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One-Year Mortality, Causes of Death, and Cardiac Interventions in Patients with Postoperative Myocardial Injury

van Waes, Judith A. R. MD; Grobben, Remco B. MD; Nathoe, Hendrik M. MD, PhD; Kemperman, Hans PhD; de Borst, Gert Jan MD, PhD; Peelen, Linda M. PhD; van Klei, Wilton A. MD, PhD; Buhre, Wolfgang F. Professor of Anesthesiology; de Graaff, Jurgen C. Anesthesiologist; Kalkman, Cor J. Professor of Anesthesiology; van Wolfswinkel, Leo Anesthesiologist; Doevendans, Pieter A. Professor of Cardiology; Grobbee, Diederik E. Professor of Epidemiology; van Solinge, Wouter W. Professor of Clinical Chemistry; Leiner, Tim Radiologist; Leenen, Loek P. H. Professor of Trauma Surgery; Moll, Frans L. Professor of Vascular Surgery

doi: 10.1213/ANE.0000000000001313
Cardiovascular Anesthesiology: Research Report
Continuing Medical Education

BACKGROUND: To evaluate the role of routine troponin surveillance in patients undergoing major noncardiac surgery, unblinded screening with cardiac consultation per protocol was implemented at a tertiary care center. In this study, we evaluated 1-year mortality, causes of death, and consequences of cardiac consultation of this protocol.

METHODS: This observational cohort included 3224 patients ≥60 years old undergoing major noncardiac surgery. Troponin I was measured routinely on the first 3 postoperative days. Myocardial injury was defined as troponin I >0.06 μg/L. Regression analysis was used to determine the association between myocardial injury and 1-year mortality. The causes of death, the diagnoses of the cardiologists, and interventions were determined for different levels of troponin elevation.

RESULTS: Postoperative myocardial injury was detected in 715 patients (22%) and was associated with 1-year all-cause mortality (relative risk [RR] 1.4, P = 0.004; RR 1.6, P < 0.001; and RR 2.2, P < 0.001 for minor, moderate, and major troponin elevation, respectively). Cardiac death within 1 year occurred in 3%, 5%, and 11% of patients, respectively, in comparison with 3% of the patients without myocardial injury (P = 0.059). A cardiac consultation was obtained in 290 of the 715 patients (41%). In 119 (41%) of these patients, the myocardial injury was considered to be attributable to a predisposing cardiac condition, and in 111 patients (38%), an intervention was initiated.

CONCLUSIONS: Postoperative myocardial injury was associated with an increased risk of 1-year all-cause but not cardiac mortality. A cardiac consultation with intervention was performed in less than half of these patients. The small number of interventions may be explained by a low suspicion of a cardiac etiology in most patients and lack of consensus for standardized treatment in these patients.

Published ahead of print April 22, 2016

From the *Department of Anesthesiology; Department of Cardiology; Department of Clinical Chemistry and Haematology; §Department of Surgery; and Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Department of Anesthesiology

Department of Anesthesiology

Department of Anesthesiology

Department of Anesthesiology

Department of Cardiology

Department of Epidemiology, Julius Center for Health Sciences and Primary Care

Department of Clinical Chemistry and Haematology

Department of Radiology

Division of Surgical Specialties

Division of Surgical Specialties

Accepted for publication February 22, 2016.

Published ahead of print April 22, 2016

Funding: This study was funded by a grant from the International Anesthesia Research Society (Clinical Scholar Research Award 2011 to Dr. Van Klei), by a grant from the Friends of the University Medical Center Utrecht foundation/the Dirkzwager-Assink Fund to Dr. Van Klei, and by departmental sources.

The authors declare no conflicts of interest.

The first two authors contributed equally to this article.

This report was previously presented, in part, at the Annual Meeting of the American Society of Anesthesiologists, October 11, 2014, New Orleans, LA.

Reprints will not be available from the authors.

Address correspondence to Judith A. R. van Waes, MD, University Medical Center Utrecht, Local Mail Q04.2.313, P. O. Box 58800, 3508 GA Utrecht, The Netherlands. Address e-mail to j.a.r.vanwaes@umcutrecht.nl.

