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Background: Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues. Methods: We compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells. Results: Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice. Conclusions: Based on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 and 2019. The in-hospital mortality rates, length of stay (LoS), and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p < 0.001). The estimated total care cost for all patients with T1DM with CCD was approximately USD 326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68–23.79), pulmonary embolism (OR 4.39, 95%CI 2.70–7.13), endocarditis (OR 3.46, 95%CI 1.22–9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92–2.77), and stroke (OR 1.47, 95%CI 1.04–2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study on the effects of oral anticoagulation in patients with device-detected atrial fibrillation (DDAF) without ECG-documented atrial fibrillation (AF). The study analyzed data from 2534 patients and compared outcomes and the effect of anticoagulation in patients with different risk factors. The results showed that anticoagulation did not appear to be more effective in patients with a high risk score, and the rate of stroke was low in patients without anticoagulation. The study suggests the need for new methods to identify high-risk patients who may benefit from anticoagulation. The article also provides information about financial disclosures and funding sources related to the authors of the study. [Extracted from the article]

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies. [ABSTRACT FROM AUTHOR]

Background: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. Objective: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. Methods: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. Results: The median age of the cohort was 67 (IQR 59–74) years old and the median monitoring duration was 1051 (IQR 478–1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736–0.737, multilayer perceptron with an AUC of 0.697–0.708, XGBoost with an AUC of 0.697–0.697, and random forest with an AUC of 0.663–0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. Conclusion: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy. [ABSTRACT FROM AUTHOR]

Objective: A diagnosis of epilepsy has been associated with adverse cardiovascular events (CEs), but the extent to which antiseizure medications (ASMs) may contribute to this is not well understood. The aim of this study was to compare the risk of adverse CEs associated with ASM in patients with epilepsy (PWE). Methods: A retrospective case–control cohort study was conducted using TriNetX, a global health federated network of anonymized patient records. Patients older than 18 years, with a diagnosis of epilepsy (International Classification of Diseases, 10th Revision code G40) and a medication code of carbamazepine, lamotrigine, or valproate were compared. Patients with cardiovascular disease prior to the diagnosis of epilepsy were excluded. Cohorts were 1:1 propensity score matched (PSM) according to age, sex, ethnicity, hypertension, heart failure, atherosclerotic heart disease, atrial and cardiac arrythmias, diabetes, disorders of lipoprotein metabolism, obesity, schizophrenia and bipolar disorder, medications, and epilepsy classification. The primary outcome was a composite of adverse CEs (ischemic stroke, acute ischemic heart disease, and heart failure) at 10 years. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) following 1:1 PSM. Results: Of 374 950 PWE included; three cohorts were established after PSM: (1) carbamazepine compared to lamotrigine, n = 4722, mean age 37.4 years; (2) valproate compared to lamotrigine, n = 5478, mean age 33.9 years; and (3) valproate compared to carbamazepine, n = 4544, mean age 37.0 years. Carbamazepine and valproate use were associated with significantly higher risk of composite cardiovascular outcome compared to lamotrigine (HR = 1.390, 95% CI = 1.160–1.665 and HR = 1.264, 95% CI = 1.050–1.521, respectively). Valproate was associated with a 10‐year higher risk of all‐cause death than carbamazepine (HR = 1.226, 95% CI = 1.017–1.478), but risk of other events was not significantly different. Significance: Carbamazepine and valproate were associated with increased CE risks compared to lamotrigine. Cardiovascular risk factor monitoring and careful follow‐up should be considered for these patients. [ABSTRACT FROM AUTHOR]

