Author Affiliations: ¹The University of Michigan Medical School, Ann Arbor, MI; ²Department of Internal Medicine, Department of Cardiology, Michigan Medicine, Ann Arbor, MI

Corresponding Author:

Timothy Baerg, BS, [email protected], 507995-7809

Conflicts of interest:

There are no conflicts of interest to disclose.

Case

A 51-year-old patient underwent a unilateral nephrectomy for targeted donation. His preoperative visits were unremarkable for contraindications to donate. After the induction of anesthesia, he tolerated insufflation. Upon incision, however, he developed bradycardia with heart rate (HR) in the 30s, mean arterial pressure (MAP) in the 40s mmHg, and an ST segment elevation in the inferior electrocardiogram (ECG) leads. He was immediately resuscitated. Atropine and dopamine were infused to maintain blood pressure and heart rate. After emergency chest compressions, the patient was sent to the intensive care unit for medical management.

Although this patient seemed to appear healthy prior to his operation, intraoperatively, his physical condition declined, and he appeared to have an intraoperative myocardial infarction. Although a myocardial infarction (MI) in such a patient is not common with a thorough cardiovascular workup prior to an operation, it is important nonetheless for physicians to be able to recognize risk factors and management strategies for a potential MI in an operative setting. This review article aims to unpack the etiology, risk factors, risk stratification, and diagnosis of MI in the surgical context.  

The Etiology of Perioperative MI

There are two mechanisms for perioperative myocardial infarction (PMI): acute coronary syndrome (type 1) and prolonged imbalance of myocardial oxygen in patients with stable coronary artery disease (type 2). For type 1 MI, an arterial plaque ruptures, leading to acute coronary thrombosis. Surgery can increase the risk of type 1 MI in vulnerable patients through various mechanisms. Stress from surgery causes elevation of catecholamines and cortisol, which is correlated with troponin elevation .[1] Tachycardia and hypertension are also common in the perioperative period and can contribute to shear stress and the rupture of plaques. Finally, lengthy surgeries promote a prothrombotic state .[1]

For type 2 MI, tachycardia is the most common cause of postoperative oxygen supply-demand imbalance .[2] There is a low threshold for ischemia after surgery. For instance, heart rates greater than 90 bpm for patients with coronary artery disease whose preoperative heart rates are in the 60s bpm can lead to prolonged ischemia and PMI .[1] Postoperative hypotension, hypertension, hypoxemia, and hypercarbia can also contribute to decreased coronary perfusion .[1]

Perioperative MI Predictive Risk Factors

The most widely used risk model to predict perioperative cardiovascular events in noncardiac surgery is the Revised Cardiac Risk Index (RCRI), which takes into account six risk factors: high-risk surgery, history of ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin-dependent diabetes mellitus, and preoperative serum creatinine >2.0 mg/dL. No risk factors, 1 risk factor, 2 risk factors, or 3 or more risk factors are associated with a 0.4%, 0.9%, 7%, and 11% chance of a cardiovascular event, respectively.[3][4] Newer risk prediction calculators have been developed, such as the Gupta Myocardial Infarction and Cardiac Arrest (MICA) and National Surgical Quality Improvement Program (NSQIP) calculators, but they have yet to be validated. Therefore, the RCRI is still the preferred tool .[5]

A recent study by Kheterpal et al[6] investigated the predictors of cardiovascular adverse events (CAE)—defined as cardiac arrest, non-ST segment elevation myocardial infarction (NSTEMI), Q wave myocardial infarction, or new cardiac dysrhythmia—within the first 30 postoperative days in patients that underwent noncardiac surgery. They found 9 independent predictors of perioperative CAE: age ≥ 68, active congestive heart failure, BMI ≥ 30 kg/m[2], emergency surgery, previous cardiac intervention, cerebrovascular disease, hypertension requiring medication, operative duration ≥ 3.8 hours, and receiving ≥ 1 unit of packed red blood cells. These results identified similar risk factors to the RCRI with the addition of obesity; however, the study did not find insulin-dependent diabetes or preoperative creatinine level to be a predictor for PMI, which is likely due to the advances in diabetes and kidney disease management.

