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Aim: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction‐associated fatty liver disease (MAFLD). Methods: We enrolled 163 individuals with biopsy‐proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra‐performance liquid chromatography coupled with tandem mass spectrometry. Results: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre‐HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. Conclusions: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy‐confirmed MAFLD. [ABSTRACT FROM AUTHOR]

Background: Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline‐containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. Methods: The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. Results: Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow‐up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01–1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24–1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31–2.36) compared with patients who remained prediabetic. Conclusions: In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow‐up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. Plain Language Summary: Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked.In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure.Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease.These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow‐up strategies, and consideration of prediabetes management in cancer care. Patients with cancer who have preexisting diabetes mellitus have a higher risk of worse outcomes, whereas prediabetes in these patients might often be overlooked. In this study of patients with cancer who received anthracyclines, prediabetes was associated with greater cardiovascular mortality and heart failure hospitalization, whereas progression to diabetes within 2 years also contributed to an increased risk of composite cardiac events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Access site complications remain common following atrial fibrillation (AF) catheter ablation. Femoral vascular closure devices (VCDs) reduce time to hemostasis compared with manual compression, although large‐scale data comparing clinical outcomes between the two approaches are lacking. Methods: Two cohorts of patients undergoing AF ablation were identified from 36 healthcare organizations using a global federated research network (TriNetX): those receiving a VCD for femoral hemostasis, and those not receiving a VCD. A 1:1 propensity score matching (PSM) model based on baseline characteristics was used to create two comparable cohorts. The primary outcome was a composite of all‐cause mortality, vascular complications, bleeding events, and need for blood transfusion. Outcomes were assessed during early (within 7 days of ablation) and extended follow‐up (within 8–30 days of ablation). Results: After PSM, 28 872 patients were included (14 436 in each cohort). The primary composite outcome occurred less frequently in the VCD cohort during early (1.97% vs. 2.60%, odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65–0.88; p <.001) and extended follow‐up (1.15% vs. 1.43%, OR 0.80, 95% CI 0.65–0.98; p =.032). This was driven by a lower rate of vascular complications during early follow‐up in the VCD cohort (0.83% vs. 1.26%, OR 0.66, 95% CI 0.52–0.83; p <.001), and fewer bleeding events during early (0.90% vs. 1.23%, OR 0.73, 95% CI 0.58–0.92; p =.007) and extended follow‐up (0.36% vs. 0.59%, OR 0.61, 95% CI 0.43–0.86; p =.005). Conclusion: Following AF ablation, femoral venous hemostasis with a VCD was associated with reduced complications compared with hemostasis without a VCD. [ABSTRACT FROM AUTHOR]

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 <.001. Metabolic unhealthy obese subjects tend to have an increased risk of the composite outcomes compared to those metabolic healthy obese (HR 1.36, 95% CI 0.91–2.02, p =.133). Metabolic healthy obese subjects were not associated with increased risk. Conclusions: Metabolic unhealthy obese subjects were associated with an increased risk of adverse outcomes in AF patients, whereas metabolically healthy obesity was not associated with an increased risk. [ABSTRACT FROM AUTHOR]

