Search

Funding Acknowledgements Type of funding sources: None. Background It is well-known that higher blood pressure (BP) is associated with a higher risk of stroke with atrial fibrillation (AF). However, there is limited data about the effect of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) on the risk of ischemic stroke in young and low-risk AF patients Methods Using the Korean Health Insurance Service database, patients who were newly diagnosed with AF between January 2009 and December 2016 and had health screening examination data within 2-year after AF diagnosis were included. Patients aged between 20 and 39 years were finally included in this analysis. During follow-up, incident ischemic stroke was evaluated as a primary outcome. Hazard ratio (HR) and the corresponding 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazard models. Results A total of 15,980 patients were included in this analysis (mean age 32.4±4.8 years, 66.9% of men). Mean CHA2DS2-VASc score was 0.7±0.8 and oral anticoagulation rate was 5.6%. During a median 5.2-year of follow-up, 73 patients had an incident ischemic stroke (incidence rate, 0.9 per 1,000 person-years). After multivariable adjustment, SBP ranging from 140 to 159 mmHg and 160 mmHg or higher were associated with a significantly higher risk of ischemic stroke by 8.4-fold and 11.6-fold compared to SBP under 100 mmHg (Figure). DBP 95mmHg or higher was associated with a higher risk of ischemic stroke by 4.2-fold than DBP under 65 mmHg (Figure). Patients with PP ranging from 50 to 59 mmHg and 60 mmHg or higher showed a significantly higher risk of ischemic stroke than those with PP ranging from 40 to 49 mmHg (HR [95% CI]; 1.81 [1.04-3.18] and 3.15 [1.49-6.64], respectively). Also, lower PP than 30 mmHg was associated with a higher risk of stroke (3.96 [1.36-11.53]). Conclusion Optimal BP control might be crucial to preventing ischemic stroke in these young and low-risk AF patients.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Sanmin project, Shenzhen, China Background There is inconclusive evidence regarding the impact of statins on the risk of atrial fibrillation (AF) related outcomes. The current study investigated whether statin use would improve outcomes among patients with non-valvular AF. Purpose To assess the association between statin use and AF-related outcomes among patients with AF. Methods Patients newly diagnosed with AF (n = 51,472) between 2010-2018 were divided into statin users (n =11,866) and statin nonusers (n =39,606), according to whether they received statin therapy after their first diagnosis of AF. The primary outcomes included ischaemic stroke (IS) and systemic embolism (SE), haemorrhagic stroke (HS), and transient ischaemic attack (TIA). An inverse probability of treatment weighting was used to balance baseline covariates between the two groups. The Fine and Grey competing risks model was applied, with death defined as the competing event. Results The median age of the cohort was 74.9 years, and 47.7% were female. During the median follow-up of 5.1 years, previous statin use was significantly associated with a lower risk of IS/SE compared with statin nonusers (subdistribution hazard ratio [SHR] = 0.83, 95%CI: 0.78-0.89). Similar patterns were found in the association between previous statin use and HS (SHR = 0.93, 95%CI: 0.89-0.98) and TIA (SHR = 0.85, 95%CI: 0.80-0.90, P Conclusion Statin use was associated with a lower risk of incident IS/SE, HS and TIA in a duration-dependent manner among AF patients.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea Background Atrial fibrillation (AF) is associated with development of impaired renal function and chronic kidney disease (CKD). Early rhythm control initiated within 1 year of AF diagnosis is associated with a lower risk of adverse cardiovascular outcomes compared to usual care among patients recently diagnosed with AF. Purpose This study aimed to assess the effects of early rhythm control on renal function in patients with AF and CKD, compared with rate control Methods This population-based cohort study included 4,151 patients with AF and CKD, from the Korean National Health Insurance Service database, undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis in 2005–2015. A composite renal outcome of ≥30% decline in estimated glomerular filtration rate (eGFR), acute kidney injury (AKI), and kidney failure was compared using propensity score overlap weighting. Results In the study population (39.1% female; median age: 70 years), a total of 628 composite renal outcome occurred during the median follow-up of 2.3 years. Early rhythm control, compared with rate control, was associated with lower risks of the composite renal outcome (weighted incidence rate: 4.1 vs. 5.3 per 100 person-years; weighted HR 0.78, 95% CI 0.65-0.94) and kidney failure (weighted HR 0.73, 95% CI 0.56-0.95). Trends toward lower risks of eGFR decline (weighted HR 0.89, 95% CI 0.58-1.37) and AKI (weighted HR 0.88, 95% CI 0.66-1.17) were observed in patients undergoing early rhythm control, compared with those undergoing rate control. Conclusion Among patients with AF and CKD, early rhythm control was associated with a lower risk of progression of kidney disease, compared with rate control, highlighting the need for future randomized studies evaluating the benefits of early rhythm control on renal outcome among patients with AF.

Funding Acknowledgements Type of funding sources: None. Background Non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over warfarin for stroke prevention for patients with atrial fibrillation (AF) in 2020 ESC guidelines. However, whether warfarin should be shifted to NOACs for patients who stayed very well with warfarin for years remains unknown. Methods From 2007 to 2010, a total of 167,176 newly-diagnosed AF patients aged ≥20 years were identified from the Taiwan National Health Insurance Research Database. Among these patients, 83,604 were alive to June 1st, 2015 and 54,803 of them who did not experience ischemic stroke or intra-cranial hemorrhage (ICH) have constituted the study population. Among the study population, 8,007 patients who continuously received warfarin and survived for at least 90 days after June 1st, 2015 were defined as the "original warfarin cohort". These patients were then categorized into 2 groups according to the stroke prevention strategies they received after June 1st, 2015; that is, staying on warfarin (n = 6,635) and shifting to NOACs (n = 1,372). Results Compared to patients staying on warfarin, the risk of ischemic stroke was lower for patients who were shifted NOACs (aHR 0.886; p=0.002). Also, the risk of major bleeding was lower for shifting to NOACs (aHR 0.849; p Conclusions Even for patients staying well on warfarin for years, shifting to NOACs was still associated with better clinical outcomes.

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is associated with important mortality. Dedicated clinical scores to predict mortality have been developed but perform modestly and are not specific for this population. Machine learning models are developing in the field of AF and may be able to outperform existing tools for the prediction of mortality. Purpose This study aimed to train and evaluate machine learning models for the prediction death occurrence within this critical period of the year following atrial fibrillation diagnosis and to compare predictive ability to usual clinical scores. Methods We used for this purpose a nationwide cohort of 2,435,541 newly diagnosed atrial fibrillation patients seen in all the French hospitals from 2011 to 2019. Three ML models (logistic regression, random forests, deep neural networks) were trained to predict mortality within the first year on a train set (70% of the cohort). The best model was selected to be evaluate on the test set (30% of the cohort). Discrimination of the best model was evaluated using the C index. We finally compared our best model with previously published scores. Results Within the first year following AF diagnosis, 342,005 patients (14.4%) died after a mean time of 83 (SD 98) days in whom 107,715 were from cardiovascular deaths (31.5%). Among 110 variables, the 18 most predictive variables were identified and selected using a Random Forest algorithm: age, metastasis, resuscitated cardiac arrest, cancer, congestive heart failure, decubitus ulcers, renal failure, pneumonia, lung disease, difficulty in walking, malnutrition, anemia, impaired mobility, liver disease, renal disease, blood transfusion and urinary tract infection. After training 3 ML algorithms, the best ML model selected was a deep neural network with a C index of 0.785 (95% CI, 0.781-0.789) on the test set. The incidence of all cause death at one year rises in a stepwise fashion from 13.8 per 1000 patients for the first quintile to 352.4 per 1000 for the fifth quintile. Compared to traditional clinical risk scores, the selected model was significantly superior to the CHA2DS2-VASc and HAS-BLED scores, and dedicated scores such as Charlson Comorbidity Index and Hospital Frailty Risk Score to predict death within the year following AF diagnosis (C indexes: 0.597; 0.562; 0.643; 0.626 respectively. P Conclusion Machine learning algorithms predict early death after AF diagnosis with a better ability than previously developed traditional clinical risk scores. A ML approach may help clinicians to better risk stratify AF patients at high risk of mortality.

Funding Acknowledgements Type of funding sources: None. Background Sodium glucose co-transporter 2 inhibitors (SGLT2i) have been associated with favourable outcomes in patients with heart failure. Studies also indicate a reduced risk of atrial fibrillation (AF). Purpose We performed an exploratory analysis to evaluate the impact of SGLT2 inhibitors in anticoagulated patients with AF. Method All anticoagulated patients with AF and type 2 diabetes between January 2014 and December 2018 were identified from a federated electronic medical record database (TriNetX), and followed up for 3 years. A 1:1 propensity score matched (PSM) analysis was performed to balance the SGLT-2i and non-SGLT-2i cohorts. The primary outcome was ischaemic stroke/ transient ischaemic attack (TIA), bleeding events, hospitalisation for AF and composite of cardioversion and ablations. Secondary outcomes included all-cause mortality, haemorrhagic stroke, ventricular arrhythmias, cardiac arrest, incident heart failure and composite of arterial and venous thrombotic events. Results A total of 236,493 and 20,841 were identified from the non-SGLT2 and SGLT2 inhibitor groups respectively. After PSM, each group had 17,968 patients. In anticoagulated AF patients, SGLT2 inhibitor use was associated with a significantly lower risk of ischaemic stroke/ TIA, hazard ratio (HR) 0.759 (95% CI 0.719-0.802), bleeding HR 0.657 (95% CI 0.619-0.697), hospitalisation for AF HR 0.875 (95% CI 0.855-0.897), and composite of cardioversion/ablations HR 0.705 (95% CI 0.655-0.759). A lower risk of all-cause mortality HR 0.481 (95% CI 0.453-0.510), haemorrhagic stroke HR 0.54 (95% CI 0.454-0.642), ventricular arrhythmias HR 0.766 (95% CI 0.719-0.816), cardiac arrests HR 0.539 (95% CI 0.476-0.611), incident heart failure HR 0.709 (95% CI 0.661-0.760) and composite of arterial and venous thrombotic events HR 0.737 (95% CI 0.712-0.763) were also observed with SGLT2 inhibitor use. Conclusion Our findings suggest that SGLT2i use is associated with a lower risk of AF-related complications such as ischaemic stroke/ TIA, bleeding, ventricular arrhythmias and reduced need for procedures such as cardioversion and ablations. Further studies are required to confirm this association.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation (PG/05/036) Primary Care Research Network-Central England. Background People of South-Asian origin have high cardiovascular morbidity, contributed by health inequalities. Hypertension is the key modifiable cardiovascular risk factor but is underdiagnosed, but its scale in South Asian communities is unknown. Left ventricular hypertrophy (LVH) on echocardiography is a measure of target organ damage related to uncontrolled hypertension. The study aims to assess prevalence of LVH in South Asian community and its impact on mortality. This study is based on the large prospective UK community Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES, age ≥45 years). Methods Left ventricular mass index (LVMI) was calculated using echocardiography. LVH was established as increased LVMI. Predictive value of LVH all-cause and cardiovascular mortality was assessed using Cox regression. Results The study included 3200 South Asians (age 59±10, 52% women, 45% had a history of hypertension). There were 182 deaths, including 64 cardiovascular deaths during a 5.8±1.0-year follow-up. LVH was found in 1568 (49%). In those with LVH, 705 (45%) did not have a diagnosis of hypertension. On Cox regression LVH was independently associated with all-cause mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.01-1.88), cardiovascular mortality (HR 2.64, 95% CI 1.21-3.73). The projected overall hypertension prevalence was 82%. Conclusion South Asians in the UK have a very high prevalence of hypertension which is often underdiagnosed and poorly controlled, leading to LVH and excess in overall and cardiovascular mortality. The findings call for more effective screening and management of hypertension with lower BP targets.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation (PG/05/036) Primary Care Research Network-Central England. Background Blood pressure (BP, mmHg) targets have been mainly determined based on the white ethnic group. Optimal BP levels have been less established in people of South Asian and African Caribbean origin. There is less data on how different office BP values influence the presence of cardiac target organ damage, left ventricular hypertrophy (LVH) and diastolic dysfunction (DD). Methods This study is based on the large prospective UK community Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES, South Asian and African-Caribbean origin, age ≥45 years). Echocardiography was used to diagnose LVH and DD following British Echocardiographic Society criteria. Optimal receiver operator curves (ROC) cut-off values for predicting LVH and DD were determined using the Leu method. Multivariable logistic regression, adjusted for age and sex, was used to determine the effects of different BP values for LVH and DD, using SBP 130- Results The study included 3200 South Asians (age 59±10, 52% women), of whom 1568 (49%) had LVH, and 1497 (47%) had diastolic dysfunction. Of people with LVH, 869 (55%) had SBP >140, and 372 (24%) had DBP >90. The optimal BP cut-off for ROC analysis was 139/80.5 for LVH and 139/80.5 for diastolic dysfunction. SBP The study included 1922 African Caribbeans (62±12 age, 55% women), of whom 1186 (62%) had LVH and 1124 (58%) had DD. Of people with LVH, 778 (66%) had SBP >140, and 333 (28%) had DBP >90. The optimal BP cut-off for ROC analysis were 139/81.5 for LVH and 138/80.5 for DD. DBP Conclusions People of South Asian origin may benefit from stricter SBP (

