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The role of complement activation on the cerebral vasculature after cardiopulmonary bypass (CPB) is unclear. The goal of the study was to assess whether heparin-coated CPB reduces complement activation, and influences cerebral blood flow velocities (CBFV). Twenty-four patients undergoing coronary surgery were randomly allocated to non-coated (NC-group) or heparin-coated (HC-group) CPB. Complement activation was assessed by measuring sC5b-9. Transcranial Doppler (TCD) was performed on middle cerebral arteries before and after CPB. Systolic (SV), diastolic (DV) and mean (MV) CBFV were measured. Significant increase of sC5b-9 (p=0.003) was observed in the NC-group and CBFV increased after CPB (SV by 27%, p=0.05; DV by 40%, p=0.06; MV by 33%, p=0.04) whereas no changes were detected in the HC-group. TCD values were higher in the NC-group than in the HC-group (SV, p=0.04; DV, p=0.03; MV, p=0.03) although cardiac index, systemic vascular resistance, haematocrit and pCO2 were similar. Postoperative SV, DV and MV were significantly correlated with sC5b-9 (r=0.583, p=0.009; r=0.581, p=0.009; r=0.598, p=0.007, respectively). Increased CBFV after CPB are correlated to the level of complement activation and may be controlled by heparin-coated circuits. [ABSTRACT FROM PUBLISHER]

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNFα), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4–6 h after the start of CPB. However, no difference was observed between the groups except for the IL-8 level in group 2, which was lower 2 h after the start of CPB (p = 0.01). Plasma levels of adhesion molecules were similar in both groups within the investigation period. Although the Carmeda equipment was more effective in reducing complement activation, the late inflammatory response was similar using either the Duraflo II or Carmeda equipment for extracorporeal circulation as reflected by the changes of cytokine and circulating adhesion molecule levels. [ABSTRACT FROM AUTHOR]

In this prospective randomized trial, we studied whether heparin-coated extracorporeal circuits (ECC), known to reduce complement activation, could improve the clinical outcome of 200 patients undergoing coronary artery surgery. Patients have been divided into two groups (heparin-coated ECC and uncoated ECC groups) which were similar in terms of age, gender, left ventricle function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping and cardiopulmonary bypass. Univariate analysis showed that heparin coating did not reduce significantly postoperative bleeding (640 +/- 311 versus 682 +/- 342 ml with uncoated ECC) nor the need for transfusion (19% of patients versus 25% with uncoated ECC). Adverse events, including all mortality and morbidity noticed during the five first postoperative days, occurred in 20 patients of the uncoated ECC group and in eight patients of the heparin-coated ECC group (p = 0.013). The most frequent complications were supraventricular arrhythmias that occurred in 13 patients of the uncoated ECC group and in four patients of the heparin-coated ECC group (p = 0.02). Multivariate analysis by stepwise logistic regression showed that only heparin coating of the ECC was shown as a significant predictive factor of adverse events reduction (p = 0.01; odds ratio = 0.34). These data suggest that heparin coating reduced postoperative complications in patients undergoing coronary artery surgery. [ABSTRACT FROM AUTHOR]

Objectives: Antiplatelet therapy increases the risk of bleeding and transfusion in patients undergoing extracorporeal circulation. Reduced goal-directed anticoagulation is a personalized approach to reduce the anticoagulation based on a lower targeted activated clotting time. We assessed whether reduced goal-directed anticoagulation using optimized extracorporeal circulation alleviates the risk of severe bleeding in patients treated by dual antiplatelet therapy (DAPT) compared to aspirin alone during coronary artery bypass grafting (CABG)., Methods: A total of 2275 patients undergoing CABG from 2002 to 2022 were selected after propensity matching from a retrospective cohort of 3018 patients. Patients treated with a combination of aspirin and prasugrel or ticagrelor or clopidogrel were included in the DAPT group (n = 1111). Patients treated with aspirin alone (ASA) constituted the control group (n = 1164). Optimized extracorporeal circulation was conducted under reduced systemic anticoagulation with a target activated clotting time 250 s. Severe bleeding was assessed using 3 validated scores of bleeding: UDPB, E-CABG, and BARC-4., Results: While all scores showed low ranges of severe bleeding (<6%), they were significantly higher after DAPT compared to ASA (P values for UDPB, E-CABG, and BARC-4 at 0.016, 0.006, and 0.063, respectively). Higher maximal activated clotting time was associated with higher rate of transfusion (P < 0.001) and bleeding (P < 0.001) after multivariate adjustment. Mortality was 1.24% in DAPT vs 0.94% in ASA group (P = NS), whereas cardiac death, myocardial infarction, stroke, and transient ischaemic attack were low (<1%) and similar between groups., Conclusions: Despite higher bleeding under DAPT compared to ASA alone, optimized extracorporeal circulation with reduced goal-directed anticoagulation alleviated severe bleeding which remained low in patients undergoing CABG., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved., Methods: We prospectively enrolled 284 unrelated MVP probands, of whom 178 (63%) had bi-leaflet MVP and 106 had PostMVP (37%). Familial screening within PostMVP patients allowed the identification of 20 families with inherited forms of PostMVP for whom whole genome sequencing was carried out in probands. Functional in vivo and in vitro investigations were performed in zebrafishand in Hek293T cells., Results: In the 20 families with inherited form of PostMVP, 38.8% of relatives had a MVP/prodromal form, mainly of the posterior leaflet, with transmission consistent with an autosomal dominant mode of inheritance. Compared with control relatives, PostMVP family patients have clear posterior leaflet dystrophy on echocardiography. Patients with PostMVP present a burden of rare genetic variants in ARHGAP24. ARHGAP24 encodes the filamin A binding RhoGTPase-activating protein FilGAP and its silencing in zebrafish leads to atrioventricular regurgitation. In vitro functional studies showed that variants of FilGAP, found in PostMVP families, are loss-of-function variants impairing cellular adhesion and mechano-transduction capacities., Conclusions: PostMVP should not only be considered an isolated degenerative pathology but as a specific heritable phenotypic trait with genetic and functional pathophysiological origins. The identification of loss-of-function variants in ARHGAP24 further reinforces the pivotal role of mechano-transduction pathways in the pathogenesis of MVP., Clinical Perspective: Isolated posterior mitral valve prolapse (PostMVP), often called fibro-elastic deficiency MVP, is at least in some patients, a specific inherited phenotypic traitPostMVP has both genetic and functional pathophysiological origins Genetic variants in the ARHGAP24 gene, which encodes for the FilGAP protein, cause progressive Post MVP in familial cases, and impair cell adhesion and mechano-transduction capacities.

Background: Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting., Methods: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view., Results: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb ® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability., Conclusions: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy., (© 2024. The Author(s).)