Open access Original research BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by Preoperative clinical model to predict myocardial injury after non-­cardiac surgery: a retrospective analysis from the MANAGE cohort in a Spanish hospital Ana Belen Serrano ‍ ‍,1 Maria Gomez-­Rojo,1 Eva Ureta,1 Monica Nuñez,1 Borja Fernández Félix,2 Elisa Velasco,3 Javier Burgos,4 Ekaterine Popova ‍ ‍,5 Gerard Urrutia,6 Victoria Gomez,4 Jose Manuel del Rey,7 Alfonso Sanjuanbenito,8 Javier Zamora,2,9,10 Juan Manuel Monteagudo,3 David Pestaña,1,11 Basilio de la Torre,12 Ángel Candela-­Toha1 To cite: Serrano AB, Gomez-­ ABSTRACT Rojo M, Ureta E, et al. Objectives To determine preoperative factors associated Strengths and limitations of this study Preoperative clinical model to myocardial injury after non-­cardiac surgery (MINS) and to predict myocardial injury ►► The main strength of the present study is its large to develop a prediction model of MINS. after non-­cardiac surgery: a sample size. Design Retrospective analysis. retrospective analysis from ►► The simplicity and transposability of our predictive the MANAGE cohort in a Setting Tertiary hospital in Spain. model allow its implementation worldwide. Spanish hospital. BMJ Open Participants Patients aged ≥45 years undergoing major ►► The main limitation is its unicentric setting, so our non-­cardiac surgery and with at least two measures of copyright. 2021;11:e045052. doi:10.1136/ model needs external validation. bmjopen-2020-045052 troponin levels within the first 3 days of the postoperative ►► The absence of preoperative troponin levels mea- period. All patients were screened for the MANAGE trial. ►► Prepublication history for surements may have favoured the inclusion of pa- Primary and secondary outcome measures We this paper is available online. tients with chronically elevated troponin. To view these files, please visit used multivariable logistic regression analysis to study ►► Retrospective analysis and recollection of some the journal online (http://​dx.​doi.​ risk factors associated with MINS and created a score data values in our study entail the usual limitations org/​10.​1136/​bmjopen-​2020-​ predicting the preoperative risk for MINS and a nomogram of observational studies with regard to potential 045052). to facilitate bed-­side use. We used Least Absolute confounders. Shrinkage and Selection Operator method to choose the Received 20 September 2020 factors included in the predictive model with MINS as Accepted 12 July 2021 dependent variable. The predictive ability of the model was evaluated. Discrimination was assessed with the area INTRODUCTION under the receiver operating characteristic curve (AUC) Perioperative cardiovascular (CV) events are and calibration was visually assessed using calibration the leading cause of morbidity and mortality plots representing deciles of predicted probability of MINS in patients undergoing major non-­ cardiac against the observed rate in each risk group and the surgery.1 These events include cardiac death, calibration-­in-­the-­large (CITL) and the calibration slope. We acute myocardial infarction, cardiogenic created a nomogram to facilitate obtaining risk estimates pulmonary oedema, ventricular fibrillation, for patients at pre-­anaesthesia evaluation. cardiac arrest and complete heart block. Results Our cohort included 3633 patients recruited Preoperative risk estimation of CV events is from 9 September 2014 to 17 July 2017. The incidence of based on validated models. Among them, the MINS was 9%. Preoperative risk factors that increased the Revised Cardiac Risk Index2 (RCRI) has been risk of MINS were age, American Status Anaesthesiology © Author(s) (or their widely used over the last 20 years probably due employer(s)) 2021. Re-­use classification and vascular surgery. The predictive model showed good performance in terms of discrimination to its simplicity. The increasing availability of permitted under CC BY-­NC. No commercial re-­use. See rights (AUC=0.720; 95% CI: 0.69 to 0.75) and calibration more specific and sensitive myocardial injury and permissions. Published by slope=1.043 (95% CI: 0.90 to 1.18) and CITL=0.00 (95% biomarkers,3 together with a deeper under- BMJ. CI: −0.12 to 0.12). standing of the pathophysiology of myocar- For numbered affiliations see Conclusions Our predictive model based on routinely dial injury after major non-­ cardiac surgery end of article. preoperative information is highly affordable and might be (MINS), has paved the way to the recogni- a useful tool to identify moderate-­high risk patients before tion as a specific entity.4 The pathophysiology Correspondence to surgery. However, external validation is needed before of MINS is multifactorial. Plaque rupture Dr Ana Belen Serrano; implementation. ​anab_​serrano@y​ ahoo.