Introduction Older people in care homes with atrial fibrillation (AF) have complex health needs and would benefit from taking part in research. This study assessed the feasibility of pharmacist implementation of the Atrial Fibrillation Better Care (ABC: Anticoagulation; Better symptoms; Cardiovascular comorbidity management) pathway, and collection of an AF-specific, resident-centred outcome. Methods Older residents (aged ≥65 years) with AF were recruited from care homes within Liverpool and Sefton and randomised to receive the pharmacist intervention, or continue their existing treatment. Resident quality of life was assessed using the Atrial Fibrillation Effect on Quality of Life Questionnaire (AFEQT). Results Twenty-two care homes were approached about the study, and seven signed up to take part between 28 September 2020 and 29 April 2021. Time taken to recruit care homes ranged from 0 to 122 days. There were 83 residents identified as potentially eligible to take part, but after screening only 28 residents (34%) were invited. Overall, 21 residents were recruited. Eleven residents received the pharmacist intervention and three had ABC recommendations made to their GPs. Two out of four recommendations were implemented. The pharmacist administered the AFEQT questionnaire to 17 residents with capacity and completion rates were 94% and 93% at baseline and six-months, respectively. Residents found the questionnaire difficult; most were unable to distinguish if symptoms were AF-related (n=3), or did not know they had AF (n=8), and questions related to physical activity were not applicable to any of the residents who were bed bound (n=5) or had severely limited mobility (n=12). Conclusion There were procedural (encountered before research starts), system (encountered during research) and resident-specific barriers that impacted this study. Barriers need addressing before wider implementation, and AF-specific quality of life measures need to be developed and validated for care home residents. A detailed commentary has been submitted for publication.

Background Atrial fibrillation (AF) is responsible for almost one third of all strokes, with the left atrial appendage (LAA) being the primary thromboembolic source due to localised stimulation of prothrombotic mechanisms; blood stasis, hypercoagulability and endothelial damage, known as Virchow's triad. Aim We propose an in-silico modelling pipeline that leverages clinical imaging data to mechanistically assess patient thrombogenicity for all aspects of Virchow's triad to improve the prediction and prevention of AF-related stroke. Methods Two AF patients undergoing Cine magnetic resonance imaging (sinus rhythm (SR) N=1 or AF N=1 during imaging) were selected for 3D left atrial (LA) modelling with patient-specific myocardial deformation prescribed from image-derived wall motion. Blood stasis was quantified by computational fluid dynamics (CFD) simulations of 5 cardiac cycles [1]. Generation of three key coagulation proteins; thrombin, fibrinogen and fibrin, were modelled to represent thrombus growth and hypercoagulability [2]. Regions prone to thrombogenesis by endothelial damage were identified by the oscillatory shear index (OSI), time averaged wall shear stress (TAWSS) and endothelial cell activation potential (ECAP) metrics in the LAA [3]. Results Patient-specific LA simulations enabled the assessment of differences between SR and AF conditions, quantified as numerical characteristics of each aspect of Virchow's triad. In SR, blood flow velocities were in the range 0–2.6 m/s with mean of 0.85 m/s in the LA cavity, while AF had a range between 0–1.6 m/s with mean of 0.55 m/s. The peak and mean LAA velocities in SR were 0.85 m/s and 0.14 m/s, while AF had a peak LAA velocity of 0.32 m/s and mean of 0.09 m/s, showing a 38% decrease during AF. The thrombin concentration reached its steady state at 1.26 mmol/m3 in the AF case after 4.7 seconds, while thrombin was washed away from the initial injury site in SR. After 5 cardiac cycles of thrombus growth dynamics, the peak fibrin concentration in the LAA was 1.3 mmol/m3 in SR and 3.8 mmol/m3 in AF, with the thrombus area in AF being 40% larger. Fibrinogen concentration decreased at a rate equal to fibrin generation in both SR and AF solely in the area of thrombus formation. ECAP in the LAA had peak values of 2.9 in SR and 3.7 in AF, with the location at highest risk of thrombogenesis above the LAA entrance. LAA OSI had an average value of 0.45 in AF versus 0.36 in SR, showing a 26% increase. Similarly, the TAWSS was 3.5x10–3 Pa on average over the LAA in AF compared to 1.4x10–3 Pa in SR. Conclusions Patient-specific LA models combining these three quantitative characteristics can be used to predict the higher thrombogenic risk in AF. After further validation, this novel approach for quantitative assessment of AF patient thrombogenicity based on modelling all factors in Virchow's triad can personalise and improve management of AF patients with a risk of stroke. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Engineering and Physical Sciences Research Council

Background There is a surging development of digital technologies for screening and diagnosis of atrial fibrillation (AF), nonetheless, how these digital technologies impact AF care remains unclear. Objectives The present study aimed to investigate the impact on AF episodes and arrhythmia burden of patient-centered self-management with using smart technologies, incorporating artificial intelligence (AI), wearable and mobile health (mHealth) technology for patient-centred self-management. Methods In this cohort study, we applied AI machine-learning (ML) model predicting AF prior to 4 hours of AF occurrence, while the timely monitoring of AF episodes with photoplethysmography (PPG) technology, and further confirmation of the diagnosis of AF with single-lead ECG, was based on wearable devices. These have been developed in AF screening study (stage 1 pre-mAFA) of Mobile Health technology for improved screening and optimizing integrated care in atrial fibrillation (mAFA II programme), while mHealth supported integrated care of AF was validated to reduce clinical events (stage 2 mAFA II cluster randomized trial). In this observational cohort, the subjects were in 2 groups: (i) subjects with monitored AF but without using mAFA (Group 1); (ii) subjects with monitored AF and using smart devices and mAFA for patient-centered self-management (Group 2). Adult subjects freely downloaded the mAFA AF App, with compatible devices, and were included into the study from across China between October 26, 2018 and Dec 1, 2021. Results From 3499461 subjects involving in AF population screening, there were 5904 subjects in Group 1 (mean age 57 years, SD,15 years; 80.7%, male), while 2667 subjects in Group 2 (51, 15; 89.7% male). The diagnosis of AF episodes was confirmed by single-lead ECG recordings, and decreased among those using mAFA in Group 2 (Confirmed AF: 602 in 1st quarter, 224 in 2nd quarter, 81 in 3rd quarter, 52 in 4th quarter) (all p value for trend AF burden was significantly reduced over time (PPG: 26% on 1st month, 19% on 12th month; ECG: 3%, 0.7%, all p On multivariate analysis, AI ML model driven mAFA-based upstream risk factor control significantly reduced the changes in AF burden of both Δ 6 month (adjusted OR, 95% CI, 0.51,0.43–0.59) and Δ 12 month (0.39,0.32–0.47, all p Conclusion mHealth-AF care increased the adherence of using smart devices for AF detection. The incorporation of smart devices and AI tools into an AF clinical care pathway, effectively reduced AF burden and detected AF episodes, through appropriate rhythm control management and upstream risk factor control. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Background European guidelines on AF management recommend a systolic blood pressure (SBP) target of 120–129 mmHg as this level is associated with the lowest risk of poor outcomes. Elevated blood pressure and AF both negatively affect renal function, but the interactions between SBP and renal function in patients with AF remains unclear. In the UK extension of the EURObservational Research Programme (EORP) Long-term Registry of patients with atrial fibrillation (AF) [AF-GEN-UK study], we assessed the combined impact of BP levels and renal (dys)function on mortality, thromboembolic and haemorrhagic events. Methods 1580 patients (60.1% males, mean (SD) age 70.6 (11.2) years) from the AF-GEN-UK registry had SBP available at baseline and were stratified into groups based on SBP: 120–129 mmHg (reference group, n=289), Results Overall OAC use was 84% and was similar between all SBP groups. Renal function (eGFR), was preserved across SBP groups; those with SBP 110–119 mmHg had the lowest level. Prevalence of heart failure was highest in those with SBP 140 mmHg) were older, more likely female and higher rates of hypertension, with correspondingly higher CHA2DS2VASc scores. SBP Adjusted Cox regression revealed that SBP Conclusion In anticoagulated patients with AF, SBP Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This project was supported by the BMS/Pfizer European Thrombosis Investigator Initiated Research Program

