Real-world evidence of early rhythm control in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The favorable benefits of early rhythm control (ERC) therapy in newly diagnosed patients with atrial fibrillation (AF) have been demonstrated in the EAST-AFNET 4 trial. However, the generalizability and applicability of ERC in real-world clinical settings remain inconclusive. METHODS: We conducted a systematic search of the PubMed and Embase databases to identify observational studies published between January 2020 and February 2024 that focused on real-world evidence pertaining to ERC. The effectiveness and safety outcomes in our study were analogous to those evaluated in the EAST-AFNET 4 trial. RESULTS: A total of 4 observational studies that fulfilled the inclusion criteria of EAST-AFNET 4 were included, involving 130,970 patients with AF, 30.7% of whom received ERC therapy. In our pooled analysis using the fixed-effects model, compared with rate control, ERC significantly decreased the occurrence risk of the primary composite outcome (hazard ratio [HR] 0.86, 95% confidence interval[CI] 0.82-0.91), cardiovascular death (HR 0.87, 95% CI 0.78-0.98), stroke (HR 0.80, 95% CI 0.73-0.87), and hospitalization with worsening heart failure (HR 0.91, 95% CI 0.84-0.99) or acute coronary syndrome (HR 0.72, 95% CI 0.59-0.87). In terms of safety outcomes, there were no differences in the composite safety outcome (HR 1.00, 95% CI 0.95-1.05) and all-cause death (HR 0.93, 95% CI 0.82-1.06) between the two studied groups. CONCLUSIONS: ERC therapy showed favorable effectiveness outcomes compared with rate control, whereas the safety outcomes between the two therapeutic strategies did not differ significantly, supporting the benefits of ERC therapy over rate control in selected real-world patients with AF. REGISTRATION: The study protocol was registered to PROSPERO (CRD42023443569).

Performance of HAS-BLED and DOAC scores to predict major bleeding events in atrial fibrillation patients treated with direct oral anticoagulants: A report from a prospective European observational registry.

BACKGROUND: The DOAC score has been recently proposed for bleeding risk stratification of patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). OBJECTIVE: To compare the performance of HAS-BLED and DOAC score in predicting major bleeding events in a contemporary cohort of European AF patients treated with DOAC. METHODS: We included patients derived from a prospective observational registry of European AF patients. HAS-BLED and DOAC scores were calculated as per the original schemes. Our primary endpoint was major bleeding events. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the scores. RESULTS: A total of 2834 AF patients (median age [IQR] 69 [62-77] years; 39.6 % female) treated with DOAC were included in the analysis. According to the HAS-BLED score, 577 patients (20.4 %) were categorized as very low risk of bleeding, as compared to 1276 (45.0 %) according to DOAC score. A total of 55 major bleeding events occurred with an overall incidence of 1.04 per 100 patient-years. Both scores showed only a modest ability for the prediction of bleeding events (HAS-BLED area under the curve [AUC], 0.65, 95 % confidence interval [CI] 0.55-0.70; DOAC score AUC 0.62, 95 % CI 0.59-0.71, p for difference = 0.332]. At calibration analysis, the DOAC score showed modest calibration, especially for patients at high risk, when compared to HAS-BLED. CONCLUSION: In a contemporary cohort of DOAC-treated AF patients, both HAS-BLED and DOAC scores only modestly predicted the occurrence of major bleeding events. Our results do not support the preferential use of DOAC score over HAS-BLED.

Stroke outcomes following cardiac and aortic surgery are improved by the involvement of a stroke team.

