AF Termination Research Articles

An in-silico comparison of anatomical and substrate based AF ablation using electro and optical flow mapping

Abstract Background The pursuit of improved outcomes for persistent AF may necessitate the utilization of innovative technologies and ablation methods. We hypothesize that combining electrophysiologic phase and optical flow mapping could offer a novel approach to identify ablation sites in persistent AF while minimizing ablation area, thereby enhancing the effectiveness of substrate-based ablation compared to a purely empiric strategy. Objective To compare the efficacy of a novel electro-optic flow-based ablation strategy (EOF) with empiric ablation for persistent AF patients using a virtual cohort of bi-atrial models. Methods An exploratory cohort (n=20) from a CT-derived bi-atrial in silico population was utilized to simulate AF. A pipeline was developed to assess ablation targets based on simulated AF and to automatically connect targets to closest inert boundaries. As part of target assessment, phase singularities (PS) and Horn-Schunck average optical flow maps were computed. An intersection of information assessed through PS and curl of average optical flow was utilized to generate EOF maps. 5 x strategies comprising purely anatomical, PS based and EOF guided ablations were simulated (1. PVI; 2. PVI+mitral/roof lines; 3. PVI+mitral/box line; 4. PS+anatomical; 5. EOF+anatomical). Ablation efficacy was determined by first examining change of rhythm via ablation and second by calculating the amount of tissue area ablated. Results Ablating PVI alone (Method 1) did not result in AF termination in any case. Ablating PVI with mitral or roof lines (Method 2) resulted in moderate outcomes (6 AF term. / 3 conv. to AT) whereas ablating PVI with mitral and box lines (Method 3) resulted in improved outcomes (9 AF term. / 4 conv. to AT). Compared to purely anatomical approaches, ablating PS or EOF targets and combining them with roof, mitral lines (Method 4 and Method 5 respectively) saw marked improvement (16 AF term. / 2 conv. to AT). Mapping based on EOF (Method 5) resulted in smaller ablation targets compared to a PS guided strategy (Method 4) with the same outcome. Conclusion AF termination to ablated tissue area ratio was higher for EOF based ablation targets compared to PS based or empiric ablations. Algorithmic generation of ablation lesion masks based on predicted targets can provide novel insights into ablation outcomes. Combining EOF targets with empiric lesions represents a potential ablation strategy of individualized substrate modification for persistent AF.Study Pipeline

Pulmonary Vein Isolation Followed by Biatrial Ablation of Rotational Activity in Patients with Persistent Atrial Fibrillation: Results of the Cryo-Vest Study.

Background and Aims: Noninvasive mapping allows the identification of patient-specific atrial rotational activity (RA) that might play a key role in the perpetuation of persistent atrial fibrillation (PsAF). So far, the impact of pulmonary vein isolation by cryoballoon (Cryo-PVI) on RA is unclear. Moreover, the long-term effect of periprocedural termination of AF during the ablation procedure is controversial. Methods: Noninvasive electrocardiographic mapping with a 252-electrode vest was performed in 42 patients with PsAF. After the first analysis, Cryo-PVI was performed. The RA was analyzed again and then targeted by radiofrequency catheter ablation. The primary clinical endpoint was periprocedural termination of AF. The secondary endpoint was freedom from any atrial arrhythmia >30 s during a 12-month follow-up. Results: In 33 patients (79%), right atrial RA was identified leading to biatrial ablation, and nine patients (21%) had left atrial RA only. Twelve patients (28.6%) converted from AF to sinus rhythm (SR) (Group A). Thirteen patients (30.9%) converted to atrial tachycardia (AT) (Group B). In 17 patients (40.5%), AF was not terminated by ablation (Group C). After a mean follow-up time of 13.8 months, 26 patients were free from AF and AT (61.9%). In terms of rhythm, control Group A (75%) and B (83.3%) showed higher success rates than Group C (33.3%) (p < 0.01). Cryo-PVI had no substantial impact on RA. Conclusions: The RA-based ablation approach showed acceptable success rates. Periprocedural termination of AF had a positive predictive impact on the outcome. No difference was observed between conversion to SR or to AT. Cryo-PVI had no impact on RA.