​es and mismatch between oxygen supply and Serrano AB, et al. BMJ Open 2021;11:e045052. doi:10.1136/bmjopen-2020-045052 1 Open access BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by demand have been considered as its main cause.3 5 Hyper/hypotension, hypoxia, sympathetic hyperactivity and inflammation are some of the aetiologies leading to thrombosis that can contribute to MINS. It has been proposed as a more suitable term for surgical patients6 since it is defined as a presumably ischaemic troponin elevation occurring within 30 days after surgery.7 It has been estimated that one out of every seven surgical patients older than 45 years with increased CV risk suffers from MINS.2 A meta-­analysis published in 2011 showed that MINS was a strong independent mortality predictor within the first year after surgery.8 Moreover, a linear correlation between the elevation of troponin and mortality9 10 has been found. Therefore, MINS is now considered a complication of great significance11 leading to poor prognosis12 that may affect millions of patients Figure 1 Flow chart of patients. MINS: myocardial injury after surgery worldwide.1 However, diagnosis is frequently after non-­cardiac surgery. missed out due to the effect of analgesic drugs commonly used as part of the immediate postoperative treatment, a reason why the vast majority of patients with MINS remain for body mass index (BMI) ≥30. We classified surgeries asymptomatic. This is why routine postoperative measure- into abdominal, urological, traumatological–ortho- ment of troponin has been proposed as a useful strategy paedic, gynaecological, vascular and thoracic surgeries. to identify MINS among the surgical population.13 14 It We also collected on preoperative medication taken at would be highly beneficial to detect patients at moderate-­ the moment of the anaesthesiologist visit. high risk of MINS and target preventive measures which The text adheres to the Strengthening the Reporting ultimately could improve clinical outcomes after surgery. for OBservational in Epidemiology)17 statement. To date, there is no specific treatment for MINS either. However, recently some authors have also suggested strat- Study population copyright. egies for its diagnosis and management.15 Many perioper- The study population corresponds to patients screened ative risk factors have been associated with postoperative in Ramón y Cajal University Hospital to participate MINS6 7 such as older age, atrial fibrillation (AF), coro- in the MANAGE18 trial (​ ClinicalTrials.​ gov, number nary artery disease (CAD), peripheral vascular disease NCT01661101) from 9 September 2014 to 17 July 2017 and stroke. However, some other as CV risk factors (figure 1). The exposure in this study was undergoing (hypertension, diabetes mellitus, hypercholesterolemia, major non-­cardiac surgery. In the MANAGE18 trial, major current history of smoking and obesity), the type of non-­cardiac surgery was defined as any surgery with an surgery (abdominal, urologic, orthopaedic, gynecologic, expected hospital length of stay for at least 2 days after thoracic) or common CV medication taken by patients surgery, and one of the following surgeries: abdominal-­ before surgery (acetyl salicylic, other antiplatelet drugs, aortic surgery, peripheral vascular surgery, laparotomy, statins, anticoagulant drugs), have not been properly major orthopaedic surgery of the hip or spine and thora- assessed and might also be risk factors (or protectors) for cotomy. All participants underwent postoperative serum MINS. In this study, we aimed to estimate the incidence of sampling and troponin concentrations were measured postoperative MINS in our setting and to develop a clin- twice during the first 3 days after surgery. ical prediction model for postoperative MINS. Patients were eligible for MANAGE if they fulfilled all of the following criteria: 1. Undergone non-­cardiac surgery. PARTICIPANTS AND METHODS 2. ≥45 Years of age. Study design and data collection 3. Have suffered MINS based on fulfilling one of the fol- A prospective cohort of 3633 patients aged ≥45 years lowing criteria: (A) elevated troponin or CK-­MB (Cre- undergoing major non-­ cardiac surgery was retrospec- atine Kinase - Myocardial Band) measurement with tively analysed for the development of MINS. one or more of the following features: (1) ischaemic We gathered demographic (age and gender) and signs or symptoms; (2) development of pathologic Q anthropometric (weight and height) data