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Background: We reported previously that, in patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery., Methods: We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red-cell transfusion strategy (transfusion if the hemoglobin concentration was <7.5 g per deciliter intraoperatively or postoperatively) or a liberal red-cell transfusion strategy (transfusion if the hemoglobin concentration was <9.5 g per deciliter intraoperatively or postoperatively when the patient was in the intensive care unit [ICU] or was <8.5 g per deciliter when the patient was in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis occurring within 6 months after the initial surgery. An expanded secondary composite outcome included all the components of the primary outcome as well as emergency department visit, hospital readmission, or coronary revascularization occurring within 6 months after the index surgery. The secondary outcomes included the individual components of the two composite outcomes., Results: At 6 months after surgery, the primary composite outcome had occurred in 402 of 2317 patients (17.4%) in the restrictive-threshold group and in 402 of 2347 patients (17.1%) in the liberal-threshold group (absolute risk difference before rounding, 0.22 percentage points; 95% confidence interval [CI], -1.95 to 2.39; odds ratio, 1.02; 95% CI, 0.87 to 1.18; P=0.006 for noninferiority). Mortality was 6.2% in the restrictive-threshold group and 6.4% in the liberal-threshold group (odds ratio, 0.95; 95% CI, 0.75 to 1.21). There were no significant between-group differences in the secondary outcomes., Conclusions: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy for red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Background: The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: (1) intraoperative, (2) remaining day of surgery, and (3) during the initial four postoperative days., Methods: This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction. Clinically important hypotension was defined as systolic blood pressure less than 90 mmHg requiring treatment. Minutes of hypotension was the exposure variable intraoperatively and for the remaining day of surgery, whereas hypotension status was treated as binary variable for postoperative days 1 to 4. We estimated the average relative effect of hypotension across components of the composite using a distinct effect generalized estimating model, adjusting for hypotension during earlier periods., Results: Among 9,765 patients, 42% experienced hypotension, 590 (6.0%) had an infarction, and 116 (1.2%) died within 30 days of surgery. Intraoperatively, the estimated average relative effect across myocardial infarction and mortality was 1.08 (98.3% CI, 1.03, 1.12; P < 0.001) per 10-min increase in hypotension duration. For the remaining day of surgery, the odds ratio was 1.03 (98.3% CI, 1.01, 1.05; P < 0.001) per 10-min increase in hypotension duration. The average relative effect odds ratio was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002) in patients with hypotension during the subsequent four days of hospitalization., Conclusions: Clinically important hypotension-a potentially modifiable exposure-was significantly associated with a composite of myocardial infarction and death during each of three perioperative periods, even after adjustment for previous hypotension.

Objective: To evaluate the perioperative course of urine levels of the renal damage biomarkers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) and to evaluate the predictive value of elevated TIMP-2 × IGFBP7 concentrations to predict acute kidney injury (AKI) early after cardiac on-pump surgery., Design: Prospective, observational cohort study., Setting: University hospital., Participants: The study comprised 110 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) between January and March 2014., Interventions: None., Measurements and Main Results: Urinary TIMP-2 × IGFBP7 levels were quantified using a commercially available kit at the following measurement points: before surgery, 1 hour after starting CPB, 4 hours after weaning from CPB, and 24 hours after weaning from CPB (time points 1-4). Postoperative AKI was defined according to Kidney Disease Improving Global Outcomes criteria. AKI after cardiac surgery was diagnosed in 9 patients (8%). The perioperative course of TIMP-2 × IGFBP7 was significantly different in patients with and without postoperative AKI (p < 0.001). TIMP-2 × IGFBP7 levels were significantly higher in patients with AKI 1 hour after CPB start and 24 hours after weaning from CPB (p < 0.05). TIMP-2 × IGFBP7 levels >0.40 (ng/mL) 2 /1,000 measured at 1 hour after starting CPB were found to be the optimal cut-off, with a sensitivity of 0.778 and a specificity of 0.641. The negative predictive value was 0.972., Conclusions: Urine levels of TIMP-2 × IGFBP7 are predictive for AKI at an