Myocardial Ischemia and Infarction

Mohammed M. Minhaj

John E. Ellis

CASE SUMMARY

A 56-year-old, 90-kg man presents for femoral-popliteal bypass surgery. He has a history of hypertension, diabetes, and hypercholesterolemia, for which he is on metoprolol, lisinopril, insulin, and atorvastatin. He also has a 30-pack-year smoking history. His preoperative laboratory values are normal, except for a hematocrit of 36%, creatinine of 1.6 mg per dL, and some nonspecific ST-T wave changes on his ECG.

After discussion with the patient and surgeon, it is decided to proceed with the case and administer the patient his prescribed metoprolol, atorvastatin, and one half his dose of insulin. During a general anesthetic, his blood pressure is often labile. He also requires two units of packed red blood cells due to loss of fluid volume and blood. Upon emergence, he is noted to be tachycardic, with a heart rate of 110 bpm, which is treated with esmolol.

In the recovery room, he is noted to have ST-T wave depressions on electrocardiogram (ECG) monitoring. A 12-lead ECG is obtained showing 1.5 mm ST-T depression on leads V1 through V3. He denies chest pain, and his vital signs are back to baseline values (150/85 mm Hg, heart rate 88 bpm). Five milligrams of intravenous metoprolol are administered with partial resolution of his ST-T depression. Serum troponin levels are sent to the laboratory, and a cardiologist is consulted. The patient subsequently rules in for an acute myocardial infarction (MI). Coronary angiography demonstrates an occluded left anterior descending artery, for which he is stented. He is placed on clopidogrel, as well as aspirin, and his preoperative medications are continued with increased doses. The rest of his hospitalization is unremarkable, and he is discharged on the seventh postoperative day.

What Is the Incidence and Epidemiologic Impact of Perioperative Cardiovascular Complications?

Cardiovascular disease continues to be the leading cause of death in the United States.¹ However, recent advances have decreased deaths related to heart disease, allowing many patients to live longer than in the past. As a consequence, more patients with a history of coronary artery disease (CAD) are presenting for noncardiac surgery. These patients are at increased risk for perioperative myocardial events. In fact, of the estimated 27 million patients undergoing noncardiac surgery in the United States each year, 1 million experience perioperative cardiac complications, ranging from congestive heart failure and MI to death, costing an estimated $20 billion.²,³ These risks are even greater in patients undergoing vascular procedures.⁴ Patients who suffer postoperative MI or death on average incur $15,000 to more than $20,000 in additional hospital costs due to prolonged hospitalizations, compared with similar patients who do not suffer MI, and are at increased risk for other noncardiac complications as well.⁵

The reduction of cardiac events in the perioperative period could potentially reduce cardiac (as well as overall) morbidity and mortality, in addition to decreasing hospital stay and overall costs. Attempts to improve the perioperative outcome of patients at risk for CAD have historically focused on three approaches: (i) preoperative identification of high-risk patients who may benefit from myocardial revascularization; (ii) improved detection of perioperative myocardial ischemia to allow for prompt therapeutic intervention; and (iii) the prophylactic use of anesthetic and anti-ischemic techniques to decrease the prevalence and severity of postoperative myocardial ischemia.

Recently, there has been considerable debate, not only over the level of preoperative assessment that is necessary for patients, but also the value of routine preoperative workups in patient populations at risk for perioperative myocardial insults. This chapter outlines some of the recent data regarding preoperative assessments and focuses on the perioperative management of these patients. The pathophysiology, demographics, and prognosis of postoperative myocardial ischemia and infarction in patients undergoing noncardiac surgery were also reviewed. In addition, patients with a history of myocardial revascularization, either by coronary stenting or angioplasty, or surgical intervention through coronary artery bypass grafts (CABG), merit special consideration in our anesthetic approach, and are discussed in detail in this chapter.

What Are the Preoperative Predictors for Cardiovascular Complications in the Perioperative Period?

Risk factors for perioperative cardiovascular complications may include diagnosed CAD, congestive heart failure, diabetes mellitus treated with insulin, peripheral vascular disease, advanced age, severely limited exercise tolerance, chronic renal insufficiency, uncontrolled hypertension, and left ventricular hypertrophy (LVH) (see Table 15.1).⁶ It should be noted that, although most of these overlap with the risks of having CAD, patients without any history of CAD are still at risk for perioperative cardiac complications. Obviously, patients with risk factors without documented CAD are at increased risk as well. Documented decompensated heart disease, such as arrhythmias, unstable angina, or congestive heart failure, places patients at a higher risk for adverse perioperative events.⁴

