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Abstract Introduction Metformin is the most prescribed medication for type 2 diabetes mellitus (T2DM); there is a well-established link with the elevated incidence of gastrointestinal (GI) adverse events (AE) limiting its administration or intensification. Objectives The objective of this systematic review and meta-analysis of observational studies was to evaluate the pooled incidence of GI AE related to metformin use in patients with T2DM. Materials and methods PUB MED/CINAHL/Web of Science/Scopus were searched from database inception until 29.07.2024 for observational studies in English describing the frequency of GI AE in patients with T2DM treated with metformin. Random-effects meta-analyses were used to derive effect sizes: event rates. Results From 7019 publications, we identified 211 potentially eligible full-text articles. Ultimately, 21 observational studies were included in the meta-analysis. The prevalence of GI AE was as follows: diarrhea 6.9% (95% CI: 0.038–0.123), bloating 6,2% (95% CI: 0.020–0.177), abdominal pain 5,3% (95% CI: 0.003–0.529), vomiting 2.4% (95%: CI 0.007–0.075), constipation 1.1% (95%: CI 0.001–0.100). The incidence of bloating (coefficient -4.46; p

Abstract Background The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. Objective To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. Methods This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. Results In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8–7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006–1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001–1.002]; P

Abstract Background There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia). Methods We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1–2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese “extremely unhealthy”); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1–2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese “extremely unhealthy”). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke. Results 2105 people with DM were included [median age 60 (IQR 45–70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06–13.47, respectively). On interaction analysis, in “extremely unhealthy” persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (Pint=0.824), but more pronounced in individuals aged

Abstract Background There is ongoing debate around rate versus rhythm control strategies for managing atrial fibrillation (AF), however, much of the data comes from Western cohorts. Kerala‐AF represents the largest prospective AF cohort study from the Indian subcontinent. Objectives To compare 12‐month outcomes between rate and rhythm control strategies. Methods Patients aged ≥18 years with non‐transient AF were recruited from 53 hospitals across Kerala. Patients were stratified by rate or rhythm control. The primary outcome was a composite of all‐cause mortality, arterial thromboembolism, acute coronary syndrome or hospitalization due to heart failure or arrhythmia at 12 months. Secondary outcomes included bleeding events and individual components of the primary. Predictors of the composite outcome were analysed by logistic regression. Results A total of 2901 patients (mean age 64.6 years, 51% female) were included (2464 rate control, 437 rhythm control). Rates of the primary composite outcome did not differ between groups (29.7% vs 30.0%; p = .955), nor did any component of the primary. Bleeding outcomes were also similar (1.6% vs 1.9%; p = .848). Independent predictors of the primary composite outcome were older age (aOR 1.01; p = .013), BMI

Abstract Background Cardiac autonomic neuropathy (CAN) in diabetes mellitus (DM) is independently associated with cardiovascular (CV) events and CV death. Diagnosis of this complication of DM is time-consuming and not routinely performed in the clinical practice, in contrast to fundus retinal imaging which is accessible and routinely performed. Whether artificial intelligence (AI) utilizing retinal images collected through diabetic eye screening can provide an efficient diagnostic method for CAN is unknown. Methods This was a single center, observational study in a cohort of patients with DM as a part of the Cardiovascular Disease in Patients with Diabetes: The Silesia Diabetes-Heart Project (NCT05626413). To diagnose CAN, we used standard CV autonomic reflex tests. In this analysis we implemented AI-based deep learning techniques with non-mydriatic 5-field color fundus imaging to identify patients with CAN. Two experiments have been developed utilizing Multiple Instance Learning and primarily ResNet 18 as the backbone network. Models underwent training and validation prior to testing on an unseen image set. Results In an analysis of 2275 retinal images from 229 patients, the ResNet 18 backbone model demonstrated robust diagnostic capabilities in the binary classification of CAN, correctly identifying 93% of CAN cases and 89% of non-CAN cases within the test set. The model achieved an area under the receiver operating characteristic curve (AUCROC) of 0.87 (95% CI 0.74–0.97). For distinguishing between definite or severe stages of CAN (dsCAN), the ResNet 18 model accurately classified 78% of dsCAN cases and 93% of cases without dsCAN, with an AUCROC of 0.94 (95% CI 0.86–1.00). An alternate backbone model, ResWide 50, showed enhanced sensitivity at 89% for dsCAN, but with a marginally lower AUCROC of 0.91 (95% CI 0.73–1.00). Conclusions AI-based algorithms utilising retinal images can differentiate with high accuracy patients with CAN. AI analysis of fundus images to detect CAN may be implemented in routine clinical practice to identify patients at the highest CV risk. Trial registration This is a part of the Silesia Diabetes-Heart Project (Clinical-Trials.gov Identifier: NCT05626413). Graphical Abstract