Aim: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN). Materials and Methods: We used motif and discord extraction techniques, alongside long short‐term memory networks, to analyse 12‐lead, 10‐s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10‐fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver‐operating characteristic curve (AUC). Results: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91–0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54–0.81). Conclusion: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large‐scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and cardiovascular outcomes of combination pioglitazone with either a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) or a sodium‐glucose cotransporter‐2 (SGLT2) inhibitor in individuals with type 2 diabetes (T2D) by conducting a systematic review, meta‐analysis, and analysis of a large international real‐world database. Methods: We searched MEDLINE, SCOPUS and Web of Science to identify relevant articles for inclusion (PROSPERO [CRD: 42023483126]). Nineteen studies assessing pioglitazone + SGLT2 inhibitors or GLP‐1RAs versus controls were identified, 16 of which were randomized controlled trials. Risk of bias was assessed using Cochrane‐endorsed tools and quality of evidence was assessed using GRADE. We additionally performed a retrospective cohort study of all individuals aged 18 years or over with T2D, using the TriNetX platform. We included propensity‐score‐matched individuals who were treated for at least 1 year with pioglitazone and a GLP‐1RA or pioglitazone and an SGLT2 inhibitor, compared against GLP‐1RA and SGLT2 inhibitor monotherapy. Outcomes were all‐cause mortality, heart failure, chronic kidney disease and composite stroke and transient ischaemic attack. Results: The average follow‐up in the included studies ranged from 24 to 52 weeks. Combination of pioglitazone with a GLP‐1RA reduced glycated haemoglobin (HbA1c) and weight greater than in controls: mean differences −1% (95% confidence interval [CI] −1.27, −0.74) and −1.19 kg (95% CI −1.80, −0.58), respectively. There was no statistically significant difference in systolic blood pressure (SBP) or mortality between groups: mean difference − 1.56 mmHg (95% CI −4.48, 1.35; p = 0.30) and relative risk (RR) 0.29 (95% CI 0.07–1.15; p = 0.08), respectively. Combination of pioglitazone with SGLT2 inhibitors reduced HbA1c, weight and SBP to a greater extent than control treatment: mean differences −0.48% (95% CI −0.67, −0.28), −2.3 kg (95% CI −2.72, −1.88) and −2.4 mmHg (95% CI −4.1, −0.7; p = 0.01), respectively. There was no statistically significant difference in mortality between groups (RR 1.81, 95% CI 0.30–10.97; p = 0.52). The included trials demonstrated a reduction in risk of heart failure with combination treatment. Similarly, from the real‐world database (n = 25 230 identified), pioglitazone and SGLT2 inhibitor combination therapy was associated with reduced risk of heart failure compared to monotherapy alone (hazard ratio 0.50, 95% CI 0.38–0.65; p < 0.001). Conclusion: Both our systematic review/meta‐analysis and the real‐world dataset show that combination of pioglitazone with either GLP‐1RAs or SGLT2 inhibitors is associated with increased weight loss and reduced risk of heart failure compared with monotherapy. [ABSTRACT FROM AUTHOR]

Introduction: There is currently no guidance on how to assess the calibration of multistate models used for risk prediction. We introduce several techniques that can be used to produce calibration plots for the transition probabilities of a multistate model, before assessing their performance in the presence of random and independent censoring through a simulation. Methods: We studied pseudo‐values based on the Aalen‐Johansen estimator, binary logistic regression with inverse probability of censoring weights (BLR‐IPCW), and multinomial logistic regression with inverse probability of censoring weights (MLR‐IPCW). The MLR‐IPCW approach results in a calibration scatter plot, providing extra insight about the calibration. We simulated data with varying levels of censoring and evaluated the ability of each method to estimate the calibration curve for a set of predicted transition probabilities. We also developed evaluated the calibration of a model predicting the incidence of cardiovascular disease, type 2 diabetes and chronic kidney disease among a cohort of patients derived from linked primary and secondary healthcare records. Results: The pseudo‐value, BLR‐IPCW, and MLR‐IPCW approaches give unbiased estimates of the calibration curves under random censoring. These methods remained predominately unbiased in the presence of independent censoring, even if the censoring mechanism was strongly associated with the outcome, with bias concentrated in low‐density regions of predicted transition probability. Conclusions: We recommend implementing either the pseudo‐value or BLR‐IPCW approaches to produce a calibration curve, combined with the MLR‐IPCW approach to produce a calibration scatter plot. The methods have been incorporated into the "calibmsm" R package available on CRAN. [ABSTRACT FROM AUTHOR]

