This study aimed to create a personalized risk assessment model for asymptomatic intracerebral hemorrhage (aICH) following endovascular thrombectomy (ET) to aid clinical decision-making. Between 2019 and 2023, 469 inpatients with acute ischemic stroke (AIS) who received ET treatment within 24 h of onset were recruited from three centers. Patients were randomly assigned to either a training or validation cohort. Univariate and multivariate logistic regression analyses were conducted to identify independent factors for aICH. A nomogram-based model was developed for personalized risk assessment for aICH following ET. The model's usability was evaluated using the receiver operating characteristic (ROC) curve, and a calibration curve was plotted to compare predicted probabilities with actual occurrences. The feasibility of the model for practical clinical application was assessed using decision curve analysis. Four independent risk factors for aICH in patients with AIS following ET were identified: preoperative Alberta Stroke Program Early Computed Tomography score [odds ratio (OR) = 0.686, 95% confidence interval (CI): 0.581-0.811], time from onset to surgery completion (OR = 1.186, 95% CI: 1.097-1.282), intraoperative arterial thrombolysis (OR = 2.405, 95% CI: 1.289-4.487), and Careggi collateral score (OR = 0.560, 95% CI: 0.422-0.743). ROC analysis indicated that the model demonstrated excellent accuracy and discrimination with area under the curve values of 0.812 (95% CI: 0.763-0.861) and 0.896 (95% CI, 0.843-0.949) for the training and validation cohorts, respectively. This nomogram-based model is a reliable personalized tool for evaluating the risk of aICH in patients with AIS after ET.

The hemostatic system and cancer display a tight interconnection, and hemostatic imbalance frequently occurs in patients with cancer. While extensive knowledge about thrombotic risk has been generated, less is known about bleeding risk and associated risk factors. However, bleeding risk is of high significance as patients with cancer frequently receive therapeutic anticoagulation for various indications and/or are candidates for primary thromboprophylaxis. The risk of bleeding in patients with cancer is variable and difficult to assess in clinical practice. Certain clinical settings such as hospitalization, specific underlying risk factors (e.g., tumor type), and medications (e.g., anticoagulation) can contribute to the individual bleeding risk of a patient with cancer. In addition, some dynamic factors such as platelet count or kidney function have an impact. Particularly, data on baseline risk of bleeding are lacking to allow for risk assessment in cancer patients without anticoagulation. In contrast, risk assessment models for the prediction of bleeding events in cancer patients receiving anticoagulation have been developed; however, these have yet to be validated. The recognition of the importance of bleeding risk in cancer patients is growing, leading to an increasing number of studies investigating and reporting bleeding complications. As study designs and reporting of bleeding events vary, it is challenging to offer a clear synthesis of evidence. In this narrative review, we provide an overview of currently available data about incidence, risk factors, and clinical impact of bleeding events in patients with cancer, and critically review risk assessment models for bleeding in cancer patients during anticoagulant therapy.

As the life expectancy of individuals with hemophilia continues to increase, the complexity of balancing bleeding risks and thrombotic management has become increasingly critical in people with hemophilia with or at a high risk of thrombosis. Advances in hemophilia therapies such as extended half-life coagulation factors, non-factor therapies, rebalancing agents, and gene therapy have expanded treatment options for a variety of people with hemophilia. The thrombotic risk of people with hemophilia in general are relatively low as compared to those without hemophilia. However, antithrombotic therapy for prevention and treatment for thrombosis should still be considered in some situations, even in hemophilia. This clinical focus highlights the use of antithrombotic therapy in the management of thrombosis in people with hemophilia. A multidisciplinary, personalized approach is essential for optimizing the safety and efficacy of antithrombotic therapy in people with hemophilia with or at a high risk of thrombosis. High performance computer based multidimensional data analysis may help in establishing the personalized antithrombotic therapy in the future.

High-sensitive (hs-) cardiac troponin assays provide prognostic information in atrial fibrillation (AF) patients. Few studies have explored the impact of long-term rate control therapy on levels of troponin in AF patients without coronary heart disease and heart failure. This substudy of the RATe control in Atrial Fibrillation (RATAF) II study aimed to compare the effects of six months' treatment with diltiazem and metoprolol on hs-troponin I (TnI) levels both at rest and during exercise testing in patients with permanent AF.

