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Thromboembolism, a serious complication in patients with liver abscesses, can lead to organ deterioration if left untreated. However, factors associated with thromboembolism in these patients remain poorly understood. We aimed to identify the factors associated with liver abscess complications, with a focus on thromboembolism and metastatic infection. Data from 325 patients diagnosed with liver abscesses between March 2019 and June 2023 were retrospectively collected. Baseline clinical and laboratory variables associated with thromboembolic events and metastatic infections were analyzed using logistic regression. A nomogram for predicting thromboembolism was constructed using significant predictors. Among the 325 patients, the median age was 68.0 years, and included 129 women. Fifty patients experienced thromboembolic events and 44 had metastatic infections. Significant predictors for thromboembolic events included white blood cell (WBC)  ≥ 20,000/µL (odds ratio [OR] 3.401, p = 0.002), platelet count < 100,000/µL (OR 3.291, p = 0.004), and abscess septation (OR 2.704, p = 0.007). Age ≥ 65 years (OR 0.457, p = 0.040), WBC  ≥ 20,000/µL (OR 3.340, p = 0.005), and abscess septation (OR 2.909, p = 0.008) were identified as factors associated with metastatic infections. A nomogram was constructed to predict thromboembolism using the following four variables: WBC  ≥ 20,000/µL platelet count < 100,000/µL, albumin < 2.8 g/dL, and abscess septation, and demonstrated an AUROC of 0.755. Our study is the first to develop a reliable nomogram for thromboembolism prediction, utilizing easily accessible clinical parameters. This innovative model enables clinicians to efficiently identify high-risk patients, facilitating the implementation of additional studies to mitigate the risk of overlooked thromboembolic events in these at-risk individuals., (© 2024. The Author(s).)

Background: Stroke and thromboembolism (TE) are significant complications in patients with atrial fibrillation (AF) and heart failure (HF). The impact of ejection fraction status on these risks remains unclear. This study aims to compare the risk of stroke and TE in patients with AF and HF with preserved (HFpEF) or reduced (HFrEF) ejection fraction., Methods: Literature search of PubMed, Embase, and Scopus databases was done for studies in adult (20 years or more) population of AF patients. Included studies had reported on the incidences of stroke and/or TE in patients with AF and associated HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Cohort (prospective and retrospective), case-control studies, and studies that were based on secondary analysis of data from a trial were eligible for inclusion. Methodological quality was assessed using the Newcastle Ottawa Scale (NOS). Pooled hazard ratio (HR) with 95% confidence intervals (CI) were reported. Exploratory analysis was conducted based on the different cut-offs used to define HFrEF and HFpEF., Results: Twenty studies were analyzed. In the overall analysis, HFrEF in AF patients was associated with a significantly reduced risk of stroke and systemic TE (HR 0.88, 95% CI: 0.81, 0.96; n = 20, I2 = 86.6%), compared to HFpEF. However, most studies showed comparable risk of stroke among the two groups of patients except for two studies that had documented significantly reduced risk. Upon doing the sensitivity analysis by excluding these two studies, we found similar risk among the two group of subjects and with no heterogeneity (HR 1.01, 95% CI: 0.99, 1.03; n = 18, I2 = 0.0%). Exploratory analysis also showed that the risk of stroke and systemic thromboembolism was similar between those with HFpEF and HFrEF., Conclusion: The findings suggest that there is no significantly different risk of stroke and systemic thromboembolism in cases of AF with associated HFpEF or HFrEF. The finding does not support integration of left ventricular ejection fraction into stroke risk assessments., (© 2024. The Author(s).)

Objective: Accurate prediction of survival prognosis is helpful to guide clinical decision-making. The aim of this study was to develop a model using machine learning techniques to predict the occurrence of composite thromboembolic events (CTEs) in elderly patients with atrial fibrillation(AF). These events encompass newly diagnosed cerebral ischemia events, cardiovascular events, pulmonary embolism, and lower extremity arterial embolism., Methods: This retrospective study included 6,079 elderly hospitalized patients (≥ 75 years old) with AF admitted to the People's Liberation Army General Hospital in China from January 2010 to June 2022. Random forest imputation was used for handling missing data. In the descriptive statistics section, patients were divided into two groups based on the occurrence of CTEs, and differences between the two groups were analyzed using chi-square tests for categorical variables and rank-sum tests for continuous variables. In the machine learning section, the patients were randomly divided into a training dataset (n = 4,225) and a validation dataset (n = 1,824) in a 7:3 ratio. Four machine learning models (logistic regression, decision tree, random forest, XGBoost) were trained on the training dataset and validated on the validation dataset., Results: The incidence of composite thromboembolic events was 19.53%. The Least Absolute Shrinkage and Selection Operator (LASSO) method, using 5-fold cross-validation, was applied to the training dataset and identified a total of 18 features that exhibited a significant association with the occurrence of CTEs. The random forest model outperformed other models in terms of area under the curve (ACC: 0.9144, SEN: 0.7725, SPE: 0.9489, AUC: 0.927, 95% CI: 0.9105-0.9443). The random forest model also showed good clinical validity based on the clinical decision curve. The Shapley Additive exPlanations (SHAP) showed that the top five features associated with the model were history of ischemic stroke, high triglyceride (TG), high total cholesterol (TC), high plasma D-dimer, age., Conclusions: This study proposes an accurate model to stratify patients with a high risk of CTEs. The random forest model has good performance. History of ischemic stroke, age, high TG, high TC and high plasma D-Dimer may be correlated with CTEs., (© 2024. The Author(s).)

Objective: To evaluate the accuracy of diagnostic algorithms developed using the International Classification of Diseases (ICD-9-CM and ICD-10-CA) diagnostic codes and physician billing codes for thromboembolism (TE) from health administrative data compared to chart review diagnoses of TE in children with cancer., Methods: Using data linkage between the Pediatric Oncology Group of Ontario Network Information System (Ontario pediatric cancer registry) and various administrative data housed at ICES, eight algorithms were developed including a single reference to one of the billing codes, multiple references with varying time intervals, and combinations of various billing codes during primary cancer therapy for the whole cohort and, for early (<04/2002) and later (≥04/2002, solely ICD-10 codes) periods. Reference standard was chart review data from prior studies (from 1990 to 2016) among children (≤19 years) with cancer and radiologically confirmed TE., Results: Records of 2056 patients diagnosed with cancer at two participating sites during study period were reviewed; 112 had radiologically confirmed TE. The algorithm with addition of anticoagulation utilization codes was the best performing algorithm (sensitivity = 0.76;specificity = 0.85). With use of ICD-10 only codes, sensitivity of the same algorithm improved to 0.84 with specificity of 0.80., Conclusion: This study provides a valid approach for ascertaining pediatric TE using real-world data., Impact: Research in pediatric thrombosis, especially cancer-related thrombosis, is limited mainly due to small-sized studies. Real-world data provide ready access to large and diverse populations. However, there are no validated algorithms for identifying thrombosis in real-world data for children. An algorithm based on combination of thrombosis and anticoagulation utilization codes had 76% sensitivity and 85% specificity to identify diagnosis of thrombosis in children in administrative data. This study provides a valid approach for ascertaining pediatric thrombosis using real-world data and offers a good avenue to advance pediatric thrombosis research., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: To investigate residual risk of thromboembolic events despite anticoagulation in patients with atrial fibrillation form the Middle East., Materials and Methods: Using data from the JoFib registry, we described the characteristics of patients treated with anticoagulants (n = 1654) and calculated the incidence rate for thromboembolic events. We constructed multivariable Cox proportional hazard models and calculated the population-attributable fraction to determine clinical factors predictive of residual thromboembolic events., Results: During the one-year follow-up, 57 thromboembolic events occurred (incidence rate 4.1 per 100 person-years). In multivariable time-to-event analysis, prior thromboembolic events (aHR 3.8, 95 %CI 2.2-6.4, p < 0.001) and diabetes (aHR 2.3, 95 %CI 1.3-4.1, p = 0.004) were independently predictive of residual thromboembolism. Percentage of thromboembolic risk attributable to prior thromboembolic events was 30.9 % (95 %CI 13.9-44.6, p = 0.001) and was 37.1 % (95 %CI 8.8-56.6, p = 0.015) for diabetes. Furthermore, the effect of diabetes on thromboembolic events depends on the type of anticoagulant, with diabetes being significantly predictive of thromboembolic events in patients anticoagulated with warfarin (aHR 4.11, 95 %CI 1.81-9.37, p = 0.001), but not non-vitamin K antagonist oral anticoagulants (aHR 1.23, 95 %CI 0.51-2.97, p = 0.643) with a p = 0.045 for interaction. Prior thromboembolism was independently predictive of thromboembolic events in both anticoagulants (aHR 2.67, 95 %CI 1.28-5.58, p = 0.009; aHR 7.33, 95 %CI 3.05-17.65, p < 0.001; respectively; p = 0.084 for interaction)., Conclusions: Middle Eastern patients with atrial fibrillation remain at significant risk of thromboembolism and its recurrence despite anticoagulation, and especially in diabetic patients. Therefore, management should focus on controlling diabetes as well as other modifiable risk factors in addition to antithrombotic therapy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management., Methods: We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed., Results: Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model., Conclusion: This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge., Clinical Trial Number: ChiCTR-OCH-13,003,729., (© 2024. The Author(s).)

