Atrial Fibrillation Pattern Research Articles

The Role of Fatty Acid-Binding Protein 4 in the Characterization of Atrial Fibrillation and the Prediction of Outcomes after Catheter Ablation.

Aims: The utility of biomarkers in characterizing atrial cardiomyopathy is unclear. We aim to test the ability of biomarkers of fibrosis (galectin-3 (Gal-3)) and adiposity (fatty acid-binding protein 4 (FABP4) and leptin) to predict: (1) the presence of low-voltage areas (LVA) in the electroanatomic voltage mapping; and (2) the recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI). Methods: Patients referred for PVI were enrolled. Areas of bipolar voltage < 0.5 mV were considered as LVA. An aggregate score incorporating AF pattern (paroxysmal, persistent and long-standing persistent) and peripheral levels of FABP4 (>20 ng/mL) was developed. Results: 299 patients were included. AF was paroxysmal in 100 (33%), persistent in 130 (43%) and long-standing persistent in 69 (23%). Multivariable analysis revealed age, left atrium area, and the proposed score as independent predictors of LVA. During a mean follow-up period of 972 ± 451 days, freedom from AF recurrence was 63%. The score incorporating AF pattern and FABP4 levels accurately predicted freedom from AF recurrence, stratifying risk into ranges from 28% (score of 1) to 68% (score of 3). Cox regression models identified the score including AF pattern + FABP4 as the best model for AF recurrence (hazard ratio 2.32; 95% CI, 1.19 to 4.5; p = 0.014). Conclusions: Traditional clinical classification of atrial cardiomyopathy may be improved by markers of adiposity (FABP4). The combination allows better prediction of the presence of LVA and AF recurrence post-PVI. Gal-3 provided no added predictive value.

Atrial fibrillation patterns and their cardiovascular risk profiles in the general population: the Rotterdam study

BackgroundClinical guidelines categorize atrial fibrillation (AF) based on the temporality of AF events. Due to its dependence on event duration, this classification is not applicable to population-based cohort settings. We aimed to develop a simple and standardized method to classify AF patterns at population level. Additionally, we compared the longitudinal trajectories of cardiovascular risk factors preceding the AF patterns, and between men and women.MethodsBetween 1990 and 2014, participants from the population-based Rotterdam study were followed for AF status, and categorized into ‘single-documented AF episode’, ‘multiple-documented AF episodes’, or ‘long-standing persistent AF’. Using repeated measurements we created linear mixed-effects models to assess the longitudinal evolution of risk factors prior to AF diagnosis.ResultsWe included 14,061 participants (59.1% women, mean age 65.4 ± 10.2 years). After a median follow-up of 9.4 years (interquartile range 8.27), 1,137 (8.1%) participants were categorized as ‘single-documented AF episode’, 208 (1.5%) as ‘multiple-documented AF episodes’, and 57 (0.4%) as ‘long-standing persistent AF’. In men, we found poorer trajectories of weight and waist circumference preceding ‘long-standing persistent AF’ as compared to the other patterns. In women, we found worse trajectories of all risk factors between ‘long-standing persistent AF’ and the other patterns.ConclusionWe developed a standardized method to classify AF patterns in the general population. Participants categorized as ‘long-standing persistent AF’ showed poorer trajectories of cardiovascular risk factors prior to AF diagnosis, as compared to the other patterns. Our findings highlight sex differences in AF pathophysiology and provide insight into possible risk factors of AF patterns.Graphical abstract

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)

Rationale and Design of the ISOLATION Study: A Multicenter Prospective Cohort Study Identifying Predictors for Successful Atrial Fibrillation Ablation in an Integrated Clinical Care and Research Pathway.

IntroductionContinuous progress in atrial fibrillation (AF) ablation techniques has led to an increasing number of procedures with improved outcome. However, about 30–50% of patients still experience recurrences within 1 year after their ablation. Comprehensive translational research approaches integrated in clinical care pathways may improve our understanding of the complex pathophysiology of AF and improve patient selection for AF ablation.ObjectivesWithin the “IntenSive mOlecular and eLectropathological chAracterization of patienTs undergoIng atrial fibrillatiOn ablatioN” (ISOLATION) study, we aim to identify predictors of successful AF ablation in the following domains: (1) clinical factors, (2) AF patterns, (3) anatomical characteristics, (4) electrophysiological characteristics, (5) circulating biomarkers, and (6) genetic background. Herein, the design of the ISOLATION study and the integration of all study procedures into a standardized pathway for patients undergoing AF ablation are described.MethodsISOLATION (NCT04342312) is a two-center prospective cohort study including 650 patients undergoing AF ablation. Clinical characteristics and routine clinical test results will be collected, as well as results from the following additional diagnostics: determination of body composition, pre-procedural rhythm monitoring, extended surface electrocardiogram, biomarker testing, genetic analysis, and questionnaires. A multimodality model including a combination of established predictors and novel techniques will be developed to predict ablation success.DiscussionIn this study, several domains will be examined to identify predictors of successful AF ablation. The results may be used to improve patient selection for invasive AF management and to tailor treatment decisions to individual patients.

