Atrial Fibrillation Drivers Research Articles

Transfer Learning for Improved Classification of Drivers in Atrial Fibrillation.

"Drivers" are theorized mechanisms for persistent atrial fibrillation. Machine learning algorithms have been used to identify drivers, but the small size of current driver datasets limits their performance. We hypothesized that pretraining with unsupervised learning on a large dataset of unlabeled electrograms would improve classifier accuracy on a smaller driver dataset. In this study, we used a SimCLR-based framework to pretrain a residual neural network on a dataset of 113K unlabeled 64-electrode measurements and found weighted testing accuracy to improve over a non-pretrained network (78.6±3.9% vs 71.9±3.3%). This lays ground for development of superior driver detection algorithms and supports use of transfer learning for other datasets of endocardial electrograms.

Catheter Ablation With Morphologic Repetitiveness Mapping for Persistent Atrial Fibrillation

Catheter ablation for persistent atrial fibrillation (AF) has shown limited success. To determine whether AF drivers could be accurately identified by periodicity and similarity (PRISM) mapping ablation results for persistent AF when added to pulmonary vein isolation (PVI). This prospective randomized clinical trial was performed between June 1, 2019, and December 31, 2020, and included patients with persistent AF enrolled in 3 centers across Asia. Data were analyzed on October 1, 2022. Patients were assigned to the PRISM-guided approach (group 1) or the conventional approach (group 2) at a 1:1 ratio. The primary outcome was freedom from AF or other atrial arrhythmia for longer than 30 seconds at 6 and 12 months. A total of 170 patients (mean [SD] age, 62.0 [12.3] years; 136 men [80.0%]) were enrolled (85 patients in group 1 and 85 patients in group 2). More group 1 patients achieved freedom from AF at 12 months compared with group 2 patients (60 [70.6%] vs 40 [47.1%]). Multivariate analysis indicated that the PRISM-guided approach was associated with freedom from the recurrence of atrial arrhythmia (hazard ratio, 0.53 [95% CI, 0.33-0.85]). The waveform similarity and recurrence pattern derived from high-density mapping might provide an improved guiding approach for ablation of persistent AF. Compared with the conventional procedure, this novel specific substrate ablation strategy reduced the frequency of recurrent AF and increased the likelihood of maintenance of sinus rhythm. ClinicalTrials.gov Identifier: NCT05333952.

Abstract 18514: A Simulation Study on the Inducibility of Atrial Fibrillation Drivers From Intra-Atrial Electrode Catheters Using Personalized Computational Models Based on LGE-MRI

Introduction: Although non-inducibility of atrial fibrillation (AF) drivers just after pulmonary vein isolation (PVI) with or without substrate ablation for persistent AF (PsAF) has been proposed as an acute outcome suggesting a successful long-term outcome, recent studies have found no association with long-term freedom from atrial tachyarrhythmias. It is unclear whether the latter finding is due to complete elimination of all AF drivers or the inadequacy of an AF induction test. Recently, patient-specific computer simulation based on late gadolinium enhancement (LGE)-MRI has been proposed to be useful for detecting rotors as PsAF drivers. Hypothesis: By investigating the accuracy of an induction test following PsAF ablation from the sites commonly used in clinical practice, particularly coronary sinus (CS), we might establish the promising method to confirm non-inducibility during ablation procedure. Methods: Thirty-five consecutive PsAF patients underwent LGE-MRI tests for fibrosis-based computational models. Rotors were induced by rapid pacing from 40 bi-atrial sites near fibrosis after PVI then ablated, repeated until obtaining non-inducibility of rotors. Each induced rotor was investigated for whether it was induced by pacing at lateral right atrium (RA), high RA or CS where electrode catheters were typically placed and used for induction test (Figure). Results: Except for 9 patients having poor LGE-MRI images or low fibrosis burden, 21 patients had a total of 136 locations capable of sustaining extra-PVI rotors. Of the total amount of rotors induced, 24% were induced by pacing at lateral RA, 11% at high RA and 45% at CS, respectively. The capture of all arrhythmogenic locations capable of sustaining rotors improved to 59% by performing induction test from all 3 pacing sites instead of a single one (p<0.01). Conclusions: Although CS is the reasonable pacing site for induction test, that from RA should be also conducted for the optimal rotor detection.

Abstract 19050: Polysomnography and Sleep Symptom-Based Patient Profiles Associated With Atrial Fibrillation Development

