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In patients with prevalent or incident atrial fibrillation (AF) after successful transcatheter aortic valve implantation (TAVI) enrolled in the EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation - in Atrial Fibrillation (ENVISAGE-TAVI AF) trial, the incidence of ischemic stroke (IS) and any stroke was numerically less in the edoxaban group than in the vitamin K antagonist (VKA) group. The present study aimed to identify risk factors associated with IS in an on-treatment subanalysis in patients from ENVISAGE-TAVI AF who received ≥1 dose of edoxaban or VKA. Baseline patient characteristics were compared in patients with and those without IS. Numerical variables were compared using a 1-way analysis of variance; categorical variables were compared using Fisher's exact test. Stepwise Cox regression determined patient characteristics associated with the first IS event. Of 1,377 patients, 41 (3.0%) experienced an IS, and 1,336 (97.0%) did not; baseline demographics and clinical characteristics were well balanced between groups. Most ISs occurred within 180 days of TAVI for edoxaban (57.9%) and VKA (68.2%). The rate of IS was 2.0/100 person-years for edoxaban versus 2.7/100 person-years for VKA. Independently associated with IS were history of systemic embolic events (hazard ratio 2.96, 95% confidence interval 1.26 to 7.00, p = 0.01) and pre-TAVI use of VKAs (hazard ratio 2.17, 95% confidence interval 1.12 to 4.20, p = 0.02). In conclusion, although the overall incidence of IS was small for patients with AF on edoxaban or VKA after successful TAVI, patients with a history of systemic embolic events or pre-TAVI use of VKAs may be at greater risk of IS after TAVI., Competing Interests: Declaration of competing interest Dr. Hengstenberg is a clinical proctor for Boston Scientific and Edwards Lifesciences and reports payment for speaker bureaus, support for attending meetings, and advisory board participation from Daiichi Sankyo in addition to institutional funding from Abbott Vascular, Amgen, Biosensors, Biotronik, Boehringer Ingelheim Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Ferrer, Medtronic, Novartis, Philips, Siemens, and Terumo. Dr. Unverdorben and Dr. Jin are employees of Daiichi Sankyo. Dr. Möllmann received personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, and Pfizer and support for attending meetings from Abbott, AstraZeneca, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, and Pfizer. Dr. Van Mieghem reports grants or contracts from Abbott, Abiomed, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Medtronic, PulseCath BV, and Siemens. Dr. Thiele is the president of the German Society of Cardiology. Dr. Nordbeck reports speaker honoraria from Bayer, Boehringer Ingelheim, Daiichi Sankyo Europe GmbH, and Pfizer. Dr. Rassaf reports personal and other fees from AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, and Novartis. Dr. Moreno reports personal fees from Abbott Vascular, Amgen, Biosensors, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Ferrer, Medtronic, Philips, and Terumo. Dr. Mehran reports research grants to institution, support for attending meetings from Bayer and Daiichi Sankyo, and consulting fees from Daiichi Sankyo. Dr. Veltkamp reports grants or contracts from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, and Medtronic and consulting or advisory board participation for AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Javelin Ventures, and Portola Pharmaceuticals. Dr. Dangas reports research grants to institution, support for attending meetings from Bayer and Daiichi Sankyo, and consulting fees from Daiichi Sankyo. Dr. Lang has no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging., Methods and Results: Following an International Prospective Register of Systematic Reviews-registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta-analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%-7.87%], P <0.01). The degree of LA fibrosis was significantly higher in patients with atrial fibrillation than healthy controls (MD, 8.22% [95% CI, 5.62%-10.83%], P <0.01). A similar degree of LA fibrosis was observed in patients with ESUS compared with patients with atrial fibrillation (MD, -0.92% [95% CI, -2.29% to 0.44%], P =0.35)., Conclusions: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.

Background: Atrial fibrillation detected after stroke (AFDAS) refers to the identification of newly diagnosed atrial fibrillation (AF) following an ischemic stroke in patients without known AF (KAF). The objective of this study was to compare the functional outcomes of patients diagnosed with AFDAS and those with KAF who underwent mechanical thrombectomy., Methods and Results: We conducted a retrospective analysis of patients who underwent mechanical thrombectomy and with either new AF diagnosed during hospitalization or KAF. We compared the baseline characteristics, clinical, and procedure-related variables between those with AFDAS and KAF. The primary outcome was the achievement of functional independence, defined as a modified Rankin Scale score of 0 to 2, at 3 months after stroke. Of the 252 patients, 101 (40.1%) were classified into the AFDAS group. The KAF group exhibited a higher rate of stroke history compared with the AFDAS group (32.5% versus 13.9%; P =0.001). Tandem occlusion was more common in the KAF group (13.2% versus 5.9%), while M2 occlusion was more common in the AFDAS group (11.3% versus 20.8%). The proportion of patients who achieved functional independence was higher in the AFDAS group (37.7% versus 52.5%; P =0.029). Multivariable analysis showed that AFDAS was associated with a favorable functional outcome (odds ratio, 2.67 [95% CI, 1.39-5.14]; P =0.003)., Conclusions: AFDAS demonstrated a positive association with functional independence in patients with stroke who underwent mechanical thrombectomy and were finally diagnosed to have AF during hospitalization. The observed disparities in occlusion site, intractable thrombus, and history of previous stroke may have contributed to these findings.

