Low bleeding acceptance is associated with increased death risk in patients with atrial fibrillation on oral anticoagulation.

Bleeding is the most feared complication of anticoagulation. We sought to investigate whether the bleeding risk acceptance has a prognostic value during long-term follow-up in the era of direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF). We studied 167 consecutive AF outpatients [aged 68.8 SD 10.6 years; 141 (84.4%) on DOACs]. The bleeding acceptance was assessed based on the Bleeding Ratio defined as the declared maximum number of major bleedings that a patient would be willing to accept to prevent one major stroke. We recorded cerebrovascular ischemic events, major or clinically relevant non-major bleeds (CRNMB), and mortality. A median Bleeding Ratio was 4 (IQR 2-5). During follow-up of 946 patient-years, cerebrovascular ischemic events and/or death were observed in 28 patients (3.3%/ year) and major bleeding or CRNMB in 33 (4.6%/ year). The Bleeding Ratio was lower in patients who experienced cerebrovascular events or death (p = 0.004), but not bleeding. Patients with the Bleeding Ratio 0-3 were more often non-persistent to the OAC therapy, and more likely to have cerebrovascular event or die than those with higher bleeding acceptance (odds ratio 2.55; 0.95% CI 1.08-6.02) which was driven by the impact on mortality. The multiple Cox proportional hazards model showed that lower Bleeding Ratio, higher CHA2DS2-VASc score, and older age predicted cerebrovascular events or death during follow-up. AF patients who are willing to accept fewer serious bleedings to avoid major stroke during anticoagulation are more likely to experience death and/or cerebrovascular ischemic events, but not bleeding, what might be related to non-persistence.

Thrombosis and Aging: Fibrin Clot Properties and Oxidative Stress.

Significance: Aging is a complex process associated with an increased risk of many diseases, including thrombosis. This review summarizes age-related prothrombotic mechanisms in clinical settings of thromboembolism, focusing on the role of fibrin structure and function modified by oxidative stress. Recent Advances: Aging affects blood coagulation and fibrinolysis via multiple mechanisms, including enhanced oxidative stress, with an imbalance in the oxidant/antioxidant mechanisms, leading to loss of function and accumulation of oxidized proteins, including fibrinogen. Age-related prothrombotic alterations are multifactorial involving enhanced platelet activation, endothelial dysfunction, and changes in coagulation factors and inhibitors. Formation of more compact fibrin clot networks displaying impaired susceptibility to fibrinolysis represents a novel mechanism, which might contribute to atherothrombosis and venous thrombosis. Alterations to fibrin clot structure/function are at least in part modulated by post-translational modifications of fibrinogen and other proteins involved in thrombus formation, with a major impact of carbonylation. Fibrin clot properties are also involved in the efficacy and safety of therapy with oral anticoagulants, statins, and/or aspirin. Critical Issues: Since a prothrombotic state is observed in very elderly individuals free of diseases associated with thromboembolism, the actual role of activated blood coagulation in health remains elusive. It is unclear to what extent oxidative modifications of coagulation and fibrinolytic proteins, in particular fibrinogen, contribute to a prothrombotic state in healthy aging. Future Directions: Ongoing studies will show whether novel therapies that may alter oxidative stress and fibrin characteristics are beneficial to prevent atherosclerosis and thromboembolic events associated with aging.

Definition and anatomical description of the left atrial appendage neck.

The left atrial appendage (LAA) is well known as a source of cardiac thrombus formation. Despite its clinical importance, the LAA neck is still anatomically poorly defined. Therefore, this study aimed to define the LAA neck and determine its morphometric characteristics. We performed three-dimensional reconstructions of the heart chambers based on contrast-enhanced electrocardiography-gated computed tomography scans of 200 patients (47% females, 66.5 ± 13.6 years old). The LAA neck was defined as a truncated cone-shaped canal bounded proximally by the LAA orifice and distally by the lobe origin and was present in 98.0% of cases. The central axis of the LAA neck was 14.7 ± 2.3 mm. The mean area of the LAA neck walls was 856.6 ± 316.7 mm2 . The LAA neck can be divided into aortic, arterial (the smallest), venous (the largest), and free surfaces. All areas have a trapezoidal shape with a broader proximal base. There were no statistically significant differences in the morphometric characteristics of the LAA neck between LAA types. Statistically significant differences between the sexes in the main morphometric parameters of the LAA neck were found in the central axis length and the LAA neck wall area. The LAA neck can be evaluated from computed tomography scans and their three-dimensional reconstructions. The current study provides a complex morphometric analysis of the LAA neck. The precise definition and morphometric details of the LAA neck presented in this study may influence the effectiveness and safety of LAA exclusion procedures.

