Perioperative Myocardial Infarction Risk Factors, Diagnosis, and Treatment

Introduction

Definitions

• PMI is a clinical or pathologic event involving myocardial cell death in the setting of myocardial ischemia.¹
• Patients with PMI are a subset of those with myocardial injury after noncardiac surgery (MINS) and are defined as elevated cardiac troponin (cTn) with at least one value above the 99th percentile upper reference limit (URL) that is presumed to be of ischemic origin.¹
• PMI incidence can range from 0.9% to 15%, depending on the specific definitions, patient risk factors, and surgical procedures used in a given study.²
• Nonischemic etiologies of cTn elevation (e.g., pulmonary embolism, sepsis, chronic obstructive pulmonary disease, myocarditis, heart failure, and subarachnoid hemorrhage) are excluded in all types of perioperative myocardial injury.^1-3
• PMI has been reproducibly demonstrated to confer more than a two-fold increase in all-cause mortality when compared to myocardial injury alone at both 30 days and 1 year.⁴
• Nearly one-third of patients with PMI either die or are readmitted within 30 days after hospital discharge.²

Etiology

• The precise etiology and mechanism of PMI are actively debated in the current literature.
• PMI can be classified into different types (Table 1).^1,3

• Based on studies including autopsy findings, perioperative coronary angiography, and postoperative ECG changes, the majority of PMIs (~65%) are thought to be a result of prolonged oxygen supply and demand mismatch (Type 2) MI.^1,2,5
  • Postmortem studies showed patients without plaque rupture (Type 2) died within the first 3 days from the date of surgery, whereas those with plaque rupture (Type 1) died at random distributions within 3 weeks from the date of surgery.
  • Thrombosis was less common in PMIs than in nonoperative MIs, despite similar plaque morphology on preoperative angiography.
  • Most PMIs are characterized by ST-segment depressions rather than elevations on ECG.

Risk Factors and Triggers

Risk Factors

• Multiple validated tools, such as the Revised Cardiac Risk Index (RCRI) and Functional Capacity Assessment (Duke Activity Status Index), are available for preoperative risk assessment.
• The STOP-Bang (Snoring, Tiredness, Observed Apnea, High Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) risk score questionnaire for obstructive sleep apnea and RCRI have both been independently associated with MINS.³
• Incidence of PMI is much higher in patients with increased age, male sex, and pre-existing cardiovascular conditions such as coronary artery disease, heart failure, and atrial fibrillation.⁶
• Traditional risk factors for cardiovascular disease, such as diabetes mellitus, hypertension, and smoking, are each independently associated with increased risk of PMI.⁷
• Importantly, preoperative risk assessment can differ substantially from the postoperative likelihood of developing PMI, which is significantly affected by the surgical course and intraoperative events.⁵
  ● Please see the OA summary on preoperative cardiac risk stratification and evaluation for a detailed discussion of preoperative cardiac assessment. Link
  ● Please see the OA summary on acute coronary syndrome for preoperative medication management. Link