Multifactorial indices, such as Goldman’s index, have been proposed to risk stratify patients. The American Heart Association (AHA) with the American College of Cardiology (ACC) has published and revised extensive guidelines for preoperative evaluation based on the patient’s preexisting disease and the surgical intervention planned.⁷,⁸ Resting echocardiographic indicators (systolic dysfunction) may also have additive predictive value (above and beyond clinical risk factors) for perioperative MI in high-risk patients. Other recent studies, however, have questioned the benefits of aggressive preoperative workups (e.g., stress testing) and coronary revascularization before surgery in improving outcomes.⁹,¹⁰

Although preoperative testing is often not completely under the direction of anesthesiologists, and in emergency situations may not be possible, there are several perioperative factors associated with cardiac events that fall under our control: Tachycardia, anemia, hypothermia, shivering, hypoxemia, and pain. All these factors negatively affect the delicate balance between myocardial oxygen supply and demand, which can precipitate perioperative cardiac events.

TABLE 15.1 Risk Factors for Perioperative Cardiac Events

Coronary artery disease

Congestive heart failure

Diabetes mellitus

Renal insufficiency

Advanced age

Major surgery

Peripheral vascular disease

Hypertension

Severely limited exercise tolerance

Hypercholesterolemia

What Is the Overall Prognosis for Surgical Patients Who Suffer Myocardial Ischemia?

Postoperative myocardial ischemia confers the increased risk of morbidity and mortality for surgical patients. Additionally, making the diagnosis can be challenging because, oftentimes, angina may not be present (silent ischemia). In fact, it has been reported that up to 50% of MIs that occur perioperatively can be missed if physicians rely only on signs and symptoms.¹¹ Postoperative myocardial ischemia increases by ninefold the risk of an in-hospital morbid cardiac event. Landesberg found that patients with ischemia lasting more than 2 hours had a greater than 30-fold increased risk of morbid cardiac events.¹² They also found that postoperative MI is usually preceded (by more than 24 hours) by long periods of severe ST-segment depression. Patients with documented severe, postoperative myocardial ischemia or troponin elevations should be referred to a cardiologist after surgery because they are at high risk for adverse short-term and long-term cardiac outcomes.¹³ Perioperative MI is still associated with up to a 50% in-hospital mortality, and is a marker for a poor prognosis after discharge in those who survive.³,¹⁴,¹⁵

How Can Perioperative Myocardial Ischemia and Infarction Be Detected?

There are multiple methods that can be used for the detection of perioperative myocardial ischemia, each of which has its own advantages and disadvantages (see Table 15.2).

▪ ELECTROCARDIOGRAM

Myocardial ischemia is actually most common in the immediate postoperative period, usually on the day of surgery or the next day. The “silent” nature of postoperative ischemia suggests that frequent 12-lead ECG monitoring may be useful. Such a strategy may detect ischemia that is severe and protracted enough to represent a prodrome to infarction, and therefore attention can be focused on the period when MI is most likely to occur. Charlson et al. found that obtaining a 12-lead ECG on the day of surgery and the next 2 days was the best strategy for detecting perioperative ischemia and infarction.¹⁶ Unfortunately, approximately one fourth of vascular surgery patients at the highest risk of adverse perioperative events will have baseline ECG abnormalities (left bundle branch block, paced rhythm, digoxin effect, LVH with strain) that preclude the detection of myocardial ischemia.

TABLE 15.2 Monitoring Techniques for Perioperative Ischemia

Monitor	Advantages	Disadvantages
ECG (most commonly ST- or T-wave changes; also new onset left bundle branch block)	Inexpensive Readily available Easily understood	Baseline abnormalities obscure ischemia Electrocautery can interfere with intraoperative use
Pulmonary artery catheter (most sudden increases in wedge pressure/PA pressure; new V-waves)	Can also monitor volume status, cardiac output	Invasive Less sensitive than TEE/ECG for ischemia
TEE (most commonly regional wall motion abnormalities)	More sensitive than ECG/PAC Reliable monitor of volume as well	Invasive Difficult to continuously monitor Not well tolerated in awake patients
Laboratory values (CK-MB, troponin, etc.)	Specific for ischemia	Cannot obtain instantaneous results
ECG, electrocardiogram; PA, pulmonary artery; TEE, transesophageal echocardiography; PAC, pulmonary artery catheter.

▪ OTHER MODALITIES

In light of these limitations of ECG monitoring, other modalities for identifying myocardial ischemia have been presented as potentially beneficial in the perioperative period. These techniques include the use of pulmonary capillary wedge pressure tracings to detect v-waves, which have not been proved to be particularly sensitive or specific, and the monitoring for regional wall motion abnormalities with transesophageal echocardiography (TEE). These techniques, however, are not without their respective drawbacks either; for example, the predictive value of pulmonary capillary wedge pressure tracings for monitoring ischemia is rather poor.

