A Stepwise strategy for coronary risk assessment for noncardiac surgery

CONTEMPORARY ISSUES IN CARDIOLOGY

0025-7125/95 $0.00

+ .20

A STEPWISE STRATEGY FOR CORONARY RISK ASSESSMENT FOR NONCARDIAC SURGERY Sumita D. Paul, MD, MPH, and Kim A. Eagle, MD

Patients undergoing noncardiac surgery are often at high risk for developing early postoperative and late cardiac complications. s, 50, 53, 72, 105 To identify patients who may do poorly after surgery, it is important to perform a careful preoperative clinical evaluation. In this article, a stepwise strategy is suggested for preoperative risk assessment for patients undergoing noncardiac surgery (Fig. 1) based on previous work of the authors and that of others. Such a stepwise approach to risk stratification includes the following: 1. Determine if the patient has undergone prior coronary revascularization. 2. Determine if the patient has had a prior coronary evaluation over the past several years. 3. Assess preoperative clinical risk of the patient. 4. Assess the patient's functional capacity. 5. Determine the pretest probability of cardiac complications for a patient based on the type of surgery and the institutional experience. 6. Assess whether the pretest probability is likely to be altered based on stress testing. 7. For truly elective surgery, weigh the benefits (of the operation) against the posttest probability of cardiac complications after surgery. 8. Determine if there are opportunities to reduce the posttest probability of cardiac complications after surgery by modifying preoperative or intra operative care. 9. Use growing knowledge regarding the physiology of the postoperative stress response and its relationship to postoperative cardiac complications in developing strategies to minimize postoperative complications.

From the Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts (SDP); and the Department of Cardiology, University of Michigan Medical Center, Ann Arbor, Michigan (KAE) MEDICAL CLINICS OF NORTH AMERICA VOLUME 79' NUMBER 5 • SEPTEMBER 1995

1241

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PAUL & EAGLE Clinical Algorithm

No

t

recurrent

LIP~ri~or~C=Qr~o~na~ry=r~etv=a=sc~u=la~riz~a~tiQ=n~?IL-________~sy~m~p~ro~m~s..... no Clinical Assessment

No

yes

I Previous coronary evaluation within 2 years? I

Adequate eval'n (ETT &Jar Cath)

...

Further

yes • Favorable result ~ , - - - - - , Clinical Status' r-,:-,----:-:-.,---,------:-".,---:1

• No d in status

needed

17"~

Low < 5 METS

MOderate-High 5-10 METS

,

Superb> 10 METS

Figure 1. Strategy for preoperative risk-assessment for patients undergoing noncardiac surgery. + = Angina, MI by history or ECG (Q waves), CHF (or VT), DM; t = uncontrolled angina, uncontrolled CHF, angina or CHF after recent MI; = moderate or high-risk surgery-vascular, thoracic, major abdominal, orthopedic; + + = low-risk surgery-head and neck, eye, prostate, hernia, breast. 0

10. Use careful postoperative surveillance and identification of nonfatal cardiac events and modifiable coronary risk factors to tailor long-term therapy and follow-up. STEP 1: IMPORTANCE OF PRIOR CORONARY REVASCULARIZATION

There is firm epidemiologic evidence of a high postoperative cardiac risk and limited long-term survival among patients with preoperative clinical evidence of coronary artery disease_ s, 50, 53, 72, 105 The risk conferred by prior manifest coronary disease varies depending on the study population and the severity of symptoms and was found to be 4% in one study" and as high as 50% in anotherY Several large retrospective studies have suggested protection against postoperative cardiac complications and improved 5-year survival after noncardiac surgery in patients who have had prior coronary artery bypass grafting (CABG) (Table 1). In a series of 1000 patients who underwent coronary angiogra-

Table 1. IMPACT OF PRIOR CORONARY BYPASS SURGERY ON EARLY AND LATE DEATH AFTER NONCARDIAC SURGERY Author

N*

Hertzer et ai, 19845°, 198651

251t

Foster et ai, 198633 Reul et ai, 1986'°3

Acinapura et ai, 1987'

14,180 1093

42

Prior Coronary Artery Bypass Graft Yes: 216 (CABG mortality 5.5%) No: 35 Yes: 1237 No: 1337 (patients with CAD) No: 1782 (patients without eviden-ce of CAD) Yes: 255 simultaneous with vascular surgery Yes: 279 during same admission as vascular surgery Yes: 559 had preoperative CABG then vascular surgery on separate admission Yes: 20+ (7-10 days preoperatively)

'Total sample size. tNumber of patients with severe, correctable coronary artery disease. :j:Number of patients with triple-vessel disease or left main disease. CABG = Coronary artery bypass grafting; CAD = coronary artery disease.

,....

IV ~ (.,J

Postoperative Death (%)

Late Death (%)