Why are redo AF ablations required and what does it take? Type of index PVI predicts pattern of redo ablations

Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation targeting isolation of the pulmonary veins (PVI) is the most effective treatment for atrial fibrillation (AF). Despite its high overall effectiveness, repeat AF ablations (re-do procedures, RDP) are often required to maintain sinus rhythm. Purpose Determine predictors for multiple and/or complex RDP, evaluate reference values for procedure duration and radiation exposure during index PVI (iPVI) and nth RDP in a large cohort. Methods and Results Data mining identified 934 (mean age 62.6 ± 12.3 years, 346 females) out of 6848 total AF ablation patients from a large German AF ablation center between 09/2008 and 09/2021 with an index PVI and at least one RDP. Analysis included 2152 procedures (out of 8750 total AF-related ablations). At iPVI, AF pattern was classified as paroxysmal AF (PAF) in 387 patients (41%). All others (59%) were classified as non-paroxysmal AF (Non-PAF). Non-PAF was significantly more frequent in males (64% vs. 49%, p&amp;lt;0.01). Median period between first PVI and RDP was 558 days (25th/75th percentiles 244.0/1175.5 days). Non-PAF patients had a significantly higher probability of multiple RDP compared to patients with PAF at iPVI (p&amp;lt;0.01, Figure 1A). 18% (8%) of patients with non-PAF had 2 (3) or more RDP while only 13% (3%) of pat. with PAF had 2 (3) or more RDP. iPVI was classified as PVI-only or PVI with additional substrate modification (SM). 724/934 patients (78%) received PVI-only as initial procedure. Of these, 572 (79%) had only 1 RDP, 116 (16%) had 2 RDP and 36 (5%) had 3 or more RDP. This distribution was 77%, 15% and 8% for 1, 2 and 3 or more RDP for patients with complex PVI as iPVI. An algorithm based on regular expressions classified all RDP as repeat PVI (Re-PVI) due to reconduction (PV reconduction), ablation of atrial tachycardia (AT) or SM, e. g. defragmentation of fractionated signals, or combinations. The results were manually quality-controlled. 798/934 (85%) patients required PV re-isolation due to PV reconduction, 298/934 (32%) required ablation for atrial tachycardia (AT) at least once during FU (Figure 1B). Comparing PVI-only iPVI patients with patients who received substrate modification during iPVI, significantly less patients with PVI-only iPVI had RDP for AT compared to those with SM during iPVI (27% vs. 50%, p&amp;lt;0.01). More PVI-only iPVI patients required PV-reisolation at any time during FU (87% vs 79%, p&amp;lt;0.01). Considering PVI-only (+/- CTI) iPVIs only, dose-area product decreased in RDP compared to first PVI, while procedure duration slightly increased (Figure 1C). Data on periprocedural complications will be reported. Conclusion Redo AF ablations procedures are mainly required due to reconnected pulmonary veins or AT. Patients with PAF at iPVI are less likely to require more than one RDP which provides indirect support for early rhythm control in treatment of AF. SM at iPVI might be a predictor for occurrence of AT in the further course.

Yearly incidence and pattern of very late recurrence of atrial fibrillation as detected by continuous electrocardiographic monitoring using an implantable loop recorder

Abstract Funding Acknowledgements Type of funding sources: None. Background A very late recurrence (VLR) of atrial fibrillation (AF) is considered present when patients have their first recurrence of AF &amp;gt; 12 months post-ablation. Little is known about the yearly rates and patterns of VLR AF recurrence. Objective To assess the yearly incidence and pattern of VLR in pts with AF who underwent cryoballoon (CB) pulmonary vein isolation (PVI). Methods We prospectively enrolled consecutive patients with AF who underwent CB PVI and had an implantable loop recorder (ILR) inserted up to 3 months post-ablation. Patients were followed for recurrent AF (excluding a 3-month post-ablation blanking period). Results Our cohort included 222 patients (66 ± 9 years; 143 [64%] male; 120 [54%] paroxysmal AF; CHA2DS2-VASc 2.6 ± 1.6). At 1-year, 111 (50%) patients remained free of AF. Two-year follow-up was available in 95 of these patients; 62 (65%) remained in sinus. Three-year follow-up was available in 42 of these patients; 36 (86%) remained in sinus (Figure). Of the 39 patients who developed AF after initially being free of AF for at least 1-year post ablation, 24 (62%) patients had either a frequent or persistent pattern of AF. Conclusions Our data show that the greatest likelihood of failure following a CB PVI occurs in the first year of ablation. The rate of failure becomes lower year by year. These data suggest that long term outcome may be driven more by the initial ablation as opposed to progressive evolution of the patient’s substrate

