Cardiac Events in Patients Undergoing Noncardiac Surgery: Shifting the Paradigm from Noninvasive Risk Stratification to Therapy

Internists and cardiologists are often asked to estimate the risk for perioperative myocardial infarction or cardiac death in patients for whom noncardiac surgery is planned. Estimating this risk in an individual patient is difficult and complex. Although two position papers on this topic have been published (by the American College of Cardiology/American Heart Association [ACC/AHA] in 1996 [1] and by the American College of Physicians [ACP] in 1997 [2, 3]), new data have emerged that prompt reconsideration of this issue, particularly from the standpoint of perioperative therapy. We review the issues on perioperative risk stratification, as well as therapies to prevent myocardial infarction and cardiac death. Magnitude of the Problem Almost 30 million patients undergo noncardiac surgery annually in the United States (4); about one third have known coronary artery disease or risk factors for atherosclerosis. The 500 000 patients who undergo peripheral vascular procedures each year are thought to have a particularly high risk for perioperative cardiac events (5). However, recent data suggest that perioperative mortality is declining, particularly for carotid endarterectomy (6-8). Of 68 631 major operations performed in the Veterans Administration system from 1991 to 1997, 30-day mortality was only 3.2% and most deaths were noncardiac (6). Mortality was 4.7% for abdominal aortic aneurysm repair and 1.2% for carotid endarterectomy. Among 45 744 carotid endarterectomies performed in Florida under Medicare from 1992 to 1996, mortality was only 0.8% (8). Technical advances in vascular surgery, such as endoluminal stenting, may further reduce perioperative risk in selected patients (9, 10). Pathophysiology of Perioperative Cardiac Complications The pathophysiology of perioperative myocardial infarction differs somewhat from that of myocardial infarction occurring in the usual setting. In the latter, rupture of a coronary arterial atherosclerotic plaque leads to platelet aggregation and thrombus formation (11). In contrast, plaque rupture occurs in only about half of perioperative myocardial infarctions (12, 13); the remainder are due to a prolonged imbalance between myocardial oxygen supply and demand in the setting of coronary artery disease. Myocardial oxygen supply may be diminished by anemia or hypotension, whereas oxygen demand may be increased by tachycardia and hypertension resulting from postoperative pain, withdrawal of anesthesia, or shifts in intravascular volume. Perioperative myocardial infarction usually occurs 1 to 4 days after surgery (14-16), when the effects of anesthesia have dissipated and perioperative pain and fluid shifts are occurring. Issues in Risk Stratification The goal of risk stratification is to reduce risk (17). First, any test used for preoperative risk stratification must be accurate. It should have a high positive and negative predictive value and should result in a change in risk from the pretest likelihood. Since predictive values depend on event rate, likelihood ratios should be calculated. The likelihood ratio of a positive or negative test result should be greater than 10 or less than 0.2, respectively, because these values indicate a substantial change in risk from the pretest level (2). The test should provide information that adds or is complementary to known risk variables. Second, risk stratification is most helpful when it influences outcome. For example, would a test lead to cancellation of surgery or alternative treatment? Would it mandate therapy to reduce perioperative risk, such as prophylactic coronary revascularization? Finally, the harmsbenefit tradeoff of risk stratification must be favorable. For example, routine preoperative imaging tests may lead to an adverse outcome by delaying needed surgery. Each clinical risk index or diagnostic test should be evaluated with these critical elements in mind (Table 1). Table 1. Critical Elements for Risk Stratification in Patients Undergoing Noncardiac Surgery Risk Stratification by Clinical Variables Cardiac Risk Index The original cardiac risk index (18) was described in 1001 patients undergoing general, orthopedic, or urologic procedures. Subsequently, this index was modified and then tested in another clinical setting in blinded fashion in patients undergoing vascular or general surgery (19). Eagle and colleagues (20) proposed a simple clinical risk index that, although widely used, has not been tested prospectively in another clinical setting. Lee and colleagues (21) described the largest and most current scheme of clinical risk assessment, the revised cardiac risk index. After identifying the following six variables in 2893 patients, they tested them in another clinical setting in 1422 patients: high-risk surgical procedure, history of ischemic heart disease (excluding previous coronary revascularization), history of heart failure, history of stroke or