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Andrea Zimmer,1 Michael Coslovsky,2 Ivo Abraham,3 Bernhard F Décard1 1Neurologic Clinic and Policlinic, Department of Medicine, University Hospital Basel, University of Basel, Basel, 2Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland; 3Center for Health Outcomes and Pharmacoeconomic Research, University of Arizona, Tuscon, AZ, USA Objectives: Adherence to multiple sclerosis (MS) treatment is essential to optimize the likelihood of full treatment effect. This prospective, observational, single-center cohort study investigated adherence to fingolimod over the 2 years following treatment initiation. Two facets of adherence – implementation and persistence – were examined and compared between new and experienced users of disease-modifying treatments (DMTs). Materials and methods: Implementation rates were based on the proportion of days covered and calculated as percentages per half-yearly visits and over 2 years, captured through refill data, pill count, and self-report. Nonadherence was defined as taking less than 85.8% of prescribed pills. Implementation rates were classified as nonadherent (

BackgroundKnowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly.AimTo evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients.MethodsNinety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL.ResultsQuality of life strongly correlated with symptom severity (r = 0.610, P

Background and purpose: The aim was to assess the feasibility and safety of fast‐track hospitalizations in a selected cohort of patients with stroke. Methods: Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion‐weighted imaging were included. Neurological deficits of the included patients were non‐disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared – fast‐track hospitalizations (≤72 h) and long‐term hospitalizations (>72 h). The primary end‐point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3–6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW). Results: Amongst the 521 patients who met the inclusion criteria, fast‐track hospitalizations were performed in 79 patients (15%). In the fast‐track group, seven patients (8.9%) met the primary end‐point, compared to 37 (8.4%) in the long‐term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42–2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end‐point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51–3.16, P = 0.61). The costs of fast‐track hospitalizations were lower, on average, by $4994. Conclusions: Fast‐track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long‐term hospitalizations. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of biomarkers in diagnosing pulmonary hypertension (PH) and distinguishing between pre- and post-capillary PH remains poorly understood. We aimed to identify biomarkers with a strong association with mean pulmonary arterial pressure, mPAP (PH diagnosis) and pulmonary vascular resistance, PVR (pre-capillary component), but not with pulmonary arterial wedge pressure, PAWP (post-capillary component)., Methods: Blood samples were collected in patients undergoing right heart catheterization within a prospective cross-sectional study. Biomarkers measured included BMP10, NT-proBNP, ANG2, ESM1/endocan, FGF23, GDF15, IGFBP7, IL6, MyBPC3, proC3, and proC6/endotrophin. Primary outcomes were mPAP, PVR, and PAWP, while secondary outcomes included PH diagnosis (mPAP > 20 mmHg) and elevated PVR (> 2 Wood units). Multivariable linear and logistic regression models were used to assess the relationship between biomarkers and outcomes., Results: Of the 127 patients included (age 66 ± 13 years, 54% female), 73% were diagnosed with PH. BMP10, NT-proBNP, ANG2, MyBPC3, and FGF23 showed a strong association with mPAP (p < 0.001). BMP10 and NT-proBNP were strongly associated with PVR (p < 0.001), while NT-proBNP and ANG2 were strongly associated with PAWP (p < 0.001). NT-proBNP had the strongest association with the diagnosis of PH (area under the curve = 0.76). BMP10 was the only biomarker associated with elevated PVR (OR 1.60, 95%CI 1.01-2.54, p = 0.04) but not with PAWP (p = 0.86)., Conclusions: Several biomarkers were strongly associated with mPAP, PAWP, and PVR. BMP10 was the only biomarker strongly associated with mPAP and PVR, but not with PAWP, thus reflecting the pre-capillary PH component. Measurement of BMP10 along with NT-proBNP may aid in diagnosing PH., (© 2024. The Author(s).)

