Complex Fractionated Atrial Electrograms Research Articles

Trapped re-entry challenges the binary view on cardiac arrhythmias

Abstract Background There is currently a binary view on cardiac arrhythmias: (1) arrhythmias are present and thereby affect the atria or ventricles as a whole, or (2) they are not present and therefore the heart is in sinus rhythm. However, complex fractionated atrial electrograms (CFAEs) under sinus rhythm (SR) are observed in patients with atrial fibrillation (AF), raising the question whether both cardiac states (arrhythmia and SR) could coexist. Although CFAEs in AF patients have been associated with functional and structural heterogeneities (e.g. dense fibrotic regions), the underlying mechanisms of fractionation under SR remain incompletely understood. Purpose To test the hypothesis that an arrhythmia can exist locally with the majority of cardiac tissue in sinus rhythm, made possible through dense local fibrotic regions forming a small electrically isolated re-entrant circuit that can "trap" excitation waves, which can only be "released" under dynamic tissue changes at an isthmus connected to the bulk of the tissue. Methods By harnessing the unique possibilities of light-gated depolarizing ion channels (CatCh) to precisely control in vitro cardiac excitability in time and space, complemented with advanced computational modelling of whole human atria, we explored the geometry of such an electrically isolated circuit and assessed its clinical relevance. Results Optical mapping studies, in monolayers of CatCh-activated neonatal rat atrial cardiomyocytes (n=8), revealed that re-entry can be established and trapped by creating an electrically isolated pathway with a bulk-connecting isthmus causing source-sink mismatch. A tachyarrhythmia was shown to exist locally with SR prevailing in the bulk of the monolayer. Next, conditions were found under which re-entry could escape this pathway, thereby converting a local dormant arrhythmic source into an active driver with global impact. Escape could be established by overcoming the source-sink mismatch through widening of the isthmus or a reduction of the gap junctional coupling. In a digital twin of the human atria, it was revealed that the conditions for "trapped re-entry" and its release can be realized as well. Unipolar pseudo-electrograms derived from these complementary computational 3D studies showed CFAEs at the site of "trapped re-entry" in coexistence with normal electrograms of SR in the bulk of the atria. Upon release of the re-entry, acute arrhythmia onset occurred, affecting the complete atria as evidenced by wave front and electrogram visualization. Conclusion Through the concept of "trapped re-entry", we not only present a new mechanism of acute manifestation of focal tachyarrhythmias, but also provide novel insight into the origin of fractionated electrograms. This insight may provide new rationales for treatment of cardiac arrhythmias, especially for ablation by site-directed targeting.Trapped re-entry in vitro and in silico

Additional ablation to pulmonary vein isolation for persistent atrial fibrillation does not reduce recurrence

Abstract Introduction Treatment with catheter ablation (CA) as rhythm control is increasingly used in atrial fibrillation (AF). Pulmonary vein isolation (PVI) alone is less effective in patients with persistent AF (peAF) compared to patients with paroxysmal AF (PAF). Strategies and methods to optimize outcome for peAF is still an ongoing challenge. Additional ablation to pulmonary vein isolation (PVI plus) compared to PVI alone has so far shown conflicting evidence and has yet to be tested in a large unselected, real-life population with longtime follow-up. Purpose To examine AF recurrence by PVI or PVI plus for CA for peAF. Method This nationwide retrospective registry study was conducted using large real-life data from Danish mandatory registries. All patients above 18 years of age, that underwent first-time CA for peAF from January 1st 2010 to December 31st 2018, were identified and included at the date of ablation. Exposure of interest was CA, and patients were stratified into PVI or PVI plus. PVI plus was defined as either roofline, mitral linear ablation, posterior wall isolation (PWI), complex fractionated atrial electrograms (CFAE) or ganglionated plexi ablation (GP). Primary endpoint was recurrent AF after a 3-months blanking period, defined by a composite endpoint of first-reached endpoint of either use of antiarrhythmic drugs (AAD), AF-admission, electrical cardioversions or AF re-ablation. 5-year risk of recurrent AF was examined by the Aalen-Johansen estimator, taking the competing risk of death into account. The relative rates of recurrent AF by ablation strategy (PVI or PVI plus) were examined by Cox proportional models using PVI as reference. The analysis was adjusted for clinically important baseline characteristics including age, sex, diagnosis-to-ablation time, procedural year, body mass index, size of left atrium, heart failure, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension and diabetes. Results The study cohort consisted of 2.444 patients with peAF undergoing first-time CA, of which 2.069 received PVI and 375 received PVI plus. Median age was 63 for the PVI group and 64 for the PVI plus group. The PVI plus group had longer diagnosis-to-ablation-time and enlarged left atrium compared to the PVI group. 5-year cumulative incidence of recurrent AF was 55% for the PVI group and 71% for the PVI plus group in the unadjusted analysis (Figure 1). The relative risk of recurrent AF showed hazard ratio of 1.11 (95% CI: 0.95-1.29) for the PVI plus group compared to the PVI group (Figure 2). Conclusion Strategies to reduce AF recurrences after CA for peAF is an ongoing challenge. This study did not find any significant reduction in recurrence of AF using PVI plus strategy compared to PVI alone. The increased absolute risk of AF recurrence in the PVI plus group is most likely accounted for by longer diagnosis-to-ablation-time and enlarged left atrium compared to the PVI group.Figure 1Figure 2