Background: The risk of subsequent myocardial infarction (MI) varies widely in patients with atrial fibrillation (AF). No convenient scoring system currently exists to identify MI in AF. While each element of the CHA2DS2-VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke or thromboembolism [doubled]; vascular disease; age 65-75 years; and sex category) score can increase the likelihood of MI, this retrospective longitudinal study aimed to determine the accuracy of the CHA2DS2-VASc score in predicting subsequent MI risk in AF., Methods: A total of 29,341 patients with AF were enrolled and followed up from January 2010 until the first occurrence of MI or until December 2020. The primary endpoint was the occurrence of subsequent MI., Results: The average age of the study population was 71 years, and 43.2% were male. The mean CHA2DS2-VASc score was found to be higher in patients with AF who had experienced an MI than in those who had not (3.56 ± 1.92 vs. 3.32 ± 1.81, p < 0.001). During the long-term follow-up, the risk of subsequent MI increased by 22% with every one-point increase in the CHA2DS2-VASc score (hazard ratio 1.22, 95% confidence interval 1.19-1.25; p < 0.001). Kaplan-Meier analysis revealed that high CHA2DS2-VASc scores were more likely to experience an MI than those with low CHA2DS2-VASc scores (log-rank p < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of MI in multivariate regression analysis., Conclusion: The CHA 2 DS 2 -VASc score is a valuable predictor of subsequent MI risk in patients with AF., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Closure of the left atrial appendage (LAA) reduces the rates of TIA/stroke in patients in atrial fibrillation (AF) but its role in patients in sinus rhythm who undergo mitral valve repair (MV) for leaflet prolapse remains unknown. This study examined the effects of closing the LAA in TIA/stroke after MV repair. Our database on patients who had MV repair for leaflet prolapse from 2000 through 2019 was reviewed. After excluding patients at higher risk of TIA/stroke, 1050 patients in sinus rhythm were entered into the study: 781 with open LAA and 269 with surgically closed LAA. Using a propensity score analysis to compensate from clinical differences, 267 pairs of patients with open and closed LAA were matched. Follow-up was truncated at 5 years because routine closure of the LAA was performed only during recent years. The cumulative incidence of TIA/stroke at 5 years in the entire cohort was 2.7% [95% CI 1.9, 4.0]; it was 2.9% [95% CI 1.9, 4.4] in patients with open LAA,and 1.8% [95% CI 0.7, 4.9] in patients with closed LAA (P = 0.53). In the matched cohorts, the cumulative incidences of TIA/stroke did not differ significantly (match-adjusted HR [95% CI] = 0.80 [0.21, 2.98], P = 0.74), and multivariable Cox proportional hazard regression analysis also confirmed no difference in the risk of TIA/stroke between the 2 groups (regression-adjusted HR [95% CI] = 0.58 [0.12, 2.9], P = 0.47). This study failed to show a reduction in the risk of TIA/stroke by closing the LAA in patients in sinus rhythm (Figure 6). Closure of the LAA during MV repair warrants a larger and more rigorous study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients., Methods: Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score., Results: Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. . Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR=0.776, 95%CI: 0.348-1.733, p=0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR=3.452, 95% CI: 1.001-11.903, p=0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR=0.994, 95% CI:0.465-2.128, p=0.988)., Conclusions: We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes., Competing Interests: Declaration of competing interest This study follows the guidelines set forth by the Strengthening the Reporting of Observational Studies in Epidemiology statement., (Copyright © 2024. Published by Elsevier Inc.)

Background: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined., Methods: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included., Results: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents., Conclusions: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH., Competing Interests: Conflict of interest: C. Durrington reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports lecture honoraria from Janssen Pharmaceuticals, outside the submitted work. C.A. Elliot reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D. De-Fonseka reports a leadership role on the Pleural Specialist Advisory Group and Pleural Disease Guideline Committee for the British Thoracic Society, outside the submitted work. A.J. Swift reports support for the present manuscript from a Wellcome Trust fellowship, and also reports grants from Janssen Pharmaceuticals, NIHR and Wellcome Trust, and consulting fees from Janssen Pharmaceuticals, outside the submitted work. K. Dwivedi reports support for the present manuscript from Wellcome 4Ward North fellowship, and also reports grants from Janssen, and lecture honoraria from Royal College of Radiologists, and is a committee member for the Royal College of Radiologists Artificial Intelligence Working Group and Royal College of Radiologists RADIANT group, outside the submitted work. A. Charalampopoulos reports lecture honoraria from Janssen and Boehringer, outside the submitted work. A. Hameed reports lecture honoraria and travel support from Janssen, outside the submitted work. A.M.K. Rothman reports grants from a Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z), MRC (experimental medicine grant MR/W026279/1), Abbott Laboratories, Medtronic Inc., Endotronix, SoniVie, NXT Biomedical, Gradient and Neptune Medical, outside the submitted work. N. Hamilton reports consulting fees and travel support from Janssen, lecture honoraria from MSD and Janssen, advisory board participation with Bayer, MSD, Janssen and Vifor, and a leadership role as pharmacist for the NHS Specialist Respiratory Clinical Reference Group, outside the submitted work. A.A.R. Thompson reports grants from the British Heart Foundation and NIHR, and lecture honoraria and travel support from Janssen-Cilag Ltd, outside the submitted work. R. Condliffe reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D.G. Kiely reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports grants from Janssen Pharmaceuticals, NIHR Sheffield Biomedical Research Centre and Ferrer, consulting fees and lecture honoraria from Janssen Pharmaceuticals, Ferrer, Altavant, MSD and United Therapeutics, travel support from Janssen, Ferrer, MSD and United Therapeutics, advisory board membership for Janssen and MSD, and leadership roles as a member of the Clinical Reference Group for Specialised Respiratory Medicine (NHS England) and lead of the UK National Audit of Pulmonary Hypertension, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Oral anticoagulation is suggested in patients with atrial fibrillation and a CHA 2 DS 2 -VASc score ≥1 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, and sex score). To assess granular differences within CHA 2 DS 2 -VASc 1, the incidence of arterial thromboembolism according to CHA 2 DS 2 -VASc 1 subgroups was examined., Methods: The Danish National Patient Registry and the Danish Prescription Registry were linked on a nationwide level to identify patients with atrial fibrillation from 2000 to 2021 without oral anticoagulation and categorized according to CHA 2 DS 2 -VASc score: CHA 2 DS 2 -VASc 0 (male and female subjects); CHA 2 DS 2 -VASc 1 (hypertension, heart failure, diabetes, vascular disease, and age 65-74 years); or CHA 2 DS 2 -VASc 2 (age ≥75 years without other risk factors). Female sex was not considered a risk factor in any risk group. The outcome was arterial thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Study groups were compared using Cox regression analysis., Results: We included 26 701 patients with a CHA 2 DS 2 -VASc 0 score; 22 915 with CHA 2 DS 2 -VASc 1 (1483 patients with heart failure, 9066 with hypertension, 843 with diabetes, 770 with vascular disease, and 10 753 who were 65 to 74 years of age); and 14 525 patients with CHA 2 DS 2 -VASc 2 (≥75 years of age without other risk factors). With a median of 1 year of observation time, the cumulative incidence of arterial thromboembolism was 0.6% (n=154 [95% CI, 0.6%-0.8%]), 1.4% (n=16 [95% CI, 0.8%-2.2%]), 1.9% (n=141 [95% CI, 1.6%-2.2%]), 1.7% (n=12 [95% CI, 0.9%-2.9%]), 2.0% (n=13 [95% CI, 1.1%-3.4%]), 2.3% (n=187 [95% CI, 2.0%-2.7%]), and 4.4% (n=533 [95% CI, 4.1%-4.8%]) for CHA 2 DS 2 -VASc 0, heart failure, hypertension, diabetes, vascular disease, age 65 to 74 years (CHA 2 DS 2 -VASc 1), and age ≥75 years (CHA 2 DS 2 -VASc 2), respectively. No statistically significant difference was identified among subgroups of CHA 2 DS 2 -VASc 1 ( P =0.15 for difference)., Conclusions: For patients with atrial fibrillation, all subgroups of CHA 2 DS 2 -VASc 1 were associated with lower incidence of arterial thromboembolism compared with age ≥75 years without other risk factors (ie, CHA 2 DS 2 -VASc 2) and a higher incidence compared with CHA 2 DS 2 -VASc 0. No statistically significant difference was identified between the subgroups of CHA 2 DS 2 -VASc 1. These findings support current recommendations that patients within this intermediate risk group could be identified with a similar risk of arterial thromboembolism., Competing Interests: Disclosures L.Ø. declares an independent research grant related to research in mitral valve regurgitation from the Novo Nordisk Foundation. J.B.O. declares speaker honoraria or consultancy fees from Bayer, Bristol-Myers Squibb, and Pfizer. S.L.K. declares speaker fees from AstraZeneca and advisory board membership for Bayer, not related to the present work. M.S. declares lecture fees from Novartis, Novo, AstraZeneca, and Boehringer. L.K. declares speaker honoraria from Astra Zeneca, Bayer, Boehringer, Novartis, and Novo. E.L.F. declares an independent research grant related to valvular heart disease and endocarditis from the Novo Nordisk Foundation and the Danish Heart Association. The other authors report no conflicts.