Introduction: Although sleep disorders are linked to atrial fibrillation (AF), the complex interplay remains unclear. Investigating sleep-based profiles associated with AF can deepen understanding and identify at-risk patients. Hypothesis: We hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF. Methods: This retrospective cohort study of Cleveland Clinic patients (age>18) who underwent PSG 11/27/2004-12/30/2015 identified patient clusters using latent class analysis of 23 sleep-related symptoms, Epworth Sleepiness Scale (ESS) score, and 24 PSG measures of sleep disordered breathing and architecture. Cox proportional hazards models with cluster membership as the independent variable and incident AF as the dependent variable were adjusted for age, sex, race, BMI, cardiopulmonary disease and risk factors, anti-arrhythmic medication, and positive airway pressure with follow up 7.6±3.4 years. Results: Of the sample (n=43,433, age 52±15, 52% male, 74% White) 9% developed AF. Five clusters were identified: 1) Hypoxic + Sleepy (n=3,245): highest % time SaO 2 below 90%, highest ESS, 2) Apneas + Arousals (n=4,592): highest AHI, highest arousal index, 3) Short sleep + Low %REM (n=6,126): shortest sleep duration, longest REM latency, lowest %REM, 4) Hypopneas (n=2,661): most hypopneas, 5) Long sleep + High %REM (n=26,809): longest sleep duration, shortest REM latency, highest %REM (reference). Compared to reference, Hypoxic + Sleepy had 48% (HR=1.48, 95%CI=1.34-1.64), Apneas + Arousals had 22% (HR=1.22, 95%CI=1.11-1.35), and Short Sleep + Low %REM had 11% (HR=1.11, 95%CI=1.01-1.22) higher risk of AF development. Internal validation indicated reasonable predictive accuracy. Sensitivity analysis excluding split night studies confirmed the associations observed. Conclusions: Of 5 patient profiles identified, Hypoxic + Sleepy conferred the strongest AF risk. Consistent with prior evidence of hypoxia as an AF driver and cardiovascular risk of the sleepy phenotype, this constellation of symptoms and physiology illustrates risk in the clinical setting, providing potential value as a risk prediction tool. Future investigation will focus on external validation of these findings.

Predictors of New Onset Atrial Fibrillation Burden in the Critically Ill

Introduction: Atrial fibrillation (AF) is common in the intensive care unit (ICU) setting and has been associated with adverse outcomes. In this context, there is increasing research interest in AF burden as a predictor of subsequent adverse events. However, the pathophysiology and drivers of AF burden in the ICU are poorly understood. This study sought to evaluate the predictors of AF burden in critical illness-associated new-onset AF (CI-NOAF). Methods: Out of 7,030 admissions in a tertiary general ICU between December 2015 and September 2018, 309 patients developed CI-NOAF. AF burden was defined as the percentage of monitored time in AF, as extracted from hourly interpretations of continuous ECG monitoring. Low and high AF burden groups were defined relative to the median AF burden. Clinical, laboratory, and echocardiographic parameters were extracted, and multivariable modelling with binary logistic regression was performed to evaluate for independent associations with AF burden. Results: The median AF burden was 7.0%. Factors associated with increased AF burden were age, dyslipidaemia, chronic kidney disease, increased creatinine, CHA₂DS₂-VASc score, ICU admission diagnosis category, amiodarone administration, and left atrial area (LAA). Factors associated with lower AF burden were previous alcohol excess, burden of ventilation, the use of inotropes/vasopressors, and beta blockers. On multivariate analysis, increased LAA, chronic kidney disease, and amiodarone use were independently associated with increased AF burden, whereas beta blocker use was associated with lower AF burden. Conclusion: Left atrial size and chronic cardiovascular comorbidities appear to be the primary drivers of CI-NOAF burden, whereas factors related to acute illness and critical care intervention paradoxically did not appear to be a substantial driver of arrhythmia burden. Further research is needed regarding drivers of AF and the efficacy of rhythm control intervention in this unique setting.

High-density mapping of the average complex interval helps localizing atrial fibrillation drivers and predicts catheter ablation outcomes.

Persistent Atrial Fibrillation (PersAF) electrogram-based ablation is complex, and appropriate identification of atrial substrate is critical. Little is known regarding the value of the Average Complex Interval (ACI) feature for PersAF ablation. Using the evolution of AF complexity by sequentially computing AF dominant frequency (DF) along the ablation procedure, we sought to evaluate the value of ACI for discriminating active drivers (AD) from bystander zones (BZ), for predicting AF termination during ablation, and for predicting AF recurrence during follow-up. We included PersAF patients undergoing radiofrequency catheter ablation by pulmonary vein isolation and ablation of atrial substrate identified by Spatiotemporal Dispersion or Complex Fractionated Atrial Electrograms (>70% of recording). Operators were blinded to ACI measurement which was sought for each documented atrial substrate area. AF DF was measured by Independent Component Analysis on 1-minute 12-lead ECGs at baseline and after ablation of each atrial zone. AD were differentiated from BZ either by a significant decrease in DF (>10%), or by AF termination. Arrhythmia recurrence was monitored during follow-up. We analyzed 159 atrial areas (129 treated by radiofrequency during AF) in 29 patients. ACI was shorter in AD than BZ (76.4 ± 13.6 vs. 86.6 ± 20.3 ms; p = 0.0055), and mean ACI of all substrate zones was shorter in patients for whom radiofrequency failed to terminate AF [71.3 (67.5-77.8) vs. 82.4 (74.4-98.5) ms; p = 0.0126]. ACI predicted AD [AUC 0.728 (0.629-0.826)]. An ACI < 70 ms was specific for predicting AD (Sp 0.831, Se 0.526), whereas areas with an ACI > 100 ms had almost no chances of being active in AF maintenance. AF recurrence was associated with more ACI zones with identical shortest value [3.5 (3-4) vs. 1 (0-1) zones; p = 0.021]. In multivariate analysis, ACI < 70 ms predicted AD [OR = 4.02 (1.49-10.84), p = 0.006] and mean ACI > 75 ms predicted AF termination [OR = 9.94 (1.14-86.7), p = 0.038]. ACI helps in identifying AF drivers, and is correlated with AF termination and AF recurrence during follow-up. It can help in establishing an ablation plan, by prioritizing ablation from the shortest to the longest ACI zone.