Background The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOACs). However, it comes with an increased risk of bleeding, and therefore, counselling patients on their individual risks is important. Although the majority of patients initiated on DOACs have been represented within the clinical trials, some cohorts are under-represented in whom clinicians cannot practice evidence-based medicine. Methods Utilising the pooled clinical trial (CT) data sourced from Medidata Enterprise Data Store, five recent open-label industry-sponsored AF trials were compared with real-world data (RWD) sourced from the HealthVerity™ Marketplace with the occurrence of bleeding events as the primary outcome of interest. Results A total of 64,421 patients were included in the analysis, with 3207 patients from the clinical DOAC trials and 61,214 patients from the RWD cohort. Overall, the patients from the RWD cohort had more co-morbidities, were older (72.2 ± 11.9 vs. 65.3 ± 10.7 years old, p < 0.001), had higher mean CHA2DS2VASc (3.98 ± 1.9 vs. 2.87 ± 1.73, p < 0.001), and HAD-BLED scores (2.13 ± 1.02 vs. 1/04 ± 0.93, p < 0.001) when compared to the trial data. When comparing the incidence of the first major bleed at 12 months post-treatment initiation, rates in the RWD cohort were significantly higher (10.69 vs. 18.97 per 100 person-years). The impact of co-morbidities such as age, CHA2DS2VASc, and HAD-BLED scores was similar in both cohorts; however, there was an under-representation of older females and more co-morbid patients within the clinical trial cohort. Conclusions DOAC-treated patients have a higher bleeding incidence rate in the RWD cohort than in clinical trials. This can be explained by the older patient age group with more complex medical h istories and higher HAS-BLED scores. The under-representation of higher-risk patients and lower proportion of females within clinical trials should be addressed to better translate clinical trial data into real-world clinical practice. [ABSTRACT FROM AUTHOR]

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

Background: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. Methods: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. Results: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454—0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529—0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478—0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231—1.880), ICH (aHR 2.045, 95% CI 1.329—3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. Conclusions: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy. [ABSTRACT FROM AUTHOR]

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

Background and purpose: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross‐sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE). Methods: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow‐up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all‐cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest. Results: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all‐cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67–2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11–2.20), heart failure (IRR = 1.26, 95% CI = 1.25–1.28), IS (IRR = 2.08, 95% CI = 2.04–2.13), VT/VF (IRR = 1.10, 95% CI = 1.04–1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04–2.20). When accounting for all‐cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55–1.63) and for cardiac arrest of 1.73 (95% CI = 1.58–1.89) demonstrated higher risk in PWE. Conclusions: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE. [ABSTRACT FROM AUTHOR]

Background: Real-world evidence on direct oral anticoagulant outcomes among Non-Valvular Atrial Fibrillation (NVAF) patients is limited. We aimed to evaluate stroke/systemic embolism (SE) and major bleeding (MB) risks among NVAF patients continuing or switching to different oral anticoagulants. Methods: Using Optum's de-identified Clinformatics® Data Mart Database, we identified NVAF patients initiating apixaban or rivaroxaban between 1 January 2013 and 31 December 2021. Patients switching therapies within 30 days before or 90 days after discontinuing their initial DOAC and those who continued initial therapy were included. The index date was the switch date for switchers, while continuers were assigned a hypothetic index date. Switchers and continuers were propensity score matched based on pre-index characteristics. Results: Among 167,868 apixaban and 65,888 rivaroxaban initiators, 2900 apixaban-to-rivaroxaban switchers were matched with 14,500 apixaban continuers, and 2873 rivaroxaban-to-apixaban switchers were matched with 14,365 rivaroxaban continuers. Apixaban-to-rivaroxaban switching was associated with higher stroke/SE risk (HR: 1.99, 95% CI: 1.38–2.88) and MB risk (HR:1.80, 95% CI: 1.46–2.23) than continuing apixaban. Rivaroxaban-to-apixaban switching had similar stroke/SE risk (HR: 0.74, 95% CI: 0.45–1.22) but lower MB risk (HR: 0.49, 95% CI: 0.38–0.65) than continuing rivaroxaban. Conclusions: These findings may aid physicians and patients in making informed decisions when considering a switch between apixaban and rivaroxaban. [ABSTRACT FROM AUTHOR]