Background: The association of a broad spectrum of infectious diseases with cardiovascular outcomes remains unclear. Objectives: We aim to provide the cardiovascular risk profiles associated with a wide range of infectious diseases and explore the extent to which infections reduce life expectancy. Methods: We ascertained exposure to 900+ infectious diseases before cardiovascular disease (CVD) onset in 453,102 participants from the UK Biobank study. Time‐varying Cox proportional hazard models were used. Life table was used to estimate the life expectancy of individuals aged ≥50 with different levels of infection burden (defined as the number of infection episodes over time and the number of co‐occurring infections). Results: Infectious diseases were associated with a greater risk of CVD events (adjusted HR [aHR] 1.79 [95% confidence interval {CI} 1.74–1.83]). For type‐specific analysis, bacterial infection with sepsis had the strongest risk of CVD events [aHR 4.76 (4.35–5.20)]. For site‐specific analysis, heart and circulation infections posed the greatest risk of CVD events [aHR 4.95 (95% CI 3.77–6.50)], whereas noncardiac infections also showed excess risk [1.77 (1.72–1.81)]. Synergistic interactions were observed between infections and genetic risk score. A dose–response relationship was found between infection burden and CVD risks (p‐trend <0.001). Infection burden >1 led to a CVD‐related life loss at age 50 by 9.3 years [95% CI 8.6–10.3]) for men and 6.6 years [5.5–7.8] for women. Conclusions: The magnitude of the infection‐CVD association showed specificity in sex, pathogen type, infection burden, and infection site. High genetic risk and infection synergistically increased the CVD risk. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between atrial fibrillation (AF) and dementia, and its subtypes (vascular‐VaD, Alzheimer, mixed and rare dementia), and identified predictors for dementia in AF patients. Methods: The analysis was based on 183,610 patients with new‐onset AF and 367,220 non‐AF controls in the United Kingdom between 1998 and 2016, identified in three prospectively collected, linked electronic health records sources. Time‐to‐event (dementia or subtypes) analyses were performed using Cox proportional hazards and weighted Cox. Sub‐analyses performed: including & censoring stroke and age (median used as cut‐off). Results: Over a median follow‐up of 2.67 years (IQR.65–6.02) for AF patients and 5.84 years for non‐AF patients (IQR 2.26–11.80), incidence of dementia in the AF cohort was 2.65 per 100 person‐years, compared to 2.02 in the non‐AF cohort. After adjustment, a significant association was observed between AF and all‐cause dementia (HR = 1.38, 95% CI: 1.31–1.45), driven by a strong association with VaD (HR = 1.55, 95% CI: 1.41–1.70). AF was also associated with mixed dementia (HR = 1.26, 95% CI: 1.01–1.56), but we could not confirm an association with Alzheimer (HR = 1.05, 95% CI:.94–1.16) and rare dementia forms (HR = 1.19, 95% CI:.90–1.56). Ischemic stroke (HR = 1.40, 95% CI: 1.26–1.56), subarachnoid haemorrhage (HR = 2.08, 95% CI: 1.47–2.96), intracerebral haemorrhage (HR = 1.95, 95% CI: 1.54–2.48) and diabetes (HR = 1.32, 95% CI: 1.24–1.41) were identified as the strongest predictors of dementia in AF patients. Conclusions: AF patients have an increased risk of dementia, independent of stroke, with highest risk of VaD. Management and prevention of the identified risk factors could be crucial to reduce the increasing burden of dementia. [ABSTRACT FROM AUTHOR]

Aims: The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF. Methods: We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all‐cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes. Results: 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02–1.69); a non‐statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI:.93–1.55). Similar results were observed for all‐cause death, while no statistically significant differences were observed for IS or ICH. Conclusion: Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF. Clinical Trial Registration: NCT00041938. [ABSTRACT FROM AUTHOR]

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

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

Aims: The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase‐4 inhibitors (DPP4i). Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. Results: After up to 5 years of follow‐up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24–0.82). SGLT2i was related to reduced risks of AF‐related hospitalisation (HR: 0.72, 95% CI: 0.56–0.93), stroke (HR: 0.75, 95% CI: 0.60–0.94), and all‐cause death (HR: 0.33, 95% CI: 0.24–0.44). The protective effects were consistent irrespective of the concurrent use of non‐vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF‐related hospitalisation, stroke, and all‐cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non‐valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. Method: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. Results: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]:.69, 95% confidence interval [CI]:.497–.951, p =.0237), doubling of the serum creatinine level (HR:.49, 95% CI:.259–.927, p =.0282) and the cardiac and renal outcome composite (HR:.67, 95% CI:.485–.913, p =.0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. Conclusion: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF. [ABSTRACT FROM AUTHOR]