Postoperative adverse cardiovascular events are a leading cause of morbidity and mortality after noncardiac surgery.1 The reported incidence of postoperative myocardial infarction (POMI) among patients undergoing noncardiac surgery is between 3% and 6%.2–4 Prevention of POMI by perioperative suppression of the compensatory sympathetic effects of surgery or by the inhibition of platelet function has showed no beneficial effect in several major clinical trials.2,3,5 Failure of such preventive strategies has led to strategies aimed at early recognition and subsequent treatment of POMI after surgery.1,6,7 Therefore, routine monitoring of cardiac biomarkers has been advocated to identify patients at risk of postoperative cardiovascular events early after surgery.8

Routine troponin I (TnI) measurements on the first 3 days after surgery followed by a cardiac consultation in patients with troponin elevation were implemented in our hospital. This clinical protocol was part of our standard postoperative care in patients aged 60 years or older undergoing all types of intermediate- to high-risk noncardiac surgery. In a previous study, we showed that postoperative myocardial injury as measured by troponin elevation above the clinical cutoff level of 0.06 μg/L with or without clinical symptoms occurred in 19% of these patients. Myocardial injury was strongly associated with short-term mortality, and troponin elevation improved risk stratification of patients at risk for death.7 Consequently, we hypothesized that this clinical protocol would facilitate cardiovascular optimization to prevent further myocardial injury, POMI, and long-term cardiovascular mortality.

The primary aim of this study was therefore to determine the association between myocardial injury and long-term death and to assess the causes of death in patients with myocardial injury. Furthermore, we aimed to evaluate the effects of implementing routine postoperative troponin measurements by studying their impact on cardiologists’ consultation recommendations and whether specific interventions were implemented in such patients.

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METHODS

Patients

This observational cohort study included consecutive patients undergoing noncardiac surgery between January 1, 2011, and December 31, 2012, at the University Medical Center, Utrecht, The Netherlands, a 1000-bed tertiary referral hospital. Some of this cohort was used in a previous study.7 Patients were eligible if they were aged 60 years or older, were undergoing intermediate- to high-risk noncardiac surgery under general or spinal anesthesia, and had an expected postoperative length of hospital stay of at least 24 hours. For patients who underwent surgery more than once, the first surgery was included in the analyses. A reoperation was included as a novel case if this surgery took place at least 1 year after the first surgery. Patients were excluded if they were lost to follow-up within 1 year after surgery.

The local medical ethics committee approved the study protocol. The need for informed consent was waived because only routinely collected patient data were used, and data were anonymized before analysis (University Medical Center Utrecht Medical Research Ethics Committee 11–120/C).

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Routine Postoperative Troponin Measurements

Routine troponin measurements were implemented as part of the standard postoperative care protocol on January 1, 2011. According to this protocol, troponin was measured daily on the first 3 days after surgery. In the first phase of the protocol implementation, troponin measurements were ordered by the attending anesthesiologist. In case of a troponin elevation above the clinical cutoff level of 0.06 μg/L, the ward physician was notified. Because the optimal treatment of patients with postoperative troponin elevation was not protocolized, it was left to the discretion of the treating physician (surgical specialist) whether further diagnostic procedures including an electrocardiogram (ECG) or cardiology consult were indicated. Thus, troponin elevation was simply considered a marker for myocardial injury, warranting additional attention.

The logistics of the protocol were changed in May 2012 because troponin was not consistently measured in all eligible patients previously, and cardiology consultations were not performed in all patients with troponin elevation. Thus, troponin measurements were subsequently ordered by dedicated anesthesiology nurses, who also requested a postoperative ECG and a cardiology consultation in positive patients. Further diagnostic procedures, such as cardiac or pulmonary computed tomography angiography, and coronary angiography (CAG), were only performed if indicated according to the consultant cardiologist. Cardiac interventions including prescription of medication were performed in concurrence with the treating physician.

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Myocardial Injury

Troponin was analyzed using the third-generation enhanced AccuTnI assay (Beckman Coulter, Brea, CA). Myocardial injury was defined as a TnI above the clinical cutoff level of 0.06 μg/L, which was the lowest value measurable with a 10% coefficient of variation above the 99th percentile of 0.04 μg/L.7 For each patient, the highest value of all routine troponin measurements was used in the analysis.