Background: Atrial fibrillation (AF) is a stroke risk factor that often remains undetected at hospital admission. Long-term Holter monitoring helps to identify patients with previously unrecognized AF. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are elevated in AF in cross-sectional studies. We analyzed ADMA, SDMA, and other L-arginine metabolites to assess their association with AF in the Find-AF trial., Methods and Results: We included 280 patients presenting with acute cerebral ischemia. Patients presenting in sinus rhythm received 7-day Holter-ECG. Biomarkers were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. We also analyzed protein methylation and L-arginine-related metabolites in human induced pluripotent stem cell-derived cardiomyocytes in vitro. ADMA and SDMA were elevated in 44 patients who presented with AF. SDMA, but not ADMA, was significantly elevated in patients newly diagnosed with AF in Holter-ECG as compared with those in sinus rhythm. SDMA plasma concentration >0.571 μmol/L significantly predicted presence of AF in Holter-ECG (area under the curve=0.676 [0.530-0.822]; P =0.029; sensitivity 0.786, specificity 0.572). SDMA levels further increased in patients with AF during the first 24 hours in hospital, and ADMA levels remained stable. In vitro, induced pluripotent stem cell-derived cardiomyocytes showed increased symmetric protein methylation and elevated SDMA during rapid pacing (2.0 Hz versus 0.5 Hz), whereas asymmetric protein methylation and ADMA were unchanged., Conclusions: SDMA at admission was significantly elevated in stroke patients presenting with AF and showed a moderate but significant prospective association with previously unrecognized AF. Thus, stroke patients with elevated SDMA concentration at admission may specifically benefit from extended Holter-ECG monitoring.

Background: Left atrial appendage (LAA) slow-flow may increase the risk of ischemic stroke. We studied LAA attenuation on cardiac computed tomography in patients with acute ischemic stroke., Methods and Results: We used data from a prospective cohort of patients with acute ischemic stroke undergoing cardiac computed tomography during the acute stroke imaging protocol. We compared characteristics, functional outcome (modified Rankin scale: higher scores indicating worse outcome), stroke recurrence and major adverse cardiovascular events after 2-year follow-up between patients with LAA thrombus (filling defect<100 Hounsfield Unit (HU)), slow-flow (filling defect ≥100 HU) and normal filling. Of 421 patients, 31 (7%) had LAA thrombus, 69 (16%) slow-flow, and 321 (76%) normal filling. Patients with thrombus or slow-flow more often had known atrial fibrillation compared with normal filling (45%, 39%, and 9%, P <0.001). Patients with thrombus had higher National Institutes of Health Stroke Scale-scores compared with slow-flow and normal filling (18 [interquartile range, 9-22], 6 [interquartile range, 3-17], and 5 [interquartile range, 2-11], P <0.001). Compared with normal filling, there was no difference with slow-flow in functional outcome (median modified Rankin scale, 3 versus 2; acOR 0.8 [95% CI, 0.5-1.4]), stroke recurrence (adjusted hazard ratio, 0.8 [95% CI, 0.3-1.9]) or major adverse cardiovascular events (adjusted hazard ratio, 1.2 [95% CI, 0.7-2.1]), while patients with thrombus had worse functional outcome (median modified Rankin scale, 6, acOR, 3.3 [95% CI, 1.5-7.4]). In cryptogenic stroke patients (n=156) slow-flow was associated with stroke recurrence (27% versus 6%, aHR, 4.1 [95% CI, 1.1-15.7])., Conclusions: Patients with slow-flow had similar characteristics to patients with thrombus, but had less severe strokes. Slow-flow was not significantly associated with functional outcome or major adverse cardiovascular events, but was associated with recurrent stroke in patients with cryptogenic stroke.

Background: Atrial fibrillation (AF) is a common arrhythmia in patients with congenital heart disease (CHD), but little is known about the risk for ischemic stroke among younger patients with CHD (aged <65 years) with AF., Methods and Results: Using data from the National Swedish Patient Register and Cause of Death Register, we identified all patients with both CHD and AF born in Sweden between 1970 and 2017. The Swedish total population register was used to identify age- and sex-matched patients without CHD; those with AF were used as controls. Bottos hierarchical classification was used to define CHD as either complex or noncomplex. Controls were followed from the onset of AF until the index ischemic stroke, death, or end of study (December 31, 2017). We identified 951 patients with CHD with AF and 606 controls with AF. Among patients with both CHD and AF, 2.9% of patients (n=28) developed ischemic stroke, compared with 0.5% (n=3) in controls. When adjusted for age, sex, hypertension, and heart failure, a hazard ratio (HR) of 5.16 (95% CI, 1.52-17.46) was acquired. The HR in noncomplex CHD was 3.84 (95% CI, 1.07-13.84), and the HR in complex CHD was 8.34 (95% CI, 2.27-30.57). For patients born in 1970 to 1989, the HR in ischemic stroke was 7.35 (95% CI, 1.70-31.75). No adjusted HR for patients with CHD born in 1990 to 2017 could be acquired due to few events., Conclusions: The risk for ischemic stroke may be 5 times higher in patients with both CHD and AF compared with patients without CHD with AF. However, larger studies may be needed to confirm/refute these results.

Background: Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear., Methods and Results: This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients)., Conclusions: Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.

Background: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk., Methods and Results: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation-treated patients with a CHA 2 DS 2 -VASc score≥2, across strata of CHA 2 DS 2 -VASc score, stroke history, and AF type, as either paroxysmal or nonparoxysmal. We included 71 794 patients with AF (median age 72 years, interquartile range, 13 years, 61.3% male) randomized to a direct oral anticoagulant or vitamin K antagonist, and followed for a mean of 2.1 (±0.8) years. The median CHA 2 DS 2 -VASc score was 4 (interquartile range, 3-5), 18.8% had a prior stroke, and 76.4% had nonparoxysmal AF. The overall rate of stroke/SE was 1.33%/y (95% CI, 1.27-1.39); 1.38%/y (95% CI, 1.31-1.45) for nonparoxysmal AF, and 1.15%/y (95% CI, 1.05-1.27) for paroxysmal AF. The rate of ischemic stroke/SE increased by a rate ratio of 1.36 (95% CI, 1.32-1.41) per 1-point increase in CHA 2 DS 2 -VASc, reaching 1.67%/y (95% CI, 1.59-1.75) ≥4 CHA 2 DS 2 -VASc points. Patients with both nonparoxysmal AF and CHA 2 DS 2 -VASc ≥4 had a stroke/SE rate of 1.75%/y (95% CI, 1.66-1.85). In patients with a prior stroke, the risk was 2.51%/y (95% CI, 2.33-2.71)., Conclusions: AF type, CHA 2 DS 2 -VASc score, and stroke history can identify patients with AF, who despite oral anticoagulation have a residual stroke/SE risk of 1.5% to 2.5% per year. Evaluation of additional stroke/SE prevention strategies in high-risk patients is warranted.