early time point (1 hour after starting CPB). Renal damage biomarkers such as TIMP-2 and IGFBP7 might be recommended as a supplement to traditionally used criteria of AKI prediction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Postoperative delirium (POD) is a common complication after cardiac surgery and is associated with increased patient morbidity and mortality. The objective of this study was to identify risk factors for long duration and overall burden of POD after cardiac surgery., Design: One-year, single-center, retrospective, observational cohort study., Setting: University hospital., Participants: Adult patients undergoing cardiac surgery with cardiopulmonary bypass in 2013., Interventions: None., Measurements and Main Results: Patients were screened for POD using the Intensive Care Delirium Screening Checklist. The primary outcome measure was the incidence of POD. Secondary outcome measures were the duration of POD and the area under the curve determined using the Intensive Care Delirium Screening Checklist score over time. Independent predictors of POD were estimated in multivariable logistic regression models. Hospital length of stay, medications, and outcome data also were analyzed. Among the 656 patients included in the cohort, 618 were analyzed. The overall incidence of POD was 39%. Older patient age (odds ratio [95% confidence interval]) 1.06 [1.04-1.09] for an increase of 1 year, p < 0.001); low preoperative serum albumin (1.08 [1.03-1.13] for a decrease of 1 g/L, p < 0.001); a history of atrial fibrillation (2.30 [1.30-4.09], p = 0.004); perioperative stroke (6.27 [1.54-43.64], p = 0.008); ascending aortic replacement surgery (2.99 [1.50-6.05], p = 0.002); longer duration of procedure (1.37 [1.16-1.63] for an increase of 1 hour, p < 0.001); and increased postoperative C-reactive protein concentration (2.16 [1.49-3.16] for a 2-fold increase, p < 0.001) were associated with higher odds of POD. Among patients affected by POD, older age, perioperative stroke, longer procedure time, and increased postoperative C-reactive protein were consistently predictive of longer duration of POD and greater area under the curve., Conclusions: Known risk factors for the development of POD after cardiac surgery also are predictive of prolonged duration and high overall burden of POD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality., Methods: We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality., Results: We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014-1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007-1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754-0.878] versus area under curve: 0.870 [95% confidence interval, 0.822-0.917], respectively; P = .012). Finally, adding hsTnT to the EuroSCORE II improved restratification by the net reassignment improvement, primarily by improving rule-out of events., Conclusions: This analysis suggests that, similar to previous assays, higher postoperative concentrations of hsTnT are independently associated with all-cause mortality in patients undergoing on-pump cardiac surgery.

Background: Elevated, single-measure, postoperative troponin is associated with adverse events after cardiac surgery. We hypothesized that increases in troponin from the first to the second postoperative day are also associated with all-cause, 12-month mortality and major adverse cardiac events (MACE)., Methods: This observational study included consecutive adults undergoing on-pump cardiac surgery with cardiac arrest. Troponin T was measured on the first and second postoperative day and was classified as "increasing" (>10%), "unchanged" (10% to -10%), or "decreasing" (<-10%). The primary endpoint was all-cause, 12-month mortality. Secondary endpoints were all-cause 12-month mortality or MACE and both outcomes at 30 days. The main analysis was by multivariable Cox regression., Results: Of 1,417 included patients, 99 (7.0%) died and 162 (11.4%) died or suffered MACE at 12 months. A significant interaction (p < 0.001) between first postoperative day troponin and the troponin trend from the first to the second postoperative day on 12-month, all-cause mortality precluded an analysis independent of first postoperative day troponin. Consequently, we stratified patients by their first postoperative day troponin (cutoff, 0.8 μg/L). Increasing troponin was associated with higher mortality in patients with first postoperative day troponin T ≥ 0.8 μg/L (hazard ratio, 1.98; 95% CI, 1.09 to 3.59; p = 0.025)., Conclusions: Troponin changes from the first to the second postoperative day should not be interpreted without consideration of the first postoperative day troponin concentration. For patients with a first postoperative day troponin ≥ 0.8 μg/L, an increase by more than 10% from the first to the second postoperative day was significantly associated with all-cause, 12-month mortality and other adverse events., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: B-type natriuretic peptide (BNP) is a predictor of mortality after on-pump cardiac surgery. However, previous limited and heterogeneous studies have focused on peak concentrations at 3 to 5 days after surgery and may not offer clinicians much help in early decision-making. After confirming the predictive value of first-postoperative-day BNP in a preliminary analysis, we explored the association between isolated second-postoperative-day BNP concentrations, second-day BNP concentrations in conjunction with first-day BNP concentrations, and the change in BNP (ie, ΔBNP) from the first to the second postoperative day and 12-month, all-cause mortality., Methods: We included consecutive patients undergoing on-pump cardiac surgery in this observational, secondary analysis of prospectively collected data. We analyzed biomarkers on the first and second postoperative day. ΔBNP was defined as BNP on the second postoperative day minus BNP on the first postoperative day. The primary end point was 12-month, all-cause mortality. The secondary end point was a composite of major adverse cardiac events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart failure. The association between BNP and outcomes was examined by receiver operating characteristic curves, as well as univariate and multivariable logistic regression, adjusting for the EuroSCORE II, cross-clamp time, and first-postoperative-day troponin T., Results: We included 1199 patients in the preliminary analysis focused on BNP on postoperative day 1. In the analyses examining BNP variables requiring second-postoperative-day BNP measurement (n = 708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or MACE. Both first- and second-postoperative-day BNP were significant independent predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds ratio [aOR], 1.040 [95% confidence interval (CI), 1.019-1.065] and 1.064 [95% CI, 1.031-1.105], respectively). When used in conjunction with one another, first-day BNP was not significant (aOR, 1.021 [95% CI, 0.995-1.048]), while second-day BNP remained significant (aOR, 1.046 [95% CI, 1.008-1.091]). The ΔBNP per 100 ng/L increase was not associated with 12-month, all-cause mortality in the univariable (OR, 0.977 [95% CI, 0.951-1.007]) or multivariable analysis (aOR, 0.989 [95% CI, 0.962-1.021])., Conclusions: Both absolute concentrations of first- and second-postoperative-day BNP are independent predictors of 12-month, all-cause mortality. When modeled together, second-postoperative-day BNP is more predictive of 12-month, all-cause mortality. Although intuitively appealing, the change in BNP from the first to the second postoperative day is a complex variable and should not routinely be used for prognostication.

Background: The clinical significance of new pathological Q waves after on-pump cardiac surgery is uncertain., Objectives: To determine whether or not either the occurrence per se or the location of new pathological Q waves after on-pump cardiac surgery is associated with 12-month, all-cause mortality and/or major adverse cardiac events (MACEs)., Design: Observational cohort study., Setting: Single university hospital from January 2007 to October 2010., Patients: Consecutive adult patients undergoing elective on-pump cardiac surgery with MACE-free survival until at least the 7th postoperative day and available ECGs both preoperatively and on the 7th postoperative day (n = 1464). We conducted a subgroup analysis in patients undergoing isolated coronary artery bypass grafting (n = 740)., Main Outcome Measure: Our primary endpoint was 12-month, all-cause mortality and/or MACE, defined as acute coronary syndrome, cardiac arrest, congestive heart failure or re-vascularisation at 12 months. Using logistic regression, we examined the prognostic value of new pathological Q waves according to the Minnesota ECG Code, adjusting for the EuroSCORE II, cardiopulmonary bypass time and peak postoperative troponin T concentrations., Results: We included 1464 patients (74% men; mean ± SD age 66 ± 10 years) and observed 103 (7.0%) all-cause deaths and/or MACEs at 12 months. A total of 236 patients (16.1%) had definite or probable new pathological Q waves according to the Minnesota ECG Code. The occurrence of new pathological Q waves per se was not associated with our primary endpoint [adjusted odds ratio, 0.970 (95% confidence interval, 0.540 to 1.648)]. However, the occurrence of a new pathological Q wave in V1 to V5 (anterior) was a strong independent predictor for poor outcome [adjusted odds ratio, 3.461 (95% confidence interval, 1.501 to 7.242)]., Conclusion: The current analysis suggests that for patients undergoing elective on-pump cardiac surgery, only new pathological Q waves in V1 to V5 (anterior) in the 7th postoperative day ECG are associated with 12-month, all-cause mortality and/or MACE., Trial Registration: Clinicaltrials.gov identifier: NCT00468598.