This was a parallel-group, randomized, investigator-blinded clinical trial. The cohort consisted of 93 patients (28 women, mean age 71 ± 7 years) with symptomatic, permanent AF with preserved left ventricular systolic function and no coronary heart disease. Participants were randomized in a 1:1 ratio to receive either diltiazem 360 mg (n = 49) or metoprolol 100 mg (n = 44) once daily for six months. Blood tests were drawn at rest and during peak exercise testing at baseline, one month and six months' treatment. This research has been supported by grants from the South-Eastern Norway Regional Health Authority and Vestre Viken Hospital Trust.

Six months' treatment with diltiazem and metoprolol significantly lowered the heart rate at rest and peak exercise. Both treatment groups exhibited a decrease in hs-TnI levels at rest (diltiazem p = 0.008, metoprolol p = 0.03) and peak exercise (diltiazem p < 0.001, metoprolol p = 0.004) at six months compared to baseline levels, with no significant differences observed between the groups.

In patients with permanent AF, six months of rate control therapy with diltiazem or metoprolol lowered levels of hs-TnI. Further research is warranted to determine whether this reduction translates into an improved prognosis.

NCT02695992. Registration date: 2015-04-28.

The hemostatic system is tightly interconnected with cancer. Research has focused predominantly on thrombotic complications, but less is known about bleeding and bleeding risk prediction. Growth differentiation factor (GDF)-15 has previously emerged as a prognostic biomarker for bleeding.

The aim of this study was to investigate the association and predictive ability of GDF-15 for bleeding risk in patients with cancer.

The CAT-BLED (Vienna Cancer, Thrombosis, and Bleeding) study is a prospective, observational cohort study including cancer patients initiating systemic anticancer therapies. Patients were followed for up to 2 years for thrombotic and bleeding events. The primary outcome was major bleeding. GDF-15 was measured at inclusion and at 3 and 6 months of follow-up.

A total of 779 patients (48% women, median age 62 years, 15% on therapeutic anticoagulation) were included. During a median follow-up period of 18 months, 79 patients (10.1%) experienced major bleeding (12-month cumulative incidence 8.8%; 95% CI: 6.7-10.9). Higher GDF-15 levels were independently associated with increased major bleeding risk (adjusted subdistribution HR per doubling: 1.29; 95% CI: 1.04-1.59), and patients with levels greater than the cohort median (1,864 ng/L) had a significantly higher 12-month cumulative incidence (13.1% vs 4.6%; P < 0.001). This association remained robust in follow-up measurements at 3 and 6 months. GDF-15 showed moderate to good discrimination for predicting 6-month major bleeding risk (C statistic = 0.69; 95% CI: 0.60-0.77). GDF-15 was not associated with venous thromboembolism but was strongly associated with mortality (adjusted HR: 1.37; 95% CI: 1.25-1.50).

GDF-15 levels predict major bleeding risk in cancer patients and are not associated with venous thromboembolism, making GDF-15 a particularly promising biomarker for bleeding risk prediction.

The most common treatment method for patients with acute ischemic stroke with large vessel occlusion is mechanical thrombectomy. However, complications such as cerebral edema and hemorrhage transformation after MT can affect patient prognoses, while decompression craniectomy considerably improves patient prognoses. The aim of this study was to identify clinical indicators, such as the neutrophil/high-density lipoprotein cholesterol ratio, to predict DC. A retrospective analysis was conducted in AIS-LVO patients who received MT at Huizhou Central People's Hospital and the Affiliated Hospital of Guilin Medical University. The patients were randomly divided into training, internal validation group and external validation group sets to generate and validate a nomogram model. Multivariate binary logistic analyses indicated that SBP > 178.5 mmHg, WBC > 12.05*109/L, PT > 14.54 s, and NHR > 8.874*109/mmol were independent risk factors for DC after MT in patients with AIS-LVO. In the training set, the area under the curve indicated good accuracy. Calibration curve results showed the average error in the training set was 0.038, and 0.036 in the validation set, showing good model fit. NHR was an independent risk factor for DC treatment after MT in AIS-LVO patients. A nomogram based on NHR accurately predicted if DC treatment was required after MT in patients with AIS-LVO.

This study aimed to dissect the aetiological subgroups of postpartum haemorrhage (PPH) that occur after vaginal delivery in women with full-term singleton pregnancies. Our goal was to craft and validate predictive models to guide clinical decision-making and optimise resource allocation.

A retrospective cohort study.

