The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation-First Insights.

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface-the endothelial glycocalyx-are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

[Xenotransplantation of solid organs]. / Xenotransplantation von Organen.

Transplantation of genetically modified porcine hearts and kidneys could become a solution to the persistent shortage of human organ donors. Progress has been made in genetic engineering of donor pigs, preservation techniques after organ harvesting and immunosuppression using co-stimulation blockade with anti-CD40/CD40L monoclonal antibodies. Progress has also been made in in the development of methods that detect pathogenic porcine viruses and prevent their transmission to the recipient. As normal land breed pig organs continue to grow in the recipient to their original size, different pig breeds (such as Auckland Island pigs) are now used which reach a final size suitable for humans. Alternatively, a knock-out of the growth hormone receptor gene has been established, e.g., in the 10GM genetically modified pigs from Revivicor/United Therapeutics, USA. The first clinical pilot studies including patients suffering from terminal heart failure are expected to start in Germany in about 2 years.

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.

Partial versus Complete Sternotomy for Aortic Valve Replacement-Multicenter Study.

BACKGROUND: The benefits of minimally invasive techniques in cardiac surgery remain poorly defined. We evaluated the short- and mid-term outcomes after surgical aortic valve replacement through partial upper versus complete median sternotomy (MS) in a large, German multicenter cohort. METHODS: A total of 2,929 patients underwent isolated surgical aortic valve replacement via partial upper sternotomy (PUS, n = 1,764) or MS (n = 1,165) at nine participating heart centers between 2016 and 2020. After propensity-score matching, 1,990 patients were eligible for analysis. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke at 30 days and in follow-up, up to 5 years. Secondary end points were acute kidney injury, length of hospital stay, transfusions, deep sternal wound infection, Dressler's syndrome, rehospitalization, and conversion to sternotomy. RESULTS: Unadjusted MACCE rates were significantly lower in the PUS group both at 30 days (p = 0.02) and in 5-year follow-up (p = 0.01). However, after propensity-score matching, differences between the groups were no more statistically significant: MACCE rates were 3.9% (PUS) versus 5.4% (MS, p = 0.14) at 30 days, and 9.9 versus 11.3% in 5-year follow-up (p = 0.36). In the minimally invasive group, length of intensive care unit (ICU) stay was shorter (p = 0.03), Dressler's syndrome occurred less frequently (p = 0.006), and the rate of rehospitalization was reduced significantly (p < 0.001). There were 3.8% conversions to full sternotomy. CONCLUSION: In a large, German multicenter cohort, MACCE rates were comparable in surgical aortic valve replacement through partial upper and complete sternotomies. Shorter ICU stay and lower rates of Dressler's syndrome and rehospitalization were in favor of the partial sternotomy group.

Current Status of Cardiac Xenotransplantation: Report of a Workshop of the German Heart Transplant Centers, Martinsried, March 3, 2023.

This report comprises the contents of the presentations and following discussions of a workshop of the German Heart Transplant Centers in Martinsried, Germany on cardiac xenotransplantation. The production and current availability of genetically modified donor pigs, preservation techniques during organ harvesting, and immunosuppressive regimens in the recipient are described. Selection criteria for suitable patients and possible solutions to the problem of overgrowth of the xenotransplant are discussed. Obviously microbiological safety for the recipient and close contacts is essential, and ethical considerations to gain public acceptance for clinical applications are addressed. The first clinical trial will be regulated and supervised by the Paul-Ehrlich-Institute as the National Competent Authority for Germany, and the German Heart Transplant Centers agreed to cooperatively select the first patients for cardiac xenotransplantation.

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.

Impact of Graft Strategies on the Outcome of Octogenarians Undergoing Coronary Artery Bypass Grafting.

PURPOSE: To analyse the outcome of coronary artery bypass grafting (CABG) in octogenarians with coronary multivessel disease and the impact of different graft strategies and other factors. METHODS: Out of 1654 patients with multivessel disease who underwent CABG at our institution between January 2014 and March 2020, we investigated 225 consecutive patients with a median age of 82.1 years for survival prediction and need for coronary reintervention; a detailed outcome analysis was performed. RESULTS: At mean follow-up of 3.3 years, the overall survival was 76.4%. An indication for emergency operation (p = 0.002), age (p <0.001), chronic pulmonary disease (p = 0.024), and reduced renal or ventricular function (p <0.001) had the highest impact on limited survival. The combination outcome of survival and coronary reintervention was 1.7-fold improved (p = 0.024) after use of the bilateral internal thoracic artery (BITA) (66.2%). Off-pump CABG (12%) revealed no impact on survival. Smokers showed a poorer outcome (p = 0.004). The logistic European System for Cardiac Operative Risk Evaluation was highly effective for evaluating long-term outcomes (p <0.001). CONCLUSIONS: BITA grafting normalizes survival and reveals a better outcome in octogenarians with multivessel disease. However, patients at risk of poorer survival were operated under emergency conditions and those with pulmonary disease and reduced ventricular or renal function.

