Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: Mitral Fibrin Study.

INTRODUCTION: The intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is compounded by an elevated risk of thromboembolic events. Existing studies offer inconclusive insights into the interplay between MR and the coagulation system. OBJECTIVES: This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on specific coagulation parameters in HF patients. PATIENTS AND METHODS: A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed (n = 27 [V2], and n = 25 [V3]). RESULTS: TEER induced changes in fibrinogen levels (P = 0.01, V3 vs. V2) and improved fibrin clot properties over a 50-day follow-up (Ks, P = 0.01, V3 vs. V2). No significant differences were observed among time points in analyzed blood clot parameters. Correlation analysis showed that baseline CLT was significantly associated with delta NT-proBNP, (P = 0.049; r = 0.40). Multivariable analysis demonstrated that baseline CLT was an independent predictor of the early post-TEER NT-proBNP change (R2 = 0.55, P = 0.02). CONCLUSIONS: We found that fibrinogen levels decreased, and permeation coefficient increased over a median 50-day post-TEER follow-up, compared to early post-procedure assessments. Other blood coagulation parameters remained unchanged from baseline to both follow-up periods after TEER. Finally, CLT was an independent predictor of early NT-proBNP increase, emphasizing its role as an indicator of the hemodynamic response to TEER.

Blood clot properties, thrombin generation, and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

BACKGROUND: There is a strong link between coronary artery disease (CAD), type 2 diabetes (T2D) on one hand, and altered fibrin clot properties, including increased clot density, and unfavorable fibrin clot structure on the other. T2D-related changes in fibrin clots can increase cardiovascular (CV) disease risk, including future CV events. We aimed to assess fibrin clot properties, thrombin generation, and platelet activation in CAD patients with prediabetes (PD) or T2D, compared to CAD patients without glycemic disorders. METHODS: We allocated patients to three groups: 1) Those with angiographically established CAD but without glycemic abnormalities (CAD group); 2) individuals with PD and established CAD (CAD+PD group); and 3) patients with T2D and CAD (CAD+T2D group). We conducted comparisons across these groups for thrombin generation, fibrin clot permeability, fibrin clot lysis, and platelet activation. RESULTS: The final analysis included 116 eligible patients: 1) CAD group (n = 31); 2) CAD+PD (n = 42); and 3) CAD+T2D (n = 43). The CAD+T2D patients enrolled had well-controlled T2D (median HbA1c level of 5.90%; IQR: 5.7%-6.3%). We found no significant differences in thrombin generation, fibrin clot properties, or platelet activation markers across the three analyzed groups (all P-values >0.20). However, elevated interleukin-6 (IL-6) levels were noted in both the highest and lowest glucose concentration quartiles. Additionally, a substantial increase in endogenous thrombin potential (ETP) was observed in patients in the highest glycated hemoglobin quintile. CONCLUSIONS: Individuals with established CAD and concomitant PD or well-controlled T2D exhibited comparable fibrin clot phenotypes, thrombin generation potential, and platelet activation when compared to CAD patients without dysglycemia.

Annual operator volume and procedural outcomes of chronic total occlusions treated with percutaneous coronary interventions: analysis based on 14,899 patients.

BACKGROUND: Low operator and institutional volume is associated with poorer procedural and long-term clinical outcomes in patients treated with percutaneous coronary interventions (PCI). This study was aimed at evaluating the relationship between operator volume and procedural outcomes of patients treated with PCI for chronic total occlusion (CTO). METHODS: Data were obtained from the national registry of percutaneous coronary interventions (ORPKI) collected from January 2014 to December 2020. The primary endpoint was a procedural success, defined as restoration of thrombolysis in myocardial infarction (TIMI) II/III flow without in-hospital cardiac death and myocardial infarction, whereas secondary endpoints included periprocedural complications. RESULTS: Data of 14,899 CTO-PCIs were analyzed. The global procedural success was 66.1%. There was a direct relationship between the annual volume of CTO-PCIs per operator and the procedural success (OR: 1.006 [95% CI: 1.003-1.009]; P<0.001). The nonlinear relationships of annualized CTO-PCI volume per operator and adjusted outcome rates revealed that operators performing 40 CTO cases per year had the best procedural outcomes in terms of technical success (TIMI flow II/III after PCI), coronary artery perforation rate and any periprocedural complications rate (P<0.0001). Among the other factors associated with procedural success, the following can be noted: multi-vessel, left main coronary artery disease (as compared to single-vessel disease), the usage of rotablation as well as PCI within bifurcation. CONCLUSIONS: High-volume CTO operators achieve greater procedural success with a lower frequency of periprocedural complications. Higher annual caseload might increase the overall quality of CTO-PCI.