2 12 1.5 6.8 1.3 4 4 0.2

12 26 21 41 20

None

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PAUL & EAGLE

phy while under consideration for elective vascular surgery at the Cleveland Clinic Foundation, 251 patients were found to have severe correctable coronary artery disease. Among these patients, 216 underwent CABG with an operative mortality of 5.5%. Among the 200 patients who subsequently underwent vascular surgery, however, there were only three (1.5%) deaths. 51 In addition, during a mean follow-up of 4.6 years, Hertzer and colleagues51 found that cardiac deaths (including the operative mortality of CABG) occurred in 12% of the 216 who had undergone preoperative coronary revascularization. For patients who survived the immediate mortality of CASG, the long-term prognosis was near that of patients without coronary artery disease. Similarly the patients enrolled in the Coronary Artery Surgery Study (CASS) Registry33 who underwent CABG before noncardiac surgery had a lower mortality (0.9%) when compared with patients who were randomized to medical therapy before noncardiac surgery (2.3%). CABG was associated with a mortality rate of 2.3%, however. Further evidence for the prophylactic role of coronary revascularization comes from a retrospective analysis of 1093 patients who underwent peripheral vascular surgery in addition to CASG between 1976 through 1984. '03 As shown in Table 1, the postoperative mortality rates were extremely low for these patients. Furthermore, in a small series of 42 patients with abdominal aortic aneurysms who underwent coronary angiography, there were no perioperative cardiac events among the 20 patients with triple-vessel disease or left main disease, who underwent coronary revascularization 7 to 10 days before aneurysmectomy.' In a cohort of 68 patients with prior CABG and 499 without prior CASG who underwent vascular surgery,9? patients who had prior CASG had significantly fewer cardiac events: 1 (1.5%) versus 45 (9%) (P <0.0001) (Fig. 2). Patients were then retrospectively classified based on the number of clinical markers, including a history of angina, myocardial infarction, Q waves on the electrocardiogram (ECG), or history of congestive heart failure. Among patients who did not have a history of prior CABG, the risk of postoperative cardiac events (nonfatal myocardial infarction or cardiac death) increased sequentially with increased number of clinical markers from 5% to 27% (P <0.0003). Although patients with prior CABG had more clinical markers of risk when compared with the no CASG group, CABG patients had significantly fewer events. Thus, as shown in Figure 2, there is compelling evidence that prior coronary • Event 0 No Event No Prior CABG (N=499) 95 92 85 76

Prior CABG (N=68) 100 100 96 100

100

73

27

o

.:.

0 0 0 0 34 01234 Number of Clinical Markers

Figure 2. Study of 68 patients with prior CABG and 499 without prior CABG who underwent vascular surgery. (From Paul SO, L'ltalien GJ, Hendel RC, et al: Influence of prior heart disease on morbidity and mortality after vascular surgery: Role of coronary artery bypass grafting. J Am Coli Cardial 1A:484A, 1994; reprinted with permission from the American College of Cardiology.)

A STEPWISE STRATEGY FOR CORONARY RISK ASSESSMENT

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revascularization confers protection against perioperative cardiac events. Obviously, if the patient has redeveloped coronary symptoms after bypass surgery or if the operation was more than 5 to 10 years previous, further evaluation may be important. Otherwise, such patients would not require further preoperative testing. STEP 2: CORONARY EVALUATION OVER THE PAST SEVERAL YEARS

If the patient has not undergone prior coronary revascularization, it is useful to determine if an adequate stress test or coronary angiography was performed within the recent past. If such testing revealed favorable results and there has been no change in the patient's clinical status since the testing was performed, retesting is usually not required. If the patient has not undergone stress testing or coronary angiography in the past several years or if the clinical status has changed since the last examination, further evaluation may be useful. STEP 3: PREOPERATIVE CLINICAL RISK ASSESSMENT

The preoperative history and physical examination are both important components of risk evaluation before noncardiac surgery. The history helps to determine if the patient has congenital heart disease, rheumatic heart disease, arrhythmias, prior heart failure, and a history of myocardial infarction or angina (or both). In addition, a thorough physical examination should seek to identify evidence of jugular venous distention, carotid bruits, cardiomegaly, a third heart sound, murmurs indicating valvular disease, and peripheral edema. Previous studies have demonstrated the value of several clinical risk indices for risk prediction. 4,24, 25, 26, 43, 44 These indices have combined various clinical features associated with poor prognosis into composite scores to help quantitate the risk for postoperative events. The Dripps-American Society of Anesthesiologists (ASA) index classified patients into classes I to V (ranging from normal healthy patients; those with mild, severe, or incapacitating systemic disease; to moribund patients who were not expected to survive more than 24 hours with or without an operation).4, 26 Although this index has been validated in large numbers of patients, it is quite subjective and provides only a general sense of postoperative risk. Subsequently the index developed by Goldman and colleagues43,44 allowed determination of a weighted score for each patient based on the presence of certain preoperative clinical markers. Using a stepwise discriminant analysis, they identified the following markers of poor prognosis: a history of a myocardial infarction within the previous 6 months; age greater than 70 years; physical examination revealing evidence of valvular aortic stenosis or jugular venous distention, a third heart sound or a combination; a preoperative ECG showing evidence of a rhythm other than sinus or premature atrial contractions or the presence of greater than five premature ventricular contractions at any time before surgery; poor general status with poor oxygenation or abnormal liver or kidney function tests; and surgery that was performed emergently or was intraperitoneal, intrathoracic, or aortic. A score was assigned depending on the presence or absence of each marker, and patients were subgrouped into classes I to IV based on the aggregate score. With progression from risk class I to