Reversal and removal of oral antithrombotic drugs in patients with active or perceived imminent bleeding.

Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications.

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.

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.

Prognostic impact of secondary prevention after coronary artery bypass grafting-insights from the TiCAB trial.

OBJECTIVES: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG. METHODS: Data were taken from the randomized 'Ticagrelor in CABG' trial. From April 2013 until April 2017, patients who underwent CABG were included. For the present analysis, we compared patients who were treated with optimal medical secondary prevention with those where 1 or more of the recommended medications were missing. RESULTS: Follow-up data at 12 months were available in 1807 patients. About half (54%) of them were treated with optimal secondary prevention. All-cause mortality [0.5% vs 3.5%, hazard ratio (HR) 0.14 (0.05-0.37), P < 0.01], cardiovascular mortality [0.1% vs 1.7%, HR 0.06 (0.01-0.46), P = 0.007] and major adverse events [6.5% vs 11.5%, HR 0.54 (0.39-0.74), P < 0.01] were significantly lower in the group with optimal secondary prevention. The multivariable model for the primary end point based on binary concordance to guideline recommended therapy identified 3 independent factors: adherence to guideline recommended therapy [HR 0.55 (0.39-0.78), P < 0.001]; normal renal function [HR 0.99 (0.98-0.99), P = 0.040]; and off-pump surgery [HR 2.06 (1.02-4.18), P = 0.045]. CONCLUSIONS: Only every second patient receives optimal secondary prevention after CABG. Guideline adherent secondary prevention therapy is associated with lower mid-term mortality and less adverse cardiovascular events after 12 months.

Hemoadsorption of Rivaroxaban and Ticagrelor during Acute Type A Aortic Dissection Operations.

OBJECTIVE: To analyze the results of hemoadsorption in patients with cardiac surgery to thoracic aortic surgery, who had been loaded beforehand with either Factor Xa inhibitor rivaroxaban or P2Y12 receptor antagonist ticagrelor. METHODS: We investigated 21 of 171 consecutive patients (median age 71 [interquartile range 62, 76] years) who underwent emergency cardiac operations for acute type A aortic dissection between 2014 and 2020. These patients were pretreated with rivaroxaban (n = 9) or ticagrelor (n = 12). In ten of 21 cases (since 2017), we installed a hemoadsorber into the heart-lung machine and compared the results to eleven patients done without hemoadsorber before that time. RESULTS: The operation time was significantly shorter in the adsorber group (286 ± 40 min vs. 348 ± 79 min; p = 0.045). The postoperative 24-hour drainage volume was significantly lower after adsorption (p <0.001; 482 ± 122 ml vs. 907 ± 427 ml) and no rethoracotomy had to be performed (compared to two rethoracotomies [18.9%] among patients without adsorber use). Also, patients without hemoadsorption required significantly more platelet transfusions (p = 0.049). CONCLUSIONS: In patients with acute type A aortic dissection who were pretreated with rivaroxaban and ticagrelor, the intraoperative use of CytoSorb hemoadsorption during cardiopulmonary bypass is reported for the first time. The method was found to be effective to prevent from bleeding and to improve the outcome in aortic dissection.

