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BACKGROUND: Peri-operative complications are common and associated with high morbidity and mortality. Optimising the use of statins might be of important benefit in peri-operative care and reduce morbidity and mortality. OBJECTIVE: To evaluate adherence to current guideline recommendations regarding statin therapy and its association with peri-operative and long-term cardiac complications. DESIGN: Prospective cohort study. SETTING: Multicentre study with enrolment from October 2014 to February 2018. PATIENTS: Eight thousand one hundred and sixteen high-risk inpatients undergoing major noncardiac surgery who were eligible for the institutional peri-operative myocardial injury/infarction (PMI) active surveillance and response program. MAIN OUTCOME MEASURES: Class I indications for statin therapy were derived from the current ESC Clinical Practice Guidelines during the time of enrolment. PMI was prospectively defined as an absolute increase in cTn concentration of the 99th percentile in healthy individuals above the preoperative concentration within the first three postoperative days. Long-term cardiac complications included cardiovascular death and spontaneous myocardial infarction (MI) within 120 days. RESULTS: The mean age was 73.7 years; 45.2% were women. Four thousand two hundred and twenty-seven of 8116 patients (52.1%) had a class I indication for statin therapy. Of these, 2440 of 4227 patients (57.7%) were on statins preoperatively. Adherence to statins was lower in women than in men (46.9 versus 63.9%, P  < 0.001). PMI due to type 1 myocardial infarction/injury (T1MI; n  = 42), or likely type 2 MI (lT2MI; n  = 466) occurred in 508 of 4170 (12.2%) patients. The weighted odds ratio in patients on statin therapy was 1.15 [95% confidence interval (CI) 1.01 to 1.31, P  = 0.036]. During the 120-day follow-up, 192 patients (4.6%) suffered cardiovascular death and spontaneous MI. After multivariable adjustment, preoperative use of statins was associated with reduced risk; weighted hazard ratio 0.59 (95% CI 0.41 to 0.86, P  = 0.006). CONCLUSION: Adherence to guideline-recommended statin therapy was suboptimal, particularly in women. Statin use was associated with an increased risk of PMI due to T1MI and lT2MI but reduced risk of cardiovascular death and spontaneous MI within 120 days. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573532.

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AIMS: Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. METHODS AND RESULTS: Among prospectively recruited patients at high cardiovascular risk (age ≥65 years or ≥45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966). CONCLUSION: Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.

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AIMS: Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery. METHODS AND RESULTS: A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]). CONCLUSIONS: Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.

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Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

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BACKGROUND: Perioperative myocardial infarction/injury (PMI) is a frequent, often missed and incompletely understood complication of noncardiac surgery. The aim of this study was to evaluate whether patient- or procedure-related factors are more strongly associated to the development of PMI in patients undergoing repeated noncardiac surgery. METHODS: In this prospective observational study, patient- and procedure-related factors were evaluated for contribution to PMI using: 1) logistic regression modelling with PMI as primary endpoint, 2) evaluation of concordance of PMI occurrence in the first and the second noncardiac surgery (surgery 1 and 2). and 3) the correlation of the extent of cardiomyocyte injury quantified by high-sensitivity cardiac troponin T between surgery 1 and 2. The secondary endpoint was all-cause mortality associated with PMI reoccurrence in surgery 2. RESULTS: Among 784 patients undergoing repeated noncardiac surgery (in total 1'923 surgical procedures), 116 patients (14.8%) experienced PMI during surgery 1. Among these, PMI occurred again in surgery 2 in 35/116 (30.2%) patients. However, the vast majority of patients developing PMI during surgery 2 (96/131, 73.3%) had not developed PMI during surgery 1 (phi-coefficient 0.150, p < 0.001). The correlation between the extent of cardiomyocyte injury occurring during surgery 1 and 2 was 0.153. All-cause mortality following a second PMI in surgery 2 was dependent on time since surgery (adjusted hazard ratio 5.6 within 30 days and 2.4 within 360 days). CONCLUSIONS: In high-risk patients, procedural factors are more strongly associated with occurrence of PMI than patient factors, but patient factors are also contributors to the occurrence of PMI.

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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.

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BACKGROUND:  Perioperative myocardial infarction/injury (PMI) diagnosed by high-sensitivity troponin (hs-cTn) T is frequent and a prognostically important complication of non-cardiac surgery. We aimed to evaluate the incidence and outcome of PMI diagnosed using hs-cTnI, and compare it to PMI diagnosed using hs-cTnT. METHODS: We prospectively included 2455 patients at high cardiovascular risk undergoing 3111 non-cardiac surgeries, for whom hs-cTnI and hs-cTnT concentrations were measured before surgery and on postoperative days 1 and 2. PMI was defined as a composite of perioperative myocardial infarction (PMIInfarct) and perioperative myocardial injury (PMIInjury), according to the Fourth Universal Definition of Myocardial Infarction. All-cause mortality was the primary endpoint. RESULTS: Using hs-cTnI, the incidence of overall PMI was 9% (95% confidence interval [CI] 8-10%), including PMIInfarct 2.6% (95% CI 2.0-3.2) and PMIInjury 6.1% (95% CI 5.3-6.9%), which was lower versus using hs-cTnT: overall PMI 15% (95% CI 14-16%), PMIInfarct 3.7% (95% CI 3.0-4.4) and PMIInjury 11.3% (95% CI 10.2-12.4%). All-cause mortality occurred in 52 (2%) patients within 30 days and 217 (9%) within 1 year. Using hs-cTnI, both PMIInfarct and PMIInjury were independent predictors of 30-day all-cause mortality (adjusted hazard ratio [aHR] 2.5 [95% CI 1.1-6.0], and aHR 2.8 [95% CI 1.4-5.5], respectively) and, 1-year all-cause mortality (aHR 2.0 [95% CI 1.2-3.3], and aHR 1.8 [95% CI 1.2-2.7], respectively). Overall, the prognostic impact of PMI diagnosed by hs-cTnI was comparable to the prognostic impact of PMI using hs-cTnT. CONCLUSIONS: Using hs-cTnI, PMI is less common versus using hs-cTnT. Using hs-cTnI, both PMIInfarct and PMIInjury remain independent predictors of 30-day and 1-year mortality.