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PAUL & EAGLE

IV, there was a step wise increase in the proportion of patients with cardiac complications. The Goldman index, however, proved cumbersome for routine use by many clinicians and surprisingly did not include the variables angina pectoris or history of congestive heart failure. Detsky and coworkers 24 ,25 subsequently modified and simplified the scoring system of the Goldman index and added angina and prior congestive heart failure to address these shortcomings, Both indices, however, have been shown to have a low sensitivity for identifying high-risk patients in an intermediate-risk range, To provide clinicians with a simplified approach to preoperative risk stratification, Eagle and colleagues 27,28 proposed and validated an index comprised of five clinical markers that clinicians can easily remember (Table 2), Patients with none of these clinical markers have been classified in to the lower clinical risk group. Those with one or two markers are at intermediate risk, and those with more than two markers are at high clinical risk. In their initial study of 61 patients,28 of the 29 low-risk patients, only one had postoperative angina, and none had a nonfatal myocardial infarction or cardiac death, This was validated in an additional 50 patients. In a subsequent study involving 200 patients, only 2 of the 64 patients at low clinical risk had a postoperative cardiac event (neither had a nonfatal myocardial infarction or died), The 20 patients at high clinical risk, however, had a 50'1'0 risk of cardiac events. 27 The utility of such a clinical evaluation has been confirmed by other investigations, IS, 67 More recently, based on the Cleveland Clinic experience,"" the authors have demonstrated a concordance between risk defined clinically and the severity of coronary stenosis defined by coronary angiography in a large cohort of patients undergoing coronary angiography routinely before elective vascular surgery (Fig. 3). This study provided an anatomic validation of the preoperative clinical risk index that was originally proposed by Eagle and colleagues. 27 Importantly the absence of a history of angina, myocardial infarction, congestive heart failure, or diabetes was associated with a negative predictive value of 96% for severe triple-vessel or left main disease in patients undergoing elective vascular surgery at the Cleveland Clinic Foundation, Thus, it is the intermediate-risk group for which there is the greatest uncertainty regarding severity of coronary stenoses, This intermediate-risk group may particularly benefit from further noninvasive testing as detailed subsequently. As shown in step 3 of the algorithm (see Fig, 1), patients who lack these clinical markers usually require no further workup. Such patients are at low clinical risk for perioperative events. Patients who have unstable clinical status are considered to be at high clinical risk and should be considered for coronary angiography if they are appropriate candidates for coronary revascularization. Markers of unstable clinical status include uncontrolled or new angina; uncontrolled or new congestive heart failure; or angina, congestive heart failure, or

Table 2. EAGLE INDEX Age> 70 years Angina Prior myocardial infarction By history By ECG-Q wave Diabetes mellitus Congestive heart failure

.ANG (+) l:I\~

,s .....

&;...

83

*

*p
DANG (-)

*

~~

Left Main

Triple Vessel

*

,71 * 50

'\'5~

:§~

.I!!;:a c:~

4

~~ ~:!l!

LOW n= 466

INT 324

HIGH 66

I

14

I

LOW HIGH 466 86

Risk Group By Clinical Index

LOW HIGH 466 66

Figure 3. Concordance of clinical risk with coronary angiography in patients undergoing vascular surgery. Ang (+) refers to the presence of stenoses identified by coronary angiography, defined as triple vessel (2: 50% stenosis in each vessel), 2 vessel (2: 50% stenosis in one vessel when the other is 2: 70% stenosis of the left anterior descending), or left main disease (2: 50% stenosis). (From Paul SD, Eagle KA, Kuntz KM, et al: Concordance of a validated clinical risk index with coronary angiography prior to vascular surgery (VAS): The Cleveland Clinic (CCF) experience. Circulation 90:1-95A, Copyright 1994 American Heart Association; with permission.)

electrical instability after recent myocardial infarction. Patients who have clinical markers stated previously but do not have an unstable clinical status should have an evaluation of their functional status. STEP 4: EVALUATION OF FUNCTIONAL CAPACITY BY HISTORY FOR PATIENTS AT INTERMEDIATE CLINICAL RISK

The determination of the patient's functional capacity has been documented in numerous studies to be of value in assessing cardiac risk before noncardiac surgery.5, 15. 21, 36. 3~, 4h. ('6, 77, 83, 115 Patients with poor functional capacity have a significantly higher risk of suffering postoperative cardiac complications. The history obtained during the preoperative clinical evaluation of the patient should therefore provide an assessment of functional capacity. This can be achieved by classifying patients according to the Specific Activity Scale (Table 3).45 Patients who are in class III or IV on the Specific Activity Scale have a low functional capacity of less than 5 metabolic equivalents (METS) and may benefit from further risk stratification even if perioperative risk based on surgical type is low. Patients who are in class I or II have moderate-to-high functional capacity (greater than or equal to 7 METS and 2: 5 but not 2: 7 METS and generally would not require further workup if the surgical risk type is low. A small fraction of patients may have superb functional capacity. These include patients who regularly run long distances or participate in organized fitness programs. Such patients often have a functional capacity exceeding 10 METS and have a low risk of perioperative cardiac events regardless of surgical type. STEP 5: DETERMINATION OF THE PRETEST PROBABILITY OF CARDIAC COMPLICATIONS BASED ON SURGICAL TYPE

The pretest probability of cardiac complications after noncardiac surgery also depends on the specific type of surgery. Those who need emergency surgery are at higher risk (fourfold to fivefold greater) than those undergoing elective surgery.43,44 In addition, patients undergoing aortic, intrathoracic, or intraperitoneal surgery have a relatively high pretest probability (nearly twofold to three-

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Table 3. SPECIFIC ACTIVITY SCALE: CORRELATION OF ACTIVITIES OF DAILY LIVING AND ENERGY REQUIRED Class

II

III

IV

Patient Can Perform to Completion Activity requiring 2::7 metabolic equivalents (METS) Carry 24 Ib up 8 steps arry objects that weigh 80 Ib Outdoor work (shovel snow, spade soil) Recreation (ski, basketball, squash, handball, jog/walk 5 mph) Activity requiring 2::5 (but not 2::7) METS Have sexual intercourse without stopping Walk at 4 mph on level ground Outdoor work (garden, rake, weed) Recreation (roller skate, dance fox trot) Activity requiring 2::2 (but not 2::5) METS Shower/dress without stopping, strip and make bed Walk at 2.5 mph on level ground Outdoor work (clean windows) Recreation (play golf, bowl) No activity requiring 2::2 METS (cannot carry out activities listed above)