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Data Collection

All preoperative and postoperative data were obtained from electronic medical and administrative records. Data collected in all patients included patient characteristics, preoperative physical status, comorbidities including factors from the Revised Cardiac Risk Index,9 postoperative troponin measurements, and death within 1 year. In addition, data on postoperative symptoms, ECG changes, the occurrence of in-hospital POMI and other diagnoses, and the treatment initiated by the consultant cardiologist were collected in those patients who had a postoperative cardiac consultation. The unique hospital patient identifier was used to merge databases. The municipal personal record database was consulted for 1-year mortality data. Causes of death were obtained from general practitioners.

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Outcomes

The primary outcome was defined as all-cause mortality within 1 year after surgery. Secondary outcomes included cardiac death within 1 year and the incidence of in-hospital POMI. Cardiac death was defined as death resulting from a cardiac arrest or heart failure. Myocardial infarction was defined according to the third universal definition of myocardial infarction.8

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Cardiac Consultations

In patients with a cardiology consultation, we determined the suspected etiology of the troponin elevation as proposed by the consultant cardiologist. These were divided into predisposing cardiac conditions and perioperative triggers.1,10 Predisposing cardiac conditions included tachyarrhythmias (supraventricular or ventricular tachycardia), preexistent coronary artery disease, cardiomyopathy, left ventricular hypertrophy, and cardiac contusion. Perioperative triggers included tachycardia, anemia, hypertension, sympathetic storm in the presence of intracranial pathology, hypotension, inflammation and sepsis, pulmonary embolism, renal failure, fluid overload, and hypoxia. Furthermore, we recorded the interventions recommended by the cardiologist.

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Statistical Analysis

Baseline characteristics were compared between patients with and without postoperative myocardial injury by using the χ2 test or 2-sample t test, as appropriate. The incidence of 1-year mortality was compared using the χ2 test and a relative risk with 95% confidence interval (CI) was calculated. The median time to death was compared by using the Mann-Whitney U test.

Multivariable log-binomial regression analysis was used to adjust the association between myocardial injury and 1-year mortality for patient and surgery characteristics and comorbidities. For this purpose, univariable regression analysis was used to identify the variables that were associated with 1-year mortality. Variables with a P value of ≤0.10 were included in the multivariable model. In this model, patients were classified according to their highest postoperative troponin value. Therefore, we defined more or less equally sized groups for the patients with troponin elevation, based on 1, 2, and 10 times the TnI cutoff level: TnI ≤0.06 μg/L, TnI 0.07–0.12 μg/L (minor elevation), TnI 0.13–0.60 μg/L (moderate elevation), and TnI >0.60 μg/L (major elevation). High-risk surgery was defined as intraabdominal, intrathoracic, or suprainguinal vascular surgery,9 and emergency surgery was defined as surgery required within 72 hours after the indication for surgery was set. Ischemic heart disease was defined as previous myocardial infarction and/or coronary revascularization, heart failure was defined as a left ventricular ejection fraction <40%, and preoperative renal failure was defined as a glomerular filtration rate <45 mL/min/1.73 m2. Next, we checked for interaction of troponin with any of the significant variables in the multivariable model by including interaction terms. We used log-binomial regression analysis to facilitate presenting effect measures as risk ratios.11

A Kaplan-Meier survival analysis was used to determine the survival of patients in each category of troponin elevation. Survival was compared by using the log rank test. Furthermore, causes of death were compared between these groups. Finally, we recorded the number of cardiology consultations and the diagnoses and interventions by the cardiologist.

All hypothesis testing was conducted 2 sided, and throughout the analyses, we used a level of significance of 0.05. The analysis was performed using SPSS (release 21.0.0 for Windows IBM SPSS Statistics for Windows, Version 21.0, IBM Corp., Armonk, NY).

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RESULTS

Table 1

Table 1

Figure 1

Figure 1

During the study period, 4099 patients were eligible for inclusion, of which 49 patients (1%) were excluded from the analyses (Fig. 1). Of the remaining 4050 patients, 826 patients (20%) were excluded because troponin was not measured during the first 3 postoperative days. Thus, 3224 patients were included in this study (Table 1). Myocardial injury occurred in 715 patients (22%): 344 (11%) had minor troponin elevations (TnI 0.07–0.12 μg/L), 255 (8%) had moderate troponin elevations (TnI 0.13–0.60 μg/L), and 116 (4%) had major troponin elevations (TnI >0.60 μg/L).