Background The AF-GEN-UK study is an extension of the EURObservational Research Programme (EORP) Long-term Registry on patients with atrial fibrillation (AF) in the UK (AF-GEN). The study aimed to establish a registry of the contemporary management of patients with AF by cardiologists, general practitioners, stroke, acute and emergency medicine physicians at baseline and 1-year of follow-up, to allow comparison between medical specialties. Methods Data on patients with AF diagnosed within the previous 12-months were collected using electronic case records from 101 sites, to permit comparison of patient characteristics and treatments between medical specialties. The impact of guideline-adherent oral anticoagulation (OAC) use on outcomes was assessed using Cox regression analysis. Results 1595 patients (mean (SD) age 70.5 (11.2) years; 60.1% male; 97.4% white) with ECG-documented AF were included (recruited between June 2017 and June 2018) and followed-up for 1-year. Overall OAC prescription rates were 84.2% at baseline and 87.1% at 1-year follow-up, with NOACs predominating (74.9% at baseline and 79.2% at 1-year) Figure, mainly apixaban. Prescription of VKA was significantly higher in primary care, with NOAC prescription higher among stroke physicians. Guideline-adherent OAC (CHA2DS2-VASc ≥2) at baseline significantly reduced risk of composite endpoint of death and stroke at 1-year (adjusted hazard ratio 0.42; 95% confidence intervals 0.25–0.70). Rhythm control was evident in approximately one-quarter, with only 1.6% receiving catheter ablation. Most patients (56.6%) reported AF symptoms, but these were severe in only 17.9%. Symptomatic patients were mainly managed by cardiologists or acute/emergency medicine; among patients managed by stroke physicians, 81.5% were asymptomatic. Quality of life did not appear significantly impaired however there was a slight but significant improvement at follow-up (70.3% vs. 71.5%; p=0.044). Symptomatic patients reported poorer quality of life related to usual activities, mental health and overall quality of life. Conclusion Overall OAC use was high (>80%) with NOAC prescription predominating but rates varied by specialty, with VKA prescription significantly higher in primary care. Guideline-adherent OAC therapy at baseline was associated with significant reduction in composite outcome of death and stroke at 1-year, regardless of specialty. Rhythm control management was only evident in around one-quarter despite AF symptoms being reported in 56.6%. This registry extends the knowledge of contemporary management of AF outside of cardiology by including other specialties and demonstrates good implementation of clinical guidelines for the management of AF, particularly in relation to stroke prevention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This project was supported by the BMS/Pfizer European Thrombosis Investigator Initiated Research Program

Background Patients with atrial fibrillation (AF) who experienced stroke before are at high risk for dementia. Although early rhythm control in patients with AF reduces the risk of stroke, there is a lack of evidence on whether early rhythm control reduces the risk of developing dementia in patients with new-onset AF and a history of prior stroke. Purpose To compare the risk of dementia between early rhythm control therapy and usual care in patients with new-onset AF and a history of prior stroke Methods Using the Korean nationwide claims database, we identified patients who were newly diagnosed as AF and had a history of prior stroke. Patients with prevalent dementia were excluded. Patients who received rhythm control therapy, including antiarrhythmic drug, direct current cardioversion, or AF catheter ablation, within 1 year after incident AF were defined as the early rhythm control group, otherwise as the usual care group. The inverse probability of treatment weighting method was used to balance baseline characteristics between the two groups. The incidence of all dementia, Alzheimer dementia, and vascular dementia were evaluated during follow-up. Results A total of 41,370 patients were included (mean age, 70±11 years; mean CHA2DS2-VASc score 5.3±1.6; 43% female); 10,213 were in the early rhythm control group and 31,157 in the usual care group. All patients received oral anticoagulants. During a median 2.7 years of follow-up, 6414 patients developed incident dementia (incidence rate, 4.9 per 100 person-years). Compared to usual care, early rhythm control was associated with lower risks of all dementia, Alzheimer dementia, and vascular dementia (weighted hazard ratio [95% confidence interval], 0.825 [0.776–0.876], 0.831 [0.774–0.893], and 0.800 [0.702–0.913], respectively, all p Conclusion Early rhythm control within 1 year after AF diagnosis might be beneficial to prevent dementia in patients with incident AF and a history of stroke. To prevent progression of further cognitive dysfunction, early rhythm control should be considered in these patients. Funding Acknowledgement Type of funding sources: None.

Background The link between hypertensive disease in pregnancy and future cardiovascular events is well established, as is the increased risk of developing type 2 diabetes mellitus after gestational diabetes (GDM). What is less well understood is the impact of GDM on future cardiovascular events. The literature is conflicting although suggestive that the risk of cardiovascular events with a history of GDM is 2 fold higher. Purpose Using the largest cohort to date and utilising robust data acquisition procedures and follow up we assessed the prognostic value of GDM for future cardiovascular events. Methods All female patients discharged from French hospitals in 2013 with at least 5 years of subsequent follow-up were identified. Those with a previous major adverse cardiovascular event, history of hypertensive disease, pre-existing diabetes or under the age of 18 years old were excluded. They were grouped depending on their history of GDM. After propensity score matching, patients with GDM were matched 1:1 with patients with no GDM. Hazard ratios for cardiovascular events during follow-up were adjusted by age at baseline. Results A total of, 1,738,101 women were included in the analysis, leaving 1,141,743 women (mean age 52.2, SD 19.7) once exclusion criteria were applied: 6998 (0.6%) had a history of GDM and the mean follow-up was 5.1 years (SD 1.3 years). Those with a history of GDM had a lower risk of new onset heart failure (HF) (hazard ratio [HR] 0.66, 95% confidence interval [CI]: 0.45–0.98) and all-cause death (HR 0.61, 95% CI 0.47–0.79). There was no significant difference in risk for myocardial infarction (HR 0.88, 95% CI 0.38–2.03), ischaemic stroke (HR 0.94, 95% CI 0.55–1.63), new onset atrial fibrillation (AF) (HR 0.61, 95% CI 0.33–1.11), cardiovascular death (HR 1.25, 95% CI 0.47–3.36) and major cardiovascular events (i.e. in-hospital cardiovascular death, myocardial infarction, ischaemic stroke or new-onset HF (MACE-HF)) (HR 0.75, 95% CI 0.56–1.01). Conclusions In a large contemporary analysis of female patient seen in French hospitals and utilising a robust data set we present the largest population analysis of the association between GDM and future cardiovascular events. Those with a history of GDM do not have a higher risk of myocardial infarction, ischaemic stroke, new onset AF, cardiovascular death or MACE-HF. Contrary to what is widely thought, a history of GDM confers a lower risk of new onset HF and all-cause death when compared to those women with no history of GDM. Funding Acknowledgement Type of funding sources: None.

Background Newly diagnosed cardiovascular complications post-stroke, termed stroke-heart syndrome, are common and associate with worsened prognosis. Purpose To investigate the sex-specific incidence and 5-year major adverse cardiovascular events following stroke-heart syndrome, stratified by pre-existing risk factors (sex, age, obesity, hypertension, type 2 diabetes mellitus, and high LDL cholesterol). Methods A retrospective cohort study was conducted using anonymised electronic medical records from 56 participating healthcare organizations. Patients with incident ischaemic stroke aged ≥18 years with 5-years of follow-up were included. Patients diagnosed with new-onset cardiovascular complications (heart failure, severe ventricular arrhythmia, atrial fibrillation, ischaemic heart disease, takotsubo syndrome) within 4-weeks of incident ischaemic stroke (exposure) were 1:1 propensity score-matched (age, sex, ethnicity, comorbidities, cardiovascular care) with ischaemic stroke patients without newly diagnosed cardiovascular complications (control). Cox proportional hazards regression models produced hazard ratios (HR) with 95% confidence intervals (CIs) and Kaplan-Meier curves for 5-year risk of all-cause mortality, recurrent stroke, and acute myocardial infarction (AMI). Results Of 486,515 patients with ischaemic stroke, 18% (n=87,786) presented with stroke-heart syndrome (47% (n=41,088) female and 52% (n=45,891) male). Following propensity score matching, composite stroke-heart syndrome associated with significantly higher risk of 5-year mortality (HR 1.66 (95% CI 1.62,1.70), P75. The risk of all adverse outcomes were relatively higher for females aged Conclusions In this cohort study of patients with incident ischaemic stroke, stroke-heart syndrome occurred in 18% of patients. The overall incidence and subsequent 5-year major adverse cardiovascular events following stroke-heart syndrome were similar for females and males, but with important sex-specific differences when stratified by pre-existing risk factors, including age, obesity, and hypertension. Funding Acknowledgement Type of funding sources: None.

Background Although non-vitamin K antagonist oral anticoagulants (NOACs) were more and more commonly prescribed for stroke prevention for patients with atrial fibrillation (AF), underuse of OACs is still not uncommon. Data about the initiations of OACs in AF patients who did not experience ischemic stroke without any OACs for years since incident AF was diagnosed were limited. We aimed to investigate the associations between the initiations of warfarin or NOACs and clinical outcomes among this population. Methods From January 1st, 2007 to December 31st, 2010, a total of 167,176 newly-diagnosed AF patients aged ≥20 years were identified from the Taiwan National Health Insurance Research Database as the study population. Among the study population, 32,917 patients with a CHA2DS2-VASc score >1 for males or >2 for females who did not receive warfarin or NOACs and survived for at least 90 days after June 1st, 2015 were defined as the “original non-OAC cohort”. These patients were then categorized into 3 groups according to the stroke prevention strategies they received after June 1st, 2015; that is, without OACs (n=31,195), warfarin (n=230) and NOACs (n=1,492). Results Compared to patients staying on non-OACs, the risk of ischemic stroke was lower for patients who initiated NOACs (aHR 0.867; p=0.043). The risk of all-cause mortality was lower for patients who started to receive warfarin (aHR 0.876; p=0.036) or NOACs (aHR 0.798; p=0.047). The composite risk of ischemic stroke or major bleeding was also lower for patients who initiated warfarin (0.849; p Conclusions Initiations of OACs, especially NOACs, should still be considered for AF patients who stayed well without OACs for years since incident AF was diagnosed. Funding Acknowledgement Type of funding sources: None.

Background There is a paucity of information on the risk of atrial fibrillation (AF) in healthy individuals taking fish oil supplements. Purpose We aimed to investigate the epidemiologic and causal relationships between fish oil supplement intake and the long-term risk of AF. Methods From the population-based UK Biobank, we selected healthy individuals without a history of AF, other cardiac arrhythmias, or cardiovascular diseases, who were not taking lipid-lowering medications or dietary supplements other than fish oil. The 10-year risk of AF in Fish-Oil-Users vs. Non-Users was evaluated in the total population and propensity-score matched cohort. The causal relationship between n-3 polyunsaturated fatty acids (PUFA) and AF was evaluated using a two-sample summary-level Mendelian randomization analysis with fixed effects robust inverse-variance weighted method, using genetic instruments from previous studies genome-wide association studies for n-3 PUFA levels and AF, respectively. Results A total of 338,199 participants (aged 55.2±8.1, 44.3% men) were analysed. Of these, 35.0% (n=118,300) was taking fish oil supplements. The 10-year risk of AF was significantly higher in the Fish-Oil-Users than in the Non-Users (3.83% vs. 2.91%, adjusted hazard ratio [HR] 1.05, 95% CI [1.01–1.10], P=0.023). The result was consistent in the propensity-score matched cohort (propensity-score matched HR 1.06, 95% CI [1.00–1.12], P=0.043). The increased risk of AF by fish oil supplement was prominent in low-risk participants with healthy lifestyles. Among n-3 PUFA, the docosapentaenoic acid (DPA) showed significant causal estimates for the increased risk of AF (odds ratio [OR] 1.15, 95% CI [1.08–1.22], P Conclusion Fish oil supplement intake significantly increased the long-term risk of AF in a healthy population. The causal effect of fish oil intake on the risk of AF may depend on the specific types of n-3 PUFA. Funding Acknowledgement Type of funding sources: None.