Medical, Interventional, and Surgical Treatment Strategies for Atrial Fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of cardiac arrhythmia; the lifetime risk for a 55-year-old person to develop atrial fibrillation is 37%. In recent years, years there have been various distinct changes in the clinical management of AF. METHODS: This review is based on a selective search for literature on the treatment of AF and the prevention of thromboembolic complications. The updated guideline of the European Society of Cardiology (ESC) for the diagnosis and treatment of AF was also taken into consideration. RESULTS: The main components of AF management are the comprehensive treatment of risk factors and concomitant diseases, as well as the prevention of thromboembolic complications, usually with non-vitamin-K-dependent oral anticoagulants or vitamin K antagonists, according to individual risk stratification. Beyond this, either rate or rhythm control are viable treatment concepts. Symptomatic patients in whom reversible causes have been ruled out should be offered rhythm-control therapy early in their course. In patients with risk factors and/or heart failure, an early rhythm control strategy has been found to be beneficial. As antiarrhythmic drugs often prove to be ineffective over the long term, catheter ablation is now becoming increasingly important in AF management. CONCLUSION: The clinical management of atrial fibrillation consists of a multimodal approach with risk stratification, lifestyle modification, prevention of thromboembolism, and, if possible, early rhythm control therapy.

Left-lateral thoracotomy for catheter ablation of scar-related ventricular tachycardia in patients with inaccessible pericardial access.

OBJECTIVES: We aimed to describe the feasibility of a surgical left thoracotomy for catheter ablation of scar-related ventricular tachycardia (VT) in patients with inaccessible pericardial access. BACKGROUND: Pericardial adhesion due to prior cardiac surgery or previous epicardial ablation procedures limits epicardial access in patients with drug-refractory VT originated from the epicardium. METHODS: Six patients who underwent a surgical left lateral thoracotomy epicardial access for catheter ablation of VT after failed subxiphoid percutaneous epicardial access were reviewed. Patients' baseline characteristics and procedural characteristics including epicardial access, mapping, and ablation were described. Epicardial access was successfully obtained in all patients by a surgical left lateral thoracotomy. RESULTS: The reasons of pericardial adhesion were prior cardiac surgery (n = 3, 50%) and previous epicardial ablation procedures (n = 3, 50%). Epicardial mapping of the lateral and inferior left ventricle was acquired, and a total of 15 different VTs originated from those regions were abolished. Unless one patient with ST elevation myocardial infarction due to periprocedural occlusion of the posterior descending artery no further complications occurred. All patients were discharged 10.2 ± 4 days after the procedure. VT recurred in 1 patient (17%) and was controlled with oral amiodarone therapy during follow-up (median follow-up: 479 days). CONCLUSIONS: A surgical left lateral thoracotomy is feasible and safe for selected patients. This approach provides epicardial ablation in patients with VT located at the infero-lateral left ventricle and pericardial adhesions due to previous cardiac surgery or previous ablation procedures.

Clinical impact of intervention strategies after failed transcatheter mitral valve repair.

AIMS: Failure of transcatheter mitral valve repair (fTMVR) therapy has a decisive prognostic influence, and complex retreatment is of higher risk. The aim of this analysis was to evaluate the survival outcome following percutaneous procedures and surgery after unsuccessful TMVR interventions for different aetiologies. METHODS AND RESULTS: Of 824 consecutive patients who had been treated with the MitraClip device at our institution, between September 2009 and May 2019, 63 (7.6%) symptomatic patients with therapy failure and persistent or recurrent mitral regurgitation (MR) underwent reinterventions. An outcome analysis for primary (PMR) and secondary mitral regurgitation (SMR) and subsequent percutaneous versus surgical treatment was carried out. MitraClip reinterventions were performed in 36 patients (57.1%; n=26 SMR, n=10 PMR), while 27 (42.9%; n=13 SMR, n=14 PMR) underwent open heart surgery. Surgical patients with PMR showed lower mortality than patients with SMR (p<0.0001) and ReClip patients with PMR (p=0.073). Atrial fibrillation (HR 2.915, 95% CI: [1.311, 6.480]), prior open heart surgery (2.820 [1.215, 6.544]) and chronic obstructive pulmonary disease (2.506 [1.099, 5.714]) increased the risk of death. The level of post-interventional MR had no relevant impact on survival. CONCLUSIONS: We conclude that, after SMR and failed TMVR, reclipping is an appropriate treatment option for symptomatic patients. For PMR patients, surgery must be favoured over a reclipping procedure. However, patients with atrial fibrillation, prior open heart surgery and chronic obstructive pulmonary disease are at risk of reduced survival after reinterventions.

Is the Use of BIMA in CABG Sub-Optimal? A Review of the Current Clinical and Economic Evidence Including Innovative Approaches to the Management of Mediastinitis.