Background: Older care home residents are a vulnerable group of people with atrial fibrillation (AF) at high risk of adverse health events. The Atrial Fibrillation Better Care (ABC: Avoid stroke; Better symptom management; Cardiovascular and other comorbidity management) pathway is the gold-standard approach toward integrated AF care, and pharmacists are a potential resource with regards to its' implementation. The aim of this study was to determine the feasibility of pharmacist-led medicines optimisation in care home residents, based on the ABC pathway compared to usual care. Methods: Individually randomised, prospective pilot and feasibility study of older (aged ≥ 65 years) care home residents with AF (ISRCTN14747952); residents randomised to ABC pathway optimised care versus usual care. The primary outcome was a description of study feasibility (resident and care home recruitment and retention). Secondary outcomes included the number and type of pharmacist medication recommendations and general practitioner (GP) implementation. Results: Twenty-one residents were recruited and 11 (mean age [standard deviation] 85.0 [6.5] years, 63.6% female) were randomised to receive pharmacist-led medicines optimisation. Only 3/11 residents were adherent to all three components of the ABC pathway. Adherence was higher to 'A' (9/11 residents) and 'B' (9/11 residents) components compared to 'C' (3/11 residents). Four ABC-specific medicines recommendations were made for three residents, and two were implemented by residents' GPs. Overall ABC adherence rates did not change after pharmacist medication review, but adherence to 'A' increased (from 9/11 to 10/11 residents). Other ABC recommendations were inappropriate given residents' co-morbidities and risk of medication-related adverse effects. Conclusions: The ABC pathway as a framework was feasible to implement for pharmacist medication review, but most residents' medications were already optimised. Low rates of adherence to guideline-recommended therapy were a result of active decisions not to treat after assessment of the net risk–benefit. [ABSTRACT FROM AUTHOR]

Aims The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. Methods and results We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. Conclusion Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms. [ABSTRACT FROM AUTHOR]

This article discusses the disparities in the use of oral anticoagulants (OAC) for stroke prevention in patients with atrial fibrillation (AF), particularly focusing on sex disparities. The article highlights that although female patients with AF have higher thromboembolic risks than men, they are often under-treated with OAC compared to men. However, the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has helped mitigate the disparities in OAC use between men and women. The study suggests that the sex disparity in OAC prescribing for stroke prevention in AF is improving over time, especially in the NOAC era, although under-prescription to female patients still persists. The article acknowledges the limitations of the study and emphasizes the need for further research to assess long-term outcomes and address disparities in other therapeutic strategies. [Extracted from the article]

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

Purpose of Review: Atrial fibrillation (AF) is a major risk factor for systemic embolism and ischaemic stroke. Furthermore, AF-related strokes are associated with higher mortality, greater disability, longer hospital stays and lower rates of hospital discharge than strokes caused by other reasons. The aim of this review to summarise the existing evidence on the association of AF with ischemic stroke and provide insights on the pathophysiological mechanisms and the clinical management of patients with AF in order to reduce the burden of ischemic stroke. Recent Findings: Beyond Virchow's triad, several pathophysiological mechanisms associated with structural changes in the left atrium, which may precede the identification of AF, may contribute to the increased risk of arterial embolism in AF patients. Individualised thromboembolic risk stratification based on CHA2DS2-VASc score and clinically relevant biomarkers provides essential tool towards a personalised holistic approach in thromboembolism prevention. Anticoagulation remains the cornerstone of stroke prevention moving from vitamin K antagonists (VKA) to safer non-vitamin K direct oral anticoagulants in the majority of AF patients. Despite the efficacy and safety of oral anticoagulation, still the equilibrium between thrombosis and haemostasis in AF patients remains suboptimal and future directions in anticoagulation and cardiac intervention may provide novel treatment options in stroke prevention. Summary: This review summarises the pathophysiologic mechanisms of thromboembolism, aiming the current and potential future perspectives in stroke prevention in AF patients. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. Methods: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. Results: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01–1.24) and for ICH (HR 1.57, 95% CI 1.25–1.99) and incident dementia (HR 1.66, 95% CI 1.30–2.12). Incident heart failure (HR 1.50, 95% CI 1.34–1.68) and mortality (HR 1.77, 95% CI 1.58–1.99) risks were increased in AF patients not receiving SGLT2i. Conclusions: In our large 'real world' analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF) is a major public health issue associated with significantly increased risk of stroke. It remains uncertain whether oral anticoagulation (OAC) in patients with heart failure and sinus rhythm (HF-SR) could improve prognosis. Methods: We performed a systematic search of PubMed and Embase databases for randomized controlled clinical trials assessing oral anticoagulants versus antiplatelets or placebo in patients with HF or ventricular dysfunction/cardiomyopathy without clinical HF and SR. The outcomes assessed were stroke/systemic embolism, major bleeding, myocardial infarction, all-cause mortality, and HF hospitalization. Results: Seven trials of 15,794 patients were eligible for our analyses. The overall follow-up duration was 32,367 patient-years corresponding to a mean follow-up of 2.05 years per patient. Four trials included patients treated with warfarin and three included patients treated with rivaroxaban. OAC was associated with reduced rate of stroke or systemic embolism compared to control (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.44, 0.73, number needed to treat (NNT): 71.9) but higher rate of major bleeding (OR: 1.92, 95% CI: 1.47, 2.50, number needed to harm (NNH): 57.1). In the subgroup analysis according to the type of OAC, rivaroxaban was associated with significantly reduced rate of stroke or systemic embolism (1.24 vs 1.97 events per 100 patient-years, respectively, OR: 0.63, 95% CI: 0.45, 0.88, NNT: 82) and higher risk of major bleeding (OR: 1.66, 95% CI: 1.26, 2.20) compared to antiplatelets or placebo. There was no significant differences between groups for the outcomes of myocardial infarction, all-cause mortality, and HF hospitalization. Conclusion: This analysis shows that any benefit of OAC for stroke prevention may be offset by an increased risk of major bleeding in HF-SR patients. A well-designed randomized controlled trial of newer safer OACs is needed in this population. [ABSTRACT FROM AUTHOR]

