persAF Patients Research Articles

Relationship between duration of atrial fibrillation and right heart structure remodeling as assessed by 3-dimensional transesophageal echocardiography

BackgroundTricuspid valve (TV) remodeling occurs in patients with atrial fibrillation (AF); however, the affecting factor related to TV remodeling in AF remains to be elucidated. We sought to explore whether the AF persistence itself affects right heart remodeling. MethodsA total of 372 lone AF patients (234 paroxysmal AF [paroxAF] and 138 persistent AF [persAF]) who underwent 3-dimensional transesophageal echocardiography (3D-TEE) was retrospectively reviewed. The duration from first-detected episode of AF to the TEE exam date was defined as AF duration. ResultsPersAF patients had a larger TV area index (625.4 vs 719.0 mm2/m2; P < 0.001) and a higher right atrium area-to-right ventricle end-systolic area ratio (RA/RVESA ratio, 1.7 vs 1.9; P = 0.005) than paroxAF patients. The prevalence of AF-tricuspid regurgitation was higher in persAF than in paroxAF patients (1.3% vs 12.3%; P < 0.001). In persAF patients, AF duration was moderately correlated with TV diameter and 3D-TEE-derived TV annular area but not in paroxAF. On multivariable analysis, AF duration was independently associated with TV annular dilatation even after adjustment for RA/RVESA ratio and tricuspid regurgitation severity (β 0.37 [95% CI: 0.77–1.81]; P < 0.001). Additionally, AF duration with cutoff values of 20 months for predicting TV annular dilatation and 37 months for predicting RA/RVESA ratio > 2.1 had both high diagnostic accuracies among persAF patients (both P < 0.01). ConclusionsAF duration itself is independently associated with right heart remodeling in persAF but not in paroxAF, such as TV annular dilatation and predominant RA remodeling which may lead to subsequent TR progression and adverse outcomes.

Left Atrial Posterior Wall Isolation with Pulsed Field Ablation in Persistent Atrial Fibrillation.

Left atrial posterior wall isolation (LAPWI) may improve rhythm control in addition to pulmonary vein isolation (PVI) in persistent atrial fibrillation (persAF) patients undergoing catheter ablation (CA). However, LAPWI may be challenging when using thermal energy sources. This study aimed to investigate the efficacy and safety of LAPWI performed by non-thermal pulsed field ablation (PFA) in CA for persAF. Consecutive persAF patients from two German centers were prospectively enrolled. There were two study cohorts: (1) the LAPWI cohort, which included PFA-guided (re-)PVI with LAPWI for first-time and/or repeat ablation procedures; and (2) a comparative persAF cohort with a PFA PVI-only approach without LAPWI for first-time ablation within the same timeframe. Patients were followed up by routine Holter ECGs. In total, 79 persistent AF patients were included in the study: 59/79 patients were enrolled in the LAPWI cohort, including 16/59 index (27%) and 43/59 repeat ablation procedures (73%). Sixteen patients (16/79; 21%) were in the PVI-only cohort without LAPWI. Of the patients treated with LAPWI, procedure time and fluoroscopy time was 91 ± 30 min and 15 ± 7 min, respectively. The acute PVI rate was 100% in all first-time ablation patients (32 patients (16 PVI only, 16 PVI plus LAPWI), 196/196 PVs). Of the 43 re-do patients in the LAPWI cohort, re-PVI was necessary in 33% (14/43) of patients (27 PVs; 1.9 PV per-patient); in 67% (29/43), all PVs were isolated, and antral ablation of the PV ostia was performed in 48% (14/29). LAPWI was performed successfully in all 59 (100%) patients of the LAPWI cohort. Two minor complications occurred. No esophageal lesion was detected in the LAPWI cohort (n = 33/59 (56%) patients underwent endoscopy). After 354 ± 197 days of follow-up, freedom from atrial arrhythmias was 79.3% (95-CI: 62-95%) in the complete LAPWI cohort (n = 14/59 (24%) on AAD: class Ic n = 9, class III n = 5). There was no difference regarding acute procedural and clinical outcome compared to the PVI-only cohort. LAPWI guided by PFA is feasible and safe in patients undergoing CA for persAF and shows favorable outcomes. In the context of durable PVI, PFA-guided LAPWI may be an effective adjunctive treatment option.

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.

Left atrial appendage volume is an independent predictor of atrial arrhythmia recurrence following cryoballoon pulmonary vein isolation in persistent atrial fibrillation.

