Plasma apixaban concentrations and thrombin generation assay parameters in response to dose reduction for atrial fibrillation.

AIMS: To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban. METHODS: This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels. RESULTS: The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations. CONCLUSION: Off-label underdosed apixaban resulted in lower apixaban concentrations than both on-label standard and reduced-dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose-reduction criteria.

Cardio-reno-vascular protection in type 2 diabetes mellitus: new insights into pharmacotherapeutic management.

INTRODUCTION: From 2008 and following the withdrawal of rosiglitazone, obligatory cardiovascular outcomes trials are performed for glucose lowering drugs introduced to the market to ensure their cardiovascular (CV) safety. Paradoxically, these studies have demonstrated CV safety but also shown additional cardio-reno-vascular protection of some therapeutic agents. Additionally, nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) have emerged as novel drugs for cardio - and renoprotection in type 2 diabetes (T2D) and chronic kidney disease (CKD). In addition to atherosclerotic CV disease, heart failure (HF) and CKD are important clinical problems in T2D leading to poor quality of life and premature death as such cardio-reno-vascular protection is an important clinical issue. AREAS COVERED: We provide new insights into pharmacotherapeutic cardio-reno-vascular protection in T2D based on the new glucose lowering drugs and ns-MRA. PUB MED/CINAHL/Web of Science/Scopus were searched (May 2024). EXPERT OPINION: The conventional glucose lowering approach alone which was implemented for decades is now replaced by the use of disease modifying drugs which lower the rates of CV events, HF decompensation, hospitalization due to HF, slow progression of CKD and all-cause mortality. Indeed, the choice of medications in T2D should be focused on underlying co-morbidities with cardio-reno-vascular protection rather than a gluco-centric approach.

Impact of bridging thrombolysis versus endovascular thrombectomy alone on outcomes in anticoagulated patients with atrial fibrillation and acute ischaemic stroke.

BACKGROUND AND PURPOSE: The impact of bridging thrombolysis prior to endovascular thrombectomy (EVT) compared to EVT alone on intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH), and death in anticoagulated atrial fibrillation (AF) patients with acute ischaemic stroke (AIS) is not well defined. METHODS: A retrospective study was conducted using data from a federated research network (TriNetX) including 114 health care organisations in the United States. Anticoagulated AF patients with AIS who received either bridging thrombolysis (BT) or EVT alone from September 2018 to November 2023 were included. Following propensity score matching, Cox regression analyses examined the risk of ICH, SAH, and death within 30 and 90 days, comparing anticoagulated AF patients receiving BT versus EVT only. RESULTS: A total of 3156 patients with AIS were treated with BT or EVT alone. Following 1:1 propensity score matching, the cohort included 766 patients in each group. ICH occurred within 30 and 90 days in 6.9% and 8.0% in the BT group compared with 7.4% and 7.7% in the EVT-only group (hazard ratios [HR] = 0.92, 95% confidence interval [CI] = 0.63-1.33 and HR = 1.01, 95% CI = 0.71-1.45, respectively). SAH occurred within 30 and 90 days in 4.2% and 4.4% of patients in the BT compared to 3.0% and 3.4% in the EVT-only group (HR = 1.38, 95% CI = 0.81-2.38 and HR = 1.29, 95% CI = 0.77-2.14, respectively). Death occurred within 30 and 90 days in 17.8% and 19.8% of patients in the BT compared to 22.2% and 27.3% in the EVT-only group (HR = 0.77, 95% CI = 0.62-0.97 and HR = 0.65, 95% CI = 0.56-0.86, respectively). CONCLUSIONS: In anticoagulated AF patients with AIS, BT was associated with a significantly lower risk of death, with no difference in ICH or SAH risk within 30 and 90 days compared to EVT only.

Development and Validation of a Predictive Model for Intracranial Haemorrhage in Patients on Direct Oral Anticoagulants.

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 < 0.001). Risk categories significantly stratified ICH risk (low risk: 0.26%, moderate risk: 0.74%, high risk: 5.51%). Finally, the model demonstrated consistent predictive performance in the internal validation. CONCLUSION: In a real-world Chinese population using DOAC therapy, this study presents a reliable predictive model for ICH risk. The XGBoost model, integrating six key risk factors, offers a valuable tool for individualized risk assessment in the context of oral anticoagulation therapy.

Global burden of metabolic diseases, 1990-2021.