High-density sequential mapping of repetitive atrial conduction patterns during atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported by PersonalizeAF project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. Background Localized AF drivers are considered candidate ablation targets for patients with persistent atrial fibrillation (AF). These drivers are expected to be associated with repetitive atrial conduction patterns during AF. Thus, tools that localize atrial sites with repetitive electrical activity might be instrumental in guiding ablation. Purpose High-density mapping catheters cover only a small portion of the atria. Combining sequential recordings from those catheters could provide a more complete picture of repetitive conduction patterns, and enable AF driver localization. We hypothesize that the repetitive activity generated by local AF drivers can be detected by means of high-coverage composite activation maps generated from spatially overlapping sequential recordings. Methods Repetitive conduction patterns were detected in a goat model of AF (249-electrode epicardial mapping array, 2.4mm inter-electrode distance, n=16) by exploiting recurrence plots (Fig 1A-C). Cross-recurrences of repetitive patterns in sequential recordings were detected in spatially overlapping recording locations. Using this information, local activation maps were aligned and combined into larger composite average activation maps (Fig. 1D-F). The proposed algorithm was tested on a dataset formed by segmenting the epicardial mapping area into four spatially overlapping regions. The proposed algorithm was then used to merge these segmented regions back together to reconstruct the original mapping area. Reconstruction accuracy was measured as the correlation between original and reconstructed average activation patterns (Fig. 2.). Statistical analyses were performed to investigate a possible relation between reconstruction accuracy and pattern properties such as duration, size, complexity, and cycle length. Patterns were classified as single peripheral, multiple waves, focal source, or re-entry based on the preferential conduction velocity directions. Results Among 1021 detected repetitive patterns, 328 spatiotemporally stable- patterns were present in all four artificially segmented recordings. In 32% of these, repetitiveness was associated with a local driver-either focal or re-entrant. Composite maps could be generated in 75% of the cases, and mainly in case of larger patterns (p&amp;lt;0.01). The average correlation between the actual activation maps and the composite maps was 0.86 ±0.16. Only pattern duration showed a statistically significant low correlation with reconstruction accuracy of composite maps (r=0.126, p&amp;lt;0.05). There was no significant difference in the reconstruction accuracy for multiple waves, focal sources and re-entries. Conclusion(s) The proposed framework could align sequentially recorded repetitive epicardial patterns over different atrial regions, to produce high-fidelity composite maps. The performance was minimally affected by pattern properties, thus suggesting potential use with a diverse range of AF patterns.

Influence of atrial fibrillation subtypes on anticoagulant therapy in a high-risk older population: the FAI project

Background and aimBenefits of oral anticoagulants (OAC) in atrial fibrillation (AF) patients with moderate-to-high risk of stroke are independent of AF pattern. We evaluated whether AF clinical subtype influenced OAC use in a representative sample of the Italian older population.MethodsA cross-sectional examination of all subjects aged 65 + years from three general practices in northern, central, and southern Italy started in 2016. A double-screening procedure was followed by clinical and ECG confirmation. Patients were categorized as having paroxysmal, persistent, or permanent AF. OAC use was evaluated in confirmed AF patients.ResultsThe sample included 6016 subjects. Excluding 235 non-eligible, participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Overall, 319 AF cases were identified: 43.0% had paroxysmal, 21.3% persistent, and 35.7% permanent AF. Frequency of OAC therapy was 91.2% in permanent, 85.3% in persistent, and only 43.0% in paroxysmal AF (P < 0.001). In multivariate analysis, controlled for baseline variables and risk scales, persistent and permanent AF were associated with a significant increase in the likelihood of receiving OAC compared with paroxysmal AF (P < 0.001). This was confirmed for permanent AF also in multivariate analyses considering separately vitamin K antagonists or direct-acting oral anticoagulants (OR, 4.37, 95% CI, 2.43–7.85; and 1.92, 95% CI, 1.07–3.42, respectively) and for persistent AF and direct-acting oral anticoagulants (OR, 4.33, 95% CI, 2.30–8.15).ConclusionsIn a population-based survey, AF pattern was an independent predictor of OAC treatment. Paroxysmal AF is still perceived as carrying a lower risk of vascular events.