Adjunctive Right Atrial Ablation for Persistent Atrial Fibrillation With Right Atrial Enlargement: A Pilot Study

BackgroundPersistent atrial fibrillation (PerAF) is often associated with right atrial (RA) enlargement. We investigated the efficacy of RA intervention in patients with PerAF and RA enlargement. MethodsPatients with PerAF and RA enlargement were randomised (1:1) to receive adjunctive RA ablation (left atrial [LA] + RA group; n = 60) or to receive LA ablation alone (LA-only group; n = 60). In the LA + RA group, RA ablation was performed if LA ablation failed to terminate AF. The primary end point was freedom from AF/atrial tachycardia (AT) recurrence at 12 months after a single ablation procedure without antiarrhythmic drug therapy. ResultsIn the LA + RA group, 40 patients (67%) required RA ablation. The LA + RA group had a higher rate of acute AF termination than the LA-only group (63.3% vs 36.7%; P = 0.003). At the end of 12-month follow-up, 42 patients (70%) in the LA + RA group were free of AF/AT recurrence, compared with 31 (51.7%) in the LA-only group (log rank P = 0.034; hazard ratio 0.549, 95% confidence interval 0.310-0.974). The rate of freedom from AF recurrence was also higher in the LA + RA group than in the LA-only group (81.7% vs 63.3%; log rank P = 0.019). The 2 groups had similar rates of adverse events (5% vs 3.3%; P = 0.648). ConclusionsAdjunctive RA ablation increased the success rate of a single ablation in patients with PerAF and RA enlargement. Chinese Clinical Trial RegistrationChiCTR220056844

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.

Atrial Fibrillation Detection Using Electrocardiogram Signal Input to LMD and Ensemble Classifier

Atrial fibrillation (AFib) is a type of heart arrhythmia, marked by an erratic and rapid contraction of the atria. Computer-aided diagnosis of AFib using electrocardiogram (ECG) sensor data may become a valuable tool in the detection and management of this common cardiac arrhythmia. In this letter, we present a new hybrid approach for the automatic classification of ECG signals using the local mean decomposition (LMD) and ensemble boosted trees classifier (EBTC). The LMD algorithm is employed to adaptively decompose the recorded ECG data into product functions (PFs). Four entropy-based features namely, log energy, sure, Shannon, and threshold entropy are computed from each PFs. The Kruskal-Wallis algorithm is employed to check the statistical significance of the obtained features and an EBTC is used for the screening of AFib episodes. The proposed technique achieved the highest classification accuracy of 92.33%, 90.33%, and 90.00% by classifying immediate terminating and non-terminating, terminates after one minute and non-terminating, immediate terminating and terminates after one minute AFib episodes, respectively. The presented method outperforms the existing machine learning-based approaches for detecting AFib using ECG data acquired from the publicly accessible AF Termination Challenge Database.

Interim analysis of a prospective randomized comparison of pulsed field ablation vs. radiofrequency ablation for longstanding persistent atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Benefits of pulsed field ablation (PFA) compared to radiofrequency ablation (RFA) are not known in patients with longstanding persistent atrial fibrillation (LSPAF). Purpose To present interim procedural and short-term clinical results of an ongoing prospective randomized comparison of PFA vs. RFA in patients with LSPAF. Methods In 9/2021-10/2022, 125 patients underwent catheter ablation for LSPAF using PFA (n=64, 69±8 years, 11 F, continuous AF 32±20 months) vs. RFA (n=61, 68±8 years, 17 F, continuous AF 29±23 months). PFA included pulmonary vein isolation (PVI) and extra-PV left atrial (LA) ablation. RFA included stepwise PVI, electrogram-guided LA ablation, CS isolation, and electrogram-guided right atrial ablation. Intermediate endpoints were PVI, mitral isthmus, LA roof and CTI blocks); sinus rhythm (SR) restoration by ablation was the desired procedural endpoint. Follow-up included 7-day ECG monitoring every 3 months during the first year, and every 6 months afterwards. Results In groups PFA vs. RFA, procedure and fluoroscopy times were 116±32 vs. 204±44 minutes, and 17±5 vs. 8±2 minutes, respectively (both p&amp;lt;0.001). AF termination (into intermediate AT or directly into SR) and SR restoration by ablation were achieved in 30 (47%) vs. 42 (69%) patients (p=0,19), and in 23 (36%) vs. 35 (57%) patients (p=0,15). Of those 48 vs. 50 patients with follow-up ≥3 months (≥6 months in 37 vs. 39 patients), freedom from any AF/AT (&amp;gt;30 s) was achieved in 38 (79%) vs. 23 (46%) patients. Conclusion Interim results of ongoing comparison suggest procedure time reduction and improved AF/AT free survival after PFA as compared to RFA in patients with LSPAF.

