Anti- and pro-fibrillatory effects of pulmonary vein isolation gaps in human atrial fibrillation digital twins

Abstract

Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm (p < 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p < 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.

Fig. 1. AF digital twins, AF induction protocol, and virtual interventions.

a We integrated the patient’s CT image and electroanatomical map to create a digital twin of LA. Virtual maps of patients, including voltage, local activation time, fiber orientation, and fibrosis maps, represent LA’s histological and electrophysiological properties. b We induced virtual AF with ramp pacing protocol. The action potential of the triangle site shows successful induction and maintenance of virtual AF. c We draw the virtual antral line, ostial line with single width (2 mm), and ostial line width triple width (6 mm) for every 50 patients. The green line indicates the ablation line. d Orange arrows indicate the gaps of PVI. The standard position of the gap is on both PVs’ upper, lower, anterior, and posterior parts. e We changed pacing sites from Bachman’s bundle area to the inside PV. AF atrial fibrillation, AP action potential, CT computed tomography, LA left atrium, PV pulmonary vein, PVI pulmonary vein isolation.

Fig. 2. Rhythm outcomes according to the number of PVI gaps and pacing sites.

a The ratio of AF at the final rhythm according to the numbers of PVI gaps (1 vs. 2 vs. 4 vs. 8). b The ratio of AF or AT at the final rhythm according to the numbers of PVI gap (1 vs. 2 vs. 4 vs. 8). c Rhythm outcomes including the final rhythm status and non-inducible rate of AF according to pacing site. d The orange arrows represent 2 mm gaps on the antral PVI line. The pink dots represent the pacing locations. Both models were created using the same patient, 4 PVI gaps, and locations. However, in the extra-PV pacing model, AF was well sustained. AF atrial fibrillation, AT atrial tachycardia, PV pulmonary vein, PVI pulmonary vein isolation.

Fig. 3. Rhythm outcomes of virtual PVI according to different PVI conditions.

Using human AF digital twin technology, we could quantitatively assess and compare the anti-fibrillatory and pro-fibrillatory effects of PVI gaps. Through our simulation experiments, we confirmed the following four key findings. First, wide antral PVI exhibited a significantly more substantial effect on AF termination when compared to ostial PVI. Second, the thickness of the PVI lines did not significantly influence AF maintenance or termination. Third, an increase in the number of PVI gaps correlated with reduced anti-AF efficacy. Lastly, the induction and maintenance of AF were found to be more facile when employing extra PV pacing than intra-PV pacing.

Fig. 4. Flow chart of the study.

We included 50 AF patients from the Yonsei AF ablation cohort. We generated digital twins of LA and induced virtual AF, and compared rhythm outcomes according to different virtual interventions. Different conditions include PVI level and width, number of PVI gaps, and pacing location. Rhythm outcomes include final rhythm status and the rate of non-inducible AF. AF atrial fibrillation, AT atrial tachycardia, LA left atrium, PV pulmonary vein, PVI pulmonary vein isolation.

Fig. 5. Possible rhythm outcomes and calculation methods after induction of virtual AF.

a The pacing started at 200 ms and decreased by 10 ms intervals until it reached 120 ms to induce AF. Red dots indicate pacing stimulation markers. b Induced AF remained after 32 s. c AF converted to regular AT at 22 s. d No activation signal was observed after 21 s. e No activation signal was observed right after 11.52 s of induction protocol. f The calculation methods of rhythm outcomes. AF atrial fibrillation, AT atrial tachycardia, PV pulmonary vein.