Aims: Although frail patients with atrial fibrillation (AF) carry a high risk of stroke and treatment-related bleeding complications, evidence for the safety and effectiveness of anticoagulation remains sparse. This study investigated the effectiveness and safety of direct oral anticoagulant (DOAC) vs. warfarin in frail AF patients., Methods and Results: Nationwide registry-based cohort study including 32 048 anticoagulation naïve frail patients (median age 80 years, 53% female) with incident AF during 2012-20. Frailty was assessed using the hospital frailty risk score. To address baseline confounding, we applied inverse probability of treatment weighting (IPTW) and marginal structural models with weighted pooled regression to compute weighted hazard ratios (wHRs) and risk differences for thromboembolism and major bleeding comparing specific DOAC doses with warfarin. After AF diagnosis, 6747 (21.1%) initiated warfarin, 17 076 (50.3%) initiated standard-dose DOAC, and 9179 (28.6%) initiated reduced-dose DOAC. Comparative effectiveness analyses in the IPTW pseudo-populations revealed similar thromboembolism risk between standard-dose DOAC and warfarin [wHR 0.95, 95% confidence interval (CI) 0.80-1.13] and between reduced-dose DOAC and warfarin (wHR 0.97, 95% CI 0.77-1.23). The 1-year thromboembolic event-free survival difference was -0.2% for DOAC, regardless of dosing, vs. warfarin. Major bleeding risk was significantly lower with standard-dose DOAC (wHR 0.69, 95% CI 0.59-0.87) and reduced-dose DOAC (wHR 0.67, 95% CI 0.55-0.81) vs. warfarin. The 1-year bleeding risk difference with DOAC ranged from -1.3% to -3.0%., Conclusion: Our findings indicate comparable thromboembolism risk and significantly lower bleeding risk with both standard and reduced DOAC regimens compared with warfarin in frail AF patients in routine care., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To describe the impact of comorbidities on in-hospital mortality and overall survival in patients with acute mesenteric ischemia (AMI) due to superior mesentery artery (SMA) thromboembolism., Methods: A retrospective study was conducted for 40 patients with AMI due to SMA thromboembolism who were treated in our hospital between February 2013 and December 2019. The presence of comorbidities was described and their severities were classified into 1-4 levels by Geriatric Index of Comorbidity (GIC), the comorbidities were defined as any distinct additional clinical entity that has existed. Univariate and cox proportional-hazards analyses were performed to determine the effect of comorbidities on in-hospital mortality and overall survival., Results: During a mean follow-up of 15.05 ± 18.02 months (range from 0.3 to 58 months) for the 40 patients with AMI due to SMA thromboembolism, In-hospital mortality rate was 52.5% (21/40). One-year, 2-year, and 3-year overall estimated survival rates by the Kaplan-Meier method were 45%, 34%, and 26.5%, respectively, the average overall survival time was 20.84 ± 3.95 (95% CI: 13.10-28.58) months. In-hospital mortality was significantly related to the GIC classification ( χ 2 = 7.86, p = 0.049). The average overall survival was significantly related to the malignant tumor in pre-existing comorbidities and GIC classification (log-rank, p = 0.001). Cox proportional-hazards regressions analysis showed that the class 4 of comorbidities was an independent prognostic factor of mortality ( p = 0.031, HR = 10.45 [95% CI: 1.24-87.70])., Conclusion: Comorbidity is common and an important factor associated with all-cause mortality in AMI patients due to SMA thromboembolism. In managing AMI patients, we recommend a timely diagnosis of both AMI condition and its associated comorbidities., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute limb ischemia (ALI) due to arterial thromboembolic occlusion is a critical emergency in vascular medicine, requiring attention for rapid diagnosis and intervention, to prevent limb loss and major amputation, which is associated with patient disability in the long term. Traditionally, surgical embolectomy has been used for the treatment of ALI. Endovascular treatment of ALI traditionally involved catheter-directed thrombolysis. This option, however, poses some limitations, including an increased risk for access site and systemic bleeding complications, especially in patients with high bleeding risk. Therefore, in the last decades, several devices have been developed and tested for the mechanical endovascular treatment of ALI. Such devices involve either rotational thrombectomy or continuous thrombus aspiration. While rotational thrombectomy is limited in rather large arteries due to the risk of dissection and perforation in arteries <3 mm, continuous thrombus aspiration can be applied in smaller vessels and tortuous anatomies. In our case series we present a minimal-invasive endovascular approach for the treatment of two patients with ALI due to thrombotic occlusion of tortious and small diameter arteries. Minimal-invasive mechanical thrombectomy using the Penumbra Aspiration System emerged as a successful alternative to surgical embolectomy, enabling prompt treatment and with a short hospital stay for both patients. Our article therefore highlights the use of continuous thrombus aspiration in small diameter vessels and tortuous anatomies, which may represent a contraindication for the use of rotational thrombectomy. In addition, this technique may be applied even in patients with higher bleeding risk since additional lysis is not necessary in patients, where complete thrombus removal can be achieved by this device.

