Atrial Fibrillation Registry Research Articles

Characteristics of Patients With Asymptomatic Atrial Fibrillation and Ischemic Stroke-Insights From the GLORIA-AF Registry (Phase 2).

Asymptomatic nonvalvular atrial fibrillation is often suspected in patients with cryptogenic stroke which constitute 20%-30% of ischemic strokes. Detection of atrial fibrillation (AF) and treatment with anticoagulation can reduce the risk of stroke. We sought to investigate the prevalence of asymptomatic atrial fibrillation (aAF) in patients with a history of stroke or an acute stroke on admission. From November 2011 until December 2014, 15,308 patients with a first episode of AF were enrolled in phase 2 of the international, prospective, multicenter global registry on long-term oral anticoagulation treatment in patients with AF (GLORIA-AF) Registry. For the present analysis, we focused on patients with aAF regarding the prevalence of stroke. One third of patients (n = 4892, 32%) had aAF. Of these, 611 (12.5%) had a history of stroke or an acute stroke on admission. In contrast, 519 of 10,416 (5.0%) patients with symptomatic AF (sAF) had a history of stroke or an acute stroke on admission. Higher age, male gender, permanent AF, stroke, and the combination of stroke, TIA or systemic embolism were associated with a higher prevalence of aAF on admission. In a multivariable analysis, patients with aAF had a 2.3-fold (95% confidence interval (CI), 2.02-2.54) risk for stroke compared to patients with sAF. Other independent risk factors for stroke were a history of prior bleeding (odds ratio 1.62, 95% CI, 1.34-1.92), chronic kidney disease (1.38, 1.21-1.56), and diabetes mellitus (1.24, 1.10-1.41). aAF is reported in about one third of patients with newly diagnosed AF and is associated with a 2.3-fold risk for stroke compared to sAF. Therefore, screening for aAF in high-risk patients might be appropriate to prevent further embolic cerebrovascular events.

Pulsed Field Ablation as First-line Therapy for Atrial Fibrillation: A Substudy of the EU-PORIA Registry.

Recent studies have demonstrated the benefit of early ablation in preventing the progression of atrial fibrillation (AF). Clinical practice has reflected this shift in AF management and no longer requires patients to fail antiarrhythmic drugs (AADs) before receiving ablation. However, there is limited evidence on outcomes with pulsed field ablation (PFA) as a first-line therapy. Examination of real-world data may shed light on clinical practices and the effectiveness of PFA with and without a prior history of AAD usage. EU-PORIA is an all-comer AF registry enrolling consecutive patients treated with the pentaspline PFA catheter at 7 high-volume centers in Europe. This subanalysis evaluates patients with a history of class I/III AAD use versus those with no documented history of class I/III AAD use (first-line patients). Patients with incomplete AAD history, long-standing persistent AF, and those undergoing a repeat ablation procedure were excluded. Patients were treated and followed based on institutional standard of care. Any episode of atrial tachycardia or AF lasting longer than 30 s was considered an arrhythmia recurrence. Of 1233 patients enrolled in EU-PORIA, 1091 met the inclusion criteria (mean age, 66 years; 40% females; and persistent AF, 36%). Pulmonary vein isolation-only was used in 90% of the patients, and 10% received extra-PV ablation. Ablation as the first-line approach was chosen in 589 patients, and 502 patients had prior class I/III AAD use. In the first-line PFA group, paroxysmal AF was more frequent (68% versus 59%; P<0.001), and pulmonary vein isolation-only was more frequent (93% versus 86%; P<0.001). At 1-year follow-up, freedom from AF/atrial tachycardia recurrence was similar in the ablation-first versus the ablation after failed AAD group (78% versus 74%, respectively; P=0.076). In this large real-world PFA registry, freedom from AF/atrial tachycardia recurrence after 1 year was similar in patients undergoing PFA as a first-line treatment and those with prior failed AAD therapy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05823818.

Impact of race and ethnicity on the rhythm control of newly diagnosed atrial fibrillation: Insights from the Get With the Guidelines Atrial Fibrillation Registry

