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Background Valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) can be completed by bioprosthetic valve fracture (BVF) to reduce final transvalvular gradients. The aim was to compare outcomes in ViV-TAVI patients with versus without BVF. Methods Consecutive patients undergoing ViV-TAVI procedure in four international centers were included, from 2010 to 2021. We used a 1:2 propensity score-matching method to compare postprocedural hemodynamic, complications, and long-term outcomes. Patients were matched for baseline characteristics, time since prior surgery, and characteristics of surgical bioprothesis (type and size). Results A total of 390 patients were analyzed, including 40 BVF. Propensity matching 1:2 yielded 38 patients in BVF group and 76 patients in no-BVF group. There was no difference in procedural complications rate and in-hospital deaths (5.1%) between the two groups. Post-procedural hemodynamic parameters significantly improved using BVF: aortic valve area (1.4 cm2 [IQR: 1.23 to 2.3] vs. 1.3 cm2 [IQR: 1.05 to 1.61], p=0.008), mean aortic gradient (12mmHg [IQR: 7.5 to 16.5] vs. 17mmHg [IQR: 11 to 22], p=0.008) and peak velocity (2.2m/s [IQR: 1.8 to 2.7] vs. 2.6m/s [IQR: 2.2 to 3.1], p=0.027). BVF had an additional benefit in the smallest surgical valve (≤21 mm). The use of BVF was independently associated with improved hemodynamic parameters. Overall survival in the matched cohort was 87.8±3.7% at 2-year follow-up, without difference between groups (87.5±6.9% in the BVF group vs. 88.4±4.2% in the no-BVF group, p=0.85). Conclusion Compared to ViV-TAVI alone, BVF was safe and improved immediate hemodynamic and long-term outcomes, especially in patients with small surgical aortic bioprosthesis. Funding Acknowledgement Type of funding sources: None.

Study question How do patients perceive the pre-IVF treatment communication by the nursing and midwifery team and how do they evaluate implemented optimization? Summary answer Patient satisfaction with the pre-IVF treatment communication by the nursing and midwifery team improved from 86% to 98% after implementation of standardized written patient information. What is known already Nurses are the main point of contact for patients undergoing medically assisted reproduction techniques (Applegarth et al., 2008). Morris (2001) suggested that infertility nurses could more specifically be involved in informative counselling in anticipation of the fertility treatment. Specific training for nurses and midwives would be required in order to achieve that central role in effective fertility counselling (Applegarth et al., 2012). However, little has been published in peer reviewed literature on how to assess and improve these pre-IVF treatment information sessions. Study design, size, duration The pre-IVF communication by the nurse/midwife was assessed by female patients with a self-developed questionnaire (cohort 1). The nursing and midwifery team was subsequently informed about the results of the questionnaire and efforts were undertaken to optimise future patient communication. Four years later, a follow-up questionnaire assessed patient satisfaction about the intervention (cohort 2). Each cohort comprised fifty patients and nurses and midwives were blinded for patient participation to the study. Participants/materials, setting, methods The study was performed at an academic fertility centre and was approved by the Investigational Review Board. Data were collected with SurveyMonkey (pre intervention) and REDCap (post intervention). A descriptive analysis of the cohorts and patient feedback was performed. The intervention consisted of (1) the optimization of patient information documents if needed (2) providing a training to the nursing and midwifery staff, and (3) a follow-up questionnaire in a second cohort of female fertility patients. Main results and the role of chance The first questionnaire revealed that overall, patients were satisfied with the informative counselling session in anticipation of the IVF treatment. However, some patients indicated that they received a lot of information at once and that specific information that was of relevance for the further treatment (e.g. oocyte pick-up) was sometimes missed. Also, the data showed that not all patients received the same information. Therefore, all information that patients needed during an IVF treatment was gathered into a patient binder. It was supplemented with a timeline of the whole IVF trajectory, QR codes to movies explaining the administration of medication, and answers to common patients’ questions. It was possible to individualize the content of the binder per patient. Ideally, patients received this binder before the informative counselling session so they could read the content in advance. The binder was developed by a member of the nursing and midwifery team and was reviewed by the medical, laboratory, and administrative staff. Then, the nursing and midwifery team was trained on the use of the patient binder. The follow-up questionnaire revealed that patient satisfaction with the pre-IVF treatment counselling was 98% after the optimization of patient documentation (compared to 86% before the optimization). Limitations, reasons for caution Eligible patients were recruited by the treating physician. As no records were kept of the number of solicited patients for this study, no assessment of the response rate is possible. The cohorts were self-selected and limited in size and could therefore not reflect the general patient population. Wider implications of the findings A patient questionnaire and follow-up is a useful tool for a centre specific assessment and improvement of pre-IVF nurse/midwife communication with patients. Clinics could make efforts to invest in complete and written information and ask colleagues of the nursing and midwifery team to be involved in its creation. Trial registration number NCT04420169