Objectives: The purpose of the clinical study was to evaluate the risk of chronic thromboembolic pulmonary hypertension (CTEPH) after splenectomy and to analyze some biochemical and coagulation parameters., Background: CTEPH caused by incomplete resolution of thromboemboli and irreversible remodeling of the pulmonary arteries is a progressive, and without treatment a fatal disease. Although the definite etiopathophysiology is not quite perfectly researched, numerous clinical conditions associated with CTEPH as history of pulmonary embolism, infected ventriculoatrial shunts or permanent intravascular devices, high-dose thyroid hormone replacement, malignancy and chronic inflammatory diseases, including osteomyelitis, inflammatory bowel diseases, are well accepted. These factors also include splenectomy., Methods: We performed a prospective follow-up of patients after splenectomy in the period of 5 years (2017-2022). The study population consisted of 62 adult post-splenectomy patients, who were divided into 3 groups based on the cause of the splenectomy - trauma, haematologic diseases, and others. The study population was analyzed in terms of gender, age, cause of splenectomy, blood group, clinical risk factors and thrombophilic conditions. Some basic haemocoagulation parameters and selected coagulation and biochemical parameters were analyzed. All patients underwent screening echocardiography, symptomatic patients repeatedly. In the presence of pulmonary hypertension (PH) unexplained by other diseases, patients underwent ventilation/perfusion lung scan performed to confirm/exclude perfusion defects typical for CTEPH. If PH and perfusion defects persisted despite effective 3-month anticoagulation therapy, patients underwent right heart catheterization to confirm/exclude CTEPH., Results: The study confirmed a higher incidence of CTEPH after splenectomy compared to published data, the 5-year cumulative incidence was 3.2 %. Other detected clinical risk factors did not affect the incidence of thromboembolism/CTEPH after splenectomy. In our study, the strongest factor in terms of the incidence of thromboembolism/CTEPH after splenectomy was the presence of a thrombophilia detected before the screening echocardiography. Tested haemocoagulation and biochemical parameters in small patient subgroup had no impact on the incidence of thromboembolism/CTEPH - however, the limiting factor was a small patient subgroup., Conclusion: The results of the study suggest that the incidence of thromboembolism after splenectomy was consistent with the present data, but the incidence of CTEPH after splenectomy was significantly higher. This suggests that post-splenectomy condition may be an independent risk factor for CTEPH and may imply different management of these patients in the future (Tab. 5, Ref. 18).

Aim: Increased venous thrombosis and arterial embolism rates are observed in the general population during or after COVID-19. Data regarding the kidney transplant population are scarce. In this study, we aim to investigate the thrombotic complications and risk factors associated with thrombotic complications in kidney transplant patients., Methods: This retrospective observational study included adult kidney transplant recipients diagnosed with COVID-19 between March 2020 and June 2022. The endpoint was the occurrence of thromboembolic events., Results: Four hundred and sixty-nine patients were followed for a median of 10.8 months after COVID-19. Forty patients (8.5%) died. Thromboembolic complications developed in 51 (11.9%) of the surviving patients. Twenty-four patients with thromboembolic events were receiving prophylactic anticoagulation before the event. The patients with mild, moderate, and severe COVID-19 were 292, 129, and 48, respectively. Patients with moderate COVID-19 had a significantly higher percentage of thromboembolic complications than patients with mild COVID-19. Older age, prior heart disease, and moderate COVID-19 were significantly associated with thromboembolic events. The incidence of thromboembolic events after COVID-19 is 10.9 per 100 patient-year., Conclusion: Thromboembolic complications were observed at increased rates in kidney transplant recipients after COVID-19. Therefore, prospective and cohort studies for post-COVID-19 complications regarding the treatment modalities are urgently needed., (© 2023 Asian Pacific Society of Nephrology.)

Background: This study was conducted to assess the net clinical benefit (NCB) for oral anticoagulant (OAC) in atrial fibrillation (AF) patients according to the CHA 2 DS 2 -VASc score., Methods: Patients with AF were prospectively recruited in the COOL AF Thailand registry from 2014 to 2017. The incidence rate of thromboembolic (TE) events and major bleeding (MB) was calculated. Cox proportional hazards model was used to compare the TE and MB rate in patients with and without OACs in CHA 2 DS 2 -VASc score of 0-1 and ≥ 2, respectively. The survival analysis was performed based on CHA 2 DS 2 -VASc score. The NCB of OACs was defined as the TE rate prevented minus the MB rate increased multiplied by a weighting factor., Results: A total of 3,402 AF patients were recruited. An average age of patients was 67.38 ± 11.27 years. Compared to non-anticoagulated patients, the Kaplan Meier curve showed anticoagulated patients with CHA 2 DS 2 -VASc score of 2 or more had the lower thromboembolic events with statistical significance (p = 0.043) and the higher MB events with statistical significance (p = 0.018). In overall AF patients, there were positive NCB in warfarin patients with CHA 2 DS 2 -VASc score of 3 or more while there were positive NCB in DOACs patients regardless of CHA 2 DS 2 -VASc score. Females with CHA 2 DS 2 -VASc score of 3 or more had a positive NCB regardless of OACs type. Good anticoagulation control (TTR ≥65%) improved an NCB in males with CHA 2 DS 2 -VASc score of 3 or more., Conclusions: AF patients with CHA 2 DS 2 -VASc score of 3 or more regardless warfarin or DOACs had a positive NCB. The NCB of OACs was more positive for DOACs compared to warfarin and for females compared to males., (© 2023. The Author(s).)

Purpose: Non-VKA oral anticoagulants (NOACs) prescription is increasing in adults with congenital heart disease (ACHD). However, data on efficacy and safety in ACHD is unclear, particularly in severe CHD. The study aimed to review the safety and efficacy of NOACs in ACHD., Methods: Retrospective evaluation of ACHD patients started on NOACs from 2014 to 2020, with the primary endpoints of bleeding or thromboembolic events (TE). CHA 2 DS 2 -VASc and HAS-BLED scores were calculated, mortality was assessed, and risk factors for bleeding were identified., Results: A total of 93 patients were included, the mean age was 52 ± 15 years, 58% were female, 55.9% had moderate CHD, and 23.7% had severe CHD (3.2% Fontan). Most (66%) had a CHA 2 DS 2 -VASc score ≥ 2 and 82% HAS-BLED ≤ 2. In a median follow-up of 41 (IQR 21) months (400.4 patient-years), there were TE in two patients. The annual risk for TE was 0.49%/patient/year. The cardiovascular mortality was 2% and all-cause mortality 5%; there were no fatal TE or bleeding events. Minor (n = 6, 6.5%) and major (n = 3, 3.2%) bleeding events were observed, a median of 12 (IQR 15) months after starting NOAC therapy. The annual risk for bleeding was 2.2%/patient/year. Renal disease (HR 14.6 [95% CI 1.23-73.6], p = 0.033) and the HAS-BLED score were predictors of major (adjusted HR 6.97 [95% CI 1.69-28.78], p = 0.007) and minor (adjusted HR 3.80 [95% CI 1.48-9.78], p = 0.006) bleeding complications., Conclusion: In this real-life cohort of selected ACHD, the use of NOACs was safe and effective, with a low incidence of bleeding events., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Atrial Fibrillation (AF) is the leading cause of stroke, which can be reduced by 70% with appropriate oral anticoagulation (OAC) therapy. Nationally, appropriate anticoagulation rates for patients with AF with elevated thromboembolic risk are as low as 50% even across the highest stroke risk cohorts. This study aims to evaluate the variability of appropriate anticoagulation rates among patients by sex, ethnicity, and socioeconomic status within the Kaiser Permanente Mid-Atlantic States (KPMAS)., Methods: This retrospective study investigated 9513 patients in KPMAS's AF registry with CHADS 2 score ≥ 2 over a 6-month period in 2021., Results: Appropriately anticoagulated patients had higher rates of diabetes, prior stroke, and congestive heart failure than patients who were not appropriately anticoagulated. There were no significant differences in anticoagulation rates between males and females (71.8% vs. 71.6%%, [OR] 1.01; 95% CI, 0.93-1.11; P = .76) nor by SES-SVI quartiles. There was a statistically significant difference between Black and White patients (70.8% vs. 73.1%, P = .03) and Asian and White patients (68.3% vs. 71.6%, P = .005). After adjusting for CHADS 2 , this difference persisted for Black and White participants with CHADS 2 scores of ≤3 (62.6% vs. 70.6%, P < .001) and for Asian and White participants with CHADS 2 scores > 5 (68.0% vs. 79.3%, P < .001)., Conclusions: Black and Asian patients may have differing rates of appropriate anticoagulation when compared with White patients. Characterizing such disparities is the first step towards addressing treatment gaps in AF., (© 2023. The Author(s).)