BackgroundAn early rhythm control strategy is the preferred management for patients newly diagnosed with atrial fibrillation (AF). A rhythm control strategy, however, has been historically underused for patients from underrepresented racial and ethnic groups (UREGs). ObjectiveWe aimed to determine whether disparities in rhythm control are present at the initial diagnosis with AF. MethodsWe used the Get With the Guidelines (GWTG)-Atrial Fibrillation registry to compare the use of a rhythm control strategy among patients with different racial and ethnic backgrounds hospitalized with a new diagnosis of AF from January 2013 through December 2023. ResultsAmong 21,567 patients hospitalized for newly detected AF across 249 hospitals, 17,659 patients (81.9%) identified as non-Hispanic White (NHW), 1,860 patients (8.6%) identified as Black, 1,232 patients (5.7%) identified as Hispanic, and 255 patients (1.2%) identified as Asian. After adjusting for age, sex, and year of presentation, NHW patients were more likely to receive rhythm control (odds ratio [OR], 1.19 [1.07, 1.33], P = .0013) compared with non-White patients at the time of initial diagnosis with AF. Black patients were less likely to receive rhythm control compared with all other racial and ethnic groups (OR, 0.80 [0.71, 0.91], P = .0005). These differences persisted after fully adjusting for demographic characteristics, clinical variables, hospital characteristics, and socioeconomic factors. ConclusionsDifferences in rhythm management exist amongst patients from different racial and ethnic groups. Efforts to mitigate disparities in AF management should include an emphasis on rhythm control at the time of initial diagnosis.

10-Year Trends of Antithrombotic Therapy Status and Clinical Outcomes in Patients With Atrial Fibrillation and Renal Dysfunction - The Fushimi AF Registry.

Anticoagulation therapy for atrial fibrillation (AF) has undergone major changes following the introduction of direct oral anticoagulants (DOAC) in 2011. However, the transition of anticoagulation therapy for AF patients with severe renal dysfunction remains to be elucidated. Follow-up data, including creatinine clearance (CrCl), were available for 3,706 patients in the Fushimi AF Registry. We divided patients into 3 groups based on CrCl as follows: (1) CrCl ≥50 mL/min; (2) 50 mL/min>CrCl≥30 mL/min; and (3) CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50>CrCl≥30 mL/min, prescription of oral anticoagulants increased year-by-year from 2011 to 2021 with a growing proportion of DOAC; however, the prescription of oral anticoagulants remained almost unchanged in those with CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50 mL/min>CrCl≥30 mL/min, the incidence of adverse events, including stroke/systemic embolism and major bleeding, was lower among patients enrolled after 2014 than before 2013. However, these trends were not seen in patients with CrCl <30 mL/min. Despite the increased use of DOAC in patients with AF since 2011, anticoagulation therapy for AF patients with severe renal dysfunction has largely remained unchanged, and a reduction in adverse events in those patients has not been observed.

Cluster-specific risk factors for suboptimal thromboprophylaxis in contemporary European cohort of patients with atrial fibrillation: the EHRA-PATHS Project

Abstract Background Oral anticoagulation (OAC) is essential to optimal thromboprophylaxis in patients with atrial fibrillation (AF). Owing to bleeding risk concerns, OAC use may be challenging in clinically complex high-risk AF patients. Comorbidities might lead to suboptimal OAC use. We assessed cluster-specific risk factors for non-prescribing OAC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was constructed using data from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific risk factors for non-prescribing OAC were identified using univariate and multivariate logistic regression analyses. Results Of 18.799 patients, 2086 (11.1%) were not prescribed with OAC. Among the three clusters (see Table), OAC non-prescribing was significantly more prevalent in Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) or Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), both P&amp;lt;0.001, with no significant difference between Clusters 2 and 3 (P=0.161). Cluster-specific multivariable risk factors for non-prescribing OAC are shown in Table. In all three clusters AF clinical type was significantly associated with OAC non-use. In Cluster 1, OAC non-use was less likely in the presence of CHA2DS2-VASc stroke risk factors, while bleeding risk factors were predominant multivariable predictors of OAC non-use among elderly (Clusters 2 and 3). Conclusion Our findings in a large contemporary European cohort suggest that different considerations prevail in treatment decision on OAC use in AF patients in clinical practice, depending on patient’s age and AF clinical type, as well as the presence and type of underlying comorbidities. Our findings could help in formulating targeted interventions to optimize stroke prevention in different subgroups of AF patients.

Cluster-specific predictors of early rhythm control in contemporary European cohort of patients with atrial fibrillation: The EHRA-PATHS Project