Distributions and number of drivers on real-time phase mapping associated with successful atrial fibrillation termination during catheter ablation for non-paroxysmal atrial fibrillation.

Real-time phase mapping (ExTRa™) is useful in determining the strategy of catheter ablation for non-paroxysmal atrial fibrillation (AF). This study aimed to investigate the features of drivers of AF associated with its termination during ablation. Thirty-six patients who underwent catheter ablation for non-paroxysmal AF using online real-time phase mapping (ExTRa™) were enrolled. A significant AF driver was defined as an area with a non-passively activated ratio of ≥ 50% on mapping analysis in the left atrium (LA). All drivers were simultaneously evaluated using a low-voltage area, complex fractionated atrial electrogram (CFAE), and rotational activity by unipolar electrogram analysis. The electrical characteristics of drivers were compared between patients with and without AF termination during the procedure. Twelve patients achieved AF termination during the procedure. The total number of drivers detected on the mapping was significantly lower (4.4 ± 1.6 vs. 7.4 ± 3.8, p = 0.007), and the drivers were more concentrated in limited LA regions (2.8 ± 0.9 vs. 3.9 ± 1.4, p = 0.009) in the termination group than in the non-termination group. The presence of drivers 2-6 with limited (≤ 3) LA regions showed a tenfold increase in the likelihood of AF termination, with 83% specificity and 67% sensitivity. Among 231 AF drivers, the drivers related to termination exhibited a greater overlap of CFAE (56.8 ± 34.1% vs. 39.5 ± 30.4%, p = 0.004) than the non-related drivers. The termination group showed a trend toward a lower recurrence rate after ablation (p = 0.163). Rotors responsible for AF maintenance may be characterized in cases with concentrated regions and fewer drivers on mapping.

0820 Integrated Polysomnographic and Sleep Symptom-Based Cluster Subtypes Associated with Incident Atrial Fibrillation

Abstract Introduction While sleep disorders are implicated in atrial fibrillation (AF), the interplay and overlap of these disorders in AF risk remains unclear and a risk stratification challenge. Sleep-based clusters associated with AF can account for this complexity and translate to actionable approaches to identify at-risk patients. We hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF. Methods Cleveland Clinic patients (age&amp;gt;18) who underwent PSG 11/27/2004-12/30/2015 were retrospectively examined. Clusters were identified using latent class analysis of 23 symptoms (e.g. related to sleep disordered breathing (SDB), sleepiness, REM intrusion, NREM parasomnias), Epworth Sleepiness Scale (ESS) score, and 24 measures of SDB and sleep architecture from PSG reports. Outcome was 5-year incident AF. Cox-proportional hazards models were adjusted for age, sex, race, body mass index, cardiovascular disease and risk factors, tobacco use, chronic obstructive pulmonary disease, anti-arrhythmic medication use, and positive airway pressure use. Results The sample included 43,433 patients: age 51.8±14.5, 51.9% (n=22,548) male, 74.4% (n=32,313) White, 7.3% (n=3,151) with baseline AF, and 4.3% (n=1,875) developed 5-year incident AF. Five clusters were identified and ranked by strength of AF association: 1) Hypoxemic (n=3,245): highest %time SaO2&amp;lt; 90% (T90), 2) Apneas+Arousals (n=4,592): most witnessed apneas, highest apnea hypopnea index (AHI), highest arousal index, least hypopneas, 3) Short sleep+NREM (n=6,126): shortest sleep time, longest REM latency, lowest %REM, 4) Hypopneas (n=2,661): most hypopneas, 5) Long sleep+REM (n=26,809): longest sleep time, shortest REM latency, highest %REM. Compared to ‘Long sleep+REM’, ‘Hypoxemic’ had 47% higher AF risk (HR=1.47,95%CI=1.27-1.69), and ‘Hypopneas’ did not differ (HR=1.05,95%CI=0.86-1.28). Conclusion Of five clusters identified, the ‘Hypoxemic’ subtype conferred the strongest AF risk with the highest degree of hypoxemia (highest T90, lowest minimum and mean SaO2), maximum end-tidal CO2, heart rate, and ESS score. Consistent with prior evidence of hypoxemia as an AF driver and cardiovascular risk of the sleepy phenotype, this constellation of symptoms and physiologic alterations illustrates risk in the clinical setting, providing potential value as a risk prediction tool. Future investigation should focus on external validation of these findings. Support (if any) Cleveland Clinic Neurological Institute Center for Outcomes Research &amp; Evaluation Pilot Grant, Transformative Research Resource Development Award

