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Background: Stroke is a common complication of infective endocarditis (IE). Our aim was to describe the prevalence and prognostic impact of stroke in a national cohort of IE., Methods: Consecutive inclusion at 46 Spanish hospitals between 2008 and 2021., Results: Out of 5667 IE cases, 1125 had acute stroke (19.8%): 818 ischemic strokes (811 cardioembolic strokes (193 with hemorrhagic transformation), 4 transient ischemic attacks, 3 lacunar infarctions), 127 intracranial hemorrhages, and 27 other neurological complications (cerebral abscesses, encephalitis, and meningitis). Compared to patients without stroke, those with stroke had a similar mean age (69 years) but were more frequently female (68.2% vs 63.7%, p = 0.04) and had a higher incidence of intracardiac complications (35% vs 30%, p = 0.01), surgical indication (69.9% vs 65.9%, p = 0.001), in-hospital mortality (40.9% vs 22.0%, p < 0.001), and 1-year mortality (46.2% vs 27.9%, p < 0.001). The following variables were independently associated with stroke: mitral location (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.34-1.8, p < 0.001), vascular phenomenon (OR = 2.9, 95% CI = 2.4-3.6, p = 0.0001), acute renal failure (OR = 1.2, 95% CI = 1.0-1.4, p = 0.021), septic shock (OR = 1.3, 95% CI = 1.1-1.6, p = 0.007), sepsis (OR = 1.3, 95% CI = 1.1-1.6, p = 0.005), surgery indicated but not performed (OR = 1.4, 95% CI = 1.2-1.7, p < 0.001), community-acquired IE (OR = 1.2, 95% CI = 1-1.4, p = 0.017), and peripheral embolization (OR = 1.6, 95% CI = 1.4-1.9, p < 0.001). Stroke was an independent predictor of in-hospital (OR = 2.1, 95% CI = 1.78-2.51, p < 0.001) and 1-year mortality (hazard ratio = 1.9, 95% CI = 1.6-2.5)., Conclusion: One-fifth of patients with IE have concomitant stroke. Stroke is associated with mortality., 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.

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.