Abstract Background Early rhythm control (ERC) using antiarrhytmic drugs, electrical cardioversion or catheter ablation for AF within a year from first diagnosis of atrial fibrillation (AF) has been shown to reduce the risk of major adverse outcomes compared to usual care, and the effects of ERC have been suggested to be consistent across all AF subgroups with different risk profiles. We aimed to identify cluster-specific predictors of ERC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was derived from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific predictors of ERC were identified using univariate and multivariate logistic regression analyses. Results Of 18,799 patients, AF was diagnosed within 1 year in 8088 (43.0%), and 3913/8088 patients (48.4%) were treated with ERC. Among the three clusters - Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) and Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), see Table, ERC was significantly more often used in Cluster 1 compared with Cluster 2 and Cluster 3 (both P&amp;lt;0.001), and in Cluster 2 compared with Cluster 3. Cluster-specific multivariable predictors of ERC are shown in Table. In all three clusters, asymptomatic AF (EHRA score I) and Northern Europe residence were inversely associated with ERC, while Western Europe residence was positively associated with ERC in Cluster 2 and 3. In Cluster 1, low stroke risk and hypertension were positively associated with ERC, while dilated left atrium (LA) and reduced left ventricular ejection fraction (LV EF) were negative predictors of ERC. In Cluster 2, age ≥80 years, enlarged LA, and CHA2DS2-VASc ≥2 for males and ≥3 for females were negatively associated with ERC. In Cluster 3, age ≥75 years, cardiomyopathy, liver disease, dementia and reduced LV EF were negative predictors of ERC. Conclusion Our study of a large European AF cohort showed that likelihood for ERC was greater in younger and healthier AF patients, as well as in elderly from Western Europe, while ERC was significantly less likely with increasing age and comorbidity (especially cardiovascular diseases). These findings likely reflect the lack of high-quality evidence supporting aggressive ERC in high-risk patients with AF. With increasing body of evidence favouring ERC such patients, a shift towards less selective consideration of ERC in daily practice may be expected.

Implications of renal function on adverse clinical events in patients with atrial fibrillation: a comparative analysis of VKA and NOAC therapy - Insights from the GLORIA-AF Registry Phase III

Abstract Background Renal function, as assessed by creatinine clearance (CrCl), plays a crucial role in determining the efficacy and safety of oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF). Purpose To investigate the relationships between CrCl and the risk of clinical adverse events in patients with AF receiving OAC therapy, comparing the safety profiles of vitamin K antagonists (VKA) and non-vitamin K antagonist oral anticoagulants (NOACs). Methods Anticoagulated AF patients from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry Phase III were studied. CrCl was calculated for renal function, according to Cockcroft-Gault equation. Restricted cubic spline (RCS) were used to explore the nonlinear association between adverse end events and CrCl, comparing VKA and NOAC therapy. Cox regression models were used to analysis the associations between adverse end events and OAC therapy in patients with different CrCl levels, adjusted by clinical features and previous disease. Patients were followed up for the composite outcome (all-cause death, thromboembolism and major bleeding), all-cause death, cardiovascular disease (CVD), major bleeding, myocardial infarction (MI) and stroke. Results In 10,594 AF patients (mean age 70.35 ± 9.92 years; 55% male; 73% on NOAC), RCS analysis revealed decreased risks of all cause death, composite outcomes and CVD with increasing CrCl in patients with CrCl &amp;lt; 80 mL/min. Multivariate Cox models indicated that NOAC therapy associated with lower risk of all cause death (HR 0.68, 95% CI 0.58-0.78), composite outcomes (HR 0.77, 95% CI 0.68-0.86), CVD (HR 0.7, 95% CI 0.56-0.87), major bleeding (HR 0.74, 95% CI 0.61-0.91) in AF patients. For CrCl &amp;gt; 95 mL/min, a lower risk of all cause death (HR 0.56, 95% CI 0.38-0.82), composite outcomes (HR 0.68, 95% CI 0.51-0.91) and major bleeding (HR 0.54, 95% CI 0.35-0.85) were associated with NOAC therapy, vs. VKA. For CrCl &amp;lt; 30 mL/min, a lower risk of all cause death (HR 0.47, 95% CI 0.28-0.81), composite outcomes (HR 0.56, 95% CI 0.35-0.89) and CVD (HR 0.43, 95% CI 0.20-0.90) were related to NOAC therapy. No significant difference in outcomes between VKA and NOAC were found in patients with moderate CrCl. Conclusion Increasing CrCl were associated with decreased risk of adverse clinical events, including all-cause death and CVD in anticoagulated AF patients. For patients with CrCl &amp;gt;= 95 and &amp;lt; 30, NOAC therapy, was associated with lower risks of adverse outcomes.Figure 1Figure 2

Dynamic recommendation for anticoagulant treatment in patients with atrial fibrillation using deep reinforcement learning method