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation in persistent AF (persAF), and cryoballoon PVI emerged as an initial ablation strategy. Symptomatic atrial arrhythmia recurrence following successful PVI in persAF is observed more frequently than in paroxysmal AF. Predictors for arrhythmia recurrence following cryoballoon PVI for persAF are not well described, and the role of left atrial appendage (LAA) anatomy is uncertain. Patients with symptomatic persAF and pre-procedural cardiac computed tomography angiography (CCTA) images undergoing initial second-generation cryoballoon (CBG2) were enrolled. Left atrial (LA), pulmonary vein (PV) and LAA anatomical data were assessed. Clinical outcome and predictors for atrial arrhythmia recurrence were evaluated by univariate and multivariate regression analysis. From May 2012 to September 2016, 488 consecutive persAF patients underwent CBG2-PVI. CCTA with sufficient quality for measurements was available in 196 (60.4%) patients. Mean age was 65.7 ± 9.5 years. Freedom from arrhythmia was 58.2% after a median follow-up of 19 (13; 29) months. No major complications occurred. Independent predictors for arrhythmia recurrence were LAA volume (HR 1.082; 95% CI, 1.032 to 1.134; p = 0.001) and mitral regurgitation ≥ grade 2 (HR, 2.49; 95% CI 1.207 to 5.126; p = 0.013). LA volumes ≥110.35 ml [sensitivity: 0.81, specificity: 0.40, area under the curve (AUC) = 0.62] and LAA volumes ≥9.75 ml (sensitivity: 0.56, specificity 0.70, AUC = 0.64) were associated with recurrence. LAA-morphology, classified as chicken-wing (21.9%), windsock (52.6%), cactus (10.2%) and cauliflower (15.3%), did not predict outcome (log-rank, p = 0.832). LAA volume and mitral regurgitation were independent predictors for arrhythmia recurrence following cryoballoon ablation in persAF. LA volume was less predictive and correlated with LAA volume. LAA morphology did not predict the clinical outcome. To improve outcomes in persAF ablation, further studies should focus on treatment strategies for persAF patients with large LAA and mitral regurgitation.

Left atrial dimensions and left atrial appendage morphology: differences in paroxysmal versus persistent atrial fibrillation patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary vein isolation (PVI) is an effective treatment strategy in symptomatic atrial fibrillation (AF) patients. However, this approach shows worse long-term results in individuals suffering from persistent compared to the paroxysmal type. Purpose The objective was to investigate differences of left atrial (LA) as well as left atrial appendage (LAA) anatomy in persistent AF (persAF) and paroxysmal (PAF) and patients. Methods An observational single center study with a blinded retrospective analysis of cardiac computed tomography angiography (CCTA) images was conducted. Dimensions of LA, posterior wall box, pulmonary veins (PV) as well as LAA size and morphology were assessed and statistically analyzed. All important measures are depicted in the attached figure. Results From 2012 to 2016 a total of 1.103 patients underwent second generation cryoballoon PVI. Prior to PVI, CCTA was available for 725 (65.7%) patients with sufficient quality for measuring in 473 (65.2%). Mean age was 66.3±9.5 years; PAF was present in 277 (58.6%) participants. In persAF LA volume [mL] (111.8; 128.8; p&amp;lt;0.001), posterior wall box area [cm2] (11.9; 13.3; p&amp;lt;0.001) and pulmonary vein ostial dimensions were significantly larger compared to PAF. LAA volume [mL] (9.0; 10.0; p=0.01) and LAA ostial perimeters (66.5; 70.0; p=0.003) were also identified to be larger in persAF. However, there was no difference in LAA morphology (overall distribution: "windsock" 51%; "chicken-wing" 20%; "cauliflower" 15% and "cactus" 13%). Conclusion Compared to PAF, persAF patients had significantly larger LA volumes, posterior wall box areas, PV ostial dimensions as well as LAA volumes and LAA ostial perimeters. LAA morphological types were distributed equally in both groups.

Assessing the impact of blocking distal coronary sinus-left atrial muscular connection on inducible rate of atrial fibrillation and follow-up recurrence in persistent atrial fibrillation patients with different fibrotic degrees of left atrial: A retrospective study.

