Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design.

BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. CONCLUSION: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757869.

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

The budget impact of implementing atrial fibrillation-screening in European countries.

A budget impact analysis estimates the short-term difference between the cost of the current treatment strategy and a new treatment strategy, in this case to implement population screening for atrial fibrillation (AF). The aim of this study is to estimate the financial impact of implementing population-based AF-screening of 75-year-olds compared with the current setting of no screening from a healthcare payer perspective in eight European countries. The net budget impact of AF-screening was estimated in country-specific settings for Denmark, Germany, Ireland, Italy, Netherlands, Serbia, Spain, and Sweden. Country-specific parameters were used to allow for variations in healthcare systems and to reflect the healthcare sector in the country of interest. Similar results can be seen in all countries AF-screening incurs savings of stroke-related costs since AF treatment reduces the number of strokes. However, the increased number of detected AF and higher drug acquisition will increase the drug costs as well as the costs of physician- and control visits. The net budget impact per invited varied from €10 in Ireland to €122 in the Netherlands. The results showed the increased costs of implementing AF-screening were mainly driven by increased drug costs and screening costs. In conclusion, across Europe, though the initial cost of screening and more frequent use of oral anti-coagulants will increase the healthcare payers' costs, introducing population screening for AF will result in savings of stroke-related costs.

COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.

COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.

Patient selection, peri-procedural management, and ablation techniques for catheter ablation of atrial fibrillation: an EHRA survey.

Catheter ablation (CA) of atrial fibrillation (AF) is the therapy of choice for the maintenance of sinus rhythm in patients with symptomatic AF. Time towards interventional treatment and peri-procedural management of patients undergoing AF ablation may vary in daily practice. The scope of this European Heart Rhythm Association (EHRA) survey was to report the current clinical practice regarding the management of patients undergoing AF ablation and physician's adherence to the European Society of Cardiology Guidelines and the EHRA/HRS/ECAS expert consensus statement on the CA for AF. This physician-based survey was conducted among EHRA members, using an internet-based questionnaire developed by the EHRA Scientific Initiatives Committee. A total of 258 physicians participated in the survey. In patients with paroxysmal or persistent AF, 42 and 9% of the physicians would routinely perform AF ablation as first-line therapy respectively, whereas 71% of physicians would consider ablation as first-line therapy in patients with symptomatic AF and left ventricular ejection fraction <35%. Only 14% of the respondents manage cardiovascular risk factors in patients referred for CA using a dedicated AF risk factor management programme. Radiofrequency CA is the preferred technology for first-time AF (56%), followed by cryo-balloon CA (40%). This EHRA survey demonstrated a considerable variation in the management of patients undergoing AF ablation in routine practice and deviations between guideline recommendations and clinical practice.

Contemporary management of atrial fibrillation and the predicted vs. absolute risk of ischaemic stroke despite treatment: a report from ESC-EHRA EORP-AF Long-Term General Registry.

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.

Atrial fibrillation and stroke prevention: 25 years of research at EP Europace journal.

Stroke prevention in patients with atrial fibrillation (AF) is one pillar of the management of this common arrhythmia. Substantial advances in the epidemiology and associated pathophysiology underlying AF-related stroke and thrombo-embolism are evident. Furthermore, the introduction of the non-vitamin K antagonist oral anticoagulants (also called direct oral anticoagulants) has clearly changed our approach to stroke prevention in AF, such that the default should be to offer oral anticoagulation for stroke prevention, unless the patient is at low risk. A strategy of early rhythm control is also beneficial in reducing strokes in selected patients with recent onset AF, when compared to rate control. Cardiovascular risk factor management, with optimization of comorbidities and attention to lifestyle factors, and the patient's psychological morbidity are also essential. Finally, in selected patients with absolute contraindications to long-term oral anticoagulation, left atrial appendage occlusion or exclusion may be considered. The aim of this state-of-the-art review article is to provide an overview of the current status of AF-related stroke and prevention strategies. A holistic or integrated care approach to AF management is recommended to minimize the risk of stroke in patients with AF, based on the evidence-based Atrial fibrillation Better Care (ABC) pathway, as follows: A: Avoid stroke with Anticoagulation; B: Better patient-centred, symptom-directed decisions on rate or rhythm control; C: Cardiovascular risk factor and comorbidity optimization, including lifestyle changes.

EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference.

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.

Integrated care for optimizing the management of stroke and associated heart disease: a position paper of the European Society of Cardiology Council on Stroke.