Background: Arrhythmogenic ventricular cardiomyopathy (AVC) is a common cause of ventricular arrhythmias and mortality, but limited data are available from large Asian cohorts. Our aim was to explore the current status of AVC and second, we examined the prevalence of ventricular tachycardia (VT), heart failure (HF) and mortality in patients with AVC in the Chinese population. Hypothesis: At present, some studies have reported that the incidence of AVC is on the rise, which may be due to the increasing number of diagnostic methods for AVC. However, there is no epidemiological data on AVC in the Chinese population, so we speculate that the incidence of AVC in the Chinese population is increasing. Methods and Results: We studied 15 888 adults from the Beijing Municipal Health Commission Information Center (BMHCIC) registry database in China from January 2010 to December 2020, and calculated the average annual percentage change (AAPC). Second, we determined the incidence of VT, HF and mortality in patients with AVC. Of the 10 318 men and 5570 women who were screened by cardiac magnetic resonance or examined by myocardial biopsy, there were a total of 256 newly diagnosed AVC patients (mean [SD]: 37.54[17.10]; 39.45% female). The incidence of AVC increased from 7.60 (3.12‐12.06) in 2010 to 19.62 (11.51‐27.75) per 1000 person‐years in 2020. Males had higher incidence of AVC than females. The AAPC for the rising incidence of AVC was 8.9 %. Males had similar VT prevalence (70.32% vs. 62.38%, p = 0.19) and mortality (1.94% vs. 1.98%, p = 0.98) but lower HF prevalence (42.58% vs. 60.40%, p = 0.006), when compared to females. Radiofrequency ablation (RFA) was more likely to be performed in males (p = 0.006). Conclusions: The rising trend in AVC incidence was evident, with two‐fold increase by 2020. Males with AVC had similar VT prevalence and mortality rate, but HF prevalence were lower than females, perhaps impacted by RFA use. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) has consistently been associated with a higher risk of incident dementia. Observational evidence has suggested catheter ablation may be associated with a lower risk of dementia in patients with AF, but further research is needed. The objectives of this study were to use a global health research network to examine associations between catheter ablation, incident dementia and mortality in older adults with AF, and amongst subgroups by age, sex, co‐morbidity status, and oral anticoagulant use. Methods: The research network primarily included healthcare organizations in the United States. This network was searched on 28th September 2022 for patients aged ≥65 years with a diagnosis of AF received at least 5 years prior to the search date. Cox proportional hazard models were run on propensity‐score matched cohorts. Results: After propensity score matching, 20,746 participants (mean age 68 years; 59% male) were included in each cohort with and without catheter ablation. The cohorts were well balanced for age, sex, ethnicity, co‐morbidities, and cardiovascular medications received. The risk of dementia was significantly lower in the catheter ablation cohort (Hazard Ratio 0.52, 95% confidence interval: 0.45–0.61). The catheter ablation cohort also had a lower risk of all‐cause mortality (Hazard Ratio 0.58, 95% confidence interval: 0.55–0.61). These associations remained in subgroup analyses in individuals aged 65–79 years, ≥80 years, males, females, participants who received OACs during follow‐up, participants with paroxysmal and non‐paroxysmal AF, and participants with and without hypertension, diabetes mellitus, ischemic stroke, chronic kidney disease and heart failure, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Conclusion: The observed lower risk of dementia and mortality with catheter ablation could be an important consideration when determining appropriate patient‐centered rhythm control strategies for patients with AF. Further studies including data on the success of ablation are required. [ABSTRACT FROM AUTHOR]

Aim: To assess the relationship of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), glucagon‐like peptide‐1 receptor analogues (GLP‐1RA) and their combination (SGLT2i + GLP‐1RA) with 5‐year risk of all‐cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes. Materials and Methods: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP‐1RA and SGLT2i + GLP‐1RA) were compared against a control cohort (no SGLT2i/GLP‐1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP‐1RA, n = 186 841; SGLT‐2i + GLP‐1RA, n = 108 504). A sub‐analysis comparing combination and monotherapy cohorts was also performed. Results: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all‐cause mortality (SGLT2i 0.49, 0.48‐0.50; GLP‐1RA 0.47, 0.46‐0.48; combination 0.25, 0.24‐0.26), hospitalization (0.73, 0.72‐0.74; 0.69, 0.68‐0.69; 0.60, 0.59‐0.61) and acute myocardial infarct (0.75, 0.72‐0.78; 0.70, 0.68‐0.73; 0.63, 0.60‐0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub‐analysis showed a significant risk reduction in all‐cause mortality for combination therapy versus SGLT2i (0.53, 0.50‐0.55) and GLP‐1RA (0.56, 0.54‐0.59). Conclusions: SGLT2i, GLP‐1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all‐cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5‐year all‐cause mortality when compared directly against either monotherapy. [ABSTRACT FROM AUTHOR]

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

Background: The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA‐II) prospective randomized trial showed the efficacy of a mobile health (mHealth) implemented 'Atrial fibrillation Better Care' (ABC) pathway for the integrated care management of patients with atrial fibrillation (AF). In this ancillary analysis, we evaluated the effect of mAFA intervention according to the history of diabetes mellitus (DM). Methods: The mAFA‐II trial enrolled 3324 AF patients across 40 centres in China, between June 2018 and August 2019. In this analysis, we assessed the interaction between history of DM and the effect of mAFA intervention on the risk of the primary composite outcome of stroke, thromboembolism, all‐cause death and rehospitalizations. Results were expressed as adjusted hazard ratio (aHR) and 95% confidence intervals (95%CI). The effect of mAFA intervention on exploratory secondary outcomes was also assessed. Results: Overall, 747 (22.5%) patients had DM (mean age: 72.7 ± 12.3, 39.6% females; 381 allocated to mAFA intervention). mAFA intervention was associated with a significant risk reduction for the primary composite outcome both in patients with and without DM (aHR [95%CI]:.36 [.18–.73] and.37 [.23–.61], respectively, p for interaction =.941). A significant interaction was found only for the composite of recurrent AF, heart failure and acute coronary syndromes (pint =.025), with lower effect of mAFA intervention in patients with DM. Conclusions: A mHealth‐technology implemented ABC pathway showed a consistent effect in reducing the risk of the primary composite outcome in AF patients with and without DM. Trial Registration: WHO International Clinical Trials Registry Platform (ICTRP) Registration number: ChiCTR‐OOC‐17014138. [ABSTRACT FROM AUTHOR]