Abstract Background Recent evidence suggests that the guideline-directed anticoagulant therapy for atrial fibrillation (AF) remains controversial. Widely-used CHA2DS2-VASc score is solely based on limited traditional cardiovascular risk factors, omitting AF characteristics and other markers of thromboembolic risk. A more efficient, safer and more personalized anticoagulant approach is warranted. Purpose To develop a data-driven deep reinforcement learning (DRL) model for guiding dynamic anticoagulant treatment in AF patients to improve cardiovascular outcomes. Methods Participants of this study were enrolled from the multicentred China Atrial Fibrillation (China-AF) Registry between August 2011 and December 2022, who were with regular follow-up every 6 months. We excluded patients on warfarin at baseline due to its declining usage trend in non-valvular AF patients in China. The DRL model was trained in 70% randomly selected patients for optimal dynamic decision-making, and then subsequently tested in the remaining 30%. Data of sociodemographic characteristics, AF characteristics, medical history, lifestyle factors, laboratory examination, and medications were input for model training. Concordance rate between DRL model’s recommendations and physicians’ actual decisions of non-vitamin-K-antagonist oral anticoagulant (NOAC) prescription among all visits before censoring was calculated for each patient. Primary outcome was the composite of cardiovascular death, ischemic stroke, transient ischemic attack or systemic embolism (SSE), and major bleeding. Shapley additive explanation analysis ranked the most important factors affecting decision-making of the DRL model. Results A total of 20068 patients (mean age: 63.0±12.0 years; 36.2% female) were randomly divided into a training cohort of 14050 patients and a testing cohort of 6018 patients. The model’s NOAC recommendations were mostly affected by age, prior NOAC prescription, body mass index, hypertension history and prior statin prescription (Figure 1). Patients with concordance rates of 50.1%-75% and 75.1%-100% had significant risk reductions for the primary outcome (adjusted HR =0.63; 95% CI, 0.46-0.85; P = 0.003 and adjusted HR =0.59; 95% CI, 0.46-0.75; P &amp;lt;0.001, respectively), compared to those with a concordance rate of 0-25%. Similar results were observed for all-cause death, cardiovascular death and SSE outcomes, that patients with the highest concordance rate had a significant lower risk, compared to those with the lowest concordance rate. There was a nonsignificant but similar trend with regard to major bleeding events (Figure 2). Conclusions This modelling study suggests that a data-driven DRL model might provide more efficient, safer and more personalized anticoagulant suggestions, potentially assisting physicians in clinical practice.

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III

Abstract Background Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use. Purpose To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients. Methods We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events. Results A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result. Conclusions DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2

Impact of rhythm control strategy on outcomes in patients with first diagnosed atrial fibrillation in an 11-year real-world registry

Abstract Background Atrial fibrillation (AF) is a highly prevalent arrhythmia with a high burden of disease. This sub-study of the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) sought to evaluate clinical characteristics, treatment strategies and outcomes in patients with first diagnosed AF (FDAF). Methods Patients with AF presenting to the emergency department (ED) of an University Hospital between June 2009 and March 2020 were consecutively enrolled. Follow-up was performed for all-cause mortality, stroke, major bleeding and myocardial infarction (MI). Outcomes were were related to patients with FDAF or pre-existing AF, as well as assigned treatement strategy (rhythm vs. rate control). The trial was registered at ClinicalTrials.gov Identifier: NCT05995561. Results Overall 2,758 (27%) of all patients presented with FDAF. Compared to FDAF, patients with pre-existing AF showed higher all-cause mortality HR 1.41 (95%CI 1.28-1.55, p&amp;lt;0.0001) and major bleeding events 1.29 (95% CI 1.06-1.56, p=0.0098). Non-implementation of rhythm control in FDAF was seen in 2,079 cases (75.4%) and was associated with an excess of all-cause mortality HR 1.66 (95%CI 1.30-1.99, p&amp;lt;0.0001) and incident MI HR 1.79 (95% CI 1.03-3.09, p=0.0385). A non-implementation of rhythm control remained an independent predictor for all-cause mortality and MI even after adjustment for significant univariate variables aHR: 1.34 (95%CI: 1.04-1.72, p=0.0234) and aHR: 1.79 (95%CI: 1.03-3.09, p=0.0385). Conclusion Real-world data from FDAF patients presenting in the setting of an ED showed a potential benefit regarding mortality and MI for rhythm control strategy. Further research is needed to validate this hypothesis.

