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Background: Device‐related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. Methods and Results: This sub‐analysis from the EUROC‐DRT‐registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p =.06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p =.01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p =.40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p =.24). Women were followed‐up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p =.51). Kaplan–Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%‐Confidence interval [95%‐CI]:.68–4.37, p =.25) and no differences in stroke (HR:.83, 95%‐CI:.30–2.32, p =.72) within 2 years after LAAC. Conclusion: Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective. [ABSTRACT FROM AUTHOR]

Left atrial appendage occlusion (LAAO) is an accepted strategy for cardioembolic events prevention in patients with non-valvular atrial fibrillation (AF) unsuitable for anticoagulation. However, uncertainties persist regarding the benefit of LAAO in highly-comorbid patients. The aim of this study was to assess the impact of the CHA 2 DS 2 -VASc score beyond thromboembolic risk in predicting clinical outcomes in patients undergoing LAAO. 160 patients who underwent LAAO were included and categorized into two groups according to their stroke risk (89 with CHA 2 DS 2 -VASc >4 vs. 71 with lower risk). The coprimary endpoints were death and stroke at follow-up. Thromboembolic and bleeding events were compared to those predicted from CHA 2 DS 2 -VASc and HAS-BLED scores. Over a median follow-up of 679 days, CHA 2 DS 2 -VASc >4 was associated with increased all-cause mortality compared with patients with lower thromboembolic risk (HR: 3.23; 95% CI: 1.28–8.19; p < 0.001). However, the rates of stroke after LAAO were not significantly different between risk groups. The observed annual rates of stroke and major bleeding were lower than predicted. Despite increased long-term mortality in patients with CHA 2 DS 2 -VASc >4, LAAO remains beneficial in reducing stroke and bleeding events in high-risk AF patients unsuitable for anticoagulation. • Benefit of LAAO remains controversial in highly comorbid patients. • Thromboembolic risk scores can also predict all-cause mortality after LAAO. • LAAO occlusion reduces stroke and bleeding events in high-risk patients. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is nowadays the most common human arrhythmia and it is considered a marker of an increased risk of embolic stroke. It is known that 99% of AF-related thrombi are generated in the left atrial appendage (LAA), an anatomical structure located within the left atrium (LA). Left atrial appendage occlusion (LAAO) has become a good alternative for nonvalvular AF patients with contraindications to anticoagulants. However, there is a non-negligible number of device-related thrombus (DRT) events, created next to the device surface. In silico fluid simulations can be a powerful tool to better understand the relation between LA anatomy, haemodynamics, and the process of thrombus formation. Despite the increasing literature in LA fluid modelling, a consensus has not been reached yet in the community on the optimal modelling choices and boundary conditions for generating realistic simulations. In this line, we have performed a sensitivity analysis of several boundary conditions scenarios, varying inlet/outlet and LA wall movement configurations, using patient-specific imaging data of six LAAO patients (three of them with DRT at follow-up). Mesh and cardiac cycle convergence were also analysed. The boundary conditions scenario that better predicted DRT cases had echocardiography-based velocities at the mitral valve outlet, a generic pressure wave from an AF patient at the pulmonary vein inlets, and a dynamic mesh approach for LA wall deformation, emphasizing the need for patient-specific data for realistic simulations. The obtained promising results need to be further validated with larger cohorts, ideally with ground truth data, but they already offer unique insights on thrombogenic risk in the left atria. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Left atrial appendage closure is an established therapy in patients with atrial fibrillation. Although device-related thrombosis (DRT) is relatively rare, it is potentially linked to adverse events. As data on DRT characteristics, outcome, and treatment regimen are scarce, we aimed to assess these questions in a multicenter approach. Methods: One hundred fifty-six patients with the diagnosis of DRT after left atrial appendage closure were included in the multinational EUROC-DRT registry. Baseline characteristics included clinical and echocardiographic data. After inclusion, all patients underwent further clinical and echocardiographic follow-up to assess DRT dynamics, treatment success, and outcome. Results: DRT was detected after a median of 93 days (interquartile range, 54–161 days) with 17.9% being detected >6 months after left atrial appendage closure. Patients with DRT were at high ischemic and bleeding risk (CHA2DS2-VASc 4.5±1.7, HAS-BLED 3.3±1.2) and had nonparoxysmal atrial fibrillation (67.3%), previous stroke (53.8%), and spontaneous echo contrast (50.6%). The initial treatment regimens showed comparable resolution rates (antiplatelet monotherapy: 57.1%, dual antiplatelet therapy: 85.7%, vitamin K antagonists: 80.0%, novel oral anticoagulants: 75.0%, and heparin: 68.6%). After intensification or switch of treatment, complete DRT resolution was achieved in 79.5% of patients. Two-year follow-up revealed a high risk of mortality (20.0%) and ischemic stroke (13.8%) in patients with DRT. Patients with incomplete DRT resolution showed numerically higher stroke rates and increased mortality rates (stroke: 17.6% versus 12.3%, P =0.29; mortality: 31.3% versus 13.1%, P =0.05). Conclusions: A substantial proportion of DRT is detected >6 months after left atrial appendage closure, highlighting the need for imaging follow-up. Patients with DRT appear to be at a high risk for stroke and mortality. While DRT resolution was achieved in most patients, incomplete DRT resolution appeared to identify patients at even higher risk. Optimal DRT diagnostic criteria and treatment regimens are warranted. [ABSTRACT FROM AUTHOR]

