Bleeding in Patients Treated With Ticagrelor or Clopidogrel Before Coronary Artery Bypass Grafting.

BACKGROUND: We evaluated perioperative bleeding after coronary artery bypass grafting (CABG) in patients preoperatively treated with ticagrelor or clopidogrel, stratified by discontinuation of these P2Y12 inhibitors. METHODS: All patients from the prospective, European Multicenter Registry on Coronary Artery Bypass Grafting (E-CABG) treated with ticagrelor or clopidogrel undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding, stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included four additional definitions of major bleeding. Propensity score matching was performed to adjust for differences in preoperative and perioperative covariates. RESULTS: Of 2,311 patients who were included, 1,293 (55.9%) received clopidogrel and 1,018 (44.1%) ticagrelor preoperatively. Mean time between discontinuation and the operation was 4.5 ± 3.2 days for clopidogrel and 4.9 ± 3.0 days for ticagrelor. In the propensity score-matched cohort, ticagrelor-treated patients had a higher incidence of major bleeding according to Universal Definition of Perioperative Bleeding when ticagrelor was discontinued 0 to 2 days compared with 3 days before the operation (16.0% vs 2.7%, p = 0.003). Clopidogrel-treated patients had a higher incidence of major bleeding according to the Universal Definition of Perioperative Bleeding when clopidogrel was discontinued 0 to 3 days compared with 4 to 5 days before the operation (15.6% vs 8.3%, p = 0.031). CONCLUSIONS: In patients receiving ticagrelor 2 days before CABG and in those receiving clopidogrel 3 days before CABG, there was an increased rate of severe bleeding. Postponing nonemergent CABG for at least 3 days after discontinuation of ticagrelor and 4 days after clopidogrel should be considered.

Impact of preoperative thrombocytopenia on the outcome after coronary artery bypass grafting.

The impact of thrombocytopenia on postoperative bleeding and other major adverse events after cardiac surgery is unclear. This issue was investigated in a series of patients who underwent isolated coronary artery bypass grafting (CABG) from the prospective, multicenter E-CABG registry. Preoperative thrombocytopenia was defined as preoperative platelet count <150 × 109/L and it was considered moderate-severe when preoperative platelet count was <100 × 109/L. Multilevel mixed-effects regression analysis was performed to adjust the effect of thrombocytopenia on outcomes for baseline and operative covariates as well as for interinstitutional differences in patient-blood management. Among 7189 patients included in this analysis, 599 (8.3%) had preoperative thrombocytopenia. Patient with preoperative thrombocytopenia had an increased chest drainage output at 12 h (mean, 519 vs. 456 mL, adjusted coeff. 39, 95%CI 18-60) and rates of severe-massive bleeding (Universal Definition of Perioperative Bleeding (UDPB) severity grades 3-4: 12.7% vs. 8.1%, adjusted OR 1.47, 95%CI 1.11-1.93; E-CABG bleeding severity grades 2-3: 10.4% vs. 6.1%, adjusted OR 1.78, 95%CI 1.30-2.43). Thrombocytopenia was associated with an increased risk of hospital/30-day death (3.2% vs. 1.9%, adjusted OR 2.02, 95%CI 1.20-3.42), 1-year death (5.7% vs. 3.4%, adjusted HR 1.68, 95%CI 1.16-2.44), deep sternal wound infection (3.5% vs. 2.4%, adjusted OR 1.65, 95%CI 1.02-2.66), acute kidney injury (28.1% vs. 22.2%, OR 1.45, 1.18-1.78), and prolonged stay in the intensive care unit (mean, 3.6 vs 2.8 days, adjusted coeff. 0.74, 95%CI 0.40-1.09). Similar results were observed in a subset of patients with moderate-severe thrombocytopenia (51 patients, 0.7%). In particular, these patients had a markedly higher rate of acute kidney injury (40%, adjusted OR, 1.94, 95%CI 1.05-3.57), resternotomy for bleeding (7.8%, adjusted OR 3.49, 95%CI 1.20-10.21), and severe-massive bleeding (UDPB severity grades 3-4: 23.5%, adjusted OR 3.08, 95%CI 1.52-6.22; E-CABG bleeding severity grades 2-3: 23.5%, adjusted OR 4.43, 95%CI 2.15-9.15) compared to patients with normal preoperative platelet count. Mild preoperative thrombocytopenia is associated with increased risk of severe-massive bleeding, mortality, and other major adverse events after CABG. Such risks are markedly increased in patients with moderate-severe preoperative thrombocytopenia.

Perioperative Bleeding in Patients With Acute Coronary Syndrome Treated With Fondaparinux Versus Low-Molecular-Weight Heparin Before Coronary Artery Bypass Grafting.

