The Relationship among Complex Fractionated Electrograms, Wavebreak, Phase Singularity, and Local Dominant Frequency in Fibrillation Wave-Dynamics: a Modeling Comparison Study

Although complex fractionated electrogram (CFE) is known to be a target for catheter ablation of fibrillation, its physiological meaning in fibrillation wave-dynamics remains to be clarified. We evaluated the spatiotemporal relationships among the parameters of fibrillation wave-dynamics by simulation modeling. We generated maps of CFE-cycle length (CFE-CL), local dominant frequency (LDF), wave break (WB), and phase singularity (PS) of fibrillation in 2-dimensional homogeneous bidomain cardiac modeling (1,000 × 1,000 cells ten Tusscher model). We compared spatiotemporal correlations by dichotomizing each maps into 10 × 10 lattice zones. In spatial distribution, WB and PS showed excellent correlation (R = 0.963, P < 0.001). CFE-CL had weak correlations with WB (R = 0.288, P < 0.001), PS (R = 0.313, P < 0.001), and LDF (R = -0.411, P < 0.001). However, LDF did not show correlation with PS or WB. PSs were mostly distributed at the periphery of low CFE-CL area. Virtual ablation (5% of critical mass) of CFE-CL < 100 ms terminated fibrillation at 14.3 sec, and high LDF ablation (5% of critical mass) changed fibrillation to organized tachycardia, respectively. In homogeneous 2D fibrillation modeling, CFE-CL was weakly correlated with WB, PS, and LDF, spatiotemporally. PSs are mostly positioned at the periphery of low CFE-CL areas, and virtual ablation targeting low CFE-CL regions terminated fibrillation successfully.ope

Clinical Usefulness of Computational Modeling-Guided Persistent Atrial Fibrillation Ablation: Updated Outcome of Multicenter Randomized Study

Objective: Catheter ablation of persistent atrial fibrillation (AF) is still challenging, no optimal extra-pulmonary vein lesion set is known. We previously reported the clinical feasibility of computational modeling-guided AF catheter ablation. Methods: We randomly assigned 118 patients with persistent AF (77.8% men, age 60.8 ± 9.9 years) to the computational modeling-guided ablation group (53 patients) and the empirical ablation group (55 patients) based on the operators' experience. For virtual ablation, four virtual linear and one electrogram-guided lesion sets were tested on patient heart computed tomogram-based models, and the lesion set with the fastest termination time was reported to the operator in the modeling-guided ablation group. The primary outcome was freedom from atrial tachyarrhythmias lasting longer than 30 s after a single procedure. Results: During 31.5 ± 9.4 months, virtual ablation procedures were available in 95.2% of the patients (108/118). Clinical recurrence rate was significantly lower after a modeling-guided ablation than after an empirical ablation (20.8 vs. 40.0%, log-rank p = 0.042). Modeling-guided ablation was independently associated with a better long-term rhythm outcome of persistent AF ablation (HR = 0.29 [0.12-0.69], p = 0.005). The rhythm outcome of the modeling-guided ablation showed better trends in males, non-obese patients with a less remodeled atrium (left atrial dimension < 50 mm), ejection fraction ≥ 50%, and those without hypertension or diabetes (p < 0.01). There were no significant differences between the groups for the total procedure time (p = 0.403), ablation time (p = 0.510), and major complication rate (p = 0.900). Conclusion: Among patients with persistent AF, the computational modeling-guided ablation was superior to the empirical catheter ablation regarding the rhythm outcome. Clinical trial registration: This study was registered with the ClinicalTrials.gov, number NCT02171364.ope

Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

BACKGROUND: Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. METHODS AND RESULTS: We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. CONCLUSIONS: SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation.ope

Pro-Arrhythmogenic Effects of Heterogeneous Tissue Curvature - A Suggestion for Role of Left Atrial Appendage in Atrial Fibrillation

BACKGROUND: The arrhythmogenic role of complex atrial morphology has not yet been clearly elucidated. We hypothesized that bumpy tissue geometry can induce action potential duration (APD) dispersion and wavebreak in atrial fibrillation (AF). Methods and Results: We simulated a 2D-bumpy atrial model by varying the degree of bumpiness, and 3D-left atrial (LA) models integrated by LA computed tomographic (CT) images taken from 14 patients with persistent AF. We also analyzed wave-dynamic parameters with bipolar electrograms during AF and compared them with LA-CT geometry in 30 patients with persistent AF. In the 2D-bumpy model, APD dispersion increased (P<0.001) and wavebreak occurred spontaneously when the surface bumpiness was greater, showing phase transition-like behavior (P<0.001). The bumpiness gradient 2D-model showed that spiral wave drifted in the direction of higher bumpiness, and phase singularity (PS) points were mostly located in areas with higher bumpiness. In the 3D-LA model, PS density was higher in the LA appendage (LAA) compared with other parts of the LA (P<0.05). In 30 persistent-AF patients, the surface bumpiness of LAA was 5.8-fold that of other LA parts (P<0.001), and exceeded critical bumpiness to induce wavebreak. Wave dynamics complexity parameters were consistently dominant in the LAA (P<0.001). CONCLUSIONS: Bumpy tissue geometry promoted APD dispersion, wavebreak, and spiral wave drift in in-silico human atrial tissue, and corresponded to clinical electroanatomical maps.ope

Clinical application of the fibrillation number in patients with an implantable cardioverter defibrillator