Streptomyces clavuligerus is a filamentous Gram-positive bacterial producer of the β-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the Streptomyces genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of Streptomyces clavuligerus was reconstructed and used to study the experimentally observed effect of oxygen and phosphate concentrations on clavulanic acid biosynthesis under high and low shear stress. A flux balance analysis based on experimental evidence revealed that clavulanic acid biosynthetic reaction fluxes are favored in conditions of phosphate limitation, and this is correlated with enhanced activity of central and amino acid metabolism, as well as with enhanced oxygen uptake. In silico and experimental results show a possible slowing down of tricarboxylic acid (TCA) due to reduced oxygen availability in low shear stress conditions. In contrast, high shear stress conditions are connected with high intracellular oxygen availability favoring TCA activity, precursors availability and clavulanic acid (CA) production. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: This article presents the annual activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) for the year 2022., Methods: All Spanish centers with catheterization laboratories were invited to participate. Data were collected online and were analyzed by an external company in collaboration with the members of the board of the ACI-SEC., Results: A total of 111 centers participated. The number of diagnostic studies increased by 4.8% compared with 2021, while that of percutaneous coronary interventions (PCI) remained stable. PCIs on the left main coronary artery increased by 22%. The radial approach continued to be preferred for PCI (94.9%). There was an upsurge in the use of drug-eluting balloons, as well as in intracoronary imaging techniques, which were used in 14.7% of PCIs. The use of pressure wires also increased (6.3% vs 2021) as did plaque modification techniques. Primary PCI continued to grow and was the most frequent treatment (97%) in ST-segment elevation myocardial infarction. Most noncoronary procedures maintained their upward trend, particularly percutaneous aortic valve implantation, atrial appendage closure, mitral/tricuspid edge-to-edge therapy, renal denervation, and percutaneous treatment of pulmonary arterial disease., Conclusions: The Spanish cardiac catheterization and coronary intervention registry for 2022 reveals a rise in the complexity of coronary disease, along with a notable growth in procedures for valvular and nonvalvular structural heart disease., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Cardiac computed tomography angiography (CCTA) appears to be an appropriate imaging technique for device surveillance after left atrial appendage occlusion (LAAO). However, the available experience is limited., Aims: The aim of this study was to determine the prevalence, mechanisms and clinical impact of left atrial appendage (LAA) patency and device-related thrombosis (DRT) following LAAO utilising a novel CCTA-based classification., Methods: Consecutively enrolled patients who underwent LAAO with an AMPLATZER device were followed up with CCTA. Mechanisms and frequency of residual patency were evaluated and correlated with clinical events. Atrial-side device thrombus, device positioning and presence of signs of device stability were also analysed., Results: A total of 137 patients were included. LAA patency was observed in 56.9% (n=78). Mechanisms and frequency of patency were: malapposition of proximal segment of the device lobe (55.1%), peri-device leak (PDL, 34.6%) and fabric permeability (5.8%). Lobe-LAA axis misalignment was the only independent predictor of device patency after LAAO (HR 38.3, 95% CI: 13.6-107.0; p<0.001). After a median follow-up of 638 days, patency was not associated with an increased risk of death (all-cause or cardiovascular death) or cerebral/peripheral embolism regardless of its mechanism. Any degree of hypo-attenuated thickening (HAT) was found in 16.8% (n=23) of patients, of whom 16 (11.7%) had low-grade HAT and 7 (5.1%) had high-grade HAT or definite DRT. Complete sealing was associated with increased rates of low-grade HAT., Conclusions: LAA patency on CCTA follow-up is a frequent phenomenon due to malapposition of the proximal segment of the device lobe, PDL or fabric permeability. Patency was not associated with adverse outcomes. Low-grade HAT may be related to a benign, uneventful, endothelialisation process favoured by complete LAAO.

Aims: Percutaneous treatment of coronary chronic total occlusion (CTO) is associated with important arterial remodelling after successful recanalisation. Bioresorbable vascular scaffold (BVS) implantation in CTO has been shown to be feasible and can be of interest when the scaffold achieves complete bioresorption. We sought to evaluate the three-year results in terms of clinical events, serial imaging outcomes and vasomotion response in CTO lesions successfully treated with BVS., Methods and Results: A total of 33 patients (35 CTO lesions) successfully treated with BVS were included in the ABSORB-CTO study. Clinical outcomes, quantitative coronary angiography (QCA) and optical coherence tomography (OCT) assessment were analysed at one- and three-year follow-up. Vasomotion examination was also performed at three years. At three years, cumulative target vessel reocclusion was observed in four lesions (11.4%). By QCA, the in-scaffold segment presented a lumen loss of 0.23±0.46 mm compared with the baseline procedure (p=0.001) and a lumen gain of 0.05±0.29 mm between one and three years (p=0.220). By OCT, the mean neointimal area stenosis progressed from 11.45% at 12 months to 17.10% at 36 months (p<0.001) and mean scaffold area increased continuously at 12 (+12%; p<0.001) and at 36 months (+14.85%; p=0.001). Late acquired incomplete scaffold apposition (LAISA) observed at 12 months in three patients was completely undetectable at three years. Most cases responded to endothelium-dependent vasomotor stimuli (69%). Vasoconstriction to acetylcholine was the predominant response (45%)., Conclusions: Successful recanalisation of coronary CTO with BVS implantation is associated with favourable clinical and imaging outcomes. Despite vessel motility restoration, successfully treated CTOs remain with signs of endothelial dysfunction.