Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Balloon-Assisted Endovascular Thrombectomy for Tibial Thromboembolism.

We present a novel approach to endovascular thrombectomy using the Penumbra Indigo® Aspiration System with balloon assistance for a thromboembolic occlusion to the tibioperoneal trunk and tibial arteries causing acute limb ischemia. This technique allows for effective suction thrombectomy of distal vessels into a shorter, large-diameter aspiration catheter, thereby overcoming the limitations of the longer but smaller aspiration catheters.

Nonatrial Fibrillation Patients With Complete P Wave Disappearance: An Overlooked Population With High Stroke Risk.

BACKGROUND AND PURPOSE: Complete P wave disappearance (CPWD) in patients without atrial fibrillation is an uncommon clinical phenomenon. We aimed to study the relationship between CPWD and thromboembolism. METHODS: Between July 2007 and December 2018, consecutive patients with CPWD on surface ECG and 24-hour Holter recording were recruited into the study from 4 centers in China. All recruited patients underwent transesophageal echocardiography or cardiac computed tomography to screen for atrial thrombus. Atrial electrical activity and scar were assessed by electrophysiological study (EPS) and 3-dimensional electroanatomic mapping. Cardiac structure and function were assessed by multimodality cardiac imaging. RESULTS: Twenty-three consecutive patients (8 male; mean age 48.5±14.7 years) with CPWD were included. Only 3 patients demonstrated complete atrial electrical silence with atrial noncapture. Thirteen patients who had invasive atrial endocardial mapping demonstrated extensive scar. Pulse-wave mitral inflow Doppler demonstrated absent and dampened A waves in 18 and 5 patients, respectively. Pulse-wave tricuspid inflow Doppler showed absent and dampened A waves in 19 and 4 patients, respectively. Upon recruitment, 8 patients had previous stroke and 3 patients had atrial thrombus. Warfarin was prescribed to all patients. During median follow-up of 42.0 months, 2 patients developed massive ischemic stroke due to warfarin discontinuation. CONCLUSIONS: Our study suggested that CPWD reflects extensive atrial electrical silence and significantly impaired atrial mechanical function. It was strongly associated with thromboembolism and the clinical triad of CPWD-atrial paralysis-stroke was proposed. Anticoagulation should be recommended in such patients.

Anticoagulation Strategies in the Management of Lemierre Syndrome: A Systematic Review of the Literature.

OBJECTIVE: To determine the optimal anticoagulation strategy in patients diagnosed with Lemierre Syndrome (LS). DATA SOURCES: A systematic review in accordance with PRISMA guidelines was conducted using PubMed, MEDLINE, Scopus, ProQuest, and CINAHL from January to April 2020. Search terms included "Lemierre Syndrome" AND "anticoagulation" NOT "prophylaxis" OR "atrial fibrillation," in addition to a list of parenteral and oral anticoagulants. Adult patients who developed a clot and required systemic anticoagulation as a result of LS were included in this review. STUDY SELECTION AND DATA EXTRACTION: A total of 4180 records were initially identified, though following the removal of duplicates and nonrelevant entries, 216 full-text articles were reviewed for inclusion; 13 articles were ultimately included. DATA SYNTHESIS: The majority (11/14) of patients developed thromboses of the internal jugular veins, which corresponds to the pathophysiology of LS. Anticoagulation strategies were varied in the included literature, though 12/14 patients initially received a parenteral product. Two patients received a direct-acting oral anticoagulant (DOAC) following either intravenous heparin or subcutaneous enoxaparin and had outcomes similar to patients transitioned to warfarin. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Anticoagulation in LS is a clinical controversy because the thromboembolic events have rarely led to significant complications; thrombi typically resolve independently, and concerns for bleeding risks are well founded; however, this review indicates both the efficacy and safety of anticoagulation. CONCLUSIONS: Anticoagulation is both efficacious and safe in LS, including treatment using a DOAC. Although further studies are needed, clinicians should consider a duration of anticoagulation of 6 to 12 weeks.