Adapted from Goldman L, Hashimoto B, Cook EF, et al: Comparitive reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new specific activity scale. Circulation 64:1227, Copyright 1981 American Heart Association; with permission; Paul SD, Eagle KA: Evaluation of patients for noncardiac surgery. In Willerson JT, Cohn IN (eds): Textbook of Cardiovascular Medicine. New York, Churchill-Livingstone, 1994; with permission.

fold) of postoperative cardiac complications"3, H largely caused by the high incidence of concomitant coronary artery disease.5() Detsky and colleagues 24,25 have found that the highest postoperative cardiac complication rates were seen for patients undergoing peripheral vascular surgery or orthopedic surgery (more than 13%»), followed by thoracic and abdominal surgery (8%), and the lowest among patients undergoing head and neck, ophthalmologic, or prostate surgery (less than 3')';»). Others have also confirmed the higher cardiac complication rate seen after vascular surgery.b, 35, 73 Among patients undergoing vascular surgery, the risks for postoperative events have been found to be independent of the type of vascular surgery (peripheral vascular surgery versus aortic surgery). Although infrainguinal patients exhibited more than twice the risk for perioperative myocardial infarction compared to aortic surgery patients (relative risk of 2.4, P <0.0008), this was found to be insignificant after adjustment for comorbid factors?" Backer and colleagues/ in a retrospective study at the Mayo Clinic involving patients undergoing ophthalmologic surgery under local anesthesia or retrobulbar block, have documented the absence of recurrent myocardial infarction or death after 195 surgeries. Thus, as shown in Figure 1, patients at intermediate clinical risk who are undergoing a low-risk procedure do not require further noninvasive testing unless they have a poor functional capacity (class III or IV on the Specific Activity Scale). STEP 6: WILL THE PRETEST PROBABILITY BE ALTERED BASED ON FURTHER NONINVASIVE TESTING?

Although certain types of noncardiac surgery are associated with a high risk of postoperative and long-term cardiac complications, performing noninvasive testing or coronary angiography on a large proportion of patients undergoing

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vascular or other types of surgery would increase health care costs tremendously and might unnecessarily expose a group of patients to the potential risks of invasive diagnostic study. Furthermore, with advances in anesthetic and surgical techniques, modern-day noncardiac surgery is associated with a low rate of serious cardiac complications. The strategy proposed by Eagle and colleagues 27 provides a rational approach to selecting patients who may benefit from further testing. Patients classified as low clinical risk generally do not need any further risk stratification. Those in the high clinical risk group have a high probability of triple-vessel disease or left main disease and deserve individual consideration for a more aggressive approach, including, in selected patients, preoperative coronary angiography and coronary revascularization before noncardiac surgery. The intermediate clinical risk group may benefit the most from noninvasive testing. As shown in Figure 1, unless the patient has a superb functional capacity or has a low surgical risk with moderate-to-high functional capacity, one should consider noninvasive testing for patients classified as intermediate clinical risk who have not previously been evaluated. The goal of noninvasive testing includes an accurate quantitation of the patient's functional capacity (and therefore cardiac reserve) as well as the identification of inducible ischemia. In addition, many types of tests allow an assessment of left ventricular function. Several noninvasive techniques that are currently in practice are described next. Exercise Stress Testing Without Perfusion Imaging

Numerous studies have examined the role of exercise stress testing for preoperative assessment of the presence and degree of inducible ischemia and functional capacity.5. 15. 21, 36, 39, 46, 66, 77, 83, 115 Most studies using preoperative exercise testing excluded unstable patients. These were patients who had a recent myocardial infarction, unstable angina, congestive heart failure, or significant ventricular arrhythmias. In a cohort of 100 patients undergoing vascular surgery, McPhail and colleagues83 examined the utility of preoperative exercise testing (60% underwent the standard Bruce protocol, and the remaining 40% underwent arm ergometry). Of the 30 patients who were able to achieve greater than 85% of predicted maximum heart rate (PMHR), only 2 (6%) had a postoperative cardiac complication compared with 17 (24%) who were unable to achieve 85°/', of PMHR. The combination of exercise-induced ischemia and a low workload was associated with the highest cardiac complication rate of 33%. Cutler and colleagues21 have also documented the importance of exercise capacity in their study of 130 patients who underwent exercise treadmill testing before vascular surgery. None of the patients who were able to achieve greater than 75'Yo of PMHR suffered a postoperative cardiac complication. Patients who had inducible ischemia at low workloads «75% of PMHR) were found to have the greatest risk of cardiac complications (10 of 26 or 38% with 5 deaths). Six of 23 (26%) patients who had ischemia at a high workload, however, had a cardiac complication (no deaths). Thus the ability to achieve 75% or 85% of the PMHR or, more importantly, to achieve a high workload (METS) during exercise has been correlated with a low risk of postoperative cardiac events. Furthermore, when poor functional capacity is associated with ischemia identified by electrocardiographic stress testing, risk of postoperative death or myocardial infarction increases dramatically. Ischemia in patients who have excellent functional capacity, however, appears to confer only a small increase in risk. Although the treadmill or bicycle exercise stress test can provide invaluable information, its utility for the preoperative assessment of the patient awaiting

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noncardiac surgery is often limited, usually because the operative condition or other comorbid condition precludes exercise testing. Also, the presence of nonspecific ST-T wave abnormalities on the baseline ECG limits the interpretability of ST-T changes identified during stress testing. In such instances, the addition of perfusion imaging or wall motion analysis appears to improve the diagnostic yield of electrocardiographic stress testing for assessing for ischemia and perioperative risk as detailed subsequently. Exercise Stress Testing with Perfusion Imaging