Improved risk prediction in patients with atrial fibrillation and clinical intermediate-risk CHA2DS2VASc-score utilizing high sensitive troponin T

Abstract Background Guidelines of the European Society of Cardiology recommend risk assessment to identify appropriate candidates for anticoagulation in patients with atrial fibrillation (AF). However, scores such as the CHA2DS2VASc-score show only a modest performance for prediction of adverse events. Methods This retrospective single-center all-comer sub-study from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) enrolled 9,995 consecutive patients with non-valvular AF, presenting to the emergency department (ED) from June 2009 until March 2020. We tested the performance of the CHA2DS2VASc-score with and without high sensitive cardiac troponin T (hs-cTnT) for prediction of a adverse events such as stroke or major bleedings. Per CHA2DS2VASc, stroke risk was classified as low (0 point in men, ≤1 point in females), intermediate, or high (≥2 points in men and ≥3 points in females). Results Performance of the CHA2DS2VASc-score for the prediction of the composite endpoint consisting of stroke and major bleeding was poor (AUC 0.600, 95%CI: 0.590-0.610) but improved after addition of hs-cTnT as a variable across all risk categories (AUC 0.618 95%CI: 0.608-0.628, ∆AUC 0.0182 95%CI: 0.0124-0.0240, p&amp;lt;0.0001), and particularly in patients at intermediate-risk (∆AUC 0.160 95%CI: 0.0653-0.254, p=0.0009). The absence of detectable hs-cTnT (&amp;lt; LoD) identified a cohort without incident events within patients with intermediate per CHA2DS2VASc. Conclusion Combination of hs-cTnT and clinical-based risk stratification in AF patients presenting to an ED with intermediate CHA2DS2VASc-score is simple and effective. Measurement of hs-cTnT improves prediction of stroke risk in patients with intermediate CHA2DS2VASc-score and may help guide decision for or against anticoagulation.

Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up

Abstract Background Frailty is a common reason to choose non-recommended (non-rec) doses of non-vitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation (AF); however, it is not known how this practice affects stroke and bleeding outcomes. Purpose To assess clinical outcomes in frail patients with AF receiving non-rec vs recommended (rec) doses of edoxaban using 4-yr follow-up data from ETNA-AF-Europe. Methods The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 yrs. In ETNA-AF-Europe, perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a simplified adaptation of the Rockwood’s Frailty Index. For objective frailty, patients with missing index were categorised as non-frail. Patients with perceived or objective frailty were combined for this analysis. Baseline characteristics and hazard ratios (HRs) with 95% confidence intervals (CIs) assessing risk of outcomes in frail patients prescribed non-rec vs rec edoxaban doses (i.e., non-rec 60mg vs rec 30mg and non-rec 30mg vs rec 60mg) are presented. Data were adjusted for age, sex, and derived versions of the CHA2DS2-VASc and HAS-BLED scores. Net clinical benefit was defined as any stroke/systemic embolic event (SEE), transient ischaemic attack, venous thromboembolic event, major bleeding, or cardiovascular death, whichever came first. Results Of 13164 patients, 1786 were frail (13.6%; perceived frailty [n=1410], age [IQR]: 82.0 [78.0-86.0] yrs, women: 57.9%; objective frailty [n=540], age [IQR]: 77.0 [71.0-82.0] yrs, women: 31.9%; both, n=164). Baseline characteristics are reported in Table 1. Risk of all-cause death was higher in frail patients treated with non-rec 30mg vs rec 60mg (HR [95% CI]: 1.44 [1.06,1.96]). The annualised rate [CI] of any stroke/SEE was non-significantly higher (HR [95% CI]:1.60 [0.80,3.20]) with non-rec 30mg (n=169; 2.25 [1.25,4.06]) vs rec 60mg (n=622; 1.54 [1.08,2.20]). There was, however, no association between treatment received and risk (HR [95% CI]) of major bleeding (1.19 [0.58,2.43]) or net clinical benefit (1.26 [0.84,1.87]) (Figure 1). In frail patients who received non-rec 60mg (n=183) vs rec 30mg (n=695), risk of any stroke/SEE (HR [95% CI]) was higher (2.15 [1.03,4.49]), but there were no significant differences in the risk (HR [95% CI]) of major bleeding (1.03 [0.52,2.01]), net clinical benefit (1.15 [0.78,1.71]), or all-cause death (0.79 [0.59,1.05]) (Figure 1). Conclusions In this large European AF registry, the presence of frailty should not drive dosing recommendations for edoxaban. In particular, when compared with the rec 60mg dose, the non-rec 30mg (reduced) dose, was associated with more all-cause death and no benefits on major bleeding.Baseline Characteristics

Characterization of sedation strategies in real-world use of pulsed field ablation: sub-analysis of the EU-PORIA registry