Background: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system., Objective: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients., Methods: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism., Results: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint., Conclusion: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients., Competing Interests: Disclosures Dr Beer reports grants from the Swiss National Foundation of Science, The Swiss Heart Foundation, and Bayer; and lecture fees from Sanofi Aventis and Amgen, to the institution outside the submitted work. Dr Blum has received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, all for work outside the submitted study. Dr Bonati has received an unrestricted research grant from AstraZeneca; consultancy or advisory board fees or speaker honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical; and travel grants from AstraZeneca and Bayer, outside the submitted work. Dr Conen received consultancy fees from Roche Diagnostics and Trimedics; and speaker fees from Servier and BMS/Pfizer, outside the submitted work. Dr Kühne received personal fees from Daiichi Sankyo and grants from the Swiss National Science Foundation, Swiss Heart Foundation, Foundation for CardioVascular Research Basel, Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo, outside the submitted work. Dr Krisai has speaker fees from BMS/Pfizer, outside the submitted work. Dr Müller reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, Zoll, and Bristol Myers Squibb; consultant fees from Biosense Webster, Medtronic, Abbott/St. Jude Medical, and Biotronik, outside the submitted work. Dr Moschovitis has received advisory board and/or speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis, and Vifor, outside the submitted work. Dr Osswald received research grants from the Swiss National Science Foundation and Swiss Heart Foundation, Foundation for CardioVascular Research Basel, and F. Hoffmann-La Roche Ltd.; and educational and speaker grants from F. Hoffmann-La Roche Ltd., Bayer, Novartis, Sanofi, AstraZeneca, Daiichi-Sankyo, and Pfizer, outside the submitted work. Dr Reichlin has recieved research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support funds; speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Farapulse, Medtronic, Pfizer-,BMS and Roche; and support for his institution’s fellowship program from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific, and Medtronic for work, outside the submitted study. Dr Zuern has received funding from the “Freiwillige Akademische Gesellschaft Basel”; and personal fees from Cardiomatics, outside the submitted work. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment., Methods: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment., Results: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained., Conclusions: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial., Competing Interests: Competing interests: JHB reports grant support from the Swiss National Foundation of Science, The Swiss Heart Foundation and the Stiftung Kardio; grant support, speakers and consultation fees to the institution from Bayer, Sanofi and Daichii Sankyo. EB reports grants from Swiss Cancer Research Foundation, Amgen, MSD, Novartis, Vifor, all outside the submitted work. MB is supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. LB reports personal fees and non-financial support from Amgen, grants from AstraZeneca, personal fees and non-financial support from Bayer, personal fees from Bristol-Myers Squibb, personal fees from Claret Medical, grants from Swiss National Science Foundation, grants from University of Basel, grants from Swiss Heart Foundation, outside the submitted work. DC received consulting fees from Roche Diagnostics, and speaker fees from Servier and BMS/Pfizer, all outside of the current work. MK reports grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik, grants and personal fees from Daiichi Sankyo. GM has received advisory board and/or speaker’s fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis and Vifor, all outside of the submitted study. AM reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, and consultant honoraria for Biosense Webster, Medtronic, Abbott/St. Jude Medcal and Biotronik. SO received research grants from the Swiss National Science Foundation and from the Swiss Heart Foundation, research grants from Foundation for CardioVascular Research Basel, research grants from Roche, educational and speaker office grants from Roche, Bayer, Novartis, Sanofi AstraZeneca, Daiichi-Sankyo and Pfizer. TR has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support fund, all for work