Abstract Female sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997–2000 with a risk of 5.6% and lowest between 2013–2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years.

Abstract 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 Rationale & objective Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. Study Design Retrospective cohort study. Setting & participants Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). Exposure or predictor Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. Outcomes Primary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome. Analytical Approach 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. Results Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p

Abstract The importance of integrated care for complex, multiple long term conditions was acknowledged before the COVID pandemic but remained a challenge. The pandemic and consequent development of Long COVID required rapid adaptation of health services to address the population’s needs, requiring service redesigns including integrated care. This Delphi consensus study was conducted in the UK and found similar integrated care priorities for Long COVID and complex, multiple long term conditions, provided by 480 patients and health care providers, with an 80% consensus rate. The resultant recommendations were based on more than 1400 responses from survey participants and were supported by patients, health care professionals, and by patient charities. Participants identified the need to allocate resources to: support integrated care, provide access to care and treatments that work, provide diagnostic procedures that support the personalization of treatment in an integrated care environment, and enable structural consultation between primary and specialist care settings including physical and mental health care. Based on the findings we propose a model for delivering integrated care by a multidisciplinary team to people with complex multisystem conditions. These recommendations can inform improvements to integrated care for complex, multiple long term conditions and Long COVID at international level.

Atrial fibrillation (AF) is common and warrants consideration of oral anticoagulant (OAC) medication. Usually, the decision is straightforward, following the pathway outlined in the European Society of Cardiology’s guideline; however, certain situations fall outside of this evidence base – such as a diagnosis of subclinical AF made via implanted devices or wearable electrocardiogram monitors, or alternatively diagnosis of ‘secondary AF’ following a major stressor. Subclinical AF is associated with stroke, though not to the extent of clinical AF, and the benefits of anticoagulation appear to be lower. Longer episodes are more clinically meaningful, and recent randomised controlled trials have demonstrated that some patients derive benefit from OAC. Similarly, when AF is triggered by sepsis or non-cardiac surgery, specific evidence supporting OAC initiation is lacking and clinician behaviour is variable. Observational data demonstrate poorer outcomes in these patients, implying that the perception of a transient, reversible phenomenon may not be correct. Contrastingly, cardiac surgery very frequently induces AF, and the benefits of anticoagulation rarely outweigh the risks of bleeding. Following ischaemic stroke, recent evidence suggests that early (re-)initiation of OAC should be considered as this does not increase the risk of haemorrhagic transformation as previously hypothesised. This narrative review summarises the available literature and outlines, where possible, practical advice for clinicians facing these common clinical dilemmas.

Objectives This study was undertaken to identify potential predictors of atrial fibrillation after cardiac surgery (AFACS) through a modified Delphi process and expert consensus. These will supplement predictors identified through a systematic review and cohort study to inform the development of two AFACS prediction models as part of the PARADISE project (NCT05255224). Atrial fibrillation is a common complication after cardiac surgery. It is associated with worse postoperative outcomes. Reliable prediction of AFACS would enable risk stratification and targeted prevention. Systematic identification of candidate predictors is important to improve validity of AFACS prediction tools.Design This study is a Delphi consensus exercise.Setting This study was undertaken through remote participation.Participants The participants are an international multidisciplinary panel of experts selected through national research networks.Interventions This is a two-stage consensus exercise consisting of generating a long list of variables, followed by refinement by voting and retaining variables selected by at least 40% of panel members.Results The panel comprised 15 experts who participated in both stages, comprising cardiac intensive care physicians (n=3), cardiac anaesthetists (n=2), cardiac surgeons (n=1), cardiologists (n=4), cardiac pharmacists (n=1), critical care nurses (n=1), cardiac nurses (n=1) and patient representatives (n=2). Our Delphi process highlighted candidate AFACS predictors, including both patient factors and those related to the surgical intervention. We generated a final list of 72 candidate predictors. The final list comprised 3 demographic, 29 comorbidity, 4 vital sign, 13 intraoperative, 10 postoperative investigation and 13 postoperative intervention predictors.Conclusions A Delphi consensus exercise has the potential to highlight predictors beyond the scope of existing literature. This method proved effective in identifying a range of candidate AFACS predictors. Our findings will inform the development of future AFACS prediction tools as part of the larger PARADISE project.Trial registration number NCT05255224.