Background Most epidemiological studies into venous thromboembolism (VTE) are based on the white Caucasian population and unrepresentative of VTE outcomes in non-white ethnicities. Purpose Our VTE registry aims to get an insight into the outcomes of VTE patients as applicable to a developed world population with a multi-ethnic background. This will guide clinicians to make appropriate decisions with regards to management and prognosis. Methods The Birmingham Black Country VTE Registry (BBC-VTE) is a multi-ethnic cohort of patients in the West Midlands region of the United Kingdom, who suffered a first episode of VTE. In this study we compared baseline characteristics, treatment patterns and outcomes, and secondly, compared these among the different ethnic groups in this region. Results Between the years 2012–2014 there was a total of 1615 patients (mean age 65.5; 53.1% female) admitted with a first episode of VTE of whom, 134 (8.3%) were Asian, 92 (5.7%) Black, and 1213 (75.1%) White. Asian patients were younger (mean age 54, SD 19.3) vs Black patients (59, SD 19.7) and White patients (68, SD 17.4); and were less often female (50.7% vs. 55.4% and 53.8%) for Black and White patients respectively. The initial VTE event was a DVT in 680 (42.1%) and a PE±DVT in 935 patients (57.9%). Below-knee and above-knee DVT occurred in 95 (5.9%) and 585 (36.2%) patients respectively. Recurrent DVT occurred in 3.2% of those with an initial below-knee DVT and 12.5% of those with an initial above-knee DVT. Recurrent PE was also more common in those with an initial above knee DVT (4.8%) compared to those with below-knee DVT (3.2%). After the initial VTE event, 1269 (78.6%) were started on long-term anticoagulation for the prevention of recurrent VTE. Of those, 65.1% stayed on anticoagulation for up to 6 months after the initial VTE event, and 34.9% continued for longer than 6 months, including those on lifelong anticoagulation. Bleeding and major bleeding occurred in 6.8% and 2.5% respectively in those on anticoagulation for 6 or less months, vs. 10.4% and 3.5% in those anticoagulated for longer than 6 months. The most common site of bleeding was gastrointestinal in 42.3% of all bleeds and this site was also responsible for 54.3% of major bleeds. From evaluating the odds ratio for VTE mortality (see Fig. 1), ethnicity did not have a significant impact. Older age; the presence of diabetes mellitus; history of malignancy; as well as admission laboratory results for C-reactive protein and neutrophil count were all significantly associated with higher odds of mortality in this patient cohort. Conclusion BBC-VTE is a contemporary multi-ethnic cohort of patients providing insights into the risk factors among multi-ethnic patients that have developed VTE. Ethnicity did not emerge as an independent risk for VTE mortality. Funding Acknowledgement Type of funding sources: None.

Introduction There is increasing concern regarding the burden of clinical complexity, beyond thromboembolic risk, in patients with atrial fibrillation (AF). Also, clinical complexity is heterogenous and entails differential impact on the patients' clinical course. Purpose To explore different complexity features in AF patients in determining differences in clinical management and outcomes. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Features of complexity were analysed in the context of the following high-risk groups: i) only CHA2DS2-VASc ≥2; ii) history of stroke/bleeding; iii) chronic kidney disease (creatinine clearance Results A total of 10285 patients (mean [SD] age 68.8 [11.5] years, 4107 [39.9%] females) were included in the analysis. Of these, 3944 (38.3%) had only CHA2DS2-VASc ≥2; 412 (4.0%); history of stroke/bleeding; 1480 (14.4%) CKD; 1007 (9.8%) were frail; 1315 (12.8%) had ≥2 criteria; and 2127 (20.7%) were low-risk. After adjustment for age, sex, type of AF and EHRA score, compared to low-risk patients, all the other groups were associated with OAC prescription but with progressively lower odds ratio, while those ≥2 criteria which were least likely prescribed with OAC (Table 1). After a mean (SD) 634.5 (223.0) days of follow-up, a total of 1432 events were recorded. After adjustment for confounders, Cox regression analysis found that all the complexity groups were associated with a higher risk of the composite outcome across the groups (Figure 1). In patients with available data about ABC (Atrial fibrillation Better Care) pathway adherence, the latter adherence was associated a significant incidence rate reduction (IRR) compared to non-ABC adherence in those with ≥2 criteria of clinical complexity (IRR 0.46, 95% CI 0.30–0.71), and in the CKD complexity group (IRR 0.57, 95% CI 0.41–0.81). Conclusions In a large contemporary cohort of European AF patients, features of clinical complexity affect differently prescriptions of OAC. All the subgroups of clinical complexity were associated with a higher risk of adverse outcomes, which were reduced by adherence to ABC pathway. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and PfizerAlliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022).

Background/Introduction Endovascular thrombectomy (EVT) has become the standard of care for the management of acute ischaemic stroke, but the risk of intracerebral haemorrhage and mortality still remains common following ischaemic stroke. The effect of concomitant atrial fibrillation (AF) on clinical outcomes in patients with acute ischaemic stroke after receiving EVT remains unclear. Purpose To investigate associations between AF and intracerebral haemorrhage (ICH) and all-cause mortality at 90 days in patients with ischaemic stroke undergoing EVT. Methods A retrospective cohort was conducted using TriNetX, a global health research network. The network was searched for people aged ≥18 years with ischaemic stroke, EVT and AF recorded in electronic medical records between 01/09/2018 and 01/09/2021. These patients were compared to controls with ischaemic stroke, EVT and no AF. Propensity score matching for age, sex, race, comorbidities, National Institutes of Health Stroke Scale (NIHSS) scores, and prior use of anticoagulation was used to balance the cohorts with and without AF. Results In total 1,388 patients were identified with history of ischaemic stroke treated by EVT. After propensity-score matching, 832 patients (mean age 68±13; 47% female) with ischaemic stroke, EVT and AF, were compared to 832 patients (mean age 67±12; 47% female) with ischaemic stroke, EVT and no history of AF. In the cohort with AF, 11.5% (n=96) experienced ICH within 90 days following EVT, compared with 12.3% (n=103 patients) in patients without AF (Odds Ratio (OR) 0.92, 95% confidence interval (CI) 0.68–1.24; p=0.59). In the patients with AF, mortality within 90 days following EVT was 18.7% (n=156), compared with 22.5% in patients without AF (n=187) (OR 0.79, 95% CI 0.63–1.01; p=0.06). Conclusion In patients with ischaemic stroke undergoing EVT, AF was not significantly associated with intracerebral haemorrhage or all-cause mortality at 90-day follow-up. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Introduction The development of post-operative atrial fibrillation (POAF) after cardiac surgeryis associated with pre-existing endothelial activation and systemic inflammation due to adhesion and transmigration of leukocytes into the interstitium. The electrical remodelling associated with AF causes changes in connexins, resulting in ineffective electrical coupling between cells and thus ineffective cell-cell communication.There is also an association between the inflammatory state, and the presence of cardiac fibrosis, oxidative stress and myocyte apoptosis. Purpose Our aim was to investigate the pathophysiologicaland regulatory mechanisms of AF through endothelial activation and inflammatory status, as well as cell-cell interactions (connexins) in relation to POAF amongst a cohort of patients undergoing cardiac surgery. Methods We studied prospective patients who underwent CABG (52.9%) or cardiac valve (47.1%) surgery without previous documented AF. Patients with permanent AF who underwent CABG or cardiac valve surgery were also included as positive controls. Plasma samples were collected at baseline and 24 hours after surgery, to assess the impact of surgery. To detect endothelial activation, vascular cell adhesion protein-1 (VCAM-1 (CD106)) was evaluated by ELISA assay in plasma samples. Expression of connexin 40 and 43 were measured by inmunohistochemistry in atrial tissue samples. Results We included 117 patients (75.2% males, median age 67 [IQR 59.5–73.0] years), of whom17 (14.5%) patients had permanent AF; 27 (23.1%) developed POAF and 73 (62.4%) had no AF detected. We found higher baseline VCAM-1 levels versus 24-hour samples overall (p=0.001). When comparing groups, baseline VCAM-1 levels were higher in patients with permanent AF compared to non-AF (p=0.035); and in permanent AF compared to POAF (p=0.049). VCAM-1 levels at 24h followed the same trends between permanent AF and non-AF (p=0.001), and permanent AF versus POAF (p=0.013) (Table 1). VCAM-1 levels over the third tertile (i.e.>49.77 ng/ml) increased the risk of AF almost 3-fold (OR 2.85, 95% CI 1.06–7.70; p=0.039). There was a significant decrease in the expression of connexion 40 in patients with AF (ie. patients with permanent AF or POAF) compared to non-AF patients (1.00 [0.50–2.31] vs. 2.48 [1.94–3.00], p=0.044), while connexin 43 was non-significantly different (1.07 [0.41–1.75] vs. 2.00 [0.63–2.25], p=0.289) (Table 2). Conclusions VCAM-1 levels were upregulated in patients with permanent AF and POAF compared to patients without AF, and remained higher even after surgery, thus demonstrating a relevantendothelial activation. The pro-inflammatory state presented in these patients with AF, along with decreased connexin 40 expression impacting cell-to-cell conduction, suggests a potential combination for atrial remodelling and incident AF. Funding Acknowledgement Type of funding sources: None.

Background Long Covid is associated with multiple symptoms and impairment in multiple organs [1]. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiovascular magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid. Purpose We conducted a prospective, longitudinal, 1-year study in individuals with Long Covid to investigate 1) the characteristics and trajectory of cardiac impairment; 2) the impact of acute hospitalisation for COVID-19 on cardiac impairment; and 3) pathways for designing and improving clinical management for individuals at risk of cardiac impairment. Methods 534 individuals with Long Covid underwent baseline CMR (quantitative T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms. If abnormal findings were reported at baseline, individuals were rescanned at 12.6 months (IQR 11.4, 14.2) (n=330). Symptoms, standardised questionnaires, and blood samples were collected at both timepoints (Figure 1). Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), impaired left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac independent AHA segments. A significant change over time was reported by comparison with 92 healthy controls. Results The technical success of this multiorgan assessment in a non-acute setting was 99.1% at baseline, and 98.3% at follow-up, with 99.6% and 98.8% for CMR, respectively. Of individuals with Long Covid, 19% had cardiac impairment at baseline; 70% had complete paired data at 12 months. Of those with paired data, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and reduced GLS were associated with cardiac impairment; however, while elevated T1 was associated with less symptom severity at 12 months, individuals with low LVEF at baseline were associated with ongoing cardiac impairment 1 year post-infection (Figure 2). Conclusion Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Radical (EU) and Innovative UK (UK national) (and others)