Introduction: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival., Methods: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression., Results: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27)., Conclusion: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: The Hungarian National Registry for Philadelphia chromosome negative myeloproliferative neoplasms was used to analyse the thromboembolic events (TE) of Hungarian patients with polycythemia vera (PV)., Methods: Data from 351 JAK2 V617F-positive patients diagnosed with PV were collected online from 15 haematology centres reporting clinical characteristics, therapeutic interventions and thromboembolic events. TE events were evaluated before and after diagnosis based upon the Landolfi and Tefferi risk assessment scales., Results: TE were reported on 102 patients before diagnosis and 100 during the follow-up period. Comparing to the frequency of major arterial events before PV diagnosis, we can notice a decreasing tendency after diagnosis: from 12.3% to 2.6% (p < .00003). There was no significant change in the rate of major venous events (from 5.1% to 8.5%; p = .1134) or minor arterial events (from 11.7% to 17.4%; p = .073). Bleeding events were recorded in 5.7% of patients. Despite treatment with HU + ASA, 44 patients (43.1%) with prior TE had recurrent thromboembolic complications. The particular analysis of our data revealed a new TE scoring system based on: age, gender, previous TE and iron deficiency at the time of diagnosis., Conclusions: Our registry enables characterisation of patients with PV. The high level of recurrent TE events highlights the need for more effective and risk-adapted therapy., (© 2023 John Wiley & Sons Ltd.)

Introduction: Venous aneurysms are rare, so their natural history is not fully understood. Indications for treatment are often determined by the location and size of the aneurysm; however, considering the scarcity of data, there are no specific recommendations. Surgery is the mainstay for venous aneurysm treatment, but some authors reported successful endovascular treatment. We intend to describe our experience with this type of rare disorder., Methods: A post hoc observational study of a prospectively maintained registry including consecutive patients admitted with the diagnosis of a venous aneurysm at different locations between January 2007 and September 2021. Demographic data, anatomic location, and medical history, including trauma or venous surgery, were analyzed. All vascular reconstructions and outcomes have been evaluated., Results: We identified 30 venous aneurysms in 24 patients. Fifteen patients were male (63%). The most common anatomical location was the popliteal vein (n=19; 63%). Four patients had multiple venous aneurysms, and three patients had synchronous arterial aneurysms. Twelve (63%) of the popliteal vein aneurysms identified were surgically treated, most commonly by tangential aneurysmectomy and lateral venorrhaphy. The average diameter at the time of surgery was 22,8±3,6 mm. After discharge, all patients were anticoagulated for 6 to 12 months, in most cases with rivaroxaban. With a median follow-up time of 32 months (12 - 168 months), primary patency was 92%. Aneurysm recurrence was only observed in one case (1/12; 8%) with non-occlusive thrombosis of the aneurysm 14 years after surgery. One patient had a 21 mm gemelar vein aneurysm, having been proposed for surgery, with thrombosis before the intervention. Two patients had common femoral vein aneurysms treated with partial aneurysmectomy and lateral venorrhaphy without thromboembolic events during follow-up. Two patients presented with portal system aneurysms, one associated with portal hypertension. No treatment was performed, and an increase in aneurysm size was observed during follow-up. Another patient presented with acute deep vein thrombosis on chronically thrombosed bilateral iliac vein aneurysms. Three patients had aneurysms of the superficial venous system associated with previous trauma, which were treated with simple ligation and excision., Conclusion: Venous aneurysms are rare and most commonly located in the popliteal vein, which seems to be associated with chronic venous disease. Treating these aneurysms, even without symptoms, can be important to avoid thromboembolic complications. However, close long-term follow-up with duplex ultrasound should be considered to detect late recurrence. Aneurysms from other locations are even rarer, and treatment decisions should be individualized, weighing the risks and benefits of the intervention.

Abstract: Anticoagulation therapy (AT) is the cornerstone of atrial fibrillation (AF) treatment for thromboembolic event prevention. The AF burden, however, is of predictive relevance and may be used as a foundation for therapeutic decisions in individuals with paroxysmal or persistent AF. Remote rhythm monitoring devices can provide early detection of the arrhythmia, long-term rhythm monitoring, and the development of anticoagulation strategies based on AF recurrence profile and the total burden of the arrhythmia. Although the exact thromboembolic cut-off value for the AF burden has not yet been established, targeted anticoagulation treatments in the new oral anticoagulants era have shown encouraging outcomes. The combined evaluation of AF burden and patient thromboembolic risk reported in some studies supports the concept of tailored anticoagulation management, at least in a subset of patients with low AF burden and intermediate thromboembolic risk, for whom the guidelines recommend that AT should be individualized based on net clinical benefit and patient values and preferences. Although it is still premature to derive firm conclusions or algorithms diverging from the current guidelines, the combination of a patient's AF burden, thromboembolic risk, and bleeding risk can lead in the future to an individualized management of patients with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years sex category (female) (CHA 2 DS 2 -VASc) score of 1 (2 for female patients), in whom the guidelines do not strictly recommend long-term AT. In this study, we provide an algorithm regarding the individualized implementation of anticoagulation strategies in AF in different patients' thromboembolic risk profiles, based on the available data on the so far tailored anticoagulation strategies in AF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with elevated hemoglobin, hematocrit, or platelets there are no consensus regarding treatment and follow up., Aims: To assess frequency of elevated blood values in patients with thromboembolic event, how many of these should be investigated further regarding myeloproliferative neoplasm and if the risk of recurrent event is depending on underlying condition., Methods: Retrospective cohort study of 3931 adult patients in the county of Norrbotten, Sweden, with thromboembolism during 2017 and 2018., Results: Of the 3931 patients, 1195 had either elevated Hb, HCT, or platelets fulfilling the 2016 revised WHO criteria for PV and ET, and out of these 411 should be evaluated regarding underlying myeloproliferative neoplasms. Unexplained thrombocytosis and secondary erythrocytosis were associated with the highest rate of recurrent event as well as the most inferior restricted mean survival time., Conclusion: Elevated blood values are common in patients with thromboembolic event and the high risk of recurrent event and inferior restricted mean survival time in patients with unexplained thrombocytosis and secondary erythrocytosis implicates the importance of finding and managing the underlying condition., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

AF patients with history of thromboembolic events are at higher risk of thromboembolic recurrences, despite appropriate antithrombotic treatment. We aimed to evaluate the effect of mobile health (mHealth) technology-implemented 'Atrial fibrillation Better Care' (ABC) pathway approach (mAFA intervention) in secondary prevention AF patients. The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) cluster randomized trial enrolled adult AF patients across 40 centers in China. The main outcome was the composite outcome of stroke or thromboembolism, all-cause death, and rehospitalization. Using Inverse Probability of Treatment Weighting (IPTW), we evaluated the effect of the mAFA intervention in patients with and without prior history of thromboembolic events (i.e., ischemic stroke or thromboembolism). Among the 3324 patients enrolled in the trial, 496 (14.9%, mean age: 75.1 ± 11.4 years, 35.9% females) had a previous episode of thromboembolic event. No significant interaction was observed for the effect of mAFA intervention in patients with vs. without history of thromboembolic events [Hazard ratio, (HR): 0.38, 95% confidence interval (CI):0.18-0.80 vs. HR 0.55, 95% CI 0.17-1.76, p for interaction = 0.587); however, a trend towards lower efficacy of mAFA intervention among AF patients in secondary prevention was observed for secondary outcomes, with significant interaction for bleeding events (p = 0.034) and the composite of cardiovascular events (p = 0.015). A mHealth-technology-implemented ABC pathway provided generally consistent reduction of the risk of primary outcome in both primary and secondary prevention AF patients. Secondary prevention patients may require further specific approaches to improve clinical outcomes such as bleeding and cardiovascular events.Trial registration: WHO International Clinical Trials Registry Platform (ICTRP) Registration number ChiCTR-OOC-17014138., (© 2023. The Author(s).)