OBJECTIVES: Post-cardiac and aortic surgery stroke is often underreported. We detail our single-centre experience the following introduction of comprehensive consultant-led daily stroke service, to demonstrate the efficacy of a stroke team in recovery from stroke following cardiac and aortic surgeries. METHODS: This retrospective, single-centre observational cohort study analysed consecutive patients undergoing cardiac and aortic surgery at our institution from August 2014 to December 2020. Main outcomes included stroke rate, predictors of stroke, and neurological deficit resolution or persistence at discharge and clinic follow-up. RESULTS: A total of 12,135 procedures were carried out in the reference period. Among these, 436 (3.6%) suffered a stroke. Overall survival to discharge and follow-up were 86.0% and 84.0% respectively. Independent risk factors for post-operative stroke included advanced age (OR 1.033, 95% CI [1.023, 1.044], p < .001), female sex (OR 1.491, 95% [1.212, 1.827], p < .001), history of previous cardiac surgeries (OR 1.670, 95% CI [1.239, 2.218], p < .001), simultaneous coronary artery bypass graft + valve procedures (OR 1.825, 95% CI [1.382, 2.382], p < .001) and CPB time longer than 240 min (OR 3.384, 95% CI [2.413, 4.705], p < .001). Stroke patients managed by the multidisciplinary team demonstrated significantly higher rates of survival at discharge (87.3% vs. 61.9%, p = .001). CONCLUSIONS: Perioperative stroke can be debilitating immediately long term. The involvement of specialist stroke teams plays a key role in reducing the long-term burden and mortality of this condition.

Systematic Review and Meta-Analysis of Prehospital Machine Learning Scores as Screening Tools for Early Detection of Large Vessel Occlusion in Patients With Suspected Stroke.

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

Five-year risk of all-cause death and cardiovascular events in women with gestational diabetes and hypertensive disorders of pregnancy.

BACKGROUND: . The long-term impact of gestational complications on cardiovascular outcomes in women remains a subject of debate. AIM: To assess the 5-year risk of cardiovascular events and all-cause mortality in women with gestational diabetes and hypertension. METHODS: Retrospective study utilising an health research network(TriNetX). The primary outcome was the composite risk of a cardiovascular event within 5 years with secondary outcomes being its components (all-cause death, acute heart failure, myocardial infarction, ischaemic stroke). Women were categorised into 8 different groups based on the ICD-codes for pregnancy related complications recorded 9 months before the delivery:1) gestational diabetes,2) gestational hypertension,3) gestational diabetes with gestational hypertension,4) gestational diabetes with gestational hypertension without pre-eclampsia or eclampsia,5) gestational diabetes with pre-eclampsia or eclampsia,6) gestational hypertension without pre-eclampsia or eclampsia,7) pre-eclampsia or eclampsia,and 8) no gestational complications. Cox-regression analyses were used to produce hazard ratios (HRs) and 95 % confidence intervals (CI) before and after propensity score matching (PSM). RESULTS: We identified, 24,402 women with gestational diabetes and gestational hypertension and 920,478 without gestational complications. After PSM, compared to women without pregnancy complications, women with gestational diabetes and gestational hypertension had a higher 5-year risk of composite outcome(HR 2.25,95 %CI 2.02-2.51), all-cause death(HR 1.64,95 %CI 1.31-2.06), acute heart failure(HR 2.06,95 %CI 1.69-2.52), myocardial infarction(HR 2.46,95 %CI 1.93-3.14), and ischemic stroke(HR 2.37,95 %CI 2.06-2.74). Women who experienced pre-eclampsia or eclampsia showed the highest risk of primary and secondary outcomes. CONCLUSIONS: Gestational complications are associated with worse long-term cardiovascular outcomes. There is a clear call to action required to improve the longitudinal management of gestational complications to improve women's long-term health.

Journal requirement for data sharing statements in clinical trials: a cross-sectional study.

OBJECTIVE: Data sharing statements are considered routine in clinical trial reporting, and represent a step towards data transparency. The International Committee of Medical Journal Editors (ICMJE) require clinical trials to publish data sharing statements. To assess requirement for data sharing statements by biomedical journals, and to explore associations between journal characteristics and requirement for data sharing statements. STUDY DESIGN AND SETTING: In this cross-sectional study, we included all biomedical journals that published clinical trials from January 1st, 2019 to December 31st, 2022 and that were indexed by the Journal Citation Reports. The study outcome was the journal requirement for data sharing statements. Multivariable logistic regression analyses were used to assess the relationship between journal characteristics and requirement for data sharing statements. RESULTS: Of the 3,229 biomedical journals included in the analyses, 2,345 (72.6%) required authors to include data sharing statements. Journals published in the UK (OR, 3.19 [95% CI, 2.43 to 4.22]) and endorsing the Consolidated Standards of Reporting Trials (CONSORT) (OR, 3.30 [95% CI, 2.78 to 3.92]) had greater odds of requiring data sharing statements. Journals that were Open Access, non-English language, in the Journal Citation Reports group of clinical medicine, and on the ICMJE list had lower odds of requiring data sharing statements, with ORs ranging from 0.18 to 0.81. CONCLUSION: Despite ICMJE recommendations, more than 27% of biomedical journals do not require clinical trials to include data sharing statements, highlighting room for improved transparency.