Elevated plasma factor XI predicts cardiovascular events in patients with type 2 diabetes: a long-term observational study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation. METHODS: In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2-10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months. RESULTS: Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46-26.87, p < 0.001 and HR 7.11, 95% CI 2.61-19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease. CONCLUSIONS: To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.

Effect of high-dose statin therapy on coagulation factors: Lowering of factor XI as a modifier of fibrin clot properties in coronary artery disease.

BACKGROUND: Multiple pleiotropic effects of statins include antithrombotic properties with formation of looser fibrin networks more susceptible to lysis. Recently, rosuvastatin 20 mg/d has been reported to decrease coagulation factors (F) VII, FVIII and FXI in venous thrombosis patients. OBJECTIVES: We investigated how high-dose statin therapy recommended in coronary artery disease (CAD) alters plasma levels of coagulation factors and if such changes might affect fibrin clot properties. METHODS: We studied 130 advanced CAD patients, who initially did not achieve the target low-density lipoprotein cholesterol (LDL-C). Before high-dose statin therapy (rosuvastatin 40 mg/d or atorvastatin 80 mg/d) and 6-12 months after its initiation, FII, FV, FVII, FVIII, FIX, FX, FXI and fibrinogen were assessed. We evaluated the impact of statin-induced alterations to the factors on plasma fibrin clot permeability (Ks) reflecting a fibrin pore size, and clot lysis time (CLT) reflecting fibrinolytic potential. RESULTS: At baseline LDL-C (median 3.2, interquartile range 2.7-3.7 mmol/L) was independently associated solely with FXI (ß = 0.58, P < 0.001). Median LDL-C reduction by 25% (P < 0.001) on high-dose statin treatment was accompanied by lowering of FVII, FVIII, and FXI (for all P < 0.001). On high-dose statin treatment, Ks (R = 0.65, P < 0.001) inversely associated with CRP (ß = -0.41, P < 0.001), LDL-C (ß = -0.26, P = 0.001), and FXI (ß = -0.18, P = 0.016). In turn, CLT (R = 0.45, P < 0.001) was positively associated with LDL-C (ß = 0.19, P = 0.043) and FXI (ß = 0.17, P = 0.049). CONCLUSIONS: High-dose statin therapy in CAD patients decreases FVII, FVIII, and FXI. The statin-induced reduction in FXI may contribute to less prothrombotic fibrin clot phenotype, indicating additional antithrombotic effect of high-dose statins.

Aortic valve fenestrations: Macroscopic assessment and functional anatomy study.

Aortic valve fenestrations are defined as a loss of aortic valve leaflet tissue. They are a common but overlooked finding with unclear significance. The aim of this study was to investigate the varied functional anatomies of aortic valve fenestrations. A total of 400 formalin-fixed autopsied human hearts were macroscopically assessed and the function of the aortic valve of 16 reanimated human hearts were imaged using Visible Heart® methodologies. Aortic valve leaflet fenestrations were present in 43.0% of autopsied hearts (in one leaflet in 24.0%, in two leaflets 16.0%, in all leaflets 3.0%). Fenestrations were mostly present in left (25.5%) followed by right (23.3%) and noncoronary leaflet (16.3%). In 93.8% of cases, the fenestrations form clusters and were mainly located at the free edge of the leaflet in the commissural area (95.4%). Hearts with aortic valve fenestrations had significantly larger aortic valve diameters and aortic valve areas (p < 0.001). The average surface area sizes of fenestrations were 23.8 ± 16.6 mm2 , and the areas were largest for left followed by right and noncoronary leaflet fenestrations (p < 0.001). The fenestration areas positively correlated with donor age (r = 0.31; p = 0.02). Significant hypermobility and subjective weakening of the leaflet adhesion levels of the fenestrated regions were observed. In conclusion, fenestrations of the aortic leaflets are frequent, and their sizes may be significant. They occur in all age groups, yet their size increase with aging. Fragments of leaflets with fenestrations show different behaviors during the cardiac cycle versus unchanged areas.