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One-Year All-Cause Mortality

Table 2

Table 2

Figure 2

Figure 2

Of the 715 patients with myocardial injury, 182 patients (26%) died within 1 year after surgery compared with 318 (13%) of the 2509 patients without myocardial injury (RR 2.0; 95% CI, 1.7–2.4; P < 0.001). The median time to death was 55 days (interquartile range [IQR], 11–173) in patients with myocardial injury when compared with 135 days (IQR, 47–236) in patients without myocardial injury (P < 0.001). The 1-year mortality rates in patients with minor, moderate, and major troponin elevations were 21%, 25%, and 40%, respectively (P < 0.001) (Fig. 2). After adjustment for variables that are known to predict death, the RR of 1-year mortality was 1.4 (95% CI, 1.1–1.8; P = 0.004) in patients with minor troponin elevations, 1.6 (95% CI, 1.3–2.1; P < 0.001) in patients with moderate troponin elevations, and 2.2 (95% CI, 1.7–2.8; P < 0.001) in patients with major troponin elevations when compared with patients without myocardial injury (Table 2). Other independent predictors of death were age, preoperative renal failure, preoperative insulin use, and emergency surgery. Interaction terms for each of these predictors with troponin in the multivariable model were not statistically significant.

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Causes of Death

Table 3

Table 3

Data on the cause of death were available for 358 of the 500 patients (72%) who died within 1 year (Table 3). Cardiac death occurred in 2 (3%), 3 (5%), and 5 patients (11%) with minor, moderate, and major troponin elevations, respectively, when compared with 9 patients (3%) without myocardial injury (P = 0.059). Predominant causes of death in patients with major troponin elevations were sepsis (20%), cerebrovascular disease (15%), and cardiac disease (11%), whereas most of the patients without myocardial injury died of cancer (43%).

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ECG Results

A postoperative ECG was performed in 424 of the 715 patients (59%) with myocardial injury. ECG changes suggestive of new ischemia were found in 96 of the 424 patients (23%) and were more frequent in patients with major troponin elevations (43 of 112 patients, 38%) when compared with patients with moderate troponin elevations (32 of 187 patients, 17%) or minor troponin elevations (21 of 135 patients, 16%). Three (0.7%) of these ECGs showed ST elevation ≥1 mm, 52 (12%) ECGs showed ST depression ≥1 mm, and 41 (10%) ECGs showed ST depression <1 mm or T-wave inversion, respectively. Twenty-five of the 715 patients (3%) with myocardial injury had typical chest pain.

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Cardiology Consultations

A cardiology consultation followed in 290 of the 715 patients (41%) with myocardial injury (i.e., 9% of the total study population). The proportion of patients with a cardiac consultation was 18%, 54%, and 79% in patients with a minor, moderate, and major troponin elevation, respectively.

Figure 3

Figure 3

For the 290 patients who had cardiology consultation, the suspected etiologies of myocardial injury as determined by the consultant cardiologist are given in Figure 3. In 119 of the 290 patients (41%) with a cardiac consultation, the myocardial injury was considered to be attributable to predisposing cardiac conditions, including tachyarrhythmia and preexistent coronary artery disease, and in 81 patients (28%), the myocardial injury was considered to be attributable to perioperative triggers. In 126 patients (43%), the etiology of myocardial injury was not specified. Of note, the number of patients within the different groups of suspected etiologies exceeds the total number of patients because 36 patients (12%) were assigned to >1 group (e.g., a patient with myocardial injury because of anemia in the presence of left ventricular hypertrophy).