Abstract Background/Introduction With the introduction of pulsed field ablation (PFA) to treat patients with atrial fibrillation (AF), there has been interest in studying workflow and sedation strategies to better understand how this new technology can be integrated into clinical practice. Purpose Characterize the use of general anesthesia (GA) versus deep sedation during real-world use of the pentaspline PFA catheter to treat AF. Methods EU-PORIA is an all-comer AF registry enrolling consecutive patients treated with the pentaspline PFA catheter at seven high-volume centers in Europe. Patients were treated based on institutional standard of care. During follow-up, any episode of atrial tachycardia (AT) or AF lasting longer than 30 seconds was considered an arrhythmia recurrence. Results EU-PORIA enrolled 1233 patients, of which 250 ablation cases were performed under GA and 983 cases were performed with deep sedation. Six out of the 7 participating centers employed a single sedation strategy (2 GA; 4 deep sedation), with one center doing a mix of both sedation and GA. The patient population treated with GA had fewer female patients (30% vs 40%; p=0.04), a lower prevalence of hypertension (43% vs 57%; p&amp;lt;0.01), and fewer paroxysmal AF patients (54% vs 62%; p&amp;lt;0.01). The ablation strategy was performed based on operator’s discretion. In the GA group, 72% of patients received a pulmonary vein isolation (PVI)-only ablation approach versus 90% of patients in the sedation group (p&amp;lt;0.01). The most common additional lesion set performed was posterior wall isolation which accounted for 23% and 7% of cases in the GA and sedation groups, respectively (p&amp;lt;0.01). Procedure times and fluoroscopy times were significantly shorter in the sedation group versus the GA group (51 [36-84] min vs 75[60-90] min; 13 [8-19] min vs 19 [15-26] min; p&amp;lt;0.01 for both). Mapping was used in 60% of cases in the GA group versus only 26% of cases in the sedation group. Overall, there were no differences in the incidence of serious adverse events, and no difference in chronic treatment success. At 1-year follow-up, 74.8% of patients (187/250) in the GA group and 73.8% of patients (725/983) in the sedation group were free from recurrent AF/AT. Conclusion(s) In this registry, the use of deep sedation for AF ablation with the pentaspline PFA catheter demonstrated a safety and efficacy profile consistent with those procedures performed under GA. The majority of the deep sedation procedures were PVI-only and performed in a less progressed AF disease state. It is worth noting that there may be certain patient populations and center restrictions where GA will remain the necessary approach for AF ablation. This characterization of real-world use warrants further evaluation to understand optimal sedation strategies that can be used with PFA technologies.

Relationship between chronic obstructive pulmonary disease and heart failure hospitalization in patients with atrial fibrillation: the Fushimi AF Registry

Abstract Background Chronic heart failure and chronic obstructive pulmonary disease (COPD) are both common diseases and often co-exist. Patients with COPD are at increased risk for hospitalizations due to cardiovascular diseases. However, in patients with atrial fibrillation (AF), the relationship between COPD and the risk of heart failure (HF) hospitalization remains unclear. Purpose The purpose of this study was to investigate the relationship between COPD and HF hospitalization in AF patients. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Japan. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. We compared patients with and without COPD with regard to clinical background and HF hospitalization during follow-up period. Results In this cohort, the proportion of pre-existing HF among patients with COPD was 30.1%, and the proportion of COPD among patients with pre-existing HF was 5.9%. Of 4,496 patients, 238 (5.3%) patients had COPD (COPD; the mean age 75.6 years, female 20.6%), and the remaining 4,258 patients did not (Non-COPD; the mean age 73.5 years, female 41.6%). Patients with COPD were older than those without COPD. However, the proportions of patients with pre-existing HF, previous stroke, vascular disease, cardiomyopathy, coronary artery disease (CAD), diuretic use, renal dysfunction, diabetes mellitus (DM) and hypertension were comparable. During the median follow-up period of 1,824 days, the incidence of HF hospitalization was significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 4.85% vs. 3.01% per person-year: p&amp;lt;0.01). In multivariate analysis adjusted by sex, age (≥ 75 years), heart disease (combined by heart failure, vascular disease, cardiomyopathy and CAD), renal dysfunction, DM, hypertension and diuretic use, COPD was an independent risk factor for HF hospitalization (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.15-2.07, P&amp;lt;0.01) (Figure 1). When we analyzed patients without pre-existing HF, the incidence of HF hospitalization was also significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 2.87% vs. 1.75% per person-year: p=0.02). In multivariate analysis after adjusting for the same factors, COPD was an independent risk factor for HF hospitalization (HR 1.63, 95% CI 1.05-2.53, P=0.03) (Figure 2). Conclusion In patients with AF, COPD was the risk of HF hospitalization. The results were consistent in AF patients without pre-existing HF.

