated [29, 30] and left atrial voltage reduction [31] and fibrosis [32] may predispose to AF development. Risk of complications may also be increased with prolonged ablation procedures. We certainly do not advocate an unnecessarily prolonged procedure with delivery of an unrestricted number of ablation lesions. Theoretically, clinical outcomes should be optimized by performing the minimum amount of ablation and left atrial damage. Further studies are necessary to address this important issue.

3.1 Study limitations

Our study has several limitations. First, asymptomatic episodes after catheter ablation of AF are well documented [33, 34]. Nevertheless, this limitation applies almost to all reports on AF ablation and results in overestimation of the true success rate. Second, achieved temperatures for each individual lesion and in each patient have not been recorded for comparative purposes. Thus, actual left atrial damage can only be inferred from total ablation time. However, although theoretically expected, an increase in duration of radiofrequency energy application may not necessarily indicate a larger mass of left atrial tissue ablated. Third, patients subjected to different ablation techniques were not randomized. They were, however, consecutive patients who were subjected to the technique that used to be our clinical practice at time of recruitment. Finally, our small sample size might have been responsible for an overestimation of the association between time of ablation and recurrence of AF, such as the observed 16% reduction in the odds of AF recurrence for one additional minute of ablation.

Acknowledging these limitations, our study indicates that the extent of left atrial damage is the main determinant of clinical success following catheter ablation techniques, regardless of the method employed for ablation. It also supports the notion of several, different mechanisms being implicated in the genesis and perpetuation of AF.

Conflict of interest statement

There is no conflict of interest to be disclosed for any author.

Copyright information

© Springer Science+Business Media, LLC 2008