Introduction and Objectives: The management of atrial fibrillation is complex and requires improvement at strategic points, such as in the control of patients treated with vitamin K antagonists. The aim of this study was to evaluate the impact on health outcomes of a nonvalvular atrial fibrillation decision support tool based on visualization of the time in therapeutic range in primary care., Methods: The present randomized clinical trial was conducted in 2018 with a 1-year follow-up in 325 primary care centers in Catalonia. In the intervention centers, the decision support tool was installed to control the time in therapeutic range of patients treated with vitamin K antagonists. The tool was not visualized in the control group., Results: In total, 44 556 patients were studied. The intervention protected against admission for stroke (adjusted odds ratio [OR], 0.70; 95% confidence interval [95%CI], 0.55-0.88). The number needed to treat was 3502 (95%CI, 3305-3725) while the number of admissions for stroke avoided was 12.63 (95%CI, 11.88-13.38). The intervention also protected against mortality (adjusted OR, 0.78; 95%CI, 0.67-0.90), with a number needed to treat of 13 687 (95%CI, 10 789-18 714) and number of deaths avoided of 3.23 (95%CI, 2.36-4.10)., Conclusions: The decision support tool was associated with slight reductions in the numbers of admissions for ischemic stroke and mortality. Although the follow-up time was short and the effect of the intervention was small, the results are valuable and could improve implementation of the tool. This clinical trial was registered with ClinicalTrials.gov (NCT03367325)., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Oral anticoagulation is the key to reduce the risk of stroke in atrial fibrillation. Although vitaminK antagonists (VKA) have classically been used for this purpose, they have been largely overcome by direct oral anticoagulants (DOAC), as demonstrated by evidence from clinical trials, real-life and population studies. In fact, all clinical practice guidelines recommend their use preferentially over VKA. However, in Spain the prescription of DOAC is subordinated to an inspection visa that includes the clinical conditions defined in the Therapeutic Positioning Report of the Spanish Medicines Agency, and that still imposes important restrictions on their use, limiting the benefits of using DOACs in patients with atrial fibrillation (AF), and also generating inequalities between the different autonomous communities. In fact, the use of DOAC in Spain is much lower than that observed in neighboring countries. This has made that while in other countries the incidence of ischemic stroke has decreased at the population level, along with a reduction in the cost per patient with AF, in Spain this decrease has been modest. For all these reasons, and for assuring the sustainability of the health care system, we ask for the elimination of the visa so that DOAC can be prescribed according to the recommendations made by the guidelines. In addition, we are also committed to reinforce medical education and decisions made by consensus with the patient, with the primary care physician acquiring a key role in the protection of the patient with AF., (Copyright © 2023 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: Coronary artery calcification (CorCa) identifies high cardiovascular risk in the general population. In this setting, aortic valve calcification (AoCa) showed contradictory results. Our goal has been to assess the prognostic power of CorCa and AoCa in patients with chest pain who underwent an ECG-gated cardiac multidetector CT (cardiac-MDCT)., Methods: A total of 528 patients without previous known coronary artery disease, with chest pain who underwent a cardiac-MDCT multidetector, were retrospectively recruited. The primary endpoint included death, acute coronary syndrome, stroke, and heart failure., Results: A total of 61 patients (11.6%) had an event during a mean follow-up of almost 6 years (5.95 ± 2.98). The most frequent event was acute coronary syndrome (6.4%). Total mortality was 4.5%. Patients with CorCa > 0 had more events than those without CorCa (17.3% versus 4.3%; p < 0.001). Likewise, when only patients without AoCa were considered (n = 118), clinical events were more frequent in those with CorCa (12.7% versus 3.6%; p = 0.004). After excluding patients with coronary artery disease, events were more frequent in those with CorCa (12.6% versus 4.3%; p = 0.004). The higher the Agatston score, the more frequent the events. Patients with AoCa  > 0 had more events than those without (16.5% versus 7.3%; p < 0.001), but in patients without CorCa, no difference in events was seen (6.2% versus 3.6%; p = 0.471). A Cox regression analysis showed age, smoking, prior stroke, and CorCa but not AoCa to be independently related to events., Conclusions: In summary, CorCa, but not AoCa, is related to cardiovascular events in patients with chest pain who undergo a cardiac-MDCT., Clinical Relevance Statement: We show that coronary artery calcification, but not aortic valve calcification, detected in a coronary CT scan is tightly related to cardiovascular events. Although this is a message already shown by other groups in the general population, we do believe that this work is unique because it is restricted to patients with chest pain sent to coronary CT. In other words, our work deals with what we face in our routine everyday practice., Key Points: • The presence and the amount of coronary artery calcification are associated with cardiovascular events in patients with chest pain. • Aortic valve calcification is not associated with cardiovascular events in patients with chest pain., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA)., Methods and Results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF., Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF., Competing Interests: Conflict of interest The 9th AFNET/EHRA consensus conference was partially supported by the European Union MAESTRIA project (grant agreement 965286) to AFNET. The following participants and authors are employees of companies active in cardiovascular health as indicated in their affiliations: M.D.M., E.D., C.E., G.H., L.H.H., T.H., R.H.v.L., M.W., and H.W. P.K. was partially supported by the European Union AFFECT-AF (grant agreement 847770) and MAESTRIA (grant agreement 965286), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers DZHK FKZ 81X2800182, 81Z0710116, and 81Z0710110), German Research Foundation (Ki 509167694), and Leducq Foundation. He receives research support for basic, translational, and clinical research projects from several drug and device companies active in AF and has received honoraria from several such companies in the past, but not in the last 3 years. He is listed as an inventor on two issued patents held by the University of Hamburg (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). J.G.A. was partially supported by the Canadian Arrhythmia Network and the Michael Smith Foundation for Health Research, Baylis Medical. He receives consulting fees/honoraria from Bayer, BMS/Pfizer Alliance, Servier, and Medtronic Inc. E.A. receives consulting fees/honoraria from Biosense Webster and Bayer. G.B. receives consulting fees/honoraria from Bayer, BMS, Boston Scientific, Daiichi Sankyo, Sanofi, and Janssen. A.J.C. receives consulting fees/honoraria from Bayer, Pfizer/BMS, Daiichi Sankyo, Menarini, Sanofi, Boston Scientific, Biosense Webster, Abbott, Acesion Pharma, Huya Bio, and Milestone. V.C. receives consulting fees/honoraria from Bayer, Boehringer Ingelheim, and Ever Pharma (paid to the institution of employment). W.D. receives consulting fees/honoraria from Reata and research grants from MicroPort, Boston Scientific, and Abbott. S.Z.D. receives consulting fees from BMS/Pfizer, Cortrium, and Acesion Pharma and speaker fees from MS/Pfizer and Bayer. He is listed as a medical advisor for Vital Beats. Dobromir D. receives consulting fees/honoraria from Elsevier, Springer Healthcare Ltd, and Daiichi Sankyo and research grants as follows: four NIH grants (partially) from Baylor College of Medicine, Houston; one NIH grant from UC Davis, one NIH grant from the University of Minnesota, and one EU-Project H2020. David D. receives consulting fees/honoraria from Abbott, Astra Zeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS/Pfizer, CVRx, Medtronic, MicroPort, and Zoll and research grants from Roche, CVRx, and Zoll. L.E. has received lecture fees from various companies in AF in the past but none related to the present work. L.F. receives consulting fees/honoraria from Roche (paid to the institution of employment). She is currently employed at the UKE and previously at the University of Birmingham. She was partially supported by the European Union AFFECT-EU (grant agreement 847770), MAESTRIA (grant agreement 965286), CATCH ME (grant agreement 633196), and the British Heart Foundation (AA/18/2/3218). D.F.-R. receives research grants from Abbott. He is listed as an inventor on two issued patents: EP3636147A1 (method for the identification of cardiac fibrillation drivers and/or the footprint of rotational activations) and PCT/EP2022/071364 (system and method of assessment of electromechanical remodelling). A.G. receives consulting fees/honoraria from Daiichi Sankyo, Bayer, BMS/Pfizer, Medtronic, Abbott, and Boston Scientific and was partially supported by the European Union MAESTRIA (grant agreement 965286). K.G.H. receives consulting fees/honoraria from Abbott, Alexion, Amarin, Astra Zeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS/Pfizer, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novaris, Portola, Premier Research, Sanofi, SUN Pharma, and W. L. Gore and Associates. J.S.H. receives speaking fees from BMS/Pfizer, Bayer, Servier, and Boston Scientific and consulting fees from Bayer and Boston Scientific. He receives research grants from BMS/Pfizer, Servier, Novartis, Boston Scientific, and Medtronic. H.H. receives lecture and consulting fees from Bayer, Biotronik, BMS/Pfizer, Daiichi Sankyo, Milestone Pharmaceuticals, Centrix India, C.T.I. Germany, ESC, Medscape, and Springer Healthcare Ltd. He receives research grants (paid to the institution of employment, University of Antwerp and/or University of Hasselt) from Abbott, Bayer, Biosense Webster, Boston Scientific, Daiichi Sankyo, Fibricheck/Qompium, Medtronic, and BMS/Pfizer. Z.H. receives consulting fees/honoraria from Boehringer Ingelheim, BMS/Pfizer, and Roche Diagnostics. He was partially supported by The Swedish Society for Medical Research (S17-0133), Hjärt-Lungfonden (The Swedish Heart-Lung Foundation, 20200722), and the institution he is currently employed at (Uppsala University Hospital). L.H.-M. receives research grants from the Spanish Ministry of Science and Innovation (PID2020-116927RB-C21) and Fondo Europeo de Desarrollo Regional (FEDER). D.K. receives consulting fees/honoraria from Bayer, Amomed, and Protherics Medicines Development. He receives research grants from the National Institute for Health Research (NIHR CDF-2015-08-074 RAE-AF; NIHR130280 DaRe2THINK; NIHR13274 D2T-NeuroVascular; and NIHR203326 Biomedical Research Centre), the British Heart Foundation (PG/17/55/33087, AA/182/3218, and FS/CDRF/21/21032), the EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074), EU Horizon and UKRI (HYPERMARKER 101095480) UK National Health Service—Data for R&D-Subnational Secure Data Environment programme, UK Department for Business, Energy Industrial Strategy Regulators Pioneer Fund, the Cook & Wolstenholme Charitable Trust, and the European Society of Cardiology supported by educational grants from Boehringer Ingelheim, BMS/Pfizer, Alliance, Bayer, Daiichi Sankyo, Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre, and the British Hear Foundation, the University of Birmingham Accelerator Award (STEEER-AF). J.L.M. receives consulting fees/honoraria from Biotronik, Medtronic, MicroPort, and Milestone Pharmaceuticals. A.M. receives consulting fees/honoraria from Medtronic, Biosense Webster, and Boston Scientific and lecture fees from Medtronic, Boston Scientific, Biosense Webster, BMS, and Bayer. L.M. receives consulting fees/honoraria from Abbott, Medtronic, Boston Scientific, and Johnson & Johnson. G.A.N. receives lecture fees from AliveCor, consultant fees from Biosense Webster, and research grants from Abbott and Biosense Webster. H.P. receives consulting fees/honoraria from Abbott, Boston Scientific, Biosense Webster, Medtronic, Daiichi Sankyo, Bayer, and Pfizer. P.S. receives consulting fees/honoraria from Medtronic, Boston Scientific, Abbott, CathRx, and PaceMate (paid to the institution of employment). He is currently employed at the University of Adelaide, which receives research grants from Medtronic, Boston Scientific, and Becton-Dickenson. R.B.S. receives consulting fees/honoraria from BMS/Pfizer. She was partially supported by the European Union Horizon 2020 research and innovation programme (grant agreement 648131 and 847770), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers 81Z1710103 and 81Z0710114), German Ministry of Research and Education (BMBF 01ZX1408A), ERACoSysMed3 (031L0239), Wolfgang Seefried project funding German Heart Foundation. U.S. receives consulting fees/honoraria from University Svizzerra Italiana, Stanford, and Johnson & Johnson and research grants from the European Union, Dutch Heart Foundation, Roche, and EP Solution. He is a shareholder of YourRhythmics B.V. T.T. receives consulting fees/honoraria from Boston Scientific and Medtronic. I.C.v.G. receives consulting fees/honoraria from Bayer (paid to the institution of employment). She is currently employed at the University of Groningen. K.V. receives consulting fees/honoraria from Abbott, Philips, Medtronic, Biosense Webster, and Boston Scientific and research grants from Medtronic and Biosense Webster. R.W. receives consulting fees/honoraria from Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Boston Scientific, Biotronik, Abiomed, and Zoll and a research grant from Boston Scientific, BMS/Pfizer, and Abiomed. S.W. receives consulting fees/honoraria from Boehringer Ingelheim, Boston Scientific, Abbott, and Bayer Vital and a research grant from Boston Scientific. All remaining authors (G.B., J.C.N., T.D.P., N.D., M.F., E.G., S.H., S.K., D.L., K.M.-R., M.O., A.S.P., U.R., M.R., D.S., C.S., G.S., D.S., S.T., R.H.v.L., and S.Z.) have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients., Methods: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation., Results: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001)., Conclusions: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Hypertension is the most prevalent modifiable risk factor for stroke and is associated with worse functional outcomes. Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid (SAHA) modulates gene expression and has emerged as a promising therapeutic approach to reduce ischaemic brain injury. Here, we have tested the therapeutic potential of SAHA administered during reperfusion in adult male spontaneously hypertensive (SHR) rats subjected to transient middle cerebral artery occlusion (tMCAO; 90 min occlusion/24 h reperfusion). Animals received a single dose of SAHA (50 mg/kg) or vehicle i.p. at 1, 4, or 6 h after reperfusion onset. The time-course of brain histone H3 acetylation was studied. After tMCAO, drug brain penetrance and beneficial effects on behavioural outcomes, infarct volume, oedema, angiogenesis, blood-brain barrier integrity, cerebral artery oxidative stress and remodelling, and brain and vascular inflammation were evaluated. SAHA increased brain histone H3 acetylation from 1 to 6 h after injection, reaching the ischaemic brain administered during reperfusion. Treatment given at 4 h after reperfusion onset improved neurological score, reduced infarct volume and oedema, attenuated microglial activation, prevented exacerbated MCA angiogenic sprouting and blood-brain barrier breakdown, normalised MCA oxidative stress and remodelling, and modulated brain and cerebrovascular cytokine expression. Overall, we demonstrate that SAHA administered during early reperfusion exerts robust brain and vascular protection after tMCAO in hypertensive rats. These findings are aligned with previous research in ischaemic normotensive mice and help pave the way to optimise the design of clinical trials assessing the effectiveness and safety of SAHA in ischaemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA., Methods: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes., Results: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P =0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P =1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P =0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P =0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P =0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P =0.80)., Conclusions: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445., Competing Interests: Disclosures Dr Rodés-Cabau has received institutional research grants from and is consultant for Edwards Lifesciences and Medtronic. Dr Ribeiro has received fees as a proctor from Medtronic, Edwards Lifesciences and Boston Scientific and research grant from Medtronic. Dr Al-Atassi has received honoraria/fees as a proctor from Edwards. Dr Nombela-Franco has received consulting fees from Edwards Lifesciences. Dr Conradi is a member of the Advisory Board of Medtronic, Abbott, and JenaValve; and has received consulting fees from Edwards Lifesciences, Boston Scientific, MicroPort, Venus Medtech, and PiCardia. Dr Moris received fees as a proctor from Medtronic and Boston Scientific. Dr Pibarot has received institutional research grants from Edwards Lifesciences, Medtronic, Pi-Cardia, and Novartis. The other authors report no conflicts.

Atherosclerosis is responsible for 20% of ischemic strokes, and severe carotid stenosis is associated with a higher incidence of first-ever and recurrent strokes. The release of pro-inflammatory mediators into the blood in severe atherosclerosis may aggravate endothelial dysfunction after stroke contributing to impair disease outcomes. We hypothesize that environments of severe carotid atherosclerotic disease worsen endothelial dysfunction in stroke linked to enhanced risk of further cerebrovascular events. We mounted nonischemic common carotid arteries from 2- to 4-month-old male Oncins France 1 mice in tissue baths for isometric contraction force measurements and exposed them to serum from men with a recent ischemic stroke and different degrees of carotid stenosis: low- or moderate-grade stenosis (LMGS; < 70%) and high-grade stenosis (HGS; ≥ 70%). The results show that serum from stroke patients induced an impairment of acetylcholine relaxations in mice carotid arteries indicative of endothelium dysfunction. This effect was more pronounced after incubation with serum from patients with a recurrent stroke or vascular death within 1 year of follow-up. When patients were stratified according to the degree of stenosis, serum from HGS patients induced more pronounced carotid artery endothelial dysfunction, an effect that was associated with enhanced circulating levels of IL-1β. Mechanistically, endothelial dysfunction was prevented by both nonselective and selective COX blockade. Altogether, the present findings add knowledge on the understanding of the mechanisms involved in the increased risk of stroke in atherosclerosis and suggest that targeting COX in the carotid artery wall may represent a potential novel therapeutic strategy for secondary stroke prevention., (© 2022. The Author(s).)