Le Groupe d’intérêt en hémostase périopératoire (GIHP) et le Groupe français d’études sur l’hémostase et la thrombose (GFHT), en collaboration avec la Société française d’anesthésie et de réanimation (SFAR) ont fait des propositions de gestion des agents antiplaquettaires (AAP) pour une procédure invasive programmée. Ces propositions ont été discutées et validées par vote ; toutes sauf une ont fait l’objet d’un accord fort. La gestion des AAP dépend de leur indication et de la procédure considérée. Le risque hémorragique lié à la procédure invasive peut être divisé en bas, intermédiaire ou élevé, selon la possibilité ou non de réaliser la procédure sous traitement (sous respectivement bithérapie antiplaquettaire, aspirine en monothérapie ou aucun AAP). Si une interruption des AAP est indiquée avant la procédure, une dernière prise d’aspirine, clopidogrel, ticagrélor et prasugrel 3, 5, 5 et 7 jours avant la procédure est proposée. Le risque thrombotique associé à l’interruption des AAP doit être évalué en fonction de l’indication des AAP. Il est plus élevé chez les patients traités par bithérapie pour un stent coronaire que chez ceux traités par monothérapie pour une prévention cardiovasculaire, un antécédent d’accident vasculaire cérébral ischémique ou une artériopathie oblitérante des membres inférieurs. Ces propositions concernent aussi le rôle potentiel des tests fonctionnels plaquettaires, la gestion des AAP pour l’anesthésie locorégionale, centrale et périphérique, et pour la chirurgie cardiaque coronaire.

Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic disease characterised by its potential severity, mainly related to thrombosis, and by difficulties regarding its diagnosis and management of affected patients. In 2002, a conference of experts mobilised by the French Society of Anaesthesia and Intensive Care Medicine (Société française d’anesthésie et de réanimation [SFAR]) drafted recommendations for the management of HIT [...]

Background Major vascular (VAC) and life-threatening or major bleeding (LT/MB) complications still represent one of the most frequent adverse outcomes of percutaneous transfemoral TAVR (TF-TAVR) and are associated with an increased risk of mortality. Ultrasound guidance technique allows to puncture in the non-calcified central and horizontal segment of common femoral artery. However the clinical impact of ultrasound (US)-guidance has never been studied in TF-TAVR in comparison of standard fluoroscopic guidance and could explain the lack of adoption of US guidance. We sought first to evaluate in our study the impact of US-guidance on the vascular and bleeding complications. Methods US-guidance for vascular access was implemented as the default approach in our institution in June 2013 for all TF-TAVR and was applied by all operators after a short training course. Thus, we defined three period and groups of consecutive patients according to the method of percutaneous puncture (fluoroscopic or US-guidance) and the generation of THV (2nd or 3rd gen.). US-guided-2nd gen. group: TF-TAVR with 2nd generation THV and performed via US-guidance. This group refers to the period patients from June 2013 to November 2014 (n=119). Fluo-guided-2nd gen. group: The last TF-TAVR with 2nd gen. THV and performed via fluoroscopic guidance (n=119). US-guided-3rd gen. group: Patients implanted with 3rd gen. THV (SAPIEN 3, Evolut R) from November 2014 to December 2018 while US-guidance was systematic for all TF-TAVR (n=308). Patients performed with US-guidance were 1:1 successfully matched with 95 patients performed with fluoroscopic guidance (fluo-guided group) with propensity-score (10 variables). We separately analyzed the consecutive patients of the US-guided-3rd gen. group. Results After propensity-matching, resulting in similar baseline characteristics, all the vascular and bleeding complications were reduced in the US-guided-2nd gen. group compared to Fluo-guided-2nd gen. group with respectively: VAC (6.3% vs 16.8%; OR=0.31; 95% CI: 0.12–0.85; p=0.023); LT/MB (22.1% vs 6.3%; OR=0.24, CI: 0.09–0.63; p=0.004); and VAC related to vascular access (12.6 vs 4.2%; OR=0.31; CI: 0.10–1.01; p=0.052). We also observed a reduction of the mean fluoroscopic time (1753±620 min vs 1228±405 min; p In the US-guided-3rd gen. group (n=308), the US-guided puncture achieved a rate of VAC of 3.2% (CI: 1.6–5.9) and of LT/MB of 3.6% (CI: 1.8–6.3). In the overall population (n=546), we observed that LT/MB (p=0.02) was associated with a 1.7-fold increase of mortality risk. Conclusion The present study is the first and the largest to evaluate the impact of US-guidance in TF-TAVR. We demonstrated that US-guided cannulation is able to reduce the risk of vascular and bleeding complications. These data endorses US-guidance as the standard method of puncture for TAVR.