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Postoperative Myocardial Infarction

POMI defined according to the third universal definition occurred in 97 of the 715 patients (14%) with myocardial injury: ST-segment elevation myocardial infarction (STEMI) in 3 patients and non-STEMI in 94 patients, that is, 3% of the total study population. However, only 18 of them who were in the group that received a cardiologist consultation were diagnosed by the cardiologist in real time as having POMI, including the 3 patients with STEMI. In addition, 5 patients who in retrospect did not fulfill the criteria of the third universal definition of myocardial infarction were diagnosed in real time as having POMI because of high TnI values with a rise-and-fall pattern in 4 patients and high TnI values with ventricular tachycardia in 1 patient. In total, 23 patients were diagnosed with POMI by the cardiologist. In all of these 23 patients, POMI was considered to be attributable to a predisposing cardiac condition, and in 9 of these 23 patients, a perioperative trigger was suspected as well.

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Interventions

A cardiac intervention was initiated in 111 of the 290 patients (38%) with a cardiology consultation. In the remaining 179 patients (62%), only follow-up of troponin was performed, and the clinical course was further awaited without any intervention. Interventions were more often done in patients with a major troponin elevation (48 of 92 patients, 52%) when compared with patients with a moderate troponin elevation (45 of 138 patients, 33%) or a minor troponin elevation (18 of 60 patients, 30%). In patients in whom the myocardial injury was considered to be attributable to predisposing cardiac conditions or perioperative triggers, a cardiac intervention was initiated in 72 of 119 patients (61%) and 45 of 81 patients (56%), respectively, whereas when the etiology of myocardial injury was not specified, a cardiac intervention was done in 20 of 126 patients (16%) (Fig. 3).

The cardiac interventions consisted of the following: in 104 of the 290 patients (36%), new medication or a dose increase was prescribed. This included β-blockers in 52 patients (18%); other antihypertensive agents, including renin-angiotensin inhibitors, diuretics, and calcium channel blockers in 21 patients (7%); aspirin in 34 patients (12%); other antiplatelet agents in 15 patients (5%); heparin (low molecular weight) in 28 patients (10%); statins in 22 patients (8%); and other medication in 25 patients (9%). In 14 patients (5%), red blood cell transfusion was advised by the cardiologist. Seventeen patients (6%) were transferred to the coronary care unit or medium care for cardiac monitoring. CAG was performed in 15 patients (5%). The median time to CAG was 10 days (IQR, 4–62). Significant coronary artery stenoses were found in 12 patients (4%). Nine patients (3%) underwent percutaneous coronary intervention (PCI), and 1 patient (0.3%) underwent coronary artery bypass graft surgery. Finally, in 2 patients (0.7%), coronary revascularization was not performed because the risk of intervention was considered too high or because it was considered not to be beneficial because of the patients’ poor condition.

Of the 3 patients with STEMI, only 1 underwent CAG and PCI. In this patient, CAG and PCI were not performed in the acute phase because of an initial diagnostic delay (>6 hours) but 14 and 33 days after STEMI was diagnosed, respectively. This patient survived the follow-up time of 1 year. In 1 STEMI patient who underwent neurosurgery, CAG (and PCI) was not performed because the risk of intracranial bleeding with antiplatelet and anticoagulant therapy was considered too high. This patient died 15 days later of cerebral empyema. In another STEMI patient, a diagnostic delay occurred because of difficulties in interpreting the ECG (preexistent ST elevation in the anterior leads because of a prior anterior wall myocardial infarction). By the time STEMI was diagnosed, the ECG was normalized and CAG was no longer considered beneficial. The patient was admitted to the medium care unit for cardiac monitoring, treated with antiplatelet therapy, and survived the follow-up time of 1 year.

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DISCUSSION

This study determined the association between postoperative myocardial injury and 1-year mortality in a large cohort of patients and assessed causes of death in patients with myocardial injury. In addition, we studied the diagnoses and cardiac interventions in these patients. Postoperative myocardial injury, as detected by troponin elevation, was found in 22% of the patients and was associated with a 1.5- to 3-fold increased risk of 1-year mortality. The protocol led to a cardiac intervention in only 111 (16%) of the 715 patients with myocardial injury.

Our hospital is one of the first that implemented routine troponin measurements after noncardiac surgery to improve early identification of patients with myocardial injury who are at risk of (silent) POMI and death. Because data from clinical care obtained in the implementation period of a new protocol were used in this study, the results represent daily care, instead of a controlled research setting.