15-month follow-up of catheter ablation for atrial fibrillation in octogenarians

Abstract Background Catheter ablation for atrial fibrillation (AF) in octogenarians poses a challenge due to comorbidities, frailty, and suspected higher complication rates. Data regarding the outcome of catheter ablation in this population is scarce. Purpose Due to the projected increase of octogenarians presenting with AF in the future, we investigated the outcome of catheter ablation in this patient population. Methods We retrospectively analysed octogenarians with symptomatic AF undergoing catheter ablation in a single centre, including first and re-ablation procedures. Catheter ablation involved pulmonary vein isolation (PVI) using radiofrequency (RF), cryoballoon (CB) and pulsed field ablation (PFA) as energy sources and also atrial tachycardia (AT) ablation including linear lesions and/or ablation of complex fractionated atrial electrograms (CFAE). Follow-up (FU) was obtained to assess arrhythmia-free survival after a 90-day blanking period, recurrences after the blanking period, management of recurrences, rhythm at FU, use of antiarrhythmic drugs (AADs) and improvement in symptoms (EHRA symptom scale). Results A total of 126 patients (mean age 82.2 ± 1.9 years, paroxysmal AF n=48, persistent AF n=78, mean CHA2DS2-VASc-Score 4.2 ± 1.5) were included. 57.1% (n=72/126) underwent an index procedure {47.2% (n=34/72) RF PVI, 37.5% (n=27/72) CB PVI, 4.2% (n=3/72) PFA PVI and 11.1% (n=8/72) PVI + AT ablation}. 42.9% (n=54/126) received repeat procedures {20.4% (n=11/54) re-PVI, 42.6% (n=23/54) re-PVI + AT ablation, 37% (n=20/54) AT ablation}. FU of 108 patients after 15.4 ± 3.6 months revealed arrhythmia-free survival after the blanking period in 64.8% (n=70/108). Recurrence after the blanking period was seen in 35.2% (n=38/108). No significant difference in recurrences was shown between index and repeat procedures (32.3%, n=20/62 after index procedures and 36.7%, n=18/49 after repeat procedures, p =0.97). Management of recurrence involved repeat ablation (47%, n=18/38), AADs (16%, n=6/38), cardioversion (21%, n=8/38), pacemaker-implantation/AV-node ablation (5%, n=2/38) and pharmacological rate control (11%, n=4/38). At FU, 88.9% (n=96/108) of patients were in sinus rhythm with 21.3% (n=23/108) receiving AADs, 7.4% (n=8/108) were in AF, 0.9% (n=1/108) in AT and 2.8% (n=3/108) pacemaker-dependant. Symptoms were significantly improved at FU (mean EHRA score at FU= 1.2 ± 0.5, before ablation= 2.4 ± 0.5, p <0.0001). Conclusion Catheter ablation for AF in octogenarians is effective in maintaining sinus rhythm and controlling AF-related symptoms. Longer term success and impact on prognosis in this patient population is unknown and should be investigated further.

Abstract 15716: Meta-Analysis of Randomized Controlled Trials Comparing Ablation Targets Beyond Pulmonary Vein Isolation versus Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation

Introduction: Catheter ablation for persistent atrial fibrillation (PeAF) is challenging and pulmonary vein isolation(PVI) alone has limited success. Adjunctive ablation strategies like posterior wall isolation (PWI), linear ablation, substrate modification utilizing complex fractionated atrial electrograms (CFAE) or MRI guided fibrosis ablations have demonstrated variable results beyond PVI alone. We performed a meta analysis of randomized controlled trials (RCTs) comparing efficacy, safety and procedural outcomes of PVI plus adjunctive ablation strategies versus PVI alone. Methods: We performed a comprehensive search of electronic databases from inception to April 2023 searching RCTs comparing PVI alone versus PVI+adjunctive strategies(linear ablations, CFAE, PWI, low voltage area ablation and MRI-guided atrial fibrosis ablation). Primary efficacy outcome was recurrence of atrial arrhythmias > 30s after a single ablation procedure, with or without antiarrhythmics. Secondary safety outcome was composite of access site complications, tamponade, hemopericardium, pericardial effusion, pericarditis, stroke/TIA, pulmonary vein stenosis, atrioesophageal fistula or phrenic nerve palsy. Procedural characteristics included mean procedural time and mean ablation time. Pooled risk ratio (RR), mean difference (MD) and 95% confidence interval (CI) were calculated. Statistical analysis was performed using RevMan5.4.1 Results: 10 RCTs with a total of 3042 patients (PVI plus adjunctive n= 1717; PVI alone n= 1325) were included. The mean age was 61.6 ± 0.14 years. The mean follow-up was 16.5 months. There was no significant difference in primary efficacy outcome (RR: 0.99; CI: 0.88-1.12; p> 0.05; I2 = 28%) or secondary safety outcome (RR: 1.46; CI: 0.97-2.18; p> 0.05; I2 = 16%), between two groups. Procedural characteristics including mean procedural time in minutes (MD: 31.84; CI: 4.92-58.75; p< 0.05; I2 = 95%) and mean ablation time in minutes (MD: 20.30; CI: 8.16-32.43; p< 0.05; I2 = 95%) were significantly shorter for PVI alone group. Conclusions: Adjunctive ablation strategies provide no additional benefit over PVI alone in PeAF, but are associated with significantly longer procedural and ablation time.

