In a pooled analysis of 14 trials of alirocumab, Robinson et al. (1) reported the safety of alirocumab even with very low levels of low-density lipoprotein cholesterol (LDL). They found that 25% of ...the patients who received alirocumab had an LDL level <25 mg/dl with the median duration of low LDL level being ~43 weeks.
ObjectiveTo examine the relative impact of three management options in patients aged <60 years with cryptogenic stroke and a patent foramen ovale (PFO): PFO closure plus antiplatelet therapy, ...antiplatelet therapy alone and anticoagulation alone.DesignSystematic review and network meta-analysis (NMA) supported by complementary external evidence.Data sourcesMedline, EMBASE and Cochrane CENTRAL.Study selectionRandomised controlled trials (RCTs) addressing PFO closure and/or medical therapies in patients with PFO and cryptogenic stroke.Review methodsWe conducted an NMA complemented with external evidence and rated certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsTen RCTs in eight studies proved eligible (n=4416). Seven RCTs (n=3913) addressed PFO closure versus medical therapy. Of these, three (n=1257) addressed PFO closure versus antiplatelet therapy, three (n=2303) addressed PFO closure versus mixed antiplatelet and anticoagulation therapies and one (n=353) addressed PFO closure versus anticoagulation. The remaining three RCTs (n=503) addressed anticoagulant versus antiplatelet therapy. PFO closure versus antiplatelet therapy probably results in substantial reduction in ischaemic stroke recurrence (risk difference per 1000 patients over 5 years (RD): −87, 95% credible interval (CrI) −100 to −33; moderate certainty). Compared with anticoagulation, PFO closure may confer little or no difference in ischaemic stroke recurrence (low certainty) but probably has a lower risk of major bleeding (RD −20, 95% CrI −27 to −2, moderate certainty). Relative to either medical therapy, PFO closure probably increases the risk of persistent atrial fibrillation (RD 18, 95% CI +5 to +56, moderate certainty) and device-related adverse events (RD +36, 95% CI +23 to +50, high certainty). Anticoagulation, compared with antiplatelet therapy, may reduce the risk of ischaemic stroke recurrence (RD −71, 95% CrI −100 to +17, low certainty), but probably increases the risk of major bleeding (RD +12, 95% CrI −5 to +65, moderate certainty).ConclusionsIn patients aged <60 years, PFO closure probably confers an important reduction in ischaemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.PROSPERO registration numberCRD42017081567.
While the fundamental mechanism by which cardiac cell therapy mitigates ventricular dysfunction in the post ischemic heart remains poorly defined, donor cell paracrine signaling is presumed to be a ...chief contributor to the afforded benefits. Of the many bioactive molecules secreted by transplanted cells, extracellular vesicles (EVs) and their proteinaceous, nucleic acid, and lipid rich contents, comprise a heterogeneous assortment of prospective cardiotrophic factors-whose involvement in the activation of endogenous cardiac repair mechanism(s), including reducing fibrosis and promoting angiogenesis, have yet to be fully explained. In the current study we aimed to interrogate potential mechanisms by which cardiac mesenchymal stromal cell (CMC)-derived EVs contribute to the CMC pro-angiogenic paracrine signaling capacity in vitro. Vesicular transmission and biological activity of human CMC-derived EVs was evaluated in in vitro assays for human umbilical vein endothelial cell (HUVEC) function, including EV uptake, cell survival, migration, tube formation, and intracellular pathway activation. HUVECs incubated with EVs exhibited augmented cell migration, tube formation, and survival under peroxide exposure; findings which paralleled enhanced activation of the archetypal pro-survival/pro-angiogenic pathways, STAT3 and PI3K-AKT. Cytokine array analyses revealed preferential enrichment of a subset of prototypical angiogenic factors, Ang-1 and Ang-2, in CMC EVs. Interestingly, pharmacologic inhibition of Tie2 in HUVECs, the cognate receptors of angiopoietins, efficiently attenuated CMC-EV-induced HUVEC migration. Further, in additional assays a Tie2 kinase inhibitor exhibited specificity to inhibit Ang-1-, but not Ang-2-, induced HUVEC migration. Overall, these findings suggest that the pro-angiogenic activities of CMC EVs are principally mediated by Ang-1-Tie2 signaling.