Background: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes., Methods and Results: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m 2 , and 50.6±17.2 versus 34.0±15.4 mL/m 2 , respectively, P <0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P =0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P <0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P <0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups., Conclusions: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.

Background: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known., Objectives: The authors sought to determine which antithrombotic regimen best balances safety and efficacy., Methods: AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y 12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint., Results: A total of 4,614 patients were enrolled. All patients were treated with a P2Y 12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death., Conclusions: In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y 12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400)., Competing Interests: Funding Support and Author Disclosures The AUGUSTUS study and this analysis were funded by Bristol Myers Squibb and Pfizer. Dr Berwanger has received research grants from AstraZeneca, Pfizer, Bayer, Amgen, Novartis, Servier, and Boehringer Ingelheim. Dr Fanaroff has received research grants from the American Heart Association and National Institutes of Health; and has received consulting fees from Abbott Laboratories. Dr Granger has received research grants from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Armetheon, AstraZeneca, U.S. Food and Drug Administration, GlaxoSmithKline, The Medicines Company, Medtronic Foundation, Medtronic Inc, and Novartis; and has received consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Abbvie, Armetheon, AstraZeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, LLC, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. Dr Mehran has received institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has received consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences Inc, and Sanofi; has consulted (no fees) for Regeneron Pharmaceuticals Inc; has received institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; is an executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; and has <1% equity in Claret Medical and Elixir Medical. Dr Aronson is an employee of Bristol Myers Squibb. Dr Windecker has received institutional research and educational grants from Abbott, Amgen, Bayer, Bristol Myers Squibb, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. Dr Goodman has received research grant support and/or speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo, Eli Lilly, Esperion, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson and Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, Tenax Therapeutics, Heart and Stroke Foundation of Ontario/University of Toronto, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, and PERFUSE. Dr Alexander has received research grants from Bristol Myers Squibb, Boehringer Ingelheim, AstraZeneca, CryoLife, CSL Behring, U.S. Food and Drug Administration, National Institutes of Health, Sanofi, and VoluMetrix; and has received consulting fees from Pfizer, Bristol Myers Squibb, AbbVie Pharmaceuticals, CSL Behring, Novo Nordisk, Portola Pharmaceuticals, Quantum Genomics, Teikoku Pharmaceuticals, VA Cooperative Studies, and Zafgen. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described., Objectives: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens., Methods: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression., Results: Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y 12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus., Conclusions: In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin., Competing Interests: Funding Support and Author Disclosures This analysis was supported by the Boston Scientific Corporation. Although Boston Scientific had no role in the data collection, development of study questions, or analytic approaches, it paid for the statistical analytical work and manuscript support. No authors were compensated for their work on this study. The views expressed here represent those of the authors, and do not necessarily represent the official views of the American College of Cardiology Foundation’s National Cardiovascular Data Registry or its associated professional societies identified at CVQuality.ACC.org/NCDR. Dr Hsu has received honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Janssen Pharmaceuticals, Bristol Myers Squibb, Pfizer, Sanofi, Zoll Medical, iRhythm, Acutus Medical, Galvanize Therapeutics, and Biosense Webster; has received research grants from Biotronik and Biosense Webster; and has equity in Vektor Medical. Dr Yeh has received research funding and consulting fees from Abbott Vascular, Boston Scientific, and Medtronic; and has received research funding from Bard, Cook, and Philips. Dr Price has received consulting honoraria, speaker fees, and proctoring fees from Abbott Vascular and Boston Scientific; has received consulting honoraria and speaker fees from Medtronic, W.L. Gore, Philips, and Shockwave; and has equity in Indian Wells, Inc. Dr Piccini is supported by grant R01AG074185 from the National Institutes of Aging; receives grants for clinical research from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips; and serves as a consultant to Abbott, Abbvie, ARCA biopharma, Bayer, Boston Scientific, Bristol Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and Up-to-Date. Drs Christen and Allocco are full-time employees and stockholders of Boston Scientific. Dr Freeman has received research funding from the National Institutes of Health/National Heart, Lung, and Blood Institute, and the American College of Cardiology National Cardiovascular Data Registry; has received consulting/advisory board fees from Medtronic, Boston Scientific, Biosense Webster, and PaceMate; and has equity in PaceMate. All other authors have reported that they have no relationships relevant to the contents of this paper., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of stroke. It remains unclear whether the risk of stroke associated with a diagnosis of COVID-19 differed with oral anticoagulation (OAC) use. The aim of this study was to evaluate the association between COVID-19 infection, OAC use, and stroke in patients with atrial fibrillation (AF)., Methods: A retrospective cohort study was conducted in individuals with established AF using data from Optum's deidentified Clinformatics ® Data Mart Database. Cox proportional hazard models with time-dependent variables were employed to assess the association between possession of OAC, COVID-19 diagnosis in both inpatient and outpatient setting, and time to ischemic stroke., Results: A total of 561,758 individuals aged 77 ± 10 were included in the study, with a mean follow up time of 1.3 years. OAC use was associated with a reduced stroke risk [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.82-0.88]. COVID-19 infection was associated with an increased risk of stroke (HR 2.11, 95% CI 1.87-2.38); this increased risk was particularly pronounced for patients diagnosed with an inpatient diagnosis of COVID-19 (HR 3.95, 95% CI 3.33-4.68). There was no significant interaction between OAC use and COVID-19 diagnosis (p value = 0.96). As a result, the relative increase in stroke risk associated with COVID-19 did not differ between patients on OAC (HR 2.12; 95% CI 1.71-2.62) and those not on OAC (HR 2.11; 95% CI 1.83-2.43)., Conclusion: In a nationwide sample of patients with established AF, we found the relative increase in stroke risk associated with COVID-19 was independent of OAC use., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited., (© 2024. The Author(s).)