Functional mapping to reveal slow conduction and substrate progression in atrial fibrillation.

The aim of our study was to analyse the response to short-coupled atrial extrastimuli to identify areas of hidden slow conduction (HSC) and their relationship with the atrial fibrillation (AF) phenotype. Twenty consecutive patients with paroxysmal AF and persistent AF (10:10) underwent the first pulmonary vein isolation procedure. Triple short-coupled extrastimuli were delivered in sinus rhythm (SR), and the evoked response was analysed: sites exhibiting double or highly fragmented electrograms (EGM) were defined as positive for HSC (HSC+). The delta of the duration of the bipolar EGM was analysed, and bipolar EGM duration maps were built. High-density maps were acquired using a multipolar catheter during AF, SR, and paced rhythm. Spatial co-localization of HSC+ and complex fractionated atrial EGMs (CFAE) during AF was evaluated. Persistent AF showed a higher number and percentage of HSC+ than paroxysmal AF (13.9% vs. 3.3%, P < 0.001). The delta of EGM duration was 53 ± 22 ms for HSC+ compared with 13 ± 11 (10) ms in sites with negative HSC (HSC-) (P < 0.001). The number and density of HSC+ were lower than CFAE during AF (19 vs. 56 per map, P < 0.001). The reproducibility and distribution of HSC+ in repeated maps were superior to CFAE (P = 0.19 vs. P < 0.001). Sites with negative and positive responses showed a similar bipolar voltage in the preceding sinus beat (1.65 ± 1.34 and 1.48 ± 1.47 mV, P = 0.12). Functional mapping identifies more discrete and reproducible abnormal substrates than mapping during AF. The HSC+ sites in response to triple extrastimuli are more frequent in persistent AF than in paroxysmal AF.

Radiofrequency ablation of atrial fibrillation: A 14 years' experience at a tertiary care center in Thailand.

The result of atrial fibrillation (AF) ablation varies across centers. Most data are derived from the Western world, while data from Southeast Asian countries are lacking. We aimed to investigate the outcomes of AF ablation in Thailand. We performed a retrospective analysis of patients who underwent AF ablation in a tertiary care center, between the years 2006-2020. Details of AF ablation, including pulmonary vein isolation (PVI), and complex fractionated atrial electrogram (CFAE) ablation, were classified. The success rate of AF ablation is determined by freedom from AF beyond 3 months blanking period. Combined success rate of AF ablation was reported along with the success rate of each technique (PVI, CFAE, and combine PVI plus CFAE). We identified a total of 171 patients who underwent the first AF ablation. Ninety-four (55%) patients went through PVI, 55 (32%) patients for CFAE ablation, and 22 (13%) patients for PVI plus CFAE ablation. Overall freedom from AF was 73% at 12 months, 66% at 24 months, and 55% at 36 months. The success rate of PVI was 79% at 12 months, 74% at 24 months, and 59% at 36 months. The success rate of CFAE ablation was 63% at 12 months, 51% at 24 months, and 47% at 36 months. Catheter ablation of AF is proven safe and effective in Thai population.

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.

High Dominant Frequencies and Fractionated Potentials Do Not Indicate Focal or Rotational Activation During AF

BackgroundDominant frequencies (DFs) or complex fractionated atrial electrograms (CFAEs), indicative of focal sources or rotational activation, are used to identify target sites for atrial fibrillation (AF) ablation in clinical studies, although the relationship among DF, CFAE, and activation patterns remains unclear. ObjectivesThis study sought to investigate the relationship between patterns of activation underlying DF and CFAE sites during AF. MethodsEpicardial high-resolution mapping of the right and left atrium including Bachmann’s bundle was performed in 71 participants. We identified the highest dominant frequency (DFmax) and highest degree of CFAE (CFAEmax) with the use of existing clinical criteria and classified patterns of activation as focal or rotational activation and smooth propagation, conduction block (CB), collision and remnant activity, and fibrillation potentials as single, double, or fractionated potentials containing, respectively, 1, 2, or 3 or more negative deflections. Relationships among activation patterns, DFmax, and potential types were investigated. ResultsDFmax were primarily located at the left atrioventricular groove and did not harbor focal activation (proportion focal waves: 0% [IQR: 0%-2%]). Compared with non-DFmax sites, DFmax were characterized by more frequent smooth propagation (22% [IQR: 7%-48%] vs 17% [IQR: 11%-24%]; P = 0.001), less frequent conduction block (69% [IQR: 51%-81%] vs 74% [IQR: 69%-78%]; P = 0.006), a higher proportion of single potentials (72% [IQR: 55%-84%] vs 6%1 [IQR: 55%-65%]; P = 0.003), and a lower proportion of fractionated potentials (4% [IQR: 1%-11%] vs 12% [IQR: 9%-15%]; P = 0.004). CFAEmax were mainly found at the pulmonary veins area, and only 1% [IQR: 0%-2%] of all CFAEmax contained focal activation. Compared with non-CFAEmax sites, CFAEmax sites were characterized by less frequent smooth propagation (1% [IQR: 0%-1%] vs 17% [IQR: 12%-24%]; P < 0.001) and more frequent remnant activity (20% [IQR: 12%-29%] vs 8% [IQR: 5%-10%]; P < 0.001), and harbored predominantly fractionated potentials (52% [IQR: 43%-66%] vs 12% [IQR: 9%-14%]; P < 0.001). ConclusionsFocal or rotational patterns of activation were not consistently detected at DFmax domains and CFAEmax sites. These findings do not support the concept of targeting DFmax or CFAEmax according to existing criteria for AF ablation.