Targeted ablation of arrhythmogenic substrate in complex cases of very long-standing persistent atrial fibrillation: successful ablation of spatio-temporal dispersions

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In persistent AF, outcomes after PVI alone is worse as the pathophysiology remains unclear. Prolonged AF duration is an independent predictor for worse success rates after catheter ablation. In this study, we investigated efficacy and safety of ablation of spatio-temporal dispersions, as additional ablation strategy after PVI in patients with long-standing persistent AF. Methods All consecutive patients with long-standing persistent AF treated with an AI-based algorithm for detection of spatio-temporal dispersion in our institution between 05/21 and 10/22 were included (n = 41, see table 1). The procedure was done using a high-density 3D-Map and an algorithm for detection of right and left atrial areas with spatio-temporal dispersion (DISPERS). Ablation of DISPERS was aiming at homogenizing, dissecting, isolating or connecting DISPERS areas to non-conducting structures. Follow-up contained regular visits at our out-patient-clinic and repetitive 7 day Holter ECGs. Late recurrence (LR) was defined as recurrence after 90 days or as recurrence, which caused further ablation. All complications requiring intervention or causing long-term sequelae were classified as major complications. Results In 24/41 pts (58.5%), the DISPERS guided ablation was the first AF ablation. Patients were suffering from very long-standing persistent AF with a mean AF duration of 64.89 ± 54.77 months. Additional to circumferential PVI, ablation of all detected left atrial (100%) and right atrial (68.3%) DISPERS areas was performed, leading to significant slowing of AF cycle length (mean 23.3%) or termination of AF to AT (5/41, 12.2%) or direct conversion to SR (6/41, 14.6%). One major complication occurred (1/41 (2.4%), pseudoaneurysm, resolving after manual compression). Three patients (7.3%) required temporary external pacing due to delayed sinus recovery after the procedure. No patient was in need of permanent pacemaker implantation. LR occurred in 25 patients (61.0 %): In 8/25 patients (32 %), LR was solely AF, whereas in 15/25 patients (60%) LR was a left AFlutt. In 2 patients (8%), AF and left AFlutt was detected. During a follow-up of 231 ± 129 days, 72.9 % of patients remained in sinus rhythm undergoing 1.6 ± 0.68 ablations (s. Figure 1; 4,9% of patients on AAD). Additionally, Figure 2 illustrates the AF-free outcome in all patients. Conclusion Ablation of arrhythmogenic substrate identified by spatio-temporal dispersion yielded in this cohort of extensively long-standing persistent AF patients in high success rates regarding elimination of AF. Most arrhythmia recurrences were reentrant AT. After a total of 1.6 procedures, freedom from AF and AT was &amp;gt;72%. Despite prolonged procedure times, complication rates remained very low. Extending study population and follow-up is needed to evaluate long-term efficacy of dispersion-guided ablation.

Patterns of pulmonary vein activity that may help identify patients who need further ablation beyond pulmonary vein isolation in persistent AF

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation Background Pulmonary vein isolation (PVI) is the cornerstone interventional treatment for AF. While this strategy is effective in paroxysmal AF, the success rate of this approach is more limited in persistent AF (PsAF). In these pts, the main challenge is to discriminate those who will respond to PVI only, from those who may require an extended ablation strategy. Purpose We aimed to evaluate whether the analysis of the electrical activity recorded within the PV may provide the key to discriminate passive PV from PV playing an active role. Methods Three-subgroups of consecutive pts who underwent first-time PVI for PsAF were considered based on the mechanism of AF: 1) definitely related to PV, based on procedural AF termination during PVI (the "PV-term" group) 2) likely PV-dependent, based on the absence of AF recurrence &amp;gt; 18 months off-antiarrhythmic drugs after PVI only (the "PV-dep" group) 3) definitely/likely independent of the PV, based on PsAF recurrence despite isolated PV or at least one redo consisting of PV reisolation only, respectively ("PV-indep"). PV activity during AF was assessed using Lasso recordings before ablation. An automatic detection algorithm was developed to extract atrial activations from intra-cardiac electrograms in order to perform further analyses. Epochs of 60-sec were used. Different methods based on the atrial cycle length variability were assessed to best characterize the potential markers of PV activity such as the occurrence of intermittent bursts of rapid activity. Each PV and the left atrial appendage (LAA) were evaluated. Results A total of 40 pts were included (mean age: 60.0 ± 9.9 years, mean PsAF duration: 4.4 ± 4.3 years) (PV-term group (n=10), PV-dep group (n=17), PV-indep group (n= 13)). The dynamics of PV activation intervals was assessed using the envelope of the PV intervals time series (Figure 1A shows representative examples of each group). Among all features evaluated, the best feature that could discriminate similarly both the PV-term and the PV-dep group from the PV-indep group, was the standard deviation of the inferior envelope relative to the median CL of the vein (p &amp;lt;0.001 and p = 0.005, respectively) (Figure 1B). Cut-off selected by ROC analysis provided a 100% sensitivity and 85% specificity to discriminate the PV-term from the PV-indep group (AUC 0.931) and a 88% sensitivity and 77% specificity to discriminate the PV-dep from the PV-indep group (AUC 0.805). We compared this feature with the Fastest PV run (mean CL of the fastest 10-beat run) as recently described (p = 0.04, AUC = 0.762 and p = 0.03, AUC = 0.738, respectively) (Figure 2). Conclusions The assessment of the CL variations recorded within the PV before PsAF ablation may provide the key to discriminate pts who may be cured by PVI only.