BackgroundThe musculature of the coronary sinus (CS), especially its distal connection with the post wall of the left atrial (LA), has been associated with the genesis and maintenance of atrial flutter (AFL) and atrial fibrillation (AF). However, the relative contributions of the distal coronary sinus (CSD)-LA connection to PersAF with various degrees of atrial fibrosis remain unknown.ObjectiveThis study aimed to explore the different roles of blocking the CSD-LA connection in the induction of acute AF and middle-term follow-up of recurrence among PersAF patients with various degrees of LA fibrosis.Methods and resultsA retrospective cohort of 71 patients with drug-refractory and symptomatic PersAF underwent ablation for the first time were studied. The population was divided into two groups according to disconnection of the CSD-LA or not. All patients enrolled accepted the unified ablation procedure (circumferential pulmonary vein isolation, non-pulmonary vein trigger ablation and ablation of the CSD-LA connection). Group A (n = 47) successfully blocked the CSD-LA electrical connection and Group B (n = 24) failed. Twenty-five patients could be induced into sustained AF in the Group A compared to 20 in the Group B (53.2 vs. 83.3%, p = 0.013). After a mean follow-up of 185 ± 8 days, 24 (33.8%) patients experienced atrial arrhythmia recurrences. The Group A had significantly fewer recurrences (25.5%) compared to Group B (50%). Meanwhile, in Group A, the ROC curve analysis suggested that in the case of blocking CSD-LA, low voltage area (LVA) of LA can act as a predictive factor for acute AF induction (AUC = 0.943, Cut-off = 0.190, P < 0.001) with sensitivity and specificity of 92.3 and 90.5%, and middle-term recurrence (AUC = 0.889, Cut-off = 0.196, P < 0.001) with sensitivity and specificity of 100 and 65.7%.ConclusionDisconnection of CSD-LA could reduce the inducible rate of acute AF and the recurrences of atrial arrhythmia during middle-term follow-up. The PersAF patients with CSD-LA muscular connection blocked, experienced a higher acute AF inducible rate with larger proportion of LVA of LA (≥19%) and a higher recurrent rate of atrial arrhythmias with a larger proportion of LA fibrosis (≥19.6%).

Novel spatiotemporal processing tools for body-surface potential map signals for the prediction of catheter ablation outcome in persistent atrial fibrillation.

Background: Signal processing tools are required to efficiently analyze data collected in body-surface-potential map (BSPM) recordings. A limited number of such tools exist for studying persistent atrial fibrillation (persAF). We propose two novel, spatiotemporal indices for processing BSPM data and test their clinical applicability through a comparison with the recently proposed non-dipolar component index (NDI) for prediction of single-procedure catheter ablation (CA) success rate in persAF patients. Methods: BSPM recordings were obtained with a 252-lead vest in 13 persAF patients (8 men, 63 ± 8 years, 11 ± 13 months sustained AF duration) before undergoing CA. Each recording was divided into seven 1-min segments of high signal quality. Spatiotemporal ventricular activity (VA) cancellation was applied to each segment to isolate atrial activity (AA). The two novel indices, called error-ratio, normalized root-mean-square error (ERNRMSE) and error-ratio, mean-absolute error (ERABSE), were calculated. These indices quantify the capacity of a subset of BSPM vest electrodes to accurately represent the AA, and AA dominant frequency (DF), respectively, on all BSPM electrodes over time, compared to the optimal principal component analysis (PCA) representation. The NDI, quantifying the fraction of energy retained after removal of the three largest PCs, was also calculated. The two novel indices and the NDI were statistically compared between patient groups based on single-procedure clinical CA outcome. Finally, their predictive power for univariate CA outcome classification was assessed using receiver operating characteristic (ROC) analysis with cross-validation for a logistic regression classifier. Results: Patient clinical outcomes were recorded 6 months following procedures, and those who had an arrhythmia recurrence at least 2 months post-CA were defined as having a negative outcome. Clinical outcome information was available for 11 patients, 6 with arrhythmia recurrence. Therefore, a total of 77 1-min AA-BSPM segments were available for analysis. Significant differences were found in the values of the novel indices and NDI between patients with arrhythmia recurrence post-ablation and those without. ROC analysis showed the best CA outcome predictive performance for ERNRMSE (AUC = 0.77 ± 0.08, sensitivity = 76.2%, specificity = 84.8%). Conclusion: Significant association was found between the novel indices and CA success or failure. The novel index ERNRMSE additionally shows good predictive power for single-procedure CA outcome.

The blanking period after atrial fibrillation ablation: an European Heart Rhythm Association survey on contemporary definition and management.