Introduction: Our aim was to investigate the prevalence of atrial fibrillation (AF) and recently diagnosed lung cancer in the outpatient oncology clinic and to describe the clinical profile, management and outcomes of this population., Methods: Among 6984 patients visited at the outpatient oncology clinics attending lung cancer patients in five university hospitals from 2017 to 2019, all consecutive subjects with recently diagnosed (<1 year) disease and AF were retrospectively selected and events in follow up were registered., Results: A total of 269 patients (3.9 % of all attended, 71 ± 8 years, 91 % male) were included. Charlson, CHA2DS2-VASc and HAS-BLED indexes were 6.7 ± 2.9, 2.9 ± 1.5 y 2.5 ± 1.2, respectively. Tumour stage was I, II, III and IV in 11 %, 11 %, 33 % and 45 % of them, respectively. Anticoagulants were prescribed to 226 patients (84 %): direct anticoagulants (n = 99;44 %), low molecular weight heparins (n = 69;30 %) and vitamin K antagonists (n = 58;26 %). After 46 months of maximum follow-up, 186 patients died (69 %). Cumulative incidences of events at 3 years were 3.3 ± 1.3 % for stroke/systemic embolism (n = 7); 8.9 ± 2.2 % for thrombotic events (n = 18); 9.9 ± 2.6 % for major bleeding (n = 16), and 15.9 ± 3,0 % for cardiovascular events (n = 33). In patients with early stages of cancer (I-II), 2-year mortality was significantly higher in those with cardiovascular events or major bleeding (85 % vs 25 %, p = 0.01)., Conclusion: Nearly 4 % or all outpatients in the oncology clinic attending lung cancer present recently diagnosed disease and AF. Major bleeding and cardiovascular event rates are high in this population, with an impact on mortality in early stages of cancer., 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 © 2023 Elsevier Inc. All rights reserved.)

Aim: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic stenosis in patients with intermediate to prohibitive surgical risk. When a single TAVI device fails and cannot be retrieved, TAVI-in-TAVI must be performed acutely, but outcomes of bailout TAVI-in-TAVI have been incompletely appraised. We aimed at analyzing patient, procedural and outcome features of patients undergoing bailout TAVI-in-TAVI in a multicenter registry., Methods: Details of patients undergoing bailout TAVI-in-TAVI, performed acutely or within 24 h of index TAVI, in 6 international high-volume institutions, were collected. For every case provided, 2 same-week consecutive controls (prior TAVI, and subsequent TAVI) were provided. Outcomes of interest were procedural and long-term events, including death, myocardial infarction, stroke, access site complication, major bleeding, and reintervention, and their composite (i.e. major adverse events [MAE])., Results: A total of 106 patients undergoing bailout TAVI-in-TAVI were included, as well as 212 controls, for a total of 318 individuals. Bailout TAVI-in-TAVI was less common in younger patients, those with higher body mass index, or treated with Portico/Navitor or Sapien devices (all p < 0.05). Bailout TAVI-in-TAVI was associated with higher in-hospital rates of death, emergency surgery, MAE, and permanent pacemaker implantation (all p < 0.05). Long-term follow-up showed that bailout TAVI-in-TAVI was associated with higher rates of death and MAE (both < 0.05). Similar findings were obtained at adjusted analyses (all p < 0.05). However, censoring early events, outlook was not significantly different when comparing the two groups (p = 0.897 for death, and p = 0.645 for MAE)., Conclusions: Bail-out TAVI-in-TAVI is associated with significant early and long-term mortality and morbidity. Thus, meticulous preprocedural planning and sophisticated intraprocedural techniques are of paramount importance to avoid these emergency procedures., (© 2023. The Author(s).)

Background: Transcatheter aortic valve implantation is an effective treatment for patients with aortic stenosis; however, complications related to paravalvular leakage (PVL) persist, including increased risk of mortality, cardiovascular mortality, and rehospitalisation., Aims: We sought to evaluate the clinical outcomes and valve performance at 1 year in patients with severe aortic stenosis treated with the ACURATE neo2 valve in a post-market clinical setting., Methods: Valve Academic Research Consortium-2 safety events were assessed up to 1 year. Independent core laboratories evaluated echocardiographic measures of valve performance and hypoattenuated leaflet thickening (HALT; as measured by four-dimensional computed tomography)., Results: The study enrolled 250 patients (64% female; mean age: 81 years; baseline Society of Thoracic Surgeons risk score: 2.9±2.0%); 246 patients were implanted with ACURATE neo2. All-cause mortality was 0.8% at 30 days and 5.1% at 1 year. The 1-year rates for stroke and disabling stroke were 3.0% and 1.3%, respectively. Overall, HALT of >50% leaflet involvement of at least one leaflet was present in 9% of patients at 30 days and in 12% of patients at 1 year. No association was observed between the presence of HALT and 1-year clinical or haemodynamic outcomes. Early haemodynamic improvements were maintained up to 1 year (mean aortic valve gradient: 47.6±14.5 mmHg at baseline, 7.6±3.2 mmHg at 1 year; mean aortic valve area: 0.7±0.2 cm 2 at baseline, 1.7±0.4 cm 2 at 1 year). At 1 year, 99% of patients had mild or no/trace PVL (<1% had moderate PVL; no patient had severe PVL)., Conclusions: The study outcomes confirm favourable performance and safety up to 1 year in patients treated with ACURATE neo2 in routine clinical practice. (ClinicalTrials.gov: NCT04655248).

Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury may induce or aggravate HF via imbalanced neural and neurovegetative control of cardiovascular regulation. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiological interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiological mechanisms, complications, clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state-of-the-art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of HF and stroke., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Heart failure (HF) and atrial fibrillation (AF) are common and coexistent conditions., Hypothesis: To investigate the adverse events and mortality risk factors in patients with AF and HF treated with rivaroxaban in Spain., Methods: Multicenter, prospective and observational study with a follow-up of 2 years, that included adults, with a diagnosis of nonvalvular AF and chronic HF, anticoagulated with rivaroxaban at least 4 months before being enrolled., Results: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, the mean age was 73.7 ± 10.9 years, 65.9% were male, 51.3% had HF with preserved ejection fraction and 58.7% were on New York Heart Association functional class II. CHA 2 DS 2 -VASc was 4.1 ± 1.5. During the follow-up, 11.6% of patients died and around one-quarter of patients were hospitalized or visited the emergency department, being HF worsening/progression the main cause (51.1%), with a 2.9% of thromboembolic events and 2.0% of acute coronary syndromes. Major bleeding occurred in 3.1% of patients, with 0.5% experiencing intracranial bleeding but no fatalities. Compliance with HF treatment was associated with a lower risk of death (hazard ratio: 0.092; 95% confidence interval: 0.03-0.31)., Conclusions: Among patients with HF and AF anticoagulated with rivaroxaban, incidences of thromboembolic or hemorrhagic complications were low. The most important factor for improving survival was compliance with HF drugs, what strengths the need for early treatment with HF disease-modifying therapy and anticoagulation., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome of the metanalysis was the incidence of major adverse cardiovascular events, defined by each study protocol. Secondary outcomes for the analyses were myocardial infarction, stroke, myocardial revascularization, cardiovascular death, and all-cause death. Results of 4 clinical trials evaluated contained a total of 17,324 patients; 9,236 received bempedoic acid for a median of 46.6 months. The mean baseline LDLc was 129.4 (22.8) mg/100 ml and treatment was associated with a mean LDLc reduction of 26.0 (12.6) mg/100 ml. Treatment with bempedoic acid significantly reduced the incidence of major adverse cardiovascular events (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81 to 0.96), myocardial infarction (HR 0.76, 95% CI 0.66 to 0.89) and myocardial revascularization (HR 0.82, 95% CI 0.73 to 0.92); the crude incidence of stroke, cardiovascular or all-cause mortality were lower in patients in the bempedoic acid groups although no significant risk reduction was observed. No heterogeneity was observed in any of the end points. In conclusion, the metanalysis of the 4 clinical trials currently available with bempedoic acid provides reliable evidence of its clinical benefit with no signs of heterogeneity or harm., Competing Interests: Declaration of Competing Interest Dr. Cordero reports honoraria for lectures from AstraZeneca, AMGEN, Bristol-Myers Squibb, Ferrer, Boehringer Ingelheim, Merck Sharp & Dohme, Daiichy Sankio, Novartis, Novo Nordisk, Sanofi and Amarin; and consulting fees from AstraZeneca, Ferrer, Sanofi, AMGEN, Novartis, Lilly, Novo Nordisk and Amarin. Dr. Fernández reports honoraria for lectures from AstraZeneca, AMGEN, Ferrer, Merck Sharp & Dohme, Daiichi Sankio, Novartis, Novo Nordisk, Sanofi, and Amarin; and consulting fees from AstraZeneca, Sanofi, AMGEN, Novartis, Novo Nordisk, and Amarin. Dr. Castellano reports honoraria from Ferrer, Servier, Daiichi Sankyo, and Pfizer. Dr. Fácila reports honoraria for lectures from Eli Lilly Co, Daiichi Sankyo, Inc., Bayer, Pfizer, Novartis Boehringer Ingelheim, and consulting fees from AstraZeneca, Boehringer, Bayer. Dr. Rodriguez-Mañero reports research grants from Fundación Mutua Madrileña, Biosense Webster, Medtronic, and the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain). Dr. Bonanad has received fees from AstraZeneca; Amgen, Bayer; Boehringer; Bristol-Myers Squibb; Daiichi Sankyo; Ferrer; Novartis AG; Pfizer; Roche Pharma; Sanofi Pharma. Dr. González Juanatey reports honoraria for lectures from Eli Lilly Co, Daiichi Sankyo, Inc., Bayer, Pfizer, Abbott, Boehringer Ingelheim, Merck Sharp & Dohme, Ferrer, and Bristol-Myers Squibb; consulting fees from AstraZeneca, Ferrer, Bayer, Boehringer Ingelheim; and research grants from AstraZeneca, Boehringer Ingelheim and Daichi-Sankyo. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome.", Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory Y.H. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. All other authors report no disclosures., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Oral anticoagulation in non-valvular atrial fibrillation is associated with an increased risk of bleeding, particularly gastrointestinal bleeding, leading to treatment withdrawal in up to 50% of patients and putting them at risk of embolic events. Left atrial appendage closure (LAAC) can be an alternative to chronic anticoagulation. We aim to describe the impact of LAAC in patients with gastrointestinal bleeding (GIB) or chronic iron deficiency anaemia (CIDA) on healthcare resources consumption., Methods: Observational retrospective study of patients who underwent LAAC for GIB or CIDA at a single centre., Results: Nineteen patients with a median age of 74 years and a median Charlson score of six points were included in the study. Angiodysplasias were the most frequent cause of GIB or CIDA. The procedural success rate of LAAC was 100% with a median anticoagulant and antiplatelet treatment duration of 92 days. One year after the LAAC, we found a significant improvement in the lowest haemoglobin concentration and a reduction in the number of red blood cells transfusion, hospital admissions due to GIB and CIDA and the number of endoscopic examinations. One patient died due to a pulmonary thromboembolism. No deaths related to GIB were observed., Conclusions: LAAC seems to be a safe and effective alternative to anticoagulation in patients with GIB or CIDA., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Aims: To evaluate the prevalence and associations of non-cardiac comorbidities (NCCs) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum., Methods and Results: The 9326 AHF patients from European Society of Cardiology (ESC)-Heart Failure Association (HFA)-EURObservational Research Programme Heart Failure Long-Term Registry had complete information for the following 12 NCCs: anaemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson's disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, and stroke/transient ischaemic attack (TIA). Patients were classified by number of NCCs (0, 1, 2, 3, and ≥4). Of the AHF patients, 20.5% had no NCC, 28.5% had 1 NCC, 23.1% had 2 NCC, 15.4% had 3 NCC, and 12.5% had ≥4 NCC. In-hospital and post-discharge mortality increased with number of NCCs from 3.0% and 18.5% for 1 NCC to 12.5% and 36% for ≥4 NCCs.Anaemia, COPD, PVD, sleep apnoea, rheumatoid arthritis, stroke/TIA, Parkinson, and depression were more prevalent in HF with preserved EF (HFpEF). The hazard ratio (95% confidence interval) for post-discharge death for each NCC was for anaemia 1.6 (1.4-1.8), diabetes 1.2 (1.1-1.4), kidney dysfunction 1.7 (1.5-1.9), COPD 1.4 (1.2-1.5), PVD 1.2 (1.1-1.4), stroke/TIA 1.3 (1.1-1.5), depression 1.2 (1.0-1.5), hepatic dysfunction 2.1 (1.8-2.5), malignancy 1.5 (1.2-1.8), sleep apnoea 1.2 (0.9-1.7), rheumatoid arthritis 1.5 (1.1-2.1), and Parkinson 1.4 (0.9-2.1). Anaemia, kidney dysfunction, COPD, and diabetes were associated with post-discharge mortality in all EF categories, PVD, stroke/TIA, and depression only in HF with reduced EF, and sleep apnoea and malignancy only in HFpEF., Conclusion: Multiple NCCs conferred poor in-hospital and post-discharge outcomes. Ejection fraction categories had different prevalence and risk profile associated with individual NCCs., Competing Interests: Conflict of interest: O. Chioncel declare no conflict of interest related to present work; ESC meeting support from Servier. L. Benson declare no conflict of interest. M. Crespo-Leiro reports unrelated to the present work: consultancy or speaker's honoraria from Novartis, AstraZeneca, Boehringer Ingelheim, Abbott, Medtronic, CareDx, Astellas and Vifor Pharma. S.D. Anker reports unrelated to the present work: Grants or contracts: Vifor Int, Abbott Vascular; Consulting fees: CVRx, Amgen, Respicardia, Novo Nordisk, Brahms, Novartis, Sanofi, Cordio; Leadership or fiduciary role in other board: Abbott Vascular, Astra Zeneca, Bayer AG, Bioventrix, Boehringer Ingelheim, Cardiac Dimension, Cardior, Impulse Dynamics, Janssen, Occlutech, Servier, Vifor Int, and V-Wave. A.J.S. Coats reports unrelated to the present work: speaker's honoraria from: Astra Zeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, and Viatris. G. Filippatos reports lecture fees and/or committee membership in trials sponsored by Bayer, Vifor, Medtronic, Novartis, Servier, Boehringer Ingelheim, and research support from the European Union. T. McDonagh reports unrelated to the present work: speaker's honoraria from Abbot, Astra Zeneca, Boeringher Ingelheim and Edwards. C. Margineanu none related to the present work. A. Mebazaa reports unrelated to the present work: Grants or contracts from and consulting fees from Roche, 4TEEN4, Corteria; speaker's honoraria from MSD; Patents: S-Form Pharma. M. Metra reports personal fees from Amgen, AstraZeneca, Abbott Vascular, Bayer, Edwards Therapeutics, Livanova, Vifor Pharma, as member of Trials' Committees or advisory boards or for speeches at sponsored meetings in the last 3 years. M. Piepoli reports unrelated to the present work: consultancy, speaker's, institutional fees from Astra-Zeneca, Boehringer- Ingelheim, CHF solution, Menarini, Novartis, Servier M. Adammo reports speaker fees from Abbott Vascular and Medtronic. G.M.C. Rosano declare no conflict of interest. F. Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Amgen, Astra Zeneca, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V- Wave, Vascular Medical, Vifor, Wissens Plus, ZOLL. The research and educational grants do not impact on Prof. Ruschitzka`s personal remuneration. G. Savarese reports unrelated to the present work: Grants or contracts: Vifor Pharma, Boehringer Ingelheim, Astra Zeneca, Merck, Cytokinetics; Consulting fees: Societa' Prodotti Antibiotici, Medical Education Global Solutions, Genesis, Agence Recherche (ANR); speaker's honoraria: Servier, Cytokinetics, Medtronic, Dynamicom Education, Vifor Pharma; Support for attending meetings: Boehringer Ingelheim; Data Safety Monitoring Bord or Advisory Board: Astra Zeneca, Uppsala Clinical Research Center, Servier. P. Seferovic reports unrelated to the present work: speaker's honoraria from Servier, Astra Zeneca, Menarini, Boehringer Ingelheim, Novartis and Roche diagnostic. M. Volterrani: none related to the present work. R. Ferrari reports unrelated to the present work: speaker's honoraria and support for attending meetings: Servier International, Merck Serono, Lupin, Sunpharma, Reddys Ltd; leadership or fiduciary role in other board: Scientific Director of Medical Trial Analysis. A. Maggioni: personal fees from AstraZeneca, Bayer, Fresenius, Novartis, outside the submitted work. L.H. Lund is supported by Supported by Karolinska Institutet, the Swedish Research Council [grant 523-2014-2336], the Swedish Heart Lung Foundation [grants 20150557, 20190310], and the Stockholm County Council [grants 20170112, 20190525] and reports unrelated to the present work: Grants: AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, MSD; Consulting: Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Life Sciences, Alleviant; Speaker's honoraria: Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, Bayer; Patent: AnaCardio; Stock ownership: AnaCardio., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA 2 DS 2 -VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA 2 DS 2 -VASc, and HAS-BLED were associated with increased risk of adverse outcomes., Competing Interests: Declaration of Competing Interest JM Rivera-Caravaca is a consultant for Idorsia Pharmaceuticals LTD. M. Anguita Sanchez has received financial compensation from Bayer for participating in the EMIR registry. M. Sanmartín Fernández has received speaker and advisory fees from the following companies in the past 3 years: Bayer, Boehringer-Ingelheim, BMS, and Pfizer. C. Rafols is an employee of the Medical Department, Bayer Hispania S.L, which is the sponsor of the EMIR study. G. Barón-Esquivias has received lecture fees from Bayer, Boehringer-Ingelheim, Daiichi Sankyo, Pfizer-BMS, Sanofi, Novartis, and Rovi; and financial compensation from Bayer for participating in the EMIR study and an institutional grant from Novartis. J. Cosín-Sales has received financial compensation from Bayer for participating in the EMIR registry. R. Freixa-Pamias has received consultancy/lecturing fees from Bayer, BMS/Pfizer, Boehringer-Ingelheim, and Daiichi Sankyo; and financial compensation from Bayer for participating in the EMIR study. I. Lekuona Goya has received financial compensation from Bayer for participating in the EMIR study. JM Vázquez Rodríguez has received lecture fees from Bayer, Boehringer-Ingelheim, Pfizer, Bristol Myers Squibb, and Daiichi Sankyo; and financial compensation from Bayer for participating in the EMIR study. AI Pérez-Cabeza has received consultancy/lecturing fees from Bayer, Boehringer-Ingelheim, Pfizer, Bristol Myers Squibb, and Daiichi Sankyo. I. Ureña Montilla has received financial compensation from Bayer for participating in The EMIR study; speaker and advisory fees from the following companies: Bayer, Novartis, Daiichi Sankyo, Vifor, Boehringer-Ingelheim, and Amgen. A. Alvarez-Vieitez Blanco has received financial compensation from Bayer for participating in the EMIR study. F. Arribas Ynsaurriaga has received consultancy/lecture fees and research funding from Daiichi Sankyo, Pulse Dynamics, Medtronic, Boston Scientific, Bayer, Bristol Myers Squibb, Arrhythmia Network Technology SL/BAROSTIM, Abbott, Novartis, Janssen-Cilag, Biosensors, and Edwards Lifesciences; and received financial compensation from Bayer for participating in the EMIR registry. F Marín has received consultancy/lecturing fees from Bayer, Boehringer-Ingelheim, Pfizer, Bristol Myers Squibb, and Daiichi Sankyo., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach., Methods and Results: The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N = 2651) were 166±25 and -14.8 ± 0.4 mmHg, respectively. Mean reductions in blood pressure ranged from -11.0--21.8 mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P < 0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses., Conclusion: Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control., Methods: We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality., Results: Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality., Conclusions: Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction., (Copyright © 2023. Published by Elsevier Inc.)