BACKGROUND: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex. METHODS: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI). RESULTS: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17]). CONCLUSION: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide.

Aspirin and Ticagrelor Versus Aspirin and Clopidogrel or Pasugrel and the Effect on Staphylococcal-Associated Infections: A Real-world Study.

PURPOSE: Antiplatelet therapy is used for the primary and secondary prevention of thrombotic diseases such as acute coronary syndrome (ACS). These patients are more vulnerable to infections, as such, strategies are required to mitigate these risks. METHODS: We conducted a retrospective cohort study using TriNetX, a global federated health research network that includes both inpatient and outpatient electronic medical records from health care organizations worldwide. Patients ≥18 years old, after ACS, who were placed on aspirin and ticagrelor were compared with patients placed on aspirin and clopidogrel or prasugrel. Patients were identified using International Statistical Classification of Diseases and Related Health Problems terminology codes. After propensity score matching (1:1), a total of 239,358 patients were identified in each cohort. The primary outcomes of interest investigated were rates of (1) acute and subacute infective endocarditis, (2) sepsis of unknown origin, (3) staphylococcus arthritis, (4) cellulitis and acute lymphangitis, (5) Staphylococcus aureus bacteremia, and (6) staphylococcal pneumonia after initiation of treatment. Outcomes were analyzed at 1, 3, and 5 years. FINDINGS: At 5 years, a combination of aspirin and ticagrelor, compared with a combination of aspirin and clopidogrel or prasugrel, was associated with significantly reduced rates of (1) acute and subacute endocarditis (hazard ratio [HR] plus 95% CI) (HR = 0.85; 0.77-0.945; P = 0.030), (2) sepsis of unknown origin (HR = 0.89; 95% CI, 0.86-0.91; P < 0.0001), (3) cellulitis and acute lymphangitis (HR = 0.89; 95% CI, 0.87-0.92; P < 0.0001, and (4) Staphylococcus aureus bacteremia (HR = 0.72; 95% CI, 0.61-0.85; P = 0.0007). However, a combination of aspirin and clopidogrel was associated with a marinally lower risk of staphylococcal pneumonia (HR = 1.04; 95% CI, 1.01-1.062; P < 0.0001). IMPLICATIONS: A combination of aspirin and ticagrelor is associated with a lower rate of a variety of bacterial infections. This combination warrants further investigation in in-vitro studies to tease out mechanisms and through clinical randomized trials in groups who have ACS and are at high infection risk.

AI-based derivation of atrial fibrillation phenotypes in the general and critical care populations.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations. METHODS: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward's minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations. FINDINGS: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations. INTERPRETATION: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions. FUNDING: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624).

The impact of gestational diabetes and gestational hypertension on future cardiovascular events: A nationwide cross-sectional cohort study.

OBJECTIVES: Cardiovascular disease is the leading cause of female death worldwide. The link between future cardiovascular events and a history of hypertensive disease in pregnancy or gestational diabetes (GDM) has been well established. Less well understood is the impact on future cardiovascular risk when gestational hypertension (GH) and GDM have occurred together. We assessed the association of GDM and GH with future cardiovascular events both alone and in combination. STUDY DESIGN: All female patients discharged from French hospitals in 2013 with 5 years of subsequent and complete follow-up were identified. They were grouped depending on their history of GDM, history of GH, history of both or history of neither. After propensity score matching, patients with GDM and/or GH were matched 1:1 with patients with no GDM or GH. Hazard ratios (HR) for cardiovascular events during follow-up were adjusted by age at baseline. RESULTS: Women with a history of GH had an increased risk of cardiovascular death (HR 5.46, 95 % confidence interval [CI] 1.93-15.49). Women with a history of GDM had no significant difference in the risk of cardiovascular events such as myocardial infarction (HR 0.88, 95 %CI 0.38-2.03) and cardiovascular death (HR 1.25, 95 %CI 0.47-3.36) during the 5 year follow up. Those with a history of both GDM and GH had a significantly increased risk of myocardial infarction (HR 23.33, 95 %CI 4.84-112.39). CONCLUSION: Women with a history of both GH and GDM are at a 23-fold increased risk of myocardial infarction within the first 5 years of their postnatal lives.

Incidence of All-Cause, Cardiovascular, and Atrial Fibrillation-Related Hospitalizations: Focus on Antiarrhythmic Drugs.