PO-686-07 THE USE OF CHANGE-FROM-BASELINE DETECTION OF AF BURDEN TO PREDICT HEALTH CARE UTILIZATION IN PATIENTS WITH ATRIAL FIBRILLATION

Atrial fibrillation (AF) is associated with increased risk of healthcare utilization (HCU), which may be triggered by onset of AF or change in burden. Change from baseline of AF burden or other parameters measured by insertable cardiac monitors (ICM) may be useful to predict near-term (HCU). To determine whether rules-based algorithms that examine change from baseline of ICM parameters can be used to stratify risk of near-term HCU. We performed a retrospective cohort study of US patients with Medtronic ICMs enrolled in Carelink® remote monitoring (2007-2019) linked to medical claims data (Optum© Clinformatics database). The ICM cohort was matched to claims data with 7 encrypted identifiers. We included matched patients with ≥1 day of ICM detected AF (any quantity) and ≥12 months continuous enrollment pre- and post-ICM implant. AF burden (total hours/day of AT/AF) was transformed into simple moving averages (SMAs) of different periods (1, 2, 3, 5, 8, 13, 21 days) for each follow-up (FU), including a cumulative SMA calculated for the time between ICM implantation and FU. AF pattern was defined as the comparison of an SMA period with its cumulative average. The same process was applied to daily activity recorded by the ICM. HCU was defined as any encounter from a hospital, emergency room, or ambulatory surgical center with a cardiovascular DRG or diagnosis code. Classification trees were used to describe which ICM detected patterns best stratified patient risk of HCU. Of 89,578 ICM patients, 2,616 (2.9%) met AF and other inclusion criteria (71±11 years, 55% male, CHA2DS2-VASc 3.7±1.9). Overall, 1,998 (76%) had a HCU over 605,363 days. Burden pattern revealed distinct groups: (A) no history of AF (reference); (B) below average burden; (C) above average burden; (D) above average burden with low level ICM-detected daily activity. Odds of HCU were increased in all groups vs reference (B vs A OR 3.82; C vs A OR 8.25; D vs A OR 11.66), including a 33% increase in HCU detection over nominal duration & quantity thresholds. Change-from-baseline analyses of ICM-detected AF and ICM-detected daily activity was strongly associated with near-term HCU, especially high burden coupled with low activity. This approach could provide actionable information to guide treatment and reduce HCU.

PO-691-01 PHYSIOLOGIC, REALISTIC, COMPUTER MODELING OF ATRIAL FIBRILLATION TO FACILITATE THE DEVELOPMENT AND TESTING OF TREATMENT STRATEGIES

An interactive, physiologically realistic (PR), and accurate computer simulation allows multiple scenarios to be tested in a “live” environment and has become a key step in the rapid development and testing of treatment strategies for atrial fibrillation (AF). Develop an accurate model of AF that allows the user to define the regions and zones of anisotropic conduction to test the effectiveness of a variety of AF treatment strategies. A model was developed using standard electrophysiologic (EP) parameters established in the literature. An advanced implementation of the Fitzhugh-Nagumo model reproduces the action potential morphology of the human atrium enabling live simulation. To reproduce the complex conduction patterns (CCPs) of AF identified in the EP lab, a bi-layer model was implemented to represent epi- and endocardial dissociation. The model allows a user to define regions of fibrosis, zones of slow conduction, and action potential duration (APD). The user graphically draws these regions and zones with gradients that span entered max and min values of conduction velocity (CV) and APD. The EP lab experience and workflow is reproduced, with CCPs visualized on a 3D anatomy and calculated potentials displayed as 2D traces. To test the CCPs and performance of the model, isolated zones of conduction were delineated on a 3D LA model, with assigned sites of pacing and recording. Model produces accurate atrial CCPs for anatomical meshes > 20k triangles, with expected source-sink block-velocity < 5 cm/s (Figure 1). Regions of anisotropic conduction were applied to match a human AF substrate mapped by Acutus AcQMap, with PVI-block plus 2 anterior, 1 posterior, 1 roof, 1 mitral-isthmus slow conduction zones (0.1 - 50 cm/s); 1 anterior APD zone (65 - 110 ms); and anterior and posterior regions of endo-epi fibrosis (density = 25%, CV = 8 - 25 cm/s). Model produced similar CCPs to human with rotational and pivoting reentry at the same locations (Figure 2). A PR model of AF was developed that allows a user to define regions of fibrosis and zones of conduction abnormalities prominent in AF. The model can be used for developing and testing advanced treatment strategies. Clinical application is feasible, including input of procedural data to achieve optimal treatment strategies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