10-Year Outcomes of Patients With Non-Paroxysmal Atrial Fibrillation Undergoing Catheter Ablation.

Radiofrequency catheter ablation (RFCA) is commonly performed in patients with non-paroxysmal atrial fibrillation (AF), but because very long-term follow-up results of RFCA are limited, we investigated the 10-year RFCA outcomes of non-paroxysmal AF.Methods and Results: We retrospectively enrolled 100 patients (89 men, mean age 53.5±8.4years) with drug-refractory symptomatic non-paroxysmal AF who underwent 3D electroanatomic-guided RFCA. Procedural characteristics at index procedures and clinical outcomes were investigated. In the index procedures, all patients had pulmonary vein isolation, 56 (56.0%), 48 (48.0%), and 32 (32.0%) underwent additional linear, complex fractionated atrial electrogram (CFAE) and non-pulmonary vein (NPV) foci ablations, respectively. After 124.1±31.7 months, 16 (16%) patients remained in sinus rhythm after just 1 procedure (3 with antiarrhythmic drugs [AAD]) and after multiple (2.1±1.3) procedures in 53 (53.0%) patients (22 with AAD). Left atrial (LA) diameter (hazard ratio HR 1.061; 95% confidence interval (CI) 1.020 to 1.103; P=0.003), presence of NPV triggers (HR 1.634; 95% CI 1.019 to 2.623; P=0.042) and undergoing CFAE ablation (HR 2.003; 95% CI 1.262 to 3.180; P=0.003) in the index procedure were independent predictors for recurrent atrial tachyarrhythmia. The 10-year outcomes of single RFCA in non-paroxysmal AF were unsatisfactory. Enlarged LA, presence of NPV triggers, and undergoing CFAE ablation in the index procedure independently predicted single-procedure recurrence. Multiple procedures are required to achieve adequate rhythm control.

193 13 SECONDS OF ASYSTOLE IN YOUNG: IS A PACEMAKER NECESSARY?

Abstract Introduction Cardioinhibitory neurocardiogenic syncope (CNS) is caused by inappropriately trigger-activated cardiac reflex which finally precipitates asystole, sinus bradycardia, or atrioventricular block. In the absence of structural heart disease, the prognosis is excellent, but frequent syncopal episodes can have a significant impact on quality of life. No medical therapy has proved to be really effective and studies concerning pacemaker implantation are often controversial. However, in young individuals, especially those under 40 years of age, implanting a pacemaker may carry more risks than benefits. Thus, alternative techniques such as ablation of the cardiac atrial parasympathetic ganglia (GP) have emerged. Case report A 34-year-old man with frequent episodes of reflex syncope performed a tilt test in March 2022 that diagnosed cardio-inhibitory syncope with 13-second asystole interrupted with external cardiac massage and intravenous atropine. In May 2022 he had an MRI scan showing normal biventricular systolic function and absence of late-gadolinium enhancement and underwent loop recorder implantation. He came to our centre in June 2022 and underwent electrophysiological study and electroanatomical mapping of the right atrium (Carto 3) during general anaesthesia. The anatomical areas of the supero-posterior and infero-posterior GPs of the right atrium were identified by electroanatomical mapping of complex fractionated atrial electrograms (CFAE). Radiofrequency pulses (Thermocool 30 watts) were delivered at these points, resulting in the disappearance of the CFAEs and an increase in basal heart rate. The greatest number of ganglia are allocated on the posterior surface of the right atrium and in particular the supero-posterior GP is the nexus point for vagal input to the GPs before innervating the atria. Therefore, it was decided to localise and ablate exclusively the GPs of the right atrium. The procedure was completed without complications. The patient has not complained of any syncopal episodes since, and the loop has not recorded any significant pauses. Conclusions The anatomic ablation of GP only in the right atrium could represent a feasible method to reduce CNS, to increase the warning symptoms period, and to delay as much as possible pacemaker implant, especially in young patients who have experienced a related physical trauma. This approach significantly decreased the procedural time and risks.