Reverse remodeling of tricuspid valve morphology and function in chronic thromboembolic pulmonary hypertension patients following pulmonary thromboendarterectomy: a cardiac magnetic resonance imaging and invasive hemodynamic study.

BACKGROUND: To investigate changes in tricuspid annulus (TA) and tricuspid valve (TV) morphology among chronic thromboembolic pulmonary hypertension (CTEPH) patients before and 12 months after pulmonary thromboendarterectomy (PEA) and compare these findings to normal control subjects. METHODS: 20 CTEPH patients and 20 controls were enrolled in the study. The patients were examined with echocardiography, right heart catherization and cardiac magnetic resonance imaging prior to PEA and 12 months after. RESULTS: Right atrium (RA) volume was significantly reduced from baseline to 12 months after PEA (30 ± 9 vs 23 ± 5 ml/m2, p < 0.005). TA annular area in systole remained unchanged (p = 0.11) and was comparable to controls. The leaflet area, tenting volume and tenting height in systole were significantly increased at baseline but decreased significantly with comparable values to controls after 12 months (p < 0.005). There was correlation between the changes of right ventricular-pulmonary artery coupling and changes of TV tenting height (r = - 0.54, p = 0.02), TV tenting volume (r = - 0.73, p < 0.001) and TV leaflet area (- 0.57, p = 0.01) from baseline to 12 months after PEA. Tricuspid regurgitation jet area/RA area was significantly (p < 0.01) reduced from baseline (30 ± 13%) to 12 months after PEA (9 ± 10%). CONCLUSION: In CTEPH patients selected for PEA, TV tenting height, volume and valve area are significantly increased whereas annulus size and shape are less affected. The alterations in TV morphology are fully reversed after PEA and correlates to improvements of right ventricular-pulmonary arterial coupling.

Effect of Supervised Training Therapy on Pulmonary Arterial Compliance and Stroke Volume in Severe Pulmonary Arterial Hypertension and Inoperable or Persistent Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. OBJECTIVES: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). METHOD: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. RESULTS: Low-dose exercise training at 4-7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group -0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15-0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group -4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5-21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. CONCLUSIONS: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings.

The effectiveness of percutaneous mechanical thrombectomy in the treatment of acute thromboembolic occlusions of lower extremity.

OBJECTIVES: The objective of this study was to evaluate the effectiveness of percutaneous mechanical thrombectomy as the initial thrombus removal method in the treatment of acute lower extremity ischemia. METHODS: The patients with acute lower limb ischemia who underwent percutaneous mechanical thrombectomy between August 2016 and February 2018 were retrospectively reviewed. The patients were diagnosed by clinical examination and computed tomography angiography. The percutaneous mechanical thrombectomy was performed as the initial thrombus removal method, followed by anticoagulation therapy. The patients were followed up by clinical examination, imaging, and ankle brachial index (ABI) examination. RESULTS: Thirty-two patients (21 males, 11 females; average age of 68.53 ± 8.05; three cases of grade III, 29 cases of grade IIB) were reviewed. Recanalization of the thromboembolic occlusions were achieved in all patients. ABI significantly (p < 0.01) increased postoperatively (preoperative ABI: 0.51 ± 0.13; postoperative ABI: 0.85 ± 0.65, ABI at three months postoperatively: 0.84 ± 0.66). Eleven patients underwent balloon dilation and three patients had stent placement. Complete thrombus removal was achieved in all patients. The primary patency at 3 months, 6 months, and 12 months postoperatively was 90%, 85%, and 56%, respectively. The secondary patency at 3 months, 6 months, and 12 months postoperatively was 93%, 87%, and 65%, respectively. CONCLUSIONS: The immediate result appeared to be effective to use percutaneous mechanical thrombectomy as the first thrombus removal method in the treatment of acute thromboembolic occlusions in the lower extremity, while the midterm result needs to be further improved.

Carboxypeptidase U (CPU, TAFIa, CPB2) in Thromboembolic Disease: What Do We Know Three Decades after Its Discovery?