Introduction: This study considers the prediction of the time until two survival outcomes have both occurred. We compared a variety of analytical methods motivated by a typical clinical problem of multimorbidity prognosis. Methods: We considered five methods: product (multiply marginal risks), dual‐outcome (directly model the time until both events occur), multistate models (msm), and a range of copula and frailty models. We assessed calibration and discrimination under a variety of simulated data scenarios, varying outcome prevalence, and the amount of residual correlation. The simulation focused on model misspecification and statistical power. Using data from the Clinical Practice Research Datalink, we compared model performance when predicting the risk of cardiovascular disease and type 2 diabetes both occurring. Results: Discrimination was similar for all methods. The product method was poorly calibrated in the presence of residual correlation. The msm and dual‐outcome models were the most robust to model misspecification but suffered a drop in performance at small sample sizes due to overfitting, which the copula and frailty model were less susceptible to. The copula and frailty model's performance were highly dependent on the underlying data structure. In the clinical example, the product method was poorly calibrated when adjusting for 8 major cardiovascular risk factors. Discussion: We recommend the dual‐outcome method for predicting the risk of two survival outcomes both occurring. It was the most robust to model misspecification, although was also the most prone to overfitting. The clinical example motivates the use of the methods considered in this study. [ABSTRACT FROM AUTHOR]

Aims: Comparative data between the HAS‐BLED, GARFIELD‐AF and ORBIT score are limited in anticoagulated Asian patients with atrial fibrillation (AF). We compared the performance of the 3 scores in a nationwide registry. Methods: AF patients treated with oral anticoagulants in the COOL‐AF registry were studied. We fitted the variables of the HAS‐BLED, GARFIELD‐AF and ORBIT score to major bleeding in Cox model. We explored a modified HAS‐BLED by addition of sex and body weight. Discrimination, calibration, net reclassification index (NRI) and decision curve analysis were used to compare the performance of the 3 models. Results: Of 3402 patients in the registry, 2568 patients who received oral anticoagulant at baseline were studied. Majority of patients (91.1%) received warfarin. The rate of major bleeding was 2.11 per 100 person‐years. The C‐statistics of the GARFIELD‐AF, HAS‐BLED, modified HAS‐BLED and ORBIT score were 0.65 (95% confidence interval [CI] 0.63–0.67), 0.66 (95%CI 0.64–0.68), 0.69 (95%CI 0.67–0.71) and 0.64 (95%CI 0.62–0.66) respectively. There was good agreement between predicted and observed bleeding in the deciles of HAS‐BLED and GARFIELD‐AF scores, while the modified HAS‐BLED score and ORBIT score overestimated the risk in the last decile. The modified HAS‐BLED score had superior NRI than the HAS‐BLED score (26.9%, 95%CI 9.7%–42.2%) and the ORBIT score (31.9%, 95%CI 9.0–53.6%). The NRI between the modified HAS‐BLED and GARFIELD‐AF score was similar. The net benefit curve of the 4 models were overlapping among different thresholds. Conclusions: The clinical utility for bleeding prediction of GARFIELD‐AF, HAS‐BLED, modified HAS‐BLED and ORBIT scores were similar in anticoagulated Asian patients with AF participating in the COOL‐AF registry. We found no advantage of the ORBIT over HAS‐BLED score for bleeding risk prediction, even in direct oral anticoagulant users. [ABSTRACT FROM AUTHOR]

This article explores the pathways to care for individuals with Long COVID (LC) and other long-term conditions (LTCs) from the perspectives of patients and healthcare professionals (HCPs). The study used the Pathways-to-Care model to examine four filters for accessing care: the decision to seek care, recognition by the General Practitioner (GP), referral to specialist care, and arrival in outpatient specialist care. The findings show that patients with LC and LTCs have similar experiences navigating these filters, with high rates of seeking care and access to primary care. However, there was a discrepancy between patients' perception of their problem being recognized and the actions taken by HCPs. The study suggests the need for improved data exchange between primary and secondary care, alternative care models, and further research on factors that impede or promote access to care for LC and LTC patients. [Extracted from the article]