Therapy with high-dose statins reduces soluble P-selectin: The impact on plasma fibrin clot properties.

OBJECTIVE: Studies on the effect of statins on platelets in patients with coronary artery disease (CAD) yielded inconsistent results. We sought to investigate whether high-dose statin therapy reduces plasma concentrations of soluble P-selectin (sP-selectin), a well-established platelet activation marker and if such changes can affect fibrin clot properties, which are unfavorably altered in CAD patients. METHODS: We studied 130 consecutive patients with advanced CAD who did not achieve the target LDL cholesterol on statins. At baseline and after 6-12 months of treatment with atorvastatin 80 mg/day or rosuvastatin 40 mg/day, soluble plasma sP-selectin, along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation and fibrinolysis proteins were determined. RESULTS: Before high-intensity statin treatment, lower Ks and longer CLT values were associated with increased sP-selectin (ß -0.27 [95% CI -0.44 to -0.10] and ß 0.21 [95% CI 0.01 to 0.41]; both p < 0.05, respectively) also after adjustment for potential confounders. sP-selectin, alongside fibrin features and other variables at baseline showed no association with lipid profile. On high-dose statin therapy, there was 32% reduction in sP-selectin levels (p < 0.001). On-treatment change (Δ) in sP-selectin correlated with ΔKs and ΔCLT (r = -0.32, p < 0.001 and r = 0.22, p = 0.011, respectively), but not with cholesterol and C-reactive protein lowering. We did not observe any associations between post-treatment sP-selectin levels and lipids, fibrin clot properties or thrombin generation. CONCLUSIONS: High-dose statin therapy reduces markedly sP-selectin levels in association with improved fibrin clot phenotype, which highlights the contribution of platelet-derived proteins to a prothrombotic state in hypercholesterolemia and statin-induced antithrombotic effects.

Continuous positive airway pressure treatment reduces ventricular arrhythmias in obstructive sleep apnea patients with nocturnal dominance of arrhythmias and severe desaturations.

INTRODUCTION: Continuous positive airway pressure (CPAP) treatment is considered effective in reducing ventricular arrhythmias (VAs) in patients with obstructive sleep apnea (OSA). OBJECTIVES: We aimed to assess the influence of this treatment and to identify determinants of antiarrhythmic response. PATIENTS AND METHODS: We included patients with OSA and VAs (corresponding to grades 2-5 in the Lown classification), who underwent CPAP treatment and controls, who refused CPAP therapy. Holter electrocardiographic monitoring was performed at baseline and after 3 months of follow­up. RESULTS: The study consisted of 46 patients in the CPAP group and 30 controls. We observed a significant reduction in premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia events (P = 0.007 and P = 0.03, respectively) in the CPAP group after 3 months, and no difference in controls. The effect of PVC reduction was significant in the patients with nocturnal dominance of PVCs (P = 0.002) and with desaturations equal to or below 80% (P = 0.001). PVC reduction rate (PVC at follow­up / PVC at baseline) correlated inversely with night / day PVC ratio at baseline (R = -0.36; P = 0.02) and the lowest saturation (R = 0.32; P = 0.03) in the CPAP group. After adjustment for clinical data, night / day PVC ratio was an independent predictor of PVC reduction rate (unstandardized coefficient B = -0.19; 95% CI, -0.37 to -0.01; P <0.05). Its value equal to or greater than 1.16 predicted good antiarrhythmic treatment response with sensitivity and specificity of 83% and 70%, respectively. CONCLUSIONS: CPAP treatment decreases VAs in OSA patients, especially those with severe desaturations and nocturnal domination of PVCs. Night / day PVC ratio might be a useful clinical parameter predicting reduction of PVCs in these patients.