Extensive ablation strategy for persistent atrial fibrillation impairs left atrial function but reduces recurrence rate

Abstract Background In catheter ablation for persistent atrial fibrillation (AF), extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might impair left atrial function more severely than PVI-alone strategy. Purpose The aim of this study is to investigate the impact of extensive ablation strategy on LA function and assess the relationship between post-ablation LA function and recurrence. Methods This study is a post-hoc subanalysis of the EARNEST-PVI randomized controlled trial, which investigated the efficacy of the PVI-alone strategy in comparison with PVI-plus strategy for persistent AF. From the 497 participants of EARNEST-PVI trial, we enrolled 191 patients with full datasets of pre- and post-ablation cardiac computed tomography (CT) at our Hospital. Patients were divided into PVI-alone and PVI-plus groups. Within one month before and 3 months after ablation, LA volume index (LAVI) and LA emptying fraction (LAEF) were calculated by using the Comprehensive Cardiac Analysis software on the Extended Brilliance Workspace. We assessed i) post-ablation LA function, ii) AF/atrial tachycardia (AT) -free rate after single and final session, and iii) relationship between post-ablation LAEF and ablation success in each group. Results The indices of baseline LA remodeling were not different between PVI-alone (N=96) and PVI-plus groups (N=95) [LAVI: 71.4 (57.8, 82.0) vs. 68.7 (61.0, 78.1), P=0.92, LAEF: 13.7 (10.0, 17.4) vs. 13.0 (10.0, 16.9), PVI-alone vs. PVI-plus, P=0.78]. In overall patients, post-ablation LAEF did not differ among them [34.4 (26.1, 40.7) vs. 31.6 (26.0, 37.4), P=0.13]. In the analysis of patients showing sinus rhythm during the CT study, LAEF was significantly higher in PVI-alone (N=87) than in PVI-plus group (N=93) [35.7 (29.0, 41.0) vs. 31.7 (26.1, 37.5), P=0.011] (Figure 1A). AF/AT-free survival rate during median follow-up of 44 months was not different after first session (63.5% vs. 68.4%, P=0.33), while PVI-plus had a tendency towards higher success rate after final session (72.9% vs. 84.2%, P=0.053) (Figure 2). In receiver operating characteristics analysis for recurrence after first session, post-ablation decreased LAEF had significantly related to recurrence after PVI-alone (AUC: 0.733, P&amp;lt;0.0001), but not after PVI-plus (AUC: 0.567, P=0.31) (Figure 1B, C). Conclusion Compared with PVI-alone strategy, PVI-plus strategy damaged LA function more severely, but tended to be related to higher success rate. Post-ablation LA function was related to recurrence in PVI-alone, but not in PVI-plus. Extensive ablation might have additional anti-arrhythmic effect regardless of iatrogenic myocardial damage. Myocardial injury by extensive ablation may less attribute to recurrence than intrinsic damage of LA. Funding Acknowledgement Type of funding sources: None.

Safety and efficacy of catheter ablation for atrial fibrillation in the very elderly

Abstract Background The incidence and prevalence of atrial fibrillation (AF) increases with age. With an ageing general population, a 2.3-fold rise in AF prevalence is expected. Catheter ablation has emerged as an effective treatment option for rhythm control therapy. However, very elderly patients (≥80 years old) have been excluded in landmark clinical trials. Current data regarding the safety and efficacy of catheter ablation in the very elderly is therefore sparse. Purpose Due to the growing demand to manage AF in an increasingly ageing population, we investigated the safety and efficacy of catheter ablation in this particular patient population. Methods Patients with symptomatic paroxysmal, persistent and long-standing persistent AF aged ≥80 years undergoing catheter ablation, including first and re-ablation procedures in a single centre, were analysed retrospectively. Catheter ablation involved pulmonary vein isolation (PVI) using radiofrequency, cryoballoon and pulsed field ablation as energy sources. Re-ablation procedures included re-PVI and consecutive atrial tachycardia ablation including atrial lines and/or ablation of complex fractionated atrial electrograms (CFAE) in persistent AF. Endpoints included acute procedural success (complete isolation of pulmonary veins and/or non-inducibility in the case of atrial tachycardia), major complications and early arrhythmia-recurrence. Results A total of eighty-eight patients (mean age 83.1±1.9 years, mean CHA2DS2-VASc-Score 4.4±1, mean left ventricular ejection fraction 56.7±7%, direct oral anticoagulation 92.1%, vitamin-K antagonists 7.9%) were included from January 2021 to October 2021. Fifty cases (56.8%) involved PVI as an index procedure (radiofrequency 58%, n=29/50, cryoballoon 36%, n=18/50, pulsed field ablation 6%, n=3/50). Thirty-eight procedures (43.2%) involved re-ablation procedures (Re-PVI 60.5%, n=23/38, linear lesions 65.8%, n=25/38, atrial tachycardia ablation 26.3%, n=10/38 and ablation of CFAE 15.8%, n=6/38). Acute procedural success was achieved in 87/88 patients (98.9%). Major complications included stroke (n=1/88, 1.1%), pericardial tamponade (n=1/88, 1.1%) and bradycardia with subsequent pacemaker implantation (n=3/88, 3.4%). No further major complications were documented. In 13/88 patients (14.8%) early arrhythmia-recurrence occurred (38.5%, n=5/13 after the index procedure and 61.5%, n=8/13 after re-ablation) during the 90-day blanking period. Conclusions Catheter ablation for atrial fibrillation in the very elderly shows favourable acute success and low complication rates. Long term success of catheter ablation and superiority to rate control in this patient population is unknown and requires investigation in the future. Funding Acknowledgement Type of funding sources: None.

