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Valproate is the most effective treatment for idiopathic generalized epilepsy. Current guidance precludes its use in females of childbearing potential, unless other treatments are ineffective or not tolerated, because of high teratogenicity. This risk was recently extended to males. New guidance will limit use both in males and females aged <55 years, resulting in withdrawal of valproate from males already taking it, as occurs for females. Whether there are risks of personal harm (including injury or death) associated with valproate withdrawal has not yet been quantified for males or females ON valproate, meaning clinicians cannot reliably counsel either sex when discussing valproate withdrawal with them, despite that this concern may be at the forefront of patients' and clinicians' minds. We assessed whether there are any morbidity or mortality risks associated with valproate withdrawal in young males and females. We performed a retrospective cohort study of internationally derived electronic health data within the TriNetX Global Collaborative Network. Included were males and females aged 16–54 years with ≥1 epilepsy disease or symptom code between 1 December 2017 and 1 December 2018, and ≥2 valproate prescriptions over the preceding 2 years (1 January 2015–30 November 2017). Five-year propensity-matched risks of mortality and a range of morbidity outcomes were compared between those remaining ON versus withdrawn from valproate during the 1 December 2017–1 December 2018 recruitment period, regardless of whether switched to another antiseizure medication. Survival analysis was undertaken using Cox-proportional hazard models, generating hazard ratios (HRs) with 95% confidence intervals (CIs). In total, 8991 males and 5243 females taking valproate were recruited. Twenty-eight per cent of males and 36% of females were subsequently withdrawn from valproate. Valproate withdrawal was associated with significantly increased risks of emergency department attendance [HRs overall: 1.236 (CI 1.159–1.319), males: 1.181 (CI 1.083–1.288), females: 1.242 (CI 1.125–1.371)], hospital admission [HRs overall: 1.160 (CI 1.081–1.246), males: 1.132 (CI 1.027–1.249), females: 1.147 (CI 1.033–1.274)], falls [HRs overall: 1.179 (CI 1.041–1.336), males: 1.298 (CI 1.090–1.546)], injuries [HRs overall: 1.095 (CI 1.021–1.174), males: 1.129 (CI 1.029–1.239)], burns [HRs overall: 1.592 (CI 1.084–2.337)] and new-onset depression [HRs overall 1.323 (CI 1.119–1.565), females: 1.359 (CI 1.074–1.720)]. The risk of these outcomes occurring was 1%–7% higher in those withdrawn from valproate than in those remaining ON valproate. Overall, valproate withdrawal was not associated with increased mortality. These results may help patients and clinicians have a more informed discussion about personal safety when considering valproate withdrawal. [ABSTRACT FROM AUTHOR]

Context The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events. Objective The relevant outcomes associated with the use of a sodium–glucose cotransporter-2 inhibitor (SGLT2i) vs glucagon-like peptide-1 receptor agonists (GLP-1RAs) among patients with type 2 diabetes (T2D) with/without concomitant AF remain unknown. Methods In this nationwide retrospective cohort study from the Taiwan National Health Insurance Research Database, there were 344 392 and 31 351 patients with T2D without AF, and 11 462 and 816 T2D patients with AF treated with SGLT2is and GLP-1RAs, respectively, from May 1, 2016, to December 31, 2019. Patients were followed from the drug index date until the occurrence of study events, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. We used propensity score–stabilized weight to balance covariates across the 2 medication groups. Results The incidence rate of all study outcomes in patients with concomitant AF was much higher than in those without concomitant AF. For the AF cohort, SGLT2i vs GLP-1RA was associated with a lower risk of hospitalization for heart failure (HF) (2.32 vs 4.74 events per 100 person-years; hazard ratio [HR] 0.48, 95% CI 0.36-0.66), with no benefit seen for the non-AF cohort (P for homogeneity <.01). SGLT2i vs GLP-1RA was associated with a lower risk of composite kidney outcomes both in the AF (0.38 vs 0.79 events per 100 person-years; HR 0.47; 95% CI 0.23-0.96) and the non-AF cohorts (0.09 vs 0.18 events per 100 person-years; HR 0.53; 95% CI 0.43-0.64). There were no significant differences in the risk of major adverse cardiovascular events and all-cause mortality in those who received SGLT2i compared with GLP-1RA for the AF or non-AF cohorts. Conclusion Considering the high risk of developing HF and/or high prevalence of concomitant HF in patients with concomitant diabetes and AF, whether SGLT2is should be the preferred treatment to GLP-1RAs for such a high-risk population requires further investigation. [ABSTRACT FROM AUTHOR]