Pinpointing atrial fibrillation drivers by informed sequential endocardial mapping in the presence and absence of fibrosis: an in-silico study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work is part of Personalize AF. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. This work was also supported by the Swiss National Supercomputing Centre (CSCS), project s1074. Background We recently developed a novel technique to localize spatially stable atrial fibrillation (AF) drivers using the combined information from sequential endocardial mapping recordings. The robustness of this technique to localize drivers in the presence of complex substrate with a high degree of fibrosis and with unstable and meandering drivers is not known. Purpose To evaluate the effect of spatial instability of drivers and high AF substrate complexity caused by atrial fibrosis on the performance of the recently developed technique for AF driver localisation using sequential endocardial mapping. Methods We used a previously validated volumetric 3D atrial model to simulate AF initiated by incremental pacing. Two sets of simulation were generated, with no structural changes (n=7), and with severe remodelling (n=11), implemented as patches of endomysial fibrosis covering 70% of the atria. Simulated endocardial unipolar electrograms were generated sequentially in a 4x4 electrode grid (3 mm spacing, 2.5 s) starting from 20 uniformly spaced positions in the atria. The subsequent catheter positions were determined by analysing the propagation direction in the grid. If the measured activity was repetitive, the dominant direction of propagation was determined, and the catheter was repositioned 10 mm upstream within the same atrium. Otherwise, the catheter was moved 5 mm in a random direction. This procedure continued until either 1) a driver (re-entry or radial spread of activations) was detected directly at the recorded region by evaluating the corresponding propagation patterns, or 2) the previous catheter positions defined an enclosed region in the atrium, encircling the AF driver. The performance of the algorithm was compared between the two remodelling stages with respect to number of steps required to locate a driver, and to the distance to the closest driver. Results In the simulations with fibrosis more drivers were present than in the simulations without fibrosis (4 [2, 6] vs. 3 [2; 4] simultaneous reentries, p &amp;lt; 0.001). Drivers were spatially unstable and meandered substantially through the atrium. The performance of the algorithm to localize the drivers was similar in both groups. The tracking procedures located a driver after 6 [IQR: 4; 9] vs. 5 [3; 8] steps (p&amp;lt;0.01). The algorithm localized the driver correctly in 72.8% vs. 78.2% (p = 0.30) of the cases and the final distances to a driver were 7.87 [5.88; 11.04] mm and 7.78 [5.55, 11.35] mm (p=0.95), respectively. More drivers were detected by encircling them with sequential catheter positions in the cases without remodelling (62.6% vs. 40.9%, p&amp;lt;0.001). Conclusion Guiding mapping catheters by functional aspects of AF and combining sequential recordings may increase the efficiency and accuracy of mapping procedures. The developed algorithm successfully localizes AF drivers even in complex substrates for AF.

Novel mapping tool to identify drivers in persistent atrial fibrillation: first clinical experience

Abstract Funding Acknowledgements Type of funding sources: None. Background Developing ablation strategies beyond pulmonary vein isolation (PVI) in persistent atrial fibrillation (persAF) is still a challenge. To date, few diagnostic tools have allowed identification of potential drivers during AF, with questionable results. There is a need for a tool that allows to consistently display and detect EGMs and identify optimal ablations targets. A novel mapping tool can provide algorithmic detection of ablation targets based on EGM properties specific to relatively stable localized rotational activations. Objective Describing an initial series of patients (pts) where Ockham mapping was used during AF to identify ablation targets and treat PersAF. Methods PersAF pts presenting in AF for were mapped using an ultra-high density mapping system (RHYTHMIA). A novel PersAF mapping feature (Ockham) was used to detect ablation targets by calculating local cycle length (LCL) and local spread of activation time within that LCL (Duty Cycle) for consistent EGMs. A scatterplot tool (F1 A) was used to identify regions of consistent (relatively stable) local activation. Among these areas, those with fast CL and high DC (&amp;gt;90%) were used to guide the optimal PVI line placement. Additionally, during remapping the same approach was used to target ablation beyond PVI.RF was delivered at 40-45 W via a StablePointTM IntallaNav OI catheter aiming at the maximum impedance drop (30 ohms).Durable PVI was verified by EGM visualization. In case of ongoing AF at the end of the procedure patients were monitored for 48 h before eventual cardioversion. Follow-up was by Holter every 3 months (more if symptoms). Data are median [IQR]. Results The novel mapping tool was used on 31 PersAF pts (68±9.5 years, 71% male, 20 De Novo).A median of 41228 [32789-46512] EGMs was collected before PVI. After PVI, 3 de novo pts had AF terminate into AT. Additional targets were identified in the other ones from a second post-PVI map. 81% of the extra-venous potential drivers identified on the post-PVI maps were already present on the pre-PVI map, supporting the reproducibility of the tool. Pts had a median of 3 [1-4.25] extra-PV drivers targets. Across all pts, following PVI and targeted ablation, there was progressive AF organization demonstrated by global activation slowing (a rightward shift of CL; F1 B), which in approximately half of the patients formed bi-modal curves clustered around 2 discrete CL values. Acutely, 88% of patients had AF terminate to SR or AT. At 10 months [5.75-13] follow-up, 3 (15%) patients had recurrence of persAF, and 2 (10%) patients had AT recurrences. No complication occurred. Discussion This clinical experience demonstrates that this tool can identify limited, but highly selective, reproducible extra-PV AF drivers. Since PersAF pts have high variability in arrhythmogenic sites, this novel tool allows efficient identification of ablation targets based on EGM properties for an individualized approach to ablation beyond PVI.