Many patients with impaired renal function have concurrent indications for anticoagulant therapy, including atrial fibrillation and venous thromboembolism. For mild chronic kidney disease, data from clinical trials and existing guidelines can be applied to clinical management. The benefits and harms of anticoagulation therapy in patients with more advanced renal impairment are nuanced, as both thrombotic and bleeding risk are increased. Until recently, data regarding anticoagulants in severe renal impairment were primarily observational, but emerging evidence includes a few small clinical trials and the emergence of novel agents hypothesized to have improved efficacy and safety in this population. In this review, we summarize existing data on anticoagulation in patients with chronic kidney disease. We suggest a framework for anticoagulation decision-making in the burgeoning worldwide population of patients with chronic kidney disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH., Areas Covered: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future., Expert Opinion: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.

Objective: Atrial fibrillation (AF) is a common arrhythmia in patients at high cardiovascular risk. COVID-19 patients with underlying cardiovascular disease are at increased risk of poor clinical outcomes. In this study, we aimed to determine hospital outcomes among patients admitted with AF and COVID-19 infection., Methods: We conducted a retrospective analysis using the 2020 California State Inpatient data, including all COVID-19 hospitalizations of individuals aged ≥18. Primary outcomes were in-hospital mortality, prolonged length of stay (above the 75th percentile), vasopressor use, mechanical ventilation, and ICU admission. We compared adverse hospital outcomes between those with and without AF and used multivariable logistic regression to adjust for confounders., Results: This analysis included 94,114 COVID-19 hospitalizations, of which 9391 (10.0%) had AF. Patients with COVID-19 and AF had higher rates of adverse outcomes, including mortality (27.2% vs. 9.6%, p  < .001), prolonged length of stay (40.0% vs. 27.1%, p  < .001), vasopressor use (4.4% vs. 1.9%, p  < .001), mechanical ventilation (19.0% vs. 9.1%, p  < .001), and ICU admission (18.4% vs. 8.8%, p  < .001) After multivariable adjustment, the odds of adverse outcomes remained significantly higher, including mortality adjusted odds ratio [OR], 2.04, 95% CI: 1.92-2.16), prolonged length of stay (aOR, 1.37, 95% CI: 1.31-1.44), vasopressor use (aOR, 1.98, 95% CI: 1.86-2.11), mechanical ventilation (aOR, 1.95, 95% CI: 1.72-2.20), and ICU admission (aOR, 2.01, 95% CI: 1.88-2.15)., Conclusion: COVID-19 hospitalized patients frequently have underlying AF, which confers a higher risk of adverse hospital outcomes and mortality, even after adjusting for baseline comorbidities. Heightened awareness is needed in the treatment of hospitalized COVID-19 patients with AF.

Introduction: Variations in the left atrial appendage (LAA) morphology are associated with different embolic risk in patients with atrial fibrillation (AF). Data are scarce regarding the association between LAA morphology and Embolic stroke of undetermined source (ESUS)., Patients and Methods: Using cardiac computed tomography (CCT) scans, LAA morphology was categorized as either chicken wing (CW), cactus, windsock, or cauliflower. Furthermore, we examined the presence of large secondary lobes arising from the main lobe, considering their existence as indicative of a complex LAA morphology. LAA morphologies were compared between ESUS ( n  = 134) and AF patients ( n  = 120); and between ESUS patients with ( n  = 24) and without ( n  = 110) subsequent AF diagnosis during long-term follow-up., Results: ESUS patients had a significantly higher prevalence of cauliflower morphology compared to AF group (52% vs 34%, respectively, p  = 0.01); however, no significant difference was found between the groups when categorizing LAA morphology to either CW or non-CW. ESUS patients had significantly higher prevalence of large secondary lobes compared with AF patients (50% vs 29%, respectively, p  = 0.001). When comparing ESUS patients with and without AF diagnosis during follow-up (20-48 months of follow-up, median 31 months), there were no significant differences in the prevalence of the "classical" morphologies, but large secondary lobes were significantly more prevalent among those without subsequent AF diagnosis., Conclusion: ESUS patients have a high prevalence of complex LAA morphology, which might be associated with an increased risk for thrombus formation even in the absence of AF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To assess the association between new-onset atrial fibrillation and dementia among patients with type 2 diabetes, a group with a high prevalence of atrial fibrillation., Materials and Methods: This cohort study included 22 989 patients with type 2 diabetes from the UK Biobank. New-onset atrial fibrillation was ascertained from hospital admission records. We used an algorithm officially released by the UK Biobank to identify all-cause dementia, Alzheimer's disease and vascular dementia. The algorithm was developed using multiple sources, including hospital admissions and the death registry. Time-varying Cox regression analyses were performed to investigate the association between new-onset atrial fibrillation and dementia., Results: A total of 2843 participants developed atrial fibrillation, whereas the remaining 20 146 did not. During the median of 12.3 years of follow-up, 844 all-cause dementia, 342 Alzheimer's disease and 246 vascular dementia cases occurred. Compared with participants without atrial fibrillation, those with atrial fibrillation had higher risks of all-cause dementia (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.80-2.57), Alzheimer's disease (HR 1.44, 95% CI 1.06-1.96) and vascular dementia (HR 3.11, 95% CI 2.32-4.17)., Conclusions: New-onset atrial fibrillation was associated with a substantially higher risk of all-cause dementia, Alzheimer's disease and vascular dementia in patients with type 2 diabetes. Our findings highlight the significance of atrial fibrillation management in mitigating the risk of dementia in this demographic., (© 2024 John Wiley & Sons Ltd.)