Shengjing Hospital of China Medical University, Liaoning Maternal and Child Health Hospital, and Shenyang Women's and Children's Hospital.

29 842 women who underwent vaginal delivery were enrolled in the study across three hospitals from 2016 to 2022.

PPH, categorised into uterine atony (UA), placental factors (PF), cervical trauma (CT), and coagulation abnormalities (CA) by aetiology.

The logistic regression for overall PPH and UA-PPH showcased high discrimination (AUCs of 0.807 and 0.794, respectively), coupled with commendable calibration and DCA-assessed clinical utility, culminating in the development of a nomogram for risk prediction. The PF-PPH model exhibited a modest AUC of 0.739, while the CT-PPH and CA-PPH models demonstrated suboptimal clinical utility and calibration.

The study identified factors associated with PPH and developed models with good performance for overall PPH and UA-PPH. The nomogram offers a valuable tool for risk prediction. However, models for PF-PPH, CT-PPH, and CA-PPH require further refinement. Future research should focus on larger samples and multicentre validation for enhanced model generalisability.

The 2-fold objective of this research is to investigate machine learning's (ML) predictive value for the incidence of depression among China's older adult population and to determine the noteworthy aspects resulting in depression.

This research selected 7,880 older adult people by utilizing data from the 2020 China Health and Retirement Longitudinal Study. Thereafter, the dataset was classified into training and testing sets at a 6:4 ratio. Six ML algorithms, namely, logistic regression, k-nearest neighbors, support vector machine, decision tree, LightGBM, and random forest, were used in constructing a predictive model for depression among the older adult. To compare the differences in the ROC curves of the different models, the Delong test was conducted. Meanwhile, to evaluate the models' performance, this research performed decision curve analysis (DCA). Thereafter, the Shapely Additive exPlanations values were utilized for model interpretation on the bases of the prediction results' substantial contributions.

The range of the area under the curve (AUC) of each model's ROC curves was 0.648-0.738, with significant differences (P < 0.01). The DCA results indicate that within various probability thresholds, LightGBM's net benefit was the highest. Self-rated health, nighttime sleep, gender, age, and cognitive function are the five most important characteristics of all models in terms of predicting the occurrence of depression.

The occurrence of depression among China's older adult population and the critical factors leading to depression can be predicted and identified, respectively, by ML algorithms.

Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndrome (ACS).

Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n = 4787) and in validation cohorts from the UK (n = 1141), Czechia (n = 927), and Germany (n = 220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated.

On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI [per log2 increase: adjusted odds ratio 1.53, 95% confidence interval (CI) 1.13-2.09, P = .007] and 30-day mortality (adjusted hazard ratio 2.73, 95% CI 1.85-4.02, P < .001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of .72 (95% CI .68-.76) for in-hospital AKI and .91 (95% CI .87-.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC .73, 95% CI .70-.77; Czechia: AUC .75, 95% CI .68-.81; Germany: AUC .71, 95% CI .55-.87) and 30-day mortality (UK: AUC .87, 95% CI .83-.91; Czechia: AUC .91, 95% CI .87-.94; Germany: AUC .96, 95% CI .92-1.00), outperforming the contrast-associated AKI score and the Global Registry of Acute Coronary Events 2.0 score, respectively.

Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple six-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS.

Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.

We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.

Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.

Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: The OAC3-PAD bleeding risk score was developed to assess the bleeding risk in patients with peripheral arterial disease (PAD), however its performance in patients treated exclusively with endovascular revascularisation has not yet been tested. We aimed to externally validate the bleeding risk score for this patient cohort. Patients and methods: A retrospective observational study, analysing the data of all PAD patients successfully treated with endovascular revascularisation in a single centre within a five-year period. The performance of the Cox proportional hazards (CPH) model, upon which the OAC3-PAD bleeding risk score is based, was tested using calibration methods, discrimination, and a scaled Brier score for overall performance. The OAC3-PAD bleeding risk score was calculated for all patients, classifying them into the four respective risk groups. Kaplan-Meier curves were plotted for all risk groups and discrimination was tested using log-rank tests. Results: While discrimination of the CPH model was adequate, calibration of the model was poor and the scaled Brier score was 3.27% (95% CI 0.65%-4.40%). Of the 1,434 patients, 33 (2.3%) experienced a major bleeding event. The frequency of bleeding was 0.4% in the low risk group (3/736 patients), 0.8% in the low-to-moderate risk group (2/243 patients), 5.8% in the moderate-to-high risk group (15/258 patients), and 6.6% in the high risk group (13/197 patients). The OAC3-PAD score successfully discriminated each of the two lower bleeding risk groups from one of the two higher risk groups, but failed to discriminate among the two lower risk groups and the two higher risk groups, respectively. Conclusions: Although the OAC3-PAD score did not stratify patients into the four respective risk groups, it allowed discrimination between the low risk patients and the high risk patients. It could therefore become a useful tool for predicting major bleeding events in patients with PAD after endovascular revascularisation.