Objective: Postmarketing observational studies report that a substantial percentage of patients with atrial fibrillation (AF) receive a reduced non-vitamin K antagonist oral anticoagulant (NOAC) dose without a clear indication. Recently, increasing evidence has become available to explore the clinical consequences of such off-label reduced dosing (OLRD). This study aims to systematically review and meta-analyse observational studies that report clinical outcomes associated with OLRD of NOACs compared with on-label non-reduced dosing (OLNRD) of NOACs in patients with AF., Methods and Analysis: We performed a systematic literature review and meta-analysis of observational studies reporting clinical outcomes in AF patients with OLRD of an NOAC compared with AF patients with OLNRD of an NOAC. Using random effects meta-analyses, we estimated the risk of stroke/thromboembolism, bleeding and all-cause mortality., Results: We included 19 studies with a total of 170 394 NOAC users. In these studies, the percentage of OLRD among patients with an indication for an on-label non-reduced NOAC dose ranged between 9% and 53%. 7 of these 19 studies met the predefined criteria for meta-analysis (n=80 725 patients). The pooled HR associated with OLRD of NOACs was 1.04 (95% CI 0.83 to 1.29; 95% prediction interval (PI) 0.60 to 1.79) for stroke/thromboembolism, 1.10 (95% CI 0.95 to 1.29; 95% PI 0.81 to 1.50) for bleeding and 1.22 (95% CI 0.81 to 1.84; 95% PI 0.55 to 2.70) for all-cause mortality., Conclusion: This meta-analysis shows no statistically significant increased risk of stroke/thromboembolism, nor a decreased bleeding risk, nor a difference in risk of all-cause mortality in patients with OLRD of NOACs. Future research may focus on differences between NOACs., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/. FR, MH and G-JG report unrestricted institutional grants for performing research in the field of atrial fibrillation from Boehringer-Ingelheim, Bayer Healthcare, BMS Pfizer and Daiichi Sankyo. CBG reports personal fees from Bayer Healthcare and Boston Scientific; grants and personal fees from Boehringer-Ingelheim, BMS Pfizer and Janssen; and grants from Daiichi-Sankyo during the conduct of the study; personal fees from AbbVie, Espero, Medscape, Medtronic, Merck, the National Institutes of Health, Novo Nordisk, Roche, Rho Pharmaceuticals, CeleCor, Correvio, Philips, Abiomed and Anthos Therapeutics; grants from Akros, AstraZeneca, the US Food and Drug Administration, Glaxo Smith Kline, Medtronic Foundation and Apple; and grants and personal fees from Novartis and The Medicines Company outside the submitted work. SvD reports an unrestricted research grant from Stoffels Hornstra. All other authors (LJ, RvM, CJvdD and AWH) declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear tohave influenced the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown., Methods: Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were "watch-naïve" at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study., Conclusion: The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment., Trial Registration: ClinicalTrials.gov Identifier: NCT04276441., Competing Interests: Conflict of Interest CMG: Research grant support from Johnson & Johnson and Apple. SS: Research grant from Janssen Pharmaceuticals; Employment with PhysIQ, Inc. DL: Research grant from AtriCure and Biosense Webster. Speakers engagement and advisory boards with Medtronic, Abbott, Boston Scientific, Biosense Webster. MPT: Related to the submitted work: Consulting fees from Johnson & Johnson. Outside of the submitted work: consulting fees from Medtronic Inc, Abbott, Pfizer, Sanofi, InCarda, 100Plus, AliveCor, Acutus, Sanofi, Bristol Myers Squibb, Medtronic; grants from Bristol Myers Squibb, American Heart Association, Sanofi, Apple, Bayer, Gilead, US Food and Drug Administration, employment from iRhythm Technologies. RP: Advisory boards for Johnson & Johnson, Abbott, Medtronic; research support Abbott and American Heart Association. WSJ: Research grants from Bayer, Boehringer Ingelheim, Janssen, Merck, Novartis, National Institute on Aging, Patient-Centered Outcomes Research Institute. TJB: Research grant support from Boehringer Ingelheim, Altathera, Boston Scientific. ABC: Advisory board for Janssen Pharmaceuticals, Medtronic Inc., Abbott, Sanofi Aventis, Milestone Pharmaceuticals, Eagle Pharmaceuticals; honoraria for speaking from Medtronic Inc., Abbott, Sanofi Aventis, Milestone Pharmaceuticals. EP: Research support from Janssen, Bristol-Myers Squibb, Amgen, Esperion; Advisory boards for Novartis, Novo Nordisk, Cerner. JR: Advisory boards for Acesion Pharma and InCarda; consultant for Advanced Medical Education, Element Science, GV, Inc.; steering committee for Janssen; stock options for AblaCor, Element Science, InfoBionic, LuxCath, NewPace, Celero Systems. LS: consultant for Abbott and executive committee member for Johnson & Johnson Heartline trial. MT: Employee of Tiltas Solutions; no other competing interests to disclose. KGT: Full-time employee of Medtronic. NM: Consultant for AtriCure Biosense Webster, Sanofi, Pfizer; honoraria for speaking: Biotronik, Bristol Myers Squibb, Sanofi; research grants from Biosense Webster, St. Jude Medical, Johnson & Johnson, Medtronic, Boston Scientific. MP: Employee of and may hold stock in Apple. AH, SK, JN, SJ, KW, and CVD: employees of Janssen and may hold stock in Johnson & Johnson. JAS: Principal investigator of grants from NIH, Abbott Vascular, and the American College of Cardiology Foundation; consultant to Janssen, Novartis, Amgen, Bristol Myers Squibb, AstraZeneca, Bayer, Terumo, Merck; Scientific Advisory Board of UnitedHealthcare and Board of Directors for Blue Cross and Blue Shield of Kansas City; Copyright owner of the KCCQ, SAQ, and PAQ., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Left atrial (LA) appendage flow velocity (LAAFV) is a classic but invasive predictor of thromboembolic events in patients with atrial fibrillation (AF). We aimed to explore the usefulness of LA diameter (LAD) combined with CHA 2 DS 2 -VASc score, which is easily available and non-invasive, as a novel score for predicting a decrease in LAAFV in non-valvular AF (NVAF)., Methods: In total, 716 consecutive NVAF patients who underwent transesophageal echocardiography were divided into the decreased LAAFV (< 0.4 m/s) and preserved LAAFV (≥ 0.4 m/s) groups., Results: The decreased LAAFV group had a larger LAD and a higher CHA 2 DS 2 -VASc score than the preserved LAAFV group (P < 0.001). Multivariate linear regression indicated that brain natriuretic peptide (BNP) concentration, persistent AF, LAD, and CHA 2 DS 2 -VASc score were remained inversely associated with LAAFV. Moreover, multivariate logistic regression revealed that BNP concentration (odds ratio [OR] 1.003, 95% confidence interval [CI] 1.001-1.005, P = 0.003), persistent AF (OR 0.159, 95% CI 0.102-0.247, P < 0.001), and LAD (OR 1.098, 95% CI 1.049-1.149, P < 0.001) were independent factors for a decrease in LAAFV. A novel score, LAD combined with CHA 2 DS 2 -VASc score, was more accurate for predicting a decrease in LAAFV among NVAF patients (area under the curve was 0.733)., Conclusion: Enlarged LAD was independent risk factor for a decrease in LAAFV among NVAF patients. LAD combined with CHA 2 DS 2 -VASc score enhanced the predictive ability for a decrease in LAAFV among NVAF patients., (© 2023. The Author(s).)

