Hybrid coronary revascularization: position paper of the European Society of Cardiology Working Group on Cardiovascular Surgery and European Association of Percutaneous Cardiovascular Interventions.

Myocardial revascularization in coronary artery disease via percutaneous coronary intervention or coronary artery bypass graft (CABG) surgery effectively relieves symptoms, significantly improves prognosis and quality of life when combined with guideline-directed medical therapy. Hybrid coronary revascularization is a promising alternative to percutaneous coronary intervention or CABG in selected patients and is defined as a planned and/or intended combination of consecutive CABG surgery using at least 1 internal mammary artery to the left anterior descending (LAD), and catheter-based coronary intervention to the non-LAD vessels for the treatment of multivessel disease. The main indications for hybrid coronary revascularization are (i) to achieve complete revascularization in patients who cannot undergo conventional CABG, (ii) to treat patients with acute coronary syndromes and multivessel disease with a non-LAD vessel as the culprit lesion that needs revascularization and (iii) in highly select patients with multivessel disease with complex LAD lesions and simple percutaneous coronary intervention targets for all other vessels. Hybrid coronary revascularization patients receive a left internal mammary artery graft to the LAD artery through a minimal incision along with percutaneous coronary intervention to the remaining diseased coronary vessels using latest generation drug-eluting stents. A collaborative environment with a dedicated heart team is the optimal platform to perform such interventions, which aim to improve the quality and outcome of myocardial revascularization. This position paper analyses the rationale of hybrid coronary revascularization and the currently available evidence on the various techniques and delves into the sequence of the interventions and pharmacological management during and after the procedure.

Haemoadsorption in infective endocarditis: a systematic review.

Infective endocarditis surgical patients suffer from high rates of severe complications such as systemic inflammatory response, septic shock, and multi-organ failure leading to high mortality. Systemic inflammatory response based on cytokines as messengers plays an important role in these patients. The concept of intraoperative haemoadsorption has been proposed to remove such elevated cytokines in patients undergoing cardiac surgery for infective endocarditis. Haemoadsorption offers the possibility to stabilise haemodynamics, reduce sepsis-related mortality, and protect organ function. However, until now, there has been no general opinion and consensus regarding the clinical effectiveness of adjunctive intraoperative haemoadsorption in infective endocarditis. Therefore, we reviewed the current literature evaluating haemoadsorption in infective endocarditis patients undergoing cardiac surgery. The review was registered at PROSPERO (CRD42023457632). Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-024-01701-0.

The role of hemoadsorption in cardiac surgery - a systematic review.

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.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

Standardized in vitro bleeding tests in a non-coated novel hybrid prosthesis for frozen elephant trunk demonstrates minimal oozing during full heparinization, supported by clinical data.

Introduction: Recent reports have questioned the blood impermeability of the novel frozen elephant trunk (FET) device E-vita Open NEO© (EO-NEO). Therefore, standardized in vitro bleeding tests using porcine heparinized blood were performed, as well as stress testing on the blood tightness of the collar suture line, to investigate this observation. Material and methods: EO-NEO prostheses were examined in vitro for blood permeability in three test series. Initially, antegrade perfusion with heparinized porcine blood [activated clotting time (ACT) of 500 s, with a 60 min duration] was performed, followed by ante/retrograde testing via the EO-NEO side port. Testing of the collar suture line under a tension of 10 Newton (N) within a suspension device (blood pressure 120 mmHg, ACT of 560 s, 1 min duration) was carried out with the suture material force fiber white (FFWs) yarn, using standard fixation (5 stitches/cm), FFWh yarn in hemostatic fixation (15 stitches/cm), and flow weave yarn (FWYh). Results: Blood permeability testing of EO-NEO through the prosthetic lumen or via the side port demonstrated minor leakage without statistical difference between the standard and hemostatic suture lines or suture materials used, or positioning on the crimped or tapered portion (p > 0.05). The specific collar anastomosis testing demonstrated leakage volumes of 140 ml/min for FFWs vs. 16 ml/min for FFWh (p = 0.02), vs. 9 ml/min with the FWYh (p = 0.01). Conclusion: Different blood leakage tests showed minimal oozing and no difference in blood loss through the fabric and different collar suture lines, but unphysiological pressurized retrograde perfusion of the collar region showed significantly less leakage using FWYh and FFWh, prompting production modification of EO-NEO. Clinical results confirmed low blood loss using this novel FET device.