This study aimed to explore the predictive value of machine learning (ML) in mild cognitive impairment (MCI) among older adults in China and to identify important factors causing MCI.

In this study, 6434 older adults were selected based on the data of the China Health and Elderly Care Longitudinal Survey (CHARLS) in 2020, and the dataset was subsequently divided into the training set and the test set, with a ratio of 6:4. To construct a prediction model for MCI in older adults, six ML algorithms were used, including logistic regression, KNN, SVM, decision tree (DT), LightGBM, and random forest (RF). The Delong test was used to compare the differences of ROC curves of different models, while decision curve analysis (DCA) was used to evaluate the model performance. The important contributions of the prediction results were then used to explain the model by the SHAP value.The Matthews correlation coefficient (MCC) was calculated to evaluate the performance of the models on imbalanced datasets. Additionally, causal analysis and counterfactual analysis were conducted to understand the feature importance and variable effects.

The area under the ROC curve of each model range from 0.71 to 0.77, indicating significant difference (P < 0.01). The DCA results show that the net benefits of LightGBM is the largest within various probability thresholds. Among all the models, the LightGBM model demonstrated the highest performance and stability. The five most important characteristics for predicting MCI were educational level, social events, gender, relationship with children, and age. Causal analysis revealed that these variables had a significant impact on MCI, with an average treatment effect of -0.144. Counterfactual analysis further validated these findings by simulating different scenarios, such as improving educational level, increasing age, and increasing social events.

The ML algorithm can effectively predict the MCI of older adults in China and identify the important factors causing MCI.

In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm control therapy. Predictors of attaining sinus rhythm at follow-up are not well known.

To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 45% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets.

Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR] .76 [95% confidence interval .65-.89], P < .001), bone morphogenetic protein 10 (BMP10) (OR .83 [.71-.97], P = .017), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR .73 [.60-.88], P < .001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (Pinteraction = .033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR .64 [.51-.80], P < .001; early rhythm control: OR .90 [.69-1.18], P = .453). External validation confirmed that low concentrations of ANGPT2, BMP10, and NT-proBNP predict sinus rhythm during follow-up.

Low concentrations of ANGPT2, BMP10, and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.

Postoperative atrial fibrillation (POAF) is common after cardiac surgery and related to endothelial activation and systemic inflammation. Herein, we investigate the pathophysiological mechanisms of AF through endothelial activation and cell-cell interactions related to the development of POAF.

Patients without previous AF undergoing cardiac surgery were studied. Permanent AF patients were included as positive controls. Interleukin (IL)-6, Von Willebrand factor (vWF), N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) were evaluated by electrochemiluminescence. Vascular cell adhesion molecule-1 (VCAM-1) and human Growth Differentiation Factor 15 (GDF-15) was assessed by ELISA. Connexins (Cxs) 40 and 43 were measured by tissue immunolabelling, and apoptosis by TUNEL assay.

We included 117 patients (median age 67: 27.8% female): 17 with permanent AF; 27 with POAF and 73 with non- AF. Patients with permanent AF and POAF had higher levels of NT-proBNP, hs-TnT, apoptotic nuclei and decrease Cx43 expression, compared to non-AF patients (all p-value <0.05). VCAM-1 and GDF-15 were significantly higher in permanent AF vs. non-AF (p=0.013 and p=0.035).

Greater endothelial activation and inflammation in AF patients compared to those without AF was found. The proinflammatory state in AF patients, in addition to the lower expression of Cx43, seems to be associated with atrial remodeling processes occurring in AF.

Patients with atrial fibrillation (AF) suffer a higher risk of death, and it is necessary to develop prediction tools for mortality risk in critically ill patients with AF. This study aimed to develop a novel predictive nomogram of in-hospital mortality after 48 h in the coronary care unit (CCU) for patients with AF.