Background Several mechanisms are suspected to thrombocytopenia under Extracorporeal Membrane Oxygenation (ECMO) such as platelet-consumption or sepsis. Shedding of glycoprotein-(GP)Ibα is a recently identified mechanism of platelet clearance. ECMO generates high shear stress forces that could impact GPIbα-shedding. We hypothesized that ECMO continuous-flow devices could directly induce thrombocytopenia through shear-induced GPIbα-shedding. Aims Determine if ECMO induce GpIb-shedding in vitro and in vivo and determinates the kinetic evolution of platelet-count and GpIb-shedding after patient's implantation. Methods Platelet GPIbα-shedding was first investigated in vitro using a high-shear pump loop model. Plasma with normal platelet count (plasma-NPC) was obtained by dilution of platelet-rich plasma obtained from healthy donors in fresh-frozen-plasma. Samples were collected before and after (5, 30, 60 and 180 min) perfusion at 37°C of plasma-NPC at intermediate and high speed (2.6 and 3.6 L min–1 respectively, n=4 each). Platelet count and GPIbα-shedding were next investigated in 20 ECMO patients before/after implantation (WITECMO trial) and in 20 healthy volunteers. The geometric mean-fluorescence-intensity (gMFI) of platelet GPIbα (PE-staining) and GPIX (FITC-staining) was measured with a Navios flow cytometer (Beckman Coulter, Miami, FL). Results are expressed as GPIbα/GPIX gMFI-ratio. Results A significant time-dependent loss of GPIbα/GPIX gMFI-ratio was already apparent after 30 min in vitro and was significantly more pronounced at high-speed compared to intermediate-speed (pANOVA Figure 1. A. Significant time-dependent loss of platelet GPIbα/GPIX gMFI-ratio (pANOVA

Background Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. Methods BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. Results The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. Conclusions There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Contains fulltext : 220931.pdf (Publisher’s version ) (Closed access) AIMS AND OBJECTIVES: To identify interventions to prevent and treat malnutrition in older adults, which can be integrated in nursing care, and to evaluate the effects of these interventions on outcomes related to malnutrition. BACKGROUND: Older adults are at great risk for malnutrition, which can lead to a number of serious health problems. Nurses have an essential role in nutritional care for older adults. Due to a lack of evidence for nursing interventions, adequate nursing nutritional care still lags behind. DESIGN: Systematic review. METHOD: We searched for and included randomised controlled trials on interventions, which can be integrated in nursing care for older adults, to prevent and treat malnutrition. We assessed the risk of bias with the Cochrane tool and evidence for outcomes with the GRADE. The PRISMA statement was followed for reporting. RESULTS: We included 21 studies of which 14 studies had a high risk of bias. Identified interventions were oral nutritional supplements, food/fluid fortification or enrichment, dietary counselling and educational interventions. In evaluating the effects of these interventions on 11 outcomes related to malnutrition, significant and nonsignificant effects were found. We graded the certainty of evidence as very low to moderate. CONCLUSION: Although slight effects were found in protein intake and body mass index, there is no convincing evidence about the effectiveness of the four identified interventions. There seems no harm in using these interventions, although it should be kept in mind that the evidence is sparse. Therefore, there is a need for high-quality research in building evidence for interventions in nursing nutritional care. RELEVANCE TO CLINICAL PRACTICE: Nurses can safely provide oral nutritional supplements and food/fluid fortification or enrichment, and give dietary counselling and education to older adults, as they are well placed to lead the essential processes of nutritional care to older adults.

International audience

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction Transcatheter aortic valve implantation (TAVI) is playing a growing role in the management of patients with symptomatic severe aortic stenosis. However, length of hospital stay (LOS) after transfemoral (TF) TAVI remains widely variable. Objective We aimed to evaluate LOS after TF TAVI and the variability of LOS among French centers using data from the FRANCE TAVI registry. Methods TAVI was performed in 12,804 patients in 48 French centers between January 2013 and December 2015. LOS was evaluated in 5,857 (45.7%) patients treated via a TF approach and discharged directly at home. LOS was calculated from TAVI procedure (day 0) to discharge. The study population was divided into 2 groups based on tertile LOS values. Results The median LOS in the studied population was 7 (5–9) days and was extremely variable among centers. Patients in the lowest tertile (LOS 6 days (n = 3,624) constituted the “Late Discharge group”. Variables independently associated with late discharge were comorbidities (history of mitral valve prosthesis, respiratory failure, atrial fibrillation, and severe pulmonary hypertension), complications occurring during or after TAVI (need for a new pacemaker, tamponade, stroke, vascular complications and acute kidney injury), the use of self-expandable valve and general anesthesia with a significant center effect. In contrast, the history of previous pacemaker before TAVI was a protective factor. Finally, we did not observe any significant difference in the rate of death and re-admission in the early versus late discharge groups. Conclusion LOS remain high after TF TAVI in France and extremely variable. As expected, co-morbidities and complications were predictive factors of late discharge after TAVI. Furthermore, our results suggest that the use of self-expandable prosthesis and general anesthesia also contributes to late discharge.