Intraoperative ticagrelor removal via hemoadsorption during on-pump coronary artery bypass grafting.

Objectives: Patients on ticagrelor undergoing urgent cardiac surgery are at high risk for perioperative bleeding complications. We sought to determine whether intraoperative hemoadsorption could remove ticagrelor and lower circulating drug concentrations. Methods: The hemoadsorption device was incorporated in the cardiopulmonary bypass (CPB) circuit and remained active for the duration of the pump run. Blood samples were collected before and after CPB. The main objective of the current analysis was to compare mean total plasma ticagrelor levels (ng/mL) at baseline with ticagrelor levels obtained at the end of CPB. Plasma ticagrelor levels were measured at a certified outside laboratory (LabConnect). Data are presented as mean ± standard deviation. Results: A total of 11 patients undergoing urgent coronary artery bypass grafting at 3 institutions were included (mean age, 67.9 ± 9.9 years; 91% male; mean European System for Cardiac Operative Risk Evaluation II of 3.0 ± 3.3%; range, 0.7%-12.4%). Mean intraoperative hemoadsorption duration was 97.1 ± 43.4 minutes with a mean flow rate through the device of 422.9 ± 40.3 mL/min. Mean ticagrelor levels pre-CPB were 103.5 ± 63.8 ng/mL compared with mean post-CPB levels of 34.0 ± 17.5 ng/mL, representing a significant 67.1% reduction (P < .001). Intraoperative integration of the device was simple and safe without any device-related adverse events reported. Conclusions: This is the first in vivo report demonstrating that intraoperative hemoadsorption can efficiently remove ticagrelor and significantly reduce circulating drug levels. Whether active ticagrelor removal can reduce serious perioperative bleeding in patients undergoing urgent cardiac surgery is currently being evaluated in the double-blinded, randomized Safe and Timely Antithrombotic Removal-Ticagrelor (STAR-T) trial.

Hedinger Syndrome-Lessons Learnt: A Single-Center Experience.

BACKGROUND: Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. METHODS: Eleven patients (58 ± 11 (range 41 to 79 years); 5 females) with HS who underwent cardiac surgery in our department between 07/2005 and 05/2023 were analysed. RESULTS: All patients showed a New York Heart Association (NYHA) class III-IV and in all the tricuspid valve (TV) was involved. Four patients received a TV replacement, and three TV reconstruction. Recently, to preserve the geometry and function of the compromised right ventricle (RV), we have applied the TV "bio-prosthesis in native-valve" implantation technique with the preservation of the valve apparatus (tricuspid valve implantation: TVI) in four cases. Concomitant procedures included pulmonary valve replacement in four, pulmonary implantation in one, and aortic valve replacement in three cases. To treat RV failure, we adapted a combined TandemHeart®-CytoSorb® haemoperfusion strategy in Patient #10 and venoarterial extracorporeal membrane oxygenation (V-A ECMO) support avoidance, after experiencing an ECMO-induced carcinoid-storm-related death in Patient #8. Mortality at 30 days was 18% (2/11). The median follow up was 2 ± 2.1 years (range 1 month to 6 years) with an overall mortality during the follow-up period of 72.7% (8/11). CONCLUSIONS: HS surgery, despite being a high-risk procedure, can efficiently prolong survival, and represents a safe and feasible procedure. However, patient selection seems to be crucial. Further follow up and larger cohorts are needed.

Hemoadsorption Using CytoSorb® in Patients with Infective Endocarditis: A German-Based Budget Impact Analysis.

A considerable number of infective endocarditis (IE) patients require cardiac surgery with an increased risk for postoperative sepsis. Intraoperative hemoadsorption may diminish the risk of postoperative hyperinflammation with potential economic implications for intensive care unit (ICU) occupation. The present study aimed to theoretically investigate the budget impact of a reduced length of ICU stay in IE patients treated with intraoperative hemoadsorption in the German healthcare system. Data on ICU occupation were extrapolated from a retrospective study on IE patients treated with hemoadsorption. An Excel-based budget impact model was developed to simulate the patient course over the ICU stay. A base-case scenario without therapy reimbursement and a scenario with full therapy reimbursement were explored. The annual eligible German IE patient population was derived from official German Diagnostic-Related Group (DRG) volume data. One-way deterministic sensitivity analysis and multivariate analysis were performed to evaluate the uncertainty over the model results. The use of intraoperative hemoadsorption resulted in EUR 2298 being saved per patient in the base-case scenario without therapy reimbursement. The savings increased to EUR 3804 per patient in the case of full device-specific reimbursement. Deterministic and probabilistic sensitivity analyses confirmed the robustness of savings, with a probability of savings of 87% and 99% in the base-case and full reimbursement scenario, respectively. Intraoperative hemoadsorption in IE patients might have relevant economic benefits related to reduced ICU stays, resulting in improved resource use. Further evaluations in larger prospective cohorts are warranted.