Background Peripheral arterial disease (PAD) is a critical clinical and public health issue with a prevalence of >10% worldwide among adults ≥50 years. Whether this occurrence has been increasing, decreasing or stable over time remains a matter of debate as contemporary population data are sparse and conflicting. Purpose To quantify changes in PAD incidence, prevalence, and mortality and provide projections for future prevalence development through 2050. Methods We conducted nationwide analyses of the entire Danish population aged ≥40 years from 2000 through 2018 to assess national trends in diagnosed PAD incidence, prevalence, and all-cause mortality, overall and by sex and age-groups. PAD was identified by primary or secondary in-hospital or outpatient clinic diagnoses, and incident cases comprised individuals whose preceding complete hospital history, potentially back to 1977, lacked a PAD diagnosis. Based on observed trends in incidence and PAD mortality between 2000–2018, and the projected future annual age distribution and population mortality obtained from Statistics Denmark, we projected the future prevalence of PAD through 2050. Results The population of Denmark aged 40–99 years between 2000 and 2018 included 4,508,932 individuals, among whom we identified 123,479 incident diagnoses of PAD during 51,4 million person-years of follow-up. The age- and sex-standardized incidence of PAD decreased from 2.70 per 1,000 person-years in 2000 to 1.79 in 2018 (incidence rate ratio 0.67, 95% confidence interval (CI) 0.65–0.70) (Figure 1). The incidence was approximately 20% higher in men than in women but the accentuation was similarly in both sexes. Concurrently, the overall prevalence of PAD in the Danish adult population increased from 0.8% to 1.7% (prevalence ratio 2.12, 95% CI 2.09–2.15). The prevalence rose considerably in the oldest age groups; in 2018 the prevalence was 5.8% in women and 8.0% in men aged ≥80 years. The age- and sex-standardized annual mortality among patients with PAD decreased from 9.9% in 2000 to 7.0% in 2018, representing a mortality ratio of 0.82 (95% CI 0.75–0.91). Projections of PAD prevalence demonstrated that the rise in the national prevalence of PAD will continue until around 2030 followed by a decline towards 2050 (Figure 2). Among individuals aged ≥80 years, the prevalence was projected to reach a maximum of 8.9% for men vs. 6.5% for women before beginning to decline. Conclusion Within an unselected nationwide population, the incidence and all-cause mortality of PAD has declined over the last two decades. Concurrently, the prevalence increased, and this increasing trend was projected continue over the coming decade before reaching a breaking point around 2030, underscoring the continued need for health service to manage PAD and its complications in years to come. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Karen Elise Jensen's Foundation

Introduction Few data exist on the impact of thromboembolic risk dynamics in determining a higher risk of adverse clinical outcomes in atrial fibrillation (AF) patients. Moreover, no evidence is available about the possible impact of integrated care, as defined by the `Atrial fibrillation Better Care' (ABC) pathway, in modulating the clinical outcomes associated with the dynamic changes in risk. Purpose To study thromboembolic risk dynamics and the relationship with integrated care, also in determining the risk of adverse outcomes in AF patients. Methods We analysed patients from the randomized controlled SPORTIF III and V trials. Thromboembolic risk was assessed according to CHA2DS2-VASc score. Integrated care was assessed according to ABC pathway adherence. The primary endpoint was the composite clinical outcome of all-cause death and major adverse cardiovascular events. Results A total of 3589 patients [mean (SD) age was 70.9 (8.8) years; 30.4% female; median [IQR] baseline CHA2DS2-VASc 3 [2–4]) were available for the analysis. Over a mean 573.8 (SD 129.5) days of follow-up, a total of 67 (1.9%) reported an increase in CHA2DS2-VASc score, with a mean (SD) delta of 0.0295 (0.2257). Among those with increasing CHA2DS2-VASc, 29 (43.3%) reported a 1-point increase, 37 (55.2%) reported a 2-point increase and only 1 (1.5%) reported a 3-point increase. A total of 948 (26.4%) patients were managed adherent to ABC pathway and overall, a median (IQR) of 2 [1–3] ABC criteria were fulfilled in the patients included. An adjusted linear regression analysis found that an increasing number of ABC pathway criteria fulfilled was inversely associated with increase in CHA2DS2-VASc score throughout follow-up (Beta −0.010, 95% CI −0.019 to −0.001), p=0.045), while considering the single ABC criteria, only the “C” criteria was inversely associated with an increase in CHA2DS2-VASc score (Beta −0.018, 95% CI −0.034 to −0.001, p=0.038). A total of 255 (7.1%) clinical events were recorded. An adjusted Cox regression analysis found that both increasing CHA2DS2-VASc score (HR 2.67, 95% CI 2.12–3.36, p Conclusions Integrated care was associated with a lower progression in the thromboembolic risk of AF patients, particular through the optimal management of cardiovascular risk factors and comorbidities. Both increasing thromboembolic risk and increasing adherence to ABC pathway were independently associated, although inversely, with occurrence of adverse clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Background The management of atrial fibrillation (AF) has evolved over the last decade with a more towards a more multidisciplinary, integrated and holistic approach. However, several conditions that may influence the prognosis and management of AF patients are still under-recognised. Purpose Our aim was to investigate if multimorbidity, frailty and malnutrition are associated with the risk of worse clinical outcomes in patients with recent diagnosis of AF starting oral anticoagulation (OAC) therapy. Methods Prospective cohort study including outpatients newly diagnosed with AF starting vitamin K antagonist (VKA) therapy from July 1, 2016 to June 30, 2018. Morbidity was assessed with the crude number of comorbidities. Frailty was assessed with the Clinical Frailty Scale (CFS). Nutrition status was assessed with the Controlling Nutritional Status (CONUT) score. During 2-years of follow-up, we recorded all ischemic strokes/transient ischemic attacks (TIAs), major bleeds (according to the 2005 International Society on Thrombosis and Haemostasis criteria), and all-cause deaths. Results We included 1050 patients (540 [51.4%] females, median age 77 [IQR 70–83] years), with median CHA2DS2-VASc of 4 [IQR 3–5] and median HAS-BLED of 2 [IQR 2–3]. The median crude number of comorbidities was 3 [IQR 2–5], whereas the median CFS and CONUT score were 2 [IQR 2–3] and 2 [IQR 1–3], respectively. The crude number of comorbidities, CFS and CONUT score demonstrated a significant positive correlation (p Conclusions Frailty and malnutrition are important risk factors for bleeding, stroke and mortality in AF. The frailty degree and nutritional status should be assessed in all AF patients in order to address them properly and provide a truly integrated management. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, through the Instituto de Salud Carlos III after independent peer review (research grant: PI17/01375 co-financed by the European Regional Development Fund)

Background The prospective Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) randomized trial demonstrated the efficacy of a mobile health (mHealth) technology implemented “Atrial fibrillation Better Care” (ABC) pathway approach (mAFA intervention) for holistic or integrated care management in reducing the risk of adverse events in in patients with atrial fibrillation (AF). Whether these benefits also apply to elderly patients (who may be less adoptive of mHealth approaches) is unclear. Purpose In this ancillary analysis of the mAFA-II trial, we evaluated the effect of the mAFA intervention among elderly AF patients (age ≥75 years). Methods The mAFA-II trial enrolled adults AF patients across 40 centres in China between June 1, 2018 and August 16, 2019. The main outcome was the composite outcome of stroke or thromboembolism, all-cause death, and rehospitalization. Effect of the mAFA intervention was assessed through Cox proportional hazard models after the adjustment for baseline risk factors and cluster effect. We also assessed the interaction between age and the mAFA intervention effect on the main trial population. Results In this analysis, 1,163 elderly AF patients (mean age: 82.6±5.3 years, 43.1% females) were included, of which 520 were allocated to mAFA intervention and 643 to usual care. The mAFA intervention was associated with a significant reduction of the composite outcome (adjusted hazard ratio [aHR]: 0.58, 95% CI: 0.35–0.97) and rehospitalizations alone (aHR: 0.47, 95% CI: 0.24–0.91). A significant interaction between age and mAFA allocation group was observed for both the composite outcome (p=0.002; Figure 1, Panel A) and rehospitalization alone (p=0.015; Figure 1, Panel B), with the beneficial effect of the mAFA intervention decreasing with increasingly higher age, particularly at age ≥80 years old. Conclusions A mHealth-technology implemented ABC pathway is effective in reducing adverse clinical events in older AF patients aged ≥75 years old. The benefits obtained with mAFA intervention were attenuated at extreme ages, especially in those aged ≥80 years old. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This research was funded by the National Natural Science Foundation of China 82170309). This study was an investigator-initiated project, with limited funding by independent research and educational grants.

Background Stroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline, as a “one-off” evaluation. However, these baseline values are usually applied to predict outcomes many years later, and therefore lack the consideration that the risk is not static. Purpose Our aim was to investigate if dynamic changes of CHA2DS2-VASc and HAS-BLED over time have an effect on the prediction of stroke and bleeding risks. Methods We included AF patients who were stable while taking vitamin K antagonists (INR 2.0–3.0) for 6 months attending a tertiary hospital (May 2007-December 2007). During 6-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), major bleeds, and all-cause deaths were recorded. CHA2DS2-VASc and HAS-BLED were recalculated every 2-years, and their predictive abilities were tested for outcomes in periods of 2-years (from year 0 to 2, year 2 to 4 and year 4 to 6). Results 1361 patients (693 [50.9%] females, median age 76 [IQR 71–81] years, mean CHA2DS2-VASc and HAS-BLED of 4.0±1.7 and 2.9±1.2, respectively) were included. The predictive ability for ischemic stroke/TIA of the baseline CHA2DS2-VASc for 2-years events was 0.662 (0.637–0.688, p The c-index of the baseline HAS-BLED for events at 2-years was 0.744 (0.720–0.767, p Conclusions In AF patients, stroke and bleeding risks are dynamic and change over time. The CHA2DS2-VASc and HAS-BLED scores should be regularly reassessed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, through the Instituto de Salud Carlos III after independent peer review (research grant: PI17/01375 co-financed by the European Regional Development Fund)

Background Residual risk of ischaemic stroke despite anticoagulation in patients with atrial fibrillation (AF) remains poorly investigated. We aimed to evaluate the incidence and risk factors for residual adverse events in AF. Methods Using data from phase II/III of the prospective GLORIA-AF registry, we studied anticoagulated patients from 935 centres across 38 participating who were consecutively enrolled with newly diagnosed AF and an increased risk of stroke (CHA2DS2-VASc ≥1). The primary outcome of interest was ischaemic stroke. Secondary outcomes were all-cause death, cardiovascular (CV) death and myocardial infarction. Risk factors for residual ischaemic stroke were identified using Cox proportional hazards analyses. Results 22410 patients were included; median age 65 (IQR 71–78) and 10044 (44.8%) females. Over 3.0 (IQR 2.2–3.1) years, the incidence per 100-PYs of ischaemic stroke was 0.60 (95% CI, 0.54–0.67), all-cause death 3.22 (95% CI, 3.08–3.37), CV death 1.08 (95% CI, 1.00–1.16) and myocardial infarction 0.59 (95% CI, 0.53–0.66). Using multivariable Cox proportional hazards analysis, independent predictors of residual ischaemic stroke were age (HR 1.05 [95% CI, 1.03–1.06]), diabetes mellitus (HR 1.42 [95% CI, 1.09–1.85]), prior thromboembolism (HR 2.32 [95% CI, 1.79–3.00]), chronic obstructive pulmonary disease (HR 1.53 [95% CI, 1.04–2.26]) and use of anti-arrhythmic drugs (HR 0.70 [95% CI, 0.51–0.96]). The incidence of ischaemic stroke was comparable among patients treated with non-vitamin K antagonist oral anticoagulants vs. vitamin K antagonist; however, there were differences in the independent predictors between both groups. Conclusion Patients with AF remain at significant risk of ischaemic stroke despite anticoagulation therapy. Risk factors for residual ischaemic stroke were prior thromboembolism, age, persistent AF, diabetes mellitus, chronic obstructive pulmonary disease and non-use of anti-arrhythmic drug therapy. This emphasises the need to treat these risk factors, if modifiable, beyond antithrombotic therapy. Funding Acknowledgement Type of funding sources: None.