Further analysis in this study revealed that patients with at least 2 of these predictors who experienced a CAE were significantly more likely to have had an episode of 40% decrease in their MAP, an episode of MAP < 50 mmHg, or an episode of HR >100 bpm during the operation .[6] Overall, predictors of CAE are increasingly well understood and can assist surgeons and anesthesiologists in preoperative planning. Additionally, a study conducted by Golubovic et al[7] found that adding biomarkers such as N-terminal brain natriuretic peptide, high-sensitivity troponin, and high-sensitivity C-reactive protein to the RCRI score preoperatively could improve predicting patients at risk for cardiac complications from the time of surgery to 3 months post-op.

Perioperative MI Risk Stratification

The selection of patients to reduce perioperative cardiac morbidity and mortality should take into account the procedure’s risk and acuity and each patient’s functional status and comorbidities.

Risk Assessment

Risk can be stratified with validated clinical scores such as the RCRI. The risk of myocardial infarction depends on the number of factors and ranges from 0.4% (no risk factors) to 11% (3+ risk factors) .[3]

Functional Status

The patient’s functional status in Metabolic Equivalent of Tasks (METs) is also relevant in the perioperative MI risk stratification. A MET corresponds to the metabolic oxygen uptake at rest; walking up steps requires roughly 4 METs while strenuous sports may require 10+ METs.

Overall Selection

Per the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, the following process can be utilized to approach perioperative cardiac risk assessment.[8][9] For non-emergent surgery, the perioperative risk of an MI should be calculated, for example, with the RCRI score. Low-risk patients with a <1% risk can proceed with the operation. For patients with >1% risk, the patient's functional status factors into management. Patients with MET ≥ 4 can proceed to surgery without any additional testing. Patients with a poor or unknown MET may require additional testing (a stress test, leading to coronary revascularization) and should be considered for guideline directed therapy versus alternate non-operative management.[8][9]

Diagnosis of Perioperative MI

Most PMIs occur without symptoms in anesthetized or sedated patients and with subtle or transient ECG findings. Thus, routine monitoring of cardiac biomarkers is recommended, both before and up to 48 to 72 hours after surgery, especially in high-risk patients.[3][8] Cardiac troponins (I or T) are the preferred cardiac biomarkers for diagnosis of PMI because they are released almost exclusively by the heart. Creatine kinase-MB isoenzyme has a limited role in surgical patients due to coexisting skeletal muscle injury. According to an ACC/AHA joint taskforce, the diagnosis of PMI requires the rise of cardiac biomarkers above the 99th percentile upper reference limit (URL) and at least one other finding of ischemia. Ischemic features include ischemic symptoms such as chest pain or dyspnea and ischemic changes on ECG such as ST segment–T wave changes, new left bundle branch block, or pathologic Q waves. Additionally, ischemia can be detected using cardiac imaging, such as echocardiography or radionuclide techniques that demonstrate wall motion abnormalities or loss of new myocardium .[8]

Diagnosis of PMI after cardiac interventions such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is challenging due to instrumentation of the heart. Some myocardial injury is unavoidable during these procedures. In PCI, ischemia—with or without ST changes—often occurs. Thus, the diagnosis of procedure-related MI requires comparing cardiac biomarkers before and 3 to 5 hours after the procedure .[9] Compared to PCI, the literature defining PMI after CABG is limited. Biomarker release varies depending on the patient’s baseline levels and techniques used such as on-pump versus off-pump CABG .[10] Due to the coexistent myocardial injury associated with cardiac interventions, the ACC/AHA guidelines define PCI-related MI and CABG-related MI as biomarker rise 5 times the 99th percentile URL and 10 times the 99th percentile URL within 48 hours, respectively, which is associated with 1 ischemic feature such as ischemic symptoms or ECG changes .[11]

Management of Perioperative MI

Perioperative MI can be subdivided into STEMI and NSTEMI. Management strategies for PMI are as follows.

Antiplatelet Therapy

In the perioperative setting, glycoprotein IIb/IIIa platelet receptor antagonists have demonstrated usefulness, as they can be delivered intravenously. These agents include the chimeric monoclonal antibody abciximab and the nonantibody agents tirofiban and eptifibatide. However, due to the risk of bleeding, these chimeric monoclonal antibody agents are less typically used for PMI .[12]

Anticoagulation

In the operative setting, intravenous unfractionated heparin should be delivered if bleeding risks are tolerable and there is a suspicion of plaque rupture. Although the risk of bleeding in the non-operative MI is taken into consideration, special care must be regarded in the operative setting, especially depending on the type of operation. For instance, although surgery of the limbs may have a higher tolerance for anticoagulation, neurosurgical operations may limit even a small amount of anticoagulation due to risks of bleeding within an enclosed space. In the postoperative patient, unfractionated heparin is the choice for both conservative management and PCI, as it is reversible with protamine .[12]

Pain Management

Opioids are the mainstay for pain management, with IV morphine being the preferred agent due to its ability to decrease preload. Pain reduction subdues the catecholaminergic system, reducing myocardial oxygen demand .[12] Nitroglycerin can reduce pain through non-endothelium dependent vasodilation, the reduction of preload, and the increased perfusion of ischemic zones.

Beta-Blockers

In the perioperative setting, intravenous beta-blockers are indicated unless contraindications are present, such as significant bradycardia (heart rate < 50 bpm), decompensated congestive heart failure, or severe chronic obstructive pulmonary disease (COPD). Beta-blockers reduce myocardial oxygen demand and offer direct reduction of the ventricular fibrillation threshold .[12]

ACE Inhibitors

ACE inhibitors may be used within the first 48 hours of PMI, but they should be discontinued in patients who do not have high-risk characteristics, such as an ejection fraction of less than 45% with clinical evidence of heart failure, mitral regurgitation, or hypotension .[12]

Percutaneous Coronary Intervention

Percutaneous coronary intervention is the preferred option for acute reperfusion therapy in the perioperative setting due to the lower risk of a major hemorrhage. Berger et al[13] examined 48 patients who underwent coronary angiography for PMI (33 STEMI and 15 NSTEMI) who had ongoing chest pain or hemodynamic instability. Of the 48 patients, 41 underwent angioplasty, 3 were referred for bypass surgery, and 1 was treated with intracoronary fibrinolytic therapy after an unsuccessful angioplasty. Of the 48 patients, 31 survived, and none had any surgical site bleeding.

Outcomes of Perioperative MI

Understanding outcomes for PMI is difficult because it is variably defined. For instance, one study found that between 2.9% to 23.9% of patients experienced an MI depending on the biomarkers utilized .[14] Furthermore, PMI outcomes are hard to characterize due to the diversity of surgical procedures, severity of illness, and level of risk factors prior to the operation.

In several studies, PMI or elevated cardiac enzymes increased short-term (30-day) mortality.[9][13][14][15][16] One international study examined patients older than 45 years of age with a risk of atherosclerotic disease undergoing noncardiac surgery .[9] A PMI in this study was defined as evidence on autopsy or elevated cardiac enzymes plus another indicator. The 30-day mortality was 11.6% among patients with a diagnosis of PMI versus 2.2% in patients without. Even patients with elevated cardiac enzyme biomarkers without a diagnosis of MI had an increased risk of nonfatal cardiac arrest and non-acute coronary revascularization.

A study[15] examining patients undergoing moderate or high risk, noncardiac surgery found that elevated cardiac troponin I levels were associated with an increased 30-day, all-cause mortality of 8.6% in patients with elevated troponin levels compared to 2.2% without. Additionally, a major elevation in troponin I levels > 0.06 µg/L was found to have increased relative risk of death within 30 days compared to a minor elevation in levels. Of patients with elevated troponin levels, only 6.4% underwent coronary angiography. Interestingly, only 0.6% of the patients in this study would have been considered to have a PMI even though risk of mortality was increased in those patients with elevated troponins alone.

Long-term mortality was also impacted by PMI in a study conducted by Khuri et al[16] which examined outcomes at Veterans Affairs surgical centers in patients undergoing 8 common, noncardiac surgeries. Postoperative MI significantly increased risk of mortality at 30 days with 30.8% mortality with an MI versus 2.8% without. This increased mortality was also seen at 1 and 5 years postoperatively. Furthermore, MI was considered one of the top 10 complications by frequency examined in this study for each of the 8 surgeries researched.

Conclusion

Physicians can prevent PMI by identifying relevant risk factors and stratifying patients prior to an operation. Deliberate perioperative monitoring and reducing the threshold for concern in at-risk patients may prevent PMI. Although treatment of PMI does not differ drastically from nonoperative MI, the physician must factor in the risk of bleeding in the operative setting. Our case demonstrated that surgeons, anesthesiologists, and cardiologists should be well equipped to manage PMI if signs arise in the perioperative setting.

References

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