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Background: BMP10 (bone morphogenic protein 10) has emerged as a novel biomarker associated with the risk of ischemic stroke and other outcomes in patients with atrial fibrillation (AF). The study aimed to determine if repeated BMP10 measurements improve prognostication of cardiovascular events in patients with AF., Methods and Results: BMP10 was measured using a prototype Elecsys immunoassay in plasma samples collected at randomization and after 2 months in patients with AF randomized to apixaban or warfarin in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial (n=2878). Adjusted Cox-regression models were used to evaluate the association between 2-month BMP10 levels and outcomes. BMP10 levels increased by 7.8% ( P <0.001) over 2 months. The baseline variables most strongly associated with BMP10 levels at 2 months were baseline BMP10 levels, body mass index, sex, age, creatinine, diabetes, warfarin treatment, and AF-rhythm. During median 1.8 years follow-up, 34 ischemic strokes/systemic embolism, 155 deaths, and 99 heart failure hospitalizations occurred. Comparing the third with the first sample quartile, higher BMP10 levels at 2 months were associated with higher risk of ischemic stroke (hazard ratio [HR], 1.33 [95% CI, 0.67-2.63], P =0.037), heart failure (HR, 1.91 [95% CI, 1.17-3.12], P =0.012) and all-cause death (HR, 1.61 [95% CI, 1.17-2.21], P <0.001). Adding BMP10 levels at 2 months on top of established risk factors and baseline BMP10 levels improved the C-indices for ischemic stroke/systemic embolism (from 0.73 to 0.75), heart failure hospitalization (0.76-0.77), and all-cause mortality (0.70-0.72), all P <0.05., Conclusions: Elevated levels of BMP10 at 2 months strengthened the associations with the risk of ischemic stroke, hospitalization for heart failure, and all-cause mortality. Repeated measurements of BMP10 may further refine risk stratification in patients with AF.

Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation., (© 2023. Springer Nature Limited.)

Background: Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA 2 DS 2 -VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up., Methods: Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA 2 DS 2 -VASc score., Results: We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45-2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20-2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11-2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02-2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00-1.86]), and hFABP (heart-type fatty acid-binding protein; aOR, 0.48 [95% CI, 0.31-0.73]). Overall performance and discrimination of the new model was superior to that of the CHA 2 DS 2 -VASc score (C statistic, 0.82 [95% CI, 0.77-0.87] versus 0.64 [95% CI, 0.58-0.70])., Conclusions: In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures., Competing Interests: Disclosures Dr De Marchis reports honoraria by Bayer, Pfizer, Medtronic and a Grant from Novartis unrelated to the present work. Industry payments are made to the research fund of the University Hospital Basel. Dr Aeschbacher reports speaker fees from Roche Diagnostics. Dr Reichlin reports consultant honoraria/grants from Abbott Laboratories, Biosense Webster, Inc, Biotronik, Boston Scientific Corporation, and Medtronic. Dr Moschovitis has received consultant fees for taking part to advisory boards from Novartis, Boehringer Ingelheim, Bayer, Astra Zeneca and Daiichi Sankyo, all outside of the submitted work. Dr Wuerfel is employed at Roche. Dr Lyrer reports honoraria from Bayer, Biogen, Boehringer Ingelheim, Pfizer – all unrelated to the present work – and grants from the Swiss National Science Foundation and University Hospital Basel (intramural grant). Dr Fischer reports grant/contracts from Alexion, Biogen, Medtronic Vascular, Penumbra, Phenox, Rapid Medical, as well as support from Stryker and CSL Behring Foundation for Research and Advancement of Patient Health. Dr Conen reports consultation fees from Roche Diagnostics and Trimedics, as well as speaker fees from Servier and Pfizer. Dr Ziegler is employed at Roche Diagnostics International. Dr Kühne reports personal fees from Bayer, personal fees from Böhringer Ingelheim, personal fees from Pfizer Bristol-Myers Squibb (BMS), personal fees from Daiichi Sankyo, personal fees from Medtronic, personal fees from Biotronik, personal fees from Boston Scientific, personal fees from Johnson&Johnson, personal fees from Roche, grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik, grants from Daiichi Sankyo. Dr Bonati reports honoraria from Amgen, AstraZeneca, Bayer, BMS, Claret Medical, grants from the Swiss National Science Foundation, Swiss Heart Foundation, University of Basel, and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung. The other authors report no conflicts.