Introduction Hemorrhagic complications, especially mucosal bleedings, are very common for using continuous-flow mechanical circulatory supports (CF-MCS) including Extracorporeal Membrane Oxygenation (ECMO). CF-MCS could impact platelets by exposing this key player in primary hemostasis to high shear stress. A proteolytic cleavage (shedding) of platelet adhesion receptors GpIb and GpVI has been described under high shear stress and could contribute to the hemorrhagic complications in patients with CF-MCS. Objective To assess whether CF-MCS promotes GpIb and GpVI shedding in vitro and in vivo and determine the kinetic evolution during the CF-MCS. Method First platelet shedding was investigated in vitro using a CF-MCS (Impella-CP®, Abiomed) loop model. Plasma with normal platelet count (plasma-NPC) was obtained by dilution of platelet-rich plasma collected from healthy donors in fresh frozen plasma. Sampling was performed before and after 2, 5, 30, 60 and 180 min perfusion of plasma-NPC in the loop model (n = 4 runs). Platelet shedding was also investigated for the blood samples collected from 20 ECMO patients (WITECMO-h trial). Platelets of 20 healthy volunteers were evaluated as a control. GpIbα and GpVI shedding was analyzed by flow cytometry. Results A significant time-dependent decrease of GpIbα (P Conclusion CF-MCS induces platelet GpIb and GpVI shedding in vitro. Increased GpIb and GpVI shedding is already present before ECMO implantation and remain significantly elevated after the implantation. Loss of the platelet receptors GPIbα and GPVI in patients with CF-MCS may contribute to hemorrhagic complications observed in these patients.

Introduction Aortic valve stenosis (AVS) is the narrowing of the aortic valve (AV) opening caused by fibrosis and calcification. Despite this paradigm, no targeted medical therapy has proven to prevent, slow down or treat AVS. Using transcriptomic approach on human valvular interstitial cells (VIC) isolated from fibrocalcific and normal valves, our team has identified an enzyme X downregulated in fibro-calcific VIC. This enzyme X and its product Y have documented anti-calcification effects in other cell types than VIC. Objective Our goal is to decipher the implication of this pathway on an in vitro model of human primary cultures of VIC in ostegenic conditions. Method Normal AV unsuitable for grafting and fibrocalcific AV from valve replacement (ATHERAO protocol) were collected. Levels of enzyme X in AV was assessing by histology and by Western Blot on tissue homogenate. VIC isolation was realized by enzymatic digestion of normal AV. Primary cultures were exposed to ostegenic media (OM) or control media with or without the product Y of the enzyme (1–1000 nM) during 7 days. Evaluation of calcification was realized by alizarin red staining, mRNA levels of calcification markers. Results We confirmed a differential expression of enzyme X on tissue by histology and by western blot (− 5.2 fold, P Conclusion Our results demonstrate the involvement of this new pathway in an in vitro model of AVS by decreasing human VIC calcification and associated markers. Enzyme X is a potential innovative pharmacological therapeutic target in AVS.

Background Periprocedural and late (>30 days) bleedings represent one of the major complications after Transcatheter Aortic Valve Replacement (TAVR) and have been identified as potential area for improved patient care. Objectives To evaluate the impact of ongoing primary hemostasis disorders on late major/life-threatening bleeding complications (MLBCs). Methods Bleedings were assessed according to the Valve Academic Research Consortium-2 (VARC-2) criteria. CT-ADP, a surrogate marker of high molecular weight von Willebrand multimers proteolysis was assessed 24 h after the procedure. Ongoing primary hemostasis disorder was defined by a CT-ADP > 180 s. Results Amongst 372 patients who survived at 30 days, MLBCs occurred in 42 patients (11.3%) at a median follow-up of 383 days (interquartile range 188 to 574 days). MLBCs were mainly of gastrointestinal origin (42.9%) and were associated with increased overall mortality (HR 5.66; 95% CI [3.10–10.31]; P 180 s (27.4 vs. 11.5%; P 180 s (HR 3.08; [1.62–5.81]; P = 0.0005) as independent predictor of MLBCs Table 1 , Fig. 1 ). Conclusion MLBCs after TAVR are frequent and associated with an increased morbidity and mortality. PVL and CT-ADP > 180s were identified as strong predictors for MLBCs. Our findings strongly suggest that the missing link between PVL and the risk of MLBCs is a persistent High Molecular Weight Von Willebrand defect. It may help physician to tailor follow-up and anti-thrombotic regimens of patients and improve clinical outcomes.

