Background: To assess occurrence of a histologically validated measure of transmural (TM) atrial ablation-pure R unipolar electrogram (UE) morphology change-at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI). Methods: Objectively annotated VISITAG TM Module and CARTOREPLAY TM (Biosense Webster Inc., Diamond Bar, CA, USA) UE morphology data were retrospectively analyzed in 23 consecutive patients undergoing PVI under general anesthesia. Results: PVI without spontaneous/dormant recovery was achieved in all, employing 16.3 (3.2) min of radiofrequency (RF; 30 W) energy. All first-ablated LAPW sites demonstrated RS UE morphology preablation, with RF-induced pure R UE morphology change in 98%. Time to pure R UE morphology was significantly shorter at left-sided LAPW sites (4.9 [2.1] vs 6.7 [2.5] s; P = .02), with significantly greater impedance drop (median 13.5 vs 9.9 Ω; P = .003). Importantly, neither firstsite RF duration (14.9 vs 15.0 s) nor maximum ablation catheter tip distance moved (during RF) was significantly different, yet the mean CF was significantly higher at right-sided sites (16.5 vs 11.2 g; P = .002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ∼6-8 Ω impedance drop and ∼30% BE decrease at the time of first pure R UE morphology change. Conclusions: Using objective ablation site annotation, UE morphology evidence of TM RF effect was demonstrated far sooner than considered biologically possible according to the "conventional" 20-40 s RF per-site approach, with significantly greater ablative effect evident at left-sided sites. This novel methodology represents a scientifically more rigorous foundation toward future research into the biological effects of RF ablation in vivo. K E Y W O R D S atrial fibrillation, contact force catheter ablation, pulmonary vein isolation, unipolar electrogram, VISITAG TM Module 1 922

Aims To assess the occurrence of a histologically validated measure of transmural (TM) atrial ablation -pure R unipolar electrogram (UE) morphology change -at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI). significantly greater impedance drop (median 13.5Ω versus 9.9Ω; p=0.003). Importantly, neither the first-site RF duration (14.9 versus 15.0s) nor the maximum ablation catheter tip distance moved (during RF) were significantly different, yet the mean CF was significantly higher at right-sided sites (16.5g versus 11.2g; p=0.002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ~6-8Ω impedance drop and ~30% BE decrease at the time of first pure R UE morphology change. Methods and results ConclusionUsing objective ablation site annotation, TM UE morphology change was typically achieved within 7s at the LAPW, with significantly greater ablative effect evident at left-sided sites. The methodology described in this report represents a novel and scientifically more rigorous foundation towards future research into the biological effects of RF ablation in vivo.. CC-BY-NC-ND4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/234799 doi: bioRxiv preprint first posted online Dec. 15, 2017; 3 KeywordsAtrial fibrillation; contact force catheter ablation; pulmonary vein isolation; unipolar electrogram; VISITAG™ Module . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/234799 doi: bioRxiv preprint first posted online Dec. 15, 2017; 4 Condensed abstractThrough appropriate use of the VISITAG™ Module and CARTOREPLAY™, unipolar electrogram morphology change indicative of histologically confirmed transmural atrial ablation in animal models, was proven to occur typically within 7s, during first-site contact force-guided ablation at the left atrial posterior wall during pulmonary vein isolation.. CC-BY-NC-ND4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/234799 doi: bioRxiv preprint first posted online Dec. 15, 2017; 5What's New?• The VISITAG™ Module provides objective, automated ablation site annotation and may be used to record and identify biophysical parameters at positions of stable radiofrequency (RF) energy delivery in vivo.• CARTOREPLAY™ permits electrogram analyses at annotated sites; together, these modules permit evaluation of histologically validated unipolar electrogram (UE) criteria for transmural (TM) atrial ablation, following pulmonary vein isolation (PVI).• At first-ablated left atrial posterior wall sites, RF-induced UE morphology change from RS to pure R occurred in 98%. The time to pure R UE morphology change w...