IntroductionCurrent research on potentially inappropriate prescribing (PIP) in polymedicated older adults with atrial fibrillation (AF) and multimorbidity is predominantly focused on PIP of oral anticoagulants (OAC). Our study aimed to assess (i) the overall prevalence of PIP in older multimorbid adults with AF, (ii) potential associated factors of PIP, and (iii) the association of PIP with adverse health outcomes in a nationwide sample of Swedish older adults.MethodsSwedish national registries were linked to establish a cohort with a 2-year follow-up of older adults (≥65y) who, on 1 January 2017, had a diagnosis of AF and had at least one comorbidity (n = 203,042). PIP was assessed using the reduced STOPP/START version 2 screening tool. The STOPP criteria identify potentially inappropriate prescribed medications (PIM), while the START criteria identify potential prescribing omissions (PPO). PIP is identified as having at least one PIM and/or PPO. Cox regression analyses were conducted to examine the association between PIP and adverse health outcomes: mortality, hospitalisation, stroke, bleeding, and falls.ResultsPIP was highly prevalent in older adults with AF, with both polypharmacy (69.6%) and excessive polypharmacy (85.9%). In the study population, benzodiazepines (22.9%), hypnotic Z-medications (17.8%) and analgesics (8.7%) were the most frequent PIM. Anticoagulants (34.3%), statins (11.1%), vitamin D and calcium (13.4%) were the most frequent PPO. Demographic factors and polypharmacy were associated with different PIM and PPO categories, with the nature of these associations differing based on the specific type of PIM and PPO. The co-occurrence of PIM and PPO, compared to appropriate prescribing, was associated with an increased risk of adverse health outcomes compared to all appropriately prescribed medications: cardiovascular (CV) (Hazard ratio (HR) [95% confidence interval] = 1.97 [1.88–2.07]) and overall mortality (HR = 2.09 [2.03–2.16]), CV (HR = 1.34 [1.30–1.37]) and overall hospitalisation (HR = 1.48 [1.46–1.51]), stroke (HR = 1.93 [1.78–2.10]), bleeding (HR = 1.10 [1.01–1.21]), and falls (HR = 1.63 [1.56–1.71]).ConclusionThe present study reports a high prevalence of PIP in multimorbid polymedicated older adults with AF. Additionally, a nuanced relationship between prescribing patterns, patient characteristics, and adverse health outcomes was observed. These findings emphasise the importance of implementing tailored interventions to optimise medication management in this patient population.

Background Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device‐detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device‐detected AF but with no ECG‐documented AF is unclear. Methods and Results This prespecified analysis of the NOAH‐AFNET 6 (Non‐Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device‐detected AF with and without a prior stroke or TIA in the randomized, double‐blind, double‐dummy NOAH‐AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device‐detected AF randomized in the NOAH‐AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time‐to‐event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient‐year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient‐year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient‐year]; no anticoagulation: 6 out of 131 [2.3% per patient‐year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). Conclusions Anticoagulation appears to have ambiguous effects in patients with device‐detected AF and a prior stroke or TIA in this hypothesis‐generating analysis of the NOAH‐AFNET 6 in the absence of ECG‐documented AF, partially due to a low rate of stroke without anticoagulation.