Risk of adverse events in anticoagulated patients with atrial fibrillation and non-alcoholic fatty liver disease.

BACKGROUND: The clinical impact of Nonalcoholic fatty liver disease(NAFLD) in patients with atrial fibrillation(AF) is still controversial. AIM: To evaluate the 1-year risk of all-cause death, thromboembolic events, and bleeding in AF-NAFLD patients. METHODS: Retrospective study with a health research network(TriNetX). AF patients on oral anticoagulation(OAC) were categorized according to the presence of NAFLD into two groups. The primary outcomes were the 1-year risks of: i) a composite cardiovascular outcome (all-cause death, myocardial infarction, stroke, cardiac arrest, and pulmonary embolism); and ii) a composite hemorrhagic outcome(intracranial hemorrhage and gastrointestinal bleeding). Cox regression analysis before and after propensity-score-matching(PSM) was used to estimate Hazard Ratio(HR) and 95% confidence intervals(95%CI). Sensitivity analyses investigated the risk associated with cirrhosis, thrombocytopenia, and type of OAC(warfarin vs non-vitamin K antagonist oral anticoagulants(NOAC). RESULTS: We identified 22,636 AF-NAFLD patients (69±12 years, 46.7% females) and 391,014 AF patients without liver disease(72±12 years, 42.7% females). NAFLD was associated with a higher risk of composite cardiovascular (HR 1.54,95%CI 1.47-1.61) and hemorrhagic (HR 1.56,95%CI 1.42-1.72) outcomes. This was consistent also for all the single outcomes. Cirrhotic and thrombocytopenic AF-NAFLD patients showed the highest risks. Compared to AF-NAFLD patients on NOAC, those on warfarin were associated with a higher risk of cardiovascular and hemorrhagic outcomes. CONCLUSION: In AF patients, NAFLD is associated with a higher 1-year risk of adverse events, with the risk of adverse events progressively increasing from non-cirrhotic to cirrhotic and from non-thrombocytopenic to thrombocytopenic patients. NOACs were associated with a better effectiveness and safety profile compared to warfarin.

Phenotypes of Polish primary care patients using hierarchical clustering: Exploring the risk of mortality in the LIPIDOGEN2015 study cohort.

BACKGROUND: Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all-cause mortality in primary care. METHODS: The baseline cohort of the LIPIDOGEN2015 sub-study involved 1779 patients recruited by 438 primary care physicians. To identify different phenotype clusters, we used hierarchical clustering and investigated differences between clinical characteristics and mortality between clusters. We then performed causal analyses using causal mediation analysis to explore potential mediators between different clusters and all-cause mortality. RESULTS: A total of 1756 patients were included (mean age 51.2, SD 13.0; 60.3% female), with a median follow-up of 5.7 years. Three clusters were identified: Cluster 1 (n = 543) was characterised by overweight/obesity (body mass index ≥ 25 kg/m2), older (age ≥ 65 years), more comorbidities; Cluster 2 (n = 459) was characterised by non-overweight/obesity, younger, fewer comorbidities; Cluster 3 (n = 754) was characterised by overweight/obesity, younger, fewer comorbidities. Adjusted Cox regression showed that compared with Cluster 2, Cluster 1 had a significantly higher risk of all-cause mortality (HR 3.87, 95% CI: 1.24-15.91), whereas this was insignificantly different for Cluster 3. Causal mediation analyses showed that decreased protein thiol groups mediated the hazard effect of all-cause mortality in Cluster 1 compared with Cluster 2, but not between Clusters 1 and 3. CONCLUSION: Overweight/obesity older patients with more comorbidities had the highest risk of long-term all-cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long-term follow-up, providing a basis for stratified phenotypic risk management.