The gender difference in cause of death in Japanese atrial fibrillation patients: The Fushimi AF Registry

Abstract Background Previously we reported that incident rate of heart failure (HF) hospitalization was higher in female than male and stroke was comparable between female and male in Japanese atrial fibrillation (AF) patients. We also reported cardiovascular death was mainly related to HF but not stroke. However, the gender difference in cause of death in Japanese AF patients is little known. Method The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. In the entire cohort, 2,677 were male and 1,819 were female. We compared clinical characteristics and cause and incidence rate of death between two groups. Result Female patients were older (female vs. male; 76.7 years vs. 71.5 years, p&amp;lt;0.01), less in body weight (51.2 kg vs. 65.0 kg, p&amp;lt;0.01), had higher pulse rate (79.4 bpm vs. 77.5 bpm, p&amp;lt;0.01), less often persistent/permanent type (48.2% vs. 52.0%, p=0.04), less likely to have previous stroke/systemic embolism (18.6% vs. 21.1%, p=0.04), diabetes mellitus (19.9% vs. 26.2%, p&amp;lt;0.01), coronary artery disease (12.3% vs. 16.0%, p&amp;lt;0.01) and more likely to have prior HF (32.2% vs. 24.0%, p&amp;lt;0.01), chronic kidney disease (39.3% vs. 33.7%, p&amp;lt;0.01)and had higher CHADS2 score (2.15 vs. 1.96, p&amp;lt;0.01). In prescription data, female patients less often received oral anticoagulant (52.1% vs. 58.2%, p&amp;lt;0.01) and antiplatelet drug (23.8% vs. 29.0%, p&amp;lt;0.01). Systolic blood pressure, hypertension and major bleeding were comparable between two groups. During the median follow-up of 2,093 days, the incidence rate of all cause death was comparable between female group and male group (5.20 vs. 4.86 % per person-year, log rank p=0.32). The incidence rate of cardiac death was significantly higher in female group than male group (0.98 vs. 0.70 % per person-year, log rank p=0.02) and the incidence rate of vascular death was also significantly higher in female group than male group (0.43 vs. 0.26 % per person-year, log rank p=0.03). The incidence rate of death due to HF, which was main cause of cardiac death, was higher in female group but not significant (0.86 vs. 0.66 % per person-year, log rank p=0.08). We analyzed the proportion of cause of death in each gender, cardiac death and stroke were higher and non-cardiovascular death was lower in female than male group. Conclusion The incidence rates of cardiac death and vascular death were significantly higher in female group than male group, and death due to HF was non-significantly higher in female group. Concerning the proportion of cause of death in each gender, cardiac death and stroke were higher in female than male. The impact of cardiovascular events may be stronger and prevention of them may be more important in female.

Effect of the longitudinal change in anemia status on clinical outcomes for patients with nonvalvular atrial fibrillation: analysis from the Hokuriku-Plus AF registry

Abstract Background Anemia is a common comorbidity in older patients with heart failure (HF)1 and atrial fibrillation (AF)2, associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF, as limited data are available on this aspect. Methods and Results We prospectively evaluated data of 1,388 patients with AF obtained from the Hokuriku-Plus AF registry (1,010 men, 72.3±9.7 years) and recorded the incidence of cardiovascular death (CVD), HF, thromboembolism, and major bleeding. Finally, 1,233 patients with AF with baseline and first year of follow up hemoglobin levels were evaluated. Patients were categorized into 3 groups based on the longitudinal changes in 1-year anemia status: AF without anemia (group 1), AF with improved anemia (group 2), and AF with sustained or new-onset anemia (group 3). During 1–5-year follow up, the incidences of CVD, HF, thromboembolism, and major bleeding were significantly higher in patients with AF and anemia than in those without (Figure1). Additionally, the incidence of CVD or HF was significantly higher in group 3 than in groups 1 and 2 (Figure 2). Multivariate analysis revealed no anemia or improvement from anemia in 1 year as an independent predictor for reducing CVD and HF. Conclusions Recovery from anemia may be associated with a favorable clinical course in AF.

Clinical Characteristics and Outcomes in Patients With Atrial Fibrillation and Pathogenic TTN Variants