PO-697-05 COMPREHENSIVE EVALUATION OF ATRIAL FIBRILLATION RECURRENCE POST CATHER ABLATION THROUGH TEMPORAL PATTERNS

After catheter ablation (CA), patients demonstrate varying temporal patterns of atrial fibrillation (AF) events. Some patients may experience a high AF Burden during the entire follow up period, but others demonstrate varying temporal patterns of sinus and AF. We aim to demonstrate a comprehensive report after an AF CA through the temporal patterns of the rhythms during follow up. Mobile electrocardiogram (ECG) recording devices was used to collect 30-second recordings every day for one year follow up from 852 patients after an CA. In our analysis, we identify the temporal patterns of sinus and AF rhythms amongst our patients. We calculated the AF burden by the number of AF recordings over the number of days. To extract reliable temporal information, we include 473 patients who have submitted recordings for over 200 days. In our analysis, we plotted a temporal report of sinus and AF rhythms over time, and identified the first date of the recurrence event, the number of times the patient’s rhythm converted from one rhythm type to another, AF burden over the first 30 days and the rest of the following period. The AF burden measured after the 30 days had a mean of 12.7%, while the average burden during the first 30 days of the follow up was 29.4%. The study population demonstrated an average of 45 days to the first recurrence event and converted from one rhythm to another 22 times. As none of the temporal features demonstrated a linear relationship to the AF Burden measured after 30 days, we used Spearman’s correlation to measure the relevance of each variable. As a result, the burden during the first 30 days had a correlation of 0.454, the number of days to the first recurrence event had 0.065, and the number of conversions had 0.812, indicating that only the number of switches had a high correlation with the AFIB burden after 30 days. Low correlation from the AF burden from the first 30 days and the number of days to the first recurrence event to the burden of the remaining follow up period indicates that a single AF recurrence event is not a reliable indicator to evaluate the outcome of an CA. Furthermore, the high correlation between the number of times a patient switched from one rhythm to another to the remaining burden is a strong indicator that a more continuous measurement of heart rhythm is necessary.

A Divergence-Based Approach for the Identification of Atrial Fibrillation Focal Drivers From Multipolar Mapping: A Computational Study.

The expanding role of catheter ablation of atrial fibrillation (AF) has stimulated the development of novel mapping strategies to guide the procedure. We introduce a novel approach to characterize wave propagation and identify AF focal drivers from multipolar mapping data. The method reconstructs continuous activation patterns in the mapping area by a radial basis function (RBF) interpolation of multisite activation time series. Velocity vector fields are analytically determined, and the vector field divergence is used as a marker of focal drivers. The method was validated in a tissue patch cellular automaton model and in an anatomically realistic left atrial (LA) model with Courtemanche–Ramirez–Nattel ionic dynamics. Divergence analysis was effective in identifying focal drivers in a complex simulated AF pattern. Localization was reliable even with consistent reduction (47%) in the number of mapping points and in the presence of activation time misdetections (noise <10% of the cycle length). Proof-of-concept application of the method to human AF mapping data showed that divergence analysis consistently detected focal activation in the pulmonary veins and LA appendage area. These results suggest the potential of divergence analysis in combination with multipolar mapping to identify AF critical sites. Further studies on large clinical datasets may help to assess the clinical feasibility and benefit of divergence analysis for the optimization of ablation treatment.

Abstract 13872: Atrial Fibrillation and Acute Ischemic Stroke: Evaluation of the Contemporary 2018 National Inpatient Sample Database

Aims: Atrial Fibrillation (AF) treatment in Acute Ischemic Stroke (AIS) is based on thromboembolism prophylaxis regardless AF type, and degree of atrial myopathy. We aim to investigate morbidity and mortality of persistent AF related stroke. Methods: Patients admitted with AIS and associated paroxysmal and persistent AF were identified in the 2018 National Inpatient Sample. The study compared in-hospital mortality, stroke-related morbidity, hospital cost, length of stay, and discharge disposition between patients with paroxysmal and persistent AF Results: A total of 26,470 patients were admitted for AIS with associated AF. AIS with persistent AF had a longer hospital length of stay (paroxysmal AF Mean(M): 5.7 days, Standard Deviation (SD) 6.8, persistent AF M: 7.4 days, SD 11.9, p&lt;0.001) and in-hospital costs (paroxysmal AF M: $15,449, SD $18,320, persistent AF M: $19,834, SD $23,312, p&lt;0.001). Indirect markers of stroke-related disability, like intracranial hemorrhage (Odds Ratio (OR): 1.9, 95% Confidence Interval (CI): 1.6-2.2), need for gastrostomy (OR: 2.1, 95% CI: 1.8-2.4), and tracheostomy (OR: 3.1, 95% CI: 2.1-4.4) were more associated with AIS and persistent AF (FIGURE 1) Conclusion: Persistent AF is associated with poor in-hospital stroke-related outcomes, possibly due to a higher embolic burden. The current recommendation of using only the CHA2DS2-VASc score without AF pattern needs be reevaluated. Further investigation is required to determine the impact of prevention of AF progression on stroke related morbidity.

