Rivaroxaban in heart failure patients with left ventricular thrombus: A retrospective study.

Background: The role of rivaroxaban in patients with heart failure (HF) combined with left ventricular (LV) thrombus remains unknown in current guideline-directed anticoagulant therapy. The aim of this study was to investigate the impact on clinical outcomes of rivaroxaban compared to vitamin K antagonists (VKAs) in patients with HF combined with LV thrombus. Methods: We retrospectively extracted clinical, echocardiographic and follow-up data of HF patients (all classifications) admitted at China-Japan Union Hospital of Jilin University from January 2017 to June 2021. A total of 198 patients with HF were identified with LV thrombus by echocardiography, 78 of them were managed with VKAs, 109 with rivaroxaban. Results: The median follow-up was 17.0 months (interquartile range: 6.0-24.0 months). High rates of major cardiovascular adverse events (MACEs) were observed in both the rivaroxaban and VKAs groups (49.5% vs. 57.7%). However, rivaroxaban versus VKAs observed a decrease in MACEs (adjusted HR:0.636; 95%CI:0.418-0.970; p = 0.035) and systemic embolism (4.6% vs. 12.8%; adjusted HR:0.318; 95%CI:0.108-0.933; p = 0.037; Gray's test p = 0.041) but was not found to have a benefit with regard to LV thrombus resolution (59.6% vs. 70.6%; adjusted HR: 1.303; 95% CI:0.898-1.890; p = 0.163; Gray's test p = 0.073). Additionally, there was no significant between-group difference in the rate of International Society on Thrombosis and Hemostasis (ISTH) bleeding events. Conclusion: Our data found that in populations with HF combined with LV thrombus, the overall prognosis in both the rivaroxaban and VKAs groups was catastrophic. Although rivaroxaban improved the prognosis to some extent, a considerable need remains for new treatments to improve their clinical course.

Prognosis and New Predictors of Early Left-Ventricular Thrombus Following ST-Elevation Myocardial Infarction.

OBJECTIVE: In the current era of primary percutaneous coronary intervention (PPCI), the prognosis of the left ventricular thrombus (LVT) is not well assessed. METHODS: We performed a retrospective, single-center study of 1305 consecutive ST-segment-elevation myocardial infarction (STEMI) patients treated with PPCI. During a mean period of 27 months of follow-up, the major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. RESULTS: The incidence of LVT (n = 47) was 3.60%. The independent risk factors of LVT included anterior STEMI, left ventricular (LV) aneurysm, reduced LV ejection fraction (LVEF), dilated LV end-diastolic dimension (LVEDD), and delayed door-to-balloon time (DTBT). During follow-up, LVT was an independent risk factor for MACCE [hazard ratio (HR)=3.46; 95% confidence interval (CI) = 2.23-3.38; P < 0.01]. Patients with LVT were more likely to have the following complications: heart failure (P < 0.001), embolic events (P = 0.034), and all-cause mortality (P = 0.020). Notably, the regression of LVT was not independently associated with those three adverse events (P > 0.05). CONCLUSION: In the era of PPCI, the presence of early LVT following STEMI was associated with adverse events. Furthermore, the prognosis of patients with LVT did not improve even if the LVT regressed. LVT was likely a generalized indicator of impaired cardiac performance, rather than the cause. This indicated that prophylactic therapy and identifying individuals with a high risk of developing LVT were of substantial importance.

Value of the platelet-to-lymphocyte ratio in the prediction of left ventricular thrombus in anterior ST-elevation myocardial infarction with left ventricular dysfunction.