Do two operators improve outcomes in left main percutaneous coronary intervention? Insights from the ORPKI Registry.

BACKGROUND: Significant left main coronary artery (LMCA) disease is prevalent in 7% of patients undergoing angiography. Limited data exists on the impact of double scrubbing in LMCA PCI. We sought to assess periprocedural outcomes in two-operator LMCA percutaneous coronary intervention (PCI). METHODS: Using data from the Polish National Registry of PCI (ORPKI), we collected data on 28,745 patients undergoing LMCA PCI from 154 centers. Patients were divided into two groups based on the number of operators performing PCI (one vs. two operators). RESULTS: LMCA PCI was performed by a single operator in 86% of the cases and by two operators in 14% of cases. Patients treated by two operators had a greater comorbidity burden including diabetes mellitus, arterial hypertension, previous myocardial infarction, and previous revascularization. In addition, these were more likely to be treated in high-volume centers, by operators with higher volume of LMCA PCIs. The risk of periprocedural death (2.37% vs. 2.44%; P=0.78), as well as cardiac arrest, coronary artery perforation, no-reflow, and puncture site bleeding was comparable between the two groups. On multivariable analysis, we found that a two-operator strategy was an independent predictor of periprocedural death, with this effect being much more profound in an elective setting (OR=5.13 [1.37-19.26]; P=0.015), compared to an urgent (ACS) setting (OR=1.32 [1.00-1.73]; P=0.047). CONCLUSIONS: Our study suggests that a two-operator approach is not necessarily routinely recommended for LMCA interventions, although it can be considered for more complex cases.

18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography imaging in assessing early stages of aortic valve degeneration after transcatheter aortic valve implantation.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a standard treatment for severe aortic stenosis, primarily in elderly patients. With an increasing number of procedures and younger patients, understanding the valve degeneration and its risk factors becomes crucial. OBJECTIVES: We aimed to utilize 18F­sodium fluoride (18F­NaF) and 18F­fluorodeoxyglucose (18F­FDG) positron emission tomography/computed tomography (PET/CT) to evaluate early TAVI valve degeneration. PATIENTS AND METHODS: In this prospective study with a prespecified follow­up protocol, 71 TAVI patients underwent baseline transthoracic and transesophageal echocardiography, and PET/CT with 18F­NaF and 18F­FDG. Of these, 31 patients completed 24­month control examinations, while the others were lost to mortality and the COVID­19 pandemic. We measured PET tracer activity and compared 18F­NaF and 18F­FDG PET/CT uptake at baseline and 24­month follow­up. RESULTS: PET/CT and echocardiography data were analyzed for 31 of the 71 enrolled TAVI patients at a median age of 84 years (interquartile range, 80-86). After TAVI, an improvement in the valve function was observed. During follow­up, the valve function remained stable. PET/CT demonstrated an increase in 18F­FDG maximal uptake in the inner (tissue­to­background ratio, P = 0.009) and outer (P = 0.01) sides of the TAVI valve stent, but no difference in 18F­NaF maximal activity (inner, P = 0.17; outer, P = 0.57). CONCLUSIONS: Twenty­four months post­TAVI, an increase in 18F­FDG uptake, indicative of inflammation, was observed in the valve, while the uptake of the calcification marker (18F­NaF) remained stable. Theseobservations might suggest early stages of TAVI valve degeneration, although further investigation is required to confirm this interpretation.

The Effect of Daylight-Saving Time on Percutaneous Coronary Intervention Outcomes in Acute Coronary Syndrome Patients-Data from the Polish National Registry of Percutaneous Coronary Interventions (ORPKI) in the Years 2014-2022.

INTRODUCTION: Many factors related to the switch to summer/winter time interfere with biological rhythms. OBJECTIVES: This study aimed to analyze the impact of time change on clinical outcomes of patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Electronic data of 874,031 patients with ACS who underwent invasive procedures were collected from the Polish National Register of Interventional Cardiology Procedures (ORPKI) between 2014 and 2021. We determined the number of patients undergoing PCI and periprocedural mortality during the day of spring or autumn time change and within the first 3 and 7 days after the time change. RESULTS: We demonstrated the impact of time changes on the periprocedural mortality of ACS patients within 1 day and the period of 3 and 7 days from the time change. We observed that the occurrence of all ACS and NSTEMI on the first day was lower for both time changes and higher in the case of UA and spring time change. The autumn time change significantly reduced the occurrence of all types of ACS. A significant decrease in the number of invasive procedures was found after autumn transition in the period from the first day to 7 days for ACS, NSTEMI, and UA. CONCLUSIONS: The occurrence of ACS and the number of invasive procedures were lower for both changes over time. Autumn time change is associated with increased periprocedural mortality in ACS and a less frequent occurrence of UA and NSTEMI within 7 days.