Radiofrequency ablation for longstanding persistent atrial fibrillation: long-term outcome of a prospective randomized comparison of mapping with multipolar catheter vs. 4-pole ablation catheter

Abstract Funding Acknowledgements Type of funding sources: None. Background In patients with longstanding persistent atrial fibrillation (LSPAF), mapping with multipolar catheter can enhance identification of arrhythmogenic sources during ongoing AF/converted atrial tachycardia (AT), reduce procedure time, and improve outcome of catheter ablation. Purpose To compare procedural characteristics and long-term outcome of radiofrequency catheter ablation (RFA) for LSPAF between two mapping approaches in a prospective randomized bi-centric study. Methods Between 1/2019-9/2021, RFA was performed in in 172 patients with LSPAF. Mapping with multipolar catheter Pentaray (group 1, n=85) vs. mapping with ablation catheter Navistar STSF (group 2, n=87) were compared. Stepwise ablation to the desired AF termination included pulmonary vein isolation (PVI), electrogram guided left atrial (LA) ablation, CS isolation, and right atrial electrogram guided ablation. PVI, mitral isthmus, LA roof, and CTI block were Intermediate endpoints proved at the procedure end. Sinus rhythm (SR) restoration by ablation was the desired procedure endpoint. Follow-up included 7-day ECG monitoring every 3 months during the first year, and every 6 months afterwards. Results In groups 1 vs. 2, AF was terminated (into SR or AT) in 70 (82%) vs. 68 (78%) patients (p=0.81); and SR was restored by ablation in 54 (64%) vs. 46 (53%) patients(p=0.46), respectively. Procedure, fluoroscopy, and RF delivery times (min) were 251±46 vs. 257±45 (p=0.35); 10,4±2,8 vs. 11,0±3,1 (p=0.17), and 70±21 vs. 70±24 (p=0.98), respectively. At the end of 13-45 months follow-up, stable SR was present in 72 (85%) vs. 69 (79%), patients following repeat ablation in 42 (49%) vs. 42 (48%) patients. Only 29 (34%) vs. 26 (30%) patients remained free from any AF/AT recurrence (&amp;gt;30 s) after single ablation (all p=NS). Conclusion Mapping with multipolar catheter vs. standard ablation catheter was associated with nonsignificant differences in procedural characteristics and clinical results of RF catheter ablation for LSPAF.