BACKGROUND: The predictors of left ventricular thrombus (LVT) formation are not well defined in the contemporary era, especially in those patients at high risk. We aimed to evaluate whether the platelet/lymphocyte ratio (PLR) is valuable in the determination of LVT formation in patients with anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. METHODS: The LVT group (n = 46) was identified from anterior STEMI patients with LV dysfunction who were treated with primary percutaneous coronary intervention (PCI) from January 2017 to December 2019 at the China-Japan Union Hospital of Jilin University. The no-LVT group (n = 92) were also selected from the same batch of patients and were age- and sex-matched to the patients with LVT. The PLR was determined at admission and was calculated as the ratio of the platelet count to the lymphocyte count using the complete blood count. The presence of LVT was determined by echocardiography. RESULTS: The PLR were significantly higher in patients with LVT than in no-LVT group (p = 0.001). In a receiver operator characteristic curve (ROC) analysis, using a cut-off value of 118.07 (AUC 0.673, 95% CI: 0.574-0.771, P = 0.001), the PLR could independently predict the occurrence of LVT. Multivariate analysis showed that an increased PLR (OR = 1.011, 95% CI: 1.004-1.018, P = 0.002), the presence of a left ventricular aneurysm (OR = 46.350, 95% CI: 5.659-379.615, P < 0.001) and increased DTBT (OR = 1.005, 95% CI: 1.001-1.009, P = 0.012) were independent predictors of LVT formation. CONCLUSIONS: In acute anterior STEMI patients with LV dysfunction, an increased PLR and DTBT and the presence of an LV aneurysm were independent predictors of LVT formation. A larger prospective study is warranted to evaluate this result. TRIAL REGISTRATION: This study was registered (May 4, 2019) on Chinese Clinical Trial Registry ( ChiCTR-DDD-17011214 ).

Degree of chemical functionalization of carbon nanotubes determines tissue distribution and excretion profile.

Getting rid of the tubes: An assessment of the retention of functionalized multi-walled carbon nanotubes (MWNTs) in the organs of mice was carried out using single photon emission computed tomography and quantitative scintigraphy (see scheme). Increasing the degree of functionalization on MWNTs enhanced renal clearance, while lower functionalization promoted reticuloendethelial system accumulation.

Cellular uptake and cytotoxic impact of chemically functionalized and polymer-coated carbon nanotubes.

The impact of nanomaterials such as carbon nanotubes on biological matter is a topic of increasing interest and concern and requires a multifaceted approach to be resolved. A modified cytotoxic (lactate dehydrogenase (LDH)) assay is developed in an attempt to offer a valid and reliable methodology for screening carbon nanotube toxicity in vitro. Two of the most widely used types of surface-modified multiwalled carbon nanotubes (MWNTs) are tested: ammonium-functionalized MWNTs (MWNT-NH3+ ) and Pluronic F127 coated MWNTs (MWNT:F127). Chemically functionalized MWNTs show significantly greater cellular uptake into lung epithelial A549 cells compared to the non-covalently Pluronic F127-coated MWNTs. In spite of this, MWNT:F127 exhibit enhanced cytotoxicity according to the modified LDH assay. The validity of the modified LDH assay is further validated by direct comparison with other less reliable or accurate cytotoxicity assays. These findings indicate the reliability of the modified LDH assay as a screening tool to assess carbon nanotube cytotoxicity and illustrate that high levels of carbon nanotube cellular internalization do not necessarily lead to adverse responses.

Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura.

The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, especially mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomographic imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura.

Cellular uptake mechanisms of functionalised multi-walled carbon nanotubes by 3D electron tomography imaging.

Carbon nanotubes (CNTs) are being investigated for a variety of biomedical applications. Despite numerous studies, the pathways by which carbon nanotubes enter cells and their subsequent intracellular trafficking and distribution remain poorly determined. Here, we use 3-D electron tomography techniques that offer optimum enhancement of contrast between carbon nanotubes and the plasma membrane to investigate the mechanisms involved in the cellular uptake of shortened, functionalised multi-walled carbon nanotubes (MWNT-NH(3)(+)). Both human lung epithelial (A549) cells, that are almost incapable of phagocytosis and primary macrophages, capable of extremely efficient phagocytosis, were used. We observed that MWNT-NH(3)(+) were internalised in both phagocytic and non-phagocytic cells by any one of three mechanisms: (a) individually via membrane wrapping; (b) individually by direct membrane translocation; and (c) in clusters within vesicular compartments. At early time points following intracellular translocation, we noticed accumulation of nanotube material within various intracellular compartments, while a long-term (14-day) study using primary human macrophages revealed that MWNT-NH(3)(+) were able to escape vesicular (phagosome) entrapment by translocating directly into the cytoplasm.