The use of a blanking period (BP) after an atrial fibrillation (AF) ablation procedure is a common practice, but recent data questions the benign nature of early recurrences of atrial tachyarrhythmias (ERATs). A physician-based survey was carried out by the European Heart Rhythm Association (EHRA) to investigate the current definition and applicability of BP and ERAT management. An online questionnaire was sent to clinical and interventional electrophysiologists. A total of 436 respondents (88% interventional electrophysiologists) reported observing ERATs in 25% (interquartile range 15-35) of patients, less commonly in paroxysmal AF (PAF) compared with persistent AF (persAF). The median reported duration of BP used by respondents was 90 days, with 22% preferring a shorter BP duration for PAF patients compared with persAF. Half of the patients with ERATs are expected to also experience late recurrences (LR). Isolated episodes of ERATs are treated conservatively by 99% of the respondents, but repeat ablation during the BP is preferred by 20% of electrophysiologists for multiple ERATs and by 16% in patients with organized atrial tachyarrhythmias. In conclusion, ERATs are commonly observed after AF ablation, particularly in persAF patients, and are perceived as predictors of LR by half of the respondents. A general adherence to a 90-day BP duration was observed. During this time period, ERAT is mainly treated conservatively, but repeat ablation during the BP is occasionally offered to patients with multiple ERATs and those with organized atrial tachyarrhythmias.

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.

Prospective evaluation of local impedance drop to guide left atrial posterior wall ablation with high power.

Local impedance (LI) drop predicts acute conduction block during pulmonary vein isolation (PVI). Whether the LI drop predicts also the achievement of left atrial posterior wall isolation (LAPWI) in persistent atrial fibrillation (PersAF) patients is unknown. We evaluated the efficacy and the safety of LI drop-guided LAPW ablation by using high power (50 watts) and investigated the impact of ablation parameters on the LI drop. We included consecutive PersAF patients underwent PVI and both roof line and floor line completion to achieve LAPWI with a novel contact force (CF)- and LI-featured catheter (IntellaNAV Stablepoint™). For each radiofrequency (RF) application, we targeted a LI drop of 25 ohms. Out of 30 patients, first-pass floor line block was achieved in 26 (87%) and first-pass roof line block in 17 (57%), resulting in first-pass LAPWI in 14 patients (47%). After touch-up ablations, LAPWI was achieved in 28 patients (93%) with endocardial ablation only. No procedural nor 1-month complications occurred. Overall, 877 RF applications were delivered: 787 ablation tags (89%) were associated with acute conduction block, while 90 (11%) were located at sites of acute gaps in either the roof or floor line. LI drop values were greater at segments with acute block than those with gaps (p < 0.001). At multivariable analysis, only LI drop and RF time remained independently associated with the acute block (p < 0.001; p = 0.001). LI drop-guided LAPWI at a fixed power of 50W was effective and did not lead to complications. LI drop was the most important predictor of acute conduction block.

Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy

BackgroundWhether atrial fibrillation (AF) pattern or timing of AF therapy modifies the effectiveness of early rhythm control (ERC) is not known. ObjectivesThis study sought to compare clinical characteristics and outcomes in patients presenting with different AF patterns on ERC vs usual care. MethodsThe effects of ERC were compared in first-diagnosed AF (FDAF), paroxysmal AF (paroxAF), and persistent AF (persAF) in this prespecified analysis of the EAST-AFNET 4 (Early treatment of atrial fibrillation for stroke prevention) trial. Associations between AF pattern and primary outcomes (first primary outcome: cardiovascular death, stroke, and hospitalization for heart failure and acute coronary syndrome; second primary outcome: nights spent in hospital per year) were compared over a mean follow-up of 5.1 years. Changes in health-related quality of life were assessed by the EQ-5D. ResultsFDAF patients (n = 1,048, enrolled 7 days after diagnosing AF) were slightly older (71 years of age, 48.0% female) than patients with paroxAF (n = 994, 70 years of age, 50.0% female) and persAF (n = 743, 70 years of age, 38.0% female). ERC reduced the primary outcome in all 3 AF patterns. Hospitalizations for acute coronary syndrome were highest in FDAF (incidence rate ratio [IRR]: 1.50; 95% CI: 0.83-2.69; P for interaction = 0.032) compared with paroxAF (IRR: 0.64; 95% CI: 0.32-1.25) and persAF (IRR: 0.50; 95% CI: 0.25-1.00). FDAF patients spent more nights in hospital (IRR: 1.38; 95% CI: 1.12-1.70; P for interaction = 0.004) than paroxAF (IRR: 0.84; 95% CI: 0.67-1.03), and persAF (IRR: 1.02; 95% CI: 0.80-1.30) patients. ERC improved health-related quality of life (EQ-5D score) in patients with paroxAF and persAF but not in patients with FDAF (P = 0.019). ConclusionsERC reduces the first primary composite outcome in all AF patterns. Patients with FDAF are at high risk for hospitalization and acute coronary syndrome, particularly on ERC. (Early treatment of atrial fibrillation for stroke prevention trial; ISRCTN04708680; Early Treatment of Atrial Fibrillation for Stroke Prevention Trial [EAST]; NCT01288352; Early treatment of Atrial fibrillation for Stroke prevention Trial [EAST]; EudraCT2010-021258-20)