The relationship between high dominant frequency and low voltage areas in patients with atrial fibrillation: digital twin study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): a grant [2022R1I1A1A0106342211] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT &amp; Future Planning (MSIP) Background It has been suggested that the high dominant frequency (DF) site plays an atrial fibrillation (AF) driver, but its relationship with the atrial substrate voltage map (Vm) in the entire chamber AF map has yet to be studied. We explored the relationship between the DF site during AF and Vm in the entire chamber maps by applying the human left atrial (LA) electroanatomical map (EAM) to the digital twin AF map. Methods We acquired LA substrate Vm (at sinus rhythm, &amp;gt;800 points bipolar electrograms) of 110 patients with persistent AF (male 72.7%, 58.7±9.8 years old) who underwent AF catheter ablation. We applied EAM to digital twins (0.4 million nodes), reflecting anatomy, histology, and electrophysiology. We evaluated the highest 10% DF areas for 6 sec after inducing virtual AF. The correlation between the highest 10% DF and the low Vm areas (&amp;lt;0.2mV) was evaluated in the LA region of 10 segments. Results The mean voltage of the entire LA area was 1.96±0.85 mV (2.19±0.82 mV extra-PV area, 1.33±0.93 mV PV area) in 110 patients. The correlation between low Vm and high DF areas was not significant in the entire LA (r=0.106, p&amp;lt;0.001), extra-PV (r=0.157, p&amp;lt;0.001), and PV (r=0.079, p=0.097) areas. In the LA 10 segment regional analysis, 72 patients (65.5%) showed the co-localization of the highest DF in the region with the lowest Vm, and 14 patients (12.7%) had the lowest Vm segment in the region with the highest DF. The mean voltage where high DF appeared was 0.69±1.35 mV, and the mean voltage of the region where high DF did not appear was 0.59±1.15 mV (p=0.171). Conclusion High DF site, a parameter representing a localized focal source, had statistically significant but very poor correlations with LA extra-PV voltage substrate in patients with persistent AF.

Artificial intelligence-enabled spatio-temporal dispersion mapping for persistent AF: Similarities and differences between pacing-induced or spontaneous AF

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Volta Medical Saint Joseph Hospital Marseille, France Background Spatiotemporal dispersion is an electrical footprint of atrial fibrillation (AF) drivers that has been successfully implemented to target extra-pulmonary veins (PVs) regions during persistent AF ablation. Purpose The aim of the study is to characterize spatiotemporal dispersion extent and location and to compare dispersion atrial localization and extent between pacing-induced AF and spontaneous AF. Methods Spatiotemporal dispersion maps were built with an artificial intelligence software (VX1, Volta Medical) and analyzed in 71 consecutives persistent (66%) and long-standing persistent (34%) AF patients admitted for a first ablation procedure. Fifty-two patients were in spontaneous AF (73%) at the outset of the procedure while AF was induced in 19 patients (27%) by burst pacing ± isoproterenol infusion. A semi-quantitative visual quantification of dispersion extent was conducted by implementing an atrial segmentation into 22 regions and a region-centered score from 0 (no dispersion) to 3 (high dispersion). Also, an automated quantification was performed as follows: (i) a gradient filter designed to extract atrial shapes from background was applied, (ii) dispersion areas were segmented using a color thresholding method, and (iii) a structuring element was used to connect segmented dispersion areas. Results The regional characterization of dispersion shows that dispersion distribution follows a similar pattern and is present in similar atrial regions, regardless of whether AF is spontaneous or induced (Figure 1). Global dispersion extent, however, is significantly higher in the left atrium of patients in spontaneous AF compared to patients with induced AF (15.43% ± 9.04 versus 9.86% ± 6.41, P=0.0025, Figure 2). Accordingly, the regional dispersion score tends to be lower when AF is induced. Dispersion hotspots are: LSPV anterior antrum -ridge (R1), RSPV anterior antrum (R5), anterior wall (R9), roof (R10), posterior wall (R11), and low left atrial septum (R15) in the left atrium. In the right atrium: low right atrial septum (R15) and posterior right atrium (R20) (Figure 1). Conclusions Artificial intelligence-enabled dispersion persistent AF mapping indicates that dispersion is reduced in induced vs. spontaneous-AF but that its distribution follows a similar pattern.