outside the submitted study. Speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Medtronic, Pfizer-BMS and Roche, all for work outside the submitted study. Support for his institution’s fellowship programme from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific and Medtronic for work outside the submitted study. MS reports grants from Swiss National Science Foundation, for the conduct of the study; grants from Amgen, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, grants and personal fees from BMS and personal fees from Sandoz, all outside the submitted work. MS-B reports grants from the European Commission outside of the present work. CS has received speaker honoraria from Biosense Webster and Medtronic and research grants from Biosense Webster, Daiichi-Sankyo and Medtronic. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF., Methods: We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system., Results: Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed., Conclusions: Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background Optimizing health-related quality of life (HRQoL) is an important aim of atrial fibrillation (AF) treatment. Little is known about patients' long-term HRQoL trajectories and the impact of patient and disease characteristics. The aim of this study was to describe HRQoL trajectories in an observational AF study population and in clusters of patients with similar patient and disease characteristics. Methods and Results We used 5-year follow-up data from the Swiss-Atrial Fibrillation prospective cohort, which enrolled 2415 patients with prevalent AF from 2014 to 2017. HRQoL data, collected yearly, comprised EuroQoL-5 dimension utilities and EuroQoL visual analog scale scores. Patient clusters with similar characteristics at enrollment were identified using hierarchical clustering. HRQoL trajectories were analyzed descriptively and with inverse probability-weighted regressions. Effects of postbaseline clinical events were additionally assessed using time-shifted event variables. Among 2412 (99.9%) patients with available baseline HRQoL, 3 clusters of patients with AF were identified, which we characterized as follows: "cardiovascular dominated," "isolated symptomatic," and "severely morbid without cardiovascular disease." Utilities and EuroQoL visual analog scale scores remained stable over time for the full population and the clusters; isolated symptomatic patients showed higher levels of HRQoL. Utilities were reduced after occurrences of stroke, hospitalization for heart failure, and bleeding, by -0.12 (95% CI, -0.18 to -0.06), -0.10 (95% CI, -0.13 to -0.08), and -0.06 (95% CI, -0.08 to -0.04), respectively, on a 0 to 1 utility scale. Utility of surviving patients returned to preevent levels 4 years after heart failure hospitalization; 3 years after bleeding; and 1 year after stroke. Conclusions In patients with prevalent AF, HRQoL was stable over time, irrespective of baseline patient characteristics. Clinical events of hospitalization for heart failure, stroke, and bleeding had only a temporary effect on HRQoL.

Background: An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking., Aims: To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients., Methods: Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education., Results: Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83-1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82-1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI = 0.66-1.80). There was no association between LDL levels and CMB progression (adjOR 1.02, 95% CI = 0.79-1.32). At follow-up 14 (1.2%) statin users had ICH versus 16 (1.3%) non-users. The age and sex adjusted hazard ratio (adjHR) was 0.75 (95% CI = 0.36-1.55). The results remained robust in sensitivity analyses excluding participants without anticoagulants., Conclusions: In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.

Background Previous randomized control trials showed mixed results concerning the effect of omega-3 fatty acids (n-3 FAs) on atrial fibrillation (AF). The associations of n-3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n-3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF. Methods and Results Total n-3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS-AF (Swiss Atrial Fibrillation cohort). Individual and total n-3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n-3 FA (odds ratio [OR], 0.97 [95% CI, 0.89-1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82-1.06]), whereas other individual n-3 FAs showed no association with nonparoxysmal AF. Higher total n-3 FAs (estimate 0.99 [95% CI, 0.98-1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97-1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89-0.99]). Conclusions We found no strong evidence for an association of n-3 FA blood levels with AF type, but higher total n-3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index.

