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Aims As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. Methods and results We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41–0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67–1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32–1.14 and RR 0.59, 95% CI 0.34–1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29–0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25–0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16–0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. Conclusion Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.

Randomized studies have reported low rates of atrial fibrillation (AF) after patent foramen ovale (PFO) closure (6%) but have relied on patient-reported symptomatic episodes, so the true incidence and timing of AF after PFO closure remain unknown.The aim of this study was to prospectively determine the incidence, timing, and determinants of supraventricular arrhythmia following PFO closure on the basis of loop recorder monitoring.Cardiac monitoring was proposed to all patients after PFO closure from June 2018 to October 2021 at a single center by means of implantable loop recorder monitoring in patients considered at higher risk for AF (age ≥ 55 years, associated cardiovascular risk factors, prior palpitations, or documented supraventricular ectopic activity) or 4-week external loop recorder monitoring in other patients. The primary endpoint was the incidence of AF, atrial flutter, or supraventricular tachycardia lasting30 seconds within 28 days of the procedure. Determinants of the primary endpoint were assessed using a stepwise logistic regression model.A total of 225 patients were included. The primary endpoint occurred in 47 patients (20.9%), including 13 (9.9%) and 24 (28.9%) among patients monitored with external loop recorders and implantable loop recorders, respectively. Overall, the median delay from procedure to arrhythmia was 14.0 days (IQR: 6.5-19.0 days), and one-half of these patients reported symptomatic episodes. Determinants of the primary endpoint were older age (adjusted OR: 1.67 per 10-year increase; 95% CI: 1.18-2.36), device left disc diameter ≥25 mm (adjusted OR: 2.67; 95% CI: 1.19-5.98) and male sex (adjusted OR: 4.78; 95% CI: 1.96-11.66).Using loop recorder monitoring for ≥28 days, supraventricular arrhythmia was diagnosed in 1 in 5 patients, with a median delay of 14 days, suggesting that this postprocedural event has so far been underestimated.

X-linked inhibitor of apoptosis protein (XIAP) exercises its biological function by locking up and inhibiting essential caspase-3, -7 and -9 toward apoptosis execution. It is overexpressed in multiple human cancers, and it plays an important role in cancer cells’ death skipping. Inhibition of XIAP-BIR3 domain and caspase-9 interaction was raised as a promising strategy to restore apoptosis in malignancy treatment. However, XIAP-BIR3 antagonists also inhibit cIAP1-2 BIR3 domains, leading to serious side effects. In this study, we worked on a theoretical model that allowed us to design and optimize selective synthetic XIAP-BIR3 antagonists. Firstly, we assessed various MM-PBSA strategies to predict the XIAP-BIR3 binding affinities of synthetic ligands. Molecular dynamics simulations using hydrogen mass repartition as an additional parametrization with and without entropic term computed by the interaction entropy approach produced the best correlations. These simulations were then exploited to generate 3D pharmacophores. Following an optimization with a training dataset, five features were enough to model XIAP-BIR3 synthetic ligands binding to two hydrogen bond donors, one hydrogen bond acceptor and two hydrophobic groups. The correlation between pharmacophoric features and computed MM-PBSA free energy revealed nine residues as crucial for synthetic ligand binding: Thr308, Glu314, Trp323, Leu307, Asp309, Trp310, Gly306, Gln319 and Lys297. Ultimately, and three of them seemed interesting to use to improve XIAP-BR3 versus cIAP-BIR3 selectivity: Lys297, Thr308 and Asp309.

BACKGROUND: Device-related thrombus (DRT) after left atrial appendage closure (LAAC) is associated with adverse outcomes, i.e. ischemic stroke or systemic embolism (SE). Data on predictors of stroke/SE in the context of DRT are limited.AIMS: This study aimed to identify predisposing factors for stroke/SE in DRT patients. In addition, the temporal connection of stroke/SE to DRT diagnosis was analyzed.METHODS: The EUROC-DRT registry included 176 patients, in whom DRT after LAAC were diagnosed. Patients with symptomatic DRT, defined as stroke/SE in the context of DRT diagnosis, were compared against patients with non-symptomatic DRT. Baseline characteristics, anti-thrombotic regimens, device position, and timing of stroke/SE were compared.RESULTS: Stroke/SE occurred in 25/176 (14.2%) patients diagnosed with DRT (symptomatic DRT). Stroke/SE occurred after a median of 198 days (IQR 37-558) after LAAC. In 45.8% stroke/SE occurred within one month before/after DRT diagnosis (DRT-related stroke). Patients with symptomatic DRT had lower left ventricular ejection fractions (50.0 ± 9.1% vs. 54.2 ± 11.0%, p = 0.03) and higher rates of non-paroxysmal atrial fibrillation (84.0% vs. 64.9%, p = 0.06). Other baseline parameters and device positions were not different. Most ischemic events occurred among patients with single antiplatelet therapy (50%), however, stroke/SE was also observed under dual antiplatelet therapy (25%) or oral anticoagulation (20%).CONCLUSION: Stroke/SE are documented in 14.2% and occur both in close temporal relation to the DRT finding and chronologically independently therefrom. Identification of risk factors remains cumbersome, putting all DRT patients at substantial risk for stroke/SE. Further studies are necessary to minimize the risk of DRT and ischemic events.