We collected information on CCU patients with AF from the "Medical Information Mart for Intensive Care-III" database and developed a nomogram model for predicting the all-cause mortality risk after 48 h in the hospital. Key variables were selected by univariate logistic and least absolute shrinkage and selection operator regression. The independent predictors with p < 0.05 were screened out by multivariate logistic regression. A predictive nomogram was constructed using these independent predictors, and the model calibration and discrimination were evaluated.

This study finally enrolled 1248 CCU patients with AF, and the in-hospital mortality was 17% (209/1248). The predictive nomogram was constructed by 13 selected independent predictors, including age, smoking status, acute kidney injury, chronic obstructive pulmonary disease, ventricular arrhythmia, shock, urea, red cell distribution width, leucocytosis, continuous renal replacement therapy, continuous positive airway pressure, anticoagulation, and heart rate. The area under the curve of the nomogram was 0.803 (95% confidence interval 0.771-0.835). The nomogram was verified to have good accuracy and calibration.

This study developed a novel nomogram containing age, acute kidney injury, and heart rate that can be a good predictor of potential in-hospital mortality after 48 h in CCU patients with AF.

Guidelines suggest indefinite anticoagulation after unprovoked venous thromboembolism (VTE) unless the bleeding risk is high, yet there is no consistent guidance on assessing bleeding risk.

This study aimed to evaluate the performance of 5 bleeding risk tools (RIETE, VTE-BLEED, CHAP, VTE-PREDICT, and ABC-Bleeding).

PLATO-VTE, a prospective cohort study, included patients aged ≥40 years with a first unprovoked VTE. Risk estimates were calculated at VTE diagnosis and after 3 months of treatment. Primary outcome was clinically relevant bleeding, as per International Society on Thrombosis and Haemostasis criteria, during 24-month follow-up. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Patients were classified as having a "high risk" and "non-high risk" of bleeding according to predefined thresholds; bleeding risk in both groups was compared by hazard ratios (HRs).

Of 514 patients, 38 (7.4%) had an on-treatment bleeding. AUROCs were 0.58 (95% CI, 0.48-0.68) for ABC-Bleeding, 0.56 (95% CI, 0.46-0.66) for RIETE, 0.53 (95% CI, 0.43-0.64) for CHAP, 0.50 (95% CI, 0.41-0.59) for VTE-BLEED, and 0.50 (95% CI, 0.40-0.60) for VTE-PREDICT. The proportion of high-risk patients ranged from 1.4% with RIETE to 36.9% with VTE-BLEED. The bleeding incidence in the high-risk groups ranged from 0% with RIETE to 13.0% with ABC-Bleeding, and in the non-high-risk groups, it varied from 7.7% with ABC-Bleeding to 9.6% with RIETE. HRs ranged from 0.93 (95% CI, 0.46-1.9) for VTE-BLEED to 1.67 (95% CI, 0.86-3.2) for ABC-Bleeding. Recalibration at 3-month follow-up did not alter the results.

In this cohort, discrimination of currently available bleeding risk tools was poor. These data do not support their use in patients with unprovoked VTE.

Atrial fibrillation (AF) is more common in patients with malignancies than in general population. The pathophysiological processes include the pro-inflammatory condition and the exaggerated inflammatory reaction to chemotherapy, radiotherapy, and surgery interventions. Thus, it is pivotal to decrease morbidity and mortality in this group by providing appropriate care and prevention. In this subset, the risk of thromboembolic and bleeding events is high and the common risk score such as CHA2DS2-VASc and HAS-BLED employed in non-oncologic patients have limited evidence in cancer patients. A paucity of evidence in the setting in individuals having both malignancies and atrial fibrillation entangle the clinician when it comes to therapeutic management. Tailored management is recommended of anticoagulation treatment could be difficult, and there is. In this review, we try to explain the mechanism of AF in cancer patients as well as its management in this setting.

Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) on oral anticoagulants (OACs) are at high risk of bleeding. Determinants of major bleeding risk in OAC users with AF and CKD are not well established and available bleeding score systems do not perform well in CKD. This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-5D.

We conducted a Swedish register-based cohort study including patients with AF and CKD G3-5D on warfarin or direct OACs (DOACs) between 2009 and 2018. Data were collected from high-quality registers including the Swedish Renal Registry and Auricula, a register for AF and OACs. Risk factors for major bleeding were investigated with Cox regression analysis.