Aim: The risks of thromboembolism and major bleeding in atrial fibrillation (AF) patients were assessed according to the "Evaluated Heartvalves, Rheumatic or Artificial" (EHRA) classification. Additionally, the safety and efficacy of vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) were compared in AF patients with EHRA type 2 valvular heart disease (VHD) versus those with no VHD., Methods: AF patients enrolled in the "Jordan Atrial Fibrillation (JoFib)" study were followed up for thromboembolic events and major bleeding at 30, 180, and 365 days. Patients in the EHRA type 2 VHD and non-VHD groups were sub-grouped to compare different OACs., Results: 2020 AF patients were recruited. The thromboembolic risk was higher in EHRA type 2 VHD patients compared to non-VHD controls. Major bleeding also occurred at higher rates in EHRA type 2 patients. In addition, NOACs were more effective in preventing thromboembolic events than VKAs and non-anticoagulation in EHRA type 2 VHD patients. Furthermore, EHRA type 2 VHD patients taking rivaroxaban had significantly less thromboembolic risk than their non-anticoagulated counterparts. At the same time, apixaban and warfarin did not significantly lower the risk of thromboembolism compared to non-anticoagulation., Conclusion: AF patients with EHRA type 2 VHD are at significant risk of thromboembolism and major bleeding. Furthermore, NOACs were more effective than VKAs in preventing thromboembolic events in this group of patients without conferring an added risk of major bleeding. Moreover, rivaroxaban appears to be particularly efficacious., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Al-Najar et al.)

COVID-19 patients may develop thrombotic complications, and data regarding an association between nasopharyngeal viral load and thrombosis is scarce. The aim of our study was to evaluate whether SARS-CoV-2 nasopharyngeal viral load upon admission is a useful prognostic marker for the development of thromboembolic events in patients hospitalized for SARS-CoV-2 infection. We performed a retrospective study of all hospitalized patients with a positive PCR test for SARS-CoV2 who had deep vein thrombosis (DVT), pulmonary embolization (PE), or arterial thrombosis diagnosed during their clinical course in a single academic center. The study population was divided according to the cycle threshold (Ct) value upon admission in patients with high viral load (Ct < 25), intermediate/medium viral load (Ct 25-30), and low viral load (Ct > 30). A regression model for propensity was performed matching in a 1:3 ratio those patients who had a thrombotic complication to those who did not. Among 2,000 hospitalized COVID-19 patients, 41 (2.0%) developed thrombotic complications. Of these, 21 (51.2%) were diagnosed with PE, eight (19.5%) were diagnosed with DVT, and 12 (29.2%) were diagnosed with arterial thrombosis. Thrombotic complications occurred as frequently among the nasopharyngeal viral load or severity stratification groups with no statistically significant differences. Univariate logistic regression revealed increased odds for thrombosis only in mechanically ventilated patients OR 3.10 [1.37, 7.03] (p = 0.007). Admission SARS-CoV-2 nasopharyngeal viral loads, as determined by Ct values, were not independently associated with thromboembolic complications among hospitalized patients with COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Optimal antithrombotic therapy in patients who underwent surgical biological aortic valve replacement (AVR) represents an issue of ongoing discussion. Additionally, the prognostic impact of anti-thrombotic treatment strategies after biological AVR and real-life data on anticoagulation strategies (AC) of patients presenting with short-term postoperative atrial fibrillation (POAF) has not clearly been investigated so far. Therefore, this study aimed to investigate the impact of therapeutic AC after biological AVR on patient outcome and whether the presence of POAF affects decision making on anti-thrombotic management., Methods: Within this prospective observational study, 200 individuals that underwent biological AVR surgery were enrolled. Participants were followed prospectively until the primary study endpoint was reached. Multivariate logistic regression analysis was performed to elucidate the effect of therapeutic AC on outcome., Results: Overall, 106 individuals received therapeutic AC at the time of discharge. The fraction of patients presenting with POAF was balanced between individuals receiving AC and the non-AC subgroup (p = 0.617). After a median follow-up time of 1418 days, 31 (15.5%) individuals died, referring to 15 (13.9%) POAF-free patients and 16 (17.4%) with POAF. We observed a strong inverse association of therapeutic AC and cardiovascular mortality, which remained stable after adjustment for potential confounders showing a HR of 0.437 (95% CI 0.202-0.943; p = 0.035), while bleeding risk was comparable (p = 0.680)., Conclusion: Within this investigation, therapeutic AC showed a strong and independent inverse association with long-term mortality in patients that underwent biological AVR. Although POAF is associated with thromboembolic adverse events, the development of this arrhythmia did not affect decision-making of the anti-thrombotic management., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The primary objective of this study is to assess the risk of thromboembolic events (TEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) and study the impact of TEs on hospital course and mortality risk during the initial height of the severe acute respiratory syndrome coronavirus-2 pandemic., Methods: A retrospective review of all adult inpatients (≥ 18 years old) with COVID-19 infection at a single academic institution from March 15, 2020 to July 1, 2020 was performed. Collected data included patient demographics, comorbidities, hospital admission type, TEs, laboratory values, use of anticoagulants/antiplatelet agents, hospital length of stay, and in-hospital mortality. A logistic regression was used to estimate associations between risk factors and TEs., Results: A total of 826 inpatients with COVID-19 were identified. Of these, 56% were male, average age was 60.9 years, and race/ethnicity was reported as Hispanic in 51%, non-Hispanic Black in 25%, and non-Hispanic White in 18%. A total of 98 TEs were documented in 87 patients (10.5%). Hypertension, coronary artery disease, and chronic limb threatening ischemia were associated with an increased incidence of thromboembolism (P < 0.05). Hispanic patients had higher incidence of thromboembolism compared to White non-Hispanic patients (odds ratio {[OR] confidence interval [CI]}: 2.237 [1.053, 4.754], P = 0.036). As D-dimer increased, the odds of TE increased by 5.2% (OR [CI]: 1.052 [1.027, 1.077], P < 0.001). Patients with TEs had longer hospital stay (median 13 vs. 6 days, P < 0.001), higher likelihood of intensive care unit admission (63% vs. 33%, P < 0.001), and higher in-hospital mortality (28% vs. 16%, P = 0.006). Arterial TEs were associated with higher in-hospital mortality than venous TEs (37% vs. 15%, P = 0.027)., Conclusions: During the initial height of the severe acute respiratory syndrome coronavirus-2 pandemic, TEs were relatively frequent in hospitalized patients with COVID-19. Racial disparities were seen with an increased proportion of minority patients admitted with respect to percentages seen in the general population. There was also a significantly increased incidence of TEs in Hispanic patients. TEs were associated with significantly longer hospital stay and higher in-hospital mortality. Patients with arterial TEs fared worse with significantly higher mortality than those with venous events. Inconsistencies in anticoagulation management early in the pandemic may have contributed to poor outcomes and more contemporary management outcomes need to be investigated., (Published by Elsevier Inc.)

Background: Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients., Methods: In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs)., Results: Increased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (the top quartile) compared with those with 8-isoprostane <250 pg/mL (the bottom quartile) had higher fibrinogen, lower VWF, higher plasminogen activator inhibitor 1, along with lower fibrin clot permeability with no difference in CHA 2 DS 2 -VASc score, CLT or ETP. Patients who experienced thromboembolic events (n = 20, 1.9%/year) had 48.6% higher 8-isoprostane concentrations compared to the remainder (P <0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17-7.03, P = 0.02). There were no associations between 8-isoprostane and major bleeding (2.0%/year) or all-cause mortality (1.9%/year)., Conclusions: Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P <0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P =0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P =0.010). Conclusions Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.