Abstract Background The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. Methods 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. Results The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16–1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51–1.75), respectively. Conclusions The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Abstract Background Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. Methods From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. Results 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49–2.09] and 1.57 [1.35–1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13–1.67] and 1.47 [1.24–1.75], respectively). Conclusions Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Abstract Background Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration. Methods Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015–2016 were grouped by DM duration: new onset and 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Abstract 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

Background NULL‐PLEASE is a simple and accurate clinical scoring system developed in a Western cohort of patients with out‐of‐hospital cardiac arrest (OHCA). The need for blood test results limits its use in early stages of care. We adapted and validated the NULL‐EASE score (without laboratory tests) in an independent, multiethnic Asian cohort of patients with out‐of‐hospital cardiac arrest. Methods and Results Using the Singapore OHCA registry, we included consecutive adult patients with out‐of‐hospital cardiac arrest who survived to hospital admission between April 2010 to December 2020. In‐hospital mortality was the primary outcome. Logistic regression analyses were performed with STATA MP v18. Of 3274 patients (median age 64, interquartile range 54–75; 67.9% male) included in the study, 2476 (75.6%) had in‐hospital mortality. NULL‐EASE score was significantly lower in survivors compared with nonsurvivors (median [inter quartile range] 3 [1–4] versus 6 [4–7]; P

Background Intracranial haemorrhage (ICH) poses a significant threat to patients on Direct Oral Anticoagulants (DOACs), with existing risk scores inadequately predicting ICH risk in these patients. We aim to develop and validate a predictive model for ICH risk in DOAC-treated patients. Methods 24,794 patients treated with a DOAC were identified in a province-wide electronic medical and health data platform in Tianjin, China. The cohort was randomly split into a 4:1 ratio for model development and validation. We utilized forward stepwise selection, Least Absolute Shrinkage and Selection Operator (LASSO), and eXtreme Gradient Boosting (XGBoost) to select predictors. Model performance was compared using the area under the curve (AUC) and net reclassification index (NRI). The optimal model was stratified and compared with the DOAC model. Results The median age is 68.0 years, and 50.4% of participants are male. The XGBoost model, incorporating six independent factors (history of hemorrhagic stroke, peripheral artery disease, venous thromboembolism, hypertension, age, low-density lipoprotein cholesterol levels), demonstrated superior performance in the development dateset. It showed moderate discrimination (AUC: 0.68, 95% CI: 0.64–0.73), outperforming existing DOAC scores (ΔAUC = 0.063, P = 0.003; NRI = 0.374, P

Aims Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF.Methods PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022. Sex-specific comparative outcomes of stroke/systemic embolism (SE), major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) between oral anticoagulants were pooled using random effects models. P values for interaction were calculated to examine differences in results between sexes. RCTs and observational studies were meta-analysed separately.Results 5 RCTs and 33 observational studies were included, totalling 1 085 931 women and 1 387 123 men. Meta-analyses showed that for both sexes, DOAC versus warfarin was generally associated with lower risk of stroke/SE, major bleeding and ICH; in DOAC–DOAC comparisons, rivaroxaban versus dabigatran had higher GIB risk. The only sex-specific difference observed was that when compared with warfarin, women had higher GIB risk with rivaroxaban (women: pooled risk ratio (pRR)=1.34, 95% CI=1.18 to 1.51; men: pRR=0.97, 95% CI=0.85 to 1.10; p value for interaction (p for interaction)

Abstract Background The primary objective was to determine the influence of obesity and associated metabolic status on clinical outcomes of Asian patients with atrial fibrillation (AF). Methods This study was based on a prospective multicenter of patients with nonvalvular AF. Patients were classified as obese and nonobese and being metabolic unhealthy was defined as having at least one of the three cardiovascular risk factors including dyslipidemia, hypertension, or diabetes mellitus. Outcomes were a primary composite outcome of all‐cause death, ischemic stroke/systemic embolism (SSE), acute myocardial infarction (MI), and heart failure (HF), as well as the individual end points. Results There were a total of 3141 enrolled patients (mean age 67.4 ± 11.1 years; 41.0% female), of whom 1566 (49.9%) were obese and 2564 (81.6%) were metabolic unhealthy. During a mean follow‐up of 32.2 ± 8.3 months, the incidence rate of the composite outcome, all‐cause death, SSE, MI, and HF were 7.21 (6.63–7.82), 3.86 (3.45–4.30), 1.48 (1.23–1.77), 0.47 (0.33–0.64), and 2.84 (2.48–3.23) per 100 person‐years, respectively. Metabolic unhealthy nonobese subjects were at higher risk of the composite outcomes than metabolic unhealthy obese subjects with hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.17–1.66, p