The management of patients with stroke is often multidisciplinary, involving various specialties and healthcare professionals. Given the common shared risk factors for stroke and cardiovascular disease, input may also be required from the cardiovascular teams, as well as patient caregivers and next-of-kin. Ultimately, the patient is central to all this, requiring a coordinated and uniform approach to the priorities of post-stroke management, which can be consistently implemented by different multidisciplinary healthcare professionals, as part of the patient 'journey' or 'patient pathway,' supported by appropriate education and tele-medicine approaches. All these aspects would ultimately aid delivery of care and improve patient (and caregiver) engagement and empowerment. Given the need to address the multidisciplinary approach to holistic or integrated care of patients with heart disease and stroke, the European Society of Cardiology Council on Stroke convened a Task Force, with the remit to propose a consensus on Integrated care management for optimizing the management of stroke and associated heart disease. The present position paper summarizes the available evidence and proposes consensus statements that may help to define evidence gaps and simple practical approaches to assist in everyday clinical practice. A post-stroke ABC pathway is proposed, as a more holistic approach to integrated stroke care, would include three pillars of management: A: Appropriate Antithrombotic therapy.B: Better functional and psychological status.C: Cardiovascular risk factors and Comorbidity optimization (including lifestyle changes).

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry.

BACKGROUND: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The 'Atrial fibrillation Better Care' (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. METHODS: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. RESULTS: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58-0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52-0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58-0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56-0.98) and composite outcome (aHR: 0.76, 95%CI 0.60-0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. CONCLUSIONS: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p < .001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01-1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23-3.99] compared to eGFR ≥90 ml/min/1.73 m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Impact of malignancy on outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EURObservational research programme in atrial fibrillation general long-term registry.

BACKGROUND: The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management. PURPOSE: To evaluate the outcomes of patients with active or prior malignancy in a contemporary cohort of European AF patients. METHODS: Patients enrolled in the EURObservational Research Programme in AF General Long-Term Registry were categorized into 3 categories: No Malignancy (NoMal), Prior Malignancy (PriorMal) and Active Malignancy (ActiveMal). The primary outcomes were all-cause death and the composite outcome MACE. RESULTS: A total of 10 383 patients were analysed. Of these, 9597 (92.4%) were NoMal patients, 577 (5.6%) PriorMal and 209 (2%) ActiveMal. Lack of any antithrombotic treatment was more prevalent in ActiveMal patients (12.4%) as compared to other groups (5.0% vs 6.3% for PriorMal and NoMal, p < .001). After a median follow-up of 730 days, there were 982 (9.5%) deaths and 950 (9.7%) MACE events. ActiveMal was independently associated with a higher risk for all-cause death (HR 2.90, 95% CI 2.23-3.76) and MACE (HR 1.54, 95% CI 1.03-2.31), as well as any haemorrhagic events and major bleeding (OR 2.42, 95% CI 1.49-3.91 and OR 4.18, 95% CI 2.49-7.01, respectively). Use of oral anticoagulants was not significantly associated with a higher risk for all-cause death or bleeding in ActiveMal patients. CONCLUSIONS: In a large contemporary cohort of AF patients, active malignancy was independently associated with all-cause death, MACE and haemorrhagic events. Use of anticoagulants was not associated with a higher risk of all-cause death in patients with active malignancies.

Clinical utility and prognostic implications of the novel 4S-AF scheme to characterize and evaluate patients with atrial fibrillation: a report from ESC-EHRA EORP-AF Long-Term General Registry.

AIMS: The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. METHODS AND RESULTS: Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60-25.9], (Sb) (aHR 1.21, 95% CI: 1.08-1.35), and (Su) (aHR 1.27, 95% CI: 1.14-1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45-2.06) and (Sy) (aHR 1.29, 95% CI: 1.00-1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55-0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16-1.56). CONCLUSION: Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

Characterization of atrial fibrillation in real-world patients: testing the 4S-AF scheme in the Spanish and French cohorts of the EORP-AF Long-Term General Registry.

AIMS: The 4S-AF scheme [Stroke risk, Symptom severity, Severity of atrial fibrillation (AF) burden, Substrate severity] has recently been described as a novel approach to in-depth characterization of AF. We aim to determine if the 4S-AF scheme would be useful for AF characterization and provides prognostic information in real-world AF patients. METHODS AND RESULTS: The Spanish and French cohorts of the EORP-AF Long-Term General Registry were included. The baseline 4S-AF scheme was calculated and related to the primary management strategy (rhythm or rate control). Follow-up was performed at 1-year with all-cause mortality and the composite of ischaemic stroke/transient ischaemic attack/systemic embolism, major bleeding, and all-cause death, as primary endpoints. A total of 1479 patients [36.9% females, median age 72 interquartile range (IQR 64-80) years] were included. The median 4S-AF scheme score was 5 (IQR 4-7). The 4S-AF scheme, as continuous and as categorical, was associated with the management strategy decided for the patient (both P < 0.001). The predictive performances of the 4S-AF scheme for the actual management strategy were appropriate in its continuous [c-index 0.77, 95% confidence interval (CI) 0.75-0.80] and categorical (c-index 0.75, 95% CI 0.72-0.78) forms. Cox regression analyses showed that 'red category' classified patients in the 4S-AF scheme had a higher risk of all-cause death (aHR 1.75, 95% CI 1.02-2.99) and composite outcomes (aHR 1.60, 95% CI 1.05-2.44). CONCLUSION: Characterization of AF by using the 4S-AF scheme may aid in identifying AF patients that would be managed by rhythm or rate control and could also help in identifying high-risk AF patients for worse clinical outcomes in a 'real-world' setting.