Procarboxypeptidase U (proCPU, TAFI, proCPB2) is a basic carboxypeptidase zymogen that is converted by thrombin(-thrombomodulin) or plasmin into the active carboxypeptidase U (CPU, TAFIa, CPB2), a potent attenuator of fibrinolysis. As CPU forms a molecular link between coagulation and fibrinolysis, the development of CPU inhibitors as profibrinolytic agents constitutes an attractive new concept to improve endogenous fibrinolysis or to increase the efficacy of thrombolytic therapy in thromboembolic diseases. Furthermore, extensive research has been conducted on the in vivo role of CPU in (the acute phase of) thromboembolic disease, as well as on the hypothesis that high proCPU levels and the Thr/Ile325 polymorphism may cause a thrombotic predisposition. In this paper, an overview is given of the methods available for measuring proCPU, CPU, and inactivated CPU (CPUi), together with a summary of the clinical data generated so far, ranging from the current knowledge on proCPU concentrations and polymorphisms as potential thromboembolic risk factors to the positioning of different CPU forms (proCPU, CPU, and CPUi) as diagnostic markers for thromboembolic disease, and the potential benefit of pharmacological inhibition of the CPU pathway.

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

Ischemic Stroke in Patients With Sinus Node Disease, Atrial Fibrillation, and Other Cardiac Conditions.

Background and Purpose- Atrial fibrillation (AF) is known to increase risk of ischemic stroke (IS), but the risk of IS in isolated sinus node disease (SND) is unclear. We compared the incidence of IS in patients with SND, patients with AF, and in a control population with other cardiac diseases (disease of the circulatory system using the International Classification of Diseases, Tenth Revision). Methods- This French longitudinal cohort study was based on the national database covering hospital care for the entire population from 2008 to 2015. Results- Of 1 692 157 patients included in the cohort, 100 366 had isolated SND, 1 564 270 had isolated AF, and 27 521 had AF associated with SND. Incidence of IS during follow-up was higher in isolated patients with AF than in AF associated with SND (yearly rate 2.22% versus 2.06%) and in isolated patients with AF than in isolated patients with SND (yearly rate 2.22% versus 1.59%). The incidence of IS was lower in a control population with other cardiac conditions (n=479 108) compared with SND and patients with AF (0.96%/y, 1.59%/y, and 2.22%/y, respectively). After 1:1 propensity score matching, SND was associated with lower incidence of IS compared to AF (hazard ratio, 0.77 [95% CI, 0.73-0.82]) but higher incidence of IS compared to control population (hazard ratio, 1.27 [95%CI, 1.19-1.35]). Conclusions- Patients with SND had a lower risk of thromboembolic events than patients with AF but a higher risk than a control population with other cardiac diseases. Randomized clinical trial in a selected SND population, with, for example, a high CHA2DS2-VASc score, would be required to determine the value of IS prevention by anticoagulation.

The assessment of patients with the antiphospholipid antibody syndrome: where are we now?

The antiphospholipid antibody syndrome (APS), a chronic autoimmune thrombophilia with an increased mortality and morbidity, has been recognized for more than three decades. Unlike other autoimmune rheumatic conditions such as systemic lupus erythematosus, myositis and Sjögren's syndrome, relatively few attempts have been made to develop activity, damage or disease-specific quality of life indices for APS. In this review of the literature, we consider those attempts that have been made to develop assessment tools for patients with APS, but also reflect upon the nature of the condition, to discuss, in particular, whether an activity index is appropriate for this disease.

The role of multimodality imaging in the diagnosis of left ventricular noncompaction.