In silico biatrial fibrosis ablation improves atrial fibrillation outcome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Medical Research Council Fellowship Background In DECAAF II, left atrial (LA) fibrosis ablation plus PVI did not improve AF outcome compared to PVI alone across the study cohort. We hypothesize that biatrial fibrosis ablation could improve AF ablation therapy outcome in a subset of patients with properties identified through a large virtual in silico trial. Purpose To investigate the effects of anatomy, fibrosis distribution, and LGE-MRI threshold on ablation outcome using a virtual cohort of 4000 patients. Methods We constructed 1000 biatrial models from a statistical shape model and we mapped pectinate muscles, Bachmann’s bundle and fibers from an atlas. For each of the 1000 anatomies we applied a randomly selected fibrosis map from a library of 100 clinical maps. We then created four versions of each case by assigning one of four randomly selected right atrial (RA) fibrosis distributions with Utah grades 1-4 (Fig 1A), giving 4000 virtual patients. Four ablation approaches were applied to each patient model after 5 seconds of AF: PVI, PVI &amp; LA fibrosis, PVI &amp; RA fibrosis, PVI &amp; biatrial fibrosis. LGE-MRI was thresholded for fibrosis ablation at either 1.2 or 1.32 image intensity ratio (IIR). The outcome was classified 5 seconds post ablation. Results Biatrial fibrosis ablation is more effective than LA ablation. For patients with high (Utah 4) RA fibrosis, biatrial fibrosis ablation increases AF termination compared to LA fibrosis ablation (Figs 1B &amp; 2A: 62% vs 14%), this compares to cases with low (Utah 1) RA fibrosis (21% vs 14%). For patients with high LA (Utah 4) fibrosis, biatrial ablation is more effective than LA ablation (Fig 2B: 52% vs 19%), this compares to patients with low (Utah 1) LA fibrosis (17% vs 7%). Increasing IIR threshold for ablation decreases termination (LA fibrosis ablation: 15.8% termination at IIR 1.2, 11.0% at IIR 1.32; biatrial: 41.5% at IIR1.2; 20.3% at IIR1.32). Anatomy has a larger effect on biatrial ablation outcome (31.2% of outcomes change between anatomies) than on PVI only ablation outcome (20.0% change). Conclusion Biatrial fibrosis ablation is superior to LA fibrosis ablation for cases with high RA fibrosis. Biatrial fibrosis distribution should be considered when targeting AF ablation therapy.

PO-01-166 OUTCOMES FROM REDO ABLATION OF PERSISTENT AF USING SPATIOTEMPORAL DISPERSION MAPPING IN AN INTERNATIONAL TWO CENTRE SERIES

Strategies for redo ablation of persistent atrial fibrillation are debated. This has led to emergence of additional ablation beyond the pulmonary veins targeting dynamically mapped mechanisms. Spatiotemporal dispersion is such a technique using stable electrograms spanning more than 75% of the cycle length over a multipolar catheter and has shown benefit in recent trials. We set out to study an international two centre series for clinical outcomes using this technique in redo ablations. We recruited consecutive patients between September 2018 to September 2021 undergoing redo ablation for persistent AF. Patients were all mapped using Pentaray to mark areas of spatio-temporal dispersion (STD) criteria before any ablation. After confirming pulmonary vein isolation, or re-isolation if connections were present, ablation of all STD areas was performed. Areas were remapped if the patient remained in AF, to prove impact of local ablation, including in the right atrium. If termination to AT occurred, this was mapped using conventional methods. Patients who terminated to sinus underwent reinduction pacing protocols to map any further AT or AF inducible. Patients were followed up at 12 months with 5-7 days continuous event monitor. In total 168 patients were studied at redo ablation for persistent AF (age 66, 68% male, LA diameter 4.8cm). They had undergone 1.4 procedures on average. Over 50% had isolated pulmonary veins at the start of the case. Termination of persistent AF to sinus rhythm (42%) or atrial flutter or tachycardia (41%) was obtained in 140 (83%). Mean procedure duration was 267 min, average number of STD sites in the LA was 2.7. The right atrium was mapped for STD sites in 79 (46%) of patients, and had 1.2 locations treated on average. At 12 months, freedom from AF or AT was 74% overall. Of the patients with recurrences, only 11 (7%) had AF, with 93% recurring with AT or AFL. Figure shows STD patterns (green arrows) on Pentarray in a 67 year old man inferior to left inferior pulmonary vein (A), where ablation terminated AF to sinus rhythm (B). In this two centre international series of redo persistent AF ablations, the use of STD mapping led to increased rates of acute termination and freedom from AF at 12 months. Clinical recurrences were most often organised atrial flutter or tachycardia. Our study informs the real world application of this technique to the more common scenario of additional clinical benefit when pulmonary veins are already isolated.

PO-02-169 PATTERNS OF PULMONARY VEIN ACTIVITY RECORDED DURING PERSISTENT AF MAY HELP IDENTIFY THEIR CONTRIBUTION TO THE MECHANISM OF AF