Natriuretic peptides and C-reactive protein in in heart failure and malnutrition: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) and malnutrition exhibit overlapping risk factors, characterized by increased levels of natriuretic peptides and an inflammatory profile. The aim of this study was to compare the differences in plasma brain natriuretic peptide (BNP), N-terminal-pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) in patients with HF and malnutrition versus normal nutrition. METHODS: From inception until July 2023, the databases, PubMed, Scopus, Web of Science, and Cochrane Library were searched. To examine the association among malnutrition [controlling nutritional status (CONUT) score ≥2; Geriatric Nutritional Risk Index (GNRI) score <92] with BNP, NT-proBNP and CRP in patients with HF, a meta-analysis using a random-effects model was conducted (CRD42023445076). RESULTS: A significant association of GNRI with increased levels of BNP were demonstrated [mean difference (MD): 204.99, 95% confidence interval (CI) (101.02, 308.96, I2 = 88%, P < 0.01)], albeit no statistically significant findings were shown using CONUT [MD: 158.51, 95% CI (-1.78 to 318.79, I2 = 92%, P = 0.05)]. GNRI [MD: 1885.14, 95% CI (1428.76-2341.52, I2 = 0%, P < 0.01)] and CONUT [MD: 1160.05, 95% CI (701.04-1619.07, I2 = 0%, P < 0.01)] were associated with significantly higher levels of NT-proBNP. Patients with normal GNRI scores had significantly lower levels of CRP [MD: 0.50, 95% CI (0.12-0.88, I2 = 87%, P = 0.01)] whereas significantly higher levels of CRP were observed in those with higher CONUT [MD: 0.40, 95% CI (0.08-0.72, I2 = 88%, P = 0.01)]. Employing meta-regression, age was deemed a potential moderator between CRP and GNRI. CONCLUSIONS: Normal nutrition scores in patients with HF are linked to lower BNP, NT-proBNP, and CRP levels compared with malnourished counterparts. Despite the significant link between CRP and malnutrition, their relationship may be influenced in older groups considering the sensitivity of GNRI due to ageing factors.

Association between changes in renal function and clinical outcomes in anticoagulated atrial fibrillation patients with marginal renal function. A nationwide observational cohort study.

Background: Renal function is one of the crucial components for determining the dose and type of oral anticoagulants in atrial fibrillation (AF) patients, and is also closely associated with the risks of stroke and bleeding. This study aimed to assess renal function changes and their impact on clinical outcomes in anticoagulated AF patients with marginal renal function. Methods: From a Korean claims database, patients with AF on anticoagulants and a baseline eGFR of 45 to <60 ml/min/1.73 m2 were studied. Patients were grouped by changes in renal function over two years-maintained, improved (eGFR >60 ml/min/1.73 m2), or worsened (eGFR <45 ml/min/1.73 m2)-the study analyzed outcomes including ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and a composite of clinical outcomes. Results: A total of 5,126 patients were included in the study: 2,170 (42.3%) in the maintained group, 2,276 (44.4%) in the improved group, and 680 (13.1%) in the group with worsened renal function. The worsened group was older and had more prevalent comorbidities than other groups. After multivariable adjustment, the worsened group was associated with significantly higher risks of major bleeding (adjusted hazard ratio, 95% confidence interval; 1.46, 1.03-2.07, p = 0.035), ESRD (1.49, 1.24-1.80, p < 0.001), all-cause death (9.29, 4.92-17.6, p < 0.001), and the composite outcome (1.57, 1.36-1.83, p < 0.001). Conclusions: In anticoagulated AF patients with marginal renal function, a substantial proportion of patients experienced renal function decline below eGFR 45 ml/min/1.73 m2 within 2 years. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death, and the composite outcome compared to those who maintained their baseline renal function.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

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.

Integrated care policy recommendations for complex multisystem long term conditions and long COVID.

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.

Statin use is associated with a lower risk of all-cause death in patients with breast cancer treated with anthracycline containing regimens: a global federated health database analysis.

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.

Outcomes of vascular closure devices for femoral venous hemostasis following catheter ablation of atrial fibrillation.

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.