from medical waves; (3) ECG changes indicative of ischaemia (ie, ST records. We also collected clinical information regarding segment elevation, ST segment depression or inver- ASA classification16 and CV risk factors (hypertension, sion of T waves); (4) new LBBB (left bundle branch diabetes, obesity, hypercholesterolemia and smoking block) or (5) new or presumed new cardiac wall mo- story). Hypertension, diabetes, hypercholesterolemia tion abnormality on echocardiography or new or pre- and current smoking were considered when they were sumed new fixed defect on radionuclide imaging. (B) documented in the clinical history. Obesity was defined elevated troponin measurement after surgery with no 2 Serrano AB, et al. BMJ Open 2021;11:e045052. doi:10.1136/bmjopen-2020-045052 Open access BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by alternative explanation (eg, pulmonary embolism) to We used least absolute shrinkage and selection operator MINS. (LASSO) method for model fitting. LASSO is a regression 4. Provide written informed consent to participate within analysis method that performs simultaneously a variable 35 days of suffering their MINS. selection and a penalisation of coefficients. The objective In our study, we considered patients developed MINS is to improve model performance while, at the same time, only when an increased troponin occurred due to reducing model over-­optimism. Over-­optimism is one of presumable ischaemic cause, or an isolated increased the major criticisms to statistical modelling and using troponin occurred without an alternative explanation (ie, regularisation techniques much as LASSO, we increased sepsis, pulmonary embolism or patients who underwent model external validity by reducing the size of the set-­off any cardiac resuscitation). Chronically elevated troponin covariates included in the final model. This is done iter- measurement was not detected, because preoperative atively applying a shrinkage factor to shrink coefficients measurement of troponin not required by MANAGE to diminish their impact on model predictions, even to study was not included. null values making a covariate to be excluded from the final model. We selected the penalty parameter (lambda) Perioperative cardiac troponin that minimised expected model deviance. Confidence Regarding the troponin assay, conventional troponin I intervals for model coefficients were obtained by boot- (cTnI) was measured from the beginning of the study strap sampling. We evaluated the discriminatory ability using an Architect I200 Abbott Diagnostics analyser by of the final predictive model by computing the C-­statistic mass immunoassay, being the cut-­ off point for MINS summarised as the area under receiver operating char- 0.1 ng/mL. High sensitive troponin I (hsTnI) replaced acteristic curve with 95% CI. Final model calibration was cTnI measurement in June 2016, and this has been the assessed by visually inspecting calibration plots repre- routinely performed test from that moment on. When senting deciles of predicted probability of MINS against using hsTnI, the cut-­off point was ≥30 pg/mL. If both the observed rate in each risk group. We also calculated types of troponins were measured in the same blood the calibration slope adjusting a logistic regression model sample, we only considered the value of the hsTn. with the linear predictor as the only covariable. A slope equals one represents perfect calibration. The calibration-­ Outcomes in-­the-­large was calculated as the intercept coefficient of We analysed the incidence of MINS within the first 3 days the logistic regression with the linear predictor as offset, copyright. after surgery. We classified the study population into being zero as the ideal value. We also calculated the ratio MINS group when cTnI was ≥0.1 ng/mL due to an isch- of expected to observed number of events (E/O). aemic cause and no-­MINS when it was under than 0.1 ng/ Finally, a simple, easy-­to-­use nomogram was developed mL or when troponin elevation did not occur. to calculate the predicted probability of MINS at the time of preanaesthetic visit. Analyses were performed Statistical analysis using Stata Software V.16.0 with nomolog user-­defined First, we performed a descriptive analysis, stratified by command.19 MINS to characterise the study population. Contin- uous variables were expressed as mean and SD while Patient involvement categorical variables were summarised as absolute and No patients were involved in proposing the research ques- relative frequencies. Incidence of MINS was computed tion or the outcome measures, nor were they involved in as the number of