The role of adenosine challenge in catheter ablation for atrial fibrillation: A systematic review and meta-analysis

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Abstract

Aims

Adenosine may unmask dormant PV conduction and facilitate consolidation of PV isolation. We performed a meta-analysis to determine the impact of adenosine administration on clinical outcomes in patients undergoing PVI.

Methods

References and electronic databases reporting AF ablation and adenosine following PVI were searched through to 22nd November 2015. The impact of adenosine on freedom from AF was assessed in twenty publications after radiofrequency ablation (RFA), and in four publications after cryoablation to achieve PVI. Relative risks were calculated and combined in a meta-analysis using random effects modeling.

Results

In patients undergoing RFA with adenosine challenge, there was a significant reduction in freedom from AF in patients with versus without adenosine induced reconnection (RR 0.86; 95%CI 0.77–0.98; p = 0.02) particularly if no further ablation was performed (RR 0.66; 95%CI 0.50–0.87; p < 0.01). There was no difference when comparing outcomes in studies of routine adenosine challenge vs no adenosine (RR 1.07; 95%CI 0.93–1.22; p = 0.36). There was a non-significant trend to an increase in freedom from AF in patients receiving routine adenosine challenge (RR 1.18 95%CI 0.99–1.42; p = 0.07) in non-randomized studies using cryoablation.

Conclusion

Adenosine induced PV reconnection following PVI is associated with a significant increase in AF recurrence, particularly if the reconnection sites are not targeted for ablation. The routine use of adenosine may be beneficial in AF ablation if given early post-PVI, at sufficient dose and reconnection is ablated.

Introduction

Pulmonary vein isolation is the cornerstone of AF ablation [1]. Despite operator experience, advances in catheter sensing and mapping technologies and alternative energy delivery sources the single procedure success remains limited to 70% [2]. At repeat procedures pulmonary vein reconnection is frequently present. Adenosine/ATP may be administered following initial pulmonary vein isolation to unmask dormant pulmonary vein conduction with the premise that additional ablation at sites of acute reconnection may improve long term freedom from AF [3], [4]. Previous non-randomized studies [5], [6], [7] reported an improvement in outcome following catheter ablation for AF if adenosine was administered and sites of dormant reconnection ablated however recent large randomized controlled trials assessing the utility of adenosine in AF ablation have reported seemingly conflicting results [8], [9]. The aim of the present review and meta-analysis was to examine the available literature to determine the role of adenosine challenge on freedom from AF following PVI.

Section snippets

Methods

We searched The Cochrane Database of Systematic Reviews, Pubmed, Medline and Embase using the search term: ‘(adenosine or ATP) AND (pulmonary vein isolation OR ablation OR atrial fibrillation OR AF)’. The search strategy was limited to English language in human subjects where abstracts were available for review. Bibliographies of relevant articles were reviewed to assess for any further citations.

Articles were included if the study included an assessment of adenosine induced pulmonary vein

Results

The search strategy generated 1359 citations (see Supplementary Fig. 1), and twenty-four publications including 3970 patients who fulfilled the inclusion/exclusion criteria. The energy source to achieve pulmonary vein isolation was radiofrequency ablation in 20 [3], [4], [5], [6], [7], [8], [9], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23] and cryoablation in four [24], [25], [26], [27].

Discussion

The major findings of this systematic review of the available literature examining the role of adenosine/ATP testing following pulmonary vein isolation for AF are:

  • 1)

    adenosine/ATP induced PV reconnection is associated with a reduction in freedom from AF compared with no adenosine/ATP induced PV reconnection;

    • a.

      in particular adenosine/ATP induced PV reconnection not targeted for ablation is associated with a significant reduction in freedom from AF,

    • b.

      there was no significant difference in freedom from

Conclusions

In this meta-analysis of heterogeneous studies, adenosine induced PV reconnection following PVI is associated with a significant increase in AF recurrence, particularly if the reconnection sites are not targeted for ablation. The routine use of adenosine may be beneficial in AF ablation if given early post-PVI, at sufficient dose and reconnection is ablated however does not replace a routine observation period for surveillance of spontaneous PV recovery.

The following are the supplementary data

Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.

Funding sources

Dr. McLellan was supported by a postdoctoral fellowship from the National Heart Foundation of Australia (Award ID 101322), a fellowship from the European Heart Rhythm Association – Asia Pacific Heart Rhythm Society, Endeavour Fellowship, and has received research support from St Jude Medical. Dr. Kumar is supported by a NHMRC early career fellowship. Dr. Ling is supported by a postdoctoral fellowship from the Australian National Heart Foundation. Professor's Kistler and Kalman are supported by

Author contributions

A. McLellan, S·Kumar, S. Prabhu, L Ling: concept/design, data collection/collation, drafting of manuscript.

P·Kistler, J. Kalman: concept design, critical revision and approval of manuscript.

C·Smith: data analysis/statistics, critical revision and approval of manuscript.

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