Aims: Atrial remodelling, defined as a change in atrial structure, promotes atrial fibrillation (AF). Bone morphogenetic protein 10 (BMP10) is an atrial-specific biomarker released to blood during atrial development and structural changes. We aimed to validate whether BMP10 is associated with AF recurrence after catheter ablation (CA) in a large cohort of patients., Methods and Results: We measured baseline BMP10 plasma concentrations in AF patients who underwent a first elective CA in the prospective Swiss-AF-PVI cohort study. The primary outcome was AF recurrence lasting longer than 30 s during a follow-up of 12 months. We constructed multivariable Cox proportional hazard models to determine the association of BMP10 and AF recurrence. A total of 1112 patients with AF (age 61 ± 10 years, 74% male, 60% paroxysmal AF) was included in our analysis. During 12 months of follow-up, 374 patients (34%) experienced AF recurrence. The probability for AF recurrence increased with increasing BMP10 concentration. In an unadjusted Cox proportional hazard model, a per-unit increase in log-transformed BMP10 was associated with a hazard ratio (HR) of 2.28 (95% CI 1.43; 3.62, P < 0.001) for AF recurrence. After multivariable adjustment, the HR of BMP10 for AF recurrence was 1.98 (95% CI 1.14; 3.42, P = 0.01), and there was a linear trend across BMP10 quartiles (P = 0.02 for linear trend)., Conclusion: The novel atrial-specific biomarker BMP10 was strongly associated with AF recurrence in patients undergoing CA for AF., Clinicaltrials.gov Identifier: NCT03718364; https://clinicaltrials.gov/ct2/show/NCT03718364., Competing Interests: Conflict of interest: P.B. received research funding from the University of Basel, the ‘Stiftung für Herzschrittmacher und Elektrophysiologie’, the ‘Freiwillige Akademische Gesellschaft Basel’, and the Swiss Heart Foundation and Johnson&Johnson, all outside the submitted work, and reports personal fees from Abbott, Boston Scientific, and Pfizer BMS. D.C. received consultancy fees from Roche Diagnostics and Trimedics and speaker fees from Servier and BMS/Pfizer. S.K. received funding from the ‘Stiftung für Herzschrittmacher und Elektrophysiologie’. M.K. received personal fees from Daiichi Sankyo and grants from the Swiss National Science Foundation, Swiss Heart Foundation, Foundation for CardioVascular Research Basel, Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo. S.O. received research grants from the Swiss National Science Foundation and Swiss Heart Foundation, Foundation for CardioVascular Research Basel, and F. Hoffmann-La Roche Ltd and educational and speaker grants from F. Hoffmann-La Roche Ltd, Bayer, Novartis, Sanofi, AstraZeneca, Daiichi Sankyo, and Pfizer. C.S. is a member of the Advisory Board of Medtronic Europe and Advisory Board of Boston Scientific Europe and has received educational grants from Biosense Webster and Biotronik, research grants from the European Union’s FP7 program and Biosense Webster, and lecture and consulting fees from Abbott, Medtronic, Biosense Webster, Boston Scientific, Micro-Port, and Biotronik. All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). We aimed to assess the predictive value of the novel atrial-specific biomarker BMP10 (bone morphogenetic protein 10) for death and MACE in patients with AF in comparison with NT-proBNP (N-terminal prohormone of B-type natriuretic peptide). Methods and Results BMP10 and NT-proBNP were measured in patients with AF enrolled in Swiss-AF (Swiss Atrial Fibrillation Study), a prospective multicenter cohort study. A total of 2219 patients were included (median follow-up 4.3 years [interquartile range 3.9, 5.1], mean age 73±9 years, 73% male). In multivariable Cox proportional hazard models, the adjusted hazard ratio (aHR) associated with 1 ng/mL increase of BMP10 was 1.60 (95% CI, 1.37-1.87) for all-cause death, and 1.54 (95% CI, 1.35-1.76) for MACE. For all-cause death, the concordance index was 0.783 (95% CI, 0.763-0.809) for BMP10, 0.784 (95% CI, 0.765-0.810) for NT-proBNP, and 0.789 (95% CI, 0.771-0.815) for both biomarkers combined. For MACE, the concordance index was 0.732 (95% CI, 0.715-0.754) for BMP10, 0.747 (95% CI, 0.731-0.768) for NT-proBNP, and 0.750 (95% CI, 0.734-0.771) for both biomarkers combined. When grouping patients according to NT-proBNP categories (<300, 300-900, >900 ng/L), higher aHRs were observed in patients with high BMP10 in the categories of low