Andrea Perrotti

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.

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.

Neutrophil Gelatinase-Associated Lipocalin as Early Predictor of Acute Kidney Injury After Cardiac Surgery in Adults With Chronic Kidney Failure

BACKGROUND To assess the utility of neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury (AKI) occurring after cardiac surgery in patients with prior chronic kidney failure. METHODS Patients with preoperative creatinine clearance 60 mL • min(-1) • 1.73 m(-2) or less according to the Cockcroft-Gault formula and scheduled to undergo cardiac surgery were eligible for inclusion. The AKI was defined as an increase in plasma creatinine greater than 50% over preoperative values. Threshold values of NGAL predictive of AKI were determined using receiver operating characteristic curve analysis, and predictive value of NGAL for AKI was evaluated by logistic regression. RESULTS Over a 1-year inclusion period, 166 patients were included. At 6 hours post-surgery, hypertension, occurrence of at least 1 postoperative complication, and NGAL greater than 155 ng/mL were shown to be independent predictors of AKI. NGAL greater than 155 ng/mL at 6 hours was associated with an odds ratio for risk of postoperative AKI of 7.1 [2.7 to 18]. On average, diagnosis of postoperative AKI was made 20 hours earlier using NGAL at 6 hours post-surgery as compared with a diagnosis based on a 50% increase in creatinine over baseline. The threshold for NGAL of 155 ng/mL at 6 hours had a sensitivity of 79% and specificity of 58% for the diagnosis of AKI. CONCLUSIONS Earlier diagnosis of AKI post-surgery based on NGAL assessment makes it possible to initiate appropriate therapy at an earlier stage in this high-risk patient population.

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).

Meta-Analysis of the Outcome After Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation in Adult Patients

OBJECTIVE This study was planned to pool existing data on outcome and to evaluate the efficacy of postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) in adult patients. DESIGN Systematic review of the literature and meta-analysis. SETTING Multi-institutional study. PARTICIPANTS Adult patients with acute heart failure immediately after cardiac surgery. INTERVENTIONS VA-ECMO after cardiac surgery. Studies evaluating only heart transplant patients were excluded from this analysis. MEASUREMENTS AND MAIN RESULTS A literature search was performed to identify studies published since 2000. Thirty-one studies reported on 2,986 patients (mean age, 58.1 years) who required postcardiotomy VA-ECMO. The weaning rate from VA-ECMO was 59.5% and hospital survival was 36.1% (95% CI 31.5-40.8). The pooled rate of reoperation for bleeding was 42.9%, major neurological event 11.3%, lower limb ischemia 10.8%, deep sternal wound infection/mediastinitis 14.7%, and renal replacement therapy 47.1%. The pooled mean number of transfused red blood cell units was 17.7 (95% CI 13.3-22.1). The mean stay in the intensive care unit was 13.3 days (95% CI 10.2-16.4). Survivors were significantly younger (mean, 55.7 v 63.6 years, p = 0.015) and their blood lactate level before starting VA-ECMO was lower (mean, 7.7 v 10.7 mmol/L, p = 0.028) than patients who died. One-year survival rate was 30.9% (95% CI 24.3-37.5). CONCLUSIONS Pooled data showed that VA-ECMO may salvage one-third of patients unresponsive to any other resuscitative treatment after adult cardiac surgery.

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.

Validation of a Predictive Scoring System for Deep Sternal Wound Infection after Bilateral Internal Thoracic Artery Grafting in a Cohort of French Patients

BACKGROUND The Gatti score is a weighted scoring system based on risk factors for deep sternal wound infection (DSWI) that was created in an Italian center to predict DSWI risk after bilateral internal thoracic artery (BITA) grafting. No external evaluation based on validation samples derived from other surgical centers has been performed. The aim of this study is to perform this validation. PATIENTS AND METHODS During 2015, BITA grafts were used as skeletonized conduits in all 255 consecutive patients with multi-vessel coronary disease who underwent isolated coronary bypass surgery at the Department of Thoracic and Cardio-Vascular Surgery, University Hospital Jean Minjoz, Besançon, France. Baseline characteristics, operative data, and immediate outcomes of every patient were collected prospectively. A DSWI risk score was assigned to each patient pre-operatively. The discrimination power of both models, pre-operative and combined, of the Gatti score was assessed with the calculation of the area under the receiver operating characteristic curve. RESULTS Fourteen (5.5%) patients had DSWI. Major differences both as the baseline characteristics of patients and surgical techniques were found between this series and the original series from which the Gatti score was derived. The area under the receiver operating characteristic curve was 0.78 (95% confidence interval: 0.64-0.92) for the pre-operative model and 0.84 (95% confidence interval: 0.69-0.98) for the combined model. CONCLUSIONS The Gatti score has proven to be effective even in a cohort of French patients despite major differences from the original Italian series. Multi-center validation studies must be performed before introducing the score into clinical practice.

Simple Scoring System to Predict In-Hospital Mortality After Surgery for Infective Endocarditis

Background Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in‐hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. Methods and Results Outcomes of 361 consecutive patients (mean age, 59.1±15.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in‐hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty‐six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate <50 mL/min (OR, 3.52; P<0.0001), New York Heart Association class IV (OR, 2.11; P=0.024), systolic pulmonary artery pressure >55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in‐hospital death. A scoring system was devised to predict in‐hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734–0.822). The score performed better than 5 of 6 scoring systems for in‐hospital death after cardiac surgery that were considered. Conclusions A simple scoring system based on risk factors for in‐hospital death was specifically created to predict mortality risk postsurgery in patients with IE.