Limited versus Radical Resection in Mitral Valve Infective Endocarditis Surgery.

Background: Mitral valve repair is preferred in patients undergoing surgical treatment for infective endocarditis (IE) of the native mitral valve, however, radical resection of infected tissue and patch-plasty might potentially lead to low or non-durable repair. We aimed to compare a limited-resection and non-patch technique with the classic radical-resection technique. Methods: Eligible candidates were patients with definitive IE of the native mitral valve undergoing surgery between January 2013 and December 2018. Patients were classified according to the surgical strategy into two groups: limited- versus radical-resection strategy. Propensity score matching was used. Endpoints were repair rate, all-cause mortality (30-day and 2-year), re-endocarditis and reoperation at q-year follow-up. Results: After propensity score matching, 90 patients were included. Follow-up was 100% complete. Mitral valve repair rate was 84% in the limited-resection versus 18% in the radical-resection strategy, p < 0.001. The 30-day and 2-year mortality were 20% versus 13% (p = 0.396) and 33% versus 27% (p = 0.490) in the limited-resection versus radical-resection strategy, respectively. The incidence of re-endocarditis during the 2-year follow-up was 4% in the limited-resection strategy versus 9% in the radical-resection strategy, p = 0.677. Three patients in the limited-resection strategy underwent reoperation of the mitral valve, while there were none in the radical-resection strategy (p = 0.242). Conclusions: Although mortality in patients with IE of the native mitral valve remains high, the limited-resection and non-patch surgical strategy is associated with a significantly higher repair rates with comparable 30-day and mid-term mortality, risk of re-endocarditis and re-operation compared to the radical-resection strategy.

Statin loading before coronary artery bypass grafting: a randomized trial.

AIMS: Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. METHODS AND RESULTS: This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74-1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69-1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

Effect of intraoperative haemoadsorption therapy on cardiac surgery for active infective endocarditis with confirmed Staphylococcus aureus bacteraemia.

OBJECTIVES: Sepsis caused by infective endocarditis (IE), due to Staphylococcus aureus, is associated with significant morbidity and mortality. Blood purification using haemoadsorption (HA) may attenuate the inflammatory response. We investigated the effect of intraoperative HA on postoperative outcomes in S. aureus IE. METHODS: Patients with confirmed S. aureus IE undergoing cardiac surgery were included in a dual-centre study between January 2015 and March 2022. Patients treated with intraoperative HA (HA group) were compared to patients not treated with HA (control group). The primary outcome was vasoactive-inotropic score within the first 72 h postoperatively and secondary outcomes were sepsis-related mortality (SEPSIS-3 definition) and overall mortality at 30 and 90 days. RESULTS: No differences in baseline characteristics were observed between groups (haemoadsorption group, n = 75, control group, n = 55). Significantly decreased vasoactive-inotropic score was observed in the haemoadsorption group at all time points [6 h: 6.0 (0-17) vs 17 (3-47), P = 0.0014; 12 h: 2 (0-8.3) vs 5.9 (0-37), P = 0.0138; 24 h: 0 (0-5) vs 4.9 (0-23), P = 0.0064; 48 h: 0 (0-2.1) vs 0.1 (0-13), P = 0.0192; 72 h: 0 (0) vs 0 (0-5), P = 0.0014]. Importantly, sepsis-related mortality (8.0% vs 22.8%, P = 0.02) and 30-day (17.3% vs 32.7%, P = 0.03) and 90-day overall mortality (21.3% vs 40%, P = 0.03) were also significantly lower with haemoadsorption. CONCLUSIONS: Intraoperative HA during cardiac surgery for S. aureus IE was associated with significantly lower postoperative vasopressor and inotropic requirements and resulted in lower sepsis-related and overall 30- and 90-day mortality. In this high-risk population, improved postoperative haemodynamic stabilization by intraoperative HA appears to improve survival and should be further tested in future randomized trials.

Intraoperative Hemoadsorption (Cytosorb™) during Open Thoracoabdominal Aortic Repair: A Pilot Randomized Controlled Trial.