Practical Considerations for the Application of Nonlinear Indices Characterizing the Atrial Substrate in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and in response to increasing clinical demand, a variety of signals and indices have been utilized for its analysis, which include complex fractionated atrial electrograms (CFAEs). New methodologies have been developed to characterize the atrial substrate, along with straightforward classification models to discriminate between paroxysmal and persistent AF (ParAF vs. PerAF). Yet, most previous works have missed the mark for the assessment of CFAE signal quality, as well as for studying their stability over time and between different recording locations. As a consequence, an atrial substrate assessment may be unreliable or inaccurate. The objectives of this work are, on the one hand, to make use of a reduced set of nonlinear indices that have been applied to CFAEs recorded from ParAF and PerAF patients to assess intra-recording and intra-patient stability and, on the other hand, to generate a simple classification model to discriminate between them. The dominant frequency (DF), AF cycle length, sample entropy (SE), and determinism (DET) of the Recurrence Quantification Analysis are the analyzed indices, along with the coefficient of variation (CV) which is utilized to indicate the corresponding alterations. The analysis of the intra-recording stability revealed that discarding noisy or artifacted CFAE segments provoked a significant variation in the CV(%) in any segment length for the DET and SE, with deeper decreases for longer segments. The intra-patient stability provided large variations in the CV(%) for the DET and even larger for the SE at any segment length. To discern ParAF versus PerAF, correlation matrix filters and Random Forests were employed, respectively, to remove redundant information and to rank the variables by relevance, while coarse tree models were built, optimally combining high-ranked indices, and tested with leave-one-out cross-validation. The best classification performance combined the SE and DF, with an accuracy (Acc) of 88.3%, to discriminate ParAF versus PerAF, while the highest single Acc was provided by the DET, reaching 82.2%. This work has demonstrated that due to the high variability of CFAEs data averaging from one recording place or among different recording places, as is traditionally made, it may lead to an unfair oversimplification of the CFAE-based atrial substrate characterization. Furthermore, a careful selection of reduced sets of features input to simple classification models is helpful to accurately discern the CFAEs of ParAF versus PerAF.

Sex Differences in the Efficacy of Pulmonary Vein Isolation Alone vs. Extensive Catheter Ablation in Patients With Persistent Atrial Fibrillation.

Women experience more severe arrhythmogenic substrates. This study hypothesized that an extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might be effective for women, whereas the PVI alone strategy (PVI-alone) might be sufficient for men to maintain sinus rhythm. The aim of this study was to test this hypothesis.Methods and Results: This study is a post-hoc subanalysis of the EARNEST-PVI trial focusing on sex differences in the efficacies of different ablation strategies. The EARNEST-PVI trial was a prospective, multicenter, randomized, and open-label non-inferiority trial in patients with persistent AF. The primary endpoint was recurrence of AF, atrial flutter, or atrial tachycardia. The EARNEST-PVI trial randomized 376 (76%) men (PVI-alone 186, PVI-plus 190) and 121 (24%) women (PVI-alone 63, PVI-plus 58). The event rate was significantly lower for men and numerically lower for women in the PVI-plus than the PVI-alone group, and there was no interaction between men and women (hazard ratio, 0.641; 95% confidence interval, 0.417-0.985; P value, 0.043 for men vs. hazard ratio, 0.661; 95% confidence interval, 0.352-1.240; P value, 0.197 for women; P value for interaction, 0.989). The superiority of the extensive ablation strategy vs. the PVI-alone strategy for persistent AF was consistent across both sexes.

An Efficient Hybrid Methodology for Local Activation Waves Detection under Complex Fractionated Atrial Electrograms of Atrial Fibrillation.

Local activation waves (LAWs) detection in complex fractionated atrial electrograms (CFAEs) during catheter ablation (CA) of atrial fibrillation (AF), the commonest cardiac arrhythmia, is a complicated task due to their extreme variability and heterogeneity in amplitude and morphology. There are few published works on reliable LAWs detectors, which are efficient for regular or low fractionated bipolar electrograms (EGMs) but lack satisfactory results when CFAEs are analyzed. The aim of the present work is the development of a novel optimized method for LAWs detection in CFAEs in order to assist cardiac mapping and catheter ablation (CA) guidance. The database consists of 119 bipolar EGMs classified by AF types according to Wells’ classification. The proposed method introduces an alternative Botteron’s preprocessing technique targeting the slow and small-ampitude activations. The lower band-pass filter cut-off frequency is modified to 20 Hz, and a hyperbolic tangent function is applied over CFAEs. Detection is firstly performed through an amplitude-based threshold and an escalating cycle-length (CL) analysis. Activation time is calculated at each LAW’s barycenter. Analysis is applied in five-second overlapping segments. LAWs were manually annotated by two experts and compared with algorithm-annotated LAWs. AF types I and II showed accuracy and sensitivity. AF type III showed accuracy and sensitivity. The results of this study highlight the efficiency of the developed method in precisely detecting LAWs in CFAEs. Hence, it could be implemented on real-time mapping devices and used during CA, providing robust detection results regardless of the fractionation degree of the analyzed recordings.