Knowledge about atrial fibrillation and anticoagulation affects the risk of clinical outcomes.

BACKGROUND: Knowledge about atrial fibrillation (AF) and oral anticoagulation (OAC) is insufficient among AF patients. OBJECTIVE: We examined the association between this knowledge and event rate. METHODS: We studied 174 anticoagulated patients with AF aged 69±10.7 years (median CHA2DS2 -VASc 4). Knowledge was assessed at baseline using the Jessa AF Knowledge Questionnaire (JAKQ). The primary endpoint was a composite of ischemic cerebrovascular events, major or non-major clinically relevant bleeding, and death, recorded during a median follow-up of 42 months. RESULTS: The primary endpoint occurred in 48 (27.5%) patients (10.5 per 100 patient-years) including 12 ischemic cerebrovascular events (2.2 per 100 patient-years) and 29 bleeding episodes (5.8 per 100 patient- years). Lower baseline JAKQ scores were associated with the primary outcome (p=0.007), solely when patients who bled during follow-up were compared with the remainder (p=0.007). Patients who were aware of the importance of a regular anticoagulant intake despite the absence of AF symptoms, had, however, a lower risk of cerebrovascular events (p<0.0001). The subjects who experienced bleeding or the primary endpoint were less likely to understand the essence of AF (p=0.03), to know safe painkillers used in combination with OAC (p<0.001), and what to do when the anticoagulant was forgotten (p=0.02). Worse knowledge about AF and OAC, longer OAC therapy, and higher CHA2DS2 -VASc score were independent predictors for the primary endpoint. CONCLUSIONS: Our study shows a prognostic value of low knowledge about AF and OAC supporting the need for improved education of AF patients.

Endothelial dysfunction in obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. METHODS: NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. RESULTS: Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S' ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. CONCLUSION: Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.

Continuous positive airway pressure treatment in sleep apnea: patient compliance and impact on the right heart.

Obstructive sleep apnea syndrome (OSAS) is considered to be an important predisposing factor for cardiovascular diseases. The main objective of this study was to investigate the impact of CPAP treatment on cardiac structure and function and to assess patient compliance over a long-term course of CPAP treatment. A total of 50 patients diagnosed with moderate-to-severe OSAS based on overnight study, without relevant concomitant diseases were enrolled. Patient compliance, along with echocardiographic and CPAP parameters, was assessed. The average time to follow-up was 38 ± 4.2 months. An increase in tricuspid annular plane systolic excursion (TAPSE) (22.1 ± 4.3-25.5 ± 4.6 mm, p = 0.005) and peak early systolic tricuspid annular velocity (S') (14 ± 3.2-17.2 ± 5.2 cm/s, p = 0.005) after CPAP treatment was noted. In patients without CPAP, no significant change in right ventricular (RV) contractility was found. There were no significant differences regarding right atrial (RA) and RV diameters, as well as tricuspid regurgitant peak gradient (TRPG) in both groups; however, a predisposition to increased RA size along with RV and tricuspid annulus diameters was revealed. The mean duration of nightly CPAP use was 3 ± 2.3 h/night in all-day analysis and 4.7 ± 2.1 h/night on days with device usage. The non-adherence rate was 57%. The use of effective CPAP therapy may lead to increased RV systolic function in patients with OSAS in long-term observation. However, long-term patient compliance is generally poor. Regardless of CPAP therapy, a gradual increase in heart size is observed.

Mitral regurgitation severity dynamic during acute decompensated heart failure treatment.