Left ventricular noncompaction (LVNC) is a heterogeneous entity and, in reality, a likely spectrum of disease which is clinically associated with arrhythmia, thromboembolic complications and sudden cardiac death. With the emergence of cardiac MRI (cMRI), the phenotype is increasingly more prevalent, resulting in clinical uncertainty regarding prognosis and management. The currently accepted hypothesis suggests an early embryonic arrest of the normal, sequential myocardial compaction process. LVNC is observed in isolation or in association with congenital heart disease, neuromuscular disease or a vast array of genetic cardiomyopathies. Definition of the entity varies among international society guidelines with differences both within and between imaging modalities, predominantly echocardiography and cMRI. Long-term prognostic data are emerging but due to the intrinsic variability in reported prevalence, selection bias and lack of pathological to prognostic correlation, there are many uncertainties regarding clinical management. This review seeks to clarify the role of multimodality imaging in diagnosis and management of the disease. We discuss the sensitivity and specificity of the current diagnostic criteria, as well as the nuances in diagnosis using the available imaging modalities.

Translational Implications of Platelets as Vascular First Responders.

Platelets play a vital role in normal hemostasis to stem blood loss at sites of vascular injury by tethering and adhering to sites of injury, recruiting other platelets and blood cells to the developing clot, releasing vasoactive small molecules and proteins, and assembling and activating plasma coagulation proteins in a tightly regulated temporal and spatial manner. In synchrony with specific end products of coagulation, primarily cross-linked fibrin, a stable thrombus quickly forms. Far beyond physiological hemostasis and pathological thrombosis, emerging evidence supports platelets playing a pivotal role in vascular homeostasis, inflammation, cellular repair, regeneration, and wide range of autocrine and paracrine functions. In essence, platelets play both structural and functional roles as reporters, messengers, and active transporters surveying the vasculature for cues of environmental or developmental stimuli and participating as first responders.1 In this review, we will provide a contemporary perspective of platelet physiology, including fundamental, translational, and clinical constructs that apply directly to human health and disease.

Distribution of Cardioembolic Stroke: A Cohort Study.

BACKGROUND: A cardiac origin in ischemic stroke is more frequent than previously assumed, but it is not clear which patients benefit from cardiac work-up if obvious cardiac pathology is absent. We hypothesized that thromboembolic stroke with a cardiac source occurs more frequently in the posterior circulation compared with thromboembolic stroke of another etiology. METHODS: We performed a multicenter observational study in 3,311 consecutive patients with ischemic stroke who were enrolled in an ongoing prospective stroke registry of 8 University hospitals between September 2009 and November 2014 in The Netherlands. In this initiative, the so-called Parelsnoer Institute-Cerebrovascular Accident Study Group, clinical data, imaging, and biomaterials of patients with stroke are prospectively and uniformly collected. We compared the proportions of posterior stroke location in patients with a cardiac stroke source with those with another stroke etiology and calculated risk ratios (RR) with corresponding 95% CI with Poisson regression analyses. To assess which patient or disease characteristics were most strongly associated with a cardiac etiology in patients with ischemic stroke, we performed a stepwise backward regression analysis. RESULTS: For the primary aim, 1,428 patients were eligible for analyses. The proportion of patients with a posterior stroke location among patients with a cardiac origin of their stroke (28%) did not differ statistically significant to those with another origin (25%), age and sex adjusted RR 1.16; 95% CI 0.96-1.41. For the secondary aim, 1,955 patients were eligible for analyses. No recent history of smoking, no hyperlipidemia, coronary artery disease, a higher age, and a higher National Institutes of Health Stroke Scale (NIHSS) score were associated with a cardiac etiology of ischemic stroke. CONCLUSIONS: We could not confirm our hypothesis that thromboembolic stroke localized in the posterior circulation is associated with a cardioembolic source of ischemic stroke, and therefore posterior stroke localization on itself does not necessitate additional cardiac examination. The lack of determinants of atherosclerosis, for example, no recent history of smoking and no hyperlipidemia, coronary artery disease, a higher age, and a higher NIHSS score are stronger risk factors for a cardiac source of ischemic stroke.

Numerical investigation on the effect of bileaflet mechanical heart valve's implantation tilting angle and aortic root geometry on intermittent regurgitation and platelet activation.