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

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies' clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future. [ABSTRACT FROM AUTHOR]

Response to letter from Du et al. regarding article 'Sodium-glucose cotransporter-2 inhibitor use was associated with lower risks of stroke and cardiac arrest but not ventricular arrhythmias? Cardiovascular disease, GLP-1, SGLT2 inhibitor, type 2 diabetes, cohort study 2022; 27. doi: 10.1111/DOM.14854 3 Rathmann W, Kostev K. Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyzer database. [Extracted from the article]

Background: The relationship between coronary artery calcium (CAC) score and incident stroke is controversial. Methods: We conducted a systematic review of the literature evaluating CAC score and incident stroke. A search of MEDLINE and EMBASE was performed, and data were extracted from relevant studies. Statistical pooling with random‐effects meta‐analysis was undertaken to evaluate the risk of incident stroke with any CAC vs. no CAC, 1–100 CAC vs. no CAC, and >100 CAC vs. no CAC. Results: Data from nine different cohort studies from the United States and Europe with a total of 61,096 patients were included in this review. The mean age of patients in the studies ranged from 44 to 69 years, and follow‐up duration ranged from a median of 5.5 years to 12.3 years. The crude stroke event varied from 1.6% to 9.5%. Meta‐analysis of risk of incident stroke with any vs. no CAC (RR 1.70 95% CI 0.87–3.31, I2 = 95%) and for CAC 1–100 vs. no CAC (RR 1.54 95% CI 0.75–3.17, I2 = 93%) was not statistically significant. For CAC >100, the risk of incident stroke was significantly higher compared with no CAC (RR 2.61 95% CI 1.51–4.52, I2 = 89%). When one study which included only young adults was excluded, there was significant increase in risk of incident stroke with all categories of CAC. Conclusions: There is an association between high CAC score and incident stroke, but more studies are needed to determine how patients with incidental CAC should be managed from the perspective of stroke prevention. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to compare the GARFIELD Refitted model and CHA2DS2‐VASc/HAS‐BLED risk scores with the new model from the COOL‐AF registry for all‐cause death, ischaemic stroke/systemic embolism (SSE) and major bleeding in Asian patients with atrial fibrillation (AF). Methods: Patients with non‐valvular AF in the nationwide COOL‐AF registry were studied. Patients were enrolled from 27 hospitals in Thailand during 2014–2017. Main outcomes were all‐cause mortality, SSE and major bleeding. Predictive models of the three outcomes were developed from the variables in the multivariable Cox‐proportional Hazard model. Predictive values of the models were evaluated by C‐statistics, calibration plots and decision curve analysis (DCA). The new COOL‐AF models were compared with the GARFIELD Refitted models and CHA2DS2‐VASc model for all‐cause mortality, SSE/HAS‐BLED model for major bleeding. Results: A total of 3405 patients were enrolled. The C‐statistics for the COOL‐AF models were 0.727 (0.712–0.742), 0.708 (0.693–0.724) and 0.706 (0.690–0.721) for all‐cause mortality, SSE and major bleeding, respectively. Calibration plots showed good agreement between predicted probability the observed outcomes for the COOL‐AF models with a calibration slope of 0.94–0.99. The predictive ability remains preserved after the internal validation with bootstraps and optimism (bias) correction. The COOL‐AF predictive models tended to be superior to the GARFIELD Refitted, CHA2DS2‐VASc and HAS‐BLED models. Conclusion: The COOL‐AF predictive models for all‐cause mortality, SSE and major bleeding in Asian patients with AF had a good predictive ability. The COOL‐AF model for all‐cause mortality was superior to the GARFIELD Refitted and CHA2DS2‐VASc model. [ABSTRACT FROM AUTHOR]