Background: The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. Objective: To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. Methods: This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. Results: In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8–7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006–1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001–1.002]; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 [1.003–1.009]; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 [1.002–1.012]; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 [1.009–1.046]; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 [1.012–1.036]; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 [1.006–1.032]; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 [0.996–0.999]; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 [0.959–0.991]; P = 0.002) and lignoceric acid (24:0) (HR 0.992 [0.984–0.999]; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality. Conclusions: In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality. [ABSTRACT FROM AUTHOR]

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

Background: The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. Objective: To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. Methods: This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. Results: In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8–7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006–1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001–1.002]; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 [1.003–1.009]; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 [1.002–1.012]; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 [1.009–1.046]; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 [1.012–1.036]; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 [1.006–1.032]; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 [0.996–0.999]; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 [0.959–0.991]; P = 0.002) and lignoceric acid (24:0) (HR 0.992 [0.984–0.999]; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality. Conclusions: In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia). Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1–2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1–2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke. Results: 2105 people with DM were included [median age 60 (IQR 45–70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06–13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (Pint=0.824), but more pronounced in individuals aged < 65 years compared to older adults (Pint= 0.028). Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach. [ABSTRACT FROM AUTHOR]

Aims Compliance with integrated care based on the Atrial fibrillation Better Care (ABC) pathway has been associated with improved clinical outcomes. The primary objective of this study was to compare clinical outcomes of AF patients according to the compliant status of each component of the ABC pathway in a hierarchical win ratio approach. Methods and results We studied AF patients in the COOL-AF registry. Each patient was followed every 6 months until 3 years. A win ratio analysis was performed, as not all clinical outcomes are equivalent. The hierarchical outcomes were (1) all-cause death, (2) intracranial haemorrhage (ICH), (3) ischaemic stroke/systemic embolism, (4) non-ICH major bleedings, and (5) acute myocardial infarction or heart failure. We also assessed win ratio and win proportion variance over the follow-up time, and the variations over time. A total of 3405 patients (mean age 67.8 ± 11.3; 41.8% female) were studied. Win ratio of ABC-compliant (all three components) vs. ABC-not-compliant was 1.57 (1.35–1.83), P < 0.001. When adding time in therapeutic range (TTR) data for compliant criteria for those who were on warfarin, the win ratio increased to 2.28 (1.89–2.75), P < 0.001. The A-compliant group (plus TTR data), B-compliant, and C-compliant had the win ratio of 1.81 (1.51–2.12), 1.82 (1.53–2.16), and 1.39 (1.18–1.62), all P < 0.001, compared to not compliant group. Conclusion Management of AF patients according to each component of the ABC pathway is associated with better clinical outcomes compared to those non-compliant to ABC pathway. This finding underscores the importance of a holistic management approach strategy for AF patients. [ABSTRACT FROM AUTHOR]

Aims The concept of "atrial cardiomyopathy" (AtCM) had been percolating through the literature since its first mention in 1972. Since then, publications using the term were sporadic until the decision was made to convene an expert working group with representation from four multinational arrhythmia organizations to prepare a consensus document on atrial cardiomyopathy in 2016 (EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication). Subsequently, publications on AtCM have increased progressively. Methods and results The present consensus document elaborates the 2016 AtCM document further to implement a simple AtCM staging system (AtCM stages 1–3) by integrating biomarkers, atrial geometry, and electrophysiological changes. However, the proposed AtCM staging needs clinical validation. Importantly, it is clearly stated that the presence of AtCM might serve as a substrate for the development of atrial fibrillation (AF) and AF may accelerates AtCM substantially, but AtCM per se needs to be viewed as a separate entity. Conclusion Thus, the present document serves as a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) to contribute to the evolution of the AtCM concept. [ABSTRACT FROM AUTHOR]

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30 days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10 years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61–0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32–0.64) compared to azithromycin non-users (n = 2434, 72 ± 11 years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study. [ABSTRACT FROM AUTHOR]

