Riccardo Gherli

European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG registry): Study Protocol for a Prospective Clinical Registry and Proposal of Classification of Postoperative Complications

BackgroundClinical evidence in coronary surgery is usually derived from retrospective, single institutional series. This may introduce significant biases in the analysis of critical issues in the treatment of these patients. In order to avoid such methodological limitations, we planned a European multicenter, prospective study on coronary artery bypass grafting, the E-CABG registry.DesignThe E-CABG registry is a multicenter study and its data are prospectively collected from 13 centers of cardiac surgery in university and community hospitals located in six European countries (England, Italy, Finland, France, Germany, Sweden). Data on major and minor immediate postoperative adverse events will be collected. Data on late all-cause mortality, stroke, myocardial infarction and repeat revascularization will be collected during a 10-year follow-up period. These investigators provided a score from 0 to 10 for any major postoperative adverse events and their rounded medians were used to stratify the severity of these complications in four grades. The sum of these scores for each complication/intervention occurring after coronary artery bypass grafting will be used as an additive score for further stratification of the prognostic importance of these events.DiscussionThe E-CABG registry is expected to provide valuable data for identification of risk factors and treatment strategies associated with suboptimal outcome. These information may improve the safety and durability of coronary artery bypass grafting. The proposed classification of postoperative complications may become a valuable research tool to stratify the impact of such complications on the outcome of these patients and evaluate the burden of resources needed for their treatment.Clinical Trials numberNCT02319083

Safety of Preoperative Use of Ticagrelor With or Without Aspirin Compared With Aspirin Alone in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Grafting

Importance The optimal timing of discontinuation of ticagrelor before cardiac surgery is controversial. Objective To evaluate the safety of preoperative use of ticagrelor with or without aspirin in patients with acute coronary syndromes (ACS) undergoing isolated coronary artery bypass grafting (CABG) compared with aspirin alone. Design, Setting, and Participants This prospective, multicenter clinical trial was performed at 15 European centers of cardiac surgery. Participants were patients with ACS undergoing isolated CABG from the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry between January and September 2015. Exposures Before surgery, patients received ticagrelor with or without aspirin or aspirin alone. Main Outcomes and Measures Severe bleeding as defined by the Universal Definition of Perioperative Bleeding (UDPB) and E-CABG bleeding classification criteria. A propensity score-matched analysis was performed to adjust for differences in baseline and operative covariates. Results Of 2482 patients from the E-CABG registry, the study cohort included 786 (31.7%) consecutive patients with ACS (mean [SD] age, 67.1 [9.3] years; range, 32-88 years), and 132 (16.8%) were female. One-to-one propensity score matching provided 215 pairs, whose baseline and operative covariates had a standardized difference of less than 10%. Preoperative use of ticagrelor was associated with a similar risk of bleeding according to the UDPB and E-CABG bleeding classifications, but the incidence of platelet transfusion was higher in the ticagrelor group (13.5% [29 of 215] vs 6.0% [13 of 215]). Compared with those receiving aspirin alone, continuing ticagrelor up to the time of surgery or discontinuing its use less than 2 days before surgery was associated with a higher risk of platelet transfusion (22.7% [5 of 22] vs 6.4% [12 of 187]) and E-CABG bleeding grades 2 and 3 (18.2% [4 of 22] vs 5.9% [11 of 187]) and tended to have an increased risk of UDPB grades 3 and 4 (22.7% [5 of 22] vs 9.6% [18 of 187]). Among patients in whom antiplatelet drug use was discontinued at least 2 days before surgery, the incidence of platelet transfusion was 12.4% (24 of 193) in the ticagrelor group and 3.6% (1 of 28) in the aspirin-alone group. Conclusions and Relevance In propensity score-matched analyses among patients with ACS undergoing CABG, the use of preoperative ticagrelor with or without aspirin compared with aspirin alone was associated with more platelet transfusion but similar degree of bleeding; in patients receiving ticagrelor 1 day before or up until surgery, there was an increased rate of severe bleeding.