Transesophageal Echocardiography

Although TEE, another monitoring tool, is extraordinarily sensitive for detecting regional wall motion abnormalities associated with ischemia (which occur before surface ECG changes), it is not practical for continuous monitoring.¹⁷ The correct use of TEE as a monitor requires a higher level of training and expertise.

Troponin Levels

With respect to laboratory values, troponin levels tend to be more specific in detecting perioperative MI than CKMB isoenzyme measurements; troponin elevations correlate with lower survival rates after vascular surgery.¹³,¹⁴ A recent study advocating the perioperative surveillance of troponin levels found that patients undergoing abdominal aortic surgery, who had abnormal but low troponin levels, were still at risk for MI and increased mortality.¹⁸ In patients undergoing CABG surgery, however, troponin levels may not be of diagnostic value in the immediate postoperative period, secondary to the nature of the surgical intervention itself.¹⁹

What Are the Proposed Mechanisms of Perioperative Myocardial Ischemia?

▪ ISCHEMIC SYNDROMES

Stable ischemic syndromes presumably occur because of the increased oxygen demand on the myocardium in the presence of fixed coronary plaques that reduce oxygen supply. Unstable syndromes are thought to be the result of endothelial dysfunction and inflammation, plaque rupture with local thrombus, and vasoreactivity that produces intermittent critical decreases in coronary oxygen supply.¹² Patients with elevated coronary calcium levels on computed tomography scan have greater rates of perioperative MI after vascular surgery.²⁰

Endothelial function is impaired in conditions such as CAD, hypertension, hypercholesterolemia, diabetes, and tobacco abuse, resulting in exaggerated vasoconstriction. Poor endothelial function is also associated with poor outcome after vascular surgery. The treatment used to “heal” the endothelium, often with agents designed to combat hypercholesterolemia such as the inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase or “statins”, improves perioperative outcome, although for therapy to be effective, it may have to begin weeks before surgery.²¹

▪ ST-SEGMENT LEVELS

In patients with LVH, diminished coronary vasodilator reserve results in poor subendocardial perfusion. Ischemia in the early postoperative period after noncardiac surgery typically correlates with ST-segment depression rather than ST elevation; ST-segment depression usually precedes postoperative cardiac complications. It is important
for the anesthesiologist to appreciate that most perioperative MIs are detected by the non-Q wave variety, although MIs identified by ST elevation can also occur and are associated with a higher mortality rate.

▪ TACHYCARDIA AND HYPOTENSION

The postoperative period is characterized by adrenergic stress, which can induce myocardial ischemia in patients with CAD, cause coronary vasoconstriction, and facilitate platelet aggregation.¹² Tachycardia not only increases oxygen demand, but limits diastolic time and coronary perfusion to the left ventricle, and it can paradoxically reduce coronary artery diameter. Hypertension and tachycardia in the postanesthesia care unit (PACU) have been shown in a large study to correlate with increased mortality and unplanned intensive care unit (ICU) admissions (although association does not necessarily mean causation).²²

▪ SURGICAL STRESS

In addition, surgery itself causes significant changes to the hematologic system. Surgical stress can induce a hypercoaguable response as a result of increased platelet number and function, diminished fibrinolysis, decreases in natural anticoagulants (including protein C and antithrombin III), and increases in procoagulants (including fibrinogen, factor VIII coagulant, and von Willebrand factor).²³ These postoperative changes may contribute to an increased likelihood of coronary artery thrombosis or rupture of preexisting coronary plaques in the postoperative period; however, their relative importance in predicting postoperative coronary events remains speculative.

Does Pharmacologic Prophylaxis Work?

Cardiologists and internists are increasingly using aggressive, long-term pharmacologic means to reduce risk in patients with CAD (Table 15.2). These strategies include cholesterol reduction with statin agents, which stabilize coronary plaques; antihypertensive therapy with angiotensin-converting enzyme (ACE) inhibitors, which also reduce sympathetic tone; β-adrenergic-blocking drugs for decreasing myocardial workload; and strict glucose control in diabetics. These treatments, although improving patient symptoms, quality of life, and prolonging lifespan, require the anesthesiologist to consult with the patient’s surgeon and primary physician to ensure that, perioperatively, medications are continued as necessary. Many of these treatments have demonstrated not only benefits for patients on a daily basis, but also in the acute perioperative setting and will be discussed in this chapter.

