Role of adenosine in atrial fibrillation

Role of adenosine in atrial fibrillation

First and foremost, it must be remembered that adenosine is not to be given in atrial fibrillation if there is an atrioventricular bypass tract (ventricular pre-excitation) like Wolff-Parkinson-White syndrome. This is because it slows conduction through the atrioventricular (AV) node, but does not affect the accessory pathway.

Secondly, adenosine can rarely induce atrial fibrillation and very rarely ventricular fibrillation.

Adenosine guided pulmonary vein ablation has been studied as adenosine might identify pulmonary veins at risk of reconnection by unmasking dormant conduction. Identifying dormant conduction will guide additional ablation to potentially improve the results of catheter ablation of atrial fibrillation. ADVICE (ADenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination) trial on this aspect was a randomized study at 18 hospitals across Australia, Europe, and North America [1]. Adenosine was administered intravenously after pulmonary vein isolation in symptomatic paroxysmal atrial fibrillation in which one anti arrhythmic drug had failed. If dormant conduction was identified, patients were randomized to additional adenosine guided ablation to abolish dormant conduction or to no further ablation.

Patients were masked to treatment allocation. Those in whom no dormant conduction was revealed, randomly selected patients were included in  a registry. Primary outcome measure was symptomatic atrial tachyarrhythmia after a single procedure in the intention-to-treat population. Adenosine unmasked dormant pulmonary vein conduction in 284 of the 534 patients. 102 of the 147 with additional adenosine guided ablation were free from symptomatic atrial tachyarrhythmia compared to 58 of the 137 patients with no further ablation (p<0·0001) [1].

Of the 115 patients without dormant pulmonary vein conduction included in the registry, 64 remained free of symptomatic atrial tachyarrhythmia (p=0·0191 vs dormant conduction with no further ablation). Similar occurrences of serious adverse events were noted in each group. Death due to massive stroke deemed probably related to ablation occurred in one patient included in the registry [1]. Authors suggested that adenosine testing to identify dormant conduction should become part of routine clinical practice.

UNDER-ATP (UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate) trial randomized 2113 patients with paroxysmal, persistent or long standing atrial fibrillation to either ATP guided pulmonary vein isolation or conventional pulmonary vein isolation [2]. Primary end point was recurrent atrial tachyarrhythmias lasting 30 s or more or those requiring repeat ablation, hospital admission or usage of Vaughan Williams class I or III antiarrhythmic drugs at 1 year. Blanking period was for 90 days after ablation. There was no significant difference in the primary end point at 1 year. Authors concluded that no significant reduction in recurrent atrial tachyarrhythmias with ATP guided pulmonary vein ablation compared to conventional pulmonary vein isolation was found.

A couple of meta analyses evaluated this aspect [3,4]. One of them identified 3524 patients and another 4099 patients. Both these meta analyses concluded that additional ablation aiming to eliminate adenosine induced transient pulmonary vein reconnection failed to reduce risk of atrial fibrillation recurrence at follow up. Additional studies to find out the actual role of adenosine in pulmonary vein isolation are needed.

References

  1. Macle L, Khairy P, Weerasooriya R, Novak P, Verma A, Willems S, Arentz T, Deisenhofer I, Veenhuyzen G, Scavée C, Jaïs P, Puererfellner H, Levesque S, Andrade JG, Rivard L, Guerra PG, Dubuc M, Thibault B, Talajic M, Roy D, Nattel S; ADVICE trial investigators. Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial. Lancet. 2015 Aug 15;386(9994):672-9.
  2. Kobori A, Shizuta S, Inoue K, Kaitani K, Morimoto T, Nakazawa Y, Ozawa T, Kurotobi T, Morishima I, Miura F, Watanabe T, Masuda M, Naito M, Fujimoto H, Nishida T, Furukawa Y, Shirayama T, Tanaka M, Okajima K, Yao T, Egami Y, Satomi K, Noda T, Miyamoto K, Haruna T, Kawaji T, Yoshizawa T, Toyota T, Yahata M, Nakai K, Sugiyama H, Higashi Y, Ito M, Horie M, Kusano KF, Shimizu W, Kamakura S, Kimura T; UNDER-ATP Trial Investigators. Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial. Eur Heart J. 2015 Dec 7;36(46):3276-87.
  3. Blandino A, Biondi-Zoccai G, Battaglia A, Grossi S, Bianchi F, Conte MR, Rametta F, Gaita F. Impact of targeting adenosine-induced transient venous reconnection in patients undergoing pulmonary vein isolation for atrial fibrillation: a meta-analysis of 3524 patients. J Cardiovasc Med (Hagerstown). 2017 Jul;18(7):478-489.
  4. Papageorgiou N, Providência R, Srinivasan N, Bronis K, Costa FM, Cavaco D, Adragão P, Tousoulis D, Hunter RJ, Schilling RJ, Segal OR, Chow A, Rowland E, Lowe M, Lambiase PD. Adenosine-guided pulmonary vein isolation versus conventional pulmonary vein isolation in patients undergoing atrial fibrillation ablation: An updated meta-analysis. Int J Cardiol. 2017 Jan 15;227:151-160.