Prevention by the CXCR2 antagonist SCH527123 of the calcification of porcine heart valve cusps implanted subcutaneously in rats

IntroductionCalcification is a main cause of bioprosthetic heart valves failure. It may be promoted by the inflammation developed in the glutaraldehyde (GA)-fixed cusps of the bioprosthesis. We tested the hypothesis that antagonizing the C-X-C chemokines receptor 2 (CXCR2) may prevent the calcification of GA-fixed porcine aortic valves.Materiel and methodsFour-week-old Sprague Dawley males were transplanted with 2 aortic valve cusps isolated from independent pigs and implanted into the dorsal wall. Four groups of 6 rats were compared: rats transplanted with GA-free or GA-fixed cusps and rats transplanted with GA-fixed cusps and treated with 1 mg/kg/day SCH5217123 (a CXCR2 antagonist) intraperitoneally (IP) or subcutaneously (SC) around the xenograft, for 14 days. Then, rats underwent blood count before xenografts have been explanted for histology and biochemistry analyses.ResultsA strong calcification of the xenografts was induced by GA pre-incubation. However, we observed a significant decrease in this effect in rats treated with SCH527123 IP or SC. Implantation of GA-fixed cusps was associated with a significant increase in the white blood cell count, an effect that was significantly prevented by SCH527123. In addition, the expression of the CD3, CD68 and CXCR2 markers was reduced in the GA-fixed cusps explanted from rats treated with SCH527123 as compared to those explanted from non-treated rats.ConclusionThe calcification of GA-fixed porcine aortic valve cusps implanted subcutaneously in rats was significantly prevented by antagonizing CXCR2 with SCH527123. This effect may partly result from an inhibition of the GA-induced infiltration of T-cells and macrophages into the xenograft

Passive leg raising can predict fluid responsiveness in patients placed on venovenous extracorporeal membrane oxygenation

International audienceABSTRACT: INTRODUCTION: In ICUs, fluid administration is frequently used to treat hypovolaemia. Because volume expansion (VE) can worsen acute respiratory distress syndrome (ARDS) and volume overload must be avoided, predictive indicators of fluid responsiveness are needed. The purpose of this study was to determine whether passive leg raising (PLR) can be used to predict fluid responsiveness in patients with ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO). METHODS: We carried out a prospective study in a university hospital surgical ICU. All patients with ARDS treated with venovenous ECMO and exhibiting clinical and laboratory signs of hypovolaemia were enrolled. We measured PLR-induced changes in stroke volume (ΔPLRSV) and cardiac output (ΔPLRCO) using transthoracic echocardiography. We also assessed PLR-induced changes in ECMO pump flow (ΔPLRPO) and PLR-induced changes in ECMO pulse pressure (ΔPLRPP) as predictors of fluid responsiveness. Responders were defined by an increase in stroke volume (SV) > 15% after VE. RESULTS: Twenty-five measurements were obtained from seventeen patients. In 52% of the measurements (n = 13), SV increased by > 15% after VE (responders). The patients' clinical characteristics appeared to be similar between responders and nonresponders. In the responder group, PLR significantly increased SV, cardiac output and pump flow (P 10% ΔPLRSV may predict fluid responsiveness. ΔPLRPP and ΔPLRPO cannot predict fluid responsiveness

Trends in SAVR with biological vs. mechanical valves in middle-aged patients: results from a French large multi-centric survey

Background/introductionCurrently, despite continued issues with durability ( 1), biological prosthetic valves are increasingly chosen over mechanical valves for surgical aortic valve replacement (SAVR) in adult patients of all ages, at least in Western countries. For younger patients, this choice means assuming the risks associated with a redo SAVR or valve-in-valve procedure.PurposeTo assess the use of mechanical vs. biological valve prostheses for SAVR relative to patient's age and implant time in a large population extracted from the French National Database EPICARD.MethodsPatients in EPICARD undergoing SAVR from 2007 to 2022 were included from 22 participating public or private centers chosen to represent a balanced representation of centre sizes and geographical discrepancies. Patients with associated pathology of the aorta (aneurysm or dissection) and requiring a vascular aortic prosthesis were excluded. Comparisons were made amongst centers, valve choice, implant date range, and patient age.ResultsWe considered 101,070 valvular heart disease patients and included 72,375 SAVR (mean age 71.4 ± 12.2 years). We observed a mechanical vs. biological prosthesis ratio (MBPR) of 0.14 for the overall population. Before 50 years old (y-o), MBPR was >1.3 (p < 0.001) while patients above 60 years-old received principally biological SAVR (p < 0.0001). Concerning patients between 50 and 60 years-old patients, MPVR was 1.04 (p = 0.03). Patients 50–60 years-old from the first and second study duration quartile (before August 2015) received preferentially mechanical SAVR (p < 0.001). We observed a shift towards more biological SAVR (p < 0.001) for patients from the third and fourth quartile to reach a MBPR at 0.43 during the last years of the series. Incidentally, simultaneous mitral valve replacement were more common in case of mechanical SAVR (p < 0.0001), while associated CABGs were more frequent in case of biological SAVR (p < 0.0001).ConclusionIn a large contemporary French patient population, real world practice showed a recent shift towards a lower age-threshold for biological SAVR as compared to what would suggest contemporary guidelines

Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡

OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approache

Bioprothèse aortique freedom solo® (un premier pas vers la non infériorité)

But de l Etude : Comparer les résultats à deux ans des nouvelles bioprothèses péricardiques sans armature Freedom SOLO® (FS) par rapport aux bioprothèses conventionnelles avec armature dans la chirurgie de remplacement valvulaire aortique (RVAo) sur anneau natif non dilaté. Méthode : D Avril 2006 à Octobre 2008, sur une population de 583 patients opérés pour RVAo dans notre centre, nous avons étudié tous les patients recevant une bioprothèse pour un diamètre d anneau =2) était significativement plus bas dans le groupe FS (p=2) was significatively lower in FS group (p<0,001). After multivariate analysis, Freedom SOLO® valve was not associated with a higher risk of mortality according to a Cox model (p=0.86), and was an independent predictor of a better functional status according to the NYHA classification (backword stepwise logistic regression) (p=0,01). Conclusion: Though limited, our study represents a first step towards the evidence of non-inferiority for the Freedom SOLO® in AVR surgery on native non-dilated annulus with a bonus concerning hemodynamic performances.AMIENS-BU Santé (800212102) / SudocSudocFranceF

La chirurgie coronaire à coeur battant est-elle une alternative à la chirurgie sous clampage aortique ? (à propos d'une série de 205 patients)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Performance du nouvel euroscore dans la chirurgie de remplacement valvulaire aortique chez le patient octogénaire (implication dans la mise en place d'un programme TAVI)

Résumé: L insuffisance de l Euroscore I pour prédire la mortalité hospitalière après chirurgie de remplacement valvulaire aortique (RVAo) chez le patient octogénaire contraste avec la recommandation de considérer un traitement alternatif au-delà d un EuroScore I >= 20. La performance du nouvel EuroScore reste à préciser concernant l évaluation du risque opératoire dans cette population de patients. But : Evaluer la performance de l EuroScore II dans la prédiction de la mortalité hospitalière (MH) actuelle après chirurgie conventionnelle de RVAo chez les patients octogénaires. Méthode : Etude rétrospective portant sur une série consécutive de 386 patients octogénaires opérés conventionnellement pour rétrécissement aortique calcifié serré entre 2005 et 2011 dans un centre ne disposant pas du traitement alternatif. L EuroScore II était calculé en ligne à partir des données du dossier médical. Le critère principal était la survenue d un décès de toute cause durant l hospitalisation. L analyse multivariée de la MH et la détermination des odds ratios a été réalisé à l aide d un modèle de régression logistique. La performance du score de risque a été estimée par l analyse c-statistique, le test de Hosmer-Lemeshow (THL) et le coefficient de corrélation. Nous avons analysé les résultats tardifs en fonction du niveau de risque des patients au moment de l intervention. Résultats : Les déterminants indépendants de la MH étaient l EuroScore II (p=0,004, OR=1,11), les antécédents de fibrillation auriculaire (p=0,02, OR=2,27) et la nécessité d un recours à une transfusion sanguine (p=0,005, OR=3,42). L EuroScore II sous estimait la MH observée dans cette série quelque soit le niveau de risque considéré. S il s avérait assez discriminant (c-statistique = 0,62), la calibration du score était mauvaise : p=0,001 (THL). De fait l EuroScore II n était pas corrélé à la MH (r=0,17). Les taux de survie à 2 et 5 ans étaient respectivement dans les groupes à risque faible, élevé et excessif de 82% et 62%, puis 74% et 54%, et enfin 60% et 24%. Le nouvel EuroScore est discriminant concernant la survie tardive. Conclusion : Il existe un manque de performance de l EuroScore II pour prédire les résultats précoces après RVAo conventionnel chez le patient octogénaire. Comme pour tous les autres scores de risque, il est nécessaire d intégrer les notions de fragilité et de vulnérabilité dans l évaluation du risque opératoire chez les patients gériatriques.Performance of EuroScore II considering AVR in octogenarian patients: Implication in a TAVI program construction. In contrast with the inaccuracy of the EuroScore I to predict in-hospital mortality after aortic valve replacement (AVR) in octogenarian, recommendations have been made to consider an alternative therapy in case of a EuroScore I >= 20. The performance of the new EuroScore in this population of patients has still to be documented. Aim: To evaluate the performance of the EuroScore II to predict actual in-hospital mortality (IHM) after conventional surgery of AVR in octogenarian patients.Method: Retrospective study including a consecutive series of 386 octogenarian patients operated on conventionally for calcified aortic stenosis between 2005 and 2012 in one surgical center with no direct access to alternative therapy. EuroScore II was calculated online based on medical data files. The mean endpoint was the occurrence of any death during the hospitalisation. Multivariate analysis of IHM and determination of Odds Ratios were based on a logistic regression model. Risk score performance was estimated by c-statistic analysis, Hosmer-Lemeshow test (HLT) and correlation coefficient. We analysed late results according to risk level at the time of operation. Results: Independent determinants of IHM were EuroScore II (p=0,004, OR=1,11), a past history of atrial fibrillation (p=0,02, OR=2,27) and the necessity tu use blood transfusion (p=0,005, OR=3,42). EuroScore II underestimated IHM in this series in whatever operative risk group considered. If relatively discriminating (c-statistic=0,62), the score calibration was poor: p=0,001 (HLT) . Thus, EuroScore II was not correlated to IHM (r=0,17). The rates of survival in 2 and 5 years were respectively in the low, high and excessive risk groups of 82% and 62%, then 74% and 54%, and finally 60% and 24%. On the other hand this New EuroScore shows a rather good correlation with the late survival. The new EuroScore is accurate to estimate late survival. Conclusion: EuroScore II lacks performance to predict early results after conventional AVR in octogenarian patients. Like with all other risk-scores, the additional consideration of frailty and vulnerability are mandatory to assess operative risk in a geriatric population.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Evaluation médico-économique d'une endoprothèse indiquée dans la dissection aortique aiguë et incluse dans le groupe homogène de séjour (intérêt pour l'inscription sur la liste des produits et prestations remboursables)