Pulmonary vein isolation (PVI) is the cornerstone interventional treatment for AF but the success of this approach is more limited in persistent AF (PsAF). In these pts, the main challenge is to discriminate those who will respond to PVI only, from those who may require an extended ablation strategy. We sought to characterize the patterns of the electrical activity recorded within the PVs based on their postulated contribution to the mechanism of PsAF. Three subgroups of consecutive pts who underwent PVI for PsAF were considered based on the mechanism of AF: 1) definitely PV-related: procedural AF termination during PVI (“PVI-term” group) 2) likely PV-related: absence of AF recurrence > 18 months off-AAD after PVI only (“PVI-success” group) 3) definitely/likely PV-unrelated: PsAF recurrence despite isolated PV or at least one redo, respectively (“PVI-failure” group). Each PV and the left atrial appendage were evaluated before ablation. An automatic detection algorithm was developed to extract atrial activations from intra-cardiac electrograms in order to perform further analyses. Epochs of 60-sec were used. Different methods based on the atrial cycle length (CL) variability were assessed to best characterize the potential markers of PV activity such as the occurrence of bursts of rapid activity. A total of 40 pts were included (mean age: 60 ± 10 years, mean AF duration: 11 ± 10 months): PVI-term group (n=10), PVI-success group (n=17), PVI-failure group (n= 13). The dynamics of PV activation intervals was assessed using the envelope of the PV intervals time series. Among all features evaluated, the best feature that could discriminate similarly both the PVI-term and the PVI-success group from the PVI-failure group, was the standard deviation of the inferior envelope relative to the median CL of the PV (p <0.001 and p = 0.005, respectively) (Fig. A-B). Cut-off selected by ROC analysis provided a 100% sensitivity and 85% specificity to discriminate the PVI-term from the PV-failure group (AUC 0.931) and a 88% sensitivity and 77% specificity to discriminate the PVI-success from the PV-failure group (AUC 0.805). This feature performed better than the recently reported “Fastest PV run” (mean CL of the fastest 10-beat run) (AUC = 0.762 and AUC = 0.738, respectively) (Fig. C). Patterns of the electrical activity recorded within the PV differ according to the mechanism of PsAF. Their evaluation may provide the key to discriminate pts who may be cured by PVI only.

A novel approach for quantitative electrogram analysis for driver identification: Implications for ablation in persistent atrial fibrillation.

This study sought to study the feasibility, efficacy, and safety of using multiscale entropy (MSE) analysis to guide catheter ablation for persistent atrial fibrillation (PsAF) and predict ablation outcomes. We prospectively enrolled 108 patients undergoing initial ablation for PsAF. MSE was calculated based on bipolar intracardiac electrograms (iEGMs) to measure the dynamical complexity of biological signals. The iEGMs data were exported after pulmonary vein isolation (PVI), then calculated in a customed platform, and finally re-annotated into the CARTO system. After PVI, regions of the highest mean MSE (mMSE) values were ablated in descending order until AF termination, or three areas had been ablated. Baseline characteristics were evenly distributed between the AF termination (n = 38, 35.19%) and the non-termination group. The RA-to-LA mean MSE (mMSE) gradient demonstrated a positive gradient in the non-termination group and a negative gradient in the termination group (0.105 ± 0.180 vs. -0.235 ± 0.256, P < 0.001). During a 12-month follow-up, 29 patients (26.9%) had arrhythmia recurrence after single ablation, and 18 of them had AF (62.1%). The termination group had lower rates of arrhythmia recurrence (15.79 vs. 32.86%, Log-Rank P = 0.053) and AF recurrence (10.53 vs. 20%, Log-Rank P = 0.173) after single ablation and a lower rate of arrhythmia recurrence (7.89 vs. 27.14%, Log-Rank P = 0.018) after repeated ablation. Correspondingly, subjects with negative RA-to-LA mMSE gradient had lower incidences of arrhythmia (16.67 vs. 35%, Log-Rank P = 0.028) and AF (16.67 vs. 35%, Log-Rank P = 0.032) recurrence after single ablation and arrhythmia recurrence after repeated ablation (12.5 vs. 26.67%, Log-Rank P = 0.062). Marginal peri-procedural safety outcomes were observed. MSE analysis-guided driver ablation in addition to PVI for PsAF could be feasible, efficient, and safe. An RA < LA mMSE gradient before ablation could predict freedom from arrhythmia. The RA-LA MSE gradient could be useful for guiding ablation strategy selection.

Evaluating spatial disparities of rotor sites and high dominant frequency regions during catheter ablation for PersAF patients targeting high dominant frequency sites using non-contacting mapping.