CA-529-01 RENEWAL THEORY: A STATISTICAL APPROACH TO IMPROVE PATIENT SELECTION FOR PULMONARY VEIN ISOLATION-ONLY STRATEGY IN ATRIAL FIBRILLATION ABLATION

Outcomes from pulmonary vein isolation (PVI)-only approach in AF remain suboptimal, especially in persistent AF (persAF) patients. However,results from STAR-AF 2 trial suggest the presence of a subgroup of persAF patients who were responders to PVI-only. While research efforts have primarily focused on which non-PVI ablation techniques to pursue in persAF patients, there has been a paucity of data to define a cohort of AF patients who are “PVI-only responders”

B-PO04-203 CARDIOVASCULAR HEALTHCARE UTILIZATION IN PERSISTENT ATRIAL FIBRILLATION PATIENTS ABLATED WITH A CONTACT FORCE CATHETER

The Persist-End trial was conducted to demonstrate that RF ablation with a magnetic sensor enabled optical contact force sensing ablation catheter was safe and effective for the treatment of drug-refractory, recurrent symptomatic persistent atrial fibrillation (PersAF). Additional analyses were conducted to quantify the impact of RF ablation on healthcare utilization and Quality of Life post-ablation in PersAF patients. In the prospective, single-arm, multi-center investigational device exemption PersistEnd clinical trial, cardiovascular healthcare utilization (cvHCU), defined as cardiovascular events resulting in hospitalization or emergency room use, was analyzed using patients as their own controls. Differences in annualized event rates (EPPY) of cvHCU were compared pre- and post-ablation using a nonparametric bootstrap method and further compared in patients stratified by the study effectiveness endpoint of ablation success. Utility-Index Scores based on EQ-5D-5L at baseline were compared across the 15-month follow-up period using paired t-test. A total of 223 PersAF patients (mean age 65.4 ± 10.1 ys, 69.1% male, 95.5% white) received ablation between Nov 2018-Sept 2019. In the 1-year pre-ablation period, 69 (30.9%) patients had 103 cvHCU (0.46 EPPY). These events reduced to 0.35 EPPY (24% reduction, p = 0.15) post-ablation. This reduction was observed in 93.8% of bootstrap simulations. Out-patient visits reduced significantly from 0.46 EPPY to 0.21 EPPY (55% reduction, p < 0.001) over the follow-up period. Subjects that passed the primary endpoint of the trial had 52% reduction in cvHCU (p = 0.02). Average EQ-5D-5L Utility-Index Scores improved from 0.86 at baseline to 0.93 (p < 0.05) at 15 months. The change in resource use before and after ablation highlights effectiveness of the therapy in reducing cardiovascular related healthcare encounters. Increases in the Utilities-Index highlight the improved quality of life that may also accompany RF ablation of PersAF.

Paroxysmal and persistent atrial fibrillation; does the clinical classification match the substrate?

Abstract Background/Introduction The classification of atrial fibrillation (AF) currently is based on clinical characteristics, however classifying underlying electropathology would assist in selecting appropriate therapy. In this study, we measured atrial conduction parameters in sinus rhythm (SR) using an intra-operative high resolution epicardial mapping approach in paroxysmal (PAF) and persistent AF (persAF) patients. Purpose To study whether the clinical classification is related to the amount and severity of conduction disorders in SR. Methods We included 47 PAF and 24 persAF patients for intra-operative measurements of SR at the right atrium (RA), Bachmann's Bundle (BB), the left atrium (LA) and the pulmonary vein area (PV). Various conduction parameters were calculated, including number of continuous conduction delay and block (cCDCB) lines, total activation time (TAT), and orientation of conduction block (CB) lines at BB. Results After adjustment for confounders, only TAT of BB was significantly longer in persAF patients, 75 [53–92] ms vs 55 [40–76] ms. This can be attributed to more CB line parts orientated perpendicular to the conduction direction and a higher number of cCDCB lines. Other conduction characteristics at BB and other atrial areas showed no difference between PAF and persAF patients. Conclusion(s) Patients with persAF have a longer activation time at BB compared to patients with PAF. Other conduction parameters show significant overlap between these groups at BB and in other atrial areas, suggesting that, in SR, the clinical classification does not match the arrhythmogenic substrate. Funding Acknowledgement Type of funding source: None