Circulatory support devices are increasingly being used to overcome cardiac or respiratory failure. Long-term devices are used either as a 'bridge to transplant' to support patients who are unable to wait any longer for a heart transplant, or, more recently, as 'destination therapy' for older patients suffering from end-stage heart failure and who have contraindications to heart transplantation. Short-term support devices for high-risk percutaneous coronary intervention, or as a 'bridge for decision' for patients suffering from refractory cardiogenic shock, have also been developed. The clinical benefit of such assist devices has been demonstrated in several important studies, but, unfortunately, thrombotic and bleeding complications are two major clinical issues in patients requiring these devices. Overcoming these issues is of major importance to allow the safe and broad use of these devices, and to consider them as true alternatives to heart transplantation. The present review focuses on thrombotic and bleeding complications, and describes how the risk of thrombosis and bleeding may vary according to the clinical indication, but also according to the type of device. We describe the current knowledge of the mechanisms underlying the occurrence of these complications, provide some guidance for choosing the most appropriate anticoagulation regimen to prevent their occurrence for each type of device and indication, and provide some recommendations for the management of patients when the complication occurs.

Cardiac cell therapy is a strategy to treat patients with chronic myocardial infarction (MI). No consensus exists regarding the optimal cell type. First, a comparison between autologous bone marrow-derived mononuclear cells (BMMNC) and mesenchymal stem cells (MSC) on therapeutic efficacy after MI was performed. Next, the effect of repetitive, NOGA-guided transendocardial injection was determined via a crossover design. Nineteen pigs were allocated in three groups: (1) placebo (at 4 and 8 weeks), (2) MSC (followed by placebo at 8 weeks), or (3) BMMNC (followed by MSC at 8 weeks) delivery including a priming strategy to enhance MSC effect. At 4 weeks, ejection fraction (EF) was significantly improved after MSC injection and not by BMMNC injection. After 8 weeks, no difference was observed in EF between cell-treated groups demonstrating the positive systolic effect of MSC. This study showed that MSC rather than BMMNC injection improves systolic function in chronic MI.

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P

Introduction Major vascular (VAC) and life-threatening or major bleeding (LT/MB) complications represent the most frequent adverse outcomes of percutaneous transfemoral TAVR (TF-TAVR). Point-of-Care Ultrasound (POCUS) guidance allows the opportunity to obtain in real-time valuable anatomic informations to puncture in the ideal non-calcified central and horizontal segment of femoral artery. We sought to evaluate in our study the impact of implementation of POCUS-guidance on the vascular and bleeding complications. Method POCUS-guidance for vascular access was implemented as the default approach in our institution in 06/2013 for all TF-TAVR and was applied by all operators after a short training course. Thus, we defined three period and groups of consecutive patients according to the method of puncture (fluoroscopic or POCUS-guidance) and the generation of THV (2nd or 3rd gen.). TF-TAVR with POCUS-guidance and 2nd generation THV and from 06/2013 to 11/2014 (POCUS-guided-2nd gen. group; n = 119) were 1:1 successfully matched with 95 patients of the Fluo-guided-2nd gen. with propensity-score (10 variables) (The last TF-TAVR with guidance with 2nd gen. THV; n = 119). TF-TAVR implanted with 3rd gen. THV from 11/2014 to 12/2018 (POCUS-guided-3rd gen. group; n = 308) were analyzed separately. Results After propensity-matching, all the vascular and bleeding complications were reduced in the POCUS-guided-2nd gen. group compared to Fluo-guided-2nd gen. group with respectively: VAC (6,3% vs. 16,8%; OR = 0,31; 95% CI = 0,12–0,85; P = 0,023); LT/MB (22,1% vs. 6,3%; OR = 0.24, CI = 0.09-0.63; P = 0,004); and VAC related to vascular access (12,6 vs. 4,2%; OR = 0,31; CI = 0.10–1.01; P = 0,052). Conclusion This is the first and the largest study to demonstrate that POCUS-guided cannulation of the femoral artery is associated with a reduction of vascular and bleeding complication and support POCUS-guidance as the gold-standard for TF-TAVR.

Introduction Aortic valve stenosis (AVS) involves inflammation, excess deposition of collagen-rich extracellular matrix (ECM) and calcification. Recent studies have shown that M1 macrophages observed in stenosed valve promote calcification of valvular interstitial cells (VIC), the most prevalent cell type in aortic valve. Objective Our aim was to investigate whether, in turn, human VIC could modulate M1 macrophages phenotype. Method Patients with severe AVS (n = 43) were included in this study. Patients without AVS (n = 129) were used as controls. Human VIC were isolated from patients with severe AVS or from normal healthy donor (control valves). Results MMP-9 expression and activity of human M1 macrophages cultivated with conditioned medium of VIC (CM-VIC) from stenosed valves are lower compared to macrophages with CM-VIC from control valves (253 ± 18 vs 182 ± 10.5; P Conclusion Taken together, these findings indicate that VIC promotes the imbalance of ECM remodeling by reducing MMP9 production from M1 macrophages that lead to excessive collagen deposition observed in AVS. Further investigation is needed to clarify the role of TGFb1 in this context.