We have previously demonstrated that accelerometer-based vibration analysis detects thromboembolism and pump thrombosis in HeartWare Left Ventricular Assist Device (HVAD) using the third harmonic frequency (pump&#95;speedx3). Thromboembolism also affected the amplitude of the nonharmonic frequencies. The aim of this study was to determine whether nonharmonic-amplitude (NHA) analysis can improve the diagnosis of thromboembolic complications. An accelerometer was attached to HVAD in three in vitro and seven in vivo experiments. Control interventions, including load and pump speed alternations (n = 107), were followed by thromboembolic events (n = 60). A sliding fast-Fourier-transform was analyzed, and changes in NHAs were quantified in the acute phase and in a steady state. Receiver operating characteristic curves were constructed with cutoff values of NHA to detect thromboembolic events. Positive predictive values were calculated on the basis of a specificity of 1. In the acute phase, NHA change was 6.5 times higher under thromboembolism than under control interventions (p < 0.001). Most thromboembolic events lead to concomitant changes in both NHA and third-harmonic amplitude. Combining the two methods improved the PPV by 8.3%. At steady state, signal changes predominantly demonstrated either NHA or third-harmonic changes. Combined signal analysis improved the PPV by 36%. This method enhanced the detection of thromboembolism and pump thrombosis in the HVAD., Competing Interests: The research was funded by the South-Eastern Norway Regional Health Authority. The company Cardiacs AS has a pending patent on the idea of using accelerometer in pump thrombosis detection. The authors Halvorsen, Espinoza, and Fosse are shareholders in the company. We report no other conflicts of interest., (Copyright © ASAIO 2022.)

Long-term and continuous ECG monitoring using cardiac implantable electronic devices and insertable cardiac monitors has improved the capability of detecting subclinical atrial fibrillation (AF) and atrial high-rate episodes. Previous studies demonstrated a high prevalence (more than 20%) in patients with cardiac implantable electronic devices or insertable cardiac monitors. Subclinical AF and atrial high-rate episodes are often suspected as the cause of prior or potential future ischemic stroke. However, the clinical significance is still uncertain, and the evidence is limited. This review aims to present and discuss the current evidence on the clinical impact of subclinical AF and atrial high-rate episodes. It focuses particularly on the association between the duration of the episodes and major clinical outcomes like thromboembolic events. As subclinical AF and atrial high-rate episodes are presumed to be associated with ischemic strokes, detection will be particularly important in patients with cryptogenic stroke and in high-risk patients for thromboembolism. In this context, it is also interesting whether there is a temporal relationship between the detection of subclinical AF and atrial high-rate episodes and the occurrence of thromboembolic events. In addition, the review will examine the question whether there is a need for a therapy with oral anticoagulation., (© 2022. The Author(s).)

Background: Significant aortic regurgitation at the time of left ventricular assist device (LVAD) implantation, requires concomitant aortic valve (AoV) replacement or repair. However, the impact of concomitant AoV surgery on morbidity remains unknown. Therefore, our aim is to determine the impact of concomitant AoV surgery on thromboembolic and bleeding events., Methods: A retrospective IMACS registry study, including patients implanted from 2013 until September 2017. Differences between different concomitant AoV surgery modalities were analyzed., Results: In total, 785 (5.1%) out of 15.267 patients (median age 58 IQR 49-66 years, 79% male) underwent concomitant AoV surgery (median age 63 IQR 54-69 years, 84% male); 386 (49%) patients received biological prostheses, 71 (9%) mechanical prostheses and 328 (42%) AoV repairs. In total, 54 (8%) patients with AoV surgery experienced a thromboembolic event and 1016 (9%) patients with no AoV surgery. Furthermore, concomitant AoV surgery was associated with an increased rate of all and nonsurgical bleedings. Following a multivariable Cox regression, concomitant AoV surgery remained an independent predictor for bleeding events., Conclusions: In LVAD patients undergoing concomitant AoV surgery, thromboembolic event rates were not higher, however both all and nonsurgical bleeding event rates were higher., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Left ventricular non-compaction (LVNC) is morphologically characterised by excessive trabeculations and deep recesses in the ventricular wall. The risk of thromboembolic disease in the paediatric patients with LVNC has not been clearly established. We conducted this systematic review to evaluate the prevalence and incidence of thromboembolism (TE) in paediatric and adult patients with LVNC and searched for risk factors for TE to explore management strategies., Methods: The primary outcome was the prevalence and incidence of TE in the patients with LVNC. The secondary outcome was the TE and mortality and heart transplantation rates between paediatric and adult patients with LVNC. We searched for studies published in MEDLINE, Embase and Cochrane Central Register of Controlled Trials between January 1950 and December 2020. A systematic search of keywords related to LVNC, anticoagulants/antiplatelets and TE was conducted. Studies that did not present original research, non-human studies, duplicated studies were excluded., Results: Fifty-seven studies met the inclusion criteria. A total of 726 paediatric and 3862 adult patients were included. The mean prevalence rates of TE in the paediatric and adult patients with LVNC were 2.6% and 6.2% (I 2 =0%; p<0.450 and I 2 =73.7%; p<0.001), respectively. The mean annual incidences of TE in paediatric and adult patients with LVNC were 1.4% and 2.9% (I 2 =99.4%; p<0.001 and I 2 =99.5%; p<0.001), respectively. Multivariate logistic regression analysis showed that TE was associated with left ventricular ejection fraction in <40% of paediatric patients (OR, 9.47; 95% CI, 1.35 to 188.23; p=0.0225)., Conclusions: The prevalence and incidence rates in paediatric patients were lower than those in adult patients. TE was associated with a reduced systolic function in paediatric patients with LVNC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF., Methods: A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated., Results: Plasma Ninj1 levels were significantly higher in patients with AF than in controls (P < 0.001). Plasma Ninj1 levels were positively correlated with LAVI (P = 0.019) and CHA2DS2-VASc score (P = 0.024). Logistic regression analysis confirmed that the Ninj1 plasma levels were associated with AF (P = 0.009). The receiver operating characteristic analysis showed that plasma Ninj1 had a predictive value for AF (P < 0.001)., Conclusions: Plasma Ninj1 levels were elevated in patients with AF, associated with left atrial enlargement and thromboembolic risk in AF., (© 2022. The Author(s).)

Background: Emerging data suggest increased arterial thrombosis risk in the months preceding a cancer diagnosis., Objectives: To assess whether patients without documented vascular risk factors or pre-existing cardiovascular disease have a higher relative risk of cancer 12 months after arterial thrombotic events (ATE), compared to unselected patients., Patients/methods: A population-based cohort study of Clalit Health Services (CHS) database included CHS members ≥25 years without prior cancer or ATE (n = 2 804 584). An iterative matching process selected 10 potential controls chronologically for each consecutive exposed, age- and sex-matched (actual controls drawn 1:1 from a lot). Study exposure, ATE, was defined as ischemic stroke, transient ischemic attack, myocardial infarction or systemic arterial thromboembolism during hospitalization. The outcome was newly-diagnosed cancer within 12 months, based on Israeli national cancer registry. Cox proportional hazards multivariate regression calculated hazard ratio (HR) for outcomes, adjusted for cancer risk factors. Analysis also performed for three subgroups: age ≤50 years; no cardiovascular risk factors; no prior cardiovascular disease., Results: The full ATE and matched control cohorts included 43 108 patients. The 12-month cumulative incidence of cancer (95% confidence interval) was 0.020 (0.019-0.022) in the ATE cohort and 0.012 (0.011-0.013) in controls, corresponding to an adjusted HR of 1.665 (1.489-1.862). The relative risk of cancer was high in all subgroups up to a HR of 3.754 (1.912-7.372) in patients without cardiovascular risk factors., Conclusion: There is an increased risk of previously undiagnosed cancer at 12 months after ATE, especially in patients without documented vascular risk factors or pre-existent cardiovascular disease., (© 2021 International Society on Thrombosis and Haemostasis.)

Objective: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery., Design: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed., Participants: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit., Setting: Academic tertiary care medical center., Interventions: None., Measurements and Main Results: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke., Conclusions: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)