The effect of timing of cardiac catheterization on acute kidney injury after cardiac surgery is influenced by the type of operation

BACKGROUND Acute kidney injury (AKI) is a vexing complication of cardiac surgery. Since exposure to contrast agents is a relevant contributing factor in the development of postoperative AKI, the optimal timing between cardiac catheterization and surgery is decisive. METHODS A total of 2504 consecutive nonemergent patients undergoing isolated coronary artery bypass grafting (CABG), valve surgery (with or without concomitant CABG), and proximal aortic procedures were enrolled. AKI was defined by consensus RIFLE (Risk, Injury, Failure, Loss of function, End-stage renal disease) criteria. The association of postoperative AKI and time between cardiac catheterization and operation was evaluated using multivariable logistic regression modeling and propensity-matched analysis. RESULTS Postoperative AKI occurred in 230 (9%) patients. The median number of days from cardiac catheterization to operation was 5 (25th to 75th percentile: 2 to 10). The incidence of AKI was significantly higher in patients operated on ≤1 day after cardiac catheterization compared to those operated on >1 day after (13% vs. 8%, p=0.004). The time interval between cardiac catheterization and surgery (tested both as a continuous and a categorical variable) was not an independent AKI predictor in the propensity-matched population or the pre-matched one. Contrast exposure≤1 day before surgery was independently associated with postoperative AKI in patients undergoing valve surgery with concomitant CABG only (post-matched: OR 3.68, 95%CI 1.30 to 10.39, p=0.014). CONCLUSIONS Delaying cardiac surgery beyond 24h of exposure to contrast agents seems to be justified only in patients undergoing valve surgery with concomitant CABG.

Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score.

Severe perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2-3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4 %. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m2 (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0-3: 2.9 % vs 3.4 %; scores 4-6: 6.8 % vs 7.5 %; scores>6: 24.6 % vs 24.2 %, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.

Glycated Hemoglobin and Risk of Sternal Wound Infection After Isolated Coronary Surgery

BACKGROUND Glycated hemoglobin (HbA1c) is a suspected risk factor for sternal wound infection (SWI) after CABG.Methods and Results:Data on preoperative HbA1c and SWI were available in 2,130 patients undergoing isolated CABG from the prospective E-CABG registry. SWI occurred in 114 (5.4%). Baseline HbA1c was significantly higher in patients with SWI (mean, 54±17 vs. 45±13 mmol/mol, P<0.0001). This difference was also observed in patients without a diagnosis of diabetes (P=0.027), in insulin-dependent diabetic (P=0.023) and non-insulin-dependent diabetic patients (P=0.034). In the overall series, HbA1c >70 mmol/mol (NGSP units, 8.6%) was associated with the highest risk of SWI (20.6% vs. 4.6%; adjusted OR, 5.01; 95% CI: 2.47-10.15). When dichotomized according to the cut-off 53 mmol/mol (NGSP units, 7.0%) as suggested both for diagnosis and optimal glycemic control of diabetes, HbA1c was associated with increased risk of SWI in the overall series (10.6% vs. 3.9%; adjusted OR, 2.09; 95% CI: 1.24-3.52), in diabetic patients (11.7% vs. 5.1%; adjusted OR, 2.69; 95% CI: 1.38-5.25), in patients undergoing elective surgery (9.9% vs. 2.7%; adjusted OR, 2.09; 95% CI: 1.24-3.52) and in patients with bilateral mammary artery grafts (13.7% vs. 4.8%; adjusted OR, 2.35; 95% CI: 1.17-4.69). CONCLUSIONS Screening for HbA1c before CABG may identify untreated diabetic patients, as well as diabetic patients with suboptimal glycemic control, at high risk of SWI.

Incidence and prognostic impact of bleeding and transfusion after coronary surgery in low-risk patients

Excessive bleeding and blood transfusion are associated with adverse outcome after cardiac surgery, but their mechanistic effects are difficult to disentangle in patients with increased operative risk. This study aimed to evaluate the incidence and prognostic impact of bleeding and transfusion of blood products in low‐risk patients undergoing coronary artery bypass grafting (CABG).

Validation of the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) Bleeding Severity Definition.