Detection of the most dominant drivers of atrial fibrillation based on repetitive activity in sequential electro-anatomical mapping

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work is part of Personalize AF. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974, This work was also supported by the Swiss National Supercomputing Centre (CSCS), project s1074. Introduction Detecting and targeting the most dominant drivers of atrial fibrillation (AF) might improve the outcome of AF ablation procedures. We hypothesize that dominant drivers entrain their vicinity in a temporally and spatially stable manner resulting in local as well as adjacent repetitive activation patterns. Purpose We present a novel approach to detect the most dominant drivers of AF based on driver repetitiveness and the degree to which they entrain their vicinity. Methods We retrospectively analyzed a dataset of high-density bi-atrial sequential mapping in ablation-naive persistent AF patients (n=13, 30s recording per site). Candidate drivers (focal activity or re-entry) were detected based on local activation time analysis of unipolar electrograms. Focal activity was defined as radial spread of activation, re-entry as a circular activation sequence on at least 4 splines of the mapping catheter that covered &amp;gt;50% of the AF cycle length. As a measure of driver stability, we determined the driver's local repetitiveness (in % of recording). As a measure of driver-associated entrainment, we determined the directionally coherent repetitiveness of adjacent recordings within 30 mm (Figure 1). Following our hypothesis, most dominant drivers can be recognized by their high local and directional coherent adjacent repetitiveness. Results A total of 459 recordings were analyzed (35±5 per patient). We detected 130 focal activities (10±3 per patient) and 42 re-entries (4±2 per patient) in total. The spatial distribution of all drivers is shown in Figure 2 (blue bars). Focal activities were more repetitive than re-entries (Figure 2, median [IQR] 3.2% [1.9%, 5.6%] vs. 1.8% [1.8%, 2.2%], p&amp;lt;0.001 Mann-Whitney U-test). When applying a 90th percentile threshold (8.2%) to both the local and directional coherent adjacent repetitiveness to detect the most dominant drivers, we were able to detect 9 dominant drivers (all focal activities, 7 patients). Most dominant drivers were located in the upper right atrium or left pulmonary vein region (Figure 2). Interestingly, only 9 of the 130 initially detected drivers (7%) showed an activation pattern in line with a repetitive entrainment of their vicinity. Furthermore, in 6 patients (46%), no dominant drivers were detected. This might indicate that not all patients have temporally and spatially stable drivers. Conclusion In this abstract we present a novel methodology to detect the most dominant drivers of AF. Using this method, we found that some (but not all) patients have temporally and spatially stable drivers that are able to entrain their vicinity.

Combining atrial activation maps for the big picture of simulated atrial fibrillation mechanisms

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by PersonalizeAF project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. Background Pulmonary vein isolation (PVI) alone is not sufficient for all persistent atrial fibrillation (AF) patients. Ablation of localized AF drivers might be a promising adjunctive ablation strategy but detecting such drivers is limited by the small field of view of current mapping catheters. Purpose We propose a technique to detect localized AF drivers that combines sequential mapping of repetitive activation patterns into a larger composite map. The performance of this technique was evaluated in several simulated scenarios of known mechanisms during AF. Methods Representative repetitive conduction patterns that may occur in AF were simulated in a detailed volumetric 3D model of the atria: a large peripheral wave, stable and meandering re-entries, and single and multiple ectopic foci. Endocardial electrograms were sequentially generated from overlapping regions in the left posterior wall (4x4 grid, 3mm spacing, 0.5-1.5 seconds), and repetitive activation patterns were detected. Overlapping areas between sequential maps were used to align the repetitive patterns. Local patterns were then combined into larger composite maps (Fig. 1A). Reconstruction performance was quantified by the average local activation time (LAT) difference between original and reconstructed activation patterns. The relation between electrode overlaps and the quality of reconstructions were assessed at different degrees of spatial overlap (approximately 10% to 25% of the grid area, corresponding to 1.6 ± 0.6 and 4.1 ± 1.2 overlapping electrodes, respectively). Results All simulated patterns could be reconstructed from sequential recordings (Fig. 1B). LAT errors in recordings with 25% overlap were low in all cases: 5±2 msec for the peripheral wave, 5±2 and 3±1 msec for focal and multifocal activities and 6±2 and 11±2 &amp; 17±3 msec for stable, meandering and highly meandering re-entries respectively (Fig. 2). Composite maps of meandering and highly meandering re-entries presented significantly higher reconstruction errors than other more stable patterns (p&amp;lt;0.01). Reducing spatial overlap to 10% did not significantly increase the errors, except for the highly meandering re-entrant activity (p&amp;lt;0.05). Conclusion We developed a novel methodology to combine high-density sequential recordings with limited coverage into larger composite activation maps. Using this method, we reconstructed highly accurate activation maps for multiple simulated AF mechanism scenarios. Results were promising even with a small overlap between sequential recording sites and relatively unstable patterns, providing a proof of principle to apply this approach in clinical recordings of human AF.

The spatiotemporal electrogram dispersion ablation targeting rotors is more effective for elderly patients than non-elderly population.