Background: Consistent adherence levels to multiple long‐term medications for patients with cardiovascular conditions are typically advocated in the range of 50% or higher, although very likely to be much lower in some populations. We investigated this issue in a large cohort covering a broad age and geographical spectrum, with a wide range of socio‐economic disability status. Methods: The patients were drawn from three different health plans with a varied mix of socio‐economic/disability levels. Adherence patterns were examined on a monthly basis for up to 12 months past the index date for myocardial infarction (MI) using longitudinal analyses of group‐based trajectory modelling. Each of the non‐adherent patterns was profiled from comorbid history, demographic and health plan factors using main effect logistic regression modelling. Four medication classes were examined for MI: betablockers, statin, ACE inhibitors and anti‐platelets. Results: The participant population for the MI/non‐MI cohorts was 1,987,605 (MI cohort: mean age 62 years, 45.9% female; non‐MI cohort: mean age 45 years, 55.3% females). Cohorts characterized by medication non‐adherence dominated the majority of MI population with values ranging from 74% to 82%. There were four types of consistent non‐adherence patterns as a function of time for each medication class: fast decline, slow decline, occasional users and early gap followed by increased adherence. The characteristics of non‐adherence profiles eligible for improvement included patients with a prior history of hypertension, diabetes mellitus and stroke as co‐morbidities, and Medicare plan. Conclusions: We found consistent patterns of intermediate non‐adherence for each of four drug classes for MI cohorts in the order of 56% who are eligible for interventions aimed at improving cardiovascular medication adherence levels. These insights may help improve cardiovascular medication adherence using large medication non‐adherence improvement programs. [ABSTRACT FROM AUTHOR]

Aims: Using advanced longitudinal analyses, this real‐world investigation examined medication adherence levels and patterns for incident atrial fibrillation (AF) patients with significant cardiovascular and noncardiovascular multimorbid conditions for each of 5 medication classes (β‐blockers, calcium channel blockers/digoxin, antiarrhythmics, anticoagulants, antiplatelets). The population was derived from a large cohort covering a wide age spectrum/diversified US geographical areas/wide range of socioeconomic–disability status. Methods: The patients were drawn from 3 different health plans. Adherence was defined in terms of the proportion of day covered (PDC), and its patterns were modelled in terms of group‐based trajectory, with each pattern profiled in terms of comorbid history, demographic variables and health plan factors using multinomial regression modelling. Results: The total population consisted of 1 978 168 patients, with the AF cohort being older (average age of 64.6 years relative to 44.7 years for the non‐AF cohort) and having fewer females (47.8% relative to 55.4 for the non‐AF cohort). The AF cohort had significant cardiovascular/noncardiovascular multimorbidities and was much sicker than the non‐AF cohort. A 6‐group based trajectory solution appears to be the most logical outcome for each medication class according to assessed criteria. For each medication class, it consisted of one consistent adherent group (PDC ≥ 0.84), one fast declining group (PDC ≤ 0.11) and 4 intermediate nonadherence groups (slow decline [0.30–0.74 PDC range], occasional users [0.24–0.55 PDC range] and early gap/increased adherence [0.62–0.75]). The most consistent adherent groups were much lower than 50% of the total population and equal to 12.5–27.0% of the population, with the fast declining nonadherent pattern in the 5.6–35.0% of the population and the intermediate nonadherence equal to ~61% of the population. Conclusion: Our findings confirm that medication adherence is of major concern among multimorbid patients, with adherence levels lower much than those reported in the literature. There are 3 patterns of intermediate nonadherence (slow decline, occasional users, early gap/increased adherence), which were found to be eligible for interventions aimed at improving their adherence levels for each medication class. This may help improve cardiovascular medication adherence using large medication nonadherence improvement programmes. [ABSTRACT FROM AUTHOR]