Background Anaemia is an independent predictor of atrial fibrillation (AF) and a common comorbidity. Real world data on the impact of anaemia on clinical outcomes, and on the benefits and risks of oral anticoagulation (OAC) are limited. Purpose To investigate the association of different degrees of anaemia with adverse outcomes in a cohort of European patients with AF. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry with baseline hemoglobin (Hb) values. Patients were stratified according to World Health Organization (WHO) definition of anaemia: (i) No anaemia (Hb≥12.0g/dl for women and Hb≥13.0g/dl for men), Mild anaemia (Hb 11.0–11.9g/dl for women and Hb 11.0–12.9g/dl for men), and moderate-severe anaemia (Hb ≤10.9 g/dl for both sexes). Primary outcomes were all-cause death, major adverse cardiac events (MACE, as the composite of any thromboembolism (TE)/acute coronary syndrome/cardiovascular death) and major bleeding. Results From the original 11,096 AF patients enrolled in the Registry, 7767 (69.9%) were included in the present analysis (median age 70 years, interquartile range [IQR] 62–77, males 58.3%, CHA2DS2VASc score median 3 [2–4], HAS-BLED median 2 [1–2]). A total of 5973 (76.9%) patients did not have anaemia, 1156 (14.9%) had mild anaemia, and 638 (8.2%) had moderate/severe anaemia. Patients with anaemia were more likely to have more comorbidities, frailty, permanent AF and polypharmacy (≥5 drugs). Overall, 318 (18.4%) patients with anaemia and an indication for anticoagulation [i.e. CHA2DS2-VASc≥1 (males), or ≥2 (females)] did not receive any OAC. After a median (IQR) follow-up of 730 (692–749) days, all-cause death was 10.5% and there were 841 (11.6%) MACE and 186 (2.5%) major bleeds. Kaplan–Meier analysis showed a higher cumulative risk for patients with moderate-severe anaemia for all the outcomes considered (Figure) (Log Rank tests, all p Conclusions In a large contemporary cohort of European AF patients, almost 25% have concomitant anaemia which is associated with an increased risk for all-cause mortality, MACE and major bleeding. Use of OAC was associated with a lower risk of all-cause mortality in patients with moderate-severe anaemia, without significant increased risk of major bleeding. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022)

Background The NULL-PLEASE score (Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood pH 7.0 mmol/L, End-stage renal disease on dialysis, Age ≥85 years, Still resuscitation, and Extracardiac cause) was developed to help identify patients with out-of-hospital cardiac arrest (OHCA) who are unlikely to survive. Although survival after OHCA differs between sexes, the performance of the NULL-PLEASE score according to sex has not been tested previously. Purpose To validate the NULL-PLEASE score separately in men and women in a nationwide setting. Methods Using Danish nationwide registry data from 2001–2019, we retrospectively identified male and female OHCA survivors with return of spontaneous circulation (ROSC) or ongoing cardiopulmonary resuscitation at hospital arrival. The primary outcome was 1-day mortality. Secondary outcomes were defined as 30-day mortality and the combination of 1-year mortality or anoxic brain damage. Logistic regression with a NULL-PLEASE score of 0 as reference was used for outcome risk estimation. The predictive ability of the score was assessed using area under the receiver operating characteristics (AUCROC) curves. Results A total of 2,601 men (median age 67 years (interquartile range (IQR) 56–76 years), and 1,280 women (median age 69 years (IQR 58–79 years) were included. One-day mortality was 31% in men and 42% in women; 30-day mortality was 56% and 71% in men and women, respectively; and 63% of men and 78% of women experienced the combined outcome. For patients with a NULL-PLEASE score ≥9, absolute risks were: 1-day mortality: 82.0% (95% confidence interval [CI]: 75.6–88.4%) for men and 79.1% (95% CI: 71.3–86.8%) for women; 30-day mortality: 98.6% (95% CI: 96.6–100.0) for men and 97.1% (95% CI: 94.0–100.0%) for women; and the combined outcome: 99.3% (95% CI: 97.9–100.0%) for men and 97.1% (95% CI: 94.0–100.0%) for women. AUCROC values for 1-day mortality were 0.827 (95% CI: 0.811–0.844) for men and 0.736 (95% CI: 0.710–0.763) for women. Results were similar for 30-day mortality and for the combined outcome. ROC curves for all outcomes are shown in Figure 1 (men) and Figure 2 (women). For a NULL-PLEASE score cut-point ≥3 to predict 1-day mortality, the positive predictive value was 91.8% in men and 91.1% in women, with a sensitivity of detecting patients who die of 47.3% in men and 51.8% in women. The corresponding negative predictive value for surviving more than 1 day was 54.6% in men and 37.7% in women, and the specificity of detecting patients who survive was 93.7% in men and 85.3% in women. Conclusions In a nationwide OHCA-cohort, the NULL-PLEASE score consistently appeared to perform better in men than in women for all outcomes. Nevertheless, its predictive ability was high among both sexes. Sex-specific differences should not be overlooked in clinical decision-making in patients surviving OHCA. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Danish Foundation TrygFonden

Background Older care home residents are a high-risk group of people with atrial fibrillation (AF) who are under-represented in clinical trials. Improved understanding of AF epidemiology and management in this population is paramount for health and social care organisations to strategically plan services. Purpose To determine the trends in AF prevalence and compare adverse health outcomes in older care home residents aged ≥65 years with AF compared to those without AF. Methods Retrospective cohort study of people entering a care home between 2003–2018 using nationwide, population-scale anonymised health and administrative data, provisioned from the Secure Anonymised Information Linkage (1 January 2000–31st December 2018). Direct standardisation was used to calculate AF prevalence by year of care entry (2010–2018). Cox regression analyses were used to estimate the risk of adverse health outcomes. Results Between 2003 and 2018, 86,602 people aged ≥65 years became new residents in care homes in Wales. Residents with AF (n=14,493) had a significantly higher risk (adjusted hazard ratio [aHR], 95% confidence interval [CI]) of cardiovascular (aHR 1.27 [1.17 to 1.37], p Conclusions This study demonstrates unique data on the epidemiology of AF and associated outcomes in older care home residents. Whilst the prevalence of AF remained stable between 2010–2018, residents with AF had significantly higher risk of adverse health events. Treatment of AF in accordance with guidelines is critical in this population to optimise management and reduce adverse health outcomes. Funding Acknowledgement Type of funding sources: None.

Introduction Individuals affected by atrial fibrillation (AF) often present with multiple comorbidities that challenge their clinical management and worsen the prognosis. Characterizing the network structure of comorbid chronic conditions in AF patients may provide insights to better tailor medical and care management. Purpose To examine and compare the network structure of comorbidities in older people with and without AF. Methods Cross-sectional data derived from the Danish National Patient Register (period 2012–2017) were examined. Patients 60+ years old by 1. January 2017 with AF were selected and matched by age and sex to non-AF controls. Chronic conditions coded according to the International Classification of Diseases, 10th revision were retrieved and grouped into 60 clinically relevant disease categories for old age. Network analysis was applied to construct the disease networks and the centrality index of expected influence was measured to estimate the disease interconnectedness in each network. The difference in network structure and disease centrality between AF and non-AF patients was formally assessed through network comparison tests. Results A total of 96,117 AF patients (72 years old; 45% women) were identified and matched with 96,117 non-AF controls. The most prevalent chronic conditions in AF were hypertension (55.1%), large bowel diseases (36.4%) and ischemic heart disease (36.0%). A significant difference of global network structure was observed between AF and non-AF patients (p Conclusions Older AF patients exhibited a complex network structure of chronic conditions that differed from age- and sex- matched non-AF patients. The network-based identification of highly co-morbid diseases in AF can improve our understanding of AF-related chronic conditions and potentially enhance prioritization and a personalized care for older patients with AF. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation programme

Background Heart failure (HF) has an intimate bidirectional association with atrial fibrillation (AF). Few data are available about the impact of HF phenotypes (HF with preserved ejection fraction, HFpEF; HF with mildly reduced ejection fraction, HFmrEF; HF with reduced ejection fraction, HFrEF) as predictors for adverse outcomes in AF patients. Purpose To investigate the association of HFpEF, HFmrEF and HFrEF with adverse outcomes in a large contemporary cohort of European AF patients and evaluate the effect of EF throughout its entire spectrum. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. HF patients were categorized according the three phenotypes and compared to those without HF (“non HF”). Main outcome was a composite outcome of all-cause death and major adverse cardiac events (MACE). Results Among the original 11,096 AF patients enrolled, 9857 (88.8%) were included in this analysis (median age 71 years, interquartile range [IQR 63–77], 40.1% females) with median EF 55% [IQR 45–61%] and CHA2DS2-VASc 3 [2–4]). In this cohort, 5935 (60.2%) were non HF patients, and 3240 (32.9%) had HF patients (with HF status and EF values data available). Accordingly, 1662 (51.2%) were categorized as HFpEF; 523 (14.1%) were HFmrEF; and 1235 (35.1%) were HFrEF. After a median follow-up of 731 days [IQR 690–748], the composite outcome was significantly higher throughout HF categories (HFpEF 19.0%, HFmrEF 21.8% and HFrEF 29.6%, compared to non HF 10.7%; p Conclusions Over a two-years follow-up, in a large contemporary cohort of European AF patients, HF phenotypes were associated with a progressively higher risk for adverse outcomes. Lower EF values increased the risk of adverse outcomes both in HF patients and overall AF patients, irrespective of HF phenotype status. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022).