Background Early diagnosis and continuity of care is vital for atrial fibrillation (AF), to reduce stroke ; There is a lack of understanding of when and how AF is being diagnosed and managed the care pathway) in in low- and middle-income countries (LMICs). We aimed to identify the AF care pathway in Northern Province, Sri Lanka and determine how the COVID-19 pandemic impacted the care pathway. Methods This descriptive longitudinal study utilised two quantitative questionnaires to evaluate the AF pathway: The first questionnaire (baseline) was used to identify where AF was being diagnosed and the second questionnaire (3 months following baseline) was used to identify where and how often AF follow-up care was being received. How the COVID-19 pandemic impacted the care pathway was asked in the second questionnaire. We aimed to recruit 236 adults (≥18 years) with AF from Jaffna Teaching Hospital. Data were collected between October 2020 and June 2021 and analysed using descriptive statistics. Results 151 participants were recruited (median age 57 years; 70% female). Most participants were diagnosed in the accident & emergency (38%) or inpatient department (26%), followed by an outpatient department (19%) or private facility (16%). Nearly all (97%) participants received follow-up care during the study period, with an average of 1.3 AF-related healthcare visits per person for a month; most visited an outpatient department (88%). The COVID-19 pandemic negatively impacted 39% of participants’ care: healthcare visits were reduced or, delayed or medications were unattainable, and longer intervals between blood tests were experienced; however, 24% of participants were able to receive their medication by ambulance, public health staff or post during lockdowns. Conclusions Primary care was not involved in the diagnosis of AF, indicating that most diagnoses occurr after a medical emergency. The frequency of blood tests was lower than the guideline recommendations of one per month which could in-part be due to the adverse impacts of the pandemic. Strengthening primary and community-based care may enable early diagnosis and improve continuity of care during and beyond future healthcare crises.

Background Enhanced detection of large vessel occlusion (LVO) through machine learning (ML) for acute ischemic stroke appears promising. This systematic review explored the capabilities of ML models compared with prehospital stroke scales for LVO prediction. Methods and Results Six bibliographic databases were searched from inception until October 10, 2023. Meta‐analyses pooled the model performance using area under the curve (AUC), sensitivity, specificity, and summary receiver operating characteristic curve. Of 1544 studies screened, 8 retrospective studies were eligible, including 32 prehospital stroke scales and 21 ML models. Of the 9 prehospital scales meta‐analyzed, the Rapid Arterial Occlusion Evaluation had the highest pooled AUC (0.82 [95% CI, 0.79–0.84]). Support Vector Machine achieved the highest AUC of 9 ML models included (pooled AUC, 0.89 [95% CI, 0.88–0.89]). Six prehospital stroke scales and 10 ML models were eligible for summary receiver operating characteristic analysis. Pooled sensitivity and specificity for any prehospital stroke scale were 0.72 (95% CI, 0.68–0.75) and 0.77 (95% CI, 0.72–0.81), respectively; summary receiver operating characteristic curve AUC was 0.80 (95% CI, 0.76–0.83). Pooled sensitivity for any ML model for LVO was 0.73 (95% CI, 0.64–0.79), specificity was 0.85 (95% CI, 0.80–0.89), and summary receiver operating characteristic curve AUC was 0.87 (95% CI, 0.83–0.89). Conclusions Both prehospital stroke scales and ML models demonstrated varying accuracies in predicting LVO. Despite ML potential for improved LVO detection in the prehospital setting, application remains limited by the absence of prospective external validation, limited sample sizes, and lack of real‐world performance data in a prehospital setting.

BackgroundData on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.ObjectivesWe prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion.MethodsThe multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose.ResultsOf 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the “marginal zone,” defined as age 75–80 years, weight 60–65 kg, and creatinine levels 1.2–1.5 mg/dL.ConclusionsIn real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

BackgroundRenal function is one of the crucial components for determining the dose and type of oral anticoagulants in atrial fibrillation (AF) patients, and is also closely associated with the risks of stroke and bleeding. This study aimed to assess renal function changes and their impact on clinical outcomes in anticoagulated AF patients with marginal renal function.MethodsFrom a Korean claims database, patients with AF on anticoagulants and a baseline eGFR of 45 to 60 ml/min/1.73 m2), or worsened (eGFR