Aim: Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. Methods: This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. Results: 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of €274/patient, from the perspective of society. Conclusion: Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.

Objectives: To analyze the long-term benefits and safety of oral anticoagulation therapy prescribed in emergency departments for elderly patients with atrial fibrillation, and to detect any sex-related differences present., Material and Methods: Post-hoc analysis of data compiled by the EMERG-AF group (Spanish acronym for Emergency Department Stroke Prophylaxis and Guidelines Implementation in Atrial Fibrillation). Consecutive patients aged 75 years or older with atrial fibrillation who were treated in 62 EDs were included. We recorded clinical data and anticoagulants prescribed. Patients were followed for 1 year. The main outcome variable was a composite of death, thromboembolism, or major bleeding within 1 year., Results: Data for 690 patients were registered; 386 (55.9%) were women. At discharge, 575 patients (83.3%) were on anticoagulants; therapy was started in the ED for 96 of them. A total of 158 patients (22.9%) had experienced at least 1 component of the main outcome within 1 year: 118 (17.1%) died, 22 (2.7%) had thromboembolic complications, and 34 (4.9%) had major bleeding. After adjustment for main clinical characteristics, hazard ratios (HRs) showed that anticoagulation therapy was associated with a reduction in the composite outcome (HR, 0.372; 95% CI, 0.236-0.587; P .001) but not specifically with major bleeding overall. When data for women were analyzed separately, anticoagulant therapy was again associated with a reduction in the composite outcome (HR, 0.372; 95% CI, 0.236-0.587; P .001) and also with death (HR, 0.281; 95% CI, 0.168-0.469; P .001), even in patients with anticoagulant prescriptions initiated on discharge from the ED. These associations did not reach statistical significance in men., Conclusion: ED anticoagulant prescription for elderly patients with atrial fibrillation is safe and contributes to a reduction in mortality. Women in this age group benefited more than men from starting anticoagulation during the acute phase in the ED.

Introduction and Objectives: Transthyretin cardiac amyloidosis (ATTR-CA) patients often have atrial fibrillation and increased bleeding/thrombogenic risks. We aimed to evaluate outcomes of left atrial appendage closure (LAAC) compared with patients without a known diagnosis of CA., Methods: Comparison at long-term of patients diagnosed with ATTR-CA who underwent LAAC between 2009 and 2020 and those without a known diagnosis of CA., Results: We studied a total of 1159 patients. Forty patients (3.5%) were diagnosed with ATTR-CA; these patients were older and had more comorbidities, higher HAS-BLED and CHA 2 DS 2 -VASc scores, and lower left ventricular function. Successful LAAC was achieved in 1137 patients (98.1%) with no differences between groups. Regarding in-hospital and follow-up complications, there were no differences between the groups in ischemic stroke (5% vs 2.5% in those without a known diagnosis of CA; P=.283), hemorrhagic stroke (2.5% and 0.8% in the control group; P=.284), major or minor bleeding. At the 2-year follow-up, there were no significant differences in mortality (ATTR-CA: 20% vs those without known CA: 13.6%, 0.248); however, the at 5-year follow-up, ATTR-CA patients had higher mortality (40% vs 19.2%; P <.001) but this difference was unrelated to hemorrhagic complications or ischemic stroke., Conclusions: LAAC could reduce the risk of bleeding complications and ischemic cerebrovascular events without increasing the rate of early or mid-term complications. Although long-term survival was impaired in ATTR-CA patients, it was comparable to that of patients without a known diagnosis of CA at the 2-year follow-up, suggesting that LAAC for patients with ATTR-CA might not be futile., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Atrial fibrillation (AF) is common and increases the risk of stroke and mortality. Previous studies have suggested that air pollution is an important risk factor for new-onset AF. Herein, we review the evidence regarding: 1) the association between exposure to particulate matter (PM) and new-onset AF, and 2) the risk of worse clinical outcomes in patients with pre-existent AF and their relation to PM exposure., Methods: A selection of studies between 2000 and 2023 linking PM exposure and AF was performed through searches in PubMed, Scopus, Web of Science, and Google Scholar., Results: 17 studies from different geographical areas demonstrated that exposure to PM was associated with an increased risk of new-onset AF, although the results were heterogeneous regarding the temporal pattern (short- or long-term) ultimately related to AF. Most of the studies concluded that the risk of new-onset AF increased between 2 %-18 % per 10 μg/m 3 increment in PM 2.5 or PM 10 concentrations, whereas the incidence (percentage of change of incidence) increased between 0.29 %-2.95 % per 10 μg/m 3 increment in PM 2.5 or PM 10 . Evidence about the association between PM and adverse events in patients with pre-existent AF was scarce but 4 studies showed a higher risk of mortality and stroke (between 8 %-64 % in terms of hazard ratio) in patients with pre-existent AF when PM exposure was higher., Conclusions: Exposure to PM (both PM 2.5 and PM 10 ) is a risk factor for AF, and a risk factor for mortality and stroke in patients who already suffer from AF. Since the relationship between PM and AF is independent of the region of the world, PM should be considered as a global risk factor for both AF and worse clinical outcomes in AF patients. Specific measures to prevent air pollution exposure need to be adopted., Competing Interests: Declaration of competing interest GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are received personally. JMRC: Consultant for Idorsia Pharmaceuticals LTD. There is nothing to disclose for other authors., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Endothelial dysfunction is a forerunner of atherosclerosis, leading to cardiovascular disease, and albuminuria is a marker of endothelial dysfunction. Circulating levels of microRNAs are emerging as potential biomarkers for cardiovascular disease. Here we estimate the predictive value of a plasma microRNAs signature associated with albuminuria in the incidence of cardiovascular events., Methods: Plasma microRNAs quantified in hypertensive patients by next generation sequencing were validated in a cohort of patients and controls by real-time quantitative PCR. The microRNAs found to be associated with albuminuria were analysed for their prognostic value in predicting cardiovascular events incidence on a retrospective, population-based study (Hortega Study), using Cox proportional hazard models., Results: A plasma microRNA profile was identified in the discovery cohort (n = 48) associated with albuminuria and three microRNAs (miR-126-3p, miR-1260b and miR-374a-5p) were confirmed in the validation cohort (n = 98). The microRNA signature discriminates urinary albumin excretion at baseline (n = 1025), and predicts the incidence of cardiovascular events and coronary heart disease and stroke in a general population retrospective study within a 14-year follow-up (n = 926). High miR-126-3p levels were associated with a shorter time free of both cardiovascular events (HR=1.48, (1.36-1.62), p < 0.0001), as well as coronary artery disease and stroke combined (HR=2.49, (2.19-2.83), p < 0.0001)., Conclusions: An increased plasma microRNAs profile was identified in hypertensive patients with albuminuria. Increased miR-126-3p suggest it may serve as a prognostic marker for cardiovascular events in a long-term general population. Further studies will assess the potential role of miR-126-3p as a guide for the status of endothelial dysfunction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Oral anticoagulation (OAC) significantly mitigates thromboembolism risks in atrial fibrillation (AF) and venous thromboembolism (VTE) patients yet concern about major bleeding events persist. In fact, clinically relevant hemorrhages can be life-threatening. Bleeding risk is dynamic and influenced by factors such as age, new comorbidities, and drug therapies, and should not be assessed solely based on static baseline factors., Areas Covered: We comprehensively review the bleeding risk associated with OAC therapy. Emphasizing the importance of assessing both thromboembolic and bleeding risks, we present clinical tools for estimating stroke and systemic embolism (SSE) and bleeding risk in AF and VTE patients. We also address overlapping risk factors and the dynamic nature of bleeding risk., Expert Opinion: The OAC management is undergoing constant transformation, motivated by the primary objective of mitigating thromboembolism and bleeding hazards, thereby amplifying patient safety throughout the course of treatment. The future of OAC embraces personalized approaches and innovative therapies, driven by advanced pathophysiological insights and technological progress. This holds promise for improving patient outcomes and revolutionizing anticoagulation practices.