NT-proBNP (all-cause death aHR, 2.28 [95% CI, 1.15-4.52], MACE aHR, 1.88 [95% CI, 1.07-3.28]) and high NT-proBNP (all-cause death aHR, 1.61 [95% CI, 1.14-2.26], MACE aHR, 1.38 [95% CI, 1.07-1.80]). Conclusions BMP10 strongly predicted all-cause death and MACE in patients with AF. BMP10 provided additional prognostic information in low- and high-risk patients according to NT-proBNP stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Background and Purpose: Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated., Methods: Patients from the multicenter Swiss-AF cohort study were included in this cross-sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score., Results: Among 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63-0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62-0.99, p = 0.04), higher brain volume (β-coefficient = 10.73, 95% CI = 2.37-19.09, p = 0.01), and higher CoCo score (β-coefficient = 0.08, 95% CI = 0.03-0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (β-coefficient = 1.40, 95% CI = 0.65-2.15, p < 0.001)., Conclusions: In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Aims of the Study: Globally, since the introduction of conjugate-vaccines against encapsulated bacteria, respiratory viruses have caused most hospitalisations for community-acquired pneumonia. The aim of this study was to describe pathogens detected and their association with clinical findings in Switzerland., Methods: Baseline data were analysed for all trial participants enrolled between September 2018 and September 2020 into the KIDS-STEP Trial, a randomised controlled superiority trial on the effect of betamethasone on clinical stabilisation of children admitted with community-acquired pneumonia. Data included clinical presentation, antibiotic use and results of pathogen detection. In addition to routine sampling, nasopharyngeal specimens were analysed for respiratory pathogens using a panel polymerase chain reaction test covering 18 viral and 4 bacterial pathogens., Results: 138 children with a median age of 3 years were enrolled at the eight trial sites. Fever (obligatory for enrolment) had been present for median 5 days before admission. Most common symptoms were reduced activity (129, 93.5%) and reduced oral intake (108, 78.3%). Oxygen saturation <92% was found in 43 (31.2%). Forty-three participants (29.0%) were already on antibiotic treatment prior to admission and 104 participants (75.4%) received antibiotic treatment on admission. Pathogen testing results were available from 132 children: 31 (23.5%) had respiratory syncytial virus detected, 21 (15.9%) human metapneumovirus. The pathogens detected showed expected seasonal and age preponderance and were not associated with chest X-ray findings., Conclusions: In the context of the predominantly viral pathogens detected, the majority of antibiotic treatment is probably unnecessary. The ongoing trial, as well as other studies, will be able to provide comparative pathogen detection data to compare pre- and post-COVID-19-pandemic settings.

Background: Emerging evidence indicates that a high atrial fibrillation (AF) burden is associated with adverse outcome. However, AF burden is not routinely measured in clinical practice. An artificial intelligence (AI)-based tool could facilitate the assessment of AF burden., Objective: We aimed to compare the assessment of AF burden performed manually by physicians with that measured by an AI-based tool., Methods: We analyzed 7-day Holter electrocardiogram (ECG) recordings of AF patients included in the prospective, multicenter Swiss-AF Burden cohort study. AF burden was defined as percentage of time in AF, and was assessed manually by physicians and by an AI-based tool (Cardiomatics, Cracow, Poland). We evaluated the agreement between both techniques by means of Pearson correlation coefficient, linear regression model, and Bland-Altman plot., Results: We assessed the AF burden in 100 Holter ECG recordings of 82 patients. We identified 53 Holter ECGs with 0% or 100% AF burden, where we found a 100% correlation. For the remaining 47 Holter ECGs with an AF burden between 0.01% and 81.53%, Pearson correlation coefficient was 0.998. The calibration intercept was -0.001 (95% CI -0.008; 0.006), and the calibration slope was 0.975 (95% CI 0.954; 0.995; multiple R 2 0.995, residual standard error 0.017). Bland-Altman analysis resulted in a bias of -0.006 (95% limits of agreement -0.042 to 0.030)., Conclusion: The assessment of AF burden with an AI-based tool provided very similar results compared to manual assessment. An AI-based tool may therefore be an accurate and efficient option for the assessment of AF burden., (© 2023 Heart.)

