Atrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and PITX2+/- deficient) using computational modeling.We included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and PITX2+/- deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks.At the baseline AF, mean DF (p = 0.003), and Smax (p < 0.001) were significantly lower in PITX2+/- deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, p < 0.001) without changing the DF or Smax. Although a PITX2+/- deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate (p = 0.014), lower DF (p < 0.001), and lower Smax (p = 0.001) in PITX2+/- deficient AF than in wild-type patients. In the clinical setting, the PITX2+/- genetic risk score did not affect the AF ablation rhythm outcome (Log-rank p = 0.273).Consistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the PITX2 genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the PITX2+/- deficient patients.
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant [HI21C0011] from the Ministry of Health and Welfare, a grant [NRF-2020R1A2B5B01001695] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT & Future Planning (MSIP), and a grant [RS-2022-00141473] from Cross-ministerial tasks. Background High-power short-duration (HPSD) ablation generates wide and contiguous but shallow lesions by radiofrequency (RF) resistive heating. It is unknown whether RF energy titration has additional benefits depending on the atrial wall thickness. Purpose We aimed to compare the efficacy and safety of HPSD energy titration depending on left atrial wall thickness (LAWT) during circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods We prospectively randomized 224 patients with PAF (69.2% males, 59.3±12.0-years-old) into either the LAWT-guided CPVI group (WT, n=113) or the conventional CPVI group (Control, n=111). We delivered 15s of constant RF (contiguous lesion 2mm dots, FlexAbility) at 60W in the Control group but titrated the RF duration in the WT group (15 s at LAWT>2.1mm, 13s at 1.4–2.1mm, and 11s at <1.4mm) referencing the computed tomogram-myocardial thickness color map. The primary endpoints were safety and AF recurrence after a single procedure; the secondary endpoints were the procedure time, cardioversion rate, and response to anti-arrhythmic drugs (AADs). Results After a mean follow-up of 13.4±7.0 months, the clinical recurrence rate (13.3% vs. 8.1%, log-rank p=0.302) and the complication rate (8.0% vs. 4.5%, p=0.427) did not differ between the two groups. The total procedure time (p=0.391) and cardioversion rate (p=1.000) did not significantly differ between the two groups. During the final follow-up, sinus rhythm was maintained without AADs in 72.6% of the WT group and 80.2% of the Control group (p=0.237). Conclusions LAWT-guided energy titration resulted in efficacy and safety equivalent to that of constant 15s 60W-HPSD CPVI in patients with PAF.
Background: Although pulmonary vein isolation (PVI) is the basis of atrial fibrillation (AF) catheter ablation (AFCA), the conditional changes of an anti-AF effect and the wave-dynamic mechanism are poorly understood. Therefore, we compared the effects of PVI based on the ablation circumference, width, and number or locations of gaps with or without amiodarone at the same condition in realistic computational modeling of human AF. Hypothesis: An anatomical level of PVI and characteristics of the PVI gap would affect the anti-AF effects of the AFCA. Methods: We included 50 patients (76.0% persistent AF) who underwent AFCA. Realistic AF modeling reflecting the computed tomography (CT) and the electroanatomical map was performed on each patient. We compared the AF defragmentation rate (DeFR; change to atrial tachycardia (AT) or termination), termination rate (TnR), and changes in the dominant frequency (DF) and the number of phase singularities (PSs) based on the PVI level (antral vs. ostial), PVI width (single vs. 3х width), number and location of 2-mm PVI gaps with or without amiodarone (10mM). We randomly assigned the number and location of the PVI gaps to the AF models. Results: The antral PVI had a significantly higher DeFR (p for trend <0.001) and TnR (p for trend <0.001) than the ostial PVI, PVI gaps, or baseline AF. However, there was no difference depending on PVI width. Among the PVI gaps, the DeFR (p for trend<0.001) decreased as the gap number increased. Additional amiodarone increased DeFR (p=0.003) and TnR (p=0.034) and reduced DF (p<0.001) and the number of PSs (p<0.001) with PVI-gap, especially with a single PVI-gap. Conclusions: In this realistic computational modeling study with integrated patients’ atrial anatomy and electrophysiology, the atrial mass reduction depending on the anatomical PVI level, number of PVI gaps, and additional antiarrhythmic drug significantly affected the AF maintenance mechanisms.