Modulating atrial fibrillation (AF) drivers has been proposed as one of the effective ablation strategies for non-paroxysmal AF (non-PAF). However, the optimal non-PAF ablation strategy is still under debate because the exact mechanisms of AF persistence including focal activity and/or rotational activity, are not well-understood. Recently, spatiotemporal electrogram dispersion (STED) assumed to indicate rotors in the form of rotational activity is proposed as an effective target for non-PAF ablation. We aimed to clarify the effectiveness of STED ablation for modulating AF drivers. STED ablation plus pulmonary vein isolation was applied in 161 consecutive non-PAF patients not undergoing previous ablation. STED areas within the entire left and right atria were identified and ablated during AF. After the procedures, the STED ablation's acute and long-term outcomes were investigated. (1) Despite a more effective acute outcome of the STED ablation for both AF termination and non-inducibility of atrial tachyarrhythmias (ATAs), Kaplan-Meier curves showed that the 24-month freedom ratio from ATAs was 49%, which resulted from the higher recurrence ratio of atrial tachycardia (AT) rather than AF. (2) A multivariate analysis showed that the determinant of ATA recurrences was only a non-elderly age, not long-standing persistent AF, and an enlarged left atrium, which were conventionally considered as key factors. STED ablation targeting rotors was effective in elderly non-PAF patients. Therefore, the main mechanism of AF persistency and the component of the fibrillatory conduction might vary between elders and non-elders. However, we should be careful about post-ablation ATs following substrate modification.

PO-04-081 ISOLATION OF PERSISTENT LEFT SIDED SUPERIOR VENA CAVA USING PULSED FIELD ABLATION

Pulmonary vein foci account for more than 90% of triggers for atrial fibrillation, most commonly treated with complete pulmonary vein isolation. Non–pulmonary vein triggers are the drivers of atrial fibrillation in a subgroup of patients. One such trigger is a persistent left superior vena cava (SVC), which may contain remnant muscular and pacemaker tissue carried over from embryonic life. However, reported complications of radiofrequency ablation of this structure are significant, including vein stenosis, tamponade and phrenic nerve injury. Pulsed field ablation is a promising new technology that may be uniquely suited to avoid such a complications. This case illustrates the first known application of pulsed field ablation of a left sided SVC. N/A The patient is a fifty-two year old male with a history of coronary artery disease and persistent atrial fibrillation refractory to medical therapy including rate and rhythm control strategies. He is status post multiple cardioversions with restoration to normal sinus rhythm for a relatively short period of time. The patient underwent an ablation procedure at which time it was discovered that he had an isolated persistent left sided SVC. Pulmonary vein isolation was performed using a combined radiofrequency and pulsed field ablation lattice tip catheter (Affera inc., Watertown, MA). Accordingly to study protocol, lesions were placed using radiofrequency anteriorly and pulsed field lesions posteriorly in the left atrium around the pulmonary veins resulting in complete isolation. The patient also developed a counterclockwise typical atrial flutter which was ablated. Given the propensity for triggers from the SVC, pulsed field ablation was performed by creating a circumferential lesion set superiorly beyond the left superior pulmonary vein region and inferiorly near the mid coronary sinus below the left inferior pulmonary vein. A linear lesion set connecting these two regions was also performed along the atrial portion of the coronary sinus, with subsequent confirmation of exit block and elimination of all local electrograms. In patients with persistent left SVC, pulsed field ablation is feasible without the risk of phrenic nerve injury or tamponade from excessive contact force. Further studies are necessary to examine whether the complications associated with LSVC isolation can be minimized.

PO-02-160 NOVEL APPLICATION OF THE WAVE DYNAMICS USING HIGH DENSITY VECTOR FIELD MAPPING FOR PERSISTENT ATRIAL FIBRILLATION

Catheter ablation for persistent atrial fibrillation (AF) has shown limited success. The vector field (VF) mapping illustrates the stationary waveform propagating during AF, can compute the global propagation patterns to demonstrate the mechanism of AF maintenance. This study aimed to visualize the global wavefront pattern during AF by using VF mapping and investigate the ablation outcome based on different pattern. In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the VF mapping algorithm, involving analysis of high similarity electrogram vectors to to display the stable wave propagation of AF. In the phase 2 study, patients with persistent AF underwent catheter ablation were prospectively enrolled. (Group 1 [N=35]: AF drivers emanating from 1 or more PVs; Group 2 [N=30]: No AF drivers emanating from 1 or more PVs). VF mapping and PRISM-guided PVI was performed in all patients. The patient characteristics and procedural data were extracted for analysis. We evaluated the single-procedure freedom from AF after first ablation procedure. We identified an average of 2.7±2.0 VF regions per patients. These regions (N=177) involved PV (N=100) and left atrium (N=77). A higher procedural AF termination rate (43%vs. 17%, P=0.03) was achieved in Gp-1 than Gp-2. Gp-1 patients had a significant reduction in all arrhythmia recurrence compared to Gp-2. After multivariate analysis, the behavior of driver emanating from PV (Hazards ratio [HR] 0.426, 95% confidence interval [CI]: 0.187-0.968, P =0.042) and the left atrial diameter (HR 1.092, 95% CI: 1.021-1.169, P = 0.011) independently predicted the recurrence. VF mapping of persistent AF revealed the waveform dynamic of the entire atrial chamber and revealed the spatially stable AF drivers with sink-to-source phenomenon to the rest of the atrium. The arrhythmogenic drivers within PVs/antra are predictive of the successful PV isolation in patients with persistent AF.