Triggers¹

• Hemodynamic changes
  • Surgical stimulation activates sympathetic tone, leading to increased circulating catecholamines (e.g., epinephrine and norepinephrine) and cortisol. This sympathetic upregulation precipitates tachycardia, which decreases the diastolic filling time of the heart. The resultant myocardial oxygen supply-demand mismatch provides a Type 2 PMI.
  • Intraoperative hypovolemia, resulting from surgical fluid shifts and/or bleeding independent of tachycardia, can decrease cardiac stroke volume and coronary perfusion. This reduction may create a myocardial oxygen supply-demand imbalance, leading to a Type 2 PMI.
  • Elevated catecholamine and cortisol levels can also result in hypertension. The associated increase in coronary artery shear stress may precipitate plaque fissuring and rupture, potentially contributing to a Type 1 PMI.
  • Diastolic hypotension resulting from decreased systemic vascular resistance due to deep anesthesia or fluid shifts can directly precipitate a myocardial oxygen supply-demand mismatch by reducing coronary perfusion pressure or indirectly contribute by triggering baroreceptor-mediated reflex tachycardia, ultimately resulting in a Type 2 PMI.
• Perioperative inflammation
  • Surgical stimulation can upregulate proinflammatory cytokines, including interleukin (IL)-1, IL-6, tumor necrosis factor-alpha, and C-reactive protein.
  • The consequent inflammation may directly contribute to plaque instability or indirectly lead to the aforementioned hemodynamic changes, thereby precipitating a Type 1 or Type 2 PMI, respectively.
• Hypercoagulable state
  • Surgical stimulation increases procoagulants (fibrinogen, factor VIII, von Willebrand factor, alpha1-anti-trypsin, and plasminogen activator inhibitor-1), while general anesthesia decreases anticoagulants (protein C and antithrombin III), increases platelet reactivity, and reduces fibrinolysis. This hypercoagulable state can precipitate a Type I PMI.
• Hypothermia
  • Hypothermia is defined as core body temperature below 35.0°C (95.0°F).
  • Intraoperative hypothermia can lead to stress hormone release with associated hemodynamic changes, as elucidated above, resulting in either Type I or Type 2 PMI.
  • Shivering from hypothermia may increase oxygen consumption, resulting in an oxygen supply-demand mismatch. This mismatch can precipitate a Type 2 PMI.
• Hypoxemia
  • Hypoxemia is defined as a reduction in arterial oxygen content.
  • Intraoperative hypoxemia can lead to a reflex increase in sympathetic tone. This results in hypoxia-induced tachycardia, thereby reducing diastolic filling time. This tachycardia decreases diastolic filling time and precipitates myocardial oxygen supply-demand mismatch, resulting in a Type 2 PMI.
  • Anemia
    If significant perioperative hemorrhage occurs, oxygen delivery decreases, precipitating a myocardial oxygen supply-demand mismatch and resulting in a Type 2 PMI.
  • Results from the Perioperative Ischemic Evaluation-2 (POISE-2) trial showed that major bleeding events were independent predictors of PMI.

Diagnosis and Management

Diagnostic Criteria

According to the Fourth Universal Definition of Myocardial Infarction:⁸

• Diagnostic criteria for Types 1-3 PMI include detection of a rise and/or fall of cTn values with at least one value above the 99th percentile URL and at least 1 of the following:
  • Symptoms of myocardial ischemia
  • New ischemic ECG changes
  • Development of pathologic Q waves
  • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
  • Identification of coronary thrombus by angiography or autopsy (not for types 2 or 3 MIs)
• Diagnostic criteria for Types 4 and 5 PMI within 48 hours of index procedure is arbitrarily defined as elevation of cTn values more than 5 times for type 4a MI and more than10 times for type 5 MI of the 99th percentile URL in patients with normal baseline cTn, or by more than 20% in those with elevated preoperative cTn values, plus at least 1 of the following:
  • New ischemic ECG changes (for type 4a only)
  • Development of new pathological Q waves
  • Imaging evidence of loss of viable myocardium that is presumed to be new and, in a pattern, consistent with an ischemic etiology
  • Angiographic findings consistent with a procedural flow-limiting complication such as coronary dissection, occlusion of a major epicardial artery or graft, side-branch occlusion-thrombus, disruption of collateral flow, or distal embolization.

Clinical Presentation

• PMI is often clinically silent secondary to perioperative amnesia, analgesia, and anesthesia, requiring evidence of ischemia from ECG and/or imaging abnormalities.^1,4
• Only about 14% of patients who experience PMI will report chest pain, and only about 53% of PMI patients will exhibit clinical signs of ischemia.⁵

Cardiac Biomarkers

• The biomarker cTn is commonly utilized to detect and diagnose PMI.^2,3,5
  • Serial cTn measurements are recommended for patients at elevated risk for MINS or PMI according to the Fourth Universal Definition of MI, or for high-risk patients with an RCRI ≥ 2.
  • Baseline preoperative cTn values should ideally be obtained for proper interpretation of postoperative cTn values.
  • Screening low-risk patients in the postoperative setting is not recommended due to cTn elevation associations with comorbidities unrelated to PMI, such as myocarditis, congestive heart failure, cardiac contusion, pulmonary embolism, chronic obstructive pulmonary disease, subarachnoid hemorrhage, and sepsis.
• Preoperative B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) may also be considered for high-risk patients, although these biomarkers require validation by prospective studies.