Trapped re-entry: a dormant source of arrhythmia

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This study was supported by the European Research Council (Starting grant 716509) to D.A. Pijnappels. Background Diseased atria are characterized by functional and structural heterogeneities (e.g. dense fibrotic regions), which add to abnormal impulse generation and propagation, like ectopy and block. These heterogeneities are thought to play a role in the origin of complex fractionated atrial electrograms (CFAEs) under sinus rhythm (SR) in patients with atrial fibrillation (AF), but also in the onset and perpetuation (e.g. re-entry) of this disorder. The underlying mechanisms, however, remain incompletely understood. Objective To test the hypothesis that dense local fibrotic regions can create an electrically isolated conduction pathway in which re-entry can be established via ectopy and block to become "trapped" (giving rise to CFAEs under SR), only to be "released" under dynamic tissue changes at a connecting isthmus (causing acute onset of arrhythmia). Methods The geometry of such a pathway, under which re-entry could be trapped and released, was explored in vitro using optogenetics by creating conduction blocks of any shape by means of light-gated depolarizing ion channels (CatCh) and patterned illumination. Insight from these studies was used for complementary investigation in a digital twin of the human atria to assess clinical relevance. Results Optical mapping studies, in monolayers of CatCh-activated neonatal rat atrial cardiomyocytes, revealed that re-entry can be established and trapped by creating an electrically isolated pathway with a bulk-connecting isthmus causing source-sink mismatch. A tachyarrhythmia was shown to exist locally with SR prevailing in the bulk of the monolayer. Next, conditions were found under which re-entry could escape this pathway, thereby converting a local dormant arrhythmic source into an active driver with global impact. Escape could be established by overcoming the source-sink mismatch through widening of the isthmus or a reduction of the gap junctional coupling. In a digital twin of the human atria, it was revealed that the conditions for "trapped re-entry" and its release can be realized as well. Unipolar pseudo-electrograms derived from these complementary computational 3D studies showed CFAEs at the site of "trapped re-entry" in coexistence with normal electrograms of SR in the bulk of the atria. Upon release of the re-entry, acute arrhythmia onset occurred, affecting the complete atria as evidenced by wave front and electrogram visualization. Conclusion This study reveals that "trapped re-entry", a previously undesignated phenomenon, can explain the observation of two designated ones: CFAEs under SR and acute arrhythmia onset. Further exploration of the concept of "trapped re-entry" may not only expand our understanding of AF initiation and perpetuation, but also termination, including ablation strategies by site-directed targeting.

Relationship between electrical activity and left atrial volume during atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pulmonary veins (PV) ostia were previously identified as the left atrium (LA) areas with the shortest refractory period during sinus rhythm. Pulmonary veins isolation (PVI) became standard of care, but clinical results are still suboptimal. Currently, atrial fibrillation (AF) cycle length mapping (CLM) is possible due to a special tool of the Carto® electroanatomical mapping, which identifies areas in the left atria with shortest refractory period, during AF. Purpose Using this new EAM feature, our study aimed to assess the relationship between short refractory period LA areas and left atrial volume and AF type, known predictors of AF relapse. Methods Retrospective analysis of an unicentric registry of individuals with symptomatic drug-refractory AF who underwent PVI AF ablation with Carto® EAM. CLM was performed. CL maps were created with a high-density mapping Pentaray® catheter before and after PVI. We assessed areas of short cycle length (SCL) (defined as 120 to 250ms), and their relationships with complex fractionated atrial electrograms (CFAE), and low-voltage zones (from 0.1 to 0.3mV). Results A total of 35 patients (21 men, median age 62 IQR 53-71 years) were included. Most patients presented with persistent AF (n=23, 66%), and 8 patients (23%) had a previous PVI. The mean shortest measured cycle length in AF was 134ms (SD ± 23ms). There was a negative correlation between LA volume and SCL areas after PVI (Spearman Correlation coefficient [ρ] = - 0.47, P = 0.037). There was no correlation between LA volume and SCL areas before the PVI procedure (ρ = -0.06, P = 0.776), nor between AF type and SCL (ρ = -0.118, P = 0.620). All patients presented areas of SCL located in the PVs or their insertion, 76% in the posterior/roof region adjacent to the left superior pulmonary vein (LSPV) and 76% in the anterior region of the wall adjacent to the right superior pulmonary vein (RSPV). These two areas remained the fastest even after PVI. The anterior mitral region rarely presented SCL (16%). SCL were related to low-voltage areas in 93% and were adjacent to CFAE in 84% of the cases. Low-voltage areas and CFAE were more frequent and had a larger LA dispersion than SCL. Conclusion Our study shows that LA volume, not AF type, is correlated with remaining SCL areas after a pulmonary vein isolation procedure. This finding suggests a possible causal link between increased LA volume and AF relapse post-PVI. More studies are needed to assess the role of the SCL areas as a potential ablation target and their impact on AF ablation outcomes.

