BackgroundAlthough rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation.MethodsMother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed.Results1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area.ConclusionMother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF.

We previously reported the feasibility and efficacy of a simulation-guided clinical catheter ablation of atrial fibrillation (AF) in an in-silico AF model. We developed a highly efficient realistic AF model reflecting the patient endocardial voltage and local conduction and tested its clinical feasibility. We acquired > 500 endocardial bipolar electrograms during right atrial pacing at the beginning of the AF ablation procedures. Based on the clinical bipolar electrograms, we generated simulated voltage maps by applying fibrosis and local activation maps adjusted for the fiber orientation. The software's accuracy (CUVIA2.5) was retrospectively tested in 17 patients and feasibility prospectively in 10 during clinical AF ablation. Results: We found excellent correlations between the clinical and simulated voltage maps (R = 0.933, p < 0.001) and clinical and virtual local conduction (R = 0.958, p < 0.001). The proportion of virtual local fibrosis was 15.4, 22.2, and 36.9% in the paroxysmal AF, persistent AF, and post-pulmonary vein isolation (PVI) states, respectively. The reconstructed virtual bipolar electrogram exhibited a relatively good similarities of morphology to the local clinical bipolar electrogram (R = 0.60 ± 0.08, p < 0.001). Feasibility testing revealed an in situ procedural computing time from the clinical data acquisition to wave-dynamics analyses of 48.2 ± 4.9 min. All virtual analyses were successfully achieved during clinical PVI procedures. We developed a highly efficient, realistic, in situ procedural simulation model reflective of individual anatomy, fiber orientation, fibrosis, and electrophysiology that can be applied during AF ablation. Catheter ablation (CA) is an effective approach for rhythm control management of atrial fibrillation (AF) 1,2. However, the recurrence rate after AF ablation procedures is still substantial 3. Although pulmonary vein isolation (PVI) is a well-established target of AF ablation, extra-pulmonary vein (PV) foci or drivers maintain AF in some patients, and extra-PV foci are more commonly found in AF patients with significant left atrial (LA) remodeling 4,5. The Substrate and Trigger Ablation for Reduction of Atrial Fibrillation trial part 2 (STAR AF2) demonstrated that an empirical extra-PV ablation did not improve the rhythm outcome compared with a circumferential PVI alone in patients with persistent AF (PeAF) 6. However, the one-year recurrence rate was higher than 40% regardless of any additional extra-PV ablation after the PVI, and the outcome of the invasive interventional catheter procedure was not adequate. Therefore, an innovative mapping technology to identify the core target of AF is needed in AF catheter ablation (AFCA). Simulation is a very useful computer-aided method for identifying appropriate intervention targets. We recently reported the feasibility of a simulation-guided PeAF ablation by applying a personalized heart computed tomography (CT) image-integrated AF simulation 7,8. To further this method, we developed a more realistic AF simulation r...

Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70%) and IK1 alone (+100%) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70%) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue.

Objective: Radiofrequency catheter ablation for persistent atrial fibrillation (PeAF) still has a substantial recurrence rate. This study aims to investigate whether an AF ablation lesion set chosen using in-silico ablation (V-ABL) is clinically feasible and more effective than an empirically chosen ablation lesion set (Em-ABL) in patients with PeAF.Methods: We prospectively included 108 patients with antiarrhythmic drug-resistant PeAF (77.8% men, age 60.8 ± 9.9 years), and randomly assigned them to the V-ABL (n = 53) and Em-ABL (n = 55) groups. Five different in-silico ablation lesion sets [1 pulmonary vein isolation (PVI), 3 linear ablations, and 1 electrogram-guided ablation] were compared using heart-CT integrated AF modeling. We evaluated the feasibility, safety, and efficacy of V-ABL compared with that of Em-ABL.Results: The pre-procedural computing time for five different ablation strategies was 166 ± 11 min. In the Em-ABL group, the earliest terminating blinded in-silico lesion set matched with the Em-ABL lesion set in 21.8%. V-ABL was not inferior to Em-ABL in terms of procedure time (p = 0.403), ablation time (p = 0.510), and major complication rate (p = 0.900). During 12.6 ± 3.8 months of follow-up, the clinical recurrence rate was 14.0% in the V-ABL group and 18.9% in the Em-ABL group (p = 0.538). In Em-ABL group, clinical recurrence rate was significantly lower after PVI+posterior box+anterior linear ablation, which showed the most frequent termination during in-silico ablation (log-rank p = 0.027).Conclusions: V-ABL was feasible in clinical practice, not inferior to Em-ABL, and predicts the most effective ablation lesion set in patients who underwent PeAF ablation.

Various maternal-infantile factors were found to affect HM composition. Interestingly, delivery mode, gender of infant, and birth height were associated with changes in HM macronutrient as well as postpartum age.