Automatic estimation of left atrial function from short axis CINE-MRI using machine learning

Abstract Introduction The importance of atrial mechanical dysfunction in atrial and ventricular pathologies is becoming increasingly recognised. Although machine learning (ML) tools have the ability to automatically estimate atrial function, to date ML techniques have not been used to automatically estimate atrial volumes and functional parameters directly from short axis CINE MRI. Purpose We introduce a convolutional neural network (CNN) to automatically segment the left atria (LA) in CINE-MRI. As a demonstration of the clinical utility of this technique, we calculated LA and left ventricular (LV) ejection fractions automatically from CINE images. Methods Short axis CINE MRI stacks, covering both ventricles and atria, were obtained in a 1.5T Philips Ingenia scanner. A 2D bSSFP ECG-gated protocol was used (FA=60°, TE/TR=1.5/2.9 ms), typical FOV =385 x 310 x 150 mm3, acquisition matrix = 172 x 140, slice thickness = 10 mm, reconstructed with resolution 1.25 x 1.25 x 10 mm3, 30–50 cardiac phases. Images were collected from 37 AF patients in sinus rythm at the time of scan (31–72 years old, 75% male, 18 with paroxysmal AF (PAF), 19 with persistent AF (persAF)). To automatically segment the LA, we used a dedicated CNN that follows a U-Net architecture and was trained in 715 images of the LA, manually segmented by an expert. Data augmentation techniques that included noise addition and linear and non-linear image transforms were also used to increase the training dataset. Ventricular structures, including the LV blood pool, were automatically segmented in these images using a CNN previously trained for this task. Volumetric time plots of LA and LV volume were produced and used to automatically compute maximal and minimal volumes, from which LA and LV ejection fractions (EFs) were assessed. A Bland-Altman analysis compared these automatically computed LA volumes and LA EFs with clinical manual estimates from the same scanning session. Results The CNN achieved very good quality LA segmentations when compared to manual ones (Fig a,b): Dice coefficients (0.90±0.07), median contour distances (0.50±1.12mm) and Hausdorff distances (6.70±6.16mm). Bland-Altman analyses show very good agreement between automatic and manual LA volumes and EFs (Fig e). A moderate linear correlation between LA and LV EFs in AF patients was found (Fig d). The measured LA EF was higher for PAF (29±8%) than PersAF patients (21±11%), although non-significantly (t-test p-value: 0.10). Conclusions We present a reliable automatic method to perform LA segmentations from CINE MRI across the entire cardiac cycle. This approachs opens up the possibility of automatically calculating more sophisticated biomarkers of LA function which take into account information about LA volumes across the entire cardiac cycle, including biomarkers of LA booster pump function. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation; EPSRC/Wellcome Centre for Medical Engineering

Unsupervised Classification of Atrial Electrograms for Electroanatomic Mapping of Human Persistent Atrial Fibrillation.

Ablation treatment for persistent atrial fibrillation (persAF) remains challenging due to the absence of a 'ground truth' for atrial substrate characterization and the presence of multiple mechanisms driving the arrhythmia. We implemented an unsupervised classification to identify clusters of atrial electrograms (AEGs) with similar patterns, which were then validated by AEG-derived markers. 956 bipolar AEGs were collected from 11 persAF patients. CARTO variables (Biosense Webster; ICL, ACI and SCI) were used to create a 3D space, and subsequently used to perform an unsupervised classification with k-means. The characteristics of the identified groups were investigated using nine AEG-derived markers: sample entropy (SampEn), dominant frequency, organization index (OI), determinism, laminarity, recurrence rate (RR), peak-to-peak (PP) amplitude, cycle length (CL), and wave similarity (WS). Five AEG classes with distinct characteristics were identified (F = 582, P<0.0001). The presence of fractionation increased from class 1 to 5, as reflected by the nine markers. Class 1 (25%) included organized AEGs with high WS, determinism, laminarity, and RR, and low SampEn. Class 5 (20%) comprised fractionated AEGs with in low WS, OI, determinism, laminarity, and RR, and in high SampEn. Classes 2 (12%), 3 (13%) and 4 (30%) suggested different degrees of AEG organization. Our results expand and reinterpret the criteria used for automated AEG classification. The nine markers highlighted electrophysiological differences among the five classes found by the k-means, which could provide a more complete characterization of persAF substrate during ablation target identification in future clinical studies.