Electrocardiogram (ECG)

• The most common ECG findings in a patient with PMI after noncardiac surgery are T-wave inversions and ST-segment depressions, rather than elevations.^1,2

• In cardiac surgery, ST-segment elevations with reciprocal changes more reliably indicate acute PMI.⁹
• Recent evidence has identified distinct ECG patterns that potentially suggest occlusion myocardial infarction, or Type I PMI, in the setting of failure to meet the criteria for ST-segment elevation.¹⁰

• Ongoing studies may challenge the traditional STEMI/NSTEMI framework by considering a more precise occlusion-versus-non-occlusion MI model, thereby further elucidating the evaluation and management of acute PMI.
• Because ECG abnormalities are often transient, serial ECGs, along with cTn measurements, are integral to reliably identifying acute PMI.

Echocardiography

• Current evidence does not support routine echocardiography in low to intermediate risk patients both preoperatively and postoperatively.³
• Nevertheless, echocardiography should be considered to identify new regional wall motion abnormalities that would indicate PMI.⁶

Cardiac Magnetic Resonance Imaging (CMRI)⁹

• CMRI is infrequently used in the immediate postoperative period.
• Late gadolinium enhancement on CMR within 2 weeks of surgery correlates with cTn elevation, which is diagnostic of type 5 PMI.
• CMR is regarded as prognostically useful but not practical in the perioperative setting.

Treatment Guidelines from 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM2

• PMI management is an active area of investigation.
• A multi-disciplinary treatment approach, including surgeons, anesthesiologists, and cardiologists, is essential.
• Current practice favors nonoperative management over invasive management of PMI due to the common NSTEMI pattern in PMI.
• For Type I PMI, patients should receive guideline-directed medical therapy (GDMT) with strong consideration of invasive coronary angiography (ICA) based on clinical presentation and risk of bleeding or thrombosis.
  • GDMT includes antiplatelet agents, statins, beta-blockers, angiotensin-converting enzyme inhibitors, and nitrates, as tolerated, based on bleeding risk and overall clinical status.
• For Type II PMI, the underlying cause of the myocardial oxygen supply-demand mismatch (e.g., hemodynamic aberrations, anemia, hypoxemia, hypothermia) should be treated, along with optimization of GDMT in accordance with postoperative hemodynamic status.
  • Vigilant prevention and treatment of the PMI triggers that precipitate myocardial oxygen supply-demand mismatch are paramount.
  • Adequate perfusion pressure, optimal oxygen-carrying capacity and delivery, sufficient anesthesia and analgesia, and balanced fluid status will facilitate maintenance of hemodynamic control.

• Please see the OA summary on acute coronary syndrome for more details. Link
• The use of aspirin and statins may reduce 30-day mortality in patients with PMI, according to a post hoc analysis of the Perioperative Ischemic Evaluation (POISE) trial.
• Dabigatran 110 mg twice daily may benefit patients with PMI by decreasing composite risk of major vascular events.
• Antiplatelets and statin therapy have been beneficial in observational studies, though they require validation from prospective studies.

Treatment for Types 4 and 5 PMI⁹

• Mechanical circulatory support with an intra-aortic balloon pump or extracorporeal membrane oxygenation (ECMO) may be considered for patients with acute PMI, low cardiac output syndrome, or cardiac arrest.
• ICA is indicated for ongoing ischemia or hemodynamic compromise.
• Reoperation may be considered if concern for graft failure is high in a patient who is status postcoronary artery bypass graft surgery.