transient ischemic attack, preoperative insulin therapy, and preoperative serum creatinine levels greater than 152.5 mol/L (>2.0 mg/dL). By receiver-operating characteristic curve analysis, the revised cardiac risk index was superior to the original and modified cardiac risk indices. We recommend the revised cardiac risk index (Table 2) for clinical risk evaluation because of its simplicity, strength of study design, and superior receiver-operating characteristic curve analysis. Table 2. Major Cardiac Event Rates by the Revised Cardiac Risk Index Does Clinical Risk Stratification Satisfy the Critical Elements? Is it accurate? Yes. The receiver-operating characteristic curve area greater than 0.8 indicates that the revised cardiac risk index is accurate in segregating patient risk groups. Does it add to pretest knowledge? Yes. Is the harmsbenefit tradeoff favorable? Yes. The revised cardiac risk index is derived inexpensively from the history, physical examination, and serum creatinine level. Risk Stratification by Diagnostic Testing For diagnostic testing to be useful in risk stratification, it should provide information that adds or is complementary to that provided by the revised cardiac risk index. Furthermore, diagnostic testing should not lead to unnecessary additional testing or harmful delays in surgery (22-25). Finally, diagnostic testing ideally should lead to proven therapy to reduce risk. Myocardial Perfusion Imaging Myocardial perfusion imaging, performed at rest and during vasodilator stress, is widely used. Since many patients referred for vascular surgery cannot ambulate effectively because of claudication, their histories may not provide an accurate assessment of symptoms or functional class. Patients with reversible or fixed perfusion defects probably have coronary artery disease, the main risk factor for perioperative cardiac events. Most patients do not develop chest pain or ST-segment depression during vasodilator stress (26). However, they have impaired vasodilator reserve in areas subtended by a stenosed coronary artery, leading to heterogeneity in radionuclide activity in different segments of myocardium. Thus, perfusion imaging is sensitive for detecting coronary artery disease, not ischemia (27). Table 3 lists large studies of myocardial perfusion imaging in which likelihood ratios could be calculated from the published data (20, 28-37). Table 3. Studies of Vasodilator Stress Nuclear Perfusion Imaging for Risk Stratification Does This Test Satisfy the Critical Elements? Is it accurate? No. The positive likelihood ratio is low. The negative likelihood ratio is good in some studies but poor in others. Two large prospective, blinded studies showed that myocardial perfusion imaging did not provide independent prognostic value beyond clinical risk stratification (34, 39). Does it influence outcome? No published prospective trials have addressed this question. Is the harmsbenefit tradeoff favorable? No. Patients with positive test results often are subjected to further evaluation, such as coronary angiography. Such a strategy is costly and may delay surgery unnecessarily. Dobutamine Stress Echocardiography Dobutamine stress echocardiography (DSE) allows a physician to evaluate left ventricular regional wall motion at rest and during dobutamine stress. It provides an adrenergic stimulus that is more similar physiologically to the stress of the perioperative period than that provided by vasodilators. Dobutamine stress echocardiography is widely available and portable and does not involve radiation exposure. Since an adequate cardiac workload is not always achieved with dobutamine alone, atropine or handgrip exercise may be used with dobutamine to ensure an adequate increase in heart rate and systemic arterial pressure (38, 39). Table 4 lists large studies that have evaluated the use of DSE for risk stratification for patients undergoing noncardiac surgery (40-43). Table 4. Studies of Dobutamine Stress Echocardiography for Risk Stratification Does This Test Satisfy the Critical Elements? Is it accurate? No. The likelihood ratio of a positive test result is poor. The negative likelihood ratio is good in all but one study. A recent large study (43) showed that DSE did not add incremental value in low- or medium-risk patients (score of 0 to 2 on the revised cardiac risk index). Does it influence outcome? No studies have addressed this prospectively. Is the harmsbenefit tradeoff favorable? No. Dobutamine stress echocardiography has a low positive predictive value. Patients with positive test results are often subjected to further evaluation, which may cause an unnecessary delay in noncardiac surgery. Coronary Angiography Coronary angiography is not recommended for risk stratification in patients undergoing noncardiac surgery (1-3). However, patients considered for noncardiac surgery who have an indication for angiography independent of the planned surgery should undergo angiography, such as those with acute coronary syndromes or angina refractory to medical