P994Does AF always beget AF? Retrospective study in patients with complex cardiac devices

Abstract Introduction Atrial fibrillation (AF) is conventionally divided in paroxysmal AF (PAF) and persistent AF (PersAF) according to episode duration, with a perceived inevitable progression of the arrhythmia in most patients: "AF begets AF". This dichotomous classification of AF is currently being challenged by continuous monitoring with implantable cardiac monitors and pacemakers which suggest different patterns of AF with considerable variation in AF burden. Purpose This study sought to examine the long-term progression of AF burden in patients with complex cardiac devices (implantable cardiac defibrillators [ICD] and cardiac resynchronisation therapy-defibrillators [CRT-D]). Methods This retrospective study examined the weekly AF burden in patients with ICDs and CRT-Ds and on remote monitoring between January 2010 and July 2019. All transmissions and electrograms were assessed for the presence of AF lasting more than 6 minutes. The first episode of AF determined was considered follow-up year 0. PersAF was defined as a weekly AF burden of 100%. Medical records were reviewed for baseline characteristics at the time of the first episode of AF and interventions that may affect burden such as direct current cardioversion (DCCV) and catheter ablations. Results Of 331 patients on remote monitoring, 106 (32%) had evidence of AF. Of these, 89% were male, age 64 ± 12 years, BMI 30 ± 6 kg/m2, LA diameter 4.5 ± 0.8 cm, 58% had an ICD, 10% had previous AF ablation and 27% had antiarrhythmic medication. Forty-six (43%) had PersAF and 60 (57%) had PAF over a total follow-up of 393 patient years (mean follow-up 4.6. ±2.1). The mean AF burden was 1.2 ± 4.4% in PAF and 66.4 ± 35.3% in PersAF at the end of the first year of follow-up. When compared to year 1, the mean annual AF burden did not increase in the PAF and PersAF groups. Moreover, the PersAF patients had a significant reduction in the mean annual AF burden up to year 7 of follow-up. In year 8, the mean annual AF burden remained below year 1; however, due to a low number of patients (5) it did not reach statistical significance (mean difference 15.1%, p = 0.06) . To further assess individual progression in PersAF patients, the annual AF burden was subdivided in 4 categories (&amp;lt;25%, 25%-50%, 50%-75% and &amp;gt;75%). In 30 (65%) patients it remained unchanged, in 5(11%) it worsened and in 11 (24%) it improved (Figure ). Moreover, 35 (76%) patients reverted to sinus rhythm following their first episode of PersAF (5 following DCCV and 2 after catheter ablation). Conclusions In this cohort, the mean AF burden did not increase; in fact, we observed a significant reduction in patients with PersAF despite a low rate of interventions. These findings reinforce the emerging concept of AF as a heterogenous disease with various phenotypes that challenge the current simplistic binary classification. Abstract Figure

P353Anticoagulation profile if an as required oral anticoagulation strategy is used in patients with complex cardiac devices

Abstract Introduction Once atrial fibrillation (AF) is detected and the threshold for oral anticoagulation (OAC) is met, patients are committed to lifelong anticoagulation. Stroke risk stratification tools, such as CHA2DS2-VAS score, do not incorporate AF burden. However, studies suggest a lower stroke risk in paroxysmal AF (pAF) and low AF burden when compared to persistent AF (persAF). Moreover, small feasibility studies have explored "as required" OAC guided by episode duration and/or AF burden in carefully selected, low-risk patients with infrequent episodes of AF. The reduction of OAC observed with stringent inclusion criteria may not be translated to real-world patients. Purpose We sought to investigate the impact of OAC reduction if an "as required" strategy is applied to an unselected population of patients with complex cardiac devices (implantable cardiac defibrillators [ICD] and cardiac resynchronisation therapy [CRT-D]). Methods All transmissions and electrograms of patients with CRT and ICD on remote monitoring were examined retrospectively. The first recorded AF episode longer than 6 minutes determined the start of follow-up. A weekly AF burden of 100% was considered persAF. We estimated the time on oral anticoagulation on an "as required" basis according to criteria used in previous studies: 1) OAC was initiated if the weekly burden was more than 0.6% (60 minutes); 2) OAC was discontinued if the weekly burden remained below 0.6 % in the following 4 weeks. Medical records were reviewed for baseline characteristics at the time of the first episode of AF. Results 106(32%) had evidence of AF from 331 patients screened. Of these, 89% were male, age 64 ± 12 years, BMI 30 ± 6 kg/m2, LA diameter 4.5 ± 0.8 cm, ejection fraction (EF) 38 ± 17 and 58% had an ICD. 46 (43%) had persAF and 60 (57%) had pAF. The CHA2DS2VASc was 1 or higher in 104 patients (98%) corresponding to 393 patient-years of OAC if standard care was used. "As required" strategy led to a significant reduction in time on OAC to 248 patient years (62.3%, p &amp;lt; 0.0001). The reduction was greater in pAF group (86.5%, p &amp;lt; 0.0001) than in persAF (46.3%, p &amp;lt; 0.0001)(Figure). Moreover, persAF patients had a higher number of episodes requiring OAC (3.6 ± 3.26 vs 2.2 ± 1.9) and of longer duration (mean difference 0.85 years, CI 0.5-1.1, p &amp;lt; 0.0001). Conclusion In an unselected cohort of patients with complex cardiac devices "as required" OAC strategy led to a significant reduction in the total time of OAC, which was more marked in patients with pAF. Abstract Figure