Background: The atrial fibrillation better care (ABC) pathway is a simple, comprehensive framework that facilitates provision of integrated care for atrial fibrillation (AF) patients. Objective: We evaluated management of AF patients in a secondary prevention cohort using the ABC pathway and examined the impact of ABC adherence on clinical outcomes. Methods: The Chinese Patients with Atrial Fibrillation registry is a prospective registry conducted in 44 sites across China between October 2014 and December 2018. The primary outcome was the composite of all‐cause mortality/any thromboembolism (TE), all‐cause death, any TE and major bleeding at 1 year. Results: Of the 6420 patients, 1588 (24.7%) had a prior stroke or transient ischemic attack and were identified as the secondary prevention cohort. After excluding 793 patients due to insufficient data, 358 (22.5%) were ABC compliant and 437 (27.5%) ABC noncompliant. ABC adherence was associated with a significantly lower risk of the composite outcome of all‐cause death/TE, odds ratio (OR) 0.28 (95% confidence interval [CI]: 0.11–0.71) and all‐cause death, OR 0.29 (95% CI: 0.09–0.90). Significant differences were not observed for TE, OR 0.27 (95% CI: 0.06–1.27) and major bleeding, OR 2.09 (95% CI: 0.55–7.97). Age and prior major bleeding were significant predictors of ABC noncompliance. Health‐related quality of life (QOL) was higher in the ABC compliant group versus the noncompliant group (EQ score 0.83 ± 0.17 vs. 0.78 ± 0.20; p =.004). Conclusion: ABC pathway adherence in secondary prevention AF patients was associated with a significantly lower risk of the composite outcome of all‐cause death/TE and all‐cause death, as well as better health‐related QOL. [ABSTRACT FROM AUTHOR]

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

Introduction: Understanding symptom patterns in atrial fibrillation (AF) can help in disease management. We report on the application of natural language processing (NLP) to electronic medical records (EMRs) to capture symptom reports in patients with newly diagnosed (incident) AF. Methods and Results: This observational retrospective study included adult patients with an index diagnosis of incident AF during January 1, 2016 through June 30, 2018, in the Optum datasets. The baseline and follow‐up periods were 1 year before/after the index date, respectively. The primary objective was identification of the following predefined symptom reports: dyspnea or shortness of breath; syncope, presyncope, lightheadedness, or dizziness; chest pain; fatigue; and palpitations. In an exploratory analysis, the incidence rates of symptom reports and cardiovascular hospitalization were assessed in propensity‐matched patient cohorts with incident AF receiving first‐line dronedarone or sotalol. Among 30 447 patients with an index AF diagnosis, the NLP algorithm identified at least 1 predefined symptom in 9734 (31.9%) patients. The incidence rate of symptom reports was highest at 0–3 months post‐diagnosis and lower at >3–6 and >6–12 months (pre‐defined timepoints). Across all time periods, the most common symptoms were dyspnea or shortness of breath, followed by syncope, presyncope, lightheadedness, or dizziness. Similar temporal patterns of symptom reports were observed among patients with prescriptions for dronedarone or sotalol as first‐line treatment. Conclusion: This study illustrates that NLP can be applied to EMR data to characterize symptom reports in patients with incident AF, and the potential for these methods to inform comparative effectiveness. [ABSTRACT FROM AUTHOR]

Background: Evidence about the associations between obesity severity, metabolic status and risk of incident cardiovascular disease (CVD) in adults with obesity remains limited. Methods: The study included 109,301 adults with obesity free of prior CVD based on the UK Biobank cohort. Metabolic status was categorized into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes) and metabolically unhealthy obesity (MUO). Obesity severity was classified into three levels: class I (body mass index of 30.0–34.9 kg/m2), II (35.0–39.9) and III (≥40.0). Cox proportional hazards models were used for analyses. Results: There were 8059 incident CVD events during a median follow‐up of 8.1 years. MUO was significantly associated with a 74% increased CVD risk compared with MHO (HR = 1.74, 95% CI: 1.62–1.83). There was a significant interaction between obesity severity and metabolic status on an additive scale regarding CVD risk. When taking class I obesity as reference, class II was nonsignificantly associated with an increased risk of CVD in the MHO group (HR = 1.07, 95% CI: 0.90–1.27), while class III was significantly related to increased risks of CVD (HR = 1.48, 95% CI: 1.12–1.96). In the MUO group, both classes II and III were significantly related to increased risks of CVD. Significant subgroup effects of age (p =.009) and sex (p =.047) were observed among participants with MUO but not in the MHO group. Conclusions: Both elevated obesity severity and MUO were significantly associated with increased risks of CVD in adults with obesity, while metabolic status could modify the relationship between obesity severity and CVD risk. More research is needed to further clarify the relationship. [ABSTRACT FROM AUTHOR]