Background: The ZFHX3 gene (16q22) is the second most highly associated gene with atrial fibrillation (AF) and is related to inflammation and fibrosis. We hypothesized that ZFHX3 is associated with extra-pulmonary vein (PV) triggers, left atrial (LA) structural remodeling, and poor rhythm outcomes of AF catheter ablation (AFCA). Methods: We included 1,782 patients who underwent a de novo AFCA (73.5% male, 59.4 ± 10.8 years old, 65.9% paroxysmal AF) and genome-wide association study and divided them into discovery (n = 891) and replication cohorts (n = 891). All included patients underwent isoproterenol provocation tests and LA voltage mapping. We analyzed the ZFHX3, extra-PV trigger-related factors, and rhythm outcomes. Result: Among 14 single-nucleotide polymorphisms (SNPs) of ZFHX3, rs13336412, rs61208973, rs2106259, rs12927436, and rs1858801 were associated with extra-PV triggers. In the overall patient group, extra-PV triggers were independently associated with the ZFHX3 polygenic risk score (PRS) (OR 1.65 [1.22-2.22], p = 0.001, model 1) and a low LA voltage (OR 0.74 [0.56-0.97], p = 0.029, model 2). During 49.9 ± 40.3 months of follow-up, clinical recurrence of AF was significantly higher in patients with extra-PV triggers (Log-rank p < 0.001, HR 1.89 [1.49-2.39], p < 0.001, model 1), large LA dimensions (Log-rank p < 0.001, HR 1.03 [1.01-1.05], p = 0.002, model 2), and low LA voltages (Log-rank p < 0.001, HR 0.73 [0.61-0.86], p < 0.001, model 2) but not the ZFHX3 PRS (Log-rank p = 0.819). Conclusion: The extra-PV triggers had significant associations with both ZFHX3 genetic polymorphisms and acquired LA remodeling. Although extra-PV triggers were an independent predictor of AF recurrence after AFCA, the studied AF risk SNPs intronic in ZFHX3 were not associated with AF recurrence.
Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2022R1I1A1A01071083). This work was also supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: RS-2022-00141473). Background In the planning of atrial fibrillation (AF)-related procedures, predicting left atrial (LA) anatomy and pulmonary vein (PV) diameter is important for the effectiveness and safety of the procedures but requires a labor-intensive measurement process. Here, we propose an artificial intelligence (AI) based PV diameter measurement algorithm for the computed tomogram (CT)-based automated PV evaluation. Methods We implemented a mesh-based convolutional neural network for the surface segmentation of four PVs and the LA appendage (LAA) in a 3D LA surface mesh. Our algorithm includes two originative methods of surface depth feature and cohesion loss function to improve the performance. We trained the model with the LA mesh of 210 AF patients’ CT scan and validated the accuracy of surface segmentation and PV diameter with independent 158 samples. Results Using an AI-based automated LA measurement model, we achieved an average Intersection over Union (IoU) of 83.4% and a regional IoU from 78.4 to 87.2 % in 158 LA meshes. When we added the surface depth feature, the IoU was improved by 31.7% compared to the conventional 3D feature. The cohesion loss function reduced the fragmentation rate of the surface label by 3.2%. Post-processed PV diameters did not differ from manually measured left (P=0.56) and right upper PV diameters (P=0.08) but differed in both lower PVs (p<0.001). The eccentricity variance of the PV ostia did not differ between AI-measured and manually measured PVs (P=0.68~0.84). Conclusion We proposed an AI-guided automated algorithm for surface segmentation and PV diameter measurement and validated it at both upper PVs and the eccentricity of the PV ostia. Our algorithm can be applied to the automated sizing of LA appendage and improve labor-intensive manual segmentation.