Background: Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring., Methods and Results: In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years. Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA 2 DS 2 -VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10-2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14-3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46-1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46-2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0., Conclusion: Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with cognitive dysfunction. However, neurocognitive function in AF patients undergoing pulmonary vein isolation (PVI) has not been well studied. The aim of this analysis is to compare neurocognitive function in patients who did or did not undergo PVI., Materials and Methods: We used data from the Swiss Atrial Fibrillation Cohort study (Swiss-AF), a prospective, observational, multicenter study in Switzerland. Patients with documented AF were enrolled and data of 1,576 patients without history of PVI and with complete information on PVI status and neurocognitive function were used. Information on PVI was collected at baseline and during 1 year of follow-up. Neurocognitive testing was performed at baseline and after 1 year of follow-up, using the Montreal Cognitive Assessment (MoCA), trail making test (TMT) A and B, digit symbol substitution test (DSST) and semantic fluency test (SFT). To investigate the association of PVI with neurocognitive function, we use propensity score matching (1:3) and inverse probability of treatment weighting (IPTW)., Results: The mean age of this population was 74 ± 8 years, 27.1% were women. Overall, 88 (5.5%) patients underwent PVI during 1 year of follow-up. Using ITPW ( n = 1576), PVI was weakly associated with the MoCA score after adjusting for time since PVI, baseline MoCA score and other covariates (β (95%CI) 1.19 (0.05; 2.32), p = 0.04). In the propensity matched comparison ( n = 352), there was no significant association between PVI and the MoCA score (β (95%CI) 1.04 (-0.19; 2.28), p = 0.1). There were no significant associations between PVI and cognitive function when using the TMT A and B, DSST or SFT independent of the method used., Conclusion: In this population of AF patients, there was no consistent evidence of an association between PVI and neurocognitive function., Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT02105844]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zwimpfer, Aeschbacher, Krisai, Coslovsky, Springer, Paladini, Girod, Hufschmid, Knecht, Badertscher, Beer, Bonati, Zuern, Roten, Reichlin, Sticherling, Conen, Osswald and Kühne.)

Background: Patients with atrial fibrillation (AF) face an increased risk of adverse cardiovascular events. Evidence suggests that early rhythm control including AF ablation may reduce this risk., Methods: To compare the risks for cardiovascular events in AF patients with and without pulmonary vein isolation (PVI), we analysed data from two prospective cohort studies in Switzerland (n = 3968). A total of 325 patients who had undergone PVI during a 1-year observational period were assigned to the PVI group. Using coarsened exact matching, 2193 patients were assigned to the non-PVI group. Outcomes were all-cause mortality, hospital admission for acute heart failure, a composite of stroke, transient ischemic attack and systemic embolism (Stroke/TIA/SE), myocardial infarction (MI), and bleedings. We calculated multivariable adjusted Cox proportional-hazards models., Results: Overall, 2518 patients were included, median age was 66 years [IQR 61.0, 71.0], 25.8% were female. After a median follow-up time of 3.9 years, fewer patients in the PVI group died from any cause (incidence per 100 patient-years 0.64 versus 1.87, HR 0.39, 95%CI 0.19-0.79, p = 0.009) or were admitted to hospital for acute heart failure (incidence per 100 patient-years 0.52 versus 1.72, HR 0.44, 95%CI 0.21-0.95, p = 0.035). There was no significant association between PVI and Stroke/TIA/SE (HR 0.94, 95%CI 0.52-1.69, p = 0.80), MI (HR 0.43, 95%CI 0.11-1.63, p = 0.20) or bleeding (HR 0.75, 95% CI 0.50-1.12, p = 0.20)., Conclusions: In our matched comparison, patients in the PVI group had a lower incidence rate of all-cause mortality and hospital admission for acute heart failure compared to the non-PVI group., Gov Identifier: NCT02105844, April 7th 2014., (© 2022. The Author(s).)