Acute decompensated heart failure (ADHF) treatment leads to significant hemodynamic changes. The aim of our study was to quantitatively analyze the dynamics of mitral regurgitation (MR) severity (evaluated by transthoracic echocardiography) which occur during the treatment of ADHF and to correlate these changes with the clinical condition of patients as well as heart failure biochemical markers. The study included 27 consecutive adult patients (40.7% females, mean age 71.19 ± 11.2 years) who required hospitalization due to signs of acute HF. Echocardiographic assessment was performed upon admission and discharge together with clinical and laboratory evaluation. Significant reduction in dyspnea intensity [0-100 scale] (81.48 ± 9.07 vs. 45.00 ± 11.04 pts, p < 0.001), body weight (84.98 ± 18.52 vs. 79.77 ± 17.49 kg, p < 0.001), and NT-proBNP level (7520.56 ± 5288.62 vs. 4949.88 ± 3687.86 pg/ml, p = 0.001) was found. The severity of MR parameters decreased significantly (MR volume 44.92 ± 22.83 vs. 30.88 ± 18.77 ml, p < 0.001; EROA 0.37 ± 0.17 vs. 0.25 ± 0.16 cm2, p < 0.001; VC 6.21 ± 1.48 vs. 5.26 ± 1.61 mm, p < 0.001). Left atrial area (35.86 ± 9.11 vs. 32.47 ± 9.37, p < 0.001) and mitral annular diameter (42.33 ± 6.63 vs. 39.72 ± 5.05. p < 0.001) also underwent statistically significant reductions. An increase in LVEF was observed (34.73 ± 13.88 vs. 40.24 ± 13.19%, p < 0.001). In 40.7% of patients, a change in MR severity class (transition from a higher class to a lower one) was observed: 6/8 (75%) patients transitioned from severe to moderate and 6/18 (33.3%) patients transitioned from moderate to mild class. Treatment of ADHF leads to a significant reduction in MR severity, together with significant reductions in left atrial and mitral annular dimensions. Quantitative measurement of MR dynamics offer valuable assistance for ADHF management.

Thromboprophylaxis in hospitalized COVID-19 patients: the efficacy and safety of the approved hospital protocol.

Introduction: Prothrombotic coagulopathy in COVID-19 has led to a strong recommendation for thromboprophylaxis in all hospitalized patients, although there are large differences in the dosage regimens among hospitals and their outcomes remain uncertain. Objectives: We aimed to determine the incidence of thrombotic events and bleeding in patients with COVID-19 using the approved local thromboprophylaxis protocol. Patients and methods: We adapted a self-developed pharmacological thromboprophylaxis protocol based on clinical and laboratory risk assessment of thrombosis in 350 consecutive patients (median age, 67 years) with confirmed COVID-19, treated in designated wards at a single center in Kraków, Poland from October 10, 2020, to April 30, 2021. We recorded in-hospital venous and arterial thromboembolic events, major or clinically relevant bleeding, and deaths along with other complications related to heparin administration. Results: Thromboprophylaxis with low-molecular-weight heparin was administered in 99.7% of patients, 57 (16%) were treated in the intensive care unit. As many as 92% of patients followed the protocol for more than 85% of hospitalization time. Thromboembolic events occurred in 16 patients (4.4%): venous thromboembolism (n = 4; 1.1%), ischemic stroke (n = 4; 1.1%), and myocardial infarction (n = 8; 2.2%). Hemorrhagic complications were observed in 31 patients (9%), including fatal bleeds (n = 3; 0.9%). The overall mortality was 13.4%. The prophylactic, intermediate, and therapeutic anticoagulation preventive strategies with heparin were not related to any of the outcomes. Conclusions: The thromboprophylaxis protocol approved in our institution was associated with a relatively low risk of thromboembolism and bleeding, which provides additional evidence supporting the adoption of institutional strategies to improve outcomes in hospitalized patients with COVID-19.