Background: Atrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the association between AD or vascular dementia and adverse outcomes in AF patients., Methods: Cohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4-years of follow-up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all-cause deaths, were recorded., Results: Two thousand three hundred seventy-seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well-matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow-up (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.33-3.70, log-rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32-fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09-1.59, log-rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01-1.31), and mortality (HR: 1.25, 95% CI: 1.01-1.58) were also higher among AF patients with vascular dementia compared to AD., Conclusions: The two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: An association with aortic aneurysm has been reported among patients with atrial fibrillation (AF). The aims of this study were to investigate the prevalence of thoracic aorta aneurysm (TAA) among patients with AF and to assess whether the co-presence of TAA is associated with a higher risk of adverse clinical outcomes., Methods and Results: Using TriNetX, a global federated health research network of anonymised electronic medical records, all adult patients with AF, were categorised into two groups based on the presence of AF and TAA or AF alone. Between 1 January 2017 and 1 January 2019, 874,212 people aged ≥ 18 years with AF were identified. Of these 17,806 (2.04%) had a TAA. After propensity score matching (PSM), 17,805 patients were included in each of the two cohorts. During the 3 years of follow-up, 3079 (17.3%) AF patients with TAA and 2772 (15.6%) patients with AF alone, developed an ischemic stroke or transient ischemic attack (TIA). The risk of ischemic stroke/TIA was significantly higher in patients with AF and TAA (HR 1.09, 95% CI 1.04-1.15; log-rank p value < 0.001) The risk of major bleeding was higher in patients with AF and TAA (OR 1.07, 95% CI 1.01-1.14), but not significant in time-dependent analysis (HR 1.04, 95% CI 0.98-1.10; log-rank p value = 0.187), CONCLUSION: This retrospective analysis reports a clinical concomitance of the two medical conditions, and shows in a PSM analysis an increased risk of ischemic events in patients affected by TAA and AF compared to AF alone., (© 2023. The Author(s).)

Background: An early diagnosis and early initiation of oral anticoagulants (OAC) are main determinants for outcomes in patients with atrial fibrillation (AF). Inter-clinician electronic consultations (e-consultations) program for the general practitioner referrals to cardiologist may improve health care access by reducing the elapsed time for cardiology care., Objective: To evaluate the effect of a reduced elapsed time to care after a inter-clinician e-consultations program implementation (2013-2019) in comparison with previous in-person consultation (2010-2012) in the outpatient health care management in a Cardiology Department., Methodology: We included 10,488 patients with AF from 1 January 2010, to 31 December 2019. Until 2012, all patients attended an in-person consultation (2010-2012). In 2013, we instituted an e-consult program (2013-2019) for all primary care referrals to cardiologists that preceded patient's in-person consultation when considered. The shared electronic patient dossier (EPD) was available between GP and cardiologist, and any change in therapy advice from cardiologist was directly implemented in this EPD., Results: During the e-consultation period (2013-2019) were referred 6627 patients by GPs to cardiology versus 3861 during the in-person consultation (2010-2012). The e-consultation implementation was associated with a reduction in the elapsed time to anticoagulation prescription (177.6 ± 8.9 vs. 22.5 ± 8.1 days, p < .001), and an increase of OAC use (61% [95% IC: 19.6%-102.4%], p < .001). The e-consult program implementation was associated with a reduction in the 1-year CV mortality (.48 [95% CI: .30-.75]) and all-cause mortality (.42 [95% CI: .29-.62]). The OAC reduces the stroke mortality (.15 [95% CI: .06-.39]) and CV mortality (.43 [95% CI: .29-.62]) and all-cause mortality (.23 [95% CI: .17-.31])., Conclusion: A shared EPD-based inter-clinician e-consultation program significantly reduced the elapsed time for cardiology consultation and initiation of OAC. The implementation of this program was associated with a lower risk of stroke and cardiovascular/all-cause mortality., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes.

Background: 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence., Aim: Our aim was to evaluate the performance of soluble low-density lipoprotein receptor-related protein 1 (sLRP1) as an indicator of carotid plaque inflammation., Methods: A prospective study was conducted among adult patients with recent (< 7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. Patients underwent an early (< 15 days from inclusion) 18 F-FDG PET, and the maximum standardized uptake value (SUVmax) within the plaque was measured. sLRP1 levels were measured in plasma samples by ELISA. The association of sLRP1 with SUVmax was assessed using bivariate and multivariable linear regression analyses. Hazard ratios (HR) were estimated with Cox regression to evaluate the association between circulating sLRP1 and stroke recurrence., Results: The study was conducted with 64 participants, of which 57.8% had ≥ 50% carotid stenosis. The multivariable linear and logistic regression analyses showed that sLRP1 was independently associated with (i) SUVmax within the plaque (β = 0.159, 95% CI 0.062-0.257, p = 0.002) and (ii) a probability of presenting SUVmax ≥ 2.85 g/mL (OR = 1.31, 95% CI 1.00-1.01, p = 0.046), respectively. Participants with stroke recurrence showed higher sLRP1 levels at baseline [6447 ng/mL (4897-11163) vs. 3713 ng/mL (2793-4730); p = 0.018]., Conclusions: sLRP1 was independently associated with carotid plaque inflammation as measured by 18 F-FDG PET in patients with recent ischemic stroke and carotid atherosclerosis., (© 2023. The Author(s).)