BackgroundTTN encodes a sarcomeric protein called titin. Pathogenic rare variants in TTN are the most common finding in patients with atrial fibrillation (AF) and positive genetic testing. ObjectivesThis study sought to define the characteristics and outcomes in patients with AF and pathogenic TTN variants compared with genotype-negative patients with AF. MethodsPatients who presented initially with AF were enrolled in an AF registry. Retrospectively they underwent research sequencing for cardiomyopathy and arrhythmia genes. TTN(+) AF cases were defined as participants with pathogenic or likely pathogenic (P/LP) rare variants located in exons with high cardiac expression. They were matched 1:2 with control subjects with no P/LP variants. Phenotyping used retrospective manual chart review. ResultsAmong 2794 participants; 57 (2.0%) TTN(+) AF cases were identified and matched with 114 control subjects. Low QRS complex voltage was present more often in TTN(+) AF cases (18% vs 5%; P < 0.01), with no difference in PR, QRS interval, or QTc. More TTN(+) AF cases had persistent AF at enrollment (44% vs 30%; P = 0.028) and had undergone multiple cardioversions (61% vs. 37%; P < 0.01). By end of follow-up (median 8.3 years; Q1, Q3: 4.5, 13.7 years), 11% of TTN(+) AF cases developed sustained ventricular tachycardia/ventricular fibrillation, 44% left ventricular (LV) systolic dysfunction (LV ejection fraction <50%), and 47% met a combined endpoint of sustained ventricular tachycardia/ventricular fibrillation or LV systolic dysfunction. ConclusionsTTN(+) AF patients undergo more cardioversions and have more persistent forms of AF. Approximately 50% develop LV systolic dysfunction and/or malignant ventricular arrhythmias. These results highlight the need for diagnostic evaluation and management in TTN(+) patients beyond the usual care for AF.

Design and rationale of a pragmatic randomized clinical trial of early dronedarone versus usual care to change and improve outcomes in persons with first-detected atrial fibrillation – the CHANGE AFIB study

BackgroundWhile there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes. MethodsIn this open-label pragmatic clinical trial nested within the Get With The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months. ConclusionCHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes. ClinicalTrials.gov #- NCT05130268

Prevalence, Characteristics, and Treatment Strategy of Different Types of Heart Failure in Patients With Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in patients with heart failure (HF). Epidemiological data regarding HF in patients with AF are lacking. We describe the epidemiology, clinical features, treatment strategies, and in-hospital outcomes in patients with AF and HF. Patients with HF and nonvalvular AF in the Improving Care for Cardiovascular Disease in China-AF cohort from February 2015 to December 2019 were included. Patients were stratified by left ventricular ejection fraction into HF with reduced EF, HF with mildly reduced EF, and HF with preserved EF groups. The primary outcome was the occurrence of hospitalization for major adverse cardiovascular events, including death, cardiogenic shock, cardiac arrest, and stroke. Overall, 16 562 patients with AF and HF were included (mean age: 72.35±11.07 years; 46.1% female). HF with preserved EF (63.1%) accounted for the largest proportion, followed by HF with mildly reduced EF (19.0%) and HF with reduced EF (17.9%). Different HF subtypes in patients with AF had unique baseline demographic and clinical characteristics after multinomial logistic regression analysis. Compared with the HF with preserved EF group, hospitalization for major adverse cardiovascular events was increased in the HF with mildly reduced EF group (odds ratio=1.55 [95% CI, 1.18-2.03]) and HF with reduced EF group (odds ratio 1.60 [95% CI, 1.21-2.13]) after adjusting for confounders. In this large Chinese AF registry, the distribution of HF differed from the non-AF population. Patients with AF with different types of HF have unique demographic and clinical characteristics. Occurrence rates of in-hospital outcomes were higher in patients with HF with mildly reduced EF and patients with HF with reduced EF compared with the HF with preserved EF group. URL: http://www.clinicaltrials.gov; Unique identifier: NCT02309398.

Impact of Preoperative Sinus Rhythm on Concomitant Surgical Ablation's One-Year Success in Patients with Atrial Fibrillation: A Prospective Registry Cohort Study.

Background: The surgical ablation (SA) of atrial fibrillation (AF) during cardiac surgery is performed in only 8-40% of patients. We performed a subgroup analysis of the 1-year follow-up from the German CArdioSurgEry Atrial Fibrillation (CASE-AF) registry to determine how preoperative sinus rhythm (SR) prior to SA affected the outcomes. Methods: The CASE-AF registry enrolled AF patients scheduled for cardiac surgery with concomitant SA. The in-hospital and one-year follow-up data were collected prospectively and analyzed retrospectively. Results: From September 2016 to August 2020, 964 patients were enrolled in the CASE-AF registry. Among them, 333 patients were in SR immediately before surgery (study cohort). A complete follow-up was achieved for 95.6%. Both the severity of the AF (modified European Heart Rhythm Association symptom classification, p < 0.001) and the frequency of AF symptoms (p = 0.006) were significantly reduced at one year compared to the preoperative baseline. Almost 90 percent of the patients underwent left atrial appendage occlusion (LAAO) during the procedure. The one-year mortality (4.1%) and stroke rates (3.2%) were low. SR was evident in 70.3% of the patients at the one-year follow-up. Conclusions: Patients with AF who have SR at the time of surgery should not be excluded from SA, as it appears to be a safe and effective procedure.