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Background: European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA) guidelines inform cardiac workup before noncardiac surgery based on an algorithm. Our primary hypotheses were that there would be associations between (i) the groups stratified according to the algorithms and major adverse cardiac events (MACE), and (ii) over- and underuse of cardiac testing and MACE., Methods: This is a secondary analysis of a multicentre prospective cohort. Major adverse cardiac events were a composite of cardiac death, myocardial infarction, acute heart failure, and life-threatening arrhythmia at 30 days. For each cardiac test, pathological findings were defined a priori. We used multivariable logistic regression to measure associations., Results: We registered 359 MACE at 30 days amongst 6976 patients; classification in a higher-risk group using the ESC/ESA algorithm was associated with 30-day MACE; however, discrimination of the ESC/ESA algorithms for 30-day MACE was modest; area under the curve 0.64 (95% confidence interval: 0.61-0.67). After adjustment for sex, age, and ASA physical status, discrimination was 0.72 (0.70-0.75). Overuse or underuse of cardiac tests were not consistently associated with MACE. There was no independent association between test recommendation class and pathological findings (P=0.14 for stress imaging; P=0.35 for transthoracic echocardiography; P=0.52 for coronary angiography)., Conclusions: Discrimination for MACE using the ESC/ESA guidelines algorithms was limited. Overuse or underuse of cardiac tests was not consistently associated with cardiovascular events. The recommendation class of preoperative cardiac tests did not influence their yield., Clinical Trial Registration: NCT02573532., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Yearly, more than 200 million people worldwide undergo noncardiac surgery, of whom about 5% will develop cardiovascular complications. Prevention, early recognition, and prompt treatment of these adverse cardiovascular events is therefore an important concern in perioperative medicine. The present narrative review aims to provide an overview and critical analysis of the currently available evidence on the role of biomarkers in perioperative cardiac risk assessment and monitoring of perioperative cardiac events before and after noncardiac surgery.

: Peri-operative Medicine is the patient-centred and value-based multidisciplinary peri-operative care of surgical patients. Peri-operative stress, that is the collective response to stimuli occurring before, during and after surgery, is, together with pre-existing comorbidities, the pathophysiological basis of major adverse events. The ultimate goal of Peri-operative Medicine is to promote high quality recovery after surgery. Clinical scores and/or biomarkers should be used to identify patients at high risk of developing major adverse events throughout the peri-operative period. Allocation of high-risk patients to specific care pathways with peri-operative organ protection, close surveillance and specific early interventions is likely to improve patient-relevant outcomes, such as disability, health-related quality of life and mortality.

Objective: Recently, daytime variation in perioperative myocardial injury (PMI) has been observed in patients undergoing cardiac surgery. We aim at investigating whether daytime variation also occurs in patients undergoing non-cardiac surgery., Methods: In a prospective diagnostic study, we evaluated the presence of daytime variation in PMI in patients at increased cardiovascular risk undergoing non-cardiac surgery, as well as its possible impact on the incidence of acute myocardial infarction (AMI), and death during 1-year follow-up in a propensity score-matched cohort. PMI was defined as an absolute increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration of ≥14 ng/L from preoperative to postoperative measurements., Results: Of 1641 patients, propensity score matching defined 630 with similar baseline characteristics, half undergoing non-cardiac surgery in the morning (starting from 8:00 to 11:00) and half in the afternoon (starting from 14:00 to 17:00). There was no difference in PMI incidence between both groups (morning: 50, 15.8% (95% CI 12.3 to 20.3); afternoon: 52, 16.4% (95% CI 12.7 to 20.9), p=0.94), nor if analysing hs-cTnT release as a quantitative variable (median morning group: 3 ng/L (95% CI 1 to 7 ng/L); median afternoon group: 2 ng/L (95% CI 0 to 7 ng/L; p=0.16). During 1-year follow-up, the incidence of AMI was 1.2% (95% CI 0.4% to 3.2%) among morning surgeries versus 4.1% (95% CI 2.3% to 6.9%) among the afternoon surgeries (corrected HR for afternoon surgery 3.44, bootstrapped 95% CI 1.33 to 10.49, p log-rank=0.03), whereas no difference in mortality emerged (p=0.70)., Conclusions: Although there is no daytime variation in PMI in patients undergoing non-cardiac surgery, the incidence of AMI during follow-up is increased in afternoon surgeries and requires further study., Clinical Trial Registration: NCT02573532;Results., Competing Interests: Competing interests: CP reports grants from PhD Educational Platform for Health Sciences and the University Hospital Basel during the conduct of the study. GLB reports grants from University of Basel during the conduct of the study. RT reports research support from the Swiss National Science Foundation (grant no. P300PB 167803), the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel and the University Hospital Basel; and speaker honoraria/consulting honoraria from Roche, Abbott, Siemens, Singulex and ThermoScientific BRAHMS. CM reports grants from the Swiss Heart Foundation and grants and non-financial support from several diagnostic companies during the conduct of the study, as well as grants, personal fees and non-financial support from several diagnostic companies outside the submitted work., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Perioperative myocardial injury (PMI) seems to be a contributor to mortality after noncardiac surgery. Because the vast majority of PMIs are asymptomatic, PMI usually is missed in the absence of systematic screening., Methods: We performed a prospective diagnostic study enrolling consecutive patients undergoing noncardiac surgery who had a planned postoperative stay of ≥24 hours and were considered at increased cardiovascular risk. All patients received a systematic screening using serial measurements of high-sensitivity cardiac troponin T in clinical routine. PMI was defined as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements. Furthermore, mortality was compared among patients with PMI not fulfilling additional criteria (ischemic symptoms, new ECG changes, or imaging evidence of loss of viable myocardium) required for the diagnosis of spontaneous acute myocardial infarction versus those that did., Results: From 2014 to 2015 we included 2018 consecutive patients undergoing 2546 surgeries. Patients had a median age of 74 years and 42% were women. PMI occurred after 397 of 2546 surgeries (16%; 95% confidence interval, 14%-17%) and was accompanied by typical chest pain in 24 of 397 patients (6%) and any ischemic symptoms in 72 of 397 (18%). Crude 30-day mortality was 8.9% (95% confidence interval [CI], 5.7-12.0) in patients with PMI versus 1.5% (95% CI, 0.9-2.0) in patients without PMI ( P <0.001). Multivariable regression analysis showed an adjusted hazard ratio of 2.7 (95% CI, 1.5-4.8) for 30-day mortality. The difference was retained at 1 year with mortality rates of 22.5% (95% CI, 17.6-27.4) versus 9.3% (95% CI, 7.9-10.7). Thirty-day mortality was comparable among patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction (280/397, 71%) versus those with at least 1 additional criterion (10.4%; 95% CI, 6.7-15.7, versus 8.7%; 95% CI, 4.2-16.7; P =0.684)., Conclusions: PMI is a common complication after noncardiac surgery and, despite early detection during routine clinical screening, is associated with substantial short- and long-term mortality. Mortality seems comparable in patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction versus those patients who do., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02573532., (© 2017 The Authors.)