Of 2453 included patients, 59% were on warfarin (time in therapeutic range 67%) and 41% on DOACs. Major bleeding rates were 8.9/100 patient-years. Factors associated with increased bleeding risk were glomerular filtration rate category, G5/5D versus G3 {hazard ratio [HR] 1.92 [95% confidence interval (CI) 1.43-2.56]}, previous gastrointestinal bleeding [HR 1.77 (95% CI 1.39-2.25)], previous other bleeding [HR 1.33 (95% CI 1.09-1.62)], congestive heart failure [HR 1.36 (95% CI 1.11-1.68)], male sex [HR 1.28 (95% CI 1.03-1.60)] and vascular disease [HR 1.35 (95% CI 1.01-1.79)].

Patients with AF and G3-5D on OACs are at a high risk of bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding. The present study also shows an association between OAC-associated bleeding and male sex, congestive heart failure and vascular disease. Knowledge about determinants of bleeding in advanced CKD is essential when deciding on when to anticoagulate or not.

Patients undergoing left atrial appendage occlusion (LAAO) are at increased risk for bleeding or thromboembolic events. Concurrently, biomarkers are of growing importance in risk stratification for atrial fibrillation patients. We aimed to evaluate the association of hematological markers and clinical characteristics with the occurrence of thromboembolic and bleeding events following LAAO.

Seven implanting centers retrospectively gathered data on hematological markers (i.e., platelet count [PC], mean platelet volume [MPV], and fibrinogen) prior to LAAO. Prespecified thromboembolic and major bleeding outcomes were collected and the association with pre-procedural hematological markers and clinical characteristics was evaluated using Cox regression analysis.

In total, 1,315 patients were included (74 ± 9 years, 36% female, CHA2DS2-VASc 4.3 ± 1.5, HAS-BLED 3.3 ± 1.1). Over a total follow-up duration of 2,682 patient years, 77 thromboembolic events and 107 major bleeding events occurred after LAAO. Baseline PC was the only biomarker showing a signal for a relation to thromboembolic events (HR 1.18, 95% CI: 1.00-1.39) per 50*109 increment, p = 0.056). Thrombotic event rates, including device-related thrombus, increased within higher PC quartiles. Thromboembolism was associated with age (HR 1.05, 95% CI: 1.00-1.10, per year increase) and prior thromboembolism (HR 2.08, 95% CI: 1.07-4.03), but with none of the biomarkers in multivariate analysis. No association of any of the hematological markers with major bleeding was observed. Major bleeding following LAAO was associated with prior major bleeding (HR 5.27, 95% CI: 2.71-10.22), renal disease (HR 1.93, 95% CI: 1.17-3.18), and discharge on dual antiplatelet therapy (DAPT) (HR 1.71, 95% CI: 1.05-2.77).

Most thrombotic events occurred in the highest PC quartile, but no association of any of the hematological markers with thromboembolism or major bleeding was observed in our analysis. In multivariate analysis, older age and prior thromboembolism were associated with thromboembolism. Prior major bleeding, renal disease and discharge on DAPT were multivariate predictors of major bleeding after LAAO.

Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events, such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. The aim of this study was to test whether biomolecule combinations can define phenotypes in patients with AF.

This pre-specified analysis of the EAST-AFNET 4 biomolecule study assigned patients to clusters using polytomous variable latent-class analysis based on baseline concentrations of 13 precisely quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow-up 2.9 years).Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest risk cluster was dominated by elevated bone morphogenetic protein 10, insulin-like growth factor-binding protein 7, N-terminal pro-B-type natriuretic peptide, angiopoietin 2, and growth differentiation factor 15. Patients in the lowest risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of C-reactive protein, interleukin-6, and D-dimer. Patients in the highest risk cluster had a five-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (Pinteraction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients.

Biomolecule concentrations identify cardiometabolic subphenotypes in patients with AF at high and low cardiovascular risk.

Lower extremity artery disease (LEAD) is an increasingly common health problem that is associated with high mortality due to thrombotic and bleeding events. Growth differentiation factor-15 (GDF15), a stress-response cytokine belonging to the transforming growth factor-beta superfamily, is associated with cardiovascular disease and its outcomes. The aim of the present study was to examine the effect of serum GDF15 levels on clinical outcomes in patients with LEAD.

We measured serum GDF15 levels in 200 patients with LEAD before their initial endovascular therapy. The primary endpoint was the all-cause mortality rate. The secondary endpoints, on the other hand, were thrombotic and bleeding events, such as cerebral infarction, acute coronary syndrome, acute limb ischemia, and Bleeding Academic Research Consortium types 3 and 5.