Background
Women undergoing atrial fibrillation catheter ablation (AFCA) have higher rates of vascular complications and major bleeding. However, most studies have been underpowered to detect ...differences in rarer complications such as stroke/transient ischemic attack (TIA) and procedural mortality.
Methods
We performed a systematic review of databases (PubMed, World of Science, and Embase) to identify studies published since 2010 reporting AFCA complications by sex. Six complications of interest were (1) vascular/groin complications; (2) pericardial effusion/tamponade; (3) stroke/TIA; (4) permanent phrenic nerve injury; (5) major bleeding; and (6) procedural mortality. For meta‐analysis, random effects models were used when heterogeneity between studies was ≥50% (vascular complications and major bleeding) and fixed effects models for other endpoints.
Results
Of 5716 citations, 19 studies met inclusion criteria, comprising 244,353 patients undergoing AFCA, of whom 33% were women. Women were older (65.3 ± 11.2 vs. 60.4 ± 13.2 years), more likely hypertensive (60.6% vs. 55.5%) and diabetic (18.3% vs. 16.5%), and had higher CHA2DS2‐VASc scores (3.0 ± 1.8 vs. 1.4 ± 1.4) (p < .0001 for all comparisons). The rates of all six complications were significantly higher in women. However, despite statistically significant differences, the overall incidences of major complications were very low in both sexes: stroke/TIA (women 0.51% vs. men 0.39%) and procedural mortality (women 0.25% vs. men 0.19%).
Conclusion
Women experience significantly higher rates of AFCA complications. However, the incidence of major procedural complications is very low in both sexes. The higher rate of complications in women may be partially attributable to older age and a higher prevalence of comorbidities at the time of ablation. More detailed studies are needed to better define the mechanisms of increased risk in women and to identify strategies for closing the sex gap.
A research article recommendation approach aims to recommend appropriate research articles to analogous researchers to help them better grasp a new topic in a particular research area. Due to the ...accessibility of research articles on the web, it is tedious to recommend a relevant article to a researcher who strives to understand a particular article. Most of the existing approaches for recommending research articles are metadata-based, citation-based, bibliographic coupling-based, content-based, and collaborative filtering-based. They require a large amount of data and do not recommend reference articles to the researcher who wants to understand a particular article going through the reference articles of that particular article. Therefore, an approach that can recommend reference articles for a given article is needed. In this paper, a new multi-level chronological learning-based approach is proposed for recommending research articles to understand the topics/concepts of an article in detail. The proposed method utilizes the TeKET keyphrase extraction technique, among other unsupervised techniques, which performs better in extracting keyphrases from the articles. Cosine and Jaccard similarity measures are employed to calculate the similarity between the parent article and its reference articles using the extracted keyphrases. The cosine similarity measure outperforms the Jaccard similarity measure for finding and recommending relevant articles to understand a particular article. The performance of the recommendation approach seems satisfactory, with an NDCG value of 0.87. The proposed approach can play an essential role alongside other existing approaches to recommend research articles.
Abstract Epidemiologic evidence has demonstrated that air pollution may impair cardiovascular health, leading to potentially life-threatening arrhythmias. Efforts have been made, with the use of ...epidemiologic data and controlled exposures in diverse animal and human populations, to verify the relationship between air pollution and arrhythmias. The purpose of this review is to examine and contrast the epidemiologic and toxicologic evidence to date that relates airborne pollutants with cardiac arrhythmia. We have explored the potential biological mechanisms driving this association. Using the PubMed database, we conducted a literature search that included the terms “air pollution” and “arrhythmia” and eventually divergent synonyms such as “particulate matter,” “bradycardia,” and “atrial fibrillation.” We reviewed epidemiologic studies and controlled human and animal exposures independently to determine whether observational conclusions were corroborated by toxicologic results. Numerous pollutants have demonstrated some arrhythmic capacity among healthy and health-compromised populations. However, some exposure studies have shown no significant correlation of air pollutants with arrhythmia, which suggests some uncertainty about the arrhythmogenic potential of air pollution and the mechanisms involved in arrhythmogenesis. While data from an increasing number of controlled exposures with human volunteers suggest a potential mechanistic link between air pollution and altered cardiac electrophysiology, definite conclusions regarding air pollution and arrhythmia are elusive as the direct arrhythmic effects of air pollutants are not entirely consistent across all studies.