The perioperative bleeding risk in patients receiving fondaparinux versus low-molecular weight heparin before coronary artery bypass grafting has not been reported. We evaluated perioperative coronary artery bypass grafting-related bleeding in patients with acute coronary syndrome preoperatively treated with fondaparinux or low-molecular weight heparin. All patients with acute coronary syndrome from the prospective, European multicenter registry on coronary artery bypass grafting preoperatively treated with fondaparinux or low-molecular weight heparin undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included 3 additional definitions of major bleeding used in cardiac surgery trials. Propensity score matching was performed to adjust for differences in pre- and perioperative covariates. 1,525 patients were included, of whom 276 (18.1%) received fondaparinux and 1,249 (81.9%) low-molecular weight heparin preoperatively. In the propensity score-matched cohort (245 pairs), the risk of major bleeding according to the universal definition of perioperative bleeding severe or massive bleeding (11.8 vs 9.0%, p = 0.285) and the 3 other major bleeding definitions was similar between the fondaparinux and low-molecular weight heparin cohorts. In conclusion, preoperative treatment with fondaparinux compared with low-molecular weight heparin was associated with similar incidence of perioperative bleeding in patients with acute coronary syndrome who underwent coronary artery bypass grafting.

Prognostic Impact of Asymptomatic Carotid Artery Stenosis in Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVES: The aim of this study was to evaluate the prognostic impact of untreated asymptomatic carotid artery stenosis (CS) in patients undergoing isolated coronary artery bypass grafting (CABG). METHODS: This was a post hoc analysis of data from a prospective multicentre observational study. Patients without history of stroke or transient ischaemic attack from the multicentre E-CABG registry who were screened for CS before isolated CABG were included. RESULTS: Among 2813 patients screened by duplex ultrasound and who did not undergo carotid intervention for asymptomatic CS, 11.1% had a stenosis of 50-59%, 6.0% of 60-69%, 3.1% of 70-79%, 1.4% of 80-89%, 0.5% of 90-99%, and 1.1% had carotid occlusion. In the screened population post-operative stroke occurred in 25 patients (0.9%), with an incidence of 1.5% among patients with CS ≥ 50% (n = 649). Pre-operative screening had not found a relevant CS in 15 of 25 patients suffering stroke after CABG. Brain imaging identified cerebral ischaemic injury in 20 patients, which was bilateral in five patients (25%), ipsilateral to a CS ≥ 50% in six (30%), and ipsilateral to a CS ≥ 70% in three (15%). In univariable analysis, the severity of CS was associated with a significantly increased risk of stroke (CS < 50%, 0.7%; 50-59%, 1.0%; 60-69%, 0.6%; 70-79%, 1.2%; 80-89%, 5.1%; 90-99%, 7.7%; occluded, 6.7%, p < .001). In multivariable analysis, a CS of 90-99% (OR 12.03, 95% CI 1.34-108.23) and the presence of an occluded internal carotid artery (OR 8.783, 95% CI 1.820-42.40) were independent predictors of stroke along with urgency of the procedure, severe massive bleeding according to the E-CABG classification, and the presence of a porcelain ascending aorta. CONCLUSIONS: Among screened patients with untreated asymptomatic patients, CS ≥ 90% was an independent predictor of post-operative stroke. As this condition has a low prevalence and when left untreated is associated with a relatively low rate of stroke, pre-operative screening of asymptomatic CS before CABG may not be justified. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov. Unique identifier: NCT02319083.

Clinical frailty scale and outcome after coronary artery bypass grafting.

OBJECTIVES: The aim of this study was to assess the impact of frailty on the outcome after coronary artery bypass grafting (CABG) and whether it may improve the predictive ability of European System for Cardiac Operative Risk Evaluation (EuroSCORE II). METHODS: The Clinical Frailty Scale (CFS) was assessed preoperatively in patients undergoing isolated CABG from the multicentre E-CABG registry, and patients were stratified into 3 classes: scores 1-2, scores 3-4 and scores 5-7. RESULTS: Of the 6156 patients enrolled, 39.2% had CFS scores 1-2, 57.6% scores 3-4, and 3.2% scores 5-7. Logistic regression adjusted for multiple covariates showed that the CFS was an independent predictor of hospital/30-day mortality [CFS scores 3-4, odds ratio (OR) 3.95, 95% confidence interval (CI) 2.19-7.14; CFS scores 5-7, OR 5.90, 95% CI 2.67-13.05] and resulted in an Integrated Improvement Index of 1.3 (P < 0.001) and a Net Reclassification Index of 55.6 (P < 0.001) for prediction of hospital/30-day mortality. Adding the CFS classes to EuroSCORE II resulted in an Integrated Improvement Index of 0.9 (P < 0.001) and Net Reclassification Index of 59.6 (P < 0.001) for prediction of hospital/30-day mortality with a significantly larger area under the receiver operating characteristics curve (0.809 vs 0.781, P = 0.028). The CFS was an independent predictor of mid-term mortality [CFS scores 3-4, hazard ratio (HR) 2.05, 95% CI 1.43-2.85; CFS scores 5-7, HR 3.05, 95% CI 1.83-5.06]. CONCLUSIONS: The CFS predicted early- and mid-term mortality in patients undergoing isolated CABG. Further studies are needed to evaluate whether frailty may improve the estimation of the operative risk of patients undergoing adult cardiac surgery. Clinicaltrials.gov number: NCT02319083.