Background: Risk stratification in patients with atrial fibrillation (AF) is important to facilitate guideline-directed therapies. The Calculator of Absolute Stroke Risk (CARS) scheme enables an individualized estimation of 1-year absolute risk of stroke in AF. We aimed to investigate the predicted and absolute risks of ischaemic stroke, and evaluate whether CARS (and CHA2DS2-VASc score) may be useful for identifying high risk patients with AF despite contemporary treatment., Methods: We utilized the EORP-AF General Long-Term Registry which prospectively enrolled patients with AF from 250 centres across 27 participating European countries. Patients with sufficient data to determine CARS and CHA2DS2-VASc score, and reported outcomes of ischaemic stroke were included in this analysis. The primary outcome of ischaemic stroke was recorded over a 2-year follow-up period., Results: A total of 9444 patients were included (mean age 69.1 [±11.4] years; 3776 [40.0%] females). There was a high uptake (87.9%) of anticoagulation therapy, predominantly with vitamin K antagonist (50.0%). Over a mean follow-up period of 24 months, there were a total of 101 (1.1%) ischaemic stroke events. In the entire cohort, the median CARS and absolute annual risks of ischaemic stroke were 2.60 (IQR 1.60-4.00) and 0.53% (95%CI 0.43-0.64%), respectively. There was no statistical difference between the predictive performance of CARS and CHA2DS2-VASc score (0.621 [95%CI 0.563-0.678] vs. 0.626 [95%CI 0.573-0.680], P = 0.725)., Conclusion: Contemporary management of AF was associated with a low risk of ischaemic stroke. CARS and CHA2DS2-VASc score may be useful to identify high risk patients despite treatment who may benefit from more aggressive treatment and follow-up., Competing Interests: Conflict of interest: G.B.: small speaker’s fees from Medtronic, Boston, Biotronik, Boehringer, and Bayer, outside of the submitted work. F.M.: receiving grants from Ferrer, and personal fees from Bayer, Pfizer/BMS. Boehringer-Ingelheim and Astra-Zeneca outside the submitted work. C.B.L.: receiving grants from Medtronic, Cardiome, and personal fees from Bayer, Sanofi, Boston Scientific, Philips, CathPrint, Organon, and Merck Sharp & Dohme outside the submitted work. T.S.P.: Consultant for Bayer and Pfizer, no fees. L.F.: consultant and speaker activities of small amounts for AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic, Novartis, Novo, XO and Zoll. G.Y.H.L.: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. Other authors declare no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI., Competing Interests: Conflict of interest: RBS has received lecture fees and advisory board fees from BMS/Pfizer outside this work and has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union's Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (8121710103); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239).EAM is employee of Daiichi Sankyo Europe GmbH producing and marketing an oral anticoagulant (edoxaban). EA has received consulting / speaker fees for Biosense Webster. GB has received speaker's fees of small amount from Boston, Bayer, Daiichi, Boehringer. SB is consultant for Medtronic, Boston Scientific, Microport, and Zoll. JC has received consulting fees / honoraria fees from Acesion, Allergan, Alta Thera, Arca, lncarda, Menarini, Milestone, Sanofi, Bayer, Daiichi Sankyo, Pfizer, Abbott, Biosense Webster, Biotronik, Boston Scientific, Lilly, Medtronic, Johnson and Johnson. BC has received in kind contribution for research Support from iRhythm. WC has received advisory board fees for Roche Diagnostics AG. MDM is employee of Medtronic. SZB has received fees as member of Advisory Board in Bristol Myers Squibb-Pfizer. DD has received fees from Abbott, Astra Zenica, Bayer, Bosten Scientific, Bristol Myers Squibb-Pfizer, Medtonic, Zoll. LE has received lecture Honoria from Medtronic, Biotronik, Boston Scientific, Boehringer Ingelheim, Daiichy Sankyo, Bayer, MMS, Pfizer, Sanofi and received research grants from DFG and DGK. CE is employee of Preventicus GmbH. LF has received institutional research grants and non-financial support from European Union, DFG, British Heart Foundation, Medical Research Council (UK), NIHR, and several biomedical companies. The Institute of Cardiovascular Research, University of Birmingham, has received an Accelerator Award by the British Heart Foundation M/18/2/34218. LF is listed as inventor of two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). BF receiving fees from Bristol-Myers Squibb and Pfizer Alliance, Bayer, Daiichi Sankyo, Omron. (largely speaker fees and travel support for speaking at session or official satellites of large international/continental society meetings) and investigator-initiated research grants to the institution from Bristol-Myers and Squibb and Pfizer Alliance and Ownership / Employee of Nil. LG and AZ are employees of Roche Diagnostics International Ltd. AG has received funding from Daiichi Sankyo, Astra Zenica, Bayer, Bristol Myers Squibb-Pfizer, Viola, Medtonic, Berlin Charitè. JHS has received Advisory board fees in Medtronic and Speaker fee from Medtronic. KGH has received fees from Abbott, Alexion, AMARIN, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Bristol-Myers-Squibb, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Pfizer, Premier Research, SUN Pharma and W. L. Gare & Associates and Research Grants from Bayer Vital, Sanofi-Aventis. JSH received fees from Boston Scientific, Servier, Bayer, Myokardia, Bristol-Myers-Squibb, Pfizer, and research grants from Medtronic, Boston Scientific, Bristol-Myers-Squibb, Abbott. HH has received lecture and consultancy fees from Abbott, Biotronik, Bristol-Myers-Squibb- Pfizer, Medscape, Daiichi Sankyo, Springer Healthcare Ltd and receive un conditional research grants through the Univerity of Antwerp and/or University of Hasselt from Abbott, Bayer, Biotronik, Biosense-Webster, Fibrickeck/Qompium, Medtronic, Bristol-Myers-Squibb- Pfizer, Boston Scientific, Daiichi Sankyo and Boehringer Ingelheim. RH has received speacker fees from BI, Bayer and Bristol-Myers-Squibb- Pfizer and AZ. TH is CEO of Preventicus GmbH. DK has received funding from Bayer, AtriCure, Protherics Medicines Development and Myokardia and Research grant from rants from the National Institute for Health Research (NIHR CDF-2015-08-074 RATE-AF; NIHR HTA-130280 DaRe2THINK; NIHR EME- 132974 D2T-NV), the British Heart Foundation (PG/17/55/33087 and AA/18/2/34218), EU/EFPIA IMI (BigData@Heart 116074),the European Society of Cardiology supported by educationalgrants from Boehringer Ingelheim/BMS-Pfizer Alliance/Bayer/Daiichi Sankyo/Boston Scientific, the NIHR/the University of Ox- ford Biomedical Research Centre, and British Heart Foundation/ the University of Birmingham Accelerator Award (STEEER-AF NCT04396418), Amomed Pharma, and IRCCS San Raffaele/Menarini (beta-blockers in Heart Failure Collaborative Group NCT0083244). MK is employee of Bristol-Myers and Squibb. CL has received fees from medtonic, Boston Scientific, Biotronik and Bristol-Myers and Squibb- Pfizer and research grants from Rennes Univerity, Metronik, Biotonik and Boston Scientific. DL has received research grant for EHRA-PATHS, NovoNordisk Young Investigator Award. MLL has received lecture fees from Bristol-Myers and Squibb and research grant from H2020 AFFECT-EU (grant No. 847770). SM has received research grant from Daiichi Sankyo (EPDAURUS IIT) and Bristol-Myers and Squibb (APPROACH ACS AF IIT). JLM has received Abbott, Boston Scientific, Biotronik, Boehringer Ingelheim, Sanofi, Microport and received research grants from Medtronic, Abbott, Microport, Biosense. RM is employee of Medtronic. LM is Stockholder for Galgomedical and Corify and receiving consuting fees from Abbott, Biosense-Webster, Bosten Scientific, Medtronik and receiving research grants from Abbott, Biosense-Webster, Bosten Scientific, Medtronik. LN has received consulting fees from Bristol-Myers and Squibb- Pfizer. GP is employee of Bayer AG. HP has received consulting fees from Abbott, Biosense-Webster, Bosten Scientific, Medtronik and receiving research grants from Abbott, Bayer, Biosense-Webster, Bosten Scientific, Medtronik, Bristol-Myers and Squibb- Pfizer. MR has received consulting fees for Medtonic, Arca BiopharmaInc, Roche and received research grants from Dutch Heart Foundation: RACE V, RED-CVD, CVON-AI, DECISION studies; grant from SJM/Abbott to institution: VIP-HF study; Grant for Medtronic to institution: Cryoballoon AF registry/biobank study. The other authors declare that there is no conflict of interest.LR has received research grants from Canadian Insititute of Health research and Byer Inc. U.S. received consultancy fees or honoraria from Università della Svizzera Italiana (USI, Switzerland), Roche Diagnostics (Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited, (United Kingdom), Bayer Healthcare (Germany). U.S. is co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht and Research grant from the Dutch Heart Foundation (CVON RACE V, CVON2014–09) European Union's Horizon 2020 Research and Innovation Program granted to MS under the Marie Sklodowska-Curie grant agreement #813716 (TRAIN-HEART Innovative Training Network), and various other programs of the European Union granted to US (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network – grant #860974; CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly – grant #633196; MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation – grant #965286; REPAIR: Restoring cardiac mechanical function by polymeric artificial muscular tissue – grant #952166). DS has received consultation fees from Biosense Webster, Abbott, Boston Scientific, Consultant with stock option: SentiAR, Arga Medtech. RS is employee of Daiichi Sankyo Europe GmbH. DS has received consultation fees from Boston Scientific, Abbott and Research grant from Biosense Webster. ES has received lecture fees from Bayer, Bristol-Myers and Squibb- Pfizer, Boehringer Ingelheim, Johnson & Johnson, Merck Sharp & Dohme and Sanofi. DT has received lecture fees from Bayer Vital, Bristol-Myers and Squibb- Pfizer, Daiichi Sankyo, Medtonic, Zoll CMS, Sanofi, St. Jude Medical and research grant from Daiichi Sankyo. MTH is employee/owner of American Foundation of women's Health /StopAfib.org and employee/owner of True Hills Inc.. BV is employee of Bayer AG. RW has received consultation fees from Boston Scientific, Biotronic, Pfizer, Daiichi Sankyo, Bayer, Adagio Medical and Research grant from Bristol-Myers and Squibb- Pfizer, Boston Scientific. CW has received consulation fees from Biotronik, Boston Scientific, Novartis and research grant from BMBF, AFNET, DZHK, Biotronik. MW is employee and shareholder of Sanofi. SW has received Consulting fees from Boston Scientific, Abbott, Bayer, Bristol-Myers and Squibb- Pfizer, Boehringer Ingelheim and research grant from Boston Scientific. HW is employee and stockholder of Pfizer Germany. MDZ has received advisory and speaker fee from Bristol-Myers and Squibb- Pfizer. PK reports grants and non-financial support from BMBF (German Ministry of Education and Research), grants from Sanofi and Abbott, grants and non-financial support from EHRA (European Heart Rhythm Association), and grants from German Heart Foundation and DZHK (German Center for Cardiovascular Research), during the conduct of the study, and grants from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and non-financial support from German Centre for Heart Research, outside the submitted work; in addition, P.K. has a patent Atrial Fibrillation Therapy WO 2015140571 issued to University of Birmingham and a patent Markers for Atrial Fibrillation WO 2016012783 issued to University of Birmingham., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aim: To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes., Methods: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non-SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all-cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest., Results: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non-SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68-0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all-cause mortality (HR 0.61, 95% CI 0.58-0.64), cardiac arrest (HR 0.70, 95% CI 0.63-0.78), incident AF (HR 0.81, 95% CI 0.76-0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88-0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88-0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71-0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88-1.00)., Conclusion: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Previous evidence indicated that atrial fibrillation (AF) patients with polypharmacy presented increased probability of adverse events. We investigated the prevalence of polypharmacy, risk factors for polypharmacy, and the impact of polypharmacy in clinical outcomes in a 'real-world' cohort of AF patients starting vitamin K antagonists (VKAs)., Methods: Prospective study including AF outpatients starting VKA therapy from July, 2016 to June, 2018. At inclusion, all concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of ≥ 5 concomitant drugs. During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), fatal/nonfatal myocardial infarctions (MIs), bleeding events, venous thromboembolisms, and all-cause deaths were recorded., Results: 1050 patients (51.5 % females, median age 77 [69-83] years) were included, and the prevalence of polypharmacy was 32.9 % (345). Female sex (OR 1.5; 95 % CI 1.11-2.03), hypertension (OR 2.53; 95 % CI 1.51-4.22), diabetes (OR 3.11; 95 % CI 2.31-4.17), vascular disease (OR 3.08; 95 % CI 2.19-4.33), heart failure (OR 1.86; 95 % CI 1.35-2.58) and dyslipidemia (OR 2.61; 95 % CI 1.9-3.58) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence of major bleeding, net clinical outcomes (composite of major bleeding, ischemic stroke/TIA, and mortality), MACE (composite of ischemic stroke/TIA, MI, and cardiovascular death), and composite thrombotic/thromboembolic events; being an independent risk factor for major bleeding (HR 1.77, 95 % CI 1.07-2.92), and composite thrombotic/thromboembolic events (HR 1.55, 95 % CI 1.05-2.31)., Conclusion: In this "real world" AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with bleeding and thromboembolic events., Competing Interests: Conflicts of interest statement JMRC: Consultant for Idorsia Pharmaceuticals LTD. SA: Consultant and speaker for Bayer, Boehringer Ingelheim and Daiichi-Sankyo. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. There is nothing to disclose for other authors., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The Atrial fibrillation Better Care (ABC) pathway was proposed for a more holistic or integrated care approach to atrial fibrillation (AF) management. We investigated whether adherence with the ABC pathway reduced the risk of adverse clinical outcomes in real-world AF patients starting vitamin K antagonist (VKAs) therapy., Methods: Prospective cohort study including AF outpatients starting VKA therapy from July 2016 to June 2018. Patients were considered as adherent if all ABC pathway criteria (A: Avoid stroke; B: Better symptom control; and C: Cardiovascular risk factors/comorbidities management) were fulfilled. The primary endpoints were all-cause mortality, net clinical outcomes (NCOs), major adverse cardiovascular events (MACE), and composite thrombotic/thromboembolic events at 2 years., Results: We enrolled 1045 patients (51.6% female; median age 77 [70-83] years). Of these, 63.0% (658) were adherent to the ABC pathway and 37% (387) were considered non-adherent. Compared to non-adherent patients, those who were ABC adherent had lower event rates for all-cause mortality (13.76 vs. 6.56; p<0.001), NCOs (19.65 vs. 11.94; p<0.001), and MACE (11.88 vs. 7.75; p=0.006) during the follow-up. Adjusted Cox regression analyses demonstrated that the ABC pathway adherent care reduced the risks of all-cause mortality (aHR 0.57, 95% CI 0.42-0.78), NCOs (aHR 0.72, 95% CI 0.56-0.92), and cardiovascular mortality (aHR 0.54, 95% CI 0.32-0.90). Event-free survivals for all-cause mortality, NCOs (both log-rank p-values <0.001), and MACE (log-rank p-value = 0.004) were also higher in ABC pathway adherent patients., Conclusions: In this real-world prospective cohort of AF patients starting VKA therapy, adherence to the ABC pathway management at baseline significantly reduced the risk of NCOs, all-cause mortality, and cardiovascular death at 2 years., (© 2022. The Author(s).)