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]

Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a "target trial") using retrospective observational data. The data will be drawn from ~250m mainly US patients in the TriNetX repository and ~60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16–54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2014–2024, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. Mortality and morbidity outcomes will be assessed and compared between groups over 1–10 years, employing time-to-first-event and recurrent events analyses. A causal prediction model will be developed from these data to aid in predicting the safest alternative antiseizure medications. Together, these findings will optimise informed decision-making about valproate withdrawal and alternative treatment selection, providing immediate and vital information for patients, clinicians and regulators. [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: 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). [ABSTRACT FROM AUTHOR]

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

Introduction: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. Materials and methods: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. Results and conclusions: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39–0.96) and MB (HR: 0.67; 95% CI: 0.50–0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73–1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52–0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs. Key point: • Patients with NVAF may switch to DOACs for effectiveness, safety, or convenience. • Risk of stroke/SE and MB may vary among patients with NVAF who switch to DOACs. • Switching to apixaban had a lower risk of MB than dabigatran/rivaroxaban. • Results may inform DOAC prescribing decisions after warfarin in patients with NVAF. [ABSTRACT FROM AUTHOR]

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

Context The presence of metabolic dysfunction–associated steatotic liver disease (MASLD) in patients with diabetes mellitus (DM) is associated with a high risk of cardiovascular disease, but is often underdiagnosed. Objective To develop machine learning (ML) models for risk assessment of MASLD occurrence in patients with DM. Methods Feature selection determined the discriminative parameters, utilized to classify DM patients as those with and without MASLD. The performance of the multiple logistic regression model was quantified by sensitivity, specificity, and percentage of correctly classified patients, and receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) assessed the model's net benefit for alternative treatments. Results We studied 2000 patients with DM (mean age 58.85 ± 17.37 years; 48% women). Eight parameters: age, body mass index, type of DM, alanine aminotransferase, aspartate aminotransferase, platelet count, hyperuricaemia, and treatment with metformin were identified as discriminative. The experiments for 1735 patients show that 744/991 (75.08%) and 586/744 (78.76%) patients with/without MASLD were correctly identified (sensitivity/specificity: 0.75/0.79). The area under ROC (AUC) was 0.84 (95% CI, 0.82-0.86), while DCA showed a higher clinical utility of the model, ranging from 30% to 84% threshold probability. Results for 265 test patients confirm the model's generalizability (sensitivity/specificity: 0.80/0.74; AUC: 0.81 [95% CI, 0.76-0.87]), whereas unsupervised clustering identified high-risk patients. Conclusion A ML approach demonstrated high performance in identifying MASLD in patients with DM. This approach may facilitate better risk stratification and cardiovascular risk prevention strategies for high-risk patients with DM at risk of MASLD. [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]

Rationale & objective: Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. Study Design: Retrospective cohort study. Setting & participants: Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). Exposure or predictor: Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. Outcomes: Primary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome. Analytical Approach: 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. Results: Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p < 0.0001). Limitations: The data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data. Conclusions: In GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: A protective role of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin. Methods: This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan–Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA1c, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed. Results: SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208). Conclusions/interpretation: Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated retinal imaging are required to determine the causal relationship with these therapies. [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]

Aims Single-lead electrocardiograms (ECGs) can be recorded using widely available devices such as smartwatches and handheld ECG recorders. Such devices have been approved for atrial fibrillation (AF) detection. However, little evidence exists on the reliability of single-lead ECG interpretation. We aimed to assess the level of agreement on detection of AF by independent cardiologists interpreting single-lead ECGs and to identify factors influencing agreement. Methods and results In a population-based AF screening study, adults aged ≥65 years old recorded four single-lead ECGs per day for 1–4 weeks using a handheld ECG recorder. Electrocardiograms showing signs of possible AF were identified by a nurse, aided by an automated algorithm. These were reviewed by two independent cardiologists who assigned participant- and ECG-level diagnoses. Inter-rater reliability of AF diagnosis was calculated using linear weighted Cohen's kappa (⁠ κ w ⁠). Out of 2141 participants and 162 515 ECGs, only 1843 ECGs from 185 participants were reviewed by both cardiologists. Agreement was moderate: κ w = 0.48 (95% confidence interval, 0.37–0.58) at participant level and κ w = 0.58 (0.53–0.62) at ECG level. At participant level, agreement was associated with the number of adequate-quality ECGs recorded, with higher agreement in participants who recorded at least 67 adequate-quality ECGs. At ECG level, agreement was associated with ECG quality and whether ECGs exhibited algorithm-identified possible AF. Conclusion Inter-rater reliability of AF diagnosis from single-lead ECGs was found to be moderate in older adults. Strategies to improve reliability might include participant and cardiologist training and designing AF detection programmes to obtain sufficient ECGs for reliable diagnoses. [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]