Distribution and risk profile of atrial fibrillation patterns among women and men from the general population

Abstract Background In a clinical setting, atrial fibrillation (AF) subgroups are defined, including paroxysmal, persistent, and permanent AF. These subgroups differ in terms of clinical characteristics, management strategy, and long-term outcomes. Application of clinical classifications in population-based settings is challenging as they are based on the duration of symptoms, recurrence, and treatment. Purpose We aim to develop an objective and standardized classification for AF patterns in the general population and examine the associated cardiovascular risk profiles and outcomes for the identified AF patterns. Methods Participants with only one reported AF episode were categorized as single-documented AF, if at least two separate AF episodes were reported as multiple-documented AF and as longstanding persistent AF if at least two consecutive ECG's at the research center showed AF, not followed by an ECG showing sinus rhythm. We fitted mixed effect models with age as time scale to characterize sex-specific cardiovascular risk factor trajectories preceding each AF pattern. We further used Cox proportional hazard modelling to describe the risk of coronary heart disease (CHD), heart failure (HF), stroke, and all-cause mortality following AF. Results We included 14,620 men and women aged ≥45 years. 1137 participants were categorized as single-documented AF, 208 as multiple-documented AF, and 57 as longstanding persistent AF. We identified significant differences in the preceding trajectories of weight, body mass index, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, and waist-hip ratio with various AF patterns. In general, both men and women with persistent-elevated levels of these risk factors were prone to longstanding persistent AF. AF was associated with a large risk for subsequent CHD, HF, stroke, and mortality in the general population. Among the different AF patterns, single-documented AF conferred the largest risk of CHD [hazard ratio, 95% confidence interval: 1.92 (1.19–3.03)] and mortality [1.70 (1.41–2.07)] as compared to multiple-documented AF, and as compared to longstanding persistent AF [1.45 (0.72–2.90) and 3.66 (2.25–5.95), respectively]. Conclusion We developed a classification for AF patterns within a general population. We identified differences in risk factor trajectories preceding each AF pattern, which implies differences in pathophysiological mechanisms underlying AF. Participants with single-documented AF showed worse prognosis than those with multiple AF episodes. This might be due to the subgroup definition, since participants should live for a longer period of time to be categorized in the multiple-documented AF and longstanding persistent AF groups. This can also imply that participants suffering from multiple AF episodes are more frequently monitored, and treated for other risk factors. However, this could also suggest that singular AF episodes are not as innocent as commonly thought. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): - Erasmus MC Mrace grant. - Netherlands Organization for the Health Research and Development (ZonMw) Figure 1Figure 2. Progosis of various AF patterns

Does radiofrequency with contact force supersede cryoballoon for atrial fibrillation ablation? A one-year follow-up retrospective study

Abstract Introduction If catheter ablation of atrial fibrillation (AF) is now proved to be a safe and superior alternative to antiarrhythmic drugs for maintenance of sinus rhythm and improvement of symptoms, the best transcatheter technique is still a matter of debate. Radiofrequency (RF) and cryoballoon (CRYO) are the principal technologies sharing the spotlight, and several observational studies and RCT have compared both techniques with conflicting results. Purpose Current RF catheters now use contact-force technologies to precisely calibrate the energy delivered to tissue, according to the force applied to adjacent tissue in grams, time of contact in seconds and more recently power delivered in watts. The purpose of our study is to evaluate the contribution of this technology in “real life ” conditions and its hypothetical potential to supersede CRYO for the ablation of AF. Methods Design and population. We conducted a single center retrospective study, spreading over two years (1st January 2018–30th December 2019) and enrolling 376 patients that underwent a first ablation procedure in this period. Endpoints. The primary endpoint was a comparison of the rate of AF recurrence for each technique, twelve months after initial procedure, respecting an initial 90 days blanking period. Recurrence was defined as documented AF, atrial flutter, atrial tachycardia lasting at least 30 seconds (12-lead ECG, holter or telemetry) or 6 minutes (for atrial high rate episode on pacemaker interrogation), and/or the need of a second ablation procedure. We evaluated secondary efficacy endpoints including death, procedure duration, fluoroscopy time and hospitalization for cardiovascular causes. Complications in direct relation with the initial procedure were the primary safety endpoint. Finally, we studied the impact of five factors on recurrence: temporal pattern of AF, left atrium dimension, arrhythmia duration, body mass index and CHADS2VA2Sc score. Results Patients who underwent RF ablation were similar to those who underwent cryoablation except for chronic kidney disease, type 2 diabetes and coronaropathy which were more prevalent in RF group. We found a trend toward lower incidence of recurrences in the cryoballoon group, despite not statistically significant. Hospitalizations for cardiovascular causes and deaths from any cause were slightly higher in the radiofrequency group. As expected, time of procedure was lower and fluoroscopy time higher in cryoballoon group. Significant association was detected between recurrence and both left atrium diameter and CHADS2VA2Sc score. Conclusion In this retrospective study, albeit using latest generation ablation catheters in the two different technics, we found no significant difference in recurrence of AF between radiofrequency and cryoballoon ablation of AF. Left atrium diameter and higher CHADS2VA2Sc score are two predictors of recurrence, easy to use in daily clinical practice. Funding Acknowledgement Type of funding sources: None. Baseline characteristics – endpointsPrimary efficacy end point