Platelet activation induced by shear stresses and non-physiological flow field generated by bileaflet mechanical heart valves (BMHVs) leads to thromboembolism, which can cause fatal consequences. One of the causes of platelet activation could be intermittent regurgitation, which arises due to asynchronous movement and rebound of BMHV leaflets during the valve closing phase. In this numerical study, the effect of intermittent regurgitation on the platelet activation potential of BMHVs was quantified by modeling a BMHV in the straight and anatomic aorta at implantation tilt angles 0°, 5°, 10°, and 20°. A fully implicit Arbitrary Lagrangian-Eulerian-based Fluid-Structure Interaction formulation was adopted with blood modeled as a multiphase, non-Newtonian fluid. Results showed that the intermittent regurgitation and consequently the platelet activation level increases with the increasing implantation tilt of BMHV. For the straight aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 20° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 8.5°, 3°, and 0°, respectively. For the anatomic aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 24° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 14°, 10°, and 7°, respectively. For all the implantation orientations of BMHVs, intermittent regurgitation and platelet activation were always higher in the anatomic aorta than in the straight aorta. The study concludes that the pivot axis of BMHV must be implanted parallel to the aortic root's curvature to minimize intermittent regurgitation and platelet activation.

Procedural Complications and Factors Influencing Immediate Angiographic Results after Endovascular Treatment of Small (<5 mm) Ruptured Intracranial Aneurysms.

BACKGROUND AND OBJECTIVE: There are technical challenges to complete occlusion of small (<5 mm) ruptured intracranial aneurysms (SRAs) using endovascular treatment (EVT). This study analyzed factors influencing immediate angiographic results in SRAs after EVT. MATERIAL AND METHODS: Intraoperative angiograms and medical records of 290 patients, who underwent EVT for SRAs at 2 stroke centers in China between January 2009 and October 2016, were retrospectively reviewed and evaluated. RESULTS: Immediate complete occlusion was achieved in 213 (73.4%) aneurysms. Aneurysms with a smaller aspect ratio, those less than 3 mm in size, irregular shape, small basal outpouching, multiple aneurysms, poorer Hunt and Hess grade, and location of communication arteries demonstrated higher rates of incomplete occlusion, although the differences were not statistically significant. Multivariate logistic regression analysis revealed that SRAs with parent artery stenosis greater than or equal to 50% and lobulation demonstrated a higher incidence of incomplete occlusion. Intra-procedural rupture occurred in 13 (6.1%) patients in the complete occlusion group, and 3 (3.9%) in the incomplete occlusion group (P = .467). Thromboembolic complications occurred in 3 (1.0%) patients, and 4 (1.9%) underwent decompressive craniotomy after EVT, all of whom were in the complete occlusion group. Nine (4.2%) patients in the complete occlusion group and 2 (2.6%) in the incomplete occlusion group (P = .733) experienced intraprocedural vasospasm, with corresponding morbidity and mortality rates of 15.0% and 2.1%, respectively. CONCLUSIONS: Proximal parent artery stenosis greater than or equal to 50% and lobulation were independent predictors of incomplete occlusion in patients with SRAs. Higher rates of intraprocedural rupture, thromboembolic complications, intraprocedural vasospasm, and mortality were found in the complete occlusion group; however, these differences were not statistically significant. Complete occlusion of SRAs may be achieved without additional mortality and perioperative complications.

Anticoagulation in Patients with Heart Failure and Sinus Rhythm.

The risk of thromboembolic events is significantly increased among patients with heart failure, even in those without atrial fibrillation. However, it is still unclear whether patients with heart failure and sinus rhythm can benefit from prophylactic anticoagulant therapy.This was a retrospective review of the pathophysiological mechanisms, epidemiological studies, and clinical trials on anticoagulation in patients with heart failure and sinus rhythm.Some subgroup analyses of clinical trials found that prophylactic anticoagulant therapy could reduce the incidence of stroke in patients with heart failure and sinus rhythm, and the risk of bleeding was significantly increased. Regarding the incidence of primary endpoint outcomes, all results from clinical trials were negative.Prophylactic anticoagulation did not improve the clinical outcome in patients with heart failure and sinus rhythm.