Second-generation cryoballoon-based pulmonary vein isolation: Lessons from a five-year follow-up

BackgroundPulmonary vein isolation (PVI) using the second-generation cryoballoon (CB2) for atrial fibrillation (AF) treatment has demonstrated encouraging procedural success rates and mid-term results. However, long-term follow-up data on outcome is sparse. The current study is reporting on five-year clinical outcomes following CB2-based PVI in patients with paroxysmal AF (PAF) and persistent AF (PersAF). MethodsA total of 139 patients underwent index CB2-based PVI patients (PAF: n = 105, 76% and PersAF: n = 34, 34%) in two electrophysiology centers. Freeze-cycle duration was 240 s. After successful PVI a bonus freeze-cycle of the same duration was applied in the first 71 patients while the bonus-freeze was omitted in 68 following patients. Three patients (2.2%) were lost to follow-up. ResultsAfter a median follow-up duration of 60 months (interquartile range: 46, 72 months) 74/136 (54.4%) patients remained in stable sinus rhythm (PAF: 62/104, 59.6%; PersAF: 15/32, 46.9%). Significant differences were observed concerning 5-year clinical outcome between PAF and PersAF patients (p = 0.0315). After a mean of 1.32 ± 0.6 procedures (2nd and 3rd procedure by radiofrequency ablation) and a median follow-up duration of 60 (37, 68) months 90/136 (66.2%) patients remained in stable sinus rhythm (PAF: 72/104 (69.2%), PersAF: 21/32 (65.6%), p = 0.0276). For the comparison of bonus-freeze vs no-bonus-freeze protocols no differences were observed (53.5% vs 57.4%, p = 0.650). ConclusionsThe five-year single-procedure success rate for CB2-based PVI was 54.4% and increased to 66.2% following repeat RF-based procedures. No differences were detected comparing bonus-freeze and no-bonus-freeze protocols.

Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.

This study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients. A total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length (SRPBM), respectively. Differentially expressed mRNAs (DE mRNAs), lncRNAs (DE lncRNAs), and circRNAs (DE circRNAs) were identified by | log2 (Fold Change) | ≥ 2 and p-value < 0.05. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein-protein, mRNA-lncRNA, and circRNA-miRNA interaction networks were constructed. In addition, logistic analysis was conducted among AF and circRNAs. A total of 285 (116 up-regulated and 169 down-regulated) and 275 (110 up-regulated and 165 down-regulated) DE mRNAs, 575 (276 up-regulated and 299 down-regulated) and 583 (330 up-regulated and 253 down-regulated) DE lncRNAs, and 83 (48 up-regulated and 35 down-regulated) and 99 (58 up-regulated and 41 down-regulated) circRNAs were detected in ParoAF and PersAF, respectively, as compared with control. MAPK signal pathway as well as voltage-dependent, L type, and alpha 1C subunit calcium channel (CACNA1C) might participate in AF occurrence by preventing atrial parasympathetic remodeling. Collagen type I alpha 1 (COL1A1) and COL1A2 mostly participated in the enriched GO and KEGG terms and connected with most of the DE mRNAs. The expression of chr10: 69902697|69948883 was a protective factor against PersAF after adjusting for age (p=0.022, 95% CI: 0.003-0.634). We found that some mRNAs, lncRNAs, circRNAs, and pathways play essential roles in AF pathogenesis and development. Moreover, one protective factor against PersAF was detected.