While advanced liver disease was previously considered to be an acquired bleeding disorder, there is increasing recognition of an associated prothrombotic state with patients being at higher risk of atrial fibrillation (AF) and stroke and venous thromboembolism (VTE) including portal vein thrombosis (PVT). We review the available literature on epidemiology, pathophysiology, and risk factors and provide guidance on anticoagulant management of these conditions in adults with cirrhosis. In patients with Child-Pugh A or B cirrhosis and AF, we recommend anticoagulation with standard-dose direct oral anticoagulants (DOACs) in accordance with cardiology guideline recommendations for patients without liver disease. In those with Child-Pugh C cirrhosis, there is inadequate evidence with respect to the benefit and risk of anticoagulation for stroke prevention in AF. In patients with cirrhosis and acute deep vein thrombosis or pulmonary embolism, we recommend anticoagulation and suggest use of either a DOAC or low-molecular-weight heparin (LMWH)/vitamin K antagonist (VKA) in Child-Pugh A or B cirrhosis and LMWH alone (or as a bridge to VKA in patients with a normal baseline international normalized ratio) in Child-Pugh C cirrhosis. We recommend anticoagulation for patients with cirrhosis and symptomatic PVT. We suggest anticoagulation for those with asymptomatic, progressing PVT and recommend continuing extended anticoagulation for liver transplant candidates with PVT., Competing Interests: Declaration of competing interests S.C. has received speaker or advisory board fees from AstraZeneca, BMS/Pfizer, Fresenius Kabi, Leo Pharma, and Servier. A.C. has served as a consultant for MingSight Pharmaceuticals, the New York Blood Center, Sanofi, and Synergy, and has received authorship royalties from UpToDate. A.G. has received travel/conference awards from Octapharma and CSL Behring. N.G. has received consulting fees or travel awards from Bayer, Bristol-Myers Squibb/Pfizer, LEO Pharma, and Diagnostica Stago. V.H.G. has received speaker fees from Cook Medical and Gore Medical. K.M. has received speaker fees from Alexion, Bayer, and CSL Behring; fees for participation in trial steering committees for Bayer and AstraZeneca; consulting fees from uniQure and Therini, and fees for participation in data monitoring and endpoint adjudication committee for Octapharma. D.M.S. has received honoraria paid indirectly to her research institute from AstraZeneca, BMS-Pfizer, Roche, and Servier for educational presentations. D.M.S. is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease. L.R. has received speaker or advisory fees from Chugai and Hemab. S.S. and T.L. have no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Congestive heart failure (CHF) as a risk of stroke in patients with atrial fibrillation (AF) mainly referred to patients with left ventricular systolic dysfunction. Whether this should include patients with preserved ejection fraction is debatable., Objective: The study aimed to investigate the variation in stroke risk of AF patients with heart failure with preserved ejection fraction (HFpEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF) for enhancing risk assessment and subsequent management strategies., Methods: In a longitudinal study using the National Taiwan University Hospital integrated Medical Database, 8358 patients with AF were observed for 10 years (mean follow-up, 3.76 years). The study evaluated the risk of ischemic stroke in patients with differing ejection fractions and CHA 2 DS 2 -VASc score, further using Cox models adjusted for risk factors of AF-related stroke., Results: Patients with HFpEF and HFmrEF had a higher mean CHA 2 DS 2 -VASc score compared with patients with HFrEF (4.30 ± 1.729 vs 4.15 ± 1.736 vs 3.73 ± 1.712; P < .001) and higher risk of stroke during follow-up (hazard ratio [HR], 1.40 [1.161-1.688; P < .001] for HFmrEF; HR, 1.184 [1.075-1.303; P = .001] for HFpEF vs no CHF) after multivariate adjustment). In patients with lower CHA 2 DS 2 -VASc score (0-4), presence of any type of CHF increased ischemic stroke risk (HFrEF HR, 1.568 [1.189-2.068; P = .001]; HFmrEF HR, 1.890 [1.372-2.603; P < .001]; HFpEF HR, 1.800 [1.526-2.123; P < .001] vs no CHF)., Conclusion: After multivariate adjustment, HFpEF and HFmrEF showed a similar risk of stroke in AF patients. Therefore, it is important to extend the criteria for C in the CHA 2 DS 2 -VASc score to include patients with HFpEF and HFmrEF. In patients with fewer concomitant stroke risk factors, the presence of any subtype of CHF increases risk for ischemic stroke., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Various treatment approaches for atrial fibrillation (AF) have demonstrated improved health status, yet the significance of these therapeutic interventions in individual patients remains unclear., Objective: This study aimed to evaluate health status changes in patients with early AF, focusing on those who experience clinically significant deterioration after treatment initiation., Methods: We analyzed data from a multicenter, prospective registry of newly diagnosed patients with AF. One-year changes in health status across different treatment strategies were assessed by the Atrial Fibrillation Effect on QualiTy-of-life Overall Summary (AFEQT-OS) score. Clinically relevant deterioration and improvement in health status were defined as ≥5-point decrease and increase in AFEQT-OS score, respectively; no change was -5 to 5 points., Results: Overall, 1960 patients with AF were evaluated. Mean AFEQT-OS scores at baseline and 1-year follow-up were 76.7 ± 17.7 and 85.4 ± 14.8, respectively. Although most patients (53.9%) experienced clinically important improvement, a considerable proportion had no change (28.7%) or deterioration (17.4%) in their health status. Proportions of patients with no change or deterioration varied by treatment strategy: 59.9%, 53.9%, and 32.0% in rate control, antiarrhythmic drug, and catheter ablation groups, respectively. The multivariable model identified older age, female sex, heart failure, coronary artery disease, and higher baseline AFEQT-OS score as independent predictors of worsening health status, regardless of treatment strategy., Conclusion: Many patients with early AF experience worsening or no change in health status irrespective of treatment strategy. Standardizing patients' health status assessment, especially for patients with comorbidities, may aid in patients' selection and their outcomes., Competing Interests: Disclosures Dr Ikemura received an unrestricted research grant from the Department of Cardiology, Keio University School of Medicine, Bristol-Myers Squibb, Japan. Dr Kohsaka received an unrestricted research grant from the Department of Cardiology at Keio University School of Medicine from Bayer Pharmaceutical and Daiichi Sankyo, grants from Bayer Yakuhin, Ltd and Daiichi Sankyo, and personal fees from Bristol-Myers Squibb. Dr Kimura received grants from Bayer Yakuhin Ltd. Dr Takatsuki received grants and personal fees from Bayer and personal fees from Daiichi Sankyo. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Disclosures The authors have no relevant conflicts to declare.