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]

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]

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

Anthracyclines are associated with enhanced oxidative stress responsible for adverse events in patients with breast cancer. However, no study has investigated the potential anti-inflammatory role of statins in counteracting anthracycline toxicity. In this retrospective study utilizing a federated health network (TriNetX), patients with breast cancer (ICD code C50) treated with anthracyclines were categorized into two groups: statin users (for at least 6 months); and statin non-users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the risk of myocardial infarction, stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). We identified 3,701 statin users (68.8 ± 10.4 years) and 37,185 statin non-users (59.6 ± 12.8 years). After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.82, 95% CI 0.74–0.91) compared to statins non-users. Analyzing the risk for secondary outcomes, only the risk of stroke was significantly increased in statin users (HR 1.27, 95% CI 1.01–1.61), while no associations were found for the other cardiovascular events. The risk of all-cause death in statin users was the lowest during the first year after the anthracycline's initiation. No significant difference was found between lipophilic and hydrophilic statins. In patients with breast cancer treated with anthracyclines, statin use is associated with a reduced risk of all-cause death. Prospective studies are needed to investigate the potential beneficial effect of statin initiation in cancer patients without other indications. [ABSTRACT FROM AUTHOR]

Introduction: Patient-reported treatment burden (TBN) refers to the patient's time and effort invested in the management of their chronic health conditions. The aim of this research was to explore TBN in patients with coronary artery disease (CAD). Methods: Consecutive patients with chronic medical condition(s) were invited to complete the study questionnaires (TBN and EQ-5D). Results: Of 514 enrolled patients, 116 (22.6%) patients had CAD. The mean TBN score for CAD vs. non-CAD was 40.49 ±21.54 and 46.17 ±21.44 (p = 0.023), respectively. Conclusions: Patients with CAD could have a lower TBN in comparison to patients with other chronic medical conditions. [ABSTRACT FROM AUTHOR]

Patients with heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM) have an increased risk of adverse events, including thromboembolism. In this analysis, we aimed to explore the association between DM and HFrEF using data from the "Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction" (WARCEF) trial. We analyzed factors associated with DM using multiple logistic regression models and evaluated the effect of DM on long-term prognosis, through adjusted Cox regressions. The primary outcome was the composite of all-cause death, ischemic stroke, or intracerebral hemorrhage; we explored individual components as the secondary outcomes and the interaction between treatment (warfarin or aspirin) and DM on the risk of the primary outcome, stratified by relevant characteristics. Of 2294 patients (mean age 60.8 (SD 11.3) years, 19.9% females) included in this analysis, 722 (31.5%) had DM. On logistic regression, cardiovascular comorbidities, symptoms and ethnicity were associated with DM at baseline, while age and body mass index showed a nonlinear association. Patients with DM had a higher risk of the primary composite outcome (Hazard Ratio [HR] and 95% Confidence Intervals [CI]: 1.48 [1.24–1.77]), as well as all-cause death (HR [95%CI]: 1.52 [1.25–1.84]). As in prior analyses, no statistically significant interaction was observed between DM and effect of Warfarin on the risk of the primary outcome, in any of the subgroups explored. In conclusion, we found that DM is common in HFrEF patients, and is associated with other cardiovascular comorbidities and risk factors, and with a worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. Methods: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI). Results: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09–1.71), thrombotic events (HR 1.37, 95%CI 1.32–1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33–1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE. Conclusion: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis. [ABSTRACT FROM AUTHOR]

Background and Aims Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. Methods The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. Results Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P <.001), and the incidence decreased both in men and women. In 2007–08, female sex was independently associated with a 20%–30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. Conclusions The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF. [ABSTRACT FROM AUTHOR]

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

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