Operator-patient sex discordance and periprocedural outcomes of percutaneous coronary intervention (from the ORPKI Polish National Registry).

Introduction: A recent study suggested that sex discordance between surgeons and patients negatively affects the outcomes of patients undergoing common surgical procedures. Aim: We sought to assess whether such an impact exists for periprocedural outcomes of percutaneous coronary intervention (PCI). Material and methods: From 2014 to 2020, data on 581,744 patients undergoing single-stage coronary angiography and PCI from 154 centers were collected. Patients were divided into four groups based on the patient and operator sex. Operator-patient sex discordance was defined as the procedure done by a male operator on a female patient or by a female operator on a male patient. Results: Of 581,744 patients treated by 34 female and 782 male operators, 194,691 patients were sex discordant with their operator (female operator with male patient 12,479; male operator with female patient 182,212) while 387,053 were sex concordant (female operator with female patient 6,068; male operator with male patient 380,985). Among female patients, no difference in the risk of periprocedural complications, including death (0.65% vs. 0.82%; p = 0.10), between patients discordant versus concordant with operators was observed. Among male patients the risk of death (0.55% vs. 0.43%; p = 0.037) and bleeding at the puncture site (0.13% vs. 0.08%; p = 0.046) was higher in patients discordant with operators. However, the differences were no longer significant after adjustment for covariates. Conclusions: No detrimental effect of operator-patient sex discordance on periprocedural outcomes was confirmed in all-comer patients undergoing PCI. Some of the observed differences in outcomes were primarily related to the differences in baseline risk profile.

Thrombus containing lesions strategies during primary percutaneous coronary interventions in ST-segment elevation myocardial infarction: insights from ORPKI National Registry.

In the era of potent P2Y12 inhibitors, according to current guidelines, treatment with glycoprotein IIb/IIIa inhibitors (GPIs) should be limited to bail-out and/or highly thrombotic situations. Similarly, the recommendation for aspiration thrombectomy (AT) is downgraded to very selective use. We examine the prevalence, and predictors of GPI and AT use in STEMI patients referred to primary percutaneous coronary intervention (PCI). Data on 116,873 consecutive STEMI patients referred to primary PCI in Poland between 2015 and 2020 were analyzed. GPIs were administered in 29.3%, AT was used in 11.6%, and combined treatment with both in 6.1%. There was a mild trend toward a decrease in GPI and AT usage during the analyzed years. On the contrary, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5 to 48.1%. Occluded infarct-related artery at baseline and no-reflow during PCI were the strongest predictors of GPI administration (OR 2.3; 95% CI 2.22-2.38 and OR 3.47; 95% CI 3.13-3.84, respectively) and combined usage of GPI and AT (OR 4.4; 95% CI 4.08-4.8 and OR 3.49; 95% CI 3.08-3.95 respectively) in a multivariate logistic regression model. Similarly, the administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies. In STEMI patients in Poland, GPIs are selectively used in one in four patients during primary PCI, and the combined usage of GPI and AT is marginal. Despite the rapid growth in potent P2Y12 inhibitors usage in recent years, GPIs are selectively used at a stable rate during PCI in highly thrombotic lesions.

Elevated factor XIa as a modulator of plasma fibrin clot properties in coronary artery disease.

INTRODUCTION: Patients with coronary artery disease (CAD) display a prothrombotic fibrin clot phenotype, involving low permeability and resistance to lysis. The determinants of this phenotype remain elusive. Circulating tissue factor (TF) and activated factor XI (FXIa) are linked to arterial thromboembolism. We investigated whether detectable active TF and FXIa influence fibrin clot properties in CAD. METHODS: In 118 CAD patients (median age 65 years, 78% men), we assessed Ks, an indicator of clot permeability, and clot lysis time (CLT) in plasma-based assays, along with the presence of active TF and FXIa. We also analysed proteins involved in clotting and thrombolysis, including fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and thrombin activatable thrombolysis inhibitor (TAFI). During a median 106 month (interquartile range 95-119) follow-up, myocardial infarction (MI), stroke, systemic thromboembolism (SE) and cardiovascular (CV) death were recorded. RESULTS: Circulating TF and FXIa, detected in 20.3% and 39.8% of patients, respectively, were associated with low Ks and prolonged CLT. Solely FXIa remained an independent predictor of low Ks and high CLT on multivariable analysis. Additionally, fibrinogen and PAI-1 were associated with low Ks, while PAI-1 and TAFI-with prolonged CLT. During follow-up low Ks and prolonged CLT increased the risk of MI and the latter also a composite endpoint of MI, stroke/SE or CV death. CONCLUSIONS: To our knowledge, this study is the first to show that circulating FXIa is associated with prothrombotic fibrin clot properties in CAD, suggesting additional mechanisms through which FXIa inhibitors could act as novel antithrombotic agents in CAD.