Premature atrial contractions are a common cardiac phenomenon. Although previously considered a benign electrocardiographic finding, they have now been associated with a higher risk of incident atrial fibrillation (AF) and other adverse outcomes such as stroke and all-cause mortality. Since premature atrial contractions can be associated with these adverse clinical outcomes independently of AF occurrence, different explanations have being proposed. The concept of atrial cardiomyopathy, where AF would be an epiphenomenon outside the causal pathway between premature atrial contractions and stroke has received traction recently. This concept suggests that structural, functional, and biochemical changes in the atria lead to arrhythmia occurrence and thromboembolic events. Some consensus about diagnosis and treatment of this condition have been published, but this is based on scarce evidence, highlighting the need for a clear definition of excessive premature atrial contractions and for prospective studies regarding antiarrhythmic therapies, anticoagulation or molecular targets in this group of patients. [ABSTRACT FROM AUTHOR]

Background: Several anthropometric measurements are used to assess cardiovascular risk and progress during clinical treatment. Most commonly used anthropometric measurements include total body weight and body mass index (BMI), with several other simple an- thropometric measures typically underused in clinical practice. Herein, we review the evidence on the relationship between different anthropometric measurements and cardiovascular risk in patients with and without cardiovascular disease (CVD). Methods: Data for this review were identified by searches in PubMed, the Web of Science, Google Scholar, and references from relevant articles by using appropriate and related terms. The last search was performed on June 22, 2022. Articles published in English and Spanish were reviewed and included, if appropriate. We included studies detailing the relationship between skinfolds thickness, waist-to-hip ratio (WHR) and Conicity index with cardiovascular risk in adults with/without CVD. Results: In patients from the general population, elevated subscapu- lar and triceps skinfolds showed a positive relationship with the development of hypertension, diabetes mellitus, hypercholesterolemia, cardiovascular mortality, and all-cause mortality. A higher subscapular skinfold was also associated with increased risk of coronary artery disease and stroke. A higher WHR, as well as other less common anthropometric measurements such as the Conicity index, was associated with an increased risk of myocardial infarction, incident CVD, major adverse cardiovascular events, and mortality in both patients with and without previous CVD. Conclusions: Non-traditional anthropometric measurements including skinfolds and WHR seem to improve the prediction of cardiovascular risk in the general population, and recurrent events in patients with previous CVD. Use of additional anthropometric techniques according to an objective and standardized method, may aid cardiovascular risk stratification in patients from the general population and the evaluation of therapeutic interventions for patients with CVD. [ABSTRACT FROM AUTHOR]