When nuclear imaging is added to the electrocardiographic response to exercise, the sensitivity for identifying subsequent cardiac events is enhanced. 41 • Rh. Illh Furthermore, imaging with thallium or sestamibi isotope can help quantify the amount of myocardium at risk for coronary ischemia by identifying the number of segments or regions with perfusion defects, which has important predictive value. h1 • h9 Nuclear imaging with thallium may also identify exerciseinduced left ventricular dysfunction by transient ventricular dilatation, which correlates with a greater likelihood of cardiac complications."" Pharmacologic Stress Testing with Perfusion Imaging

Dipyridamole-thallium imaging has been the most widely used method of pharmacologic stress testing before noncardiac surgery. Dipyridamole acts by inhibiting the reuptake of adenosine by the endothelium and red blood cells. 2• hO Through its vasodilating properties, myocardial regions that are hypoperfused owing to obstructive coronary disease can be identified. s4 The utility of preoperative dipyridamole-thallium imaging for risk stratification before noncardiac surgery was first defined by Boucher and colleagues." Numerous other studies have confirmed that thallium redistribution on dipyridamole-thallium testing is associated with an increased risk of perioperative cardiac events. 27 • 2H. 68. HO More recently, Lane and colleagues 63 as well as Levinson and colleagues 6Y have described the usefulness of semiquantitation of dipyridamole-thallium scintigraphy in assessing cardiovascular risk. Increasing numbers of regions of thallium redistribution were associated with increasing risk of cardiac complications. Patients with multiple thallium defects are likely to have multi vessel disease and are at the greatest risk for cardiac complications. Although initial studies identified thallium redistribution only to be independent predictors of postoperative cardiac complications,'l' 63. 68. 69 fixed thallium defects have since been recognized also to be of prognostic value, particularly for late cardiac complications. 14• 18. 55. 65 Fixed defects may represent scars from prior infarcts and as such serve as markers of left ventricular dysfunction or severely ischemic myocardium with underlying fixed stenosis. Finally, Coley and colleague SIB as well as Brown and colleagues '4 have shown the potential value of dipyridamole-thallium testing to evaluate cardiac risk in patients undergoing nonvascular surgery. Thus, numerous studies have documented the usefulness of preoperative dipyridamole-thallium imaging with sensitivity and specificity for identifying coronary artery disease similar to exercise thallium testing. 55. 65 Because the overall risk of perioperative cardiac death or myocardial infarction is low with present-day surgical and anesthetic approaches, however, the positive predictive value of dipyridamole-thallium for untoward outcomes is generally less than

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20%.116 Furthermore, there have been several reports of dipyridamole-thallium testing being associated with poor sensitivity and specificity when used for preoperative risk stratification?4,76 Failure to apply testing in intermediate-risk or high-risk patients and to quantitate the degree of test abnormality may explain, at least in part, these observations, Pharmacologic Stress Testing with Echocardiography

There has been increasing experience with dobutamine stress echocardiography. The development of regional wall motion abnormalities or loss of myocardial thickening has been documented to be a sign of advanced coronary artery disease with a sensitivity of nearly 90'% for identifying a 50% or greater stenosis in one or more coronary arteries.109 In one study of 93 patients who underwent dobutamine echocardiography before vascular surgery, 23 patients were found to develop new wall motion abnormalities during the test. 23 Of the 23 patients with ischemia on stress testing, 19 underwent coronary angiography, of whom 13 were revascularized for significant coronary artery disease. One out of 13 patients who underwent coronary revascularization had a postoperative cardiac event compared with 4 out of 10 patients who did not undergo coronary revascularization (including myocardial infarction in 2 and death in 1). The wall motion abnormalities were more severe among patients who suffered a postoperative cardiac event. Patients who had a negative dobutamine stress study had no postoperative cardiac events. A normal dobutamine echocardiogram was also found to have long-term prognostic significance. These results have been confirmed by Langan and colleagues 64 in their study of 81 patients who underwent dobutamine stress echocardiography before infrarenal aortic surgery. None of the 56 patients who had a normal study or resting wall motion abnormalities without dobutamine-induced ischemia had a postoperative cardiac complication. Of the 25 with dobutamine-induced ischemia, however, 4 underwent CABG (2 of them subsequently died), and 5 had surgery deferred. Of the remaining 16 who underwent surgery, 3 suffered a postoperative myocardial infarction. In another study involving 75 patients undergoing major vascular surgery,29 preoperative dobutamine stress echocardiography was found to have a sensitivity of 100% as well as a negative predictive value of 100'1'0; however, the specificity was 69°;;" and the positive predictive value was only 19%. Similarly, studies done by Poldermans,98 Lalka/1 and Lane 62 and their colleagues have also demonstrated the clinical utility of preoperative dobutamine stress echocardiography. In contrast to dobutamine echocardiography, there are relatively few data on the utility of dipyridamole echocardiography or adenosine echocardiography for preoperative risk stratification?5, 112 Further study is needed to determine the sensitivity, specificity, and predictive accuracy before these modalities can be recommended for widespread usage. With the increasing availability of dobutamine stress echocardiography, it becomes important to understand the relative benefits and disadvantages of echocardiography when compared with perfusion imaging as a method for identifying the presence of ischemia. One advantage for using echo cardiography for the detection of ischemia is that this modality can provide additional information regarding valvular abnormalities and left ventricular dysfunction. This method, however, may be less useful in patients with resting wall motion abnormalities, in whom delineating ischemia from scar is especially challenging.