Background: Atrial fibrillation (AF) is associated with the development of dementia, and observational studies have shown that oral anticoagulation and catheter ablation reduce dementia risk. However, such studies did not consistently report on periprocedural anticoagulation and long-term oral anticoagulation coverage, for which reason the separate effect of AF ablation on dementia risk could not be established., Objective: We evaluated the protective effect of AF ablation in a large cohort of patients who received optimized anticoagulation and compared them with patients who were managed medically., Methods: We retrospectively included 5912 consecutive patients who underwent first-time catheter ablation for AF between 2008 and 2018 and compared them with 52,681 control individuals from the Swedish Patient Register. Propensity score matching produced 2 cohorts of equal size (n = 3940) with similar baseline characteristics. Dementia diagnosis was identified by International Classification of Diseases codes from the patient register., Results: Most propensity score-matched patients were taking an oral anticoagulant at the start (94.5%) and end (75.0%) of the study. Mean follow-up was 4.9 ± 2.8 years. Catheter ablation was associated with lower risk for the dementia diagnosis compared with the control group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.86; P = .017). The result was similar when including patients with a stroke diagnosis before inclusion (HR, 0.50; 95% CI, 0.28-0.89; P = .019) and after adjustment for the competing risk of death (HR, 0.41; 95% CI, 0.20-0.86; P = .018)., Conclusion: Catheter ablation of AF in patients with optimized oral anticoagulation therapy was associated with a reduction in dementia diagnosis, even after adjustment for potential confounders and for competing risk of death., Competing Interests: Disclosures Nikola Drca and Astrid Paul-Nordin have received speaker fees from Johnson & Johnson. Finn Åkerström is a consultant for Johnson & Johnson and Abbott. Mats Jensen-Urstad is a consultant for Johnson & Johnson and Medtronic and has received research grants from Medtronic. Frieder Braunschweig is a consultant for Medtronic and Biotronik and has received speaker fees from Biosense Webster, Biotronik, Boston Scientific, Abbott, Pfizer, Novartis, Amgen, and Orion. For the remaining authors, no conflicts of interest are declared., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The epidemiology of atrial fibrillation (AF)-associated thromboembolic complications outside of ischemic strokes has not been thoroughly elucidated., Objective: The aim of this study was to describe the epidemiology of AF-associated systemic infarcts and relevant interactions by sex and race/ethnicity., Methods: Using the Office of Statewide Health Planning and Development, we performed a longitudinal analysis of patients aged ≥18 years who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2015. We determined the distribution of infarct locations and risks of systemic infarcts for patients with AF. Interaction analyses by sex and race/ethnicity were conducted., Results: Of 1,321,694 patients with AF, the average annual rate of systemic infarct was 2.1% ± 0.18% compared with 0.56% ± 0.06% in the 22,944,488 patients without AF. The increased frequency of these infarcts was observed for every body area investigated. After adjustment for potential confounders and mediators, patients with AF experienced a 45% increased risk of a systemic infarct (hazard ratio, 1.45; 95% confidence interval, 1.44-1.47; P < .001). Women, Asians, Blacks, and Hispanics each exhibited a statistically significant heightened relative risk of systemic infarcts in the presence of AF., Conclusion: AF increases the risk of infarcts throughout the body. Susceptibility to these systemic infarcts varies by sex and race/ethnicity in patterns similar to differential risks for stroke. The presence of a systemic infarct in the absence of a clear cause should raise suspicion for AF, and the potential benefits of AF prevention and anticoagulation should be considered beyond only infarcts to the brain., Competing Interests: Disclosures Dr Marcus receives research funding from the National Institutes of Health and PCORI and is a consultant for and holds equity in InCarda. The remaining authors have nothing to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients., Methods: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications., Results: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54-1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22-0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms., Conclusions: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management., Competing Interests: Declaration of competing interest Y. Sotomi has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan, and NIPRO, and personal fees from Abiomed, Abbott Medical Japan, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Boston Scientific Japan, Bayer, Daiichi Sankyo, Eli Lilly, Novartis, TERUMO, Medtronic, and Pfizer Pharmaceuticals. S. Hikoso has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, Actelion Pharmaceuticals; and personal fees from AstraZeneca, Daiichi Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company, and Ono Pharmaceutical. D. Nakatani has received personal fees from Roche Diagnostics. T. Dohi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study. A. Sunaga has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study and personal fees from Bayer, Daiichi Sankyo, and Medtronic, outside the submitted work. M. Masuda has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Boston Scientific, Abbott, Nihon Kohden, Otsuka Pharmaceutical, AstraZeneca, and Medtronic, outside the submitted work. T. Watanabe has received personal fees from Biosense Webster, Abbott, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Nihon Kohden, and Fukuda Denshi, outside the submitted work. H. Minamiguchi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study, and personal fees from Medtronic, Abbott, Johnson & Johnson, Nihon Kohden, Biotronik, Japan Lifeline, Daiichi Sankyo, Bayer, Pfizer, Squibb, Boehringer Ingelheim, Kowa, Ono Pharmaceutical, and Otsuka Pharmaceutical, outside the submitted work. Y. Egami has received personal fees from Japan Lifeline and Medtronic, and non-financial support from Johnson & Johnson, Abbott, and Medtronic, outside the submitted work; T. Oka has received personal fees from Medtronic, Biotronik, Abbott, Daiichi Sankyo, Beyer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, and AstraZeneca, outside the submitted work. Y. Matsuda has received personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Medtronic, Boston Scientific Japan, Japan Lifeline, Asahi Kasei ZOLL Medical, Synaptic Medical Japan and Biotronik, outside the submitted work. M. Kawasaki has received personal fees from Medtronic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Bristol-Myers Squibb, and Abbott, and grants from Osaka Heart Club, outside the submitted work. K. Inoue has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Medtronic, outside the submitted work. Y. Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K. and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Co, Biosense Webster, Inc., Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. Other authors have nothing to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Background:  We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk., Methods:  This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies., Results:  The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 ( n  = 427) and 93.3 ± 57.8 ng/mL ( n  = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 ( n  = 79; 12.4 ± 12.1 and n  = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group ( n  = 83; 25.1 ± 36.6 and n  = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study ( n  = 39; 18.4 ± 11.2 and n  = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not., Conclusion:  PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight., Competing Interests: T.Y. received personal fees from Daiichi Sankyo Co., Ltd. during the conduct of the study; grants and personal fees from Daiichi Sankyo Co., Ltd., Bayer Yakuhin, Ltd., and Bristol Myers Squibb K.K.; personal fees from Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Toa Eiyo Ltd., Novartis Pharma K.K., and Otsuka Pharmaceutical Co., Ltd. outside the submitted work. Y.I., M.F., and T.H. are employees of Daiichi Sankyo Co., Ltd. S.H. is an employee of Certara, Inc. K.O. received grants and personal fees from Daiichi Sankyo Co., Ltd. during the conduct of the study; personal fees from Daiichi Sankyo Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., Medtronic Japan Co., Ltd., Johnson and Johnson K.K., and Bayer Yakuhin, Ltd. outside the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Artificial intelligence (AI)-enabled sinus rhythm (SR) electrocardiogram (ECG) interpretation can aid in identifying undiagnosed paroxysmal atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS)., Objective: The purpose of this study was to assess the efficacy of an AI model in identifying AF based on SR ECGs in patients with ESUS., Methods: A transformer-based vision AI model was developed using 737,815 SR ECGs from patients with and without AF to detect current paroxysmal AF or predict the future development of AF within a 2-year period. Probability of AF was calculated from baseline SR ECGs using this algorithm. Its diagnostic performance was further tested in a cohort of 352 ESUS patients from 4 tertiary hospitals, all of whom were monitored using an insertable cardiac monitor (ICM) for AF surveillance., Results: Over 25.1-month follow-up, AF episodes lasting ≥1 hour were identified in 58 patients (14.4%) using ICMs. In the receiver operating curve (ROC) analysis, the area under the curve for the AI algorithm to identify AF ≥1 hour was 0.806, which improved to 0.880 after integrating the clinical parameters into the model. The AI algorithm exhibited greater accuracy in identifying longer AF episodes (ROC for AF ≥12 hours: 0.837, for AF ≥24 hours: 0.879) and a temporal trend indicating that the AI-based AF risk score increased as the ECG recording approached the AF onset (P for trend <.0001)., Conclusions: Our AI model demonstrated excellent diagnostic performance in predicting AF in patients with ESUS, potentially enhancing patient prognosis through timely intervention and secondary prevention of ischemic stroke in ESUS cohorts., Competing Interests: Disclosures Dr Joonghee Kim developed the algorithm and founded a start-up company ARPI Inc. He is the CEO of the company. Dr Youngjin Cho works for the company as a research director. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Healey has received an unrestricted grant for the conduct of the ARTESIA trial from BMS/Pfizer and Medtronic and a grant for the LAAOS4 trial from Boston Scientific. He has served on the scientific advisory board of Boston Scientific. He has received speaking fees for presentations from BMS/Pfizer, Servier, Novartis, and Boston Scientific. He has served as an expert witness for Bayer. He has served as a data and safety monitoring board member for the PRAETORIAN DFT trial of Boston Scientific.

Introduction and Objectives: Hospitalization for heart failure (HHF) is common in patients with atrial fibrillation (AF) and is associated with increased mortality. The aims of this study were to determine the incidence of HHF, identify the clinical predictors of its occurrence, and develop a new risk scale., Methods: The incidence of HHF was estimated using data from the prospective single-center REFLEJA registry of outpatients with AF (October 2017-October 2018). A multivariate Cox regression model was calculated to detect HHF predictors, and a nomogram was created for individual risk assessment., Results: Of the 1499 patients included (mean age 73.8±11.1 years, 48.1% women), 127 had HHF (incidence rate of 8.51 per 100 persons/y) and 319 died (rate of death from any cause of 21.1 per 100 persons/y) after a 3-year follow-up. The independent predictors of HHF were age, diabetes, chronic kidney disease, pulmonary hypertension, previous pacemaker implantation, baseline use of diuretics, and moderate-severe aortic regurgitation. The c-statistic for predicting the event was 0.762 (95%CI after boostrapping resampling, 0.753-0.791). The cumulative incidences of the main outcome for the risk scale quartiles were 1.613 (Q1), 3.815 (Q2), 8.378 (Q3), and 20.436 (Q4) cases per 100 persons/y (P <.001)., Conclusions: HHF was common in this AF cohort. The combination of certain clinical characteristics can identify patients with a very high risk of HHF., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The benefit of catheter ablation for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain., Objective: We performed a systematic review and meta-analysis to compare catheter ablation and medical therapy (antiarrhythmics for rhythm or rate control) in patients with AF and HFpEF., Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials. Outcomes were the composite end points of death or heart failure (HF) hospitalization, all-cause death, cardiovascular death, all-cause rehospitalization, and HF hospitalization. Statistical analysis was performed using R statistical software, version 4.3.2 (R Foundation for Statistical Computing). Heterogeneity was assessed