Enhanced neutrophil extracellular traps formation in AF patients with dilated left atrium.

BACKGROUND: Atrial fibrillation (AF) is associated with cardiac remodelling and prothrombotic state. Enhanced neutrophil extracellular traps (NETs) formation has been reported in AF, contributing to thromboembolism. PURPOSE: We investigated whether increased left atrium (LA) diameter and reduced left ventricular ejection fraction (LVEF) affect NETs formation and prothrombotic state in AF patients. METHODS: In 243 AF patients (median CHA2 DS2 -VASc = 4) we measured LA diameter and LVEF, 123 of them with LVEF<50%. Moreover, we determined 3 markers of NETosis: circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and peptidylarginine deiminase 4 (PAD4), along with prothrombotic markers, including endogenous thrombin potential, plasma fibrin clot permeability (Ks ) and clot lysis time (CLT). Ischaemic cerebrovascular events, major bleeding and death were recorded during a median follow-up of 53 months, on anticoagulation. RESULTS: LA diameter correlated positively with H3cit, MPO and PAD4, while LVEF was inversely associated with the same NETosis markers. After adjustment for age and body mass index, concentrations of MPO (per 10 units; ß = -1.9, 95%CI -3.40;-0.42) and H3cit (per 10 units; ß = 2.02, 95%CI 0.61-3.42) were independently associated with LVEF and LA diameter. LA diameter, but not LVEF, correlated inversely with Ks and positively with CLT. The Cox regression analysis revealed that H3cit >6.16 ng/mL (HR = 21.76, 95%CI 2.85-166.28, p = .003) and LA diameter > 46 mm (HR = 2.89, 95%CI 1.04-8.03, p = .043) independently predicted cerebrovascular ischaemic events (1.9%/year). CONCLUSIONS: This hypothesis-generating study suggests that in AF enlarged LA diameter and reduced LVEF are associated with enhanced NETs formation, which might have clinical importance and contribute to thromboembolic events despite anticoagulation.

Application of HoloLens-based augmented reality and three-dimensional printed anatomical tooth reference models in dental education.

Tooth anatomy is fundamental knowledge used in everyday dental practice to reconstruct the occlusal surface during cavity fillings. The main objective of this project was to evaluate the suitability of two types of anatomical tooth reference models used to support reconstruction of the occlusal anatomy of the teeth: (1) a three-dimensional (3D)-printed model and (2) a model displayed in augmented reality (AR) using Microsoft HoloLens. The secondary objective was to evaluate three aspects impacting the outcome: clinical experience, comfort of work, and other variables. The tertiary objective was to evaluate the usefulness of AR in dental education. Anatomical models of crowns of three different molars were made using cone beam computed tomography image segmentation, printed with a stereolithographic 3D-printer, and then displayed in the HoloLens. Each participant reconstructed the occlusal anatomy of three teeth. One without any reference materials and two with an anatomical reference model, either 3D-printed or holographic. The reconstruction work was followed by the completion of an evaluation questionnaire. The maximum Hausdorff distances (Hmax) between the superimposed images of the specimens after the procedures and the anatomical models were then calculated. The results showed that the most accurate but slowest reconstruction was achieved with the use of 3D-printed reference models and that the results were not affected by other aspects considered. For this method, the Hmax was observed to be 630 µm (p = 0.004). It was concluded that while AR models can be helpful in dental anatomy education, they are not suitable replacements for physical models.

Diabetes Mellitus Is Still a Strong Predictor of Periprocedural Outcomes of Primary Percutaneous Coronary Interventions in Patients Presenting with ST-Segment Elevation Myocardial Infarction (from the ORPKI Polish National Registry).