Background Atrial fibrillation (AF) is the most common sustained arrhythmia and results in a high risk of stroke. The number of immigrants is increasing globally, but little is known about potential differences in AF care across migrant populations.Aim To investigate if initiation of oral anticoagulation therapy (OAC) differs for patients with incident AF in relation to country of origin.Methods A nationwide register-based study covering 1999–2017. AF was defined as a first-time diagnosis of AF and a high risk of stroke. Stroke risk was defined according to guidelines from the European Society of Cardiology (ESC). Poisson regression adjusted for sex, age, socioeconomic position and comorbidity was made to compute incidence rate ratios (IRR) for initiation of OAC.Results The AF population included 254 586 individuals of Danish origin, 6673 of Western origin and 3757 of non-Western origin. Overall, OAC was initiated within −30/+90 days relative to the AF diagnosis in 50.3% of individuals of Danish origin initiated OAC, 49.6% of Western origin and 44.5% of non-Western origin. Immigrants from non-Western countries had significantly lower adjusted IRR of initiating OAC according to all ESC guidelines compared with patients of Danish origin. The adjusted IRRs ranged from 0.73 (95% CI: 0.66 to 0.80) following the launch of the 2010 ESC guideline to 0.89 (95% CI: 0.82 to 0.97) following the launch of the 2001 ESC guideline.Conclusion Patients with AF with a high risk of stroke of non-Western origin have persistently experienced a lower chance of initiating OAC compared with patients of Danish origin during the last decades.

Abstract 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 We aimed to investigate the relationship between time in target range of systolic blood pressure (SBP-TTr) and clinical outcomes in patients with atrial fibrillation (AF). We analyzed the results from multicenter AF registry in Thailand. Blood pressure was recorded at baseline and at every 6 monthly follow-up visit. SBP-TTr were calculated using the Rosendaal method, based on a target SBP 120–140 mmHg. The outcomes were death, ischemic stroke/systemic embolism (SSE), major bleeding, and heart failure. A total of 3355 patients were studied (mean age 67.8 years; 41.9% female). Average follow-up time was 32.1 ± 8.3 months. SBP-TTr was classified into 3 groups according to the tertiles. The incidence rates of all-cause death, SSE, major bleeding, and heart failure were 3.90 (3.51–4.34), 1.52 (1.27–1.80), 2.2 (1.90–2.53), and 2.83 (2.49–3.21) per 100 person-years, respectively. Patients in the 3rd tertile of SBP-TTr had lower rates of death, major bleeding and heart failure with adjusted hazard ratios 0.62 (0.48–0.80), p

Background Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited. Methods and Results Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow‐up of 11.9 years (first quartile–third quartile, 11.6–13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person‐years (95% CI, 4.86–4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91–1.00) for second quartile; HR=0.92 (95% CI, 0.88–0.96) for third quartile; and HR=0.85 (95% CI, 0.81–0.89) for fourth quartile (P for trend

BackgroundPatients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF.ObjectivesWe investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence.MethodsWe analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF.ResultsAmong 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan.ConclusionsIn hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.

Introduction There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk.Methods and analysis Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis.Ethics and dissemination The London—Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee.Trial registration number ISRCTN72104369.

Background In older adults, obstructive sleep apnea (OSA) has been associated with several cardiovascular complications. Whether young patients diagnosed with OSA also are at higher risk of developing subsequent cardiovascular disease is uncertain. We aimed to estimate the risk of developing an incident cardiovascular event among young patients diagnosed with OSA. Methods and Results We linked nationwide Danish health registries to identify a cohort of patients aged ≤50 years with OSA using data from 2010 through 2018. Cases without OSA from the general population were matched as controls (1:5). The main outcome was any cardiovascular event (including hypertension, diabetes, atrial fibrillation, ischemic heart disease, ischemic stroke, heart failure, and venous thromboembolism). All‐cause mortality was a secondary outcome. The study included 20 240 patients aged ≤50 years with OSA (19.6% female; mean±SD age 39.9±7.7 years) and 80 314 controls. After 5‐year follow‐up, 31.8% of the patients with OSA developed any cardiovascular event compared with 16.5% of the controls, with a corresponding relative risk (RR) of 1.96 (95% CI, 1.90–2.02). At 5‐year follow‐up, 27.3% of patients with OSA developed incident hypertension compared with 15.0% of the controls (RR, 1.84 [95% CI, 1.78–1.90]). Incident diabetes occurred in 6.8% of the patients with OSA and 1.4% of controls (RR, 5.05 [95% CI, 4.60–5.54]). Conclusions Similar to older adults, young adults with OSA demonstrate increased risk of developing cardiovascular events. To prevent cardiovascular disease progression, accumulation of cardiovascular risk factors, and mortality, risk stratification and prevention strategies should be considered for these patients.