Background: Atrial fibrillation (AF) is associated with an increased risk of hospital admission, but few data on reasons for hospitalization and on the role of anti-arrhythmic drugs are available. Objectives: The purpose of this study was to investigate the incidence rate and factors associated with all-cause, cardiovascular, and AF-related hospitalizations. Methods: Prospective ongoing ATHERO-AF (Atherosclerosis in Atrial Fibrillation) cohort study enrolling AF patients on oral anticoagulants. Primary end points were all-cause, cardiovascular, and AF-related hospitalization, the latter defined as AF recurrences for paroxysmal AF and high-rate symptomatic AF episodes for persistent/permanent AF patients. Results: 2,782 patients were included (43.5% female; mean age was 74.6 ± 9.1 years). During a mean follow-up of 31 ± 26.8 months, 1,205 (12.1%/year) all-cause, 533 cardiac (5.7%/year), and 180 (2.0%/year) AF-related hospitalizations occurred. Predictors of AF-related hospitalizations were the use of flecainide/propafenone in both paroxysmal and persistent/permanent AF patients (HR: 1.861; 95% CI: 1.116 to 3.101 and 1.947; 95% CI: 1.069 to 3.548, respectively). Amiodarone (HR: 3.012; 95% CI: 1.835-4.943), verapamil/diltiazem (HR: 2.067; 95% CI: 1.117-3.825), and cancer (HR: 1.802; 95% CI: 1.057-3.070) but not beta-blockers and digoxin were associated with an increased risk of AF-related hospitalizations in persistent/permanent AF patients. Conclusions: Elderly AF patients frequently undergo hospitalizations for both cardiovascular and noncardiovascular causes. The use of anti-arrhythmic drugs was associated with an increased risk of AF-related hospitalization suggesting a scarce effect of these drugs in preventing AF episodes. Therefore, their use should be carefully considered and reserved for symptomatic patients with frequent AF recurrences.

Artificial intelligence-based classification of cardiac autonomic neuropathy from retinal fundus images in patients with diabetes: The Silesia Diabetes Heart Study.

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).

One-year outcomes of rate versus rhythm control of atrial fibrillation in the Kerala-AF Registry.

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 <18 (aOR 1.51; p = .025), permanent AF (aOR 0.78; p = .010), HFpEF (aOR 1.40; p = .023), HFrEF (aOR 1.39; p = .004), chronic kidney disease (aOR 1.36; p < .001), and prior thromboembolism (aOR 1.31; p = .014). Conclusion: In the Kerala-AF registry, 12-month outcomes did not differ between rate and rhythm control cohorts.

QRS detection in single-lead, telehealth electrocardiogram signals: Benchmarking open-source algorithms.

BACKGROUND AND OBJECTIVES: A key step in electrocardiogram (ECG) analysis is the detection of QRS complexes, particularly for arrhythmia detection. Telehealth ECGs present a new challenge for automated analysis as they are noisier than traditional clinical ECGs. The aim of this study was to identify the best-performing open-source QRS detector for use with telehealth ECGs. METHODS: The performance of 18 open-source QRS detectors was assessed on six datasets. These included four datasets of ECGs collected under supervision, and two datasets of telehealth ECGs collected without clinical supervision. The telehealth ECGs, consisting of single-lead ECGs recorded between the hands, included a novel dataset of 479 ECGs collected in the SAFER study of screening for atrial fibrillation (AF). Performance was assessed against manual annotations. RESULTS: A total of 12 QRS detectors performed well on ECGs collected under clinical supervision (F1 score ≥0.96). However, fewer performed well on telehealth ECGs: five performed well on the TELE ECG Database; six performed well on high-quality SAFER data; and performance was poorer on low-quality SAFER data (three QRS detectors achieved F1 of 0.78-0.84). The presence of AF had little impact on performance. CONCLUSIONS: The Neurokit and University of New South Wales QRS detectors performed best in this study. These performed sufficiently well on high-quality telehealth ECGs, but not on low-quality ECGs. This demonstrates the need to handle low-quality ECGs appropriately to ensure only ECGs which can be accurately analysed are used for clinical decision making.

Telehealth-aided outpatient management of acute heart failure in a specialist virtual ward compared with standard care.