Introduction An invasive strategy is beneficial in non ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the optimal delay for performing the coronary angiogram (CA) in NSTE-ACS patients is unresolved especially in the absence of P2Y12-ADP-receptor inhibitor pretreatment. Objective To assess the impact of the delay of the invasive strategy in NSTE-ACS patients managed without pretreatment. Method This analysis focuses on the subgroup of 80 patients included between 2016 and 2018 at Lille University Hospital in a prospective, randomized, controlled, open-label, parallel-group study. Patients were eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. In the control group (DG, N = 40), a delayed strategy is adopted with the CA between 12 and 72 hours after randomization. In the experimental group (EG, N = 40), a very early invasive strategy was performed within 2 hours. The primary endpoint was the composite of cardiovascular (CV) death, myocardial infarction (MI), CV hospitalization, and recurrent ischemic event at 6 months. Results The mean age was 61. The GRACE and CRUSADE scores were of 141.2 and 22.8, respectively in the EG. In the DG, they were of 144 and 25, respectively. In both groups, 23 patients (28.8%) had no significant coronary lesions at CA. The mean time between randomization and the CA was 1h in the EG and 25h in the DG. At 6 months, there was a trend for an increase in the composite primary endpoint in the EG as compared with the DG (15% vs. 32.5%, P = 0.06). Among secondary endpoints, there was a significant difference in the rate of urgent revascularization that occurred in 15% of the DG patients vs. 2.5% of the EG patients (P = 0.04). Conclusion Although no definitive conclusions could be drawn, an immediate invasive strategy was safe and feasible, and was associated with a trend of less ischemic events in intermediate- and high-risk NSTE-ACS patients managed without pretreatment.

Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR.BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women.The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH.There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Stem cell therapy is a treatment strategy for ischaemic heart disease patients. Meta-analysis of randomized human trials showed5% improvement in left ventricular ejection fraction (LVEF). Meta-analysis of available pre-clinical data of ischaemic heart disease could provide important clues to design human clinical trials.Random-effects meta-analysis was performed on pig, dog, or sheep studies investigating the effect of cardiac stem cell therapy in ischaemic cardiomyopathy (52 studies; n = 888 animals). Endpoints were LVEF and death. Ischaemia/reperfusion infarction was performed in 23 studies and chronic occlusion in 29 studies. Pooled analysis showed a LVEF difference of 7.5% at follow-up after cell therapy vs. control (95% confidence interval, 6.2-8.9%; P0.001). By exploratory multivariable meta-regression, significant predictors of LVEF improvement were: cell type [bone marrow mononuclear cells (BM-MNC) showed less effect than other cell types, e.g. mesenchymal stem cells; P = 0.040] and type of infarction (left anterior descending artery 8.0 vs. left circumflex artery 5.8%; P = 0.045). Cell therapy was not associated with increased mortality (P = 0.68). Sensitivity analysis showed trends towards more improvement with higher cell number (≥10(7)), chronic occlusion models, and late injections (1 week). After follow-up of 8 weeks, the effect of cell therapy decreased to 6%.This meta-analysis showed that large animal models are valid to predict the outcome of clinical trials. Our results showed that cell therapy is safe and leads to a preserved LVEF. Future trials should focus on cell types other than BM-MNC, large infarction, and strategies to obtain sustained effects.

Introduction The Carmat bioprosthetic Total Artificial Heart (C-TAH) is a mechanical circulatory support device providing an alternative to the heart transplant for patients in advanced heart failure. Objectives One of the most original components of the C-TAH is its biocompatible hybrid membrane made of bovine pericardial tissue and polyurethane separating the actuating liquid of the pump from blood inside ventricles. The aim of our study is to evaluate safety of the hybrid membrane in terms of mechanical aging, risks of calcification, and impact on the hemodynamics inside ventricles on red blood cells, platelet and von willebrand factor (vWF) impairment. Methods Hybrid membranes were aged in a custom-designed endurance bench then evaluated in terms of mechanical proprieties and physical degradation. Erosion areas were explored in electronic microscopy and surface topography. Samples were subcutaneously implanted in Wistar rats as a model for calcification. Hemodynamic simulation using computational model has been used to reproduce shear stress in both ventricles. Results Compliance of the membrane is not significantly modified from 9 month to a 4 years aging simulating process. Physical proprieties as glass transition temperature and infrared spectrum are not modified. Exploration of erosion areas showed no oil diffusion through the membrane. Implantation in wistar rats demonstrated that anticalcification pretreatment with FET was able to significantly reduce the calcium concentration. We confirmed the absence of calcification in the areas in contact with blood by microtomography in the feasability study. The hemodynamic simulation showed no significant stress able to trigger hemolysis, platelet activation or the degradation of the vWFmultimers, confirmed with the patients implanted in feasibility study. Conclusion Mechanical aging, calcification model and hemodynamic simulation allowed us to confirm safety of the hybrid membrane used in the C-TAH.