Background Heart failure (HF) has close association with atrial fibrillation (AF). The ESC guideline recommended Atrial fibrillation Better care (ABC) pathway aims to reduce major cardiovascular adverse outcomes with an integrated care approach. Optimal medical treatment (OMT) represents the cornerstone in HF management. Purpose To investigate the variables affecting OMT treatment and its impact, in conjunction with ABC pathway adherence (vs non-adherence, ie.no ABC), in a large contemporary cohort of European AF patients with HF enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Methods OMT was defined as treatment with Angiotensin-converting-enzyme inhibitors (ACE-i)/ Angiotensin receptor blockers (ARBs) with Beta-Blockers and/or Mineralocorticoid receptor antagonists (MRAs), and compared to non-OMT adherence (“no OMT”). A logistic regression analysis explored factors associated with OMT adherence. We identified three patient groups: (i) HF with no OMT/no ABC; (ii) HF with OMT/no ABC; (iii) HF with OMT/ABC. Primary outcome was a composite outcome of all-cause death and major adverse cardiac events (MACE). Results Among the original 11096 patients enrolled, 9857 (88.8%) were included in this analysis. Among these, 3819 (38.7%) had HF. Compared to non HF patients, those with HF were older, more likely female, had more comorbidities and higher thromboembolic risk. OMT prevalence was 2228/3819 (58.3%), while ABC adherence was 23.3%. On logistic multivariable regression, increasing age, higher BMI and higher frailty index were associated with OMT adherence, while male sex, anemia, renal disease and EHRA II–IV were inversely associated with OMT adherence. According to three HF groups, the rates of composite outcome progressively decreased (HF with no OMT/no ABC 26.4%; HF with OMT/no ABC 24%, HF with OMT/ABC 19%; p Conclusions After two years of follow-up, in a large contemporary cohort of European AF patients with HF, OMT adherence was suboptimal, being influenced by several clinical factors, determining a low adherence to the ABC pathway. OMT alone showed a non-significant reduction in composite outcome events. Conversely HF patients managed with OMT in the context of ABC pathway adherence showed the best reduction in risk of adverse outcomes. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022). - I agree that this information can be anonymised and then used for statistical purposes only

Background Atrial fibrillation (AF) and cancer are frequently coexisting in elderly patients. Pooled metanalytic data on the impact of cancer on outcomes in AF patients are lacking. Purpose We want to investigate the impact of cancer in patients with AF, particularly in relation to the incidence of bleeding and ischemic events Methods Systematic review and meta-regression analysis of clinical studies retrieved from Medline (PubMed) and Cochrane (CENTRAL) databases according to PRISMA guidelines. Safety endpoints included any, major, gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Efficacy endpoints included myocardial infarction (MI), ischemic stroke/systemic embolism (IS/SE), cardiovascular (CV) and all-cause death. Results 15 studies were included in the metanalysis: 4 prospective, 3 randomized clinical trials and 8 retrospective studies with 2,868,010 AF patients, of whom 479,571 (16.7%) had cancer. The pooled HR for cancer was 1.43 (95% CI 1.42–1.44) for any bleeding, 1.27 (95% CI 1.26–1.29) for major bleeding, 1.17 (95% CI 1.14–1.19) for GI bleeding, and 1.07 (95% CI 1.04–1.11) for ICH. The risk of major bleeding increased with the proportion of breast cancer. Cancer increased the risk of all-cause death (HR 2.00, 95% CI 1.99–2.02) whereas no association with MI (HR 0.97, 95% CI 0.94–1.01) and CV death (HR 1.01, 95% CI 0.99–1.03) was found. Patients with AF and cancer were less likely to suffer from IS/SE (HR 0.91, 95% CI 0.89–0.94). Conclusion The presence of cancer modifies the clinical history of AF patients, mainly increasing the risk of bleeding. Further analyses according to the type and stage of cancer is necessary to better stratify bleeding risk in these patients. Funding Acknowledgement Type of funding sources: None.

Background Prescription of oral anticoagulants (OAC) is paramount for stroke prevention in people with atrial fibrillation (AF), but treatment decisions in older care home residents are complicated by frailty, multi-morbidity and heightened stroke and bleeding risk. There is a paucity of data on factors influencing the decision to prescribe OAC in this high-risk population who are under-represented in research studies. Purpose To explore the factors associated with OAC prescription for care home residents aged ≥65 years with AF. Methods Nationwide retrospective cohort study of people aged ≥65 years entering a care home in Wales between 1 January 2003 and 31 December 2018, using anonymised individual-level electronic health record and administrative data sources available within the Secure Anonymised Information Linkage Databank. Unadjusted and adjusted logistic regression models were used to explore the association between resident characteristics and OAC prescription or non-prescription. Results Between 2003 and 2018, 14,493 people with AF aged ≥65 years became new residents in care homes in Wales and 7,057 (48.7%) were prescribed OAC (32.7% in 2003 compared to 72.7% in 2018), Figure 1. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per one year age increase [95% confidence interval, 0.95 to 0.96] and aOR 0.91 [0.84 to 0.98], respectively). Conversely, prior venous thromboembolism (aOR 4.06 [3.17 to 5.20]), advancing frailty (mild: aOR 4.61 [3.95 to 5.38]; moderate: aOR 6.69 [5.74 to 7.80]; severe: aOR 8.42 [7.16 to 9.90]) and year of care home entry in the post-non-vitamin K antagonist oral anticoagulant (NOAC) era from 2011 onwards (aOR 1.91 [1.76 to 2.06]) were associated with higher odds of OAC prescription, Figure 2. Conclusions The proportion of care home residents prescribed OAC therapy has increased over time with the introduction of NOACs in 2011, but OAC prescription rates are still sub-optimal. Although there is an expected rise in OAC prescribing for increasingly frail people, further work is needed to investigate the interaction with deprivation and other socio-economic and demographic factors to assess potential inequalities in prescribing across these groups. Targeted educational tools for clinicians are needed to address barriers to OAC prescription for AF, such as older age and separate indications for antiplatelet therapy. Funding Acknowledgement Type of funding sources: None.

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 analyzed the impact of the ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analyzed clinically complex AF patients, defined as the presence of frailty (according to a 40-items Frailty Index), 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 the risk of all-cause death, major adverse cardiovascular events (MACEs) and the composite outcome of all-cause death and MACE was analyzed through Cox-regression analyses, and delay of event (DoE) analyses; number needed to treat (NNT) was also estimated at 1 year of follow-up. Results Among 9,966 AF patients, 8,289 (92.3%) were clinically complex. Risk of all outcomes was higher among clinically complex patient. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.71, 95% CI 0.57–0.89), major adverse cardiovascular events (MACEs, aHR: 0.68, 95% CI 0.53–0.87) and composite outcome (aHR: 0.69, 95% CI: 0.57–0.84). Using cluster analysis, we identified a high clinical complexity group of AF patients. Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.73, 95% CI 0.55–0.96) and composite outcome (aHR: 0.69, 95% CI 0.57–0.84) 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-cause death (Figure 1), MACEs, and composite outcome in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the NNTs 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 amongst clinically complex AF patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, several companies have supported the programme with unrestricted grants.

Background The impact of Atrial Fibrillation Better Care (ABC) pathway adherence among high-risk subgroups of patients with atrial fibrillation (AF), ie. those with chronic kidney disease (CKD), advanced age and/or prior thromboembolism remains unknown. We evaluated the impact of ABC pathway adherence on clinical outcomes in these high-risk AF patients. Methods The 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 Results A total of 6646 patients with AF were included (median age was 70 [IQR 61–77] years; 40.2% females). There were 3304 (54.2%) `high risk' patients with either CKD (n=1750), older age (n=2236) or prior thromboembolism (n=728). Among these there were 924 (28.0%) managed as adherent to ABC. At 2-year follow-up, a total of 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 [Table]. Using multivariable Cox proportional hazards analysis, ABC adherence in the high-risk cohort was independently associated with a lower risk of 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, as well as in the individual subgroups [Figure]. Conclusion In a large, contemporary European AF cohort there was a significant proportion of high-risk patients. Among these, a low prevalence of integrated care, as assessed by adherence to ABC pathway, was found. Nonetheless, a clinical management adherent to the ABC pathway was associated with a significant reduction in the risk of adverse outcomes, the benefits of which were more significant with increasing number of ABC criteria adherent. Funding Acknowledgement Type of funding sources: None.

Background and aims The integrated approach for management of atrial fibrillation (AF) has been proposed in recent years for reducing AF-related mortality, morbidity, and hospitalizations. We evaluated the trends in the risk of ischemic stroke, intracranial bleeding, hospitalization for heart failure, cardiovascular mortality and all-cause death among newly diagnosed patients with AF in a nationwide cohort study since 2010. Methods This French longitudinal cohort study was based on the national hospitalization database covering hospital care from for the entire population. All adults hospitalized in French hospitals with AF from January 1, 2010 to December 31, 2018, were identified. Among them, 1,938,269 newly diagnosed patients with AF who survived 60 days after AF was diagnosed were included in the analysis. The 1-year risk of ischemic stroke, intracranial bleeding, and mortality of patients with AF diagnosed in each year were compared to those diagnosed in 2010 using the logistic regression analysis adjusted for age, sex, hypertension, diabetes mellitus, heart failure, prior stroke, vascular diseases, chronic obstructive pulmonary disease, hyperlipidemia, inflammatory diseases, cancer, abnormal renal function, abnormal liver function, anemia, and history of bleeding. Results The age of newly diagnosed patients with AF was stable from 77.1±11.8 years in 2010 to 76.9±12.6 years in 2018. Mean CHA2DS2-VASc scores of patients with incident AF showed a significant increasing trend for each year (from 3.32 in 2010 to 3.54 in 2018, p Temporal trends for the risk of adverse events at 1-year follow-up in newly diagnosed patients with AF compared to 2010 are shown in the Figure 1. Compared with 2010, the risk of ischemic stroke was significantly lower in all subsequent years from 2011 to 2018 (adjusted hazard ratios [HR] 0.940 to 0.854; p ranging from p=0.001 to 0.50). The risk of hospitalization for heart failure was significantly lower in all subsequent years after 2010 (adjusted HRs 0.927 to 0.820; all p Conclusion We observed a constant reduction in the risk of ischemic stroke, major bleeding, hospitalization for HF, cardiovascular death and all-cause death in AF patients seen in French hospitals in recent years. This may be related to an increasing use of oral anticoagulants (including NOACs) and by a more holistic and integrated approach to AF management that has been proposed in the more recent guidelines. Funding Acknowledgement Type of funding sources: None.

Introduction The association between cancer types and specific bleeding events in atrial fibrillation (AF) patients has been scarcely investigated. Also, the performance of bleeding risk scores in this high-risk subgroup of patients is unclear. Purpose We investigated the rate of intracranial haemorrhage (ICH), major (MB) and gastrointestinal bleeding (GB) according to cancer types in AF patients. We also tested the predictive value of HAS-BLED, ATRIA and ORBIT bleeding risk scores. Methods Observational retrospective cohort study including 399,344 AF patients with cancer (mean age 77.9±10.2 years; 63.2% men). MB was defined according to Bleeding Academic Research Consortium (BARC) definitions. Results The highest ICH rates were found in leukaemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year) and pancreas cancer (1.41%/year). GBs were highest in liver (7.54%/year), pancreas (7.42%/year) and gastric (5.51%/year). Receiver operating characteristic (ROC) analysis showed that an ORBIT score ≥4 had the highest predictivity for MBs (AUC 0.805) followed by HAS-BLED and ATRIA (AUC 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for ICH (AUC 0.744 and 0.742, respectively), better than ATRIA (AUC 0.635). For GB, ORBIT ≥4 had the highest predictivity (AUC 0.756), followed by the HAS-BLED (AUC 0.702) and ATRIA (AUC 0.662). Conclusions Some cancer types carry a greater bleeding risk in AF patients. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up Conclusions Some cancer types carry a greater bleeding risk in AF patients. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up. Funding Acknowledgement Type of funding sources: None.