Purpose: Several studies have emphasised the significance of high dominant frequency (HDF) and rotors in the perpetuation of AF. However, the co-localisation relationship between both attributes is not completely understood yet. In this study, we aim to evaluate the spatial distributions of HDF regions and rotor sites within the left atrium (LA) pre and post HDF-guided ablation in PersAF. Methods: This study involved 10 PersAF patients undergoing catheter ablation targeting HDF regions in the LA. 2048-channels of atrial electrograms (AEG) were collected pre- and post-ablation using a non-contact array (EnSite, Abbott). The dominant frequency (DF, 4–10 Hz) areas with DF within 0.25 Hz of the maximum out of the 2048 points were defined as “high” DF (HDF). Rotors were defined as PSs that last more than 100 ms and at a similar location through subsequent phase frames over time. Results: The results indicated an extremely poor spatial correlation between the HDF regions and sites of the rotors in pre-versus post-ablation cases for the non-terminated (pre: CORR; 0.05 ± 0.17. vs. post: CORR; −0.030 ± 0.19, and with terminated patients (pre: CORR; −0.016 ± 0.03. post: CORR; −0.022 ± 0.04). Rotors associated with AF terminations had a long-lasting life-span post-ablation (non-terminated vs. terminated 120.7 ± 6.5 ms vs. 139.9 ± 39.8 ms), high core velocity (1.35 ± 1.3 mm/ms vs. 1.32 ± 0.9 mm/ms), and were less meandering (3.4 ± 3.04 mm vs. 1.5 ± 1.2 mm). Although the results suggest a poor spatial overlapping between rotors’ sites and sites of AFCL changes in terminated and non-terminated patients, a higher correlation was determined in terminated patients (spatial overlapping percentage pre: 25 ± 4.2% vs. 17 ± 3.8% vs. post: 8 ± 4.2% vs. 3.7 ± 1.7% p < 0.05, respectively). Conclusion: Using non-contact AEG, it was noted that the correlation is poor between the spatial distribution of HDF regions and sites of rotors. Rotors were longer-lasting, faster and more stationary in patients with AF termination post-ablation. Rotors sites demonstrated poor spatial overlapping with sites of AFCL changes that lead to AF termination.

Ablation and antiarrhythmic drug effects on PITX2 +/- deficient atrial fibrillation: A computational modeling study.

IntroductionAtrial 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.MethodsWe 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.ResultsAt 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).ConclusionConsistent 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.

Simultaneous Whole-Chamber Non-contact Mapping of Highest Dominant Frequency Sites During Persistent Atrial Fibrillation: A Prospective Ablation Study.

PurposeSites of highest dominant frequency (HDF) are implicated by many proposed mechanisms underlying persistent atrial fibrillation (persAF). We hypothesized that prospectively identifying and ablating dynamic left atrial HDF sites would favorably impact the electrophysiological substrate of persAF. We aim to assess the feasibility of prospectively identifying HDF sites by global simultaneous left atrial mapping.MethodsPersAF patients with no prior ablation history underwent global simultaneous left atrial non-contact mapping. 30 s of electrograms recorded during AF were exported into a bespoke MATLAB interface to identify HDF regions, which were then targeted for ablation, prior to pulmonary vein isolation. Following ablation of each region, change in AF cycle length (AFCL) was documented (≥ 10 ms considered significant). Baseline isopotential maps of ablated regions were retrospectively analyzed looking for rotors and focal activation or extinction events.ResultsA total of 51 HDF regions were identified and ablated in 10 patients (median DF 5.8Hz, range 4.4–7.1Hz). An increase in AFCL of was seen in 20 of the 51 regions (39%), including AF termination in 4 patients. 5 out of 10 patients (including the 4 patients where AF termination occurred with HDF-guided ablation) were free from AF recurrence at 1 year. The proportion of HDF occurrences in an ablated region was not associated with change in AFCL (τ = 0.11, p = 0.24). Regions where AFCL decreased by 10 ms or more (i.e., AF disorganization) after ablation also showed lowest baseline spectral organization (p < 0.033 for any comparison). Considering all ablated regions, the average proportion of HDF events which were also HRI events was 8.0 ± 13%. Focal activations predominated (537/1253 events) in the ablated regions on isopotential maps, were modestly associated with the proportion of HDF occurrences represented by the ablated region (Kendall’s τ = 0.40, p < 0.0001), and very strongly associated with focal extinction events (τ = 0.79, p < 0.0001). Rotors were rare (4/1253 events).ConclusionTargeting dynamic HDF sites is feasible and can be efficacious, but lacks specificity in identifying relevant human persAF substrate. Spectral organization may have an adjunctive role in preventing unnecessary substrate ablation. Dynamic HDF sites are not associated with observable rotational activity on isopotential mapping, but epi-endocardial breakthroughs could be contributory.

Similarity Score for the Identification of Active Sites in Patients With Atrial Fibrillation.