BACKGROUND: The efficacy of cytokine adsorption in controlling the early inflammation cascade after open thoracoabdominal aortic (TAAA) repair has not been investigated. The aim of this pilot randomized controlled trial was to assess the feasibility and effect of perioperative hemoadsorption during open TAAA repair. METHODS: Patients scheduled for open TAAA repair with the use of cardiopulmonary bypass (CPB) were included. The patients were randomized the day before surgery to either intraoperative hemoadsorption during CPB or standard of care. RESULTS: A total of 10 patients were randomly assigned to the intervention group, whereas the control group consisted of 17 patients (mean age of the total cohort, 51.1 ± 11.2 years, 67% male, 3 patients not randomized). The majority of baseline and perioperative characteristics were similar, and no device-related adverse events were reported. A trend to shorter ventilation times in the intervention group was observed (median 88 h vs. 510 h, p = 0.08, Δ422). Severe acute respiratory distress syndrome was significantly less in the intervention patients (p = 0.02). CONCLUSIONS: This is the first pilot study showing that the intraoperative use of hemoadsorption in open TAAA repair patients may be feasible and safe, yet larger trials are needed to evaluate whether intraoperative hemoadsorption is associated with improved clinical outcomes.

Transcatheter aortic valve replacement in the management of aortic insufficiency secondary to left ventricular assist device implantation: a case report.

Background: Left ventricular assist device (LVAD) is considered either a destination therapy for patients with end-stage heart failure or heart transplantation bridging. LVAD implantation often causes aortic insufficiency (AI), which requires aortic valve repair. However, severe acute AI does not respond well to medication, and re-operation means higher risk to the patients; the most effective therapeutic strategies for LVAD-induced AI still need further exploration. In this report, we present the first described case of new-onset, severe LVAD-induced AI in China with a patient who underwent transcatheter aortic valve replacement (TAVR) and achieved significant improvement in functional capacity and symptoms with lower operation risk. Case Description: A 55-year-old male patient was diagnosed with dilated cardiomyopathy for 14 years. The effect of the medication gradually deteriorated, LVAD (HeartCon®) was implanted one year earlier. The patient complained of intermittent chest tightness for one week, which had been aggravated for two days before hospitalization. Echocardiographic findings revealed new-onset, severe LVAD-induced AI. TAVR was performed with a self-expandable stent-valve (TAV30, Vitaflow Liberty). Within minutes, the patient recovered with rapid disappearance of chest tightness and stable vital signs. Before discharge, the position of the artificial valve was fixed without incomplete closure nor thrombus attachment, yielding a left ventricular ejection fraction (LVEF) of 35%. The patient was hospitalized for 38 days, and followed up with outpatient treatment, the condition was stable until 19 June 2023. Conclusions: TAVR could be an effective, safe, and less invasive means of restoring ejection fraction for patients with a LVAD who develop severe AI.

Graft flow evaluation with intraoperative transit-time flow measurement in off-pump versus on-pump coronary artery bypass grafting.

Objective: We aimed to compare transit-time flow measurement (TTFM) parameters for on-pump (ONCAB) and off-pump (OPCAB) coronary artery bypass procedures. Methods: The database of the Registry for Quality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery (REQUEST) study was retrospectively reviewed. Only single grafts were included (ie, no sequential or Y/T grafts). Primary end points were mean graft flow (MGF), pulsatility index (PI), diastolic fraction (DF), and backflow (BF). Unadjusted and propensity score-matching comparisons were performed. Results: Of 1016 patients in the REQUEST registry, 846 had at least 1 graft for which TTFM was performed. Of these, 512 patients (60.6%) underwent ONCAB and 334 (39.4%) OPCAB procedures. Mean arterial pressure (MAP) during measurements was higher in the OPCAB group. After propensity score-matching, 312 well balanced pairs were left. In these matched patients, MGF was higher for the ONCAB versus the OPCAB group (32 vs 28 mL/min, respectively, for all grafts [P < .001]; 30 vs 27 mL/min for arterial grafts [P = .002]; and 35 vs 31 mL/min for venous grafts [P = .006], respectively). PI was lower in the ONCAB group (2.1 vs 2.3, for all grafts; P < .001). Diastolic fraction was slightly lower in the ONCAB group (65% vs 67.5%; P < .001). The backflow was also lower in the ONCAB group (0.6 vs 1.3; P < .001) with trends similar to MGF and PI for venous and arterial grafts. There were 21 (3.3%) revisions in the OPCAB group and 14 (2.1%) in the ONCAB group (P = .198). Conclusions: ONCAB surgery was associated with higher MGF and lower PI values, especially in venous grafts. Different TTFM cutoff values for ONCAB versus OPCAB surgery might be considered.

Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent.

Background: Patients on direct oral anticoagulants are at high risk of perioperative bleeding complications. We analyzed the results of intraoperative hemoadsorption (HA) in patients undergoing cardiac surgery who were also on concurrent therapy with apixaban. Methods: we included 25 consecutive patients on apixaban who underwent cardiac surgery with the use of cardio-pulmonary bypass (CPB) at three sites. The first 12 patients underwent surgery without hemoadsorption (controls), while the next 13 consecutive patients were operated with the Cytosorb® (Princeton, NJ, USA) device integrated into the CPB circuit (HA group). The primary outcome was perioperative bleeding assessed by the Bleeding Academic Research Consortium (BARC) definition and secondary outcomes included 24 h chest-tube-drainage (CTD) and need for 1-deamino-8-d-arginine-vasopressin (desmopressin (DDAVP)) administration to achieve hemostasis. Results: Preoperative mean daily dose of apixaban was higher in the HA group (8.5 ± 2.4 vs. 5.6 ± 2.2 mg, p = 0.005), while time since last apixaban dose was longer in the controls (1.3 ± 0.9 vs. 0.6 ± 1.2 days, p < 0.001). No BARC-4 bleeding events and no repeat-thoracotomies occurred in the HA group compared with 3 and 1, respectively, in the controls. Postoperative 24 h CTD volume was significantly lower in the HA group (510 ± 152 vs. 893 ± 579 mL, p = 0.03) and there was no need for DDAVP compared to controls, who received an average of 10 ± 13.6 mg (p = 0.01). Conclusions: In patients on apixaban undergoing emergent cardiac surgery, the intraoperative use of hemoadsorption was feasible and safe. Compared to patients operated on without hemoadsorption, BARC-4 bleeding complications did not occur and the need for 24 h CTD and DDAVP was significantly lower.

Intracerebroventricular dosing of N-sulfoglucosamine sulfohydrolase in mucopolysaccharidosis IIIA mice reduces markers of brain lysosomal dysfunction.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease. Enzyme replacement therapy has been proposed, but further evaluation of the treatment strategy is needed. Here, we used Chinese hamster ovary cells to produce a highly soluble and fully active recombinant human sulfamidase (rhSGSH). We discovered that rhSGSH utilizes both the CI-MPR and LRP1 receptors for uptake into patient fibroblasts. A single intracerebroventricular (ICV) injection of rhSGSH in MPS IIIA mice resulted in a tissue half-life of 9 days and widespread distribution throughout the brain. Following a single ICV dose, both total HS and the MPS IIIA disease-specific HS-NRE were dramatically reduced, reaching a nadir 2 weeks post dose. The durability of effect for reduction of both substrate and protein markers of lysosomal dysfunction and a neuroimmune response lasted through the 56 days tested. Furthermore, seven weekly 148 µg doses ICV reduced those markers to near normal and produced a 99.5% reduction in HS-NRE levels. A pilot study utilizing every other week dosing in two animals supports further evaluation of less frequent dosing. Finally, our dose-response study also suggests lower doses may be efficacious. Our findings show that rhSGSH can normalize lysosomal HS storage and markers of a neuroimmune response when delivered ICV.

Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery-a systematic review.

Background: Antithrombotic drugs increase the risk of bleeding, especially in patients who need urgent surgery without an adequate wash-out period. This review aims to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications. Methods: As a first step, we searched for relevant articles, over the last 10 years, in Medline (PubMed) and abstracted clinical information based on pre-defined criteria for bleeding complications. In the next step, an additional search evaluating potential solutions to mitigate bleeding complications was performed. The literature screening and selection process followed the principles derived from the PRISMA statement. Results: From all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs and 10 papers evaluating antithrombotic drug reversal or removal in the setting of cardiovascular surgery. Reported bleeding rates ranged between 18% and 41%. The variability of the reported data is remarkable. Idarucizumab is reported to provide optimal perioperative hemostasis in up to 93% of patients. It has been observed that andexanet alfa causes unresponsiveness to the anticoagulant effects of heparin. Antithrombotic removal by intraoperative hemoadsorption is found to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization. Discussion: Bleeding complications in patients treated with DAPT or DOACs in cardiac surgery are high. New costly reversal agents are available but have not been sufficiently tested in the cardio-surgical setting so far. Interestingly, bleeding-related complications seem to be effectively reduced by applying innovative intraoperative hemoadsorption techniques. Expected results from the ongoing trials should provide better insights concerning the efficacy and safety of several potential solutions. Currently, the variability of reports and the deficit of high-quality studies in this specific setting represent the major limitation for the unbiased conclusion of this review.