Objective To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. Methods Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. Results There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8–90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised , the overall prevalence of AF was 17.4% (95% confidence interval 17.1–17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9–17.9) in 2010 to 17.0% (16.1–18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17–1.37], P  < 0.001), all-cause mortality (adjusted HR 1.14 [1.11–1.17], P  < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36–1.76], P  < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22–1.34], P  < 0.001). Conclusions Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy. [ABSTRACT FROM AUTHOR]

Background: We examined the associations between family income and educational attainment with incident atrial fibrillation (AF), myocardial infarction (MI), stroke and cardiovascular (CV) death among patients with newly‐diagnosed heart failure (HF). Methods: In a nationwide Danish registry of HF patients diagnosed between 2008 and 2018, we established a cohort for each outcome. When examining AF, MI and stroke, respectively, patients with a history of these outcomes at diagnosis of HF were excluded. We used cause‐specific proportional hazard models to estimate hazard ratios for tertile groups of family income and three levels of educational attainment. Results: Among 27,947 AF‐free patients, we found no association between income or education and incident AF. Among 27,309 MI‐free patients, we found that lower income (hazard ratio 1.28 [95% CI 1.11–1.48] and 1.11 [0.96–1.28] for lower and medium vs. higher income) and education (1.23 [1.04–1.45] and 1.15 [0.97–1.36] for lower and medium vs. higher education) were associated with MI. Among 36,801 stroke‐free patients, lower income was associated with stroke (1.38 [1.23–1.56] and 1.27 [1.12–1.44] for lower and medium vs. higher income) but not education. Lower income (1.56 [1.46–1.67] and 1.32 [1.23–1.42] for lower and medium vs. higher income) and education (1.20 [1.11–1.29] and 1.07 [0.99–1.15] for lower and medium vs. higher education) were associated with CV death. Conclusions: In patients with newly‐diagnosed HF, lower family income was associated with higher rates of acute MI, stroke and cardiovascular death. Lower educational attainment was associated with higher rates of acute MI and cardiovascular death. There was no evidence of associations between income and education with incident AF. [ABSTRACT FROM AUTHOR]

Aims: The Atrial fibrillation Better Care (ABC) pathway is endorsed by guidelines to improve care of patients with atrial fibrillation (AF). However, whether the benefit of ABC pathway-concordant care is consistent across anticoagulants remains unclear. We assessed the association between ABC-concordant care and outcomes in this post hoc analysis from the ENGAGE AF-TIMI 48 trial, which was reported prior to the initial description of the ABC pathway.Methods and Results: Patients were retrospectively classified as receiving ABC-concordant care based on optimal anticoagulation, adequate rate control, management of co-morbidities and lifestyle measures. Associations between ABC-concordance and outcomes were assessed with adjustment for components of the CHA2DS2-VASc and HAS-BLED scores. Of 20 926 patients, 7915 (37.8%) satisfied criteria of ABC-concordant care, which was associated with significantly lower incidence of stroke or systemic embolic event [stroke/SEE: hazard ratio (HRadj): 0.54; 95% confidence interval (CI): 0.47-0.63], major bleeding (HRadj 0.66; 95% CI: 0.58-0.75), major adverse cardiac events (HRadj 0.53; 95% CI: 0.48-0.58), primary net clinical outcome (composite of stroke/SEE, major bleeding or death; HRadj 0.61; 95% CI: 0.56-0.65), cardiovascular (CV) hospitalization (HRadj 0.78; 95% CI: 0.74-0.83), CV death (HRadj 0.52; 95% CI: 0.46-0.58), and all-cause mortality (HRadj 0.56; 95% CI: 0.51-0.62), P < 0.001 for each. These associations were qualitatively consistent for both edoxaban and warfarin and across patient subgroups.Conclusion: Atrial fibrillation Better Care pathway-concordant care is associated with reductions across multiple CV endpoints and all-cause mortality, with benefit in edoxaban- and warfarin-treated patients and across patient subgroups. Increasing implementation of ABC-concordant care may improve clinical outcomes of patients with AF irrespective of anticoagulant. [ABSTRACT FROM AUTHOR]

Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static 'one off' assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing 'best practice' when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients.Methods: We systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model.Results: A total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86-0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71-0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69-0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70-0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88-0.92), and ACS (HR = 0.86, 95% CI: 0.76-0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results.Conclusions: Our current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year.Registration: The study protocol was registered to PROSPERO (CRD42021295405). [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine associations between use of oral anticoagulation (OAC) and stroke and bleeding‐related outcomes for older people ≥80 years with atrial fibrillation (AF), and to determine trends over time in prescribing of OAC for this population. Methods: A retrospective cohort study was conducted. People aged ≥80 years with AF receiving (1) no OAC; (2) warfarin; or (3) a non‐vitamin‐K antagonist oral anticoagulant (NOAC) between 2011 and 2019 were included. Propensity score matching was used to balance cohorts (no OAC, warfarin or a NOAC) on characteristics including age, sex, ethnicity, and co‐morbidities. Cox proportional hazard models were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The proportion of people aged ≥80 years receiving any OAC increased from 32.4% (n = 27,647) in 2011 to 43.6% (n = 110,412) in 2019. After propensity score matching, n = 169,067 individuals were included in the cohorts receiving no OAC or a NOAC. Compared to no OAC, participants receiving a NOAC had a lower risk of incident dementia (hazHR 0.68, 95% CI 0.65–0.71), all‐cause mortality (HR 0.49, 95% CI 0.48–0.50), first‐time ischaemic stroke (HR 0.87, 95% CI 0.83–0.91), and a higher risk of major bleeding (HR 1.08, 95% CI 1.05–1.11). Compared to participants receiving warfarin, participants receiving a NOAC had a lower risk of dementia (HR 0.90, 95% CI: 0.86–0.93), all‐cause mortality (HR 0.74, 95% CI: 0.72–0.76), ischaemic stroke (HR 0.86, 95% CI: 0.82–0.90) and major bleeding (HR 0.88, 95% CI: 0.85–0.90). Similar results were observed when only including people with additional bleeding risk factors. Conclusions: The proportion of people aged ≥80 years receiving OAC has increased since the introduction of NOACs, but remains low. Use of a NOAC was associated with improved outcomes compared to warfarin, and compared to no OAC, except for a small but statistically significant higher risk of major bleeding. [ABSTRACT FROM AUTHOR]

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

Introduction: The impact of low-density lipoprotein cholesterol (LDL-C) on the risk of different types of strokes is unclear. Therefore, we systematically evaluated the impact of LDL-C levels (cohort studies) and lipid-lowering agents (LLAs) (randomized controlled trials) on the different types of stroke.Material and methods: PubMed, SCOPUS, Web of Science and Google Scholar were searched up to 1st September 2019. The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. The leave-one-out method was performed as sensitivity analysis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 35% reduction in outcomes after administration of LLAs.Results: Participants in the highest category of LDL-C had a lower risk of hemorrhagic stroke (RR = 0.91, 95% CI: 0.85-0.98, I2 = 0%) compared with the lowest category of LDL-C. Subjects with the highest category of LDL-C had a higher risk of ischemic stroke (RR = 1.11, 95% CI: 1.07-1.14, I2 = 0%) compared to the lowest LDL-C category. LLAs decreased the risk of all types of strokes for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.88, 95% CI: 0.80-0.96, absolute risk reduction (ARR): 0.7%, number needed to treat (NNT): 143, I2 = 53%, n = 13). Statin therapy decreased the risk of all strokes (RR = 0.88, 95% CI: 0.80-0.97, ARR = 0.6%, NNT = 167, I2 = 56%). With regard to ischemic stroke only, LLAs decreased the risk of ischemic stroke for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.75, 95% CI: 0.67-0.83, ARR = 1.3%, NNT = 77, I2 = 0%); the same was observed for statins (RR = 0.76, 95% CI: 0.69-0.84, ARR = 1.3%, NNT = 77, I2 = 32%). TSA indicated that both benefit boundaries and optimal sample size were reached. There was no significant effect of LLAs regardless of the achieved level of LDL-C on the risk of hemorrhagic stroke; however, TSA indicated that further studies are needed to settle the question and most of the effects were subject to high levels of heterogeneity.Conclusions: Our study sheds light on the debatable association between low LDL-C and different type of strokes. This information can help determine the optimal LDL-C range for stroke prevention, and help plan future LLA studies. [ABSTRACT FROM AUTHOR]