with I 2 statistics., Results: We included 20,257 patients from 8 studies. Of those, 3 were derived from RCTs, either through post hoc analysis or subgroup analysis, and 5 were observational studies. The median follow-up ranged from 24.6 to 61.2 months. Compared with medical therapy, catheter ablation was associated with a statistically significant lower risk of death or HF hospitalization (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.47-0.83; P = .001; I 2 = 66%), all-cause death (HR 0.68; 95% CI 0.46-0.99; P = .047; I 2 = 61%), cardiovascular death (HR 0.42; 95% CI 0.21-0.84; P = .014; I 2 = 22%), and HF hospitalization (HR 0.43; 95% CI 0.23-0.82; P = .011; I 2 = 87%)., Conclusion: In this meta-analysis, catheter ablation was associated with a lower risk of all-cause death, cardiovascular death, HF hospitalization, and all-cause rehospitalization in comparison to medical therapy in patients with AF and HFpEF., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The optimal treatment of atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF) remains unsettled., Objective: The purpose of this study was to assess the efficacy of catheter ablation (CA) and medical therapy compared to medical therapy alone in patients with AF and HFrEF., Methods: We performed a systematic review of randomized controlled trials (RCTs) comparing CA with guideline-directed medical therapy for AF in patients with HFrEF (left ventricular ejection fraction [LVEF] ≤ 40%). We systematically searched PubMed, Embase, and Cochrane for eligible trials. A random effects model was used to calculate the risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs)., Results: Six RCTs comprising 1055 patients were included, of whom 530 (50.2%) were randomized to CA. Compared with medical therapy, CA was associated with a significant reduction in heart failure (HF) hospitalization (RR 0.57; 95% CI 0.45-0.72; P < .01), cardiovascular mortality (RR 0.46; 95% CI 0.31-0.70; P < .01), all-cause mortality (RR 0.53; 95% CI 0.36-0.78; P < .01), and AF burden (MD -29.8%; 95% CI -43.73% to -15.90%; P < .01). Also, there was a significant improvement in LVEF (MD 3.8%; 95% CI 1.6%-6.0%; P < .01) and quality of life (Minnesota Living with Heart Failure Questionnaire; MD -4.92 points; 95% CI -8.61 to -1.22 points; P < .01) in the ablation group., Conclusion: In this meta-analysis of RCTs of patients with AF and HFrEF, CA was associated with a reduction in HF hospitalization, cardiovascular mortality, and all-cause mortality as well as a significant improvement in LVEF and quality of life., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether advances in management of acute coronary syndrome (ACS) and introduction of novel oral anticoagulants have changed outcomes in patients with ACS with concomitant atrial fibrillation (AF)., Objective: This study aimed to examine the incidence of AF in patients admitted for ACS and to evaluate its association with adverse outcomes, given the recent advances in management of both diseases., Methods: Natural language processing search algorithms identified AF in patients admitted with ACS across 13 Northwell Health Hospitals from 2015 to 2021. Hierarchical generalized linear mixed modeling was used to assess the association between AF and in-hospital mortality, bleeding, and stroke outcomes; marginal Cox regression modeling was used to assess the association between AF and postdischarge mortality., Results: Of 12,315 patients admitted for ACS, 3018 (24.5%) had AF with 1609 (53.3%) newly diagnosed. AF patients more commonly received anticoagulation with an oral anticoagulant (80.4% vs 12.3%) or heparin (61.9% vs 56.9%), had lengthier intensive care unit stay (72 vs 49 hours), and underwent fewer percutaneous coronary interventions (31.9% vs 53.1%). In-hospital bleeding, stroke, and mortality were higher in the AF group (15.3% vs 5.0%, 7.4% vs 2.4%, and 6.9% vs 2.1%, respectively). AF was an independent risk factor for all in-hospital outcomes (odds ratios of 2.5, 2.7, and 2.0 for bleeding, stroke, and mortality, respectively) as well as for postdischarge mortality (hazard ratio, 1.3; 95% CI, 1.2-1.5)., Conclusion: AF is present in 25% of ACS patients and increases risk of in-hospital and postdischarge adverse outcomes. Additional data are required to direct optimal management., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous left atrial appendage closure (LAAC) is an effective alternative strategy for stroke prevention in patients with atrial fibrillation (AF) at high risk for bleeding with anticoagulation (AC). Efficacy of this strategy in hypertrophic cardiomyopathy (HCM) remains uncertain., Objective: The study aimed to compare risk of stroke in HCM-AF patients treated with LAAC with those treated with AC., Methods: By use of the TriNetX Global Research Network, HCM-AF patients from 2015 to 2024 were assigned to categories of treatment with LAAC and treatment solely with AC and observed for 3 years for ischemic stroke, systemic embolism, and all-cause mortality. Propensity score matching was used to limit confounders., Results: Of 14,867 HCM-AF patients identified, 364 (2.5%) were treated with LAAC vs 14,503 (97.5%) treated with AC. HCM LAAC patients were older (72 vs 67 years; P < .001) and had more comorbidities and more prior bleeding events, including higher rate of prior gastrointestinal bleeding (68% vs 18%; P < .001), compared with HCM patients treated solely with AC. After propensity score matching, there was no baseline difference between groups including prior bleeding events (P > .05). During follow-up, HCM patients treated with LAAC had higher rates of ischemic stroke (13% vs 8%; hazard ratio, 1.9; P = .006) and systemic embolism (14% vs 9%; hazard ratio, 1.8; P = .006) but no difference in mortality compared with matched HCM patients receiving AC., Conclusion: These real-world data do not support percutaneous LAAC in HCM-AF patients as the primary treatment strategy during long-term AC to reduce stroke risk. However, LAAC may remain a reasonable option for HCM-AF patients who are unable to tolerate AC because of prohibitive bleeding risk., Competing Interests: Disclosures Martin S. Maron: consultant for Cytokinetics, iRhythm (with grant), Imbria Pharmaceuticals, Takeda Pharmaceuticals (with grant). Ethan J. Rowin: research funding from Pfizer, iRhythm. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking., Objective: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF., Methods: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded., Results: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model., Conclusion: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA 2 DS 2 -VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)