Background: Several studies have evaluated preoperative B-type natriuretic peptides (NPs) for predicting mortality after surgery; however, the number of deaths in each study was small, limiting the power of these studies. We conducted a systematic review and meta-analysis of studies addressing preoperative NP levels to predict mortality after cardiac and noncardiac surgery., Methods: We searched MEDLINE and EMBASE using the terms "natriuretic peptides," "surgery or surgical procedures," and a validated combination of prognostic and diagnostic terms. Two investigators independently assessed studies for eligibility and extracted data. The end points were all-cause mortality at ≥6 months and at ≤90 days. We used a bivariate model to derive measures of prognostic accuracy and their heterogeneity. We calculated the pooled positive predictive value (PPV) and negative predictive value (NPV) by Bayesian Markov chain Monte Carlo methods., Results: Of the 1558 retrieved articles, 23 studies satisfied the predefined eligibility criteria. After cardiac surgery, the diagnostic odds ratio of NP was 4.11 (95% confidence interval, 2.22-7.60) for ≥6-month mortality, the PPV 0.17 (95% Bayesian confidence interval, 0.07-0.36), and the NPV 0.96 (0.90-0.98). After noncardiac surgery, the diagnostic odds ratio of NP was 4.97 (3.06-8.07) for ≥6-month mortality. The corresponding PPV was 0.24 (0.14-0.38) and the NPV 0.94 (0.88-0.97). Results were similar for ≤90-day mortality., Conclusions: Preoperative NP concentrations were associated with mortality after cardiac and noncardiac surgery. NP had high NPVs for both types of surgery suggesting that preoperative NP concentrations may be helpful in preoperative risk stratification., (© 2011 International Anesthesia Research Society)

Objectives: Postoperative delirium after cardiac surgery is associated with increased morbidity and mortality as well as prolonged stay in both the intensive care unit and the hospital. The authors sought to identify modifiable risk factors associated with the development of postoperative delirium in elderly patients after elective cardiac surgery in order to be able to design follow-up studies aimed at the prevention of delirium by optimizing perioperative management., Design: A post hoc analysis of data from patients enrolled in a randomized controlled trial was performed., Setting: A single university hospital., Participants: One hundred thirteen patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass., Interventions: None. MEASUREMENTS AND MAINS RESULTS: Screening for delirium was performed using the Confusion Assessment Method (CAM) on the first 6 postoperative days. A multivariable logistic regression model was developed to identify significant risk factors and to control for confounders. Delirium developed in 35 of 113 patients (30%). The multivariable model showed the maximum value of C-reactive protein measured postoperatively, the dose of fentanyl per kilogram of body weight administered intraoperatively, and the duration of mechanical ventilation to be independently associated with delirium., Conclusions: In this post hoc analysis, larger doses of fentanyl administered intraoperatively and longer duration of mechanical ventilation were associated with postoperative delirium in the elderly after cardiac surgery. Prospective randomized trials should be performed to test the hypotheses that a reduced dose of fentanyl administered intraoperatively, the use of a different opioid, or weaning protocols aimed at early extubation prevent delirium in these patients., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The prognostic value of troponin T for midterm outcome in cardiac surgery is insufficiently known. We aimed to assess the value of troponin T to predict 12-month outcome after cardiac surgery, as a single predictor and in combination with the European system for cardiac operative risk evaluation (EuroSCORE)., Methods: This cohort study included consecutive patients undergoing on-pump cardiac surgery between January 2005 and December 2006. We evaluated postoperative troponin T (TNT) on days 1 and 2 and the EuroSCORE as predictor variables. The primary composite endpoint was all-cause mortality or any major adverse cardiac event (MACE) at 12 months. Logistic regression was used to study the prognostic effect of TNT in a univariate analysis and after adjustment for EuroSCORE. The area under the receiver-operator curve (AUC) was calculated to report the discriminatory performance of the models., Results: Seven hundred forty-one patients were available for analysis. Within 12 months after surgery, 92 (12.4%) patients had a MACE, 48 (6.5%) of whom died. A multivariate model of continuous TNT and the continuous logistic EuroSCORE showed a significant independent association between TNT and the composite endpoint (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02 to 1.04 per 0.1 microg/L increase in TNT). The AUC for the prediction of the composite endpoint of the model combining TNT and the EuroSCORE was 0.72; when based on EuroSCORE alone it was 0.64 (p < 0.0001)., Conclusions: Postoperative TNT increase (per 0.1 microg/L) is a strong independent predictor of 12-month outcome after on-pump cardiac surgery. Updating the preoperative EuroSCORE risk with postoperative TNT allows for better prediction of 12-month MACE and all-cause mortality.