Adenosine in human atrial fibrillation modulates and re-distributes atria-wide dominant frequencies and directs to reentry ablation sites with improved outcome.

Understanding and therapy of persistent atrial fibrillation (AF) are suboptimal partly because the dynamics, mapping, and ablation of rotational activity that has been proposed to drive AF remain elusive. In the present work we challenge AF with Adenosine, an agonist activating the Kir3.x subfamily of inward rectifier potassium channels and known to accelerate rotors, while performing non-invasive panoramic mapping. We studied 25 persistent AF patients who underwent mapping twice at baseline (B1, B2) and again during 12 mg Adenosine (Ado) peak effect. Post-procedure, spatial distributions of dominant frequencies (DFs) and differences (ΔDFs) were analyzed. During baseline, highest 50% DF sites strongly associated with |ΔDF|≤ 0.4 Hz between B1 and B2 and most stable DFs (|ΔDF|≤ 0.1 Hz) had highest DFs. During Adenosine, rotational domains displayed cycle length shortening in agreement with DF increase. However, the DF modulation by Adenosine was heterogeneous and transformed a single to a bi-modal DF distribution. A new DFAdo Stability Index (DFASI) was thereafter calculated at each virtual node as the normalized DFAdo weighted by normalized stability (1-|ΔDF|Norm) to locate regions with the highest acceleration relative to baseline variations. Distributions of DFASI ≥ 0.8 domains and rotational domains approximate each other, but their joint probability was 0.3249 indicating not all DFASI ≥ 0.8 and rotational domains co-localized. On follow up, higher all arrhythmia freedom was observed in patients in which all DFASI ≥ 0.8 domains were ablated than in patients in which not all such domains were ablated. The study proposes a new method for identifying reentries driving AF and a physiologically-based guidance for their ablation.