More emphasis is being placed on the aggressive management of these patients throughout the perioperative period. There are several classes of pharmacologic agents that have enabled patients with CAD to enjoy not only a longer lifespan, but also a better quality of life. These agents may play vital roles in the prophylaxis against perioperative ischemia, as well as in its treatment (see Table 15.3). It is imperative for the anesthesiologist to determine which of the agents that a patient is taking should be continued through the perioperative period and which may be initiated to facilitate the patient’s anesthetic.

What Is the Role of β-Blockers and Other Antianginal Agents in Reducing Adverse Cardiac Events?

▪ β-BLOCKERS

β adrenergic-blocking drugs, through their ability to suppress perioperative tachycardia, appear most efficacious clinically and economically in preventing perioperative myocardial ischemia.²⁴,²⁵,²⁶,²⁷,²⁸ They are well tolerated by most surgical patients and may reduce long-term cardiac events. β adrenergic-blocking drugs have been approved for the treatment of hypertension, supraventricular tachycardias, ventricular arrhythmias, angina, and MI. They are the cornerstone of acute and chronic post-MI therapy and are recommended by the AHA, as they are thought to reduce episodes of reinfarction.⁸

The antihypertensive effects of β-blockers can be very useful during adrenergic activation such as occurs in endotracheal intubation, extubation, electroconvulsive therapy (ECT), and sternotomy. They also blunt tachycardia during these events, which is likely the predominant mechanism of their anti-ischemic effects.

Several trials that document the ability of β-blockers to improve perioperative cardiac outcomes have been published, although recent trials have questioned this conclusion in certain patient populations, notably diabetics.²⁹ A recent meta-analysis of several randomized, controlled trials demonstrated that perioperative β-blockade reduced myocardial ischemia and infarction, as well as short-term and long-term cardiac mortality.²⁸ Another retrospective study examining a large cohort of patients found that perioperative β-blockers reduced the risk of in-hospital death among high-risk patients, but not low-risk patients, undergoing major noncardiac surgery.²⁷ The benefit in outcome from perioperative blockade in high-risk patients may persist for up to 2 years after vascular surgery.²⁴

There are, however, several limitations to consider when using perioperative β-adrenergic blockade. β1 selective drugs are less likely to cause bronchospasm, even in patients with reactive airway disease. Nevertheless, asthma and chronic obstructive pulmonary disease are relative contraindications to β-blockade. Additionally,
there is a very small subset of patients with severe CAD (markedly positive stress tests in multivessel distributions) in whom β-blockade or medical management has not reduced cardiac events, but rather may be considered candidates for myocardial revascularization.³⁰

TABLE 15.3 Pharmacologic Agent Actions that May Have Benefit with Respect to Myocardial Ischemia

Agent	Potential Role	Drawbacks	Perioperative Recommendation
β-adrenergic blockers	Benefit in reducing myocardial ischemia by reducing myocardial work; also demonstrated reduced perioperative morbidity and mortality in patients with CAD	Caution with use in patients with underlying chronic lung disease, as can lead to bronchoconstriction	Continue throughout perioperative period
Antiplatelet agents	Aspirin decreases platelet activity and is beneficial in acute coronary ischemia and for chronic management	May contribute to perioperative bleeding and be contraindication to regional anesthetic techniques	Continue aspirin through day of surgery Clopidrogel and ticlopidine should be held 7 d before surgery
Statins	Reduce cholesterol levels and progression of atherosclerosis, and are plaque-stabilizing	Most perioperative data is retrospective; may cause hepatic side effects	Continue throughout perioperative period; check liver function tests preoperatively
Volatile anesthetics	Theoretic benefit of myocardial preconditioning that may limit ischemic damage if it occurs	Mostly animal data with minimal human studies demonstrate benefit	Useful if general anesthesia is chosen
α₂ agonists	Reduce norepinephrine release and intraoperative ischemia	Data on newer agent dexmedetomidine lacking for perioperative ischemia prevention	Continue clonidine through perioperative period
ACE inhibitors	Potential for plaque stabilization after MI Decrease remodeling of left ventricle post MI	Data not well established for benefit; may be associated with profound hypotension after induction of general anesthesia	Debatable; some withhold morning of surgery, whereas others continue it throughout
CAD, coronary artery disease; MI, myocardial infarction; ACE, angiotensin converting enzyme.

Although the validity of the data regarding the use of perioperative β-blockers has recently been questioned, their use is still advocated in most patients.⁸,³¹,³² Most of the debate around the purported evidence is in regard to the factors used in the individual studies such as power, analysis, or exclusion criteria. There is a large, multicenter, randomized, double-blinded, placebo-controlled, prospective study being undertaken that should elucidate more information on the benefits of perioperative β-blockade.³² Given that the vast majority of the evidence is favorable, the use of β-blockers in the perioperative period is currently widely advocated.

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