Utility of glycated hemoglobin screening in patients undergoing elective coronary artery surgery: Prospective, cohort study from the E-CABG registry.

BACKGROUND: Patients with increased glycated hemoglobin (HbA1c) seem to be at increased risk of sternal wound infection (SWI) after coronary artery bypass grafting (CABG). However, it is unclear whether increased baseline HbA1c levels may affect other postoperative outcomes. MATERIAL AND METHODS: Data on preoperative levels of HbA1c were collected from 2606 patients undergoing elective isolated CABG from 2015 to 2016 and included in the prospective, multicenter E-CABG registry. RESULTS: The prevalence of HbA1c ≥ 53 mmol/mol (7.0%) among non-diabetics was 5.3%, among non-insulin dependent diabetics was 53.5% and among insulin dependent diabetics was 67.1% (p < 0.001). The prevalence of HbA1c > 75 mmol/mol (9.0%) among non-diabetics was 0.5%, among non-insulin dependent diabetics was 5.8% and among insulin dependent diabetics was 10.6% (p < 0.001). Baseline levels of HbA1c ≥ 53 mmol/mol (7.0%) was a significant predictor of any SWI (10.7% vs. 3.3%, adjusted p-value: <0.001), deep SWI/mediastinitis (3.8% vs. 1.3%, adjusted p-value: 0.001) and acute kidney injury (27.4% vs. 19.8%, adjusted p-value: 0.042). These findings were confirmed in multilevel mixed effect logistic regression adjusted for participating centers. Among patients with diabetes, HbA1c ≥ 53 mmol/mol (7.0%) was predictive of SWI (11.1% vs. 4.8%, p = 0.001). CONCLUSIONS: HbA1c is increased in a significant proportion of patients undergoing elective CABG and these patients are at higher risk of SWI. Less clear is the impact of increased HbA1c on other postoperative outcomes. These results do not support screening of HbA1c in patients without history of diabetes. Preoperative screening of HbA1c is valuable only to identify diabetics at risk of SWI.

Venoarterial extracorporeal membrane oxygenation after coronary artery bypass grafting: Results of a multicenter study.

BACKGROUND: The evidence of the benefits of using venoarterial extracorporeal membrane oxygenation (VA-ECMO) after coronary artery bypass grafting (CABG) is scarce. METHODS: We analyzed the outcomes of patients who received VA-ECMO therapy due to cardiac or respiratory failure after isolated CABG in 12 centers between 2005 and 2016. Patients treated preoperatively with ECMO were excluded from this study. RESULTS: VA-ECMO was employed in 148 patients after CABG for median of 5.0days (mean, 6.4, SD 5.6days). In-hospital mortality was 64.2%. Pooled in-hospital mortality was 65.9% without significant heterogeneity between the centers (I2 8.6%). The proportion of VA-ECMO in each center did not affect in-hospital mortality (p=0.861). No patients underwent heart transplantation and six patients received a left ventricular assist device. Logistic regression showed that creatinine clearance (p=0.004, OR 0.98, 95% CI 0.97-0.99), pulmonary disease (p=0.018, OR 4.42, 95% CI 1.29-15.15) and pre-VA-ECMO blood lactate (p=0.015, OR 1.10, 95% CI 1.02-1.18) were independent baseline predictors of in-hospital mortality. One-, 2-, and 3-year survival was 31.0%, 27.9%, and 26.1%, respectively. CONCLUSIONS: One third of patients with need for VA-ECMO after CABG survive to discharge. In view of the burden of resources associated with VA-ECMO treatment and the limited number of patients surviving to discharge, further studies are needed to identify patients who may benefit the most from this treatment.

CD244 is expressed on dendritic cells and regulates their functions.

Signaling lymphocytic activation molecule (SLAM) receptors have an important role in the development of immune responses because of their roles, for exampe, in NK cell cytotoxicity and cytokine production by NK, T cells and myeloid cells. The SLAM receptor CD244 (2B4, SLAMf4) is expressed on a variety of immune cell types but most of its functions have been examined on NK and T cells. In the present study, we investigated expression and function of CD244 in murine subsets of dendritic cells (DCs). We report that all subsets of murine DCs examined expressed CD244, although the expression levels of CD244 varied between subsets. Splenic and resident mesenteric lymph node (MLN) DCs from CD244(-/-) mice expressed lower levels of CD86 and MHC class II compared with wild-type mice. Upon Toll-like receptor (TLR) stimulation, no differences in surface expression of these molecules were observed between DCs from CD244(-/-) and wild-type mice. However, splenic DCs from CD244(-/-) mice upon stimulation with TLR binding ligands lipopolysaccharide (LPS) and CpG produced significantly higher levels of pro-inflammatory cytokines. In addition, DCs from CD244(-/-) mice elicited increased NK cell activation in vitro. These data add CD244 to a growing list of immuno-modulatory receptors found on DCs.