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Limitations

Several limitations must be addressed. First, because troponin was only measured on the first 3 days after surgery, myocardial injury that may have occurred after the third postoperative day was missed. However, previous research has shown that myocardial injury occurs primarily within the first 3 postoperative days.12–14 Second, because troponin was not measured in 20% of patients, selection bias may have been present. However, we showed in a previous report including a part of this cohort that there were no large differences between patients with and without troponin measurements and that imputation of the missing troponin values did not alter the association between myocardial injury and death.7 Third, exclusion of patients who were lost to follow-up (1%) may have introduced potential bias. Fourth, troponin was not measured before surgery; hence, the results could not be adjusted for possible preexisting troponin elevations.15–17 Fifth, in evaluating postoperative troponin measurements, the occurrence of complications of resulting interventions (e.g., bleeding caused by anticoagulants)3,18,19 would have been valuable to report, but these data were not available for all patients. Finally, data on the cause of death were not available for all patients. Because the cause of death may have been reported as “unknown” in some patients with sudden death, the incidence of sudden cardiac death may be underestimated.

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Literature

The association between postoperative myocardial injury and long-term mortality has been assessed in several smaller cohort studies that included patients undergoing major surgery. Myocardial injury as measured by troponin elevation was reported to be associated with a 2- to 41-fold increased risk of death within 1 year after surgery, which is consistent with the result of our study.20–33 In the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) trial, even troponin levels below the upper limit of normal were found to be related to mortality.4 Cardiac death occurred in 19 of the 3224 patients (0.6%) in our study, which is in accordance with the incidence of cardiovascular death in the PeriOperative ISchemic Evaluation-2 (POISE-2) trial (0.7%).3 Furthermore, Chong et al.20 reported that cardiovascular death occurred more frequently in patients who suffered from postoperative myocardial injury after orthopedic surgery, as in our study.

The incidence of POMI according to the third universal definition of myocardial infarction (3%) is comparable to previous reports (3%–6%).2–4 It should be noted that only 0.7% of patients were diagnosed with POMI in real time by the cardiologist. This implies that, in clinical practice, myocardial injury in the postoperative phase is evaluated differently than outside the perioperative setting, for example, in patients who are suspected of myocardial infarction in the emergency department. Also, POMI appears to be less often diagnosed in a daily clinical care setting than in a controlled research setting, even if routine postoperative monitoring of troponin is used.

Because many of the patients with postoperative myocardial injury do not fulfill the criteria of myocardial infarction, a new diagnosis of Myocardial Injury after Noncardiac Surgery, defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery, was proposed to guide timely diagnosis and intervention.34 Current guidelines concur that early postoperative troponin measurements could have therapeutic consequences and therefore that it may be considered in high-risk patients,35 but it is emphasized that its usefulness is uncertain in the absence of established risks and benefits of a defined management strategy,36 which is confirmed by our study.

Although many causes of postoperative myocardial injury have been put forward, including noncardiac causes,1,10 it is not known in how many patients and to what extent perioperative factors contribute to the development of myocardial injury. Furthermore, if POMI is diagnosed, there is uncertainty whether this is mainly caused by plaque rupture with thrombosis (type 1 myocardial infarction) or an imbalance between myocardial oxygen supply and demand (type 2 myocardial infarction),37–40 which hampers the initiation of proper treatment options. Moreover, even in patients with type 2 myocardial infarction outside the perioperative setting, there are no established treatment guidelines.41

Few studies evaluated cardiac treatment initiated after surgery in patients with postoperative myocardial injury. Foucrier et al.42 studied the effect of cardiovascular medical optimization in 667 patients undergoing elective major vascular surgery. They reported that patients with treatment optimization, consisting of prescription or a dose increase of antiplatelet drugs, β-blockers, angiotensin-converting enzyme inhibitors, and statins, had a lower risk of adverse cardiac events than patients without treatment optimization. Treatment interventions were much more frequent (65%) than in our study (16%), which may be explained by the type of patients included, that is, those at higher risk of cardiovascular complications who may have had more benefit from cardiovascular optimization. Chong et al.43 randomly assigned 70 patients with troponin elevation after orthopedic surgery to cardiology care, consisting of assessment by a cardiologist and admission to a coronary care unit, versus standard treatment. Prescription of new medication, mainly β-blockers and aspirin, was more frequent (83% of the patients) compared with our study (36% of the patients with cardiology consultation). However, cardiology care had no effect on in-hospital cardiac complications and 1-year mortality.

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Clinical Implications

Several strategies to prevent the occurrence of POMI, including suppression of the sympathetic nervous system and antiplatelet therapy, have failed to show an effect or the beneficial effect was outweighed by severe side effects.3,5 As an alternative strategy, in those patients in whom postoperative myocardial injury has occurred, further myocardial injury and infarction may be prevented by adequate treatment early after surgery and, consequently, prognosis in terms of survival may be improved.6,7 Indeed, we found that among patients with postoperative myocardial injury, the most common causes of death were cardiac disease, cerebrovascular disease, and sepsis (Table 3), whereas among the patients without myocardial injury, most patients died of cancer. Although we showed that it is feasible to identify these patients at risk early after surgery by routine troponin measurements, this resulted in treatment interventions in less than half (38%) of the patients who had a cardiac consultation. In patients in whom the myocardial injury was considered to be due to predisposing cardiac conditions, a cardiac intervention was performed in 60% of patients. However, in many patients (43%), the etiology of the myocardial injury was not clear; hence, it was likely not known what treatment should be initiated to prevent further injury and death. Furthermore, in about half of the patients with perioperative triggers for troponin elevation, no treatment was initiated. In a part of these patients who were at high risk of death, the myocardial injury may have been inherent to the underlying disease, for example, in patients with myocardial injury due to sympathetic storm in the presence of intracranial pathology or in patients with severe sepsis. Hence, it is conceivable that cardiac interventions were not performed in these patients because this may not have been beneficial.

The findings from the current study support that attempts to improve prognosis in patients with myocardial injury are limited by insufficient knowledge of the underlying pathophysiology, adequate treatment options in individual cases, and insufficient capability to select those patients in whom cardiac treatment may be beneficial. It is likely that 1 single intervention is not simply beneficial in all patients. Given the high mortality rate in patients who suffer from postoperative myocardial injury, future research efforts should first and foremost focus on unraveling the pathophysiology of postoperative myocardial injury to guide treatment options and on identifying the patients who may benefit from (different) treatments. As long as these questions are not answered, we would recommend carefully weighing the benefits and risks of measuring troponin routinely in all patients after noncardiac surgery.

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CONCLUSIONS

Postoperative myocardial injury as detected by routine troponin measurements is associated with 1-year mortality. However, implementation of a clinical protocol including a cardiology consultation in patients with postoperative myocardial injury to improve the prognosis in these patients resulted in a cardiac consultation and intervention in less than half of the patients with myocardial injury. The low number of interventions may be explained by the suspicion of a cardiac condition in only a minority of the patients and the lack of a standardized treatment protocol in our study, which in turn is attributable to a lack of knowledge of the underlying pathophysiology and treatment options in patients with postoperative myocardial injury.

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DISCLOSURES

Name: Judith A. R. van Waes, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Judith A. R. van Waes has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Remco B. Grobben, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Remco B. Grobben approved the final manuscript.

Name: Hendrik M. Nathoe, MD, PhD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Hendrik M. Nathoe approved the final manuscript.

Name: Hans Kemperman, PhD.

Contribution: This author helped design the study and write the manuscript.

Attestation: Hans Kemperman approved the final manuscript.

Name: Gert Jan de Borst, MD, PhD.

Contribution: This author helped design the study and write the manuscript.

Attestation: Gert Jan de Borst approved the final manuscript.

Name: Linda M. Peelen, PhD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Linda M. Peelen approved the final manuscript.

Name: Wilton A. van Klei, MD, PhD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Wilton A. van Klei has seen the original study data and approved the final manuscript.

This manuscript was handled by: Martin J. London, MD.

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ACKNOWLEDGMENTS

We acknowledge Sabine Cuijpers, Wietze Pasma, and the trial office nurses under the direction of Sandra Numan for their contributions in data collection. We thank our collaborators, the Cardiac Health After SurgEry (CHASE) investigators at University Medical Center Utrecht.

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