Assessment and mitigation of bleeding risk in atrial fibrillation and venous thromboembolism: A Position Paper from the ESC Working Group on Thrombosis, in collaboration with the European Heart Rhythm Association, the Association for Acute CardioVascular Care and the Asia-Pacific Heart Rhythm Society.

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.

Epidemiology and impact of frailty in patients with atrial fibrillation in Europe.

BACKGROUND: Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. OBJECTIVES: We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. METHODS: A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. RESULTS: Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55-0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. CONCLUSIONS: In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones.

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry.

BACKGROUND: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients' clinical phenotypes and analyse the differential clinical course. METHODS: We performed a hierarchical cluster analysis based on Ward's Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. RESULTS: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients' prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27-3.62; HR 3.42, 95%CI 2.72-4.31; HR 2.79, 95%CI 2.32-3.35), and Cluster 1 (HR 1.88, 95%CI 1.48-2.38; HR 2.50, 95%CI 1.98-3.15; HR 2.09, 95%CI 1.74-2.51) reported a higher risk for the three outcomes respectively. CONCLUSIONS: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.

Out-of-hospital cardiac arrest: A systematic review of current risk scores to predict survival.

IMPORTANCE: The arrest and the post-arrest period are an incredibly emotionally traumatic time for family and friends of the affected individual. There is a need to assess prognosis early in the patient pathway to offer objective, realistic and non-emotive information to the next-of-kin regarding the likelihood of survival. OBJECTIVE: To present a systematic review of the clinical risk scores available to assess patients on admission following out-of-hospital cardiac arrest (OHCA) which can predict in-hospital mortality. EVIDENCE REVIEW: A systematic search of online databases Embase, MEDLINE and Cochrane Central Register of Controlled Trials was conducted up until 20th November 2020. FINDINGS: Out of 1,817 initial articles, we identified a total of 28 scoring systems, with 11 of the scores predicting mortality following OHCA included in this review. The majority of the scores included arrest characteristics (initial rhythm and time to return of spontaneous circulation) as prognostic indicators. Out of these, the 3 most clinically-useful scores, namely those which are easy-to-use, comprise of commonly available parameters and measurements, and which have high predictive value are the OHCA, NULL-PLEASE, and rCAST scores, which appear to perform similarly. Of these, the NULL-PLEASE score is the easiest to calculate and has also been externally validated. CONCLUSIONS: Clinicians should be aware of these risk scores, which can be used to provide objective, nonemotive and reproducible information to the next-of-kin on the likely prognosis following OHCA. However, in isolation, these scores should not form the basis for clinical decision-making.

Obstructive sleep apnoea testing and management in atrial fibrillation patients: a joint survey by the European Heart Rhythm Association (EHRA) and the Association of Cardiovascular Nurses and Allied Professions (ACNAP).

Obstructive sleep apnoea (OSA) is highly prevalent in atrial fibrillation (AF) patients and associated with reduced response to rhythm control strategies. However, there is no practical guidance on testing for OSA in AF patients and for OSA treatment implementation. We sought to evaluate current practices and identify challenges of OSA management in AF. A descriptive cross-sectional study was performed with a content-validated survey to evaluate OSA management in AF by healthcare practitioners. Survey review, editing, and dissemination occurred via the European Heart Rhythm Association and the Association of Cardiovascular Nursing and Allied Professions and direct contact with arrhythmia centres. In total, 186 responses were collected. OSA-related symptoms were ranked as the most important reason to test for OSA in AF patients. The majority (67.7%) indicated that cardiologists perform 'ad-hoc' referrals. Only 11.3% initiated systematic testing by home sleep test or respiratory polygraphy and in addition, 10.8% had a structured OSA assessment pathway in place at the cardiology department. Only 6.7% of the respondents indicated that they test >70% of their AF patients for OSA as a component of rhythm control therapy. Various barriers were reported: no established collaboration between cardiology and sleep clinic (35.6%); lack in skills and knowledge (23.6%); lack of financial (23.6%) and personnel-related resources (21.3%). Structured testing for OSA occurs in the minority of AF patients. Centres apply varying methods. There is an urgent need for increased awareness and standardized pathways to allow OSA testing and treatment integration in the management of AF.