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Additionally, dobutamine infusion is generally avoided in patients with a history of significant arrhythmias. Dipyridamole stress testing with perfusion imaging may have the advantage of allowing a more accurate quantitation of the size of the ischemic zone. The disadvantages, however, are its potential to induce bronchospasm, making it ill advised in patients with asthma or bronchospasm associated with chronic obstructive pulmonary disease. Dipyridamole's tendency to cause hypotension also makes it less desirable in patients with critical carotid stenosis. Finally the published experience of the use of dipyridamole myocardial perfusion imaging is relatively much greater than that of dobutamine stress echocardiography to assess cardiac risk before noncardiac surgery. Assessment of Left Ventricular Function

Although initial studies suggested that a resting ejection fraction of 35% or less measured by radionuclide angiography was an important predictor of perioperative myocardial infarction in patients undergoing vascular surgery,57. 85.89.02 others have not been able to confirm these results. 34 • 5h. 58. 79. 80 Patients with severe coronary artery disease who have not had a prior myocardial infarction may have a normal resting left ventricular ejection fraction. After accounting for functional capacity or coronary ischemia, the left ventricular ejection fraction was not found to be an independent predictor of postoperative cardiac events. STEP 7: WEIGHING THE BENEFITS OF ELECTIVE SURGERY AGAINST THE POSTTEST PROBABILITY OF CARDIAC COMPLICATIONS

After risk assessment has been completed, the consultant, surgeon, and anesthesiologist must decide whether the risk for postoperative cardiac events is acceptably low to warrant proceeding with the surgery. For patients at high cardiac risk who are not appropriate candidates for coronary revascularization, the decision is often difficult. This may result in canceling a truly elective procedure or doing a less extensive procedure. Once the decision to proceed with noncardiac surgery has been made, the next decision point is whether cardiac risk can be modified by additional therapies, including selective coronary revascuIarization in high-risk individuals. The increased risk of cardiac complications for patients with severe coronary disease has to be weighed against the periprocedural complication rate of CABG (or percutaneous transluminal coronary angioplasty [PTCAj), especially in patients who have peripheral vascular disease. STEP 8: REDUCE THE POSTTEST PROBABILITY OF CARDIAC COMPLICATIONS AFTER SURGERY BY MODIFYING PREOPERATIVE OR INTRAOPERATIVE CARE

Preoperative coronary revascularization has been proposed as a strategy for reducing the posttest probability of cardiac complications. I. 30. 33. 51. 52. 54. 97. 10.1 A lack of randomized trials examining the role of preoperative CABG for this purpose, however, leaves clinicians reliant on the accumulated knowledge regarding the role of CABG for patients with coronary artery disease regardless of patients' presentation for noncardiac surgery.20. 37. 38. ]13 CABG is indicated for

A STEPWISE STRATEGY FOR CORONARY RISK ASSESSMENT

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ischemia inadequately controlled by medical therapy or for survival advantage in patients with left main disease or severe triple-vessel disease, especially in those with poor left ventricular function. If such patients can be identified during the preoperative period and they have acceptable CABG risk, it is reasonable to proceed with preoperative CABG. Although there are convincing data from nonrandomized trials suggesting a long-term mortality benefit for prophylactic CABG in high-risk subsets,L 33. 51. 97.103 the role of preoperative PTCA is less clear.3. 30. 52. 54 In a Mayo Clinic study,52 involving 55 patients with severe coronary artery disease who underwent PTCA before noncardiac surgery, 5 (n;,) patients required emergent CABG after unsuccessful PTCA. Even among those in whom PTCA was successful, three (5%) patients had an acute myocardial infarction in the postoperative period, and one died. Another study examined 110 patients who underwent PTCA before major vascular surgery.54 Three patients required emergent CABG because PTCA was unsuccessful, and four had procedure-related non-Q wave infarctions. There were three postoperative nonfatal myocardial infarctions and one death. Finally, Elmore and colleagues 30 retrospectively analyzed a cohort of 2452 patients who underwent abdominal aortic aneurysmorrhaphy at the Mayo Clinic between 1980 and 1990. Among this large cohort of patients, only 14 had preoperative PTCA and 86 had a prior CABG. Perioperative mortality was 5.8% in the CABG group and 0 in the prior PTCA group. Of PTCA patients, however, 57% had late cardiac events compared with 27'1'0 of CABG patients. It is difficult to make any general recommendations for prophylactic PTCA based on these data because the accumulated experience is so limited. Thus, at present insufficient data exist to define the appropriate role of prophylactic PTCA to reduce the incidence of postoperative cardiac complications. The type of anesthesia used has not been found to play a significant role in the development of postoperative cardiac complications. n . 81. 82 In one study, 100 patients undergoing elective vascular surgery were randomized to receive either epidural anesthesia followed by epidural analgesia or general anesthesia followed by intravenous patient-controlled analgesia. '7 Management of anesthesia was standardized. There were no significant differences in the rates of perioperative and 6-month complications between the two groups. Because general anesthetics have a negative inotropic action, however, spinal anesthesia may be a preferred choice for patients with severe left ventricular dysfunction or a history of congestive heart failure. Goldman and colleagues,"4 in their study of 1001 patients undergoing noncardiac surgery, found that 4.3% of patients who received general anesthetics developed new congestive heart failure, and 22'1'0 had a worsening of preexisting failure. Patients who received spinal or epidural anesthesia did not develop such symptoms. The use of perioperative hemodynamic monitoring with pulmonary artery catheters has been implicated as part of improved surgical techniques and decreasing surgical mortality.44 Rao and colleagues"12 have reported an improvement of perioperative outcomes in patients who had hemodynamic monitoring while undergoing noncardiac surgery soon after an acute myocardial infarction. Using historical controls, they were able to demonstrate a reduction in the reinfarction rate from 1977 through 1982, when hemodynamic monitoring was used, as compared with the rate from 1973 through 1976, when monitoring was not used. Although there is evidence that such monitoring may be valuable in patients with limited ventricular reserve, there is little to recommend it for the purposes of monitoring for ischemia.