AIMS: The aim of this propensity score matched cohort study was to assess the outcomes of telehealth-guided outpatient management of acute heart failure (HF) in our virtual ward (HFVW) compared with hospitalized acute HF patients. METHODS AND RESULTS: This cohort study (May 2022-October 2023) assessed outcomes of telehealth-guided outpatient acute HF management using bolus intravenous furosemide in a HF-specialist VW. Propensity score matching (PSM) was performed using logistic regression to adjust for potential differences in baseline patient characteristics between HFVW and standard care [Get With The Guidelines-HF score, clinical frailty score (CFS), Charlson co-morbidity index (CCI), NT-proBNP, and ejection fraction]. Clinical outcomes (re-hospitalizations and mortality) were compared at 1, 3, 6, and 12 months versus standard care-SC (acute HF patients managed without telehealth in 2021). Five hundred fifty-four HFVW ADHF patients (age 73.1 ± 10.9 years; 46% female) were compared with 404 ADHF patients (74.2 ± 11.8; P = 0.15 and 49% female) in the standard care-SC cohort. After propensity score matching for baseline patient characteristics, re-hospitalizations were significantly lower in the HFVW compared with SC (1 month-HFVW 8.6% vs. SC-21.5%, P < 0.001; 3 months-21% vs. 30%, P = 0.003; 6 months-28% vs 41%, P < 0.001 and 12 months-47% vs. 57%, P = 0.005) and mortality was also lower at 1 month (5% vs. 13.7%; P < 0.001), 3 months (9.5% vs. 15%; P = 0.001), 6 months (15% vs. 21%; P = 0.03), and 12 months (20% vs. 26%; P = 0.04). Multivariate logistic regression analysis showed that compared with standard care, HFVW management was associated with lower odds of readmission (1-month odds ratio (OR) = 0.3 [95% Confidence Interval CI 0.2-0.5], P < 0.0001; 3 month OR = 0.15 [0.1-0.3], P < 0.0001; 6-month OR = 0.35 [0.2-0.6], P = 0.0002; 12-month OR = 0.25 [0.15-0.4], P ≤ 0.001 and mortality (1-month OR = 0.26 [0.14-0.48], P < 0.0001; 3-month OR = 0.11 [0.04-0.27], P < 0.0001; 6-month OR = 0.35, [0.2; 0.61], P = 0.0002; 12-month OR = 0.6 [0.48; 0.73], P = 0.03. Higher GWTG-HF score independently predicted increased odds of re-hospitalization (1-month OR = 1.2 [1.1-1.3], P < 0.001; 3-month OR = 1.5 [1.37; 1.64], P < 0.0001; 6-month OR = 1.3 [1.2-1.4], P < 0.0001; 12-month OR = 1.1 [1.05-1.2], P = 0.03) as well as mortality (1-month OR = 1.21 [1.1-1.3], P < 0.0001; 3-month OR = 1.3 [1.2-1.4], P < 0.0001; 6-month OR = 1.2 [1.1-1.3], P < 0.0001; 12-month OR = 1.3 [1.1-1.7], P = 0.02). Similarly higher CFS also independently predicted increased odds of re-hospitalizations (1-month OR = 1.9 [1.5-2.4], P < 0.0001; 3-month OR = 1.8 [1.3-2.4], P = 0.0003; 6-month OR = 1.4 [1.1-1.8], P = 0.015; 12-month OR 1.9 [1.2-3], P = 0.01]) and mortality (1-month OR = 2.1 [1.6-2.8], P < 0.0001; 3-month OR = 1.8 [1.2-2.6], P = 0.006; 6-month OR = 2.34 [1.51-5.6], P = 0.0001; 12-month OR = 2.6 [1.6-7], P = 0.02). Increased daily step count while on HFVW independently predicted reduced odds of re-hospitalizations (1-month OR = 0.85[0.7-0.9], P = 0.005), 3-month OR = 0.95 [0.93-0.98], P = 0.003 and 1-month mortality (OR = 0.85 [0.7-0.95], P = 0.01), whereas CCI predicted adverse 12-month outcomes (OR = 1.2 [1.1-1.4], P = 0.03). CONCLUSIONS: Telehealth-guided specialist HFVW management for ADHF may offer a safe and efficacious alternative to hospitalization in suitable patients. Daily step count in HFVW can help predict risk of short-term adverse clinical outcomes.

The association of haemoglobin A1c variability with adverse outcomes in patients with atrial fibrillation prescribed anticoagulants.