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BACKGROUND: Perioperative cardiovascular guidelines endorse functional capacity estimation, based on 'cut-off' daily activities for risk assessment and climbing two flights of stairs to approximate 4 metabolic equivalents. We assessed the association between self-reported functional capacity and postoperative cardiac events. METHODS: Consecutive patients at elevated cardiovascular risk undergoing in-patient noncardiac surgery were included in this predefined secondary analysis. Self-reported ability to walk up two flights of stairs was extracted from electronic charts. The primary endpoint was a composite of cardiac death and cardiac events at 30 days. Secondary endpoints included the same composite at 1 yr, all-cause mortality, and myocardial injury. RESULTS: Among the 4560 patients, mean (standard deviation) age 73 (SD 8 yr) yr, classified as American Society of Anesthesiologists physical status ≥3 in 61% (n=2786/4560), the 30-day and 1-yr incidences of major adverse cardiac events were 5.7% (258/4560) and 11.2% (509/4560), respectively. Functional capacity less than two flights of stairs was associated with the 30-day composite endpoint (adjusted hazard ratio 1.63, 95% confidence interval [CI] 1.23-2.15) and all other endpoints. The addition of functional capacity information to the revised cardiac risk index (RCRI) significantly improved risk classification (functional capacity plus RCRI vs RCRI: net reclassification improvement [NRI]Events 6.2 [95% CI 3.6-9.9], NRINonevents19.2 [95% CI 18.1-20.0]). CONCLUSIONS: In patients at high cardiovascular risk undergoing noncardiac surgery, self-reported functional capacity less than two flights of stairs was independently associated with major adverse cardiac events and all-cause mortality at 30 days and 1 yr. The addition of self-reported functional capacity to surgical and clinical risk improved risk classification. CLINICAL TRIAL REGISTRATION: INCT 02573532.

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BACKGROUND: The impact of obesity on the incidence of perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery is not well understood. METHODS: We performed a prospective diagnostic study enrolling consecutive patients undergoing non-cardiac surgery, who were considered at increased cardiovascular risk. All patients were screened for PMI, defined as an absolute increase from preoperative to postoperative sensitive/high-sensitivity cardiac troponin T (hs-cTnT) concentrations. The body mass index (BMI) was classified according to the WHO classification (underweight< 18 kg/m2, normal weight 18-24.9 kg/m2, overweight 25-29.9 kg/m2, obesity class I 30-34.9 kg/m2, obesity class II 35-39.9 kg/m2, obesity class III > 40 kg/m2). The incidence of PMI and all-cause mortality at 365 days, both stratified according to BMI. RESULTS: We enrolled 4277 patients who had undergone 5413 surgeries. The median BMI was 26 kg/m2 (interquartile range 23-30 kg/m2). Incidence of PMI showed a non-linear relationship with BMI and ranged from 12% (95% CI 9-14%) in obesity class I to 19% (95% CI 17-42%) in the underweight group. This was confirmed in multivariable analysis with obesity class I. showing the lowest risk (adjusted OR 0.64; 95% CI 0.49-0.83) for developing PMI. Mortality at 365 days was lower in all obesity groups compared to patients with normal body weight (e.g., unadjusted OR 0.54 (95% CI 0.39-0.73) and adjusted OR 0.52 (95% CI 0.38-0.71) in obesity class I). CONCLUSION: Obesity class I was associated with a lower incidence of PMI, and obesity in general was associated with a lower all-cause mortality at 365 days.

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Perioperative morbidity and mortality remains a substantial problem and is strongly associated with patients' cardiac comorbidities. Guidelines for the cardiovascular assessment and management of patients at risk of cardiac issues while undergoing non-cardiac surgery are traditionally based on the exclusion of active or unstable cardiac conditions, determination of the risk of surgery, the functional capacity of the patient, and the presence of cardiac risk factors. In the last two decades, strong evidence showed an association between cardiac biomarkers and adverse cardiac events, with newer guidelines incorporating this knowledge. This review describes a biomarker-based risk-stratification pathway and discusses potential treatment strategies for patients suffering from postoperative myocardial injury or infarction.

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AIMS: Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood. METHODS AND RESULTS: We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9-1.8] and in 3.7% (95% CI 3.0-4.5), haemodynamically relevant arrhythmias in 1.2% (95% CI 0.9-1.8) and in 2.1% (95% CI 1.6-2.8), AHF in 1.6% (95% CI 1.2-2.2) and in 4.2% (95% CI 3.4-5.1), spontaneous MI in 0.5% (95% CI 0.3-0.9) and in 1.6% (95% CI 1.2-2.2), and PMI in 13.2% (95% CI 11.9-14.7) and in 14.8% (95% CI 13.4-16.4) within 30 days and within 365 days, respectively. The MACE-incidence was increased above presumed baseline rate until Day 135 (95% CI 104-163), indicating a vulnerable period of 3-5 months. CONCLUSION: One out of five high-risk patients undergoing non-cardiac surgery will develop one or more MACE within 365 days. The risk for MACE remains increased for about 5 months after non-cardiac surgery. TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.

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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.

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