Background: There is a plethora of real-world data on the safety and effectiveness of direct-acting oral anticoagulants (DOACs); however, study heterogeneity has contributed to inconsistent findings. We compared the effectiveness and safety of apixaban with those of other direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKA e.g., warfarin). Methods: A systematic review and meta-analysis was conducted retrieving data from PubMed, SCOPUS and Web of Science from January 2009 to December 2021. Studies that evaluated apixaban (intervention) prescribed for adults (aged 18 years or older) with AF for stroke prevention compared to other DOACs or VKAs were identified. Primary outcomes included stroke/systemic embolism (SE), all-cause mortality, and major bleeding. Secondary outcomes were intracranial haemorrhage (ICH) and ischaemic stroke. Randomised controlled trials and non-randomised trials were considered for inclusion. Results: In total, 67 studies were included, and 38 studies were meta-analysed. Participants taking apixaban had significantly lower stroke/SE compared to patients taking VKAs (relative risk (RR) 0.77, 95% confidence interval (CI) 0.64–0.93, I2 = 94%) and dabigatran (RR 0.84, 95% CI 0.74–0.95, I2 = 66%), but not to patients administered rivaroxaban. There was no statistical difference in mortality between apixaban and VKAs or apixaban and dabigatran. Compared to patients administered rivaroxaban, participants taking apixaban had lower mortality rates (RR 0.83, 95% CI 0.71–0.96, I2 = 96%). Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52–0.65, I2 = 90%), dabigatran (RR 0.79, 95% CI 0.70–0.88, I2 = 78%) and rivaroxaban (RR 0.61, 95% CI 0.53–0.70, I2 = 87%). Conclusions: Apixaban was associated with a better overall safety and effectiveness profile compared to VKAs and other DOACs. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is one of the most common cancers worldwide, and the treatments are frequently cardiotoxic. Whether BC is associated with a higher risk of cardiovascular events is a matter of debate. We evaluated the associations among BC and incident cardiovascular events in a contemporary population. Methods: All female patients discharged from French hospitals in 2013 with at least 5 years of follow‐up and without a history of major adverse cardiovascular event (myocardial infarction [MI], heart failure [HF], ischaemic stroke or all‐cause death, and MACE‐HF, which includes cardiovascular death, MI, ischaemic stroke or HF) or cancer (except BC) were identified. After propensity score matching, patients with BC were matched 1:1 with patients with no BC. Hazard ratios (HRs) for cardiovascular events during follow‐up were adjusted on age, sex and smoking status at baseline. Results: 1,795,759 patients were included, among whom 64,480 (4.3%) had history of BC. During a mean follow‐up of 5.1 years, matched female patients with BC had a higher risk of all‐cause death (HR 3.55, 95% confidence interval [CI]: 3.47–3.64), new‐onset HF (HR 1.08, 95% CI 1.04–1.11), major bleeding (HR 1.43, 95% CI 1.36–1.49), MACE‐HF (HR 1.07, 95% CI 1.04–1.11) and net adverse clinical events (NACE) including all‐cause death, MI, ischaemic stroke, HF or major bleeding (HR 2.53, 95% CI 2.48–2.58) compared with those with no BC. By contrast, risks were not higher for cardiovascular death (HR 0.94, 95% CI 0.88–1.00) and were lower for MI (HR 0.81, 95% CI 0.75–0.88) and ischaemic stroke (HR 0.85, 95% CI 0.79–1.11). Conclusions: In a large and contemporary analysis of female patients seen in French hospitals, women with history of breast cancer had a higher risk of all‐cause mortality, new‐onset heart failure and major bleeding compared to a matched cohort of women without breast cancer. In contrast, they have a reduced risk of cardiovascular mortality, MI and stroke. [ABSTRACT FROM AUTHOR]

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