L utilisation des dispositifs medicaux est en constante augmentation dans notre systeme de soin. Le systeme d acces au marquage CE, pour les laboratoires qui les commercialisent, mais aussi pour les professionnels de sante, reste obscur et difficile a maitriser de part sa complexite. Les etapes sont longues et necessitent une connaissance avertie de la reglementation en vigueur, sans cesse en mouvement, et qu il faut pouvoir anticiper face a des technologies qui peuvent etre tres vite supplantees. Le djumbodis dissection systeme, endoprothese en acier inoxydable implante dans les dissections aortiques de type A (DATA), a accede au marquage CE en 2000. Ce dispositif medical implantable (DMI) onereux, reference au CHU d Amiens depuis 2006, n est pas pris en charge par l ARS (Agence Regionale de Sante). Son remboursement reste au frais de l etablissement implanteur. Afin de pouvoir justifier de son referencement dans l etablissement et dans une demarche de projet d inscription sur la LPPR par le laboratoire, nous avons entrepris l analyse de l impact clinique et medico-economique de ce stent nu dans la prise en charge de la dissection aortique. Il s agit d une etude controlee, retrospective et monocentrique incluant 45 patients operes pour DATA entre 2006 et 2011, et beneficiant ou non d un stenting nu selon le choix du chirurgien. L analyse medico-economique presentee dans ce memoire, avec un recul de 2 ans, permet d observer un benefice clinique du stenting nu de l aorte thoracique, en offrant une stabilisation des diametres globaux de l aorte thoracique dans le groupe stente par rapport au groupe temoin. L effet d un remodelage de l'aorte global doit etre confirme par une prolongation du suivi. L etude economique, par une comparaison des couts et des recettes engages par patient, enonce une sous-evaluation globale de la prise en charge des dissections aortiques aigues. De plus, le prix du dispositif medical, considere comme eleve a premiere vue, se revele etre totalement fondu dans les montants de prise en charge des patients stentes, comparativement au groupe temoin de l etude. Le raisonnement du cout dans sa globalite est donc de mise dans la strategie d achat de ce type de dispositif medical. Dans un contexte economique restreint, le recours a l analyse medico-economique offre une analyse interessante, permettant d adopter une politique d achat en coherence avec les lignes directrices donnees par les autorites de sante. Le partage des expertises a la fois chirurgicale, pharmaceutique et industrielle a permis d aboutir a l elargissement de l innovation, ou le principal gagnant reste avant tout le patient dans sa prise en charge.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Métabolisme énergétique et transplantation cardiaque

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF