INTRODUCTION — Among patients 45 years of age or older undergoing in-hospital noncardiac surgery, complications of cardiac death, nonfatal myocardial infarction (MI), heart failure, or ventricular tachycardia occur in up to 5 percent. Of these, perioperative MI is the most common.
In addition, there is a larger group of patients who have a rise in troponin, a biomarker of cardiac injury, but no symptoms and no evidence of myocardial ischemia on an electrocardiogram. They are labelled as having myocardial injury after noncardiac surgery (MINS) when there is no evidence of a nonischemic etiology (eg, sepsis, pulmonary embolism, rapid atrial fibrillation, chronic troponin elevation).
This topic will focus on the identification and management of patients with perioperative MI or MINS. Related topics include:
●(See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Perioperative MI'.)
●(See "Evaluation of cardiac risk prior to noncardiac surgery".)
●(See "Management of cardiac risk for noncardiac surgery".)
●(See "Perioperative management of heart failure in patients undergoing noncardiac surgery".)
DEFINITIONS OF MYOCARDIAL INFARCTION AND MYOCARDIAL INJURY — The terms myocardial infarction (MI) and myocardial injury after noncardiac surgery (MINS) need to be defined. According to the 2018 Joint Task Force of the European Society of Cardiology, American College of Cardiology Foundation, the American Heart Association, and the World Health Federation (ESC/ACCF/AHA/WHF), MI is defined as a clinical (or pathologic) event in the setting of myocardial ischemia in which there is evidence of myocardial injury [1]. (See "Diagnosis of acute myocardial infarction", section on 'Definitions'.)
Myocardial injury is defined in the Fourth Universal Definition when there is evidence of elevated cardiac troponin values (cTn) with at least one value above the 99th percentile upper reference limit. The myocardial injury is considered acute if there is a rise and/or fall of cTn values. Clinical manifestations do not have to be present.
MINS is defined as myocardial cell injury during the first 30 days after noncardiac surgery due to an ischemic etiology (ie, no evidence of a nonischemic etiology like sepsis, rapid atrial fibrillation, pulmonary embolism, cardioversion, chronically elevated troponin, etc) and is independently associated with mortality. MINS includes MI (both symptomatic and non-symptomatic) and patients with postoperative elevations in troponin but who do not have symptoms, electrocardiographic abnormalities, or other criteria that meet the universal definition described above, and have no evidence of a nonischemic etiology for their troponin elevation [2].
MECHANISM — The pathophysiology of perioperative myocardial infarction (MI) is debated. Although supply-demand mismatch (eg, hypertension, hypotension, or tachycardia in the setting of a fixed coronary artery stenosis) has long been thought to explain many perioperative MIs, the evidence to support this explanation is limited. However, plaque rupture may play a central role in some cases. In one angiographic study, nearly 50 percent of patients with perioperative acute coronary syndrome had evidence of plaque rupture [3].
A study that evaluated patients who had perioperative MI (n = 30) with matched cases who had a non-operative MI (n = 30) using optical coherence tomography, an advanced imaging modality to detect coronary thrombus during cardiac catheterization, identified thrombus as the culprit lesion in 13 percent of the perioperative MI cases and 67 percent of the nonoperative cases [4]. Patient characteristics and MI presentation (eg, ischemic symptoms, level of troponin elevation, and electrocardiographic ischemic findings) did not identify which patients had a thrombotic perioperative MI. Although thrombus was a less common etiology in perioperative MI compared with nonoperative MI, the underlying culprit lesion was fibroatheroma in 60 percent of the perioperative MI cases and 67 percent of the nonoperative MI cases. (See "Mechanisms of acute coronary syndromes related to atherosclerosis", section on 'Fibroatheroma'.)
In patients with myocardial injury after noncardiac surgery (MINS), the most common pathologies are either underlying obstructive coronary artery disease, which can cause elevations of cardiac troponin due to a supply-demand mismatch, or an acute thrombus [5-7]. Those who propose use of the term MINS do not apply it to patients in whom myocardial injury is likely due to a nonischemic etiology such as pulmonary embolism, sepsis, or cardioversion.
Three large prospective cohort studies in which adjudicators attempted to evaluate each case of an elevated troponin for evidence of a nonischemic etiology found that over 85 percent of troponin elevations after surgery were likely due to myocardial ischemia [2,8,9]. Regardless of the etiology, these elevations have important prognostic relevance. (See 'Prognosis' below.)
INCIDENCE — Studies that have evaluated the incidence of perioperative cardiac troponin (cTn) elevation attempt to report whether the elevation is a myocardial infarction (MI) or myocardial injury after noncardiac surgery (MINS) (see 'Definitions of myocardial infarction and myocardial injury' above). In these studies, the incidence of MINS ranges between 8 and 19 percent. MI accounts for about 40 percent of MINS when a non-high sensitivity cTn is evaluated, and about 20 to 30 percent of these events when a high sensitivity cTn (hs-cTn) assay is used.
Factors that explain between-study differences in the incidence of MINS and the percent of MINS that are labelled as MI include:
●Most patients are receiving analgesic medication that can mask cardiac ischemic symptoms during the first 48 hours after surgery, when most MIs occur (see 'Clinical presentation' below). Had patients been symptomatic, they would likely have been classified as MI. Also, electrocardiograms (ECGs) are mainly ordered after the detection of an elevated troponin, which may be 12 to 24 hours after the event, and ECG changes may have resolved by the time the ECG is obtained [10].
●The incidence of MINS is influenced by the sensitivity of the biomarker used. As demonstrated across the VISION cohort studies discussed later in this section, as the sensitivity of cTn assays improved (ie, from a non-high sensitivity to an hs-cTn assay), the frequency of identifying perioperative troponin elevations increased.
●The characteristics of the study population, such as severity of patient risk and the risk of surgery, will influence incidence.
●A baseline troponin facilitates determining if a postoperative troponin elevation represents an acute or chronic event. Some studies have not rigorously compared postoperative with preoperative troponin values.
Four large studies have evaluated the incidence of troponin elevations after noncardiac surgery [2,9,11-13]. The best data on incidence of MINS and MI come from the following two studies:
●The VISION Study was a prospective cohort study that included a representative sample of patients ≥45 years of age undergoing in-hospital noncardiac surgery, and all of the participants had troponin measurements after surgery. Two cohorts have been reported:
•In the first VISION cohort of 15,065 patients, a non-high sensitivity fourth generation cTn assay was measured during the first three postoperative days [2]. Among the patients with an elevated troponin, all were assessed for ischemic symptoms, had ≥1 ECG obtained, and had two independent adjudicators to determine if there was evidence of a non-ischemic cause (eg, pulmonary embolism, sepsis) of the troponin elevation. Baseline cTnT values were not available for the majority of patients. Study adjudicators determined that 93 percent of patients with a troponin elevation had an ischemic etiology for their troponin elevation and that 1200 (8 percent) patients suffered MINS. Among the MINS patients, 41.8 percent fulfilled the universal definition of MI. A limitation of this study is that preoperative troponin measurements were not obtained systematically.
•In the second VISION cohort of 21,842 patients, which followed the same procedures as the first cohort, an hs-cTn assay was measured during the first three postoperative days; 40.4 percent of the participants had a preoperative troponin measurement [8]. Study adjudicators determined that 11 percent had evidence of a non-ischemic etiology for their elevated troponin, and among the patients who had an elevated perioperative troponin measurement, 13.8 percent had a preoperative high-sensitivity troponin T measurement that was greater than or equal to the peak postoperative troponin value. In this cohort with high-sensitivity troponin T measurements, 3904 patients (17.9 percent) were adjudicated as having suffered MINS, and among these patients, 21.7 percent fulfilled the universal definition of MI.
●A 2017 prospective, diagnostic study of 2018 patients (2546 surgeries) at increased cardiovascular risk and undergoing noncardiac surgery routinely measured hs-cTnT before and after surgery [9]. Perioperative myocardial injury was defined as an absolute increase in hs-CTnT of ≥14 ng/L above preoperative values. Perioperative myocardial injury occurred in 16 percent of surgeries. Of these, 6 percent had typical chest pain, 18 percent had any ischemic symptom, and 29 percent had one or more of the following: an ischemic symptom, a diagnostic change on an ECG, or evidence of loss of myocardial viability on imaging.
Additional information regarding incidence of perioperative MI in the troponin era comes from over 8000 patients in the randomized POISE trial of perioperative beta blocker therapy in patients at increased cardiovascular risk undergoing noncardiac surgery [14]. In POISE, perioperative MI was defined as an elevated cardiac biomarker or enzyme level (with separate definitions for troponin or creatine kinase MB fraction), and one or more of the following: ischemic symptoms, ECG changes in two contiguous leads (ie, development of pathologic Q waves, ST-segment elevation, ST-segment depression, or T-wave inversion), coronary artery intervention, or evidence of MI on cardiac imaging or autopsy [14]. The incidence of MI in POISE was 5 percent at 30 days (4.2 and 5.7 in the beta blocker and placebo groups, respectively), and the majority of these MIs (74 percent) occurred within 48 hours of surgery [13]. It is not clear that guideline-recommended cut-off values were used in POISE, which relied on local values. Thus, from the biochemical perspective, these data probably underestimate the true frequency of elevated cTn measurements and thus perhaps the true frequency of MI as well. In POISE, 65 percent of the patients who had a perioperative MI did not experience ischemic symptoms. Perioperative, asymptomatic MIs were associated with a similar increased risk of 30-day mortality (adjusted odds ratio 4; 95% CI 2.65-6.06) as with symptomatic MIs (adjusted odds ratio, 4.76; 95% CI 2.68-8.43). (See "Management of cardiac risk for noncardiac surgery", section on 'Patients without indications for long-term therapy'.)
PREDICTORS — Risk factors for cardiovascular events (including myocardial infarction [MI]) after noncardiac surgery have been identified and incorporated into validated risk models. The revised Goldman cardiac risk index is the best validated risk index and appears to have greater predictive value than other risk indices (table 1). Risk factors include high-risk surgery, history of ischemic heart disease, heart failure, cerebrovascular disease, diabetes mellitus requiring treatment with insulin, and preoperative serum creatinine >2.0 mg/dL. (See "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Risk assessment'.)
The CARP trial specifically evaluated predictors of MI in patients with coronary artery disease undergoing elective vascular surgery [15]. In this very-high-risk group, age greater than 70 years, abdominal aortic surgery, diabetes mellitus, angina, and baseline ST-T abnormalities were significantly associated with the development of MI.
While high-risk surgery such as abdominal aortic surgery is associated with the development of perioperative MI, other surgeries such as total hip and knee replacement also place patients at risk. (See "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Risk factors'.)
In the POISE trial, in addition to the Goldman risk predictors, serious bleeding (disabling or requiring ≥2 units of blood) and an increase in every 10 beats in baseline heart rate were significant independent predictors of perioperative MI (adjusted odds ratio 3.62, 95% CI 2.07-6.36; and 1.29, 95% CI 1.13-1.50, respectively) [13].
Perioperative hemorrhage as a predictor of MI (or stroke) was also evaluated in a study of 651,775 patients who underwent surgery between 2005 and 2009 at centers participating in the United States National Surgical Quality Improvement Program [16]. Major hemorrhage, defined as bleeding necessitating transfusion of more than four units of packed red blood cells or whole blood, occurred in 0.80 percent of patients. Q-wave MI occurred in 0.24 percent, and stroke in 0.20 percent. Hemorrhage was independently associated with MI (hazard ratio [HR] 2.7, 95% CI 2.1-3.4) and stroke (HR 2.3, 95% CI 1.9-3.3), and the risk was related to the severity of bleeding. The risk of MI may be an underestimate due to the use of Q-wave MI as the definition of MI, rather than the use of biomarkers and clinical findings.
In the POISE-2 trial comparing low-dose aspirin with placebo and low-dose clonidine with placebo in 10,010 adults undergoing noncardiac surgery, the following preoperative independent predictors of perioperative MI were found: history of coronary artery disease, peripheral arterial disease, congestive heart failure, estimated glomerular filtration rate <60 mL/minute/1.73m2, and age ≥75 years. Intraoperative and postoperative predictors included clinically important hypotension and all major bleeds that occurred before MI [17]. (See "Management of cardiac risk for noncardiac surgery", section on 'Antiplatelet therapy'.)
PREVENTION — All patients undergoing noncardiac surgery, and in particular those at increased risk of a perioperative myocardial infarction, should have their risk of a cardiovascular event assessed and managed before surgery. (See "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Our approach' and "Management of cardiac risk for noncardiac surgery".)
CLINICAL PRESENTATION — Patients with perioperative myocardial infarction (MI) may have symptoms and (rarely) signs similar to the broad group of patients with an acute coronary syndrome. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Clinical presentation'.)
However, due to the influence of anesthetic/analgesic/amnestic agents, symptoms are often muted, atypical, or absent. In the POISE trial, approximately 65 percent of the patients with MI did not experience ischemic symptoms [14]. We recommend that all patients with symptoms or signs suggestive of myocardial ischemia or those suspected for other reasons, such as hemodynamic instability or respiratory distress, receive a 12-lead electrocardiogram and serial (two or three) troponin measurements.
DIAGNOSIS — In the setting of noncardiac surgery, the diagnosis of perioperative myocardial infarction (MI) is confirmed with a highly sensitive troponin with at least one of the following present: symptoms of ischemia, new or presumed new significant ST-segment/T wave changes or new left bundle branch block, development of pathological Q waves on the electrocardiogram (ECG), new or presumed new imaging evidence of loss of viable myocardium or regional wall motion abnormality, or identification of an intracoronary thrombus by angiography or autopsy [1,18]. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction".)
Since the key to the diagnosis of MI is the presence of a rising and/or falling pattern of values of cardiac troponin (see 'Definitions of myocardial infarction and myocardial injury' above), an attempt should be made to compare the postoperative value with a preoperative one.
In patients in whom troponin was not measured or was measured at a time that could have missed the clinical event, we believe that new pathologic Q waves on the ECG can define acute MI. For patients in whom the diagnosis remains uncertain after considering symptoms, ECG changes, and the results of biomarker testing, information from additional noninvasive studies (such as a new wall-motion abnormality or fixed defect on echocardiography, or radionuclide myocardial perfusion imaging) may be needed. (See "Noninvasive testing and imaging for diagnosis in patients at low to intermediate risk for acute coronary syndrome".)
For those patients who have an elevated troponin, the ECG shows a new ischemic abnormality in a minority. In the first VISION study, which used non-high sensitivity troponin (see 'Definitions of myocardial infarction and myocardial injury' above), about 35 percent of patients had an ischemic ECG finding. T wave inversion and ST depression were the most common findings (23 and 16 percent, respectively). It is likely that a higher proportion of patients who suffer myocardial injury after noncardiac surgery (MINS) experienced ischemic ECG changes at some point in their postoperative course, but these changes are likely frequently missed for the following reasons: Most patients do not experience ischemic symptoms to trigger obtaining an ECG during the period of ischemia; most ECGs are obtained after detection of an elevated troponin, which is usually obtained at 24-hour intervals after surgery; and a troponin elevation only occurs hours after the initiation of an ischemic event. If clinicians are suspicious, additional studies are warranted.
Some may find it appropriate to use the diagnosis of MINS (see 'Definitions of myocardial infarction and myocardial injury' above) only when a diagnosis of acute MI is not fulfilled. In this case, MINS would be deemed present when there is an elevated troponin but no symptoms or ECG or noninvasive testing abnormalities. In addition, these patients should have had a nonischemic cause of an elevated troponin excluded. (See 'Definitions of myocardial infarction and myocardial injury' above and 'Differential diagnosis' below.)
DIFFERENTIAL DIAGNOSIS — Potential causes of an elevated troponin in the absence of criteria for MI or MINS include pulmonary embolus, sepsis, rapid atrial fibrillation, or chronic kidney disease. This issue is discussed in detail elsewhere. (See "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome".)
SCREENING — Screening for myocardial injury after noncardiac surgery (MINS) refers to the perioperative measurement of troponin and procurement of an electrocardiogram (ECG) in the perioperative period in patients who have no symptoms (or signs) of myocardial ischemia but who are at relatively high risk (table 1). (See "Troponin testing: Clinical use", section on 'Noncardiac surgery'.)
Troponin — We suggest screening for perioperative MINS in patients at high risk for a perioperative myocardial infarction (MI). High risk is defined as in-hospital surgery with one or more additional risk factors from the revised cardiac risk score (table 1). Other research has defined high risk as patients ≥65 years of age or patients with known atherosclerotic disease [19]. A highly sensitive troponin should be obtained at 6 to 12 hours and on days one, two, and three after surgery (see 'Predictors' above). In addition, some of us obtain a baseline preoperative cardiac troponin (cTn) in these patients since an isolated elevated postoperative cTn may represent a chronic process rather than an acute event.
The risk of MI is elevated, and the likelihood of missing the diagnosis based on symptoms or ECG changes is significant, as was shown in the POISE trial discussed above [20] (see 'Incidence' above). The principal argument against obtaining a baseline troponin is that patients in whom an elevation is identified (such as those with chronic elevations) may have their surgery unnecessarily postponed.
Some experts have suggested that somewhat lower-risk patients, such as those with risk factors for cardiovascular disease (eg, smoking, hypertension, or dyslipidemia), undergo screening given the worse short- and long-term outcomes associated with perioperative MI [13]. As the use of screening has not been well studied in these patients, we do not routinely screen them. (See 'Prognosis' below.)
Screening with troponin may identify individuals with MINS; that is, they did not have symptoms of myocardial ischemia and the ECG was normal, unchanged, or nondiagnostic. The rationale for this screening recommendation is that a positive troponin will lead to recommendations for preventative therapies such as aspirin and statin use and will prompt evaluation by additional ECGs or imaging studies that might not otherwise be done, which could reveal an MI. (See 'Myocardial injury without MI' below.)
For patients found to have an elevated screening perioperative troponin, two issues should be kept in mind before a diagnosis of MINS is made (see 'Definitions of myocardial infarction and myocardial injury' above):
●The diagnosis should not be based only on a postoperative elevation in troponin, as this may represent a chronic elevation. This possibility is why a baseline troponin value is so important. The baseline (preoperative) value may be available either because it had been performed as a routine test, as discussed below, or because a preoperative residual sample can be tested. The diagnosis requires either a normal baseline value or a typical rise and fall of the biomarker. A challenge to clinicians is that many patients may not have a preoperative baseline troponin value to compare. In such instances, a prior sample may be available and used to test for cTn.
In the VISION high-sensitivity cohort study (see 'Incidence' above), among the patients who had an elevated perioperative troponin measurement, 13.8 percent had a preoperative high-sensitivity troponin T measurement that was greater than or equal to the peak postoperative troponin value. This study highlights the importance of a baseline value to differentiate if an elevated troponin represents a new event that occurred during or after surgery started.
●Elevated troponin measurements after surgery can occur due to nonischemic etiologies and should prompt an evaluation of the patient to ensure a nonischemic etiology has not been missed. (See 'Mechanism' above and 'Differential diagnosis' above.)
Role of BNP — Although pre- and postoperative elevations in plasma B-type natriuretic peptide (BNP) are associated with an increased risk of adverse cardiovascular events (including MI) at 30 days, its role in the care of patients undergoing noncardiac surgery has not been established (see 'Prognosis' below). Until this issue is studied further, some of our contributors routinely order BNP before noncardiac surgery for prognostic purposes. The use of BNP in other settings is discussed separately. (See "Natriuretic peptide measurement in heart failure" and "Natriuretic peptide measurement in non-heart failure settings".)
A 2009 meta-analysis, which included seven studies of 2841 patients, found a statistically significant association between a preoperative elevation in BNP and the cardiovascular outcomes of death, cardiac death, and nonfatal MI at 30 days (adjusted odds ratio 19.3) [21]. A 2011 meta-analysis that evaluated mortality at six months or later came to a similar conclusion [22].
Electrocardiogram — We suggest at least one 12-lead ECG in all patients with symptoms of myocardial ischemia. However, the issue of when to obtain a screening ECG(s) in asymptomatic patients is not well studied. Although the evidence to support the routine performance of a postoperative ECG(s) in high-risk patients is weak compared with that for the use of troponin, some of our experts believe such practice is reasonable. High risk is defined as in-hospital surgery with one or more additional risk factors of the revised cardiac risk score or any patients with complications of a possible cardiovascular etiology (table 1). Some of our experts routinely perform a postoperative ECG in lower-risk patients, such as those with risk factors for coronary heart disease [10]. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Unexpected absence of diagnostic findings'.)
Similar to our rationale to obtain a preoperative troponin in high-risk patients, we obtain a baseline ECG in these patients. (See 'Troponin' above.)
Recommendations of others — The 2014 American College of Cardiology/American Heart Association guideline on the perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery states that the usefulness of postoperative screening of high-risk patients using troponin and ECG is uncertain [23,24].
The 2014 European Society of Cardiology perioperative guidelines state that assessment of cardiac troponins in high-risk patients, both before and 48 to 72 hours after major surgery, may be considered [25].
The fourth Universal Definition of MI international expert consensus document recommends measuring troponin before and up to 48 to 72 hours after noncardiac surgery in high-risk patients [1].
The 2017 Canadian Cardiovascular Society Guidelines for patients undergoing noncardiac surgery recommend obtaining daily cTn measurements for 48 to 72 hours after noncardiac surgery in patients with a baseline risk >5 percent for cardiovascular death or nonfatal MI at 30 days after surgery (ie, patients with an elevated NT-proBNP/BNP measurement before surgery or, if there is no NT-proBNP/BNP measurement before surgery, in those who have a Revised Cardiac Risk Index [RCRI] score ≥1, age 45 to 64 years with significant cardiovascular disease, or age ≥65 years) [26].
PROGNOSIS — Short- and long-term mortality are significantly increased in patients with a perioperative increase in cardiac troponin (cTn) irrespective of whether they are labelled as having myocardial infarction (MI) or myocardial injury after noncardiac surgery (MINS) [2,13,27-31]. In addition, nonfatal perioperative MI is an important independent risk factor for recurrent nonfatal acute coronary syndrome, nonfatal cardiac arrest, heart failure, rehospitalization within 30 days, or progressive angina requiring revascularization later after surgery [5,10,13,15,32,33].
Multiple studies have found an increase in short-term (in-hospital and 30-day) mortality, with in-hospital mortality ranging between 5 and 25 percent [2,13,27-30]. The following are representative examples:
●In the 2017 report from the VISION study (see 'Incidence' above), death within 30 days occurred in 1.2 percent [8]. An absolute change of 5 ng/L across any two perioperative measurements of high sensitivity cTn (hs-cTn) was independently associated with an increase in 30-day mortality (adjusted hazard ratio 4.69; 95% CI 3.52-6.25). In addition, the peak value had prognostic significance. Compared with a reference group (peak hs-TnT <5 ng/L), patients with peak postoperative hs-TnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0, 9.1, and 29.6 percent (adjusted hazard ratios 23.63, 70.34, and 227.01, respectively, and all were statistically significant).
●In the 2017 prospective, diagnostic study of 2018 patients discussed above (see 'Incidence' above), crude 30-day mortality was 8.9 percent in patients with myocardial injury compared with 1.5 percent in patients without (adjusted hazard ratio 2.7, 95% CI 1.5-4.8) [9]. Importantly, the study also found no difference in 30-day mortality between those with myocardial injury not fulfilling any other criteria for acute MI and those with at least one addition criterion (10.4 versus 8.7 percent; P = 0.684). Both the absolute hs-TnT value and the increase from the baseline value (the "delta") were associated with increasing mortality rates.
Long-term mortality is increased in patients with MINS. In the 2017 study mentioned above, mortality at one year was significantly higher in patients with MINS (22.5 versus 9.3 percent, respectively). Similarly, in a 2011 meta-analysis of 15 studies (over 4000 patients) of various types of noncardiac surgery with follow-up ranging between 3 and 48 months, an elevation of either troponin or creatine kinase MB fraction was associated with a significantly increased risk of all-cause mortality (adjusted odds ratio 3.4, 95% CI 2.2-5.2; and 2.5, 95% CI 1.5-4.0, respectively) [31]. In the MANAGE trial (see 'Management' below), all-cause mortality was 13 percent in the placebo group at 16-month follow-up [34].
Despite the clear relationship between perioperative MI or MINS and prognosis, the benefit from screening at-risk patients for perioperative MI has been questioned. We believe MANAGE supports an argument for screening. Our recommendations for screening are presented above. (See 'Screening' above.)
Outcomes in the subset of perioperative MI patients who are referred for coronary angiography within seven days of noncardiac surgery were evaluated in a 2016 report from the Cleveland Clinic [30]. In this study, 1093 such individuals were referred for angiography for marked elevations of cTn (>fivefold). It is unclear if a rising and/or falling pattern of values was observed. Overall mortality at 30 days and one year was 5.2 and 15 percent, respectively. Of these 1093 patients, 281 (40 ST-elevation MI and 241 non-ST elevation MI) underwent percutaneous coronary intervention. Mortality at 30 days was 11.3 percent; the 30-day death rates in the ST-elevation and non-ST elevation MI cohorts were 31.2 and 8.5 percent, respectively. Risk factors for 30-day mortality after PCI were a bleeding event after PCI (odds ratio [OR] 4.33), peak troponin T level (OR 1.2), and underlying peripheral artery disease (OR 4.86). Important risk predictors for long-term mortality were bleeding after PCI, renal insufficiency, and vascular surgery.
A large United States database study (nearly 10,000,000 individuals) identified 8085 patients who were diagnosed with perioperative MI [33]. Among patients diagnosed with a perioperative MI during the index hospitalization, compared with patients not diagnosed with a perioperative MI, the absolute incidence of mortality was 13 percent higher, and the length of stay was six days longer (p<0.001 for both comparisons). The rate of rehospitalization within 30 days was higher in those MI patients who survived the initial hospitalization compared with those without MI (19.1 versus 6.5 percent; adjusted odds ratio 1.39, 95% CI 1.31-1.48). Approximately 25 percent of the readmissions were due to cardiovascular complications, and an additional 16 percent of patients had an acute cardiovascular complication, although it was not the primary indication for readmission. However, these patients were identified clinically and may be very different from those diagnosed more sensitively with surveillance troponin values.
The relationship between postoperative B-type natriuretic peptides (BNP) and cardiovascular outcomes was evaluated in a 2013 meta-analysis of 18 studies (n = 2051) in which BNP was sampled less than seven days after surgery [35]. The primary outcome of death or nonfatal MI at 30 days occurred more often in patients with a BNP ≥245 pg/mL or an N-terminal proBNP ≥718 pg/mL (adjusted odds ratios 4.5, 95% CI 2.74-7.4). A subsequent analysis of these 18 studies found that the addition of a postoperative BNP enhanced risk stratification for the composite outcomes of death or nonfatal MI at 30 days and >180 days compared with a preoperative BNP [36].
MANAGEMENT — The optimal management strategy for those patients who sustain MINS with or without MI in the perioperative period is unknown given the paucity of data upon which recommendations can be made. We believe that the care of such patients needs to be individualized and based on characteristics such as likely mechanism of MI (see 'Mechanism' above), risks of therapy, information derived from subsequent risk stratification, and comorbidities [18].
At a minimum, all such individuals should receive aspirin and a statin. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction".)
Evidence to support the use of aspirin and statin in patients with perioperative MINS comes from the broad population of patients with MI who benefit from these drugs, as well as from the POISE trial [13]. In an observational sub-study of POISE, aspirin and statin use were each associated with a reduction in the risk for 30-day mortality among patients who had suffered a perioperative MI (adjusted odds ratios 0.54, 95% CI 0.29-0.99; and 0.26, 95% CI 0.13-0.54, respectively). (See "Management of cardiac risk for noncardiac surgery", section on 'Patients taking beta blockers'.)
We typically start atorvastatin 80 mg (40 mg in patients who cannot receive 80 mg daily) and aspirin 81 to 325 mg (when the risk of bleeding after surgery is acceptable); patients are discharged on the same daily dose of atorvastatin and aspirin 75 to 100 mg daily. (See "Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome", section on 'Summary and recommendations' and "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy".).
In addition to aspirin and a statin, we consider treating patients whose bleeding risk permits with the oral anticoagulant (OAC) dabigatran for two years after MINS. One of our contributors routinely starts dabigatran in these individuals.
Our use of dabigatran in MINS patients is based on the 2018 MANAGE trial (see 'Screening' above), as well as other evidence of a beneficial effect of OAC in patients with coronary artery disease.
●MANAGE evaluated dabigatran in 1754 patients (20 percent met criteria for myocardial infarction [MI]) not at high bleeding risk with an elevated postoperative troponin thought to be due to MI or without evidence of a non-ischemic cause. Patients were randomly assigned within 35 days of surgery to dabigatran 110 mg or placebo twice daily for a maximum of two years or until termination of the trial [34]. Seventy-four percent of patients received a single antiplatelet agent, usually aspirin, and 7 percent of patients took dual antiplatelet therapy. At a mean follow-up of 16 months, the risk of the primary efficacy end point of major vascular complication (a composite of vascular mortality and non-fatal MI, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism) was lower with dabigatran (11 versus 15 percent; hazard ratio [HR] 0.72, 95% CI 0.55-0.93). With the exception of non-hemorrhagic stroke (which had few clinical events), none of the components of the end point met statistical significance. There was no difference in the rate of the primary safety outcome, a composite of life threatening, and major and critical organ bleeding (3 versus 4 percent, respectively; HR 0.92, 95% CI 0.55-1.53). Trial recruitment was slower than expected and funding was curtailed during the conduct of the trial. Consequently, the primary outcome and sample size were changed without knowledge of the results.
●Following an acute coronary syndrome, low-dose rivaroxaban has been shown to be beneficial when added to dual antiplatelet therapy. (See "Acute coronary syndrome: Oral anticoagulation in medically treated patients", section on 'Rivaroxaban'.)
●In patients with stable coronary artery disease but at high cardiovascular risk, low-dose rivaroxaban when added to aspirin is beneficial. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Anticoagulant therapy'.)
In addition to aspirin and statin, and possibly dabigatran, continuous electrocardiographic monitoring (potentially in a monitored setting) for at least 24 hours is advised, particularly if the diagnosis is made within the first 24 hours of surgery.
The following discussion presents specific comments based on the type of perioperative event: ST-elevation MI (STEMI), non-ST elevation MI (NSTEMI), and troponin elevation without other criteria for MI (MINS).
ST-elevation MI — Patients with perioperative STEMI are at high risk for death without usual STEMI care, including reperfusion therapy, and are at high risk for a bleeding complication with it. In most patients, fibrinolytic therapy is not an option given the recent surgical procedure. We usually proceed with urgent primary percutaneous coronary intervention after careful discussion of the benefits and risks with all managing healthcare providers. The patient and family are involved in this process.
We recommend aspirin and statin for these STEMI patients. A P2Y12 receptor blocker is added as soon as a decision is made to implant an intracoronary stent. For patients who receive no reperfusion therapy, we also recommend one year of aspirin plus a P2Y12 receptor blocker (dual antiplatelet therapy). (See "Acute ST-elevation myocardial infarction: Antiplatelet therapy", section on 'Patients not reperfused'.)
We also recommend starting a beta blocker in these patients. However, the potential for hypotension should be considered in the choice of timing and dose.
The general approach to MI patients is discussed elsewhere. (See 'Management' above and "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the nonacute management of ST-elevation myocardial infarction".)
Non-ST elevation MI — Our approach to the management of patients with perioperative NSTEMI is as follows:
●We start aspirin (when the bleeding risk is acceptable) and statin in all such patients, as the benefit-to-risk ratio is likely to be in favor of their use. (See 'Management' above.)
●Our experts have differing approaches to the use of beta blockers, with some recommending their use in all patients and some recommending use only in those with moderate or large MI, untreated hypertension, or those who need rate control in atrial fibrillation. If possible, we wait until day two or three postoperatively prior to initiating a beta blocker (in patients not already on beta blockers) in an attempt to avoid hypotension during this period.
●For hemodynamically unstable patients or those with recurrent ischemia, we recommend early coronary angiography. The decision to revascularize and use aggressive antithrombotic therapy (including dual antiplatelet therapy) will need to take into consideration the benefits and risks of such an approach in the patient with recent surgery.
●For hemodynamically stable patients without evidence of recurrent ischemia, we perform risk stratification when feasible after surgery. Risk stratification can be with noninvasive testing, coronary angiography, or both. We recommend coronary angiography when it is felt that the knowledge of the coronary anatomy will influence decisions regarding revascularization or changes in medical therapy. (See "Non-ST-elevation acute coronary syndromes: Revascularization", section on 'Conservative approach'.)
Myocardial injury without MI — For patients who are troponin positive but do not meet the criteria for MI (see 'Definitions of myocardial infarction and myocardial injury' above), we start aspirin and a statin, as they are likely to have coronary artery disease with fixed obstruction. Since the troponin rise may have been due to supply-demand mismatch, rather than plaque rupture or fissure, we are not prepared to recommend adding a second antiplatelet agent. This recommendation for aspirin and statin in this population is based on extrapolation of evidence of benefit in the broad population of patients with coronary artery disease. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Summary and recommendations'.)
Our experts have differing approaches to the use of beta blockers in this population with some starting them and others not.
Evidence to support the initiation of secondary preventive measures after MINS comes from a propensity-matched study of 66 MINS patients and 132 matched non-MINS patients who underwent major vascular surgery [37]. Among MINS patients, 43 received therapeutic intensification of ≥1 of 4 cardiac medications (aspirin, statin, beta-blocker, or angiotensin converting enzyme inhibitor) and 23 patients did not receive therapeutic intensification after MINS. The primary end point was 12-month survival without a major cardiac event (ie, death, MI, coronary revascularization, or pulmonary edema requiring hospitalization). MINS patients not receiving therapeutic intensification had a hazard ration (HR) for the primary outcome of 1.77; 95% CI 1.13-2.42, whereas MINS patients receiving therapeutic intensification had HR 0.63; 95% CI, 0.10-1.19.
Our contributors also consider starting dabigatran in these patients. (See 'Management' above.)
For these patients who become symptomatic or in whom there is a concern about a high risk of arrhythmia, we suggest continuous electrocardiographic monitoring for 24 to 48 hours. (See "Overview of primary prevention of cardiovascular disease" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Summary and recommendations'.)
When the patient has recovered from surgery, risk stratification with stress testing is reasonable unless another clear explanation for an elevated troponin is present.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Perioperative cardiovascular evaluation and management".)
SUMMARY AND RECOMMENDATIONS
●Myocardial infarction (MI) in patients undergoing noncardiac surgery is defined as a rise in troponin in association with suggestive symptoms or electrocardiographic changes. Myocardial injury after noncardiac surgery (MINS) requires only an elevated troponin postoperatively when there is no evidence of a non-ischemic cause. (See 'Diagnosis' above.)
●With regard to measurement of troponin (see 'Troponin' above):
•We recommend troponin measurement in all perioperative patients with symptoms or electrocardiographic changes suggestive of ischemia or MI (two or three serial troponin values).
•For all asymptomatic patients at high cardiac risk, we recommend screening with high sensitivity troponin (Grade 1B). High risk is defined as in-hospital surgery with one or more additional risk factors of the revised cardiac risk score, age ≥65 years, or known atherosclerotic disease (table 1). We suggest obtaining troponin before surgery and at 6 to 12 hours, and days one, two, and three after surgery. Some of our experts routinely perform screening of lower-risk patients.
●With regard to obtaining a 12-lead electrocardiogram (see 'Management' above):
•We recommend performing 12-lead electrocardiography for all patients with symptoms of myocardial ischemia.
•For all asymptomatic patients at high cardiac risk for perioperative MI (table 1), we suggest obtaining a 12-lead electrocardiogram (Grade 2C). We obtain one at baseline and daily for two and possibly three days.
●For all patients with perioperative MI or MINS, we recommend treatment with statin and aspirin therapy (Grade 1B). On day one of therapy, we typically give atorvastatin 80 mg and aspirin 81 to 325 mg; we continue with the same dose of atorvastatin and aspirin 75 to 100 mg daily.
●For all patients with perioperative MI or MINS who are not at increased bleeding risk, we suggest treatment with dabigatran (Grade 2B). We treat with dabigatran 110 mg twice daily for two years.
●For patients with ST-elevation MI, we recommend treatment with a beta blocker (Grade 1B).
In addition, we usually proceed with urgent primary percutaneous coronary intervention after careful discussion of the benefits and risks with all managing healthcare providers. (See 'ST-elevation MI' above.)
●For patients with non-ST elevation MI, our experts have differing approaches to the use of beta blockers, with some recommending their use in all patients and some recommending their use only in those with moderate or large MI, untreated hypertension, or those who need rate control in atrial fibrillation. (See 'Non-ST elevation MI' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff would like to thank Jonathan B. Shammash, MD, Stephen E. Kimmel, MD, MS, Scott Solomon, MD, and the late Emile R Mohler, III, MD, for their contributions to an earlier version of this topic review.