Background Randomized controlled trials evaluating patent foramen ovale (PFO) percutaneous closure only included patients with recent embolic event. We aimed to evaluate outcomes following percutaneous PFO closure outcomes according to the delay from the last embolic episode. Methods This international ambispective cohort included consecutive patients from two centers in France and Canada undergoing PFO percutaneous closure for secondary prevention of paradoxical embolic event. The primary endpoint was the composite of stroke or transient ischemic attack (TIA). Logistic regression model was used to evaluate determinants of late PFO closure procedures. Results A total of 1,179 patients (mean age 49±12.7 years; 44.4% female) underwent PFO closure from 2001 to 2021 (Figure 1). The median delay from last embolic event to procedure was 6.0 (3.4–11.2) months. Determinants of late PFO closure procedure were the center (France versus Canada) adjusted Odds Ratio (aOR) 1.65 95% confidence interval (CI) 1.25–2.19, year of procedure (≥2018 versus Conclusion This analysis provides indirect evidence that delay from last ischemic event does not impact outcomes following PFO percutaneous closure for secondary prevention. Funding Acknowledgement Type of funding sources: None.

Background Data on Device-related Thrombus (DRT) after left atrial appendage closure (LAAC) remain scarce. This study aimed to investigate risk factors for DRT from centers reporting to the EUROC-DRT registry. Methods We included 537 patients (112 with DRT and 425 without DRT) who had undergone LAAC between 12/2008 and 04/2019. Baseline and implantation characteristics, anti-thrombotic treatment and clinical outcomes were compared between both groups in uni- and multivariate analyses. Additional propensity-score matching (PSM) was conducted to focus on the role of implantation characteristics. Results Patients with DRT showed higher rates of previous stroke/transient ischemic attack (TIA) (49.1% vs. 34.7%, p < 0.01), spontaneous echocardiographic contrast (SEC) (44.9% vs. 27.7%, p < 0.01) and lower left atrial appendage (LAA) peak emptying velocity (35.4 +/- 18.5 vs. 42.4 +/- 18.0 cm/s, p= 0.02). Occluders implanted in DRT patients were larger (25.5 +/- 3.8 vs. 24.6 +/- 3.5 mm, p =0.03) and implanted deeper in the LAA (mean depth: 7.6 +/- 4.7 vs. 5.7 +/- 4.7 mm, p

Resume Objectifs L’objectif de cette etude est d’evaluer les styles d’attachement dans une population de patients rencontres en Equipe Mobile Psychiatrie Precarite a Paris, hormis les migrants, afin d’aider a l’etablissement d’une alliance de travail et d’ameliorer le suivi de ces patients. Methodes Dix-huit patients en situation d’exclusion sociale rencontres en Equipe Mobile Psychiatrie Precarite, hormis les migrants, âges de 28 a 65 ans, ont ete recrutes entre decembre 2018 et juillet 2019. Les styles d’attachement des sujets ont ete evalues a l’aide du questionnaire Relationship Style Questionnaire–Codage Revise, afin d’obtenir la prevalence de chaque style d’attachement dans cet echantillon. Resultats Les analyses montrent un taux d’attachement insecure de 83 % dans cette population, avec une predominance du style detache retrouve chez 39 % des sujets. Conclusions Le taux d’insecurite de l’attachement tres eleve dans cette population pointe l’importance du role de Base de securite que devraient representer les Equipes Mobiles Psychiatrie Precarite pour les patients rencontres, premiere etape indispensable pour pouvoir les amener a des soins psychiques prolonges. La pertinence de therapies basees sur l’attachement dans cette population est discutee. Ces equipes pourraient avoir un role de soin a part entiere, au-dela de leur fonction d’interface et d’orientation.

Aims The European Society of Cardiology (ESC) has released three consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores, and cholesterol treatment. This study aims to evaluate whether the 2021 ESC guidelines improved the eligibility of individuals for primary prevention statin therapy before their first ST-segment elevation myocardial infarction (STEMI), and for intensive lipid-lowering treatments in secondary prevention. Methods and results The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 vs. 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up low-density lipoprotein cholesterol (LDL-C) and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021 and 2019 vs. 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, P Conclusion The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first myocardial infarction. In secondary prevention, 70% of patients kept LDL-C levels above 55 mg/dL: increasing the statin dose and adding ezetimibe were the most frequently recommended therapeutic actions.