Introduction
Catheter ablation of ventricular tachycardia (VT) can be an effective therapy to reduce VT burden, but often it is limited by the potential for hemodynamic instability. Percutaneous left ...ventricular assist devices (pLVADs) have been used to maintain hemodynamic support during VT ablation but the evidence regarding its clinical impact has been inconclusive.
Methods and Results
We sought to assess the clinical impact of pLVAD when used in VT ablation by conducting a meta‐analysis of the current evidence. We searched Pubmed and found nine observational studies that compared clinical outcomes of VT ablation in patients with pLVAD support to controls with no pLVAD support.
The pooled data did not show a significant difference in mortality between both groups, nor a difference in acute procedural success or in recurrence of VT. There was also no difference in the number of patients receiving a cardiac transplant or being enrolled in the transplant list. Although there was no difference in the ablation time between the groups, patients in the pLVAD group had a longer total procedural time and more procedure‐related adverse effects.
Conclusion
This meta‐analysis did not show clinical benefits from using pLVAD support during VT ablation, whereas it was associated with longer procedure times and more complications. This study was, however, limited by the observational nature of the data. In view of these data, the risk and benefit of pLVAD support during VT ablation should be considered on an individual basis.
Topographic LIDAR can be used to estimate elevation values for dry areas down to the river water level during the extraction of river cross-sections (XS). However, LIDAR cannot accurately predict the ...submerged topography, which causes uncertainty in river XS area estimation. This uncertainty affects the channel water level and flood inundation depth estimation in in situ sparse data. Therefore, an alternative approach is presented to estimate unknown submerged topography (UST) using topographic LIDAR. The one dimension/two dimension Hydrologic Engineering Center River Analysis System (1D/2D HEC-RAS) model is used to simulate the estimated river XS with the help of in situ river water level and flow data which is later validated using in situ data. The results show that the proposed approach accurately estimates water level (error >0.5 m), channel flow areas, and floodplain water depths. Notably, the extent of the estimated floodplain overflow by UST models was in 94% agreement with the real XS.
Background
Noninvasive electrocardiographic mapping of ventricular tachycardia (VT) and ablation using stereotactic radiotherapy was recently reported. This strategy does not directly evaluate the ...critical diastolic components and assumes that the epicardial exit site of VT subtends closely over the endocardial mid‐diastolic isthmus.
Objective
To determine if the epicardial exit site of VT spatially corresponds to the critical diastolic components of ischemic scar‐related VT.
Materials and methods
Intraoperative simultaneous endocardial and epicardial mapping were performed during VT using a 112‐bipole endocardial balloon and 112‐bipole epicardial sock array. In eight patients, nine VTs having entire diastolic circuit mapped were included in the study. The diastolic path and VT‐exit sites (epicardial and endocardial) were determined.
Results
The diastolic path was mapped in the endocardium for all nine VTs (median length, 50; interquartile range IQR, 28 mm). The tachycardia cycle length ranged from 210‐500 ms. The VT‐exit site was early in the endocardium for six VTs and on the epicardium for three VTs. The mid‐diastolic isthmus and endocardial exit site of the six endocardial VTs were spatially distant from their epicardial exit site by a median distance of 32 and 27 mm, respectively. For the three VTs with an early epicardial exit, the isthmus and endocardial exit sites were distant from the epicardial exit site by a median distance of 34 and 38 mm, respectively.
Conclusion
The epicardial exit site and the mid‐diastolic isthmus sites were spatially distant and discrepant. Surface electrocardiography (ECG)‐derived strategy in identifying epicardial exit site to select noninvasive ablation targets is prone to identify epicardial exit sites and may not identify critical targets in ischemic scar VT.
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