Outcomes of radiofrequency catheter ablation for persistent and long-standing persistent atrial fibrillation

ObjectiveTo assess one-year outcomes in patients with persistent and long-standing persistent atrial fibrillation (AF) treated by catheter ablation. MethodsA retrospective observational study was conducted of consecutive patients referred for catheter ablation of persistent or long-standing persistent AF between May 2016 and October 2018. Patients underwent two different ablation strategies: pulmonary vein isolation (PVI) plus complex fractionated atrial electrograms (CFAE) (from May 2016 to June 2017) or a tailored approach (from July 2017 to October 2018). The overall recurrence rate at one year was analyzed. The secondary endpoint was arrhythmia recurrence according to the type of AF (persistent vs. long-standing persistent AF) and according to the ablation strategy employed. ResultsDuring the study period, 67 patients were included (40% with long-standing persistent AF). During a mean follow-up of 16±6 months, 27% of the patients had arrhythmia recurrence. Patients with long-standing persistent AF had a higher recurrence rate than those with persistent AF (44.4% vs. 15%, p=0.006), while patients who underwent a tailored approach presented better outcomes than those undergoing PVI plus CFAE ablation (17.5% vs. 40.7%, p=0.024). Ablation strategy (HR 6.457 [1.399-29.811], p=0.017), time in continuous AF (HR 1.191 [1.043-1.259], p=0.010) and left atrial volume index (HR 1.160 [1.054-1.276], p=0.002) were independent predictors of arrhythmia recurrence. ConclusionCatheter ablation is an effective treatment for patients with persistent and long-standing persistent AF. Patients with persistent AF and those undergoing a tailored approach presented lower arrhythmia recurrence.

PO-622-02 PREDICTOR OF ATRIAL TACHYARRHYTHMIA RECURRENCE AMONG ABLATION STRATEGIES AFTER ABLATION INDEX-GUIDED ATRIAL FIBRILLATION ABLATION

Ablation index (AI)-guided atrial fibrillation (AF) ablation improved the procedural success and long-term outcome, but it remained unsatisfactory, especially in non-paroxysmal AF (non-PAF). Various ablation strategies were performed to improve the outcome. However, the strategies vary with the institutions and operators, and predictors of recurrence of atrial tachyarrhythmia (AT) among the strategies remain to be elucidated. We analyzed the predictors of AT recurrence, focusing on high-power radiofrequency application (50W, HP), first-pass pulmonary vein (PV) isolation (FPI), and extra-PV ablation strategies such as left atrium roof linear ablation (LARLA), superior vena cava (SVC) isolation, left atrium posterior wall box isolation (POBI) and complex fractionated atrial electrogram (CFAE) ablation. We retrospectively investigated 1384 patients undergoing the first AI-guided AF ablation from January 2018 to October 2020 (mean age, 67±10 years; female, 422 [31%]; non-PAF, 598 [43%]). HP was performed for 1074 patients (78%) undergoing ablation procedures since November 2018. SVC isolation was performed in all patients with SVC sleeve ≥ 20mm and the other extra-PV ablation strategies at the operator’s discretion. We performed univariate and multivariate analyses by cox proportional hazard model to define the predictors of AT recurrence. During follow-up (mean, 371±160 days), any ATs recurred in 317 patients (24%). Univariate analysis revealed that HP (Hazard ratio [HR], 1.08 [95% confidence interval, 0.83-1.40], p=0.57), FPI in both PV sides (HR, 1.08 [0.87-1.36], p=0.49), and FPI in at least one side (HR, 0.85 [0.61-1.19], p=0.36) had no effect on AT recurrence. Multivariate analysis revealed that LARLA had a negative effect (HR, 1.86 [1.21-2.86], p=0.005) and SVC isolation had a positive effect (HR, 0.71 [0.56-0.89], p=0.003); however, POBI (HR, 1.03 [0.77-1.38], p=0.84) and CFAE ablation (HR, 1.10 [0.78-1.56], p=0.59) had no effect on AT recurrence. The present analysis of a large number of AI-guided AF ablation revealed that HP, FPI, POBI, and CFAE ablation showed no effect, LARLA showed a worsening effect, and SVC isolation showed a protective effect on AT recurrence.

PO-660-01 “TRAPPED REENTRY”: A DORMANT SOURCE OF ARRHYTHMIA

Diseased atria are characterised by functional and structural heterogeneities (e.g. dense fibrotic regions), which add to abnormal impulse generation and propagation, like ectopy and block. These heterogeneities are thought to play a role in the origin of complex fractionated atrial electrograms (CFAEs) under sinus rhythm (SR) in atrial fibrillation (AF) patients, but also in the onset and perpetuation (e.g. reentry) of this disorder. The underlying mechanisms, however, remain incompletely understood.