Cerebral Embolic Protection Devices During Transcatheter Aortic Valve Implantation: Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Silent ischemic embolic lesions are common after transcatheter aortic valve implantation (TAVI). The use of embolic protection devices (EPD) may reduce the occurrence of these embolic lesions. Thus, a quantitative overview and credibility assessment of the literature was necessary to draw a robust message about EPD. Therefore, the aim of this meta-analysis was to study whether the use of EPD reduces silent ischemic and clinically evident cerebrovascular events associated with TAVI. METHODS: We conducted a comprehensive search to identify studies that evaluated patients undergoing TAVI with or without EPD. Random-effects meta-analyses were performed to estimate the effect of EPD compared with no-EPD during TAVI using aggregate data. RESULTS: Sixteen studies involving 1170 patients (865/305 with/without EPD) fulfilled the inclusion criteria. The EPD delivery success rate was reported in all studies and was achieved in 94.5% of patients. Meta-analyses evaluating EPD versus without EPD strategies could not confirm or exclude any differences in terms of clinically evident stroke (relative risk, 0.70; 95% confidence interval [CI], 0.38-1.29; P=0.26) or 30-day mortality (relative risk, 0.58; 95% CI, 0.20-1.64; P=0.30). There were no significant differences in new-single, multiple, or total number of lesions. The use of EPD was associated with a significantly smaller ischemic volume per lesion (standardized mean difference, -0.52; 95% CI, -0.85 to -0.20; P=0.002) and smaller total volume of lesions (standardized mean difference, -0.23; 95% CI, -0.42 to -0.03; P=0.02). Subgroup analysis by type of valve showed an overall trend toward significant reduction in new lesions per patient using EPD (standardized mean difference, -0.41; 95% CI, -0.82 to 0.00; P=0.05), driven by self-expanding devices. CONCLUSIONS: The use of EPD during TAVI may be associated with smaller volume of silent ischemic lesions and smaller total volume of silent ischemic lesions. However, EPD may not reduce the number of new-single, multiple, or total number of lesions. There was only very low quality of evidence showing no significant differences between patients undergoing TAVI with or without EPD with respect to clinically evident stroke and mortality.

Adenosine as a Marker and Mediator of Cardiovascular Homeostasis: A Translational Perspective.

Adenosine, a purine nucleoside, is produced broadly and implicated in the homeostasis of many cells and tissues. It signals predominantly via 4 purinergic adenosine receptors (ADORs) - ADORA1, ADORA2A, ADORA2B and ADOosine signaling, both through design as specific ADOR agonists and antagonists and as offtarget effects of existing anti-platelet medications. Despite this, adenosine has yet to be firmly established as either a therapeutic or a prognostic tool in clinical medicine to date. Herein, we provide a bench-to-bedside review of adenosine biology, highlighting the key considerations for further translational development of this proRA3 in addition to non-ADOR mediated effects. Through these signaling mechanisms, adenosine exerts effects on numerous cell types crucial to maintaining vascular homeostasis, especially following vascular injury. Both in vitro and in vivo models have provided considerable insights into adenosine signaling and identified targets for therapeutic intervention. Numerous pharmacologic agents have been developed that modulate adenmising molecule.

Evaluation of Plasma Adenosine as a Marker of Cardiovascular Risk: Analytical and Biological Considerations.

Background Adenosine is a ubiquitous regulatory molecule known to modulate signaling in many cells and processes vital to vascular homeostasis. While studies of adenosine receptors have dominated research in the field, quantification of adenosine systemically and locally remains limited owing largely to technical restrictions. Given the potential clinical implications of adenosine biology, there is a need for adequately powered studies examining the role of plasma adenosine in vascular health. We sought to describe the analytical and biological factors that affect quantification of adenosine in humans in a large, real-world cohort of patients undergoing evaluation for coronary artery disease. Methods and Results Between November 2016 and April 2018, we assessed 1141 patients undergoing angiography for evaluation of coronary artery disease. High-performance liquid chromatography was used for quantification of plasma adenosine concentration, yielding an analytical coefficient of variance (CVa) of 3.2%, intra-subject variance (CVi) 35.8% and inter-subject variance (CVg) 56.7%. Traditional cardiovascular risk factors, medications, and clinical presentation had no significant impact on adenosine levels. Conversely, increasing age (P=0.027) and the presence of obstructive coronary artery disease (P=0.026) were associated with lower adenosine levels. Adjusted multivariable analysis supported only age being inversely associated with adenosine levels (P=0.039). Conclusions Plasma adenosine is not significantly impacted by traditional cardiovascular risk factors; however, advancing age and presence of obstructive coronary artery disease may be associated with lower adenosine levels. The degree of intra- and inter-subject variance of adenosine has important implications for biomarker use as a prognosticator of cardiovascular outcomes and as an end point in clinical studies.