MINS cases over the total number of the design or implementation of the study. No patients patients included, along with the Clopper-­Pearson 95% were asked to participate on interpreting or writing up CI. Comparisons between MINS and no-­ MINS groups of results. Patients who developed MINS were advised to were made using Student’s t-­test or χ2 test for continuous visit a cardiologist after hospital discharge. In case they or categorical variables, respectively. We admitted those already were chronically followed-­up by one, we insisted comparisons as statistically significant where p value was on scheduling earlier appointment and to inform doctors below 0.05. about their new condition. There are no plans to dissemi- nate the results of the research to study participants. Development of the predictive model A logistic regression model was used to analyse the risk of MINS associated to clinical and demographic factors. RESULTS We derived a multivariable predictive model including all Characteristics of the patient population the variables under studies as we thought they are all clin- A cohort of 3633 patients undergoing non-­cardiac surgery ically relevant. Given that we did not collect actual values screened for the MANAGE trial in our institution from of the BMI of patients, we decided not to progress with September 2014 to July 2017 was retrospectively analysed for the analysis of this factor as categorical. A non-­linear rela- the development of MINS within the first 3 days after surgery tionship between age (continuous) and log odds of MINS (figure 1). Overall, 328 patients (9.0% (95% CI: 8.1% to was assessed using simple transformations and restricted 10.0%)) developed this complication. Among our study cubic splines. population of 1712 patients, 47.1% were men. Mean age Serrano AB, et al. BMJ Open 2021;11:e045052. doi:10.1136/bmjopen-2020-045052 3 Open access BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by Table 1 Comparison of the studied characteristics between patients with and without MINS Overall population No MINS MINS Variables (n=3633) (n=3305) (n=328) P value Demographics  Age 72.9 (11.7) 72.3 (11.6) 78.5 (11.1) <0.001  Male 1712 (47.1) 1578 (47.7) 136 (40.96) 0.017 ASA classification <0.001  I 106 (2.9) 105 (3.2) 1 (0.3)  II 2013 (55.5) 1917 (58.1) 96 (29.3)  III 1217 (33.5) 1079 (32.7) 138 (42.1)  IV 294 (8.1) 201 (6.1) 93 (28.3) Presence of at least one 2996 (82.5) 2702 (81.8) 294 (89.6) <0.001 cardiovascular risk factor  Hypertension 2346 (64.6) 2093 (63.3) 253 (77.1) <0.001  Diabetes 814 (22.4) 717 (21.7) 97 (29.6) 0.001  Current smoking 453 (12.5) 415 (12.6) 38 (11.7) 0.627  Hypercholesterolemia 1387 (38.2) 1238 (37.5) 149 (45.4) 0.005  BMI >30 710 (19.5) 663 (20.1) 47 (14.3) 0.013 Types of surgeries <0.001  Abdominal 822 (22.6) 756 (22.9) 66 (20.1)  Vascular 159 (4.4) 131 (4.0) 28 (8.5)  Orthopaedic–traumat 2.122 (58.4) 1.910 (57.8) 212 (64.6)  Others 530 (14.6) 508 (15.4) 22 (6.7) copyright.    Urology 482 462 20    Ginecology 19 18 1    Thoracic 27 27 0    Others 2 1 1 Emergent cases 36 (1.0) 32 (1.0) 4 (1.2) 0.661 Medications  Aspirin 726 (20.0) 637 (19.3) 89 (27.1) 0.001  Statines 1250 (34.4) 1116 (33.8) 134 (40.8) 0.010  Other antiplatelet 145 (4.0) 127 (3.8) 18 (5.5) 0.147  Anticoagulants 629 (17.3) 530 (16.1) 99 (30.2) <0.001 ASA classification, American Status Anaesthesiology classification; BMI, body mass index; MINS, myocardial injury after non-­cardiac surgery. was 72.9 years. The more frequent ASA classification was II statins (OR 1.3 CI 1.1 to 1.7), (8) other antiplatelet medica- followed by III (55% and 33%, respectively). A high propor- tion (OR 1.4; 95% CI: 0.8 to 2.3) and (9) anticoagulant drugs tion (82.5%) of patients presented at least one CV risk factor taken before surgery (OR 2.2; 95% CI 1.7 to 2.9). Oppositely, (table 1). Traumatological–orthopaedic and abdominal we found that obesity decreased the risk of postoperatory surgeries were the most commonly performed interventions, MINS (OR 0.6; 95% CI: 0.5 to 0.9). the majority of them being elective cases (99%). Candidate predictors Development of MINS prediction model using LASSO Univariate analysis identified nine potential risk factors: (1) regression analysis age (OR 1.05; 95% CI: 1.04 to 1.06), (2) female (OR 1.3; Multivariate regression carried out using complete data 95% CI: 1.1 to 1.7), (3) ASA classification (ref ASA I–II; ORASA (n=3633) (table 2), showed only three variables with a statisti- 2.7; 95% CI: 2.0 to 3.5; ORASA IV 9.5; 95% CI: 6.9 to 13.1), (4) cally significant association with MINS and were included in III presence of at least one of the assessed CV risk factors (OR our final prediction model: age (OR 1.02), vascular surgery 1.9; 95% CI: 1.3 to 2.8), (5) vascular surgery (OR 2.3; CI 1.5 to (OR 1.71) and ASA classification (ORASA III 2.1 and ORASA IV 3.5), (6) acetyl salicylic acid (OR 1.6; 95% CI 1.2 to 2.1), (7) 6.4). 