INTRODUCTION: Although ventricular tachycardia/fibrillation (VT/VF) develops suddenly with catastrophic results, its prediction is limited. We tested the fibrillation number (FibN) for potential predictor of VT/VF using clinical data of implantable cardioverter-defibrillator (ICD) patients after validating the number by computational modeling. METHODS: For clinical application of FibN, we used electrocardiography and echocardiography data: QRS width, QTc, and left ventricular (LV) end-systolic dimension (FibNVT/VF1) or LV end-diastolic dimension (FibNVT/VF2). We compared the maintenance duration of VT/VF for various FibN values using computational modeling, and tested FibNVT/VF in 142 patients with ICD for secondary prevention and 426 patients in age-sex matched control group (81.9% male, 56.1 ± 12.3 years old). RESULTS: 1. Computational results showed a positive correlation between VT/VF maintenance duration and FibN (R = 0.82, p < 0.001). 2. FibNVT/VFs were significantly higher in patients with ICD than in control (both FibNVT/VF1 and FibNVT/VF2, p < 0.001). 3. Within ICD group, FibNVT/VF values were higher in patients with cardiomyopathy than those without (both FibNVT/VF1 and FibNVT/VF2, p < 0.001). 4. During 50 ± 39 months follow-up period, the frequency of appropriate ICD therapy was higher in the high FibNVT/VF group (FibNVT/VF1, p = 0.001; FibNVT/VF2, p = 0.002). Both FibNVT/VF1 (HR 2.51, 95%CI 1.48-4.24, p = 0.001) and FibNVT/VF2 (HR 2.11, 95%CI 1.25-3.55, p = 0.005) were independently associated with appropriate ICD therapy in multi-variate analyses. CONCLUSION: FibNVT/VF, a parameter based on wavelength and heart size, correlates well with maintenance of VT/VF in computational modeling, and may have predictive value for VT/VF events in patients with ICD for secondary prevention.ope

Virtual ablation for atrial fibrillation in personalized in-silico three-dimensional left atrial modeling: comparison with clinical catheter ablation

BACKGROUND: Although catheter ablation is an effective rhythm control strategy for atrial fibrillation (AF), empirically-based ablation has a substantial recurrence rate. The purposes of this study were to develop a computational platform for patient-specific virtual AF ablation and to compare the anti-fibrillatory effects of 5 different virtual ablation protocols with empirically chosen clinical ablations. METHODS: We included 20 patients with AF (65% male, 60.1 ± 10.5 years old, 80% persistent AF [PeAF]) who had undergone empirically-based catheter ablation: circumferential pulmonary vein isolation (CPVI) for paroxysmal AF (PAF) and additional posterior box lesion (L1) and anterior line (L2) for PeAF. Using patient-specific three-dimensional left atrial (LA) geometry, we generated a finite element model and tested the AF termination rate after 5 different virtual ablations: CPVI alone, CPVI + L1, CPVI + L1,2, CPVI with complex fractionated atrial electrogram (CFAE) ablation, and CFAE ablation alone. RESULTS: 1. Virtual CPVI + L1,2 ablation showed the highest AF termination rate in overall patients (55%) and PeAF patients (n = 16, 62.5%). 2. The virtual AF maintenance duration was shortest in the case of virtual CPVI + L1,2 ablation in overall patients (2.19 ± 1.28 vs. 2.91 ± 1.04 s, p = 0.009) and in patients with PeAF (2.05 ± 1.23 vs. 2.93 ± 10.2 s, p = 0.004) compared with other protocols. CONCLUSION: Virtual AF ablation using personalized in-silico model of LA is feasible. Virtual ablation with CPVI + L1,2 shows the highest antifibrillatory effect, concordant with the empirical ablation protocol in patients with PeAF.ope

Prediction of flow fields around a sabot configuration using weighted average flux method

학위논문(석사) - 한국과학기술원 : 항공우주공학과, 1997.2, [ iv, 42 p. ]한국과학기술원 : 항공우주공학과, 1997.

Fibrillation number based on wavelength and critical mass in patients who underwent radiofrequency catheter ablation for atrial fibrillation

The heart characteristic length, the inverse of conduction velocity (CV), and the inverse of the refractory period are known to determine vulnerability to cardiac fibrillation (fibrillation number, FibN) in in silico or ex vivo models. The purpose of this study was to validate the accuracy of FibN through in silico atrial modeling and to evaluate its clinical application in patients with atrial fibrillation (AF) who had undergone radiofrequency catheter ablation. We compared the maintenance duration of AF at various FibNAF values using in silico bidomain atrial modeling. Among 60 patients (72% male, 54±13 years old, 82% with paroxysmal AF) who underwent circumferential pulmonary vein isolation (CPVI) for AF rhythm control, we examined the relationship between FibN AF and postprocedural AF inducibility or induction pacing cycle length (iPCL). Clinical FibNAF was calculated using left atrium (LA) dimension (echocardiogram), the inverse of CV, and the inverse of the atrial effective refractory periods measured at proximal and distal coronary sinus. In silico simulation found a positive correlation between AF maintenance duration and FibNAF ( R = 0.90, ). After clinical CPVI, FibNAF ( 0.296±0.038 versus 0.192±0.028, ) was significantly higher in patients with postprocedural AF inducibility ( n = 41) than in those without ( n = 19 ). Among 41 patients with postprocedural AF inducibility, FibNAF ( P = 0.935, ) had excellent correlations with induction pacing cycle length. FibNAF, based on LA mass and wavelength, correlates well with AF maintenance in computational modeling and clinical AF inducibility after CPVI.ope