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and precursor to other cardiac diseases. Catheter ablation is associated with limited success rates in patients with persistent AF. Currently, existing mapping systems fail to identify critical target sites for ablation. Recently, we proposed and validated several individual techniques, such as dominant frequency (DF), multiscale frequency (MSF), kurtosis (Kt), and multiscale entropy (MSE), to identify active sites of arrhythmias using simulated intracardiac electrograms (iEGMs). However, the individual performances of these techniques to identify arrhythmogenic substrates are not reliable.ObjectiveThis study aimed to develop a similarity score using various iEGM analysis techniques to more accurately identify the spatial location of active sites of arrhythmia in patients with AF.MethodsClinical bipolar iEGMs were obtained from patients with AF who underwent either successful (m = 4) or unsuccessful (m = 4) catheter ablation. A similarity score (0–3) was developed via the earth mover’s distance (EMD) approach based on a combination of DF, MSF, MSE, and Kt techniques.ResultsIndividual techniques successfully discriminated between successful and unsuccessful AF ablation patients but were not reliable in identifying active spatial sites of AF. However, the proposed similarity score was able to pinpoint the spatial sites with high values (active AF sites) that were observed only in patients with unsuccessful AF termination, suggesting that these active sites were missed during the ablation procedure.ConclusionArrhythmogenic substrates with abnormal electrical activity are identified in patients with unsuccessful AF termination after catheter ablation, suggesting clinical efficacy of similarity score.

Multilevel Classification and Detection of Cardiac Arrhythmias With High-Resolution Superlet Transform and Deep Convolution Neural Network

Atrial fibrillation and ventricular fibrillation are the two most common cardiac arrhythmia. These cardiac arrhythmias cause heart strokes and other heart complications leading increased risk of heart failure. Early and accurate cardiac arrhythmia detection is vital to preventing various heart-related diseases. Electrocardiogram (ECG) is a popular and reliable method to detect cardiac arrhythmia and heart-related diseases. However, sometimes it becomes difficult and time-consuming to interpret the ECG signal, even for a cardiac expert. This study proposes a deep learning-based method to effectively classify and detect cardiac arrhythmias (atrial fibrillation and ventricular fibrillation) using a time-frequency spectrogram of ECG records. The proposed framework utilizes superlet transform (SLT) to transform the one-dimensional (1-D) ECG signal into a two-dimensional (2-D) time-frequency spectrogram. The last layer of the pre-trained convolutional neural networks, namely, AlexNet, GoogLeNet, and DenseNet, are modified and then used to classify the ECG records into healthy heart, atrial fibrillation, and ventricular fibrillation. The proposed method is tested using ECG signals from the MIT-BIH arrhythmia database, MIT-BIH malignant database, Fantasia database, AF termination challenge database, and CU ventricular tachyarrhythmia database. The proposed method with DenseNet-201 architecture provides the best performance with an overall test accuracy of 96.2%. The proposed method reduces the system complexity as it does not require noise removal, hand-crafted features, and beat detection. Further, the proposed system automatically classifies the ECG signal into healthy heart, atrial fibrillation, and ventricular fibrillation.

Very long term outcome after linear versus electrogram guided ablation for persistent atrial fibrillation

The optimal ablation strategy for persistent atrial fibrillation (PsAF) remains to be defined. We sought to compare very long-term outcomes between linear ablation and electrogram (EGM)-guided ablation for PsAF. In a retrospective analysis, long-term arrhythmia-free survival compared between two propensity-score matched cohorts, one with pulmonary vein isolation (PVI) and linear ablation including roof/mitral isthmus line (LINE-group, n = 52) and one with PVI and EGM-guided ablation (EGM-group; n = 52). Overall, 99% of patients underwent successful PVI. Complete block following linear ablation was achieved for 94% of roof lines and 81% of mitral lines (both lines blocked in 75%). AF termination by EGM-guided ablation was accomplished in 40% of patients. Non-PV foci were targeted in 7 (13%) in the LINE-group and 5 (10%) patients in the EGM-group (p = 0.76). During 100 ± 28 months of follow-up, linear ablation was associated with superior arrhythmia-free survival after the initial and last procedure (1.8 ± 0.9 procedures) compared with EGM-group (Logrank test: p = 0.0001 and p = 0.045, respectively). In multivariable analysis, longer AF duration and EGM-guided ablation remained as independent predictors of atrial arrhythmia recurrence. Linear ablation might be a more effective complementary technique to PVI than EGM-guided ablation for PsAF ablation.

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation – The NOVA Study

Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.