4 Serrano AB, et al. BMJ Open 2021;11:e045052. doi:10.1136/bmjopen-2020-045052 Open access BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by Table 2 Multivariate analysis of predictors of MINS. Final model Variables OR 95% bootstrap CI Age (years) 1.02 1.01 to 1.03 ASA classification  I–II Ref.  III 2.10 1.58 to 2.97  IV 6.42 4.34 to 9.90 Vascular surgery 1.71 1.00 to 3.15 The equation of the model risk for MINS was as follows: probability (MINS)=exp (Y)/(1+exp (Y)) where Y=−3.647+0.020×(age−45)+0.744 (ASA III)+1.859 (ASA IV)+0.536 (vascular surgery). ASA classification, American Status Anaesthesiology classification; MINS, myocardial injury after non-­cardiac surgery. The apparent C-­statistic for the model was 0.72 (95% CI 0.69 to 0.75). The calibration plot (figure 2) showed an overall good connection between the predicted and observed risks, and the calibration slope was 1.04 (95% CI 0.90 to 1.18). The model is presented as a graphical calculator (nomogram) in figure 3. The equation of the model risk for MINS was as follows: Figure 3 Nomogram of the predictive model for risk of Probability (MINS)=exp (Y)/(1+exp (Y)) MINS. To know the probability of developing MINS using this where Y=−3.517+0.020×(age−45)+0.744 (ASA III)+1.859 nomogram, three steps have to be taken. First, find out the copyright. (ASA IV)+0.536 (vascular surgery). value of each variable (ASA classification, whether vascular surgery is going to be performed or not and age) projecting a perpendicular line on the score line. Second, sum all these DISCUSSION value scores and obtain a total score. Third, move to the total Statement of principal findings score line and project this value on the probability line. To Our study was designed to draft a predictive model of obtain the percentage value, multiply it by 100. For example, preoperative risks factors for MINS in patients ≥45 years a patient ASA III, 50 years old who is going to vascular surgery has a probability of 11% to develop MINS as his total score is 7.4 points. ASA classification: American Status Anaesthesiology classification; MINS: myocardial injury after non-­cardiac surgery. undergoing a major non-­cardiac surgery. We have identi- fied three preoperative independent predictors of MINS: (1) age, (2) vascular surgery and (3) ASA scores III and IV. Based on these predictors we developed a risk score of MINS in order to stratify patients before surgery and to provide an estimated percentage risk for MINS. The incidence of MINS in our cohort of 3633 patients undergoing major non-­cardiac surgery was 9% a similar value to that published in the VISION study (8%),7 the largest cohort of surgical patients screened for myocar- dial injury. In other type of surgeries such as vascular Figure 2 Calibration plot. Calibration plot representing procedures, this value becomes higher (19.1%).20 expected and observed risk of MINS grouped by deciles of risk. Calibration slope=1.04 (95% CI: 0.90 to 1.18), calibration Comparison with other studies in the large=0.00 (95% CI: −0.12 to 0.12) and C-­statistic Perioperative cardiac risk estimation based on clinical risk (AUC)=0.72 (95% CI: 0.69 to 0.75). AUC: area under the indexes has been used for over 20 years, with the incep- receiver operating characteristic curve; MINS: myocardial tion of the RCRI, long before the definition of MINS was injury after non-­cardiac surgery. established. In fact MINS is just one among many possible Serrano AB, et al. BMJ Open 2021;11:e045052. doi:10.1136/bmjopen-2020-045052 5 Open access BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by cardiac events, although notably, the most frequent. importance of the need for tools that can provide early VISION investigators7 identified 12 independent preop- identification of the patients with risk of MINS, especially erative predictors of MINS, doubling the number of risk in settings where troponin measurement is not available. factors included in the RCRI, including age (75 years or There is no doubt on the theoretical relevance of older), CV risk factors, known CV disease and surgical these studies, but remains unclear whether all these new priority (urgent/emergent surgery). Known risk factors models have helped physicians in their daily clinical prac- for developing MINS during the intraoperative period tice. Their complexity and sometimes the need for extra include excessive sympathetic