A cyclic triphenylamine dimer for organic field-effect transistors with high performance.

A cyclic ethylene linked triphenylamine dimer formed highly crystalline thin film via vapor deposition. Meanwhile, the corresponding linear molecule only resulted in amorphous films under the same condition. The performance as FET semiconductor also improved significantly when the molecular structure derived from linear to cyclic type. The cyclic molecule displayed mobilities in excess of 10-2 cm2 V-1 s-1 and high on/off ratios up to 107.

Effect of a Residual Stenosis by Quantitative Angiography on the Myocardial Contrast Defect Observed Following Coronary Reperfusion Using Intermittent Harmonic Ultrasound Imaging and Intravenous Perfluorocarbon Ultrasound Contrast.

Intermittent harmonic imaging following intravenously injected perfluorocarbon-containing microbubbles can detect myocardial perfusion abnormalities caused by ischemia. It is unknown whether this technique can differentiate viable, ischemic myocardium from infarcted myocardium immediately following coronary reperfusion. The objective of this paper was to determine whether intermittent harmonic imaging with intravenous microbubbles could define myocardial perfusion abnormalities following reperfusion. In 26 dogs, a prolonged total coronary occlusion (mean occlusion time 2.1 +/- 0.4 hours) was followed by coronary reperfusion. Wall thickening (WT) and peak myocardial video intensity (PMVI) within and outside the risk area (PMVI ratio) were measured following intravenous perfluorocarbon microbubbles under resting conditions and during a 5 µg/kg per minute dobutamine [low dose dobutamine (LDD)] infusion in the presence and absence of a >/= 50% diameter stenosis in the reperfused vessel. Infarct size was determined postmortem. The resting contrast defect in all dogs correlated closely (r = 0.93) with infarct size when no residual stenosis was present but correlated more closely with risk area (r = 0.88) when a >/= 50% diameter residual stenosis was present. In dogs with infarction involving > 50% of the risk area, the PMVI ratio was lower under resting conditions (0.51 +/- 0.27) than in dogs with no or partial infarction when no residual stenosis was present. However, in dogs with no or partial infarction, the PMVI ratio fell significantly when a >/= 50% diameter stenosis was present, both under resting conditions and during LDD. We conclude that the myocardial contrast defect observed with intermittent harmonic imaging and intravenous ultrasound contrast is affected by both the infarct size and the presence of a significant residual stenosis.

Differences in Myocardial Contrast Produced with Transient Response Imaging When Using Intravenous Microbubbles Containing Gases of Different Molecular Weight.

The purpose of this study was to determine the effect of different microbubble gases on the amount of myocardial contrast (MC) produced from intravenously (IV) injected dextrose albuinin microbubbles when using a new imaging modality termed transient response imaging (TRI). In 6 dogs (4 closed chest, 2 open chest) the peak anterior myocardial videointensity (PMVI) and visual degree of MC were determined following IV injections of equivalent doses of perfluorocarbon exposed sonicated dextrose albumin (PESDA), sulfur hexafluoride-exposed sonicated dextrose albumin (SHESDA), and room air exposed sonicated dextrose albumin (RASDA) microbubbles. TRI was performed by triggering ultrasound impulses to 1 point every one to two cardiac cycles. The PMVI produced with TRI was compared to conventional 30 Hz frame rate imaging (CI) for each gas. Visual anterior and posterior MC was evident with TRI in all six dogs using PESDA, but not in any dog with CI. Although RASDA and SHESDA did not produce MC with CI, visually evident anterior MC was seen after 7 of 8 SHESDA and 4 of 9 RASDA injections when using TRI with both gases. PESDA produced the highest peak PMVI of all three microbubbles when using TRI, while SHESDA produced a significantly higher PMVI than RASDA. We conclude that although MC can be produced with TRI using microbubble gases of lower molecular weight, the brightest and most consistent contrast is produced with fluorocarbon containing microbubbles.