Influence of obstructive sleep apnea on right heart structure and function.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder associated with increased cardiovascular morbidity and mortality. This study aimed to investigate heart structure and function and their correlation with the degree of OSAS and sleep indexes in patients diagnosed with OSAS. MATERIALS AND METHODS: A cohort of 77patients (48 males, aged 58.1 ± 11.0 years, body mass index [BMI] = 32.4 ± 6.2) admitted to the hospital due to suspected OSAS was examined using echocardiography and polysomnography. RESULTS: Patients with moderate-to-severe OSAS compared to patients without diagnosed OSAS or with mild OSAS had greater right ventricular outflow tract (RVOT) dimensions (32.6 ± 3.6 vs 30.9 ± 2.4 mm; p < 0.05), larger right atrial area (RAA; 21.1 ± 4.8 vs 17.2 ± 3.2 mm; p = 0.002), greater right ventricular mid-cavity diameter (RVD; 35.5 ± 7.0 vs 32.2 ± 4.7 mm; p = 0.02), and diminished tricuspid annular plane systolic excursion (TAPSE, 21.9 ± 4.5 vs 25.8 ± 4.4 mm; p = 0.04), while there were no significant differences in tissue doppler imaging (TDI) parameters (S' and E') and in valvular regurgitation gradient for both groups. Moreover, significantly greater RVOT dimensions (31.6 ± 2.6 vs 30.9 ± 3.0 mm, p = 0.04), RVD (39.3 ± 7.0 vs 32.7 ± 5.2 mm, p = 0.003), and RAA (21.4 ± 4.4 vs 18.1 ± 4.2 mm, p = 0.02) as well as reduction in TAPSE (20.9 ± 5.3 vs 25.0 ± 4.3 mm, p = 0.01) were observed in patients having ≥ 10 episodes of obstructive apnea (OA) per hour. CONCLUSIONS: In moderate-to-severe OSAS patients, right ventricular (RV) enlargement was observed together with RV dysfunction as measured by TAPSE. Examination using TDI is not superior to standard echocardiography for the detection of heart pathology in OSAS patients. Right heart pathology is present predominantly in patients with obstructive apnea.

Plasma fibrin clot properties and cardiovascular mortality in patients with type 2 diabetes: a long-term follow-up study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM. METHODS: We studied 133 T2DM patients aged 43-83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-Dmax) and rate of increase in D-dimer concentration (D-Drate) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded. RESULTS: Cardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-Dmax (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99-14.79), or decreased D-Drate (< 0.07 mg/l/min, HR 2.97, 95% CI 1.07-8.23), or increased peak thrombin (> 283.5 nM, HR 5.65, 95% CI 2.07-15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02-18.96; HR 8.98, 95% CI 2.99-26.96; and HR 5.35, 95% CI 1.62-17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-Dmax > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l. CONCLUSIONS: This study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.

Acceptance of a potential major bleeding among patients with venous thromboembolism on long-term oral anticoagulation: the knowledge of the disease and therapy matters.

BACKGROUND: We investigated the bleeding tolerance and its determinants in anticoagulated patients with venous thromboembolism (VTE). METHODS: In 153 outpatients after VTE which occurred in the absence of any identifiable risk factor (aged 52 ±â€¯15.7 years, 54.9% male), anticoagulated for at least one month (for median 29, interquartile range [IQR] 11-72 months), the Bleeding Ratio was determined basing on the declared maximum number of major bleeds that patients can accept to prevent one similar recurrent VTE episode. The modified Jessa AF Knowledge Questionnaire (JAKQ-VTE) was used to assess the knowledge of VTE and anticoagulation. RESULTS: The median of the Bleeding Ratio was 4 (IQR 2-6, minimum 1, maximum 10). Compared with patients with a high Bleeding Ratio (≥4 accepted bleedings, n = 91, 59.5%), those with a low Bleeding Ratio (0-3 accepted bleedings, n = 62, 40.5%) more frequently suffered from isolated deep vein thrombosis (DVT), recurrent VTE, and diabetes. The low Bleeding Ratio group had lower overall scoring in the JAKQ-VTE compared with the remainder (median, 60.4% vs 67.6%, p = 0.003). The independent predictors of a low Bleeding Ratio were: age (odds ratio [OR], 1.36; 95% confidence interval [CI] 1.06-1.75), history of isolated PE (OR, 0.24; 95% CI, 0.08-0.66), scores in the JAKQ-VTE (OR, 0.74; 95% CI, 0.57-0.95), and time since VTE diagnosis (OR, 1.05; 95% CI, 0.98-1.13). CONCLUSIONS: The current study suggests that the acceptance of potential major bleedings is associated not only with age and clinical factors, but also with the knowledge of VTE and anticoagulation, which highlights the need for educational efforts among patients requiring long-term anticoagulant therapy.