Objective: To examine sex differences in prevalence, volume and distribution of vascular brain lesions on MRI among patients with atrial fibrillation (AF)., Methods: In this cross-sectional analysis, we included 1743 patients with AF (27% women) from the multicentre Swiss Atrial Fibrillation study (SWISS-AF) with available baseline brain MRI. We compared presence and total volume of large non-cortical or cortical infarcts (LNCCIs), small non-cortical infarcts, microbleeds (MB) and white matter hyperintensities (WMH, Fazekas score ≥2 for moderate or severe degree) between men and women with multivariable logistic regression. We generated voxel-based probability maps to assess the anatomical distribution of lesions., Results: We found no strong evidence for an association of female sex with the prevalence of all ischaemic infarcts (LNCCI and SNCI combined; adjusted OR 0.86, 95% CI 0.67 to 1.09, p=0.22), MB (adjusted OR 0.91, 95% CI 0.68 to 1.21, p=0.52) and moderate or severe WMH (adjusted OR 1.15, 95% CI 0.90 to 1.48, p=0.27). However, total WMH volume was 17% larger among women than men (multivariable adjusted multiplicative effect 1.17, 95% CI 1.01 to 1.35; p=0.04). Lesion probability maps showed a right hemispheric preponderance of ischaemic infarcts in both men and women, while WMH were distributed symmetrically., Conclusion: Women had higher white matter disease burden than men, while volume and prevalence of other lesions did not differ. Our findings highlight the importance of controlling risk factors for cerebral small vessel disease in patients with AF, especially among women., Competing Interests: Competing interests: AA reports no disclosures; DC received speaker fees from Servier, Canada, outside of the current work; JW is an employee of MIAC AG, has received funding from EU (Horizon2020), Else-Kröner-Fresenius Foundation, Novartis Foundation, and consultancy, steering committee, advisory board and speaker honoraria from Actelion, Bayer, Biogen, Idorsia, Roche, Sanofi-Genzyme and Teva; LHB received grants from the Swiss National Science Foundation (PBBSB-116873, 33CM30-124119, 32003B-156658; Berne, Switzerland), The Swiss Heart Foundation (Berne, Switzerland, and the University of Basel (Basel, Switzerland). LHB has received an unrestricted research grant from AstraZeneca, and consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical, and travel grants from AstraZeneca and Bayer; MC reports no disclosures; MD received honoraria for lectures from Pfizer, Bayer and Sonofi Genzyme, is a consultant for Hovid Berhad and Roche Pharma; MK reports personal fees from Bayer, personal fees from Böhringer Ingelheim, personal fees from Pfizer BMS, personal fees from Daiichi Sankyo, personal fees from Medtronic, personal fees from Biotronik, personal fees from Boston Scientific, personal fees from Johnson&Johnson, grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik; MRB reports no disclosures; NR received a grant from the Swiss Heart Foundation; SA reports no disclosures; SC reports no disclosures; SE-D reports no disclosures; SN reports no disclosures; SO reports no disclosures; TS reports no disclosures., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Aims: We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients., Methods and Results: We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [-0.12 (-0.22; -0.07)] than patients without new brain infarcts [0.07 (-0.09; 0.25)]. New WML or Mb were not associated with cognitive decline., Conclusion: In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Objective: Serum neurofilament light chain (sNfL) is increasingly used as a neuroaxonal injury biomarker in the elderly. Besides age, little is known about how other physiological factors like renal function and body mass index (BMI) alter its levels. Here, we investigated the association of estimated glomerular filtration rate (eGFR) and BMI with sNfL in a large sample of elderly patients with atrial fibrillation (AF)., Methods: This is a cross-sectional analysis from the Swiss-AF Cohort (NCT02105844). We measured sNfL using an ultrasensitive single-molecule array assay. We calculated eGFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine (eGFR crea ) and creatinine-cystatin C (eGFR crea-cys ) formulas, and BMI from weight and height measurements. We evaluated the role of eGFR and BMI as determinants of sNfL levels using multivariable linear regression and the adjusted R 2 (R 2 adj )., Results: Among 2,277 Swiss-AF participants (mean age 73.3 years), eGFR crea showed an inverse curvilinear association with sNfL after adjustment for age and cardiovascular comorbidities. BMI also showed an independent, inverse linear association