Background: Copeptin, a novel marker of endogenous stress, has shown diagnostic and prognostic value in nonsurgical patients with a suspected coronary event. We aimed to assess the incremental value of copeptin in addition to established preoperative risk indices to predict the occurrence of postoperative myocardial injury., Methods: This secondary analysis of prospectively collected data included adults undergoing noncardiac surgery with risk factors for adverse perioperative cardiac events based on preoperative risk stratification. We examined preoperative copeptin in patients without elevated preoperative troponin and its association with myocardial injury by receiver operator characteristic curves, logistic regression, and net reassignment indices., Results: Of the 190 patients included, 33 (17.4%) experienced myocardial injury within 48 hours, and 17 (8.9%) experienced cardiac death and/or major adverse cardiac events within the first postoperative year. Preoperative copeptin showed an area under the receiver operator characteristic curve of .66 (95% confidence interval, .55-.76) for myocardial injury and an optimal cutoff of 9.6 pmol/L. This cutoff was an independent predictor of myocardial injury, with an odds ratio of 4.67 (95% confidence interval, 2.06-11.19) when adjusted for age, sex, and the revised cardiac risk index. The net reassignment improvement for myocardial injury was between 39% and 50% for both events and nonevents when adding copeptin to established preoperative risk indices. No significant difference in major adverse cardiac event and/or cardiac death was observed., Conclusions: Copeptin (≥9.6 pmol/L) was associated with significantly higher rates of myocardial injury and improved risk stratification in patients scheduled for noncardiac surgery with nonelevated preoperative troponin.

Purpose of Review: To review myocardial injury after noncardiac surgery (MINS), focusing on recent studies, including data on high-sensitivity troponin, which is likely to alter our understanding of MINS., Recent Findings: MINS is greatly underappreciated by clinicians, possibly because of its silent presentation. However, MINS is both common and clinically important. In total, 8% of at-risk patients will suffer a MINS, an event that is associated with death within 30 days with an odds ratio of 3.87 (95% CI 2.96-5.08). Most patients suffering MINS do not fulfill the criteria for perioperative myocardial infarction as they are asymptomatic. Consequently, postoperative troponin measurement is imperative for MINS detection. Evidence from randomized trials on how to prevent or how to treat MINS is still lacking., Summary: Currently, we are limited to appreciating the vast extent of the MINS problem and applying recommendations based on observational data or derived from the nonoperative setting. Routine troponin measurements after noncardiac surgery and the increasing use of high-sensitivity troponins have revealed the larger underwater iceberg of perioperative myocardial injury and ischemia. Clinicians should be sensitized for this important complication and search for it using a perioperative troponin screening.

Background: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not., Methods: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days., Results: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata., Conclusions: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability., Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days., Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02)., Conclusions: Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

Context: Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days., Objective: To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality., Design, Setting, and Participants: A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery., Main Outcome Measures: Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death., Results: A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001)., Conclusion: Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.

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)