Comparison of the CytoSorb® 300 mL and Jafron HA380 hemoadsorption devices: an in vitro study.

INTRODUCTION: We performed an analysis of two blood purification systems to determine their performance for removing interleukins (ILs)-6 and 10, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 from blood. MATERIAL AND METHODS: An in vitro hemoperfusion blood recirculation circuit was used to compare the CytoSorb® 300 mL (CytoSorbents Inc., Princeton, NJ) and Jafron HA 380 (Jafron Biomedical Co., Ltd., Zhuhai City, China) devices. The removal of purified recombinant human IL-6, IL-10, TNFα and MCP-1 by the adsorbers was compared at various timepoints. Three runs were completed and removal was evaluated as the mean area under the curve (AUC). RESULTS: Both devices showed effective removal of the tested cytokines. IL-6, IL-10, TNFα and MCP-1 were removed faster and to a higher extent by the CytoSorb® 300 mL device. At maximal time of 12 h, overall removal according to AUC of remaining concentrations was significantly lower with CytoSorb® 300 mL compared with HA 380 (IL-6: 1075.5 ± 665.9 vs. 4345.1 ± 1499.3 (p = 0.01), IL-10: 5065.7 ± 882.5 vs. 11,939.7 ± 4523.1 (p = 0.03), TNF-α: 6519.9 ± 997.6 vs. 10,303.7 ± 2347.0 (p = 0.03) and MCP-1: 278.9 ± 40.7 vs. 607.3 ± 84.4 (p = 0.001)). CONCLUSIONS: Both the CytoSorb® and the Jafron HA 380 devices are capable of removing cytokines from blood in a benchtop model. The CytoSorb® 300 device was significantly more efficient achieving the bulk of the removal in the first 120 min.

Intraoperative hemoadsorption in high-risk patients with infective endocarditis.

BACKGROUND: Postoperative sepsis is an important cause of morbidity and mortality in patients with infective endocarditis undergoing surgical therapy. Blood purification using hemoadsorption therapy shows promising results in the treatment of sepsis. In this study, the clinical effects of intraoperative hemoadsorption in high-risk patients with infective endocarditis were evaluated. METHODS: Eligible candidates were high-risk patients with infective endocarditis undergoing cardiac surgery between January 2014 and December 2019. Patients with intraoperative hemoadsorption (hemoadsorption) were compared to patients without hemoadsorption (control). The endpoints were the incidence of postoperative sepsis, sepsis-associated death and in-hospital mortality. Additionally, postoperative vasopressor need, systemic vascular resistance indices and Sequential Organ Failure Assessment (SOFA) scores were compared. RESULTS: After propensity score matching, 70 high-risk patients were included. Postoperative sepsis occurred in 14 patients in the hemoadsorption group and in 16 patients in the control group, p = 0.629. Four patients died due to postoperative sepsis in the hemoadsorption group, while 11 postoperative septic patients died in the control group, p = 0.041. In-hospital mortality was 34% in the hemoadsorption group versus 43% in the control group, p = 0.461. On ICU-admission and the first postoperative day, the cumulative vasopressor need was 0.17 versus 0.25 µg/kgBW/min, p = 0.123 and 0.06 versus 0.11 µg/kgBW/min, p = 0.037, and the systemic vascular resistance index was 1448 versus 941 dyn·s·cm-5, p = 0.013 and 1156 versus 858 dyn·s·cm-5, p = 0.110 in the hemoadsorption versus control group, respectively. Postoperative course of SOFA score normalized significantly (p = 0.01) faster in the hemoadsorption group. CONCLUSIONS: In high-risk cardiac surgical patients with infective endocarditis, intraoperative hemoadsorption significantly reduced sepsis-associated mortality. Furthermore, intraoperative hemoadsorption resulted in significant faster recovery of hemodynamics and organ function. Intraoperative hemoadsorption seems to attenuate the severity of postoperative sepsis.