0312: Characterization of human valvular interstitial cells isolated from normal and fibrocalcified aortic valves

PurposeAortic Valve Stenosis (AVS) affects 2% to 6% of population over 65 years in industrialized countries. This atherosclerosis-like pathology involves Valve Interstitial Cell (VIC) proliferation and commitment to osteoblast- like cells. This prevalent cell type of aortic valve presents five identifiable phenotypes: embryonic progenitor endothelial/mesenchymal cells, progenitor, quiescent, activated and osteoblastic VICs. To study the pathophysiology of AVS, their in vitro cultures are frequently used. Our purpose is to characterize VICs isolated from normal and fibrocalcified human aortic valves and analyze their in vitro behavior.MethodsWe collected 5 normal and 5 fibrocalcified human aortic valves. VICs were isolated by collagenase digestion. Characterization is assessed at different passages (2 to 5) by immunofluorescence. Analyzed markers consist of progenitor cell markers (SSEA4, ABCG2, CD90, NG2 and OsteoBlast CaDHerin (OB-CDH)), fibroblast markers (vimentin and HSP47) and smooth muscle cell (SMC) marker (α-actin). By blue trypan and MTS, we compared the viability and proliferation of VICs in standard and starvation medium at 48 hours.ResultsIndependently of their origin, VICs express all progenitor cell markers. Fibroblasts markers are expressed twice more by pathological VICs and four times more for SMC marker. In standard medium, VICs viability is similar (96,7±2,4% vs 96,4±2,3% ; normal vs pathological ± SEM). Pathological VICs proliferate more than normal VICs (2,2±0,7 vs 1,6±0,4 ; OD/OD control). In starvation medium, viability is significantly reduced for pathological VICs (89,6±7,9% vs 76,5±5,3%) but still proliferate in opposition with normal VICs (1,7±0,6 vs 1,2±0,3).ConclusionAll VICs phenotypes are found in vitro with no culture selection but in different ratios according to their origin. These new data in VICs isolated from normal or pathological human aortic valves allow us to approve their use in vitro

Automated 3D Analysis of Pre-Procedural MDCT to Predict Annulus Plane Angulation and C-Arm Positioning Benefit on Procedural Outcome in Patients Referred for TAVR

<p>OBJECTIVES The aim of this study was to determine whether pre-procedural analysis of multidetector row computed tomography (MDCT) scans could accurately predict the "line of perpendicularity" (LP) of the aortic annulus and corresponding C-arm angulations required for prosthesis delivery and impact the outcome of the procedure.</p><p>BACKGROUND Optimal positioning of the transcatheter aortic prosthesis is paramount to transcatheter aortic valve replacement (TAVR) procedural success.</p><p>METHODS All patients referred for TAVR at our center underwent a routine pre-procedural MDCT scan. A 3-dimensional (3D) analysis using software dedicated to define the LP of the aortic annulus and the corresponding C-arm positioning was performed in 71 consecutive patients. In 35 patients, the results of the MDCT analysis were not available at the time of the procedure (angiography cohort). In that cohort the position of the C-arm was determined during the procedure using ad-hoc angiography. In 36 patients, the MDCT analysis was performed pre-procedure and results were available at the time of the procedure (MDCT cohort). In that cohort the position of the C-arm was derived from the MDCT analysis rather than by ad-hoc angiography.</p><p>RESULTS Intraobserver and interobserver reproducibility of MDCT analysis to predict the LP of the aortic annulus were excellent (kappa = 1 and 0.94, respectively). Patient variations of the LP ranged >70 degrees. Compared with the angiography cohort, the MDCT cohort was associated with a significant decrease in implantation time (p = 0.0001), radiation exposure (p = 0.02), amount of contrast (p = 0.001), and risk of acute kidney injury (p = 0.03). Additionally, the combined rate of valve malposition and aortic regurgitation was also reduced (6% vs. 23%, p = 0.03).</p><p>CONCLUSIONS Automated 3D analysis of pre-implantation MDCT accurately predicts the LP of the aortic annulus and the corresponding C-arm position required for TAVR. With this approach, the implantation of the balloon-expandable prosthetic valve can be performed without an aortogram in the majority of cases and still be safe, with a low rate of valve malpositioning and regurgitation. (J Am Coll Cardiol Img 2013;6:238-48) (C) 2013 by the American College of Cardiology Foundation</p>

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions

Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures

Effets indésirables « graves » du tramadol : bilan 2010-2011 de pharmacovigilance en France

Objectif. Le tramadol est un opioïde de palier 2 indiqué en France dans les douleurs modérées à sévères. Une enquête nationale de pharmacovigilance a été mise en place après le retrait du dextropropoxyphène. Méthodes. Nous avons analysé les notifications françaises d’effets indésirables « graves » (EIG) imputées au tramadol et parvenues aux Centres régionaux de pharmacovigilance (CRPV) ou aux firmes pharmaceutiques entre le 1er août 2010 et le 31 juillet 2011. Résultats. Durant la période d’enquête, 296 cas d’EIG ont été notifiés aux CRPV et 59 aux firmes. Outre les EI opioïdes, nous avons identifié plusieurs EI sérotoninergiques, dont des convulsions et des syndromes sérotoninergiques. Nous avons aussi mis en évidence des EI « inattendus », certains méconnus des professionnels de santé (hypoglycémie, hyponatrémie), d’autres n’ayant jamais fait l’objet de publications (œdèmes des membres inférieurs, pancréatites). Conclusion. Ce suivi montre qu’à côté des EI opioïdes ou sérotoninergiques bien décrits, le tramadol peut aussi déterminer 2 autres EI relativement peu connus : hypoglycémie et hyponatrémie

Effets indésirables « graves » du tramadol : bilan 2011–2015 de pharmacovigilance en France

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