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STEP 9: UNDERSTANDING THE PATHOPHYSIOLOGY OF THE POSTOPERATIVE PERIOD AND ATTEMPTING TO MODIFY IT

Prior studies have reported the existence of a postoperative fibrinolytic shutdown. 59 , 71, 88, 94, 108, 1J4 Vermylen and Chamone l14 have found that the impairment of the fibrinolytic system was associated with postoperative venous thrombosis. Others have found a postoperative surge in catecholamine levels after noncardiac surgeryY' 12, 13, 47, 99, 104, 107 An increased pro thrombotic tendency or these changes in catecholamines (or both) may be associated with postoperative cardiac events. Although the exact mechanism of the postoperative catecholamine surge is not clear, it is possible that this is a physiologic response to pain. Anesthetic agents such as high-dose fentanyl that block afferent pain signals tend to blunt postoperative catecholamine surges. l1O It has also been suggested that epidural anesthesia blocks the catecholamine surges after surgery by decreasing afferent pain signals,31 although Riles and colleagues 104 have not confirmed these findings. The pathophysiologic significance of these postoperative neurohumoral changes is intriguing. Three potential mechanisms by which catecholamine surges could result in perioperative myocardial ischemia include lO an increase in myocardial oxygen demand owing to catecholamine-induced increases in heart rate and blood pressure, a decrease in myocardial oxygen supply owing to catecholamine-mediated stimulation of alpha 1-adrenergic receptors resulting in coronary vasoconstriction, and a postoperative prothrombotic milieu. The use of alpha2-adrenergic agonists in the perioperative period as an adjunct to anesthesia has been suggested to be beneficial in several studies,32, 40, 48 resulting in less intraoperative hypertension and tachycardia. In addition, Flacke and colleagues32 have shown that the use of clonidine could blunt the catecholamine response to surgery. Although the use of clonidine appears to be mechanistic ally justified to prevent catecholamine-mediated myocardial oxygen supply-demand imbalances, the impact of alpha 2-adrenergic agonists on postoperative myocardial ischemia is as yet undefined. Further indirect evidence of the role of postoperative neurohumoral changes in the pathogenesis of myocardial ischemia comes from the beneficial effects of perioperative use of beta-blockers in reducing cardiac complications (Table 4). In a cohort of 128 patients undergoing abdominal, peripheral, or vascular surgery, Stone and colleagues l l l randomly assigned patients to four groups: (1) control group that received no pretreatment with beta-blockers or groups that received a single oral dose of (2) 100 mg of labetalol, (3) 50 mg of atenolol, or (4) 20 mg of oxprenolol, 2 hours before the induction of anesthesia. Of the 39 patients in the control group, 11 (28%) developed myocardial ischemia compared with 2 out of 89 (2%) patients who received a single dose of any of the beta-blockers. In two subsequent studies performed by Pasternack and colleagues,90,91 the role of perioperative beta-blockers was examined. In their initial study,'!o 48 patients undergoing vascular surgery received 50 mg of metoprolol immediately before surgery and were compared with a comparable group of 152 patients who did not receive metoprolol. Patients receiving metoprolol had significantly fewer number of episodes of ischemia as well as less total duration of ischemia. In their subsequent study,91 a group of 32 patients undergoing vascular surgery received 50 mg of oral metoprolol immediately before surgery, 10 to 15 mg given intravenously on arrival to the recovery room and subsequently continued

Table 4. IMPACT OF ANTI-ISCHEMIC MEDICATIONS ON PERIOPERATIVE MYOCARDIAL ISCHEMIA IN NONCARDIAC SURGERY Author

Medication

Modality of Ischemic Detection

Type of Surgery

No. of Patients

Stone" 1

Oral beta-blockers

Pasternack 90

Oral metoprolol

Continuous lead V? or oscilloscope with intermittent paper recordings Holter monitor

Pasternack 91

Oral metoprolol

Holter monitor

Abdominal aortic aneurysm

83

Godet42

Intravenous diltiazem Intravenous nitroglycerin

Holter monitor

Vascular

30

Holter monitor

Abdominal and vascular

45

Coriat '9

Comment

Abdominal and vascular

128

13 of 128 had ischemia; 2 of 89 treated patients vs. 11 of 39 untreated

Vascular

200

48 treated patients, 152 untreated (historical controls); treatment resu Ited in twofold to th reefold decrease in ischemic episodes and duration of ischemia 10 of 83 head M I; 1 of 32 treated patients vs. 9 of 51 untreated (historical controls) 17 of 83 had ischemia; 6 of 15 treated patients vs. 11 of 15 untreated 18 of 45 had ischemia; 14 of 22 on 0.5 j.Lg/kg/min vs. 4 of 23 on 1.0 j.Lg/kg/ min

Adapted from Abraham SA, Coles NA, Coley CM, et al: Coronary risk of noncardiac surgery. Progress in Cardiovascular Diseases 34:205-234, 1991; with permission.