Background Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of adverse events in patients with atrial fibrillation (AF); however, few data are available on this topic in Asian populations. Methods and Results Prospective observational study conducted on patients with AF enrolled in the Asia‐Pacific Heart Rhythm Society (APHRS) AF Registry. The diagnosis of COPD was based on data reported in the case report form by the investigators. Cox‐regression models were used to assess the 1‐year risk of a primary composite outcome of all‐cause death, thromboembolic events, acute coronary syndrome, and heart failure. Analysis on single outcomes and cardiovascular death was also performed. Interaction analysis was used to assess the risk of composite outcome and all‐cause death in different subgroups. The study included 4094 patients with AF (mean±SD age 68.5±12 years, 34.6% female), of whom 112 (2.7%) had COPD. Patients with COPD showed a higher incidence of the primary composite outcome (25.1% versus 6.3%, P

Introduction Chronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the ‘Activate Your Heart’ cardiac rehabilitation programme for people with chronic stable angina compared with usual care.Methods and analysis ACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the ‘Activate Your Heart’ web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months’ follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months’ follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost–utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme.Ethics and dissemination North of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication.Trial registration number ISRCTN10054455.

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.

Background: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. Methods: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of the modified RoPE score in identifying the presence of a PFO in patients with acute ischemic stroke (AIS). Results: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without a PFO (median 63 years vs. 71 years, p < 0.001) and fewer were female (46.1% vs. 49.7%, p < 0.001). The patients with PFO had greater mean modified RoPE scores (4.0 vs. 3.3, p < 0.001). The area under the curve for the RoPE score in predicting PFOs was 0.625 (95%CI 0.620–0.629). The best diagnostic power of the RoPE score was achieved with a cut-off point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut-off point of ≥5 increased the specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFOs was deep vein thrombosis (OR 3.97, 95%CI 3.76–4.20). Conclusions: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

BackgroundThe impact of early rhythm control (ERC) combined with healthy lifestyle (HLS) on the risk of ischemic stroke in elderly patients with atrial fibrillation (AF) remains unaddressed.ObjectiveTo evaluate the impact of combined ERC and HLS on the risk of stroke in elderly patients with new-onset AF.MethodsUsing the Korean National Health Insurance Service database, we included patients aged ≥75 years with new-onset AF from January 2009 to December 2016 (n = 41,315). Patients who received rhythm control therapy within 2 years of AF diagnosis were defined as the ERC group. Non-smoking, non-to-mild alcohol consumption (

Background Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction‐associated fatty liver disease. This study aimed to investigate whether serum hs‐CRP (high‐sensitivity C‐reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction‐associated fatty liver disease and a normal left ventricular ejection fraction. Methods and Results The study enrolled consecutive individuals with metabolic dysfunction‐associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non‐HF, pre‐HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle‐aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre‐HFpEF were 34.2% and 34.5%, with a median serum hs‐CRP level of 4.5 mg/L (interquartile range, 1.9–10 mg/L) and 5.0 mg/L (interquartile range, 2.1–10.1 mg/L), respectively. Serum hs‐CRP levels were significantly higher in the pre‐HFpEF and HFpEF groups than in the non‐HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non‐HF, 20.8% in pre‐HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs‐CRP quartile had a ≈4.5‐fold increased risk of being hospitalized for HF compared with those in the lowest hs‐CRP quartile (adjusted‐hazard ratio, 4.42 [95% CI, 3.72–5.25]). Conclusions There was a high prevalence of baseline pre‐HFpEF and HFpEF in patients with metabolic dysfunction‐associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs‐CRP levels.

Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged

BackgroundAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. AF increases the risk of stroke 5-fold, though the risk can be reduced with appropriate treatment. Therefore, early diagnosis is imperative but remains a global challenge. In low-and middle-income countries (LMICs), a lack of diagnostic equipment and under-resourced healthcare systems generate further barriers. The rapid development of digital technologies that are capable of diagnosing AF remotely and cost-effectively could prove beneficial for LMICs. However, evidence is lacking on what digital technologies exist and how they compare in regards to diagnostic accuracy. We aim to systematically review the diagnostic accuracy of all digital technologies capable of AF diagnosis.MethodsMEDLINE, Embase and Web of Science will be searched for eligible studies. Free text terms will be combined with corresponding index terms where available and searches will not be limited by language nor time of publication. Cohort or cross-sectional studies comprising adult (≥18 years) participants will be included. Only studies that use a 12-lead ECG as the reference test (comparator) and report outcomes of sensitivity, specificity, the diagnostic odds ratio (DOR) or the positive and negative predictive value (PPV and NPV) will be included (or if they provide sufficient data to calculate these outcomes). Two reviewers will independently assess articles for inclusion, extract data using a piloted tool and assess risk of bias using the QUADAS-2 tool. The feasibility of a meta-analysis will be determined by assessing heterogeneity across the studies, grouped by index device, diagnostic threshold and setting. If a meta-analysis is feasible for any index device, pooled sensitivity and specificity will be calculated using a random effect model and presented in forest plots.DiscussionThe findings of our review will provide a comprehensive synthesis of the diagnostic accuracy of available digital technologies capable for diagnosing AF. Thus, this review will aid in the identification of which devices could be further trialed and implemented, particularly in a LMIC setting, to improve the early diagnosis of AF.Trial registrationSystematic review registration: PROSPERO registration number is CRD42021290542. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290542.

BackgroundChronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range. ObjectiveThis study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population. MethodsThe analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (

Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system. Thus, the widespread prevalence of hypertension brings enormous health problems and socioeconomic burdens worldwide. The goal of hypertension management is to prevent the risk of hypertension-mediated organ damage and excess mortality of cardiovascular diseases. To achieve this goal, hypertension guidelines recommend accurate monitoring of blood pressure and assessment of associated target organ damage. Early identification of organ damage mediated by hypertension is therefore crucial. Plasma biomarkers as a non-invasive test can help identify patients with organ damage mediated by hypertension who will benefit from antihypertensive treatment optimization and improved prognosis. In this review, we provide an overview of some currently available, under-researched, potential plasma biomarkers of organ damage mediated by hypertension, looking for biomarkers that can be detected by simple testing to identify hypertensive patients with organ damage, which is of great significance in clinical work. Natriuretic peptides (NPs) can be utilized as a traditional biomarker to detect hypertension-mediated organ damage, especially for heart failure. Nevertheless, we additionally may need to combine two or more plasma biomarkers to monitor organ damage in the early stages of hypertension.

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.

ST-elevation myocardial infarction (STEMI) is a life-threatening emergency that can result in cardiac structural complications without timely revascularization. A retrospective study from the National Inpatient Sample included all patients with a diagnosis of STEMI between 2016 and 2020. Primary outcomes of interest were in-hospital mortality, length of stay (LoS), and healthcare costs for patients with and without structural complications. There were 994,300 hospital admissions included in the analysis (median age 64 years and 32.2% female). Structural complications occurred in 0.78% of patients. There was a three-fold increase in patients with cardiogenic shock (41.6% vs. 13.6%) and in-hospital mortality (30.6% vs. 10.7%) in the group with structural complications. The median LoS was longer (5 days vs. 3 days), and the median cost was significantly greater (USD 32,436 vs. USD 20,241) for patients with structural complications. After adjustments, in-hospital mortality was significantly greater for patients with structural complications (OR 1.99, 95% CI 1.73–2.30), and both LoS and costs were greater. There was a significant increase in mortality with ruptured cardiac wall (OR 9.16, 95% CI 5.91–14.20), hemopericardium (OR 3.20, 95% CI 1.91–5.35), and ventricular septal rupture (OR 2.57, 95% CI 1.98–3.35) compared with those with no complication. In conclusion, structural complications in STEMI patients are rare but potentially catastrophic events.