Clinical relevance of incomplete device endothelialization after left atrial appendage closure.

PURPOSE: This study aimed to assess the incidence, potential risk factors and clinical impact of incomplete device endothelialization(IDE) after left atrial appendage closure (LAAC). METHODS: A total of 101 consecutive patients with nonvalvular atrial fibrillation (AF) who underwent successful LAAC and received antithrombotic treatment using a standard regimen were prospectively followed up to 6 months after the procedure. The status of device endothelialization and device-related thrombus (DRT) were evaluated using cardiac computed tomography (CT). Major adverse cardio-cerebral events (MACCE) including all-cause death, heart failure(HF) hospitalization, acute ischemic stroke, transient ischemic attack(TIA), peripheral vascular embolism, and major bleeding were recorded. RESULTS: IDE was detected in 65 (64.4%) patients. Patients with IDE or complete device endothelialization (CDE) did not significantly differ with respect to baseline clinical characteristics and interventional procedure features. Multivariate analysis model revealed that persistent AF, left atrial appendage ostial diameter and left atrial size were independent risk factors for IDE. During 6-month follow-up, the incidence of DRT was 4.6% in patients with IDE and 2.8% in those with CDE, respectively (p > 0.05), and the overall rate of MACCE was non-significantly higher in the IDE group (7.7% vs. 2.8%, p = 0.32). CONCLUSION: IDE is common after LAAC, especially in patients with persistent AF, higher left atrial appendage ostial diameter and left atrial size. IDE confers an increased risk for DRT, but may be not necessarily associated with thromboembolic events and poor clinical outcome, providing careful monitoring and continued antithrombotic therapy are given.

TREM-1 Modulates Dendritic Cells Maturation and Dendritic Cell-Mediated T-Cell Activation Induced by ox-LDL.

Atherosclerosis is a chronic inflammatory disease. The triggering receptor expressed on myeloid cells-1 (TREM-1) plays a crucial role in inflammatory diseases; recently, it was identified as a major upstream proatherogenic receptor, but its mechanism is still unclear. In this study, we explore the role of TREM-1 on dendritic cells maturation and inflammatory responses induced by ox-LDL and its possible mechanism. Human dendritic cells were differentiated from blood monocytes and treated with ox-LDL. Naive autologous T cells were cocultured with pretreated DCs or treated directly. The expression of TREM-1 and inflammatory factors were evaluated by real-time PCR, western blot, and ELISA methods. And the expression of immune factors to evaluate the DCs maturation and T-cell activation were determined by the FACS. Our study showed that ox-LDL induced TREM-1 expression, DC maturation, and T-cell activation. T cells exposed to ox-LDL-treated DCs produced interferon-γ and interleukin-17 (IL-17). Blocking TREM-1 suppressed the DC maturation, showing lower expression of CD1a, CD40, CD86, CD83, and HLA-DR, and limited their production of tumor necrosis factor-alpha (TNF-α), IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1), meanwhile increased transforming growth factor-ß(TGF-ß) and IL-10 production. Ox-LDL induced miR-155, miR-27, Let-7c, and miR-185 expression; however, TREM-1 inhibiting decreased miRNA-155 expression. Furthermore, silencing miRNA-155 restores SOCS1 repression induced by ox-LDL. Experiments with T cells derived from carotid atherosclerotic plaques or healthy individuals showed similar results. Our results uncover a new link between ox-LDL and TREM-1 and may provide insight into this interaction in the context of atherosclerosis.

Elevated FURIN levels in predicting mortality and cardiovascular events in patients with acute myocardial infarction.

OBJECTIVES: Proprotein convertase subtilisin/kexin (PCSK) family member 3 (FURIN) has been suggested to be involved in the development of atherosclerosis. The aim of this study was to investigate the prognostic implication of FURIN in patients after acute myocardial infarction (AMI). METHODS: This prospective study analyzed data from a total of 1312 consecutive patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction from August 2013 to June 2016. FURIN levels were analyzed in plasma obtained from AMI patients. RESULTS: The study included 1312 AMI patients. The patient population was predominantly male (63%) with a median age of 66 years (IQR: 19 years), and 59% were STEMI patients. During a follow-up of 2 years, 117 patients died, and 377 patients reached the combined endpoints of major adverse cardiac events (MACE). Patients with elevated FURIN levels had increased risk of MACE, all-cause mortality, recurrent MI and hospitalization for HF (log-rank test, p < 0.0001). After adjusting for clinical risk factors and established markers, the association of FURIN concentrations with the risk of MACE and its individual components and cardiovascular death was statistically significant in the higher tertile of FURIN concentrations. After the addition of FURIN to the models, FURIN showed additive prognostic significance for 2-year clinical outcomes. Variable importance plots of the models showed that FURIN was of high importance to predict both occurrence of MACE and all-cause mortality. CONCLUSIONS: We found that FURIN was associated with all-cause mortality and recurrent cardiovascular events in AMI patients independent of conventional risk factors and established markers.

Prognostic Utility of Soluble TREM-1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be critical for inflammatory signal amplification and involved in the development of atherosclerosis. TREM-1 is significantly increased in patients with myocardial infarction. The aim of this study was to investigate the association between soluble TREM-1 (sTREM-1) and mortality and cardiovascular events in patients with acute myocardial infarction. METHODS AND RESULTS: We included 838 consecutive patients with acute myocardial infarction from October 7, 2012 to December 5, 2014. Blood samples were collected from patients with acute myocardial infarction immediately after diagnosis. During follow-up, 88 patients died, and 180 patients reached the combined end points of major adverse cardiovascular event (MACE). Patients with high sTREM-1 (higher than the median) had increased risk of all-cause mortality and MACE compared with those with low sTREM-1 (log-rank test, P<0.001). After adjustment for confounding risk factors by Cox regression analysis, high sTREM-1 remained an independent predictor of all-cause mortality (hazard ratio, 1.978; 95% confidence interval, 1.462-2.675; P<0.001) and MACE (hazard ratio, 2.413; 95% confidence interval, 2.022-2.879; P<0.001). After the addition of sTREM-1 to the reference model, the C-statistic for all-cause mortality increased from 0.86 to 0.89, and the difference was 0.023 (95% confidence interval, 0.0009-0.0477), and the C-statistic for MACE increased from 0.71 to 0.80, and the difference was 0.087 (95% confidence interval, 0.053-0.122). sTREM-1 levels were consistently positively associated with risks of all-cause mortality and MACE in various subpopulations, and there was no significant interaction among prespecified subgroups. CONCLUSIONS: sTREM-1 was significantly associated with all-cause mortality and MACE, independent of established conventional risk factors in patients with acute myocardial infarction.

2-[3-(Trifluoro-meth-yl)phen-oxy]ethyl 1-oxo-2,6,7-trioxa-1λ-phosphabicyclo-[2.2.2]octane-4-carboxyl-ate.

In the crystal structure of the title compound, C(14)H(14)F(3)O(7)P, the central chain, which connects the phosphate bicyclic system and the benzene ring, is made up of an approximately planar C-C(O)-O-C(H(2)) fragment and a C(H(2))-O-C(Ph) link; the mean planes make a dihedral angle of 75.9 (2)°. The F atoms are disordered over two positions; the site occupancy factors are ca 0.6 and 0.4.