Pancreatic injury in COVID-19: pathogenesis and challenges.

Apart from the mechanisms reported by Fernandes et al, the thromboembolic pathogenesis should also be taken into account in patients with severe COVID-19 and prophylaxis with low molecular weight heparin should be implemented.

Inherited Risk Factors of Thromboembolic Events in Patients with Primary Nephrotic Syndrome.

Background and objectives. Venous thromboembolic events (VTEs) are among the most important complications of nephrotic syndrome (NS). We conducted a study that aimed to determine the prevalence of inherited risk factors for VTE in NS and to identify which factors are independent predictors of VTE. Materials and Methods. Thirty-six consecutive patients with primary NS that underwent percutaneous kidney biopsy between January 2017 and December 2017 were enrolled in this retrospective, observational study. VTEs were the primary outcome. Baseline demographic and biochemical data were collected from medical records, and genetic testing was done for polymorphisms of Factor V, PAI, MTHFR, and prothrombin genes. Results. The incidence of VTE was 28%, and the median time to event was 3 months (IQR: 2-9). The prevalence of inherited risk factors was 14% for Factor V Leiden mutation, 5.6% for prothrombin G20210A, 44.5% for PAI, and 27.8% for each of the two polymorphisms of the MTHFR gene. On multivariate analysis, the presence of at least two mutations was independently associated with the risk of VTE (HR, 8.92; 95% confidence interval, CI: 1.001 to 79.58, p = 0,05). Conclusions. These findings suggest that genetic testing for inherited thrombophilia in NS could play an important role in detecting high-risk patients that warrant prophylactic anticoagulation.

Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation: Should We Use a CHA2DS2-VA Score Rather Than CHA2DS2-VASc?

BACKGROUND: Stroke risk in atrial fibrillation is assessed by using the CHA2DS2-VASc score. Sex category (Sc, ie, female sex) confers 1 point on CHA2DS2-VASc. We hypothesized that female sex is a stroke risk modifier, rather than an overall risk factor, when added to a CHA2DS2-VA (sex-independent thromboembolism risk) score scale. METHODS: Using 3 nationwide registries, we identified patients with incident nonvalvular atrial fibrillation from January 1, 1997, through December 31, 2015. Patients receiving oral anticoagulant treatment at baseline were excluded, and person-time was censored at the time of treatment initiation (if any). CHA2DS2-VA scores were calculated for men and women, and were followed for up to 1 year in the Danish National Patient Registry. The primary outcome was a primary hospital code for ischemic stroke or systemic embolism (thromboembolism). We calculated crude event rates for risk strata as events per 100 person-years. For quantifying absolute risk of stroke, we calculated risks based on the pseudovalue method. Female sex as a prognostic factor was investigated by inclusion as an interaction term on the CHA2DS2-VA score to calculate the thromboembolic risk ratio for different score points. RESULTS: A total of 239 671 patients with atrial fibrillation (48.7% women) contributed to the analyses. The mean ages for women and men were 76.6 years and 70.3 years, respectively; the mean CHA2DS2-VA scores were 2.7 for women and 2.3 for men. The overall 1-year thromboembolic rate per 100 person-years for women was 7.3 and 5.7 for men. The 1-year absolute risk of thromboembolism was 0.5% among men and women with a CHA2DS2-VA score of 0 and increased up to >7% among very comorbid patients (score >5). The risk ratio (male as reference) across points >1 indicated that women exhibit a higher stroke risk. The interaction was statistically significant (P<0.001). CONCLUSIONS: Female sex is a risk modifier for stroke in patients with atrial fibrillation. Initial decisions on oral anticoagulant treatment could be guided by a CHA2DS2-VA score (ie, excluding the sex category criterion), but the Sc risk component modifies and accentuates stroke risk in women who would have been eligible for oral anticoagulant treatment on the basis of ≥2 additional stroke risk factors.