Minor bleeding affects the level of knowledge in patients with atrial fibrillation on oral anticoagulant therapy.

BACKGROUND: Anticoagulant therapy in patients with atrial fibrillation (AF) increases the risk of minor bleeding, which is mostly accepted by patients. We aimed to assess whether continuation of anticoagulation despite minor bleeding is associated with a higher level of knowledge on AF and anticoagulation. METHODS AND RESULTS: In 1525 patients with AF on oral anticoagulation who completed the Jessa AF Knowledge Questionnaire (JAKQ) (median age: 72 years [range, 65-79 years]; men: 54.6%), persistent self-reported minor bleeding was recorded. Minor bleeding was observed in 567 patients (37.2%) including 224 patients (39.5%) on vitamin K antagonists (VKAs) and 343 (60.5%) on non-vitamin K antagonist oral anticoagulants (NOACs). The risk of minor bleeding was lower among patients on NOACs than on VKAs (33.5% vs 44.6%; P < .0001). Multiple logistic regression showed that minor bleeding was associated with the use of NOACs (odds ratio [OR] 0.75; 95% CI 0.59-0.97), female gender (OR 2.19; 95% CI, 1.74-2.75; P < .0001), history of major bleeding (OR 2.85; 95% CI, 1.96-4.14; P < .0001), time since AF diagnosis (OR 1.04; 95% CI, 1.01-1.06; P < .0001), concomitant vascular disease (OR 1.43; 95% CI, 1.10-1.87; P = .0008) and diabetes mellitus (OR 1.3; 95% CI, 1.02-1.65, P = .03). Patients with minor bleeding, compared with the remaining subjects scored higher on the JAKQ (median, 62.5% vs 56.2%, respectively, P < .0001). The former group knew more about the purpose of anticoagulant therapy (71.8% vs 65.7%, P = .01) and bleeding as its key side effect (66.1% vs 52.7%, P < .0001), and were better informed on the safest painkillers to use in combination with anticoagulation (48% vs 35%, P < .0001). CONCLUSION: This study suggests that AF patients who accept persistent minor bleeding have better knowledge on the disease and anticoagulation therapy compared with those free of these side effects.

Bleeding Tolerance Among Patients With Atrial Fibrillation on Oral Anticoagulation.

BACKGROUND: Oral anticoagulation increases the bleeding risk. We investigated how clinical factors and the level of atrial fibrillation (AF) knowledge affect the bleeding acceptance in patients with AF. METHODS: In 173 consecutive anticoagulated outpatients with AF (aged 68.7 ± 10.7 years, 39.3% male), the bleeding ratio was assessed based on the declared maximum number of major bleeds the people were willing to endure to avert 1 stroke. The Jessa AF Knowledge Questionnaire was used to assess the knowledge of AF. RESULTS: Compared with patients with the high bleeding ratio (≥ 4 accepted bleedings, n = 88, 50.9%), subjects with the low bleeding ratio (0-3 accepted bleedings, n = 85, 49.1%) were older, with longer duration of AF, suffered more commonly from heart failure, and were free of cerebrovascular events. Patients after major bleeding (n = 33, 19.1%) and those reporting minor bleeds on anticoagulation (n = 77, 44.5%) had lower bleeding ratio. The independent predictors of the low bleeding ratio were older age (odds ratio [OR], 2.50; 95% confidence interval [CI], 1.69-3.70), major bleeds on anticoagulation (OR, 3.33; 95% CI, 1.16-10.0), minor bleeds on anticoagulation (OR, 3.45; 95% CI, 1.67-7.14), and prior stroke/transient ischemic attack (OR, 0.47; 95% CI, 0.22-0.99). The level of knowledge of AF did not affect the bleeding ratio. CONCLUSIONS: The key determinants of the bleeding ratio among anticoagulated patients with AF are age, and prior thromboembolic and bleeding episodes. The study could support identification of patients with AF who need additional effort to increase their acceptance of a life-long oral anticoagulation therapy.