The serum GDF15 levels increased with advancing Fontaine class. Kaplan-Meier analysis revealed that the high-GDF15 group (≥ 2,275 pg/mL) had higher rates of all-cause deaths and thrombotic and bleeding events than the low-GDF15 group (＜2,275 pg/mL). Multivariate Cox proportional-hazards regression analysis revealed that GDF15 was an independent predictor of all-cause mortality and thrombotic and bleeding events after adjusting for confounding risk factors. When the ABC-AF-bleeding score was substituted for GDF15, similar results were obtained.

Serum GDF15 levels were associated with all-cause mortality and thrombotic and bleeding events in patients with LEAD. Serum GDF15 is a potentially useful marker of clinical outcomes, specifically for tracking thrombotic and bleeding events in patients with LEAD.

A notable increase in direct oral anticoagulant (DOAC) use has been observed in the last decade. This trend has surpassed the prescription of vitamin K antagonists (VKAs) due to the absence of the need for regular laboratory monitoring and the more favorable characteristics in terms of efficacy and safety. However, it is very common that patients on DOACs need an interventional or surgical procedure, requiring a careful evaluation and a challenging approach. Therefore, perioperative anticoagulation management of patients on DOACs represents a growing concern for clinicians. Indeed, while several surgical interventions require temporary discontinuation of DOACs, other procedures that involve a lower risk of bleeding can be conducted, maintaining a minimal or uninterrupted DOAC strategy. Therefore, a comprehensive evaluation of patient characteristics, including age, susceptibility to stroke, previous bleeding complications, concurrent medications, renal and hepatic function, and other factors, in addition to surgical considerations, is mandatory to establish the optimal discontinuation and resumption timing of DOACs. A multidisciplinary approach is required for managing perioperative anticoagulation in order to establish how to face these circumstances. This narrative review aims to provide physicians with a practical guide for DOAC perioperative management, addressing the most controversial issues.

To compare outcomes after left atrial appendage occlusion (LAAO) via implanted device vs no LAAO in a matched cohort of patients with atrial fibrillation (AF).

This longitudinal retrospective cohort study was based on the national database covering hospital care for the entire French population. Adults (≥18 years of age) who had been hospitalized with AF (January 1, 2015, to January 1, 2020) who underwent LAAO were identified. Propensity score matching was used to control for potential confounders of the treatment-outcome relationship. The primary outcome was a composite of ischemic stroke, major bleeding, or all-cause death during follow-up.

After propensity score matching, 1216 patients with AF who were treated with LAAO were matched with 1216 controls (patients AF who were not treated with LAAO). Mean follow-up was 14.5 months (median, 13 months; IQR, 7-21 months). Patients with LAAO had a lower risk of the composite outcome (HR, 0.48; 95% CI, 0.42 to 0.55). Total events (309 for LAAO vs 640 for controls) and event rates (23.3% vs 44.0%/year, respectively) were lower for LAAO, driven primarily by a decreased risk of all-cause death (HR, 0.39; 95% CI, 0.33 to 0.46; P<.0001), whereas ischemic stroke risk was higher (HR, 1.75; 95% CI, 1.17 to 2.64). Significant interactions were observed in subgroups with a history of ischemic stroke (P<.001) and of bleeding (P=.002).

Among AF patients at high bleeding risk, our nationwide study highlights a high risk of clinical events during follow-up. LAAO appeared less effective than no LAAO in preventing stroke but more effective in preventing death. Left atrial appendage occlusion is particularly effective in patients with previous ischemic stroke or any episode of bleeding.

Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC).

This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65 years and the ability to perform at least three PPG recordings within 6 months. Exclusion criteria are the presence of a cardiac implantable device, advanced dementia or a severe tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after a positive PPG recording, a confirmatory electrocardiogram is performed. Patients undergo a comprehensive geriatric assessment and a frailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6 months, 12 months and 3 years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality.

The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population.

NCT05337202.