BACKGROUND This study evaluated the prognostic significance of a novel bleeding severity classification in adult patients undergoing cardiac operations. METHODS The European multicenter study on Coronary Artery Bypass Grafting (E-CABG) bleeding severity classification proposes 4 grades of postoperative bleeding: grade 0, no need of blood products with the exception of 1 unit of red blood cells (RBCs); grade 1, transfusion of platelets, plasma, or 2 to 4 units of RBCs, or both; grade 2, transfusion of 5 to 10 units of RBCs or reoperation for bleeding, or both; grade 3, transfusion of more than 10 units of RBCs. This classification was tested in a cohort of 7,491 patients undergoing CABG or valve operations, or combined procedures. RESULTS The E-CABG bleeding severity grading method was an independent predictor of in-hospital death, stroke, acute kidney injury, renal replacement therapy, deep sternal wound infection, atrial fibrillation, intensive care unit stay of 5 days or more, and composite adverse events of death, stroke, renal replacement therapy, and intensive care unit stay of 5 days or more. The area under the receiver operating characteristic curve of the E-CABG bleeding severity grading method for predicting in-hospital death was 0.858 (95% confidence interval, 0.827 to 0.889). E-CABG bleeding severity grades 0 to 3 were associated with in-hospital mortality rates of 0.2%, 1.1%, 7.9%, and 29.0%, respectively (p <0.001), and with composite adverse events of 2.7%, 9.6%, 29.7%, and 75.8%, respectively (p <0.001). CONCLUSIONS The E-CABG bleeding severity classification seems to be a valuable tool in the assessment of the severity and prognostic effect of perioperative bleeding in cardiac operations.

Validation of a New Classification Method of Postoperative Complications in Patients Undergoing Coronary Artery Surgery

OBJECTIVE The authors aimed to validate the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) classification of postoperative complications in patients undergoing coronary artery bypass grafting (CABG). DESIGN Retrospective, observational study. SETTING University hospital. PARTICIPANTS A total of 2,764 patients with severe coronary artery disease. Complete baseline, operative, and postoperative data were available for patients who underwent isolated CABG. INTERVENTIONS Isolated CABG. MEASUREMENTS AND MAIN RESULTS The E-CABG complication classification was used to stratify the severity and prognostic impact of adverse postoperative events. Primary outcome endpoints were 30-day, 90-day, and long-term all-cause mortality. The secondary outcome endpoints was the length of intensive care unit stay. Both the E-CABG complication grades and additive score were predictive of 30-day (area under the receiver operating characteristics curve 0.866, 95% confidence interval [CI] 0.829-0.903; and 0.876; 95% CI 0.844-0.908, respectively) and 90-day (area under the receiver operating characteristics curve 0.850, 95% CI 0.812-0.887; and 0.863, 95% CI 0.829-0.897, respectively) all-cause mortality. The complication grades were independent predictors of increased mortality at actuarial (log-rank: p<0.0001) and adjusted analysis (p<0.0001; grade 1: hazard ratio [HR] 1.757, 95% CI 1.111-2.778; grade 2: HR 2.704, 95% CI 1.664-4.394; grade 3: HR 5.081, 95% CI 3.148-8.201). When patients who died within 30 days were excluded from the analysis, this grading method still was associated with late mortality (p<0.0001). The grading method (p<0.0001) and the additive score (rho, 0.514; p<0.0001) were predictive of the length of intensive care unit stay. CONCLUSIONS The E-CABG postoperative complication classification seems to be a promising tool for stratifying the severity and prognostic impact of postoperative complications in patients undergoing cardiac surgery.

The impact of minor blood transfusion on the outcome after coronary artery bypass grafting

Purpose To investigate the impact of minor perioperative bleeding requiring transfusion of 1–2 red blood cell (RBC) units on the outcome after coronary artery bypass grafting (CABG). Methods Sixteen cardiac surgical centers contributed to the prospective European CABG registry (E‐CABG). 1014 patients receiving 1–2 RBC units during or after isolated CABG were compared to 2264 patients not receiving RBCs. Results In 827 propensity score matched pairs, transfusion of 1–2 RBC units did not affect the risk of in‐hospital/30‐day death (p = 0.523) or stroke (p = 0.804). However, RBC transfusion was associated with an increased risk of acute kidney injury (p = 0.008), sternal wound infection (p = 0.001), postoperative use of antibiotics (p = 0.001), prolonged use of inotropes (p < 0.0001), use of intra‐aortic balloon pump (p = 0.012), length of intensive care unit stay (p < 0.0001) and length of in‐hospital stay (p < 0.0001). Matched paired analysis excluding pre‐ and postoperative critical hemodynamic conditions showed that RBC transfusion was associated with an increased risk of major complications except in‐hospital/30‐day death. Conclusion Minor perioperative bleeding and subsequent transfusion of 1–2 RBC units did not affect the risk of early death, but increased the risk of other major adverse events. Minimizing perioperative bleeding and prevention of even low‐volume RBC transfusion may improve the outcome after CABG. Highlights1–2 red cell units did not affect the risk of early death after coronary surgery.Transfusion was associated with an increased risk of other major adverse events.‐The results persisted after excluding patients with critical hemodynamic conditions.

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.