The impact of diabetes mellitus (DM) on outcomes of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) was confirmed by several studies. However, it is unclear whether this effect is still present in large groups of unselected patients undergoing up-to-date treatment. Thus, we sought to assess the impact of DM on periprocedural outcomes of primary PCI in STEMI using data from the Polish National Registry of PCI. Data on 150,782 STEMI patients undergoing primary PCI were collected. Of them, 26,360 (17.5%) patients had DM. Patients with DM were higher-risk individuals who experienced longer reperfusion delays and were less likely to have closed infarct-related artery at baseline (TIMI 0 + 1 flow: 73.2% vs. 72.0%; p < 0.0001) and achieve optimal reperfusion after PCI (TIMI 3 flow: 91.8% vs. 88.5%; p < 0.0001). The periprocedural mortality (1.1% vs. 1.9%; p < 0.0001) was higher in patients with DM and DM was identified as an independent predictor of periprocedural death. In conclusion, despite continuous progress in STEMI treatment, DM remains a strong predictor of periprocedural mortality. However, this detrimental effect of DM may be partially explained by the overall higher risk profile of diabetic patients.

Cardiometabolic predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots in patients at high cardiovascular risk: an 8-year prospective cohort study.

INTRODUCTION: Adiposity has a few phenotypes associated with various levels of risk for diabetes mellitus (DM), but their exact predictive value is not well understood. OBJECTIVES: We aimed to assess the predictive value of anthropometric parameters, vascular ultrasound indexes, and fat depots for long­term cardiometabolic risk. PATIENTS AND METHODS: A total of 150 patients with chronic coronary syndrome (CCS) scheduled for elective coronary angiography were enrolled and a comprehensive clinical and ultrasound assessment of adiposity was performed (2012-2013). Of them, 143 individuals were followed for 8 years for insulin resistance (IR) and / or DM development. RESULTS: At baseline, DM and prediabetes were found in 22% and 8% of the patients, respectively. It was established that 11.7% of the participants died during the follow­up. The rate of DM increased to 46% with a decrease in the prediabetes rate (3.5%). Significant correlations with the Homeostatic Model Assessment of Insulin Resistance and glycated hemoglobin were observed for major anthropometric and ultrasound variables. In the multivariable analysis, independent predictors of IR were preperitoneal fat thickness (PreFT) (per 10mm increase: odds ratio [OR], 1.63; 95% CI, 1.22-2.33; P = 0.003) and body surface area (per 0.1m2 increase: OR, 1.59; 95% CI, 1.11-2.39; P = 0.02). DM was independently predicted by the high­density lipoprotein cholesterol concentration (OR, 0.93; 95% CI, 0.87-0.97; P = 0.005) and body fat mass (OR, 1.09; 95% CI, 1.03-1.17; P = 0.003). CONCLUSIONS: A complex assessment of the adipose tissue in patients with CCS is a valuable method for improving metabolic risk stratification. Some anthropometric and ultrasound parameters, such as PreFT or body surface area, were associated with IR and DM development.

Elevated 8-isoprostane concentration is associated with thromboembolic events in patients with atrial fibrillation.

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 CHA2DS2-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.

Markers of NET formation and stroke risk in patients with atrial fibrillation: association with a prothrombotic state.

INTRODUCTION: Neutrophil extracellular traps (NETs) formation contributes to thrombosis but its role in atrial fibrillation (AF) is poorly explored. We investigated whether increased circulating NETs markers in relation to a hypercoagulable state can predispose to ischemic stroke in anticoagulated AF patients during long-term follow-up. MATERIALS AND METHODS: In this cohort study 243 AF patients (median age 69 years) were assessed. Serum levels of citrullinated histone H3 (H3cit), myeloperoxidase (MPO), and peptidylarginine deiminase 4 (PAD4), along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolysis proteins were measured. Stroke/transient ischemic attacks (TIA), major bleeding, and mortality were recorded during a median follow-up of 53 months while on anticoagulation. RESULTS: Ischemic cerebrovascular events were observed in 20 patients (1.9%/year) who had at baseline higher H3cit, MPO, and PAD4 levels, all positively associated with CLT. Increased thrombin generation correlated positively with H3cit and PAD4, while Ks was inversely associated with H3cit levels. The independent predictors of ischemic stroke/TIA were H3cit (hazard ratio [HR] 9.48, 95% confidence interval [CI] 3.88-22.41, p < 0.0001) and VWF (HR 1.20, 95% CI 1.11-1.49, p = 0.001). Major bleeding (2.0%/year) and all-cause mortality (1.9%/year) were not related to NETs markers. CONCLUSIONS: Enhanced NETs formation related to prothrombotic markers is associated with increased risk of stroke/TIA in AF patients, suggesting a prognostic value of NETosis in AF.