Background Atrial fibrillation (AF) detection could be effective with photoplethysmography (PPG) signal monitoring by a wearable device. Purpose We aimed to validate the performance of AF detection among ambulatory patients who underwent electrical cardioversion for AF using a smart ring capable of continuous PPG monitoring and deep learning analysis. Methods In this prospective single-arm study, participants who underwent successful electrical cardioversion for AF were enrolled. The participants equipped a smart ring (CardioTracker, Sky Labs Inc., Seongnam, Republic of Korea) after the electrical cardioversion. The smart ring then continuously monitored PPG over 14 days to detect AF recurrence. The smart ring alarmed AF episodes based on deep learning analysis of PPG. The participants were asked to measure at least three daily ECGs using the smart ring to validate AF recurrence detected by PPG. All ECG snapshots were recorded along with lead I and saved with simultaneous PPG. ECG data were examined by the three cardiologists independently (SK, SRL, and EKC). The monitoring time, analyzable proportions of monitored signals, detection rates of AF episodes, and the diagnostic performance of PPG-based deep learning were evaluated. At the end of the monitoring, a survey on the use of the smart ring was performed. Results A total of 35 participants (mean age 58.9 years, male 74.3%) were enrolled. Figure 1 illustrates an example of PPG monitoring and PPG-ECG snapshots by the smart ring. The study participation period was a median of 14 days and the wearing time of the smart ring was a median of 9.2 days (IQR 7.1–11.5 days). Signal artifacts during daily activity decreased the analyzable proportions of monitored PPG by 68.5%. Irregular pulse episodes were detected by the smart ring in 29 (82.9%) participants after a median of 1 day from the cardioversion (Figure 2). A total of 2532 PPG-ECG snapshots were acquired and 1623 (64.1%) were interpretable by both the cardiologists (using ECG) and the deep learning analysis (using PPG). Comparing PPG by simultaneous ECG, the performance of AF detection by the smart ring was 98.7% for sensitivity, 97.8% for specificity, 2.2% for false positives, and 1.3% for false negatives (Figure 2). After using the smart ring, 76.9% of the participants responded that they had no discomfort in using the smart ring in daily activity and another 76.9% responded that it was helpful to monitor their disease. Conclusion Despite the signal artifacts during daily activity, AF detection with PPG monitoring by a smart ring could be effective for AF screening among ambulatory patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This work was supported by Sky Labs Inc, Seongnam, Republic of Korea, and by the grant No. 0320202040 from the Seoul National University Hospital Research Fund.

Funding Acknowledgements Type of funding sources: None. Background Although the prevalence of atrial fibrillation (AF) is increasing worldwide, little is known about the exact risk factors of AF; and the disease"s association with socioeconomic status (SES) is under debate. Purpose This study aimed to examine the association between SES and the risk of AF in Korean patients with diabetes mellitus. Methods We studied 2,429,610 diabetic patients (mean age 56.9 years, female 40%) who underwent health check-ups from 2009 to 2012, using the National Health Insurance Service (NHIS) database of Korea. Subjects were categorized into 6 groups according to the number of times (0 through 5) entitled for medical aid (MA) recipient, within the past 5 years from the date of check-up. (Fig. 1) Division of Medical Care Assistance in the Ministry of Health and Welfare selects the medical aid beneficiaries. The recipients should not have a reliable caregiver, nor their income be more than 40% of the standard median income. Among the study population, 64,818 were classified as MA group: 10,697 in MA 1, 11,005 in MA 2, 12,431 in MA 3, 10,689 in MA 4, 19,996 in MA 5, respectively. The remaining 2,364,792 were never entitled to MA recipients within 5 years and were assigned to the non-MA group. The incidence rate and hazard ratio of AF were then calculated for each group. Results Risk factors for cardiovascular disease were measured at baseline. More current smokers were in MA 5 group (28.7% in MA 5, 26.7% in non-MA, 26.2% in MA 1, 23.8% in MA 2, 23% in MA 3, 23.2% in MA 4, respectively, p Hypertension and dyslipidemia were generally higher in MA groups than in the non-MA group (hypertension, 60.8–65.8% in MA groups vs. 54.8% in non-MA group; dyslipidemia, 44.1–54.9% in MA groups vs. 39.6% in non-MA group, all, p 80,257 were newly identified as AF in the retrospective 5 years. All the MA groups showed a higher risk of AF than the non-MA group: hazard ratio (95% confidence interval [CI]) for each group, 1.44 (1.32–1.58) in MA 1, 1.58 (1.45–1.73) in MA 2, 1.52 (1.39–1.65) in MA 3, 1.53 (1.40–1.68) in MA 4, and 1.35 (1.24–1.45) in MA 5. Adjusting with multi-variables, the MA 5 showed 54% increased risk of AF compared to the non-MA group (HR, 1.54, [95% CI, 1.42–1.67]). (Fig. 2) Conclusion The risk of AF increased more than 50% in patients who needed medical aid 5 years in a row, and the risk also rose greatly in patients with only a short experience of socioeconomic hardship. Based on the findings, we need more attention to individuals with recent socioeconomic deprivation to provide timely management for AF and its complications. Abstract Figure. Fig. 1

Background Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. Methods We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1‑year follow-up data were gathered. Results At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). Conclusions Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Background In the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial, low-dose edoxaban (15mg once daily) showed better efficacy for stroke prevention and positive net clinical benefit compared to placebo in very elderly and high bleeding risk patients with atrial fibrillation (AF) who often excluded from oral anticoagulation (OAC) therapy. However, there are limited data to generalize the ELDERCARE-AF results into daily practice. Purpose To investigate the optimal OAC strategy for the best net clinical benefit in ELDERCARE-AF-like patients. Methods Using the Korean nationwide claims database, we included patients with incident non-valvular AF aged 80 years or older between 2014 and 2017. Among these, patients with one or more of the following criteria were finally included in the analysis: a low creatinine clearance (15 to 30 mL/min), a history of bleeding from a critical area or organ or gastrointestinal bleeding, low body weight (≤45kg), continuous use of nonsteroidal anti-inflammatory drugs, or current use of an antiplatelet drug. The risks of ischemic stroke, major bleeding, all-cause death, and composite clinical outcome (ischemic stroke+major bleeding+all-cause death) as a measure of net clinical outcome were evaluated during follow-up. The inverse probability of treatment weighting (IPTW) method was used to balance covariates between the groups. Results A total of 23,858 patients were finally included (no OAC, n=16,575; warfarin, n=2390; and direct oral anticoagulants (DOACs), n=4893, respectively). Among DOAC group, 69% used low-dose including rivaroxaban 15 mg once daily, dabigatran 110 mg twice daily, apixaban 2.5 mg twice daily, and edoxaban 30 mg once daily and 9% used very low dose including rivaroxaban 10 mg once daily and edoxaban 15 mg once daily (Figure). Median follow-up duration was 2 years (interquartile ranges, 1 to 3 years). Baseline characteristics were well-balanced after IPTW. Compared to the no OAC group, the DOAC group was associated with a lower risk of ischemic stroke (hazard ratio [HR], 95% confidence interval [CI]: 0.81, 0.68–0.95) and all-cause death (0.90, 0.85–0.95), and a higher risk of major bleeding (1.43, 1.20–1.69) (Figure). Patients treated with DOAC showed a lower risk of composite clinical outcome compared to those without OAC treatment (0.93, 0.88–0.98). Warfarin treatment did not reduce the risk of ischemic stroke (1.03, 0.85–1.23) and all-cause death (1.05, 0.99–1.12), but increased the risk of major bleeding (1.60, 1.32–1.92) and the composite clinical outcome (1.08, 1.02–1.15) compared to no OAC group. Conclusion In very elderly patients with non-valvular AF who had one or more frail components, DOACs which were currently prescribed in usual clinical practice showed better effectiveness and positive net clinical benefit compared to no OAC treatment. Compared to the latter, warfarin did not show benefit and possible harm. Funding Acknowledgement Type of funding sources: None.

Background The presence of cancer worsens the prognosis of patients with atrial fibrillation (AF). However, the association between cancer type and specific bleeding events has been scarcely investigated. Furthermore, the performance of bleeding risk scores, such HAS-BLED, ORBIT and ATRIA, in this high-risk subgroup of AF patients is unclear. Purpose To investigate the incidence rate (IR) of major, gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH) according to cancer types. We also investigated the performance of HAS-BLED, ATRIA and ORBIT scores. HASBLED ≥3, ATRIA ≥5 and ORBIT ≥4 were defined as high-risk. Methods Observational retrospective cohort study including 399,344 patients with AF and cancer. Results Mean age was 77.9±10.2 years and 63.2% were men. During a mean follow-up of 2.0 years, the IR of major bleeding was as high as 8.41%/year, GI bleeding was 3.61%/year and ICH 1.33%/year. Major bleedings were more frequent in liver (12.68%/year), leukaemia (12.39%/year), pancreas (11.71%/year), bladder (11.67%/year) and myeloma (11.64%/year). GI bleeding were highest in liver (7.54%/year), pancreas (7.42%/year) and gastric (5.51%/year). The highest IR of ICH was found in leukaemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year) and pancreas cancer (1.41%/year). Figure 1 shows the hazard ratios and AUC values for the three scores against each endpoint. All the three scores were significantly associated with major, GI and ICH. The HAS-BLED score performed better than others for ICH prediction, while the ORBIT score showed the best predictivity for major and GI bleedings (p Conclusions Cancer increases the risk of bleeding in patients with cancer, with specific differences according to each cancer type. HAS-BLED score identified patients at highest risk for ICH and the ORBIT score for major and GI bleeding. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Diabetes is one of the most common chronic disorders worldwide and is an important cause of cardiovascular disease. Large studies investigating the risk of atrial fibrillation (AF) in diabetic patients taking different diabetes medications are still missing. Methods The analysis was based on the EGB (“Echantillon Généraliste des Bénéficiaires”) database, a 1/97 representative sample of the French nationwide claims and hospitalisation database. A cohort comprising 25,117 adult patients with diabetes and no previous AF seen between 2010 and 2018 was created and followed until December 2018 for incidence of new-onset AF. Among these diabetic patients, 36.0% were treated with metformin, 32.0% were treated with Sulfonylureas, 7.0% were treated with DPP4-inhibitors, 1.6% were treated with GLP1- analogues and 19.6% were treated with insulin. A Cox proportional hazards model was used to determine factors and different oral diabetes medications independently associated with the risk of AF during follow-up. Results During a follow-up of 4.8±3.5 years, there were 3,300 patients with new onset AF (yearly rate 2.7%). In multivariable analysis, among baseline characteristics, we found that older age, male sex, hypertension, heart failure, aortic stenosis, chronic kidney disease, anemia and diuretic use were independently associated with a higher risk of new AF. Among diabetes medications included in the multivariable model, use of sulfonylureas was independently associated with a lower risk of AF (HR 0.86, 95% CI 0.80–0.92, p Conclusions Patients with different diabetes medications have significantly different long-term risk of AF. Specifically, sulfonylureas use was associated with a lower risk of incident AF whilst other antidiabetic drugs were associated with a higher risk of AF during follow-up. Funding Acknowledgement Type of funding sources: None.