Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel

Background Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel. Objectives We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel. Methods After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61(+), CD62p(+)), fibrinogen(+), phosphatidylserine (PS+), leukocytes (CD45(+)), endothelial cells (CD31(+), 146(+)), and erythrocytes (CD235a(+)) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity. Results Concentrations of platelet, fibrinogen(+), PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P = .17). Conclusions Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.Peer reviewe

Expression of miR-223 to predict outcomes after transcatheter aortic valve implantation

Background: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at increased surgical risk. Up to 29% of patients annually experience major adverse cardiac and cerebrovascular events (MACCE) after TAVI. MicroRNAs (miRNA) are currently widely investigated as novel cardiovascular biomarkers. The aim of this study was to determine the influence of TAVI on the expressions of selected miRNAs associated with platelet function (miR-125a-5p, miR-125b and miR-223), and evaluate the predictive value of these miRNAs for MACCE in 65 patients undergoing TAVI. Methods: Venous blood samples for miRNA expression analysis were collected 1 day before TAVI and at hospital discharge. The expression of miR-223, miR-125a-5p, miR-125b was evaluated in platelet-depleted plasma. Results: The expression of miR-223 and miR-125b increased after TAVI, compared to the measurement before (p = 0.020, p = 0.003, respectively). Among 63 patients discharged from the hospital, 18 patients experienced MACCE (29%) during the median 15 months of observation. Baseline low miR-223 expression was a predictor of MACCE in univariate Cox regression analysis (hazard ratio [HR]: 2.71, 95% confidence interval [CI]: 1.04–7.01; p = 0.041). After inclusion of covariates, age, gender (male), New York Heart Association class and diabetes into the multivariate Cox regression model, miR-223 did not reach statistical significance (HR: 2.56, 95% CI: 0.79–8.33; p = 0.118). Conclusions: To conclude, miR-223 might improve risk stratification after TAVI. Further studies are required to confirm the clinical applicability of this promising biomarker

Transient analysis of bang-bang phase locked loops

This work gives insight into the behaviour of second-order bang-bang phase locked loops in the far from lock region. This region, while largely unexplored, is of particular interest as PLL behaviour in this region determines locking time and capture range. By analysing PLL cycle slipping behaviour in this region, the transient response for the system is derived. Expressions for first-order system stability and locking time are also presented

Intuitive community digital assistant user interfaces based on wireless devices

We present the concept, implementations and capabilities of Community Digital Assistant (CDA) a wireless home infrastructure supporting easy interaction. Our goal was to explore input and output devices to CDA that eliminate the standard computer-like interface which can be difficult to use for the elderly or small children. Another idea was to use physical objects to allow a user to interact wirelessly and enable this way an intuitive and seamless interaction of users with the communication computer (CDA). We experimented with and integrated into the CDA commercial devices such as digital pen, digital notepad, handheld scanner and also developed a prototype of a novel interface device “fridge magnet” using RFID tags to enable physical objects to act as computer interface