Oral anticoagulation is the key to reduce the risk of stroke in atrial fibrillation. Although vitaminK antagonists (VKA) have classically been used for this purpose, they have been largely overcome by direct oral anticoagulants (DOAC), as demonstrated by evidence from clinical trials, real-life and population studies. In fact, all clinical practice guidelines recommend their use preferentially over VKA. However, in Spain the prescription of DOAC is subordinated to an inspection visa that includes the clinical conditions defined in the Therapeutic Positioning Report of the Spanish Medicines Agency, and that still imposes important restrictions on their use, limiting the benefits of using DOACs in patients with atrial fibrillation (AF), and also generating inequalities between the different autonomous communities. In fact, the use of DOAC in Spain is much lower than that observed in neighboring countries. This has made that while in other countries the incidence of ischemic stroke has decreased at the population level, along with a reduction in the cost per patient with AF, in Spain this decrease has been modest. For all these reasons, and for assuring the sustainability of the health care system, we ask for the elimination of the visa so that DOAC can be prescribed according to the recommendations made by the guidelines. In addition, we are also committed to reinforce medical education and decisions made by consensus with the patient, with the primary care physician acquiring a key role in the protection of the patient with AF.

When high thromboembolic and bleeding risks coexist, the former tends to influence physicians' decision making for anti-coagulation therapy. However, the ideal is to weigh the risk of major bleeding and stroke together to ensure effective anti-coagulation treatment, which is a limitation of traditional guideline recommended CHA2DS2-VASc and HAS-BLED. This meta-analysis assesses the performance of the two new scores - ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED for major bleeding and stroke outcomes in patients with atrial fibrillation (AF) on anticoagulation therapy.

MEDLINE and Cochrane central were searched from 2010 to February 2023 that compared GARFIELD-AF and/or ABC with CHA2DS2-VASc and/or HAS-BLED scores using C-statistics to assess their discriminative ability.

12 studies were included in this meta-analysis. When assessing stroke risk prediction, GARFIELD-AF stroke (C-Statistic: 0.71; 95 % CI: 0.70-0.72; I2 = 0 %, p < 0.05) was found to be significantly better than ABC-stroke (C-Statistic: 0.67; 95 % CI: 0.65-0.68; I2 = 0 %, p < 0.05), and CHA2DS2-VASc (C-Statistic: 0.64; 95 % CI: 0.60-0.67; I2 = 92 %, p < 0.05). Additionally, when assessing bleeding risk prediction, ABC-bleeding (C-Statistic: 0.66; 95 % CI: 0.61-0.70; I2 = 84 %, p < 0.05), GARFIELD-AF (C-Statistic: 0.64; 95 % CI: 0.60-0.68; I2 = 95 %, p < 0.05), and HAS-BLED (C-Statistic: 0.64; 95 % CI: 0.62-0.66; I2 = 85 %, p < 0.05) all showed equivalent performances.

The GARFIELD-AF stroke score showed superior performance to the well-established CHA2DS2-VASc score as well as the ABC-stroke score. Therefore, new guidelines should favor GARFIELD-AF use in clinical practice.

In a world increasingly confronted by cardiovascular diseases (CVDs) and an aging population, accurate risk assessment prior to cardiac surgery is critical. Although effective, traditional risk calculators such as the Japan SCORE, Society of Thoracic Surgeons score, and EuroSCORE II may not completely capture contemporary risks, particularly due to emerging factors such as frailty and sarcopenia. These calculators often focus on regional and ethnic specificity and rely heavily on evaluations based on age and underlying diseases. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that has been identified as a potential biomarker for sarcopenia and a tool for future cardiac risk assessment. Preoperative plasma GDF-15 levels have been associated with preoperative, intraoperative, and postoperative factors and short- and long-term mortality rates in patients undergoing cardiac surgery. Increased plasma GDF-15 levels have prognostic significance, having been correlated with the use of cardiopulmonary bypass during surgery, amount of bleeding, postoperative acute kidney injury, and intensive care unit stay duration. Notably, the inclusion of preoperative levels of GDF-15 in risk stratification models enhances their predictive value, especially when compared with those of the N-terminal prohormone of brain natriuretic peptide, which does not lead to reclassification. Thus, this review examines traditional risk assessments for cardiac surgery and the role of the novel biomarker GDF-15. This study acknowledges that the relationship between patient outcomes and elevated GDF-15 levels is not limited to CVDs or cardiac surgery but can be associated with variable diseases, including diabetes and cancer. Moreover, the normal range of GDF-15 is not well defined. Given its promise for improving patient care and outcomes in cardiovascular surgery, future research should explore the potential of GDF-15 as a biomarker for postoperative outcomes and target therapeutic intervention.