AIMS: The association of haemoglobin A1c (HbA1c) variability with the risk of adverse outcomes in patients with atrial fibrillation (AF) prescribed anticoagulants remains unclear. This study aimed to evaluate the association of HbA1c variability with the risk of ischaemic stroke (IS)/systemic embolism (SE) and all-cause mortality among patients with non-valvular AF prescribed anticoagulants. METHODS AND RESULTS: Patients newly diagnosed with AF from 2013 to 2018 were included. Variability in HbA1c, indexed by the coefficient of variation (CV), was determined for those with at least three HbA1c measurements available from the time of study enrolment to the end of follow-up. To evaluate whether prevalent diabetes would modify the relationship between HbA1c variability and outcomes, participants were divided into diabetes and non-diabetes groups. The study included 8790 patients (mean age 72.7% and 48.5% female). Over a median follow-up of 5.5 years (interquartile range 5.2, 5.8), the incident rate was 3.74 per 100 person-years for IS/SE and 4.89 for all-cause mortality in the diabetes group. The corresponding incident rates in the non-diabetes group were 2.41 and 2.42 per 100 person-years. In the diabetes group, after adjusting for covariates including mean HbA1c, greater HbA1c variability was significantly associated with increased risk of IS/SE [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.27-2.13) and all-cause mortality (HR = 1.24, 95% CI: 1.05-1.47) compared with the lowest CV tertile. A similar pattern was evident in the non-diabetes group (IS/SE: HR = 1.58, 95% CI: 1.23-2.02; all-cause mortality: HR = 1.35, 95% CI: 1.10-1.64). CONCLUSION: Greater HbA1c variability was independently associated with increased risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetic status.

In patients with atrial fibrillation (AF), greater haemoglobin A1c (HbA1c) variability was independently associated with increased risk of ischaemic stroke/systemic embolism and all-cause mortality, regardless of diabetic status. The usefulness of HbA1c variability as a risk predictor is significant and could be integrated into the stratification of patients with AF. Even if HbA1c measurements are within standard guideline limits, patients with larger fluctuations in HbA1c level may be at higher risk of thromboembolism and death than patients with more stable HbA1c level.

Accumulated ß-catenin is associated with human atrial fibrosis and atrial fibrillation.

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 ß-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 ß-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues . METHODS: We compared the difference of ß-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of ß-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 ß-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, ß-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 3ß (GSK-3ß) and Adenomatous Polyposis Coli (APC), which participated in the degradation of ß-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 ß-catenin expression in the AF model mice. CONCLUSIONS: Based on human atrial pathological and molecular analyses, our findings provided evidence that ß-catenin was associated with atrial fibrosis and AF progression.

The Burden of Inpatient Hospitalizations with Cardiac and Cerebrovascular Diseases in Patients with Type 1 Diabetes: Insights from the National Inpatient Sample in the US.

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.

Risk of stroke in male and female patients with atrial fibrillation in a nationwide cohort.

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.

The association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation.

BACKGROUND: The impact of post-stroke antithrombotic regimen in atrial fibrillation (AF) is uncertain. OBJECTIVE: To describe antithrombotic therapy prescribing patterns following ischemic stroke, and its impact on outcomes. METHODS: A total of 23,165 AF patients experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite outcomes. RESULTS: Among those who were non-anticoagulated before a stroke, 33.5% remained non-anticoagulated and 39.2% were prescribed only antiplatelets (AP) post-stroke. Compared to NOACs post-stroke, there was a significant increase in ischemic stroke and mortality in non-anticoagulated (aHRs 2.09 and 3.92) and antiplatelet users (aHRs 1.32 and 1.28). Post-stroke warfarin was associated with a significantly incresaed risk of major bleeding compared to NOACs (aHR 1.23). Among 769 patients receiving NOACs before stroke and continuing NOAC post-stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR 2.07) and composite outcomes (aHRs 1.36-1.85) with no difference in ICH, major bleeding or mortality compared to those on the same NOAC post-stroke. Among patients receiving NOACs before stroke, the risks of clinical events were similar between patients on NOACs alone and those on NOAC plus AP post-stroke. CONCLUSIONS: NOAC alone post-stroke was associated with a better clinical outcome compared to non-anticoagulation, AP or warfarin. Among patients already taking NOACs before stroke, the addition of AP didn't confer additional benefits compared to NOACs alone. A change of NOAC types post-stroke was associated with a two-fold higher risk of ischemic stroke and composite outcomes.

Impact of prior oral anticoagulation therapies on post-discharge outcomes after COVID-19: Results from a global federated health network analysis.

BACKGROUND: The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy. METHODS: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation. RESULTS: We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936). CONCLUSION: COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.