Carcass decomposition results in the release of nitrogenous compounds into associated soil. The current study investigated the release of ninhydrin reactive nitrogen (NRN) following burial (∼40 cm depth) and decomposition on the soil surface. Also investigated was the lateral extent of NRN in gravesoil. NRN concentration increased significantly in gravesoil collected from the center of graves (∼20 cm depth) during the initial two months of burial. A similar finding was also observed in the base of the grave during the initial six months of burial. However, no change in NRN concentration was observed 60 cm from buried carcasses. Carcasses decomposing on the soil surface were associated with higher NRN during the initial 97 days of decomposition. We conclude that the analysis of soil NRN can be a presumptive test for gravesoil within two months postmortem following burial and up to 97 days postmortem on the surface. © 2009 Elsevier Ireland Ltd. All rights reserved.

Resume Les procedures interventionnelles realisees dans les lesions coronaires thrombotiques et dans les pontages veineux degeneres sont frequemment associees a des complications thromboemboliques incluant les phenomenes de non-reperfusion, d'occlusion de branche, et d'infarctus periprocedural. L'interet d'une technique complementaire de thromboaspiration par la sonde RESCUE™, a ete teste sur 21 patients consecutivement. Une artere native etait concernee dans 19 cas et deux lesions se situaient dans un pontage veineux ; toutes etaient composees majoritairement de thrombus ; un geste de thromboaspiration fut realise initialement et dans 81 % des cas la procedure s'est poursuivie par un geste d'angioplastie avec pose d'un stent. Un flux coronaire normal defini par un stade TIMI ≥ 2, est passe de 42,9 % avant thromboaspiration a 95,2 % en fin de procedure. Le taux de MACE durant la phase hospitaliere est de 4,76 %. Cette technique de thrombectomie est apparue comme relativement simple, rapide et efficace en presence de thrombus angiographique.

Restenosis remains the major limitation of coronary angioplasty. The objective of this study was to develop microspheres able to be delivered at the angioplasty site for long-term drug release and to test their effects in a model of balloon angioplasty. Polylactic-co-glycolide acid microspheres (5-10 microm in diameter) were prepared by using an oil-in-water emulsion-solvent evaporation method. In vitro experiments with hydrocortisone-loaded microspheres revealed a hydrocortisone release for 4 weeks. We studied the in vivo effect of injection of microspheres into the arterial wall of New Zealand White rabbits by using a perforated balloon. Deep penetration of microspheres in the arterial wall was documented immediately after angioplasty. Intimal hyperplasia was assessed in iliac arteries 4 weeks after angioplasty. The morphometric analysis was performed in four groups of animals; the first group was subjected only to conventional angioplasty (control, n = 10), whereas the other three groups after conventional angioplasty were received perforated balloon angioplasty with saline (n = 10), microspheres (n = 10), or hydrocortisone-loaded microspheres (n = 7). Intramural injection of saline did not induce greater intimal hyperplasia compared with control (0.17 +/- 0.03 vs. 0.18 +/- 0.03 mm2, respectively). Microspheres injection was associated with a trend toward a greater degree of intimal hyperplasia that did not reach statistical significance. Hydrocortisone-loaded microspheres were associated with a significant reduction in intimal hyperplasia compared with unloaded microspheres (0.16 +/- 0.02 vs. 0.26 +/- 0.03 mm2, respectively). The polylactic-co-glycolide acid microspheres are well tolerated, easily injected into the arterial wall, and the increase of intimal hyperplasia is easily inhibited by release of hydrocortisone for 4 weeks after initial injury.