with sNfL. The R 2 adj of models with age, eGFR crea , and BMI alone was 0.26, 0.35, and 0.02, respectively. A model with age and eGFR crea combined explained 45% of the sNfL variance. Sensitivity analyses (i) further adjusting for vascular brain lesions ( N = 1,402 participants with MRI) and (ii) using eGFR crea-cys yielded consistent results., Interpretation: In an elderly AF cohort, both renal function and BMI were associated with sNfL, but only renal function explained a substantial proportion of the sNfL variance. This should be taken into account when using sNfL in elderly patients or patients with cardiovascular disease., Competing Interests: GM: consultant fees from Astra Zeneca, Bayer, Boehringer-Ingelheim, Novartis, outside of the submitted work. GMDM: Support from SNSF, “Spezialprogramm Nachwuchsförderung Klinische Forschung,” University of Basel, Science Funds (Wissenschaftspool) University Hospital Basel, Swiss Heart Foundation, Bangerter-Rhyner-Stiftung, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr. Ettore Balli, De Quervain research grant, Thermo Fisher GmbH; Travel honoraria Bayer, BMS/Pfizer; Speaker honoraria Bayer, Medtronic; Steering committee PACIFIC Stroke, Industry payments to the research fund of the University Hospital Basel. SE: Travel or speaker honoraria from Bayer, Boehringer-Ingelheim, Daiichi-Sankyo; Scientific advisory boards Bayer, Boehringer-Ingelheim, BMS/Pfizer, MindMaze; Editorial board of Stroke; Research funding to his institutions from Pfizer, Stago, Daiichi-Sankyo, Science Funds [Wissenschaftsfonds] University Hospital Basel, University Basel, “Wissenschaftsfonds Rehabilitation” University Hospital for Geriatric Medicine Felix Platter, “Freiwillige Akademische Gesellschaft Basel,” Swiss Heart Foundation, SNSF. DC: consulting fees from Roche Diagnostics, outside of the current work. MK: fees from Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi-Sankyo, Medtronic, Biotronik, Boston Scientific, Johnson&Johnson, Roche; grants from Bayer, Pfizer, Boston Scientific, BMS, Biotronik, Daiichi-Sankyo. LB: fees and non-financial support from Amgen, Bayer; fees from BMS, Claret Medical and InnovHeart; grants from AstraZeneca, SNSF, University of Basel, Swiss Heart Foundation, outside the submitted work. JK: speaker fees, research support, travel support, and/or advisory boards Swiss Multiple Sclerosis Society, SNSF, University of Basel, Progressive Multiple Sclerosis Alliance, Bayer, Biogen, Celgene, Merck, Novartis, Octave Bioscience, Roche, Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Polymeris, Helfenstein, Benkert, Aeschbacher, Leppert, Coslovsky, Willemse, Schaedelin, Blum, Rodondi, Reichlin, Moschovitis, Wuerfel, De Marchis, Engelter, Lyrer, Conen, Kühne, Osswald, Bonati, Kuhle and the Swiss-AF Investigators.)

Background: Patients at high-bleeding risk (HBR) undergoing percutaneous coronary intervention represent a challenging patient population. The use of drug-coated balloon (DCB) allows shorter duration of dual antiplatelet therapy compared with drug-eluting stents (DES) and reduces thrombotic risk due to the absence of a permanent implant. The present analysis aimed to investigate if the effect of DCB versus DES differed between patients with and without HBR treated with percutaneous coronary intervention in small coronary arteries., Methods: This prespecified subgroup analysis of a multicenter, randomized, noninferiority trial included 758 patients with de novo lesions in coronary vessels <3 mm and an indication for percutaneous coronary intervention, randomized to DCB (n=382) or second-generation DES (n=376). Patients were followed over 3 years for major adverse cardiac events., Results: Of the 758 patients randomized, 155 (20%) had HBR; these patients had higher mortality at 3 years (hazard ratio [95% CI], 3.09 [1.78-5.36]; P <0.001). Rates of major bleeding events were overall low but tended to be lower after DCB versus DES (1.6% versus 3.7%; P =0.064), were similar in patients with HBR (4.5% versus 3.4%) but less frequent in DCB-versus DES-treated patients without HBR (0.9% versus 3.8%). There was no difference in major adverse cardiac events between DCB and DES regardless of bleeding risk (HBR, hazard ratio: 1.16 [0.51-2.62]; P =0.719 versus non-HBR, 0.96 [0.62-1.49]; P =0.863)., Conclusions: DCBs were similarly safe and effective as current-generation DES in the treatment of coronary arteries <3 mm, regardless of bleeding risk. In patients treated with DCB, there was a trend towards a reduction of severe bleeding events at 3 years., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01574534.

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE., (© 2022. The Author(s).)