The discrimination learning of multiple odors, in which multi-odor can be associated with different responses, is important for responding quickly and accurately to changes in the external environment. However, very few studies have been done on multi-odor discrimination by animal sniffing. Herein, we report a novel multi-odor discrimination system by detection rats based on the combination of 2-Choice and Go/No-Go (GNG) tasks into a single paradigm, in which the Go response of GNG was replaced by 2-Choice, for detection of toluene and acetone, which are odor indicators of lung cancer and diabetes, respectively. Three of six trained rats reached performance criterion, in 12 consecutive successful tests within a given set or over 12 sets with a success rate of over 90%. Through a total of 1300 tests, the trained animals (N = 3) showed multi-odor sensing performance with 88% accuracy, 87% sensitivity and 90% specificity. In addition, a dependence of behavior response time on odor concentrations under given concentration conditions was observed, suggesting that the system could be used for quantitative measurements. Furthermore, the animals’ multi-odor sensing performance has lasted for 45 days, indicating long-term stability of the learned multi-odor discrimination. These findings demonstrate that multi-odor discrimination can be achieved by rat sniffing, potentially providing insight into the rapid, accurate and cost-effective multi-odor monitoring in the lung cancer and diabetes.
Abstract Aims Whether adjusting the duration of ablation based on left atrial wall thickness (LAWT) provides extra benefits for pulmonary vein (PV) isolation for atrial fibrillation (AF) is uncertain. We studied the safety and efficacy of tailored cryoballoon PV isolation (CB-PVI) based on LAWT for paroxysmal AF. Methods and results 277 patients with paroxysmal AF refractory to anti-arrhythmic drug were randomized 1:1 to either LAWT-guided CB-PVI (n=135) and empirical CB-PVI (n=142). Empirical CB-PVI was performed using a 28-mm cryoballoon with recommended application for 240 seconds per ablation. Cryoapplication in the LAWT-guided group was titrated (additional application for 120 seconds at PVs, where >25% of the circumference includes segments with LAWT >2.5mm and reduced baseline application to 180 seconds at PVs where >75% of the circumference includes segments with LAWT <1.5mm) according to the computed tomogram-LAWT color map. The primary endpoint was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication, after a single ablation procedure. During a mean follow-up of 18.7 months, patients in the LAWT-guided CB-PVI group (70.8%) had a higher event-free rate from primary endpoint than those in the empirical CB-PVI group (54.4%; HR 0.64, 95% CI 0.42-0.99; P=0.043). No differences were observed between the groups in complication rates (3.0% in LAWT-guided vs. 4.9% in empirical CB-PVI). The total procedure time was extended in the LAWT group than in the empirical group (mean 70.2 vs. 65.2 minutes, respectively). Conclusions The LAWT-guided energy titration strategy improved freedom from atrial arrhythmia recurrence, compared with conventional strategy.
Background Although pulmonary vein isolation (PVI) gaps contribute to recurrence after atrial fibrillation (AF) catheter ablation, the mechanism is unclear. We used realistic computational human AF modeling to explore the AF wave-dynamic changes of PVI with gaps (PVI-gaps). Methods We included 40 patients (80% male, 61.0 ± 9.8 years old, 92.5% persistent AF) who underwent AF catheter ablation to develop our realistic computational AF model. We compared the effects of a complete PVI (CPVI) and PVI-gap (2-mm × 4) on the AF wave-dynamics by evaluating the dominant frequency (DF), spatial change of DF, maximal slope of the action potential duration restitution curve (Smax), and AF defragmentation rate (termination or change to atrial tachycardia), and tested the effects of additional virtual interventions and flecainide on ongoing AF with PVI-gaps. Results Compared with the baseline AF, CPVIs significantly reduced extra-PV DFs ( p < 0.001), but PVI-gaps did not. COV-DFs were greater after CPVIs than PVI-gaps ( p < 0.001). Neither CPVIs nor PVI-gaps changed the mean Smax. CPVIs resulted in higher AF defragmentation rates (80%) than PVI-gaps (12.5%, p < 0.001). In ongoing AF after PVI-gaps, the AF defragmentation rates after a wave-breaking gap ablation, extra-PV DF ablation, or flecainide were 60.0, 34.3, and 25.7%, respectively ( p = 0.010). Conclusion CPVIs effectively reduced the DF, increased its spatial heterogeneity in extra-PV areas, and offered better anti-AF effects than extra-PV DF ablation or additional flecainide in PVI-gap conditions.
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