Time for primary review 32 days. Interventional strategies for patients with coronary artery disease such as percutaneous transluminal coronary angioplasty or coronary stent implantation invariably result in a marked degree of vascular injury (deendothelialization, mechanical damage to the medial and adventitial layers) [1–3]. The loss of the endothelial monolayer is associated with a variety of deleterious consequences such as thrombus formation, neointimal thickening, and abnormal responses to endothelium-dependent agonists [3–5]. These effects may contribute to each of the known limitations of these techniques (vessel occlusion, restenosis, coronary spasm). The objective of the present review will be to present applied reendothelialization as a possible treatment for patients with coronary artery disease undergoing mechanical revascularization. Our aim will be twofold: first, to summarize current knowledge on the beneficial effect of endothelial regrowth after arterial injury; second, to discuss the potential role of growth factors or other compounds to accelerate reendothelialization. Occupying a strategically important location between circulating blood and tissues and having the ability to respond to changes in its physical, chemical, and humoral environment by the production of bioactive substances, the normal endothelium controls the tone and the proliferative state of the underlying vascular smooth muscle cells (VSMCs) and maintains a non-adhesive luminal surface. Modulation of VSMC tone is mediated by the synthesis and release of endothelium-derived relaxing and contracting factors. The proliferative state of VSMCs is controlled through these endothelium-derived factors and through the secretion of matrix proteins. Anticoagulant, fibrinolytic, and antithrombotic properties of the endothelium contribute to the maintenance of the fluidity of the blood. ### 1.1 Endothelium-dependent vasomotion #### 1.1.1 Relaxing factors Prostacyclin (PGI2), a potent vasorelaxant and platelet-inhibitory metabolite of arachidonic acid was the first endothelium-derived vasoactive factor discovered [6]. After the seminal observation of Furchgott and Zawadski in 1980 [7]that an intact endothelial layer was required for acetylcholine-induced vasorelaxation, … * Corresponding author. Service de Cardiologie B, Hopital Cardiologique, Boulevard du Professeur J. Leclercq, 59037 Lille Cedex, France. Tel. (+33-3) 2044 5302; Fax (+33-3) 2053 5874; E-mail: cbauters@chru-lille.fr

Recent in vitro studies suggest that angiotensin converting enzyme (ACE) inhibitors stimulate endothelial cell proliferation and migration. The present study was designed to test the hypothesis that an ACE inhibitor may accelerate endothelial regrowth in vivo. Twenty eight New Zealand White rabbits were randomized to receive placebo or the ACE inhibitor perindopril and underwent iliac balloon denudation. Endothelial regrowth, quantified 28 days after injury using Evans blue, was significantly greater in perindopril-treated animals than in controls (131 +/- 9 mm2 vs 69 +/- 8 mm2; P < .001). These results were confirmed by scanning electron microscopy and by specific immunostaining for endothelial cells. These data provide the first in vivo demonstration that ACE inhibitors accelerate endothelial regrowth after arterial injury. This effect may contribute to the benefit observed with ACE inhibition following arterial injury.

Background Because prior studies have established the critical role of the endothelium in preventing vascular thrombosis and intimal thickening, we designed a series of experiments to determine the feasibility of percutaneous local catheter delivery of recombinant protein to accelerate development of an intact endothelial monolayer after stent implantation. Methods and Results Balloon injury followed by percutaneous delivery of a 15-mm-long, balloon-expandable metallic stent was performed in 64 rabbit external iliac arteries (baseline diameter, 2.67±0.07 mm). Planimetric time-course analysis disclosed P =.045), local ChB delivery of 100 μg VEGF overcame this catheter effect: By day 7, stent endothelialization was nearly complete (91.8±3.8%) ( P P =.006). Occlusive thrombus was seen only in the absence of local VEGF administration. Conclusions (1) Local delivery of recombinant protein to the arterial wall is feasible after stent implantation, and (2) local delivery of the endothelial cell mitogen VEGF accelerates stent endothelialization, reducing stent thrombosis. These results thus establish a novel means by which the safety and/or bioactivity of endovascular stents may be further enhanced.

Intravascular metallic stents are increasingly used in the non-surgical management of coronary atherosclerosis. Despite intensive anticoagulation, subacute stent thrombosis, which usually has serious clinical consequences, and major haemorrhagic complications remain major problems after stent implantation. In addition, conventional management with anticoagulant therapy requires prolonged hospitalization. In a prospective multicentre study, we investigated the efficacy of a combination of two antiplatelet agents, ticlopidine 500 mg daily and aspirin 200 mg daily, without oral anticoagulation after stent implantation. Since November 1993, 529 consecutive patients, in whom 545 vessels were successfully stented with conventional (non-heparin coated) stents have been enrolled. Stenting was performed as a bailout procedure for failed angioplasty in 112 patients, for a suboptimal result after angioplasty in 314 patients, and electively in the remaining 103 patients. Coronary events related, or possibly related, to stent thrombosis occurred in 5.4% of patients stented as a bailout procedure and in 1.8% of patients stented for a suboptimal result. Serious bleeding complications occurred in 5.4% of patients stented as a bailout procedure and 1.5% of patients stented for a suboptimal result. Neither stent thrombosis nor serious bleeding complications were seen in patients stented electively. Ticlopidine therapy was discontinued in 1.9% of patients due to neutropenia (0.6%) or rash (1.3%). Mean hospital stay decreased from 6.16 +/- 2.14 days to 4.2 +/- 2.15 days during the study period. A combination of two antiplatelet agents can be employed in the vast majority of patients after coronary stent implantation. Subacute stent thrombosis rates and bleeding complications compare favourably with those reported using conventional therapy and the duration of hospitalization is reduced.