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

Aim: To investigate the impact of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes. Methods: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity‐score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non‐SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all‐cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest. Results: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non‐SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68‐0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all‐cause mortality (HR 0.61, 95% CI 0.58‐0.64), cardiac arrest (HR 0.70, 95% CI 0.63‐0.78), incident AF (HR 0.81, 95% CI 0.76‐0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88‐0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88‐0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71‐0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88‐1.00). Conclusion: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to develop and validate a new bleeding risk score to predict warfarin‐associated major bleeding for patients with mitral valve stenosis with atrial fibrillation (MSAF) or mechanical heart valves (MHV). Methods: A multicentre, retrospective cohort study was conducted at 3 hospitals in Thailand. Adult patients with MSAF or MHV receiving warfarin for ≥3 months during 2011–2015 were identified. Data collection and case validation were performed electronically and manually. Potential variables were screened using the least absolute shrinkage and selection operator. Multivariate logistic regression analysis using stepwise backward selection was used to construct a risk score. Predictive discrimination of the score was evaluated using the C‐statistic. Calibration was assessed using the Hosmer–Lemeshow goodness‐of‐fit test. Results: There were 1287 patients (3903.41 patient‐year of follow‐up), with 192 experiencing bleeding (4.92 event/100 patient‐year) in the derivation cohort. A new bleeding risk score termed, the HEARTS‐60 + 3 score (hypertension/history of bleeding; external factors, e.g., alcohol/drugs [aspirin or nonsteroidal anti‐inflammatory drugs]; anaemia/hypoalbuminaemia; renal/hepatic insufficiency; time in therapeutic range of <60%; stroke; age ≥60 y; target international normalized ratio of 3.0 [2.5–3.5]), was developed and showed good predictive performance (C‐statistic [95% confidence interval] of 0.88 [0.85–0.91]). In the external validation cohort of 832 patients (2018.45 patient‐year with a bleeding rate of 4.31 event/100 patient‐year), the HEARTS‐60 + 3 score showed a good predictive performance with a C‐statistic (95% confidence interval) of 0.84 (0.81–0.89). Conclusion: The HEARTS‐60 + 3 score shows a potential as a bleeding risk prediction score in MSAF or MHV patients. [ABSTRACT FROM AUTHOR]

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

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

Aim: To clarify the importance of HbA1c reduction and antidiabetic drug use in preventing major adverse cardiovascular events (MACE) for patients with type 2 diabetes (T2D). Materials and Methods: We conducted an updated systematic review of contemporary large randomized controlled trials assessing the relative efficacy and safety of antidiabetic drugs with less hypoglycaemia risk in adult T2D patients. Mixed‐effects meta‐regression was performed to examine the associations of HbA1c reduction with subsequent risk of macrovascular and microvascular events. We evaluated the potential mediating role of HbA1c reduction in the relationship between antidiabetic drugs and MACE. Results: Eighteen placebo‐controlled trials comprising 155 610 participants were included. The effects of treatment differed among antidiabetic drug classes for most adverse outcomes with high heterogeneity (I2: 63.7%‐95.8%). Mean HbA1c reduction was lowest with dipeptidyl peptidase‐4 inhibitors (0.30%), followed by sodium‐glucose co‐transporter‐2 inhibitors (0.46%), and was highest with glucagon‐like peptide‐1 receptor agonists (0.58%) and thiazolidinediones (0.60%). Lower relative risks of MACE were significantly associated with larger reductions in achieved HbA1c (β −0.3182; 95% CI: −0.5366 to −0.0998; P =.0043), even after adjusting for drug classes. When considering HbA1c lowering as a mediator to be controlled, beneficial effects owing to specific antidiabetic treatment for MACE were not observed (χ2 = 1.4494; P =.6940). The proportion mediated by HbA1c reduction was 50.0%‐63.5% for these antidiabetic agents. Conclusions: The main benefits of antidiabetic agents might result from the reduction in blood sugar levels and are generally independent of drugs used. Risk reduction in MACE was proportional to the magnitude of HbA1c decrease conferred by antidiabetic agents with less hypoglycaemic hazard. [ABSTRACT FROM AUTHOR]

Aims: Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta‐analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs. Methods: Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random‐effects model was used. Results: We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68–0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83–0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80–0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77–0.89) and apixaban (HR: 0.75, 95% CI: 0.65–0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03–1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31–1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44–0.52), apixaban (HR: 0.60, 95% CI: 0.49–0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65–0.81) were associated with lower risk of ICH compared to VKA. Conclusion: Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA. [ABSTRACT FROM AUTHOR]

Aims: The evidence of a protective effect of proton‐pump inhibitor (PPI) in oral anticoagulant (OAC)‐treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta‐analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy. Methods: A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random‐effect meta‐analysis and reported as odds ratios and 95% confidence interval. Results: A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62–0.74) for total and 0.68 (0.63–0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non‐Asians (P‐for‐difference, total GIB =.70, major GIB =.75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24–44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti‐inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS‐BLED ≥3 or underlying gastrointestinal diseases. Conclusion: In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB. [ABSTRACT FROM AUTHOR]

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