Bilateral internal mammary artery (BIMA) in coronary artery bypass grafting (CABG) has traditionally been limited. This review looks at the recent outcome data on BIMA in CABG focusing on the management of risk factors for mediastinitis, one of the potential barriers for more extensive BIMA utilization. A combination of pre-, intra- and postoperative strategies are essential to reduce mediastinitis. Limited data indicate that the incidence of mediastinitis can be reduced using closed incision negative-pressure wound therapy as a part of these strategies with the possibility of offering patients best treatment options by extending BIMA to those with a higher risk of mediastinitis. Recent economic data imply that the technology may challenge the current low uptake of BIMA by reducing the short-term cost differentials between single internal mammary artery and BIMA. Given that most published randomized controlled trials and meta-analyses of observational long-term outcome data favor BIMA, if short-term complications of BIMA including mediastinitis can be controlled adequately, there may be opportunities for more extensive use of BIMA leading to improved long-term outcomes. An ongoing study looking at BIMA in high-risk patients may provide evidence to support the hypothesis that mediastinitis should not be a factor in limiting the use of BIMA in CABG.

Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial.

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

Cytosorb Adsorption During Emergency Cardiac Operations in Patients at High Risk of Bleeding.

BACKGROUND: The purpose of this study was to analyze the results of Cytosorb (CytoSorbents, Monmouth Junction, NJ) adsorption during emergency open heart operations in patients at high risk of bleeding due to treatment with coagulation-active substances. METHODS: We investigated 55 consecutive patients (median age 70 years; interquartile range: 60 to 77) who underwent emergency cardiac surgery at our institution between June 2016 and June 2018. All patients were receiving therapy with either ticagrelor (n = 43) or rivaroxaban (n = 12). In 39 of 55 cases, we routinely installed standardized Cytosorb adsorption into the heart-lung machine. Bleeding complications during and after surgery were analyzed in detail and compared with 16 patients without adsorption. RESULTS: In the Cytosorb adsorption group, no rethoracotomies had to be performed. Drainage volumes in 24 hours were only 350 mL (interquartile range: 300 to 450 mL) after ticagrelor administration and 390 mL (interquartile range: 310 to 430 mL) after rivaroxaban therapy. In the majority of patients, transfusions of blood products were not needed. Compared with that group, among the group of patients without adsorption, multiple bleeding complications occurred. These were associated with longer total operation (p = 0.0042), higher drainage volumes (p = 0.0037), more transfusions of red blood cells (p = 0.0119) and platelets (p = 0.0475), a significantly higher rethoracotomy rate (p = 0.0003), significantly prolonged stay in the intensive care unit (p = 0.0141), and a longer hospital stay (p = 0.0244). CONCLUSIONS: The intraoperative use of Cytosorb adsorption of ticagrelor and rivaroxaban in emergency open heart operations is reported for the first time. The data show that the strategy is safe and is an effective method to reduce bleeding complications. We recommend the use for safety in patients with ticagrelor or rivaroxaban undergoing emergency cardiac surgery.

The impact of biventricular heart failure on outcomes after transcatheter aortic valve implantation.

AIMS: We sought to assess the impact of different manifestations of heart failure (HF) at baseline on the short- and long-term outcomes of transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS). METHODS AND RESULTS: Of 361 patients undergoing TAVI between May 2013 and April 2015, 185 (51%) showed clinical signs of HF at the time of admission. HF was diagnosed as isolated left ventricular (LV) and biventricular in 63 (34%) and 122 patients (66%), respectively. Acute device success (VARC-2) was achieved in 97% of patients without HF, in all patients with LV HF, and in 97% of patients with biventricular HF. Follow-up for a median of 427 days revealed significantly poorer survival in patients with biventricular HF (1-year estimate, 72.1% [95% confidence interval, 64.0-80.2%]) than in patients with LV HF (84.5% [75.2-93.8%]; p = 0.0203) or no HF (94.3% [90.7-97.9%]; p < 0.0001). Survival in the latter two patient subgroups was statistically not different. A diagnosis of biventricular HF was associated with a hazard ratio of 2.62 (p = 0.0089) vs. no HF in the likelihood of death; NT-proBNP and the logistic EuroSCORE were not significantly associated with survival. Half of all deaths in patients with biventricular HF occurred within 42 days of TAVI. CONCLUSION: Biventricular HF is a strong predictor of mortality following TAVI for severe AS. AS in patients with LV HF should be treated without delay to avoid progression to biventricular HF. Patients with AS and biventricular HF should be monitored closely after TAVI to possibly prevent early death.