stimulation,21 tachycardia diagnostic tests count against them. and hypotension,22 23 surgery-­ related hypercoagula- We present our predictive model and risk score of bility,24 bleeding,25 hypothermia,26 hypoxia, pain27 28 and MINS as an easy and additional tool not only to identify prolonged surgical time. House et al29 developed a score patients at moderate to high risk of suffering this isch- to assess the impact of intraoperative haemodynamics in aemic complication, but with the intention to serve as a the development of myocardial injury. Moreover, other simple guide for clinical practice among surgical patients. known postoperative independent risk factors of MINS Our risk score tool is easy to use and suitable for a vast are the development of acute kidney injury, the use of majority of patients undergoing elective surgery world- vasopressors, higher Acute Physiology and Chronic Health wide. However, external validation is needed before Evaluation II scores,30 lower mean arterial pressure31 and implementation. Another feature of our model that has hypoxemia.32 Durmuş et al33 also found the neutrophil to be highlighted is the fact that it includes preopera- to lymphocyte ratio for a period of 3 days postoperatively tive parameters in order physicians to have the chance can be used as an easy predictor of MINS. In an effort of seeking counsel during both the intraoperative and to improve the discrimination of RCRI to predict MINS, postoperative periods. For example, making a bigger Douville et al34 incorporated genetic information using a effort to avoid tachycardia, hypotension, anaemia and Polygenic Risk Score of CAD. Although associated with hypothermia during the intraoperative and postoperative MINS, the addition of the genetic score did not improve periods or even targeting these goals in a narrower range discrimination. In order to develop our predictive model, in moderate to high risk patients can be considered an we have focused on easily accessible and common clinical initial preventive step. Keeping anti-­atherosclerosis medi- variables usually assessed in the preoperative period (age, cation should also be of potential benefit37 38 in patients at gender, ASA classification, presence of hypertension, moderate to high risk. Withholding aspirin15 and statins39 copyright. diabetes, hypercholesterolemia, current tobacco use, prior to surgery in high risk patients are other preventive type of surgery and previous CV medication). The incor- approaches that are currently being assessed. poration of intraoperative variables can certainly improve Our proposal is to avoid sampling troponin postopera- model prediction and discrimination. Although, the tively in low risk patients as it is very unlikely that these will advantage of preoperative communication of risk to the develop MINS but measuring it in patients with moderate patient is to some extent lost, the information obtained to high risk. We consider patients are under moderate risk can be used to make decisions about measuring post- for MINS when they score a 10% estimated percentage operative troponin. Measuring troponin routinely after risk according to our model; meaning an overall result surgery to diagnose MINS is still a matter of controversial of >7 in our score nomogram (figure 3). Therefore, debate. The ACC/AHA (American College of Cardiology/ this should be the cut-­off point for both the screening American Heart Association) preoperative CV evalua- of MINS by measuring troponin levels in the immediate tion guidelines13 concluded that routine measurement postoperative period (if available) as well as for the imple- of postoperative troponin levels in unselected patients mentation of potentially preventive measures throughout without signs or symptoms of myocardial ischaemia or the perioperative period. myocardial infarction is not useful for guiding perioper- ative management. On the contrary, Canadian Cardio- Limitations vascular Society Guidelines on perioperative cardiac risk This study was primarily limited by its unicentric setting assessment and management for patients undergoing what makes our results are not totally generalisable else- non-­cardiac surgery14 ‘made a strong recommendation where, even though the sample size is large. In order to to obtain daily troponin measurements for 48–72 hours assure its universalisation, an external validation would be after surgery in patients with a baseline risk higher than necessary. Futhermore, as we described in the Methods 5% for CV deaths or nonfatal myocardial infarction at 30 section, we only considered for MINS diagnosis troponin days after surgery’. Measuring