PO-01-164 CATHETER ABLATION WITH MORPHOLOGIC REPETITIVENESS ABLATION ON PERSISTENT ATRIAL FIBRILLATION: A PROSPECTIVE MULTICENTER TRIAL

Catheter ablation for persistent atrial fibrillation (AF) has shown limited success. AF drivers could be accurately identified by PeRIodicity and SiMilarity (PRISM) mapping and ablated. We aimed to determine whether PRISM mapping can improve ablation results for persistent AF when added to pulmonary vein isolation (PVI). This PRISM trial was an investigator-initiated, multicenter, prospective, single-blinded trial conducted at three centers across Asia. Patients with persistent AF referred for ablation were enrolled from June 2019 to December 2020. Patients were assigned to the PRISM-guided approach (Group 1, Figure) or the conventional approach (Group 2) at a 1:1 ratio. Outcome assessments were blinded to the treatment received. The primary outcome was freedom from AF for longer than 30 seconds at 6 and 12 months. 170 patients (age 62.0 ± 12.3 years; 136 men) were enrolled. We assigned 85 patients to group 1 and 85 patients to group 2. There were more group 1 patient who achieved freedom of AF at 12 months compared with group 2 patients. (71.6% [60/85] vs. 47.1% [40/85], p=0.003). Multivariate analysis indicated that the PRISM-guided approach was associated with freedom from the recurrence of AF [hazard ratio: 0.531, 95% confidence interval: 0.331-0.852, p=0.009]. Complication rates between the two groups were not significantly different. Our study showed that for persistent AF ablation, a specified substrate modification guided by PRISM mapping could eliminate AF sources and maintain sinus rhythm for 12 months.

PO-02-065 CATHETER ABLATION WITH TERMINATION OF PERSISTENT ATRIAL FIBRILLATION USING SPATIOTEMPORAL DISPERSION

Several strategies of electrogram (EGM) guided catheter ablation of atrial fibrillation (AF) have been previously described. A spatiotemporal dispersion (SD) ablation strategy targeting AF drivers with very high termination rates has been reported; however, these sites have not been well characterized. The purpose of this study is to validate the prior experience with SD ablation in the persistent AF cohort and further characterize the regions of AF termination. Consecutive patients with persistent AF undergoing radiofrequency catheter ablation were included. Electroanatomic mapping of SD areas was performed during AF. Ablation was delivered initially at sites of continuous SD, followed by pulmonary vein isolation in all patients. If AF did not terminate, additional regions of intermittent SD were ablated. If AF terminated to atrial tachycardia or flutter, additional electroanatomic mapping and ablation was performed to achieve sinus rhythm. Representative EGMs at sites of continuous SD, intermittent SD, and no SD are shown in Figures 1A, 1B, and 1C, respectively. Left atrial (LA) volume and surface area, termination sites, and procedural characteristics are reported. A total of 20 consecutive patients (13 male, 67 ± 9 years) with persistent AF (median time from diagnosis 5 years) undergoing ablation were included in the study. The majority of continuous SD was seen on the anterior wall (18/20 patients) and septum (15/20 patients) and occasionally on the posterior wall (8/20 patients). 17/20 (85%) patients successfully terminated to sinus rhythm during the procedure. The majority of the termination sites were on the septum and anterior wall (12/17) with none on the posterior wall. LA volume by echocardiography was smaller in the termination group (84 vs. 105 mL, p < 0.01) and fluoroscopy use was less in the termination group (2.3 vs. 4.8 min, p = 0.03). There was no difference in ejection fraction, LA surface area, radiofrequency time, or procedure time (p = NS). A very high termination rate of persistent AF was achievable with ablation of SD regions. These regions likely represent drivers of AF and seem to localize predominantly on the septum and anterior wall of the LA, and rarely on the posterior wall. Ablation incorporating SD mapping may allow for patient-tailored approach to AF ablation.

AF driver detection in pulmonary vein area by electropcardiographic imaging: Relation with a favorable outcome of pulmonary vein isolation.

Pulmonary vein isolation (PVI) is the most successful treatment for atrial fibrillation (AF) nowadays. However, not all AF patients benefit from PVI. In this study, we evaluate the use of ECGI to identify reentries and relate rotor density in the pulmonary vein (PV) area as an indicator of PVI outcome. Rotor maps were computed in a set of 29 AF patients using a new rotor detection algorithm. The relationship between the distribution of reentrant activity and the clinical outcome after PVI was studied. The number of rotors and proportion of PSs in different atrial regions were computed and compared retrospectively in two groups of patients: patients that remained in sinus rhythm 6months after PVI and patients with arrhythmia recurrence. The total number of rotors obtained was higher in patients returning to arrhythmia after the ablation (4.31 ± 2.77 vs. 3.58 ± 2.67%, p = 0.018). However, a significantly higher concentration of PSs in the pulmonary veins was found in patients that remained in sinus rhythm (10.20 ± 12.40% vs. 5.19 ± 9.13%, p = 0.011) 6 months after PVI. The results obtained show a direct relationship between the expected AF mechanism and the electrophysiological parameters provided by ECGI, suggesting that this technology offers relevant information to predict the clinical outcome after PVI in AF patients.