Stroke risk based on classification of atrial fibrillation: real-world vs clinical trial

Abstract Background The most widely accepted clinical classification of atrial fibrillation (AF) is according to temporal rhythm-based patterns, reflecting the notion that most patients initially suffer from transient episodes that prolong over time due to atrial substrate remodelling as the disease progresses. Therefore, it may be speculated that patients with extended episodes of “continuous” AF (persistent, long-standing persistent and permanent AF) may be at higher risk of stroke complications compared to paroxysmal AF (pAF). However, the risk of stroke according to clinical classification of AF remains poorly defined. In this study, we assessed the impact of AF type on stroke risk in patients with AF from “real-world” and “clinical trial” cohorts. Methods Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. All patients were anticoagulated. Patients were grouped into those with pAF and non-pAF. pAF was defined as AF that terminates spontaneously or with intervention within seven days of onset. Non-pAF was defined as AF that lasted longer than seven days, including persistent, long-standing persistent and permanent AF subtypes. Study endpoint was the incidence rate of ischaemic stroke. A modified CHA2DS2-VAS“c” score that applied one additional point for a “c” criterion of continuous AF (i.e. non-pAF) was calculated. Results 5,917 patients were included; 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Real-world patients had a median age of 76 (interquartile range [IQR] 71–81) years with 51.3% females compared to a median age of 71 (IQR 64–77) years with 33.5% females among clinical trial participants. Baseline demographics were comparable in both groups in the real-world cohort but clinical trial participants with non-pAF were older, predominantly male and had more comorbidities compared to those with pAF. Crude stroke rates were comparable between the groups in real-world patients (incidence rate ratio [IRR] 0.72 [95% CI, 0.37–1.28], p=0.259) though clinical trial participants with non-pAF (vs. pAF) had a significantly higher crude rate of stroke events (IRR 4.66 [95% CI, 2.41–9.48], p&amp;lt;0.001). Using multivariable cox regression analysis, AF type was not independently associated with stroke risk in the real-world (adjusted hazard ratio [HR] 1.41 [95% CI, 0.80–2.50], p=0.239) and clinical trial (adjusted HR 1.17 [95% CI, 0.62–2.20], p=0.621) cohorts, after accounting for known risk factors using the CHA2DS2-VASc score. Using receiver operating characteristic curves analysis, we found no significant improvement in the CHA2DS2-VAS“c” compared to CHA2DS2-VASc score in either cohort (p&amp;gt;0.05). Conclusion Overall, there was no association between the temporal rhythm-based patterns of AF and stroke risk among anticoagulated patients, suggesting that this should not be a consideration when assessing the need for anticoagulation in AF. Funding Acknowledgement Type of funding sources: None.

Mortality risk and temporal patterns of atrial fibrillation in the nationwide registry.

AimsPersistent and permanent atrial fibrillation (AF) often occurs in the presence of multiple comorbidities and is linked to adverse outcomes. It is unclear whether the sustained pattern of AF itself is prognostic or if it is confounded by underlying comorbidities. Here, we tested the association between the temporal patterns of AF and the risks of ischemic stroke and all‐cause mortality.Methods and ResultsIn a prospective multicenter cohort, 3046 non‐valvular AF patients were consecutively enrolled and followed for adverse outcomes of all‐cause mortality and ischemic stroke. The risks of both outcomes were adjusted for underlying comorbidities, and compared between the patterns of AF. At baseline, the patients were classified as paroxysmal (N = 963, 31.6%), persistent (N = 604, 19.8%), and permanent AF (N = 1479, 45.6%) according to the standard definition. Anticoagulants were administered in 75% of all patients and 83% of those with CHA2DS2‐VASc score ≥2 in males or ≥3 in females. During a mean follow up of 26 (SD 10.5) months, all‐cause mortality occurred less in paroxysmal AF (2.5 per 100 patient‐years) than in persistent AF (4.4 per 100 patient‐years; adjusted hazard ratio [HR] 0.66, 95% CI, 0.46‐0.96; P = .029) and permanent AF (4.1 per 100 patient‐years; adjusted HR 0.71, 95% CI, 0.52‐0.98; P = .036). The risk of ischemic stroke was similar across all patterns of AF.ConclusionsIn this multicenter cohort of AF patients, persistent and permanent AF was associated with higher all‐cause mortality than paroxysmal AF, independent of baseline comorbidities.Clinical Trial RegistrationThai Clinical Trial Registration; Study ID: TCTR20160113002 (http://www.thaiclinicaltrials.org/show/TCTR20160113002).

Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors.

The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Season of birth and cardiovascular mortality in atrial fibrillation: a population-based cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Background. Month and season of birth may be indicators for a variety of prenatal and early postnatal exposures and they have been associated with life expectancy in adulthood. It is suggested that people born in the autumn on the northern hemisphere live longer than those born during the spring or summer, who may have an increase in cardiovascular disease specific mortality. Only few studies have followed populations longitudinally and no study has investigated the relation between season of birth and mortality in patients with established cardiac conditions. Methods. All patients with atrial fibrillation (AF) seen in an academic institution were identified in a database. We examined the clinical course of 8962 consecutive patients with AF seen over a 10-year period. The adverse outcomes were investigated during follow-up and we identified the causes of death. The relation between season of birth (autumn, winter, spring and summer) and mortality risk was assessed using Cox proportional hazard regression models using autumn as the reference. Analyses were also made separately for men and women. Results. In these 8962 patients (age 70 ± 10 years, CHA2DS2VASc score 3.1 ± 1.7), 1253 deaths were recorded during a follow-up of 2.5 ± 3.0 years (median 1.2, interquartile 4.3 years, yearly rate of death 5.5%) and 97% of causes of death were identified. Cardiovascular deaths accounted for 54% and 43% for non-cardiovascular. The three main causes of death were heart failure (29%), infection (18%) and cancer (12%). Season of birth was a significant predictor of cardiovascular mortality (overall p = 0.0006). The lowest mortality was seen for people born in autumn or winter and the highest mortality in those born in spring and summer. This was mainly related to a higher cardiovascular mortality in males (hazard ratio [HR] 1.46, 95%CI 1.10-1.93, p = 0.009 for males born in spring and HR 1.44, 95%CI 1.08-1.91, p = 0.01 for those born in summer when compared to males born in autumn as the reference) while this effect was not seen in women. In a model adjusted for age, CHA2DS2VASc score, HASBLED score, cardiovascular risk factors, other comorbidities, AF pattern, antithrombotic use and other cardiovascular drugs use, a higher cardiovascular mortality was still seen in males born in spring (adjusted HR 1.43, 95%CI 1.05-1.96, p = 0.03) or in summer (adjusted HR 1.46, 95%CI 1.07-1.99, p = 0.02) when compared to those born in autumn while this was not seen in women. Conclusion. Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients. Further studies should aim at clarifying the mechanisms behind this association, which would support the so-called fetal origins hypothesis.

Association Between Sex and Treatment Outcomes of Atrial Fibrillation Ablation Versus Drug Therapy: Results From the CABANA Trial.

Among patients with atrial fibrillation (AF), women are less likely to receive catheter ablation and may have more complications and less durable results. Most information about sex-specific differences after ablation comes from observational data. We prespecified an examination of outcomes by sex in the 2204-patient CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). CABANA randomized patients with AF age ≥65 years or <65 years with ≥1 risk factor for stroke to a strategy of catheter ablation with pulmonary vein isolation versus drug therapy with rate/rhythm control agents. The primary composite outcome was death, disabling stroke, serious bleeding, or cardiac arrest, and key secondary outcomes included AF recurrence. CABANA randomized 819 (37%) women (ablation 413, drug 406) and 1385 men (ablation 695, drug 690). Compared with men, women were older (median age, 69 years versus 67 years for men), were more symptomatic (48% Canadian Cardiovascular Society AF Severity Class 3 or 4 versus 39% for men), had more symptomatic heart failure (42% with New York Heart Association Class ≥II versus 32% for men), and more often had a paroxysmal AF pattern at enrollment (50% versus 39% for men) (P<0.0001 for all). Women were less likely to have ancillary (nonpulmonary vein) ablation procedures performed during the index procedure (55.7% versus 62.2% in men, P=0.043), and complications from treatment were infrequent in both sexes. For the primary outcome, the hazard ratio for those who underwent ablation versus drug therapy was 1.01 (95% CI, 0.62-1.65) in women and 0.73 (95% CI, 0.51-1.05) in men (interaction P value=0.299). The risk of recurrent AF was significantly reduced in patients undergoing ablation compared with those receiving drug therapy regardless of sex, but the effect was greater in men (hazard ratio, 0.64 [95% CI, 0.51-0.82] for women versus hazard ratio, 0.48 [95% CI, 0.40-0.58] for men; interaction P value=0.060). Clinically relevant treatment-related strategy differences in the primary and secondary clinical outcomes of CABANA were not seen between men and women, and there were no sex differences in adverse events. The CABANA trial results support catheter ablation as an effective treatment strategy for both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00911508.