troponin seems appealing values from the immediate postoperative period, without particularly in patients at high risk for MINS. The costs knowing troponin value previous to surgery. So, we were associated with a troponin T monitoring programme to unable to identify patients with chronically elevated detect MINS was found to be moderate.35 Also, Torborg troponin. This could be overcome by demonstrating et al36 have published a pharmaco-­economic analysis of proving uptrending or downtrending troponin values routine postoperative troponin screening suggesting that (especially with hsTn). However, we do not believe this is such monitoring may be in fact cost-­effective. We essen- very likely as the MINS incidence found in our study was tially agree with these findings although we insist on the similar to some other important study published in the 6 Serrano AB, et al. BMJ Open 2021;11:e045052. doi:10.1136/bmjopen-2020-045052 Open access BMJ Open: first published as 10.1136/bmjopen-2020-045052 on 4 August 2021. Downloaded from http://bmjopen.bmj.com/ on April 3, 2023 at Sant Paul Hospital Consortia. Protected by medical literature.7 Another limitation of our analysis was interpretation of data: ABS, AC-­T, JZ and BFF. Drafting of the manuscript: ABS, AC-­T, that retrospective analysis and recollection of some data MG-­R, JZ and BFF. The final manuscript was critically revised and approved by all authors. values were performed despite The MANAGE study was Funding The authors have not declared a specific grant for this research from any conducted with a prospective design. This entailed the funding agency in the public, commercial or not-­for-­profit sectors. usual limitations of observational studies with regard to Competing interests None declared. potential confounders. Including non-­modifiable predic- tive factors in our model can be another limitation, as it Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. precludes clinicians from using preoperative measures to reduce risk of MINS. Finally, because patient inclusion Patient consent for publication Not required. was dependent on investigator’s availability, and some Ethics approval The study was approved by the Ethical Committee of the Ramón y Cajal University Hospital, Madrid, Spain. Trial registration code in this institution potential candidates may have been lost. LUXHOMBRO01/2018. Provenance and peer review Not commissioned; externally peer reviewed. Future research Consequently, due to the lack of information about both Data availability statement Data are available upon reasonable request. The data used in this study are part of a larger dataset. The data not used for this manuscript the prevention of MINS and its treatment, more studies will be employed in future manuscripts. with adequate design are needed in order to explore Open access This is an open access article distributed in accordance with the those issues and obtain further results. Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-­commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use CONCLUSIONS AND CLINICAL IMPLICATIONS is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. We have created a score for the prediction of the risk of postoperative MINS. Our proposal is to use it in all ORCID iDs Ana Belen Serrano http://​orcid.​org/​0000-​0002-​6370-​5089 individuals undergoing non-­ cardiac major surgery in Ekaterine Popova http://​orcid.​org/​0000-​0002-​8781-​9873 order to classify patients into low or moderate-­high risk development of MINS. Patients at low risk should not be submitted to troponin sampling in the recent post- operative period. On the contrary, patients at moderate-­ REFERENCES 1 Devereaux PJ, Sessler DI. Cardiac complications in patients high risk of MINS should be monitored with troponin undergoing major noncardiac surgery. N Engl J Med copyright. values whenever possible. Additionally, moderate-­ high 2015;373:2258–69. 2 Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and risk patients should receive all the available preventive prospective validation of a simple index for prediction of cardiac risk approaches during both intraoperative and postoperative of major noncardiac surgery. Circulation 1999;100:1043–9. 3 Iddagoda MT. The role of high-­sensitive troponin measurement period. In countries where troponin measurement is not as a biomarker during the postoperative period for the detection fully available, this predictive model could also be used as of myocardial injury after non-­cardiac surgery. J Perioper Pract a screening tool for MINS. 2021;31:1–6. 4 Biccard BM. 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