Background and Purpose: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil β 1 adrenoceptors (β1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that β1AR blockade will improve stroke outcomes., Experimental Approach: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective β1AR blocker metoprolol (12.5 mg·kg -1 ) when injected i.v. 10 min before reperfusion., Key Results: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1 + ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via β1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, β1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates., Conclusions and Implications: Our findings describe that β1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction and Objectives: Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up., Methods: We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up., Results: Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046)., Conclusions: Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults., Competing Interests: Conflict of interest: The authors declare that none received specific funding in relation to the work: ‘Acute, periprocedural and longterm antithrombotic therapy in older adults: 2022 Update by the ESC Working Group on Thrombosis’ by Felicita Andreotti, Tobias Geisler, Jean-Philippe Collet, Bruna Gigante, Diana A Gorog, Sigrun Halvorsen, Gregory YH Lip, Joao Morais, Eliano Pio Navarese, Carlo Patrono, Bianca Rocca, Andrea Rubboli, Dirk Sibbing, Robert F. Storey, Freek W.A. Verheugt, and Gemma Vilahur., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry., Methods and Results: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy., Conclusions: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.', Clinical Trial Registration: http://www., Clinicaltrials: gov identifier: NCT01991795., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Effects of Atrial Fibrillation Better Care (ABC) adherence among high-risk atrial fibrillation (AF) subgroups remains unknown. We aimed to evaluate the impact of ABC adherence on clinical outcomes in these high-risk patients., Methods: EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. High-risk patients were defined as those with either CKD (eGFR <60 mL/min/1.73m 2 ), elderly patients (≥75 years) or prior thromboembolism. Primary outcome was a composite event of all-cause death, thromboembolism and acute coronary syndrome., Results: 6646 patients with AF were screened (median age was 70 [IQR 61 - 77] years; 40.2% females). There were 3304 (54.2%) patients with either CKD (n = 1750), older age (n = 2236) or prior thromboembolism (n = 728). Among these, 924 (28.0%) were managed as adherent to ABC. At 2-year follow-up, 966 (14.5%) patients reported the primary outcome. The incidence of the primary outcome was significantly lower in high-risk patients managed as adherent to ABC pathway (IRR 0.53 [95%CI, 0.43 - 0.64]). Consistent results were obtained in the individual subgroups. Using multivariable Cox proportional hazards analysis, ABC adherence in the high-risk cohort was independently associated with a lower risk of the primary outcome (aHR 0.64 [95%CI, 0.51 - 0.80]), as well as in the CKD (aHR 0.51 [95%CI, 0.37 - 0.70]) and elderly subgroups (aHR 0.69 [95%CI, 0.53 - 0.90]). Overall, there was greater reduction in the risk of primary outcome as more ABC criteria were fulfilled, both in the overall high-risk patients (aHR 0.39 [95%CI, 0.25 - 0.61]), as well as in the individual subgroups., Conclusion: In a large, contemporary cohort of patients with AF, we demonstrate that adherence to the ABC pathway was associated with a significant benefit among high-risk patients with either CKD, advanced age (≥75 years old) or prior thromboembolism., (Copyright © 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: Patients with atrial fibrillation (AF) treated with oral anticoagulation still suffer from cardiovascular complications including cardiovascular death, stroke, and major bleeding. To identify risk factors for predicting stroke and bleeding outcomes in anticoagulated patients, we assessed 2-year outcomes in patients with AF treated with edoxaban in routine care. We also report the age-adjusted risk predictors of clinical outcomes., Methods and Results: The Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF) Europe (NCT02944019) is a prospective, multi-centre, post-authorisation, observational study with an overall 4-year follow-up conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Of the 13 133 patients with AF (mean age: 73.6 ± 9.5 years), 5682 (43.3%) were female. At the 2-year follow-up, 9017/13 133 patients were still on edoxaban; 1830 discontinued treatment including 937 who died (annualised event rate of all-cause death was 3.87%). 518 (2.14%) patients died of cardiovascular causes; 234 (0.97%) experienced major bleeding and 168 (0.70%) experienced stroke or systemic embolic events (SEE). Intracranial haemorrhage was noted in 49 patients (0.20%). History of transient ischaemic attack (TIA) at baseline was the strongest predictor of ischaemic stroke or SEE (Wald χ2: 73.63; P < 0.0001). Low kidney function at baseline was the strongest predictor of major bleeding (Wald χ2: 30.68; P < 0.0001). History of heart failure (HF) was the strongest predictor of all-cause (Wald χ2: 146.99; P < 0.0001) and cardiovascular death (Wald χ2: 100.38; P < 0.0001)., Conclusion: Patients treated with edoxaban in ETNA-AF-Europe reported low 2-year event rates in unselected AF patients. Prior stroke, reduced kidney function, and HF identify patients at high risk of stroke, bleeding and all-cause/cardiovascular death, respectively., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static 'one off' assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing 'best practice' when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice., Competing Interests: Conflict of interest: A.R.: speaker for Bayer, Daiichi-Sankyo, and Boehringer-Ingelheim. D.A.G.: grants from Bayer, Medtronic. Speaker for Bayer, Boehringer-Ingelheim, and AstraZeneca. D.L.: grants from BMS and Boehringer-Ingelheim; consultant and speaker for BMS, Boehringer-Ingelheim, and Bayer. F.M.: consultant and speaker for AstraZeneca and Boehringer-Ingelheim; grants from Bayer, Boehringer Ingelheim, and Daiichi-Sankyo. G.V.: speaker for AstraZeneca. G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. H.F.T.: grants from Abbott, Amgen, AstraZeneca, Bayer, Cooks Medical, Boehringer Ingelheim, Boston Scientific, Daichi Sankyo, Medtronic, Novartis, Pfizer, and Sanofi. J.L.F.: Speaker for AstraZeneca, Ferrer, Pfizer, Abbott Medical, Boehringer Ingelheim, Daiichi Sankyo, BMS, and Royi. K.H.: speaker for AstraZeneca, Bayer, and Boehringer-Ingelheim. L.F.: consultant and speaker activities for AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic, Novartis, Novo, and XO. The other authors have no conflict of interest to declare., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)