Aims: Several biomarkers are associated with clinical outcomes in patients with atrial fibrillation (AF), but a causal relationship has not been established. This study aimed to evaluate angiopoietin-2, a novel candidate biomarker of endothelial inflammation and vascular remodelling, in patients with AF., Methods and Results: Angiopoietin-2 was measured in plasma obtained from patients with AF treated with aspirin monotherapy (exploration cohort, n = 2987) or with oral anticoagulation (validation cohort, n = 13 079). Regression models were built to assess the associations between angiopoietin-2, clinical characteristics, and outcomes. In both cohorts, plasma angiopoietin-2 was independently associated with AF on the baseline electrocardiogram and persistent/permanent AF, age, history of heart failure, female sex, tobacco use/smoking, body mass index, renal dysfunction, diabetes, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Angiopoietin-2 was independently associated with subsequent hospitalization for heart failure after adjusting for age, creatinine, and clinical characteristics in the exploration cohort [c-index 0.79, 95% confidence interval (CI) 0.75-0.82; third vs. first quartile, hazard ratio (HR) 1.74, 95% CI 1.26-2.41] and in the validation cohort (c-index 0.76, 95% CI 0.74-0.78; HR 1.58, 95% CI 1.37-1.82). In both cohorts, the association persisted when also adjusting for NT-proBNP (P ≤ 0.001). In full multivariable models also adjusted for NT-proBNP, angiopoietin-2 did not show statistically significant associations with ischaemic stroke, cardiovascular and all-cause death, or major bleeding that were consistent across the two cohorts., Conclusions: In patients with AF, plasma levels of angiopoietin-2 were independently associated with subsequent hospitalization for heart failure and provided incremental prognostic value to clinical risk factors and NT-proBNP., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The Integrated Treatment Pathway Stroke Tyrol was introduced for the care of people after an acute stroke event and includes four phases: acute prehospital care, inpatient treatment, inpatient rehabilitation and ambulatory, outpatient rehabilitation. For the 4th phase, the ambulatory rehabilitation of patients after discharge, the ICT platform "StrokeNet Tyrol" was established., Methods: Requirements and processes along the pathway and between the interdisciplinary team were taken into account for implementation based on a modular software architecture. Flexible rights and role concept was developed to support efficient collaboration of the heterogenic professions., Results: The routine usage of 342 users with 8 different roles, 2,219 registered patient cases within the last 4 years and first results of the integrated benchmarking solution give a positive impression regarding feasibility and effectiveness., Conclusion: To this point, a comprehensive infrastructure for the Ambulatory Tyrolean Stroke Pathway has been established. Results from outcome analyses and comparative studies could help to further improve usability and to expand the area of application for other indications.

Aims: Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC)., Methods and Results: BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death., Conclusion: The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF., One-Sentence Summary: In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation., Competing Interests: Conflict of interest: Dr Hijazi reports lecture and consulting fees from Boehringer Ingelheim, Bristol Myers Squibb, Pfizer and Roche Diagnostics International. Dr Benz has nothing to disclose. Mr Lindbäck reports institutional research grant from Roche Diagnostics International. Dr Alexander reports institutional research grants from Artivion/CryoLife, Bayer, Bristol Myers Squibb, CSL Behring, Ferring, Humacyte, and XaTek and consulting or honoraria payments from AbbVie, Akros, Artivion/CryoLife, AtriCure, Bristol Myers Squibb, Ferring, GlaxoSmithKline, Janssen, Pfizer, Portola, and Quantum Genomics. Dr Connolly reports institutional research grants and honoraria from Boehringer Ingelheim, Portola/Alexion Pharmaceuticals, Bristol Myers Squibb/Pfizer, Bayer, and Daiichi Sankyo. Dr Eikelboom reports institutional research grants and honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, and Sanofi. Dr Granger reports grants and consulting fees from Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Janssen Pharmaceutica Products, L.P., Medtronic Foundation, Novartis; grants from Daiichi Sankyo, AKROS, Apple, GlaxoSmithKline, AstraZeneca, the U.S. Food and Drug Administration; consulting fees from Abbvie, Abiomed, Athos Therapeutic, LLC, Bayer Corporation US, Boston Scientific Corporation, Espero BioPharma, National Institutes of Health, Philips, Rhoshan Pharmaceuticals, Roche Diagnostics, CeleCor Therapeutics, Correvio, Merck, NovoNordisk. Drs. Kastner and Ziegler are employees of Roche Diagnostics GmbH. Dr Lopes reports institutional research grants and consulting fees from Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; consulting fees from Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck, and Portola. Dr Oldgren reports institutional research grants and fees paid to his institution for advisory boards and lectures from Roche Diagnostics International; fees paid to his institution for advisory boards, study steering committees, and lectures from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, and Sanofi; fees paid to his institution for advisory boards, safety committees, and lectures from Daichii Sankyo. Dr Siegbahn reports institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, and Roche Diagnostics International. Dr Wallentin reports institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, GlaxoSmithKline, Roche Diagnostics International, Merck & Co; consulting fees from Abbott; holds two patents involving GDF-15 licensed to Roche Diagnostics (EP2047275B1 and US8951742B2)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Stroke is one of third most common causes of death and the main cause for permanent disabilities. The Tyrol Stroke Pathway covers, all steps from stroke onset to outpatient rehabilitation., Objectives: The main objective of this paper is to describe how the paper-based documentation in the outpatient rehabilitation can be implemented in an eHealth service for integrated care., Methods: First a state analysis followed by a requirement analysis was performed. An interactive mock-up was designed for further discussion with the stakeholders. After the implementation of the system the evaluation was performed in two steps: feedback from a virtual test phase and a pilot operation was analyzed., Results: First experiences during the virtual test phase with key stakeholders of the therapy pathway showed a high level of acceptance. Users reported an improvement in the communication and documentation processes., Conclusion: Initial results illustrate how a shift from paper-based documentation to an integrated eHealth service can improve communication and documentation in an independent therapy network.