>-'

N \Il \Il

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every 12 hours for 5 days. These 32 patients were then compared with a group of 51 matched historical controls undergoing similar surgery. Among the betablocker group, only one (3%) patient had a perioperative myocardial infarction compared with nine (18%) in the control group not on beta-blockers (P <0.05). Thus, although there have not been any large-scale randomized trials for the perioperative use of beta-blockers, the accumulated body of evidence to date suggests a beneficial effect. Few data exist to support, however, the perioperative utility of calcium channel42 blockers and nitroglycerin. 19 Observations regarding perioperative catecholamine surges become even more relevant in the clinical setting because numerous investigators have linked perioperative myocardial ischemia to poor postoperative and long-term cardiac prognosis. 73, 78, 87, 89, lOO, 101 In a cohort of 474 men undergoing noncardiac surgery, Mangano and colleagues 73 found postoperative ischemia to be present in 41 % of monitored patients and associated with a 9.2-fold increase in the odds of an ischemic cardiac event (95% confidence interval, 2-42, P <0.004). By multivariate analysis, other preoperative clinical variables and the occurrence of ischemia before or during surgery were not found to be independent predictors of ischemic cardiac events, These findings were validated by Raby and colleagues,lOD who documented a relative risk of 16 for developing postoperative cardiac events among patients with postoperative ischemia. The authors generally recommend the use of perioperative invasive hemodynamic monitoring for all moderate-risk to high-risk patients undergoing vascular surgery, Ischemia monitoring should also be considered for such patients beginning immediately after surgery and continuing for at least 48 hours after surgery. For high-risk patients, the authors recommend the use of beta-blockers if there are no contraindications. These should be initiated the day before surgery if not earlier. Care should be taken to avoid anemia and hypovolemia. In addition, for the high-risk patient, the use of anticoagulation with heparin or antiplatelet agents such as aspirin should be considered depending on the bleeding risk. STEP 10: LONG-TERM RISK STRATIFICATION

Both preoperative clinical evaluation to determine evidence of coronary artery disease, left ventricular dysfunction, or diabetes mellitus and noninvasive testing for evidence of poor functional capacity, evidence of inducible ischemia, or ejection fraction have been found to be valuable for long-term risk stratification for patients undergoing noncardiac surgery.22, 49, 95, 177 Thus, care of the patient after surgery should involve assessing for and treating modifiable cardiac risk factors, including hypertension, hyperlipidemia, smoking, obesity, and inactivity. In addition, the development of nonfatal cardiac complications during the perioperative period are predictive of late cardiac events l6, 73, 95 (in a sense, this is similar to a positive stress test, the stress being surgery). Cheney and colleagues l6 have found that perioperative myocardial infarction was an important harbinger of future cardiac events, In a cohort of 1864 consecutive patients undergoing vascular surgery, they identified 103 patients who sustained a perioperative myocardial infarction. Over a mean follow-up period of 32 months, there were significantly more deaths among those who had experienced a perioperative infarct when compared with matched controls (50% versus 22%, P <0.0001), in addition to a higher incidence of late myocardial infarction (23% versus 12%, P <0.05). Thus, identification of patients prone to develop

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perioperative myocardial infarction may have long-range implications for efforts to prevent late cardiac morbidity and mortality. The authors have previously shown95 that unstable angina during the perioperative period is an important predictor of subsequent poor outcomes. In addition, Mangano and colleagues 73 have identified postoperative myocardial ischemia to be one of the most important predictors of subsequent cardiac events. Thus, an aggressive approach is recommended for patients who have suffered a perioperative nonfatal cardiac event. Such an approach begins with beta-blockers and aspirin with subsequent evaluation by coronary angiography in selected instances. Further studies are needed to determine the optimal strategy of management of such patients. For the present, the authors suggest individual consideration of high-risk patients for coronary revascularization on a subsequent admission (to avoid the postoperative prothrombotic milieu along with the catecholamine surges seen after surgery). SUMMARY

Physicians should adapt a systematic approach to cardiac risk stratification for patients being considered for noncardiac surgery, involving clinical evaluation, functional assessment, and surgical risk assessment for all patients and then deciding which patient needs to undergo noninvasive testing, coronary angiography and revascularization, perioperative monitoring, and aggressive postoperative care. References 1. Acinapura AJ, Rose DM, Kramer MD, et al: Role of coronary angiography and coronary artery bypass surgery prior to abdominal aortic aneurysmectomy. J Cardiovasc Surg 28:552, 1987 la. Abraham SA, Coles NA, Coley CM, et al: Coronary risk of noncardiac surgery. Program in Cardiovascular Diseases 34:205-234, 1991 2. Alfonso S, O'Brien GS: Mechanism of enhancement of adenosine action by dipyridamole and lidoflazine in dogs. Arch Int Pharmacodyn Ther 194:181, 1971 3. Alien JR, Hellino- TS, Hartzler GO: Operative procedures not involving the heart after percutaneous transluminal coronary angioplasty. Surg Gynecol Obstet 173:285, 1991 4. American Society of Anesthesiologists: New classification of physical status. Anesthesiology 24:111, 1963 5. Arous EI, Baum PL, Cutler BS: The ischemic exercise test in patients with peripheral vascular disease: Implications for management. Arch Surg 119:780, 1984 6. Ashton CM, Petersen NI, Wray NP, et al: The incidence of perioperative myocardial infarction in men undergoing noncardiac surgery. Ann Intern Med 118:504, 1993 7. Backer CL, Tinker JH, Robertson DM, et al: Myocardial reinfarction following local anesthesia for ophthalmic surgery. Anesth Analg 59:257, 1980 8. Blombery P A, Ferguson lA, Rosengarten DS, et al: The role of coronary artery disease in complications of abdominal aortic aneurysm surgery. Surgery 101:150, 1987 9. Boucher CA, Brewster DC, Darling RC, et al: Determination of cardiac risk by dipyridamole-thallium imaging before peripheral vascular surgery. N Engl J Med 312:389, 1985 10. Breslow MJ: The role of stress hormones in perioperative myocardial ischemia. Int Anesth Clin 1:100, 1992 11. Breslow MJ, Jordan DA, Christopherson R, et al: Epidural morphine decreases postoperative hypertension by attenuating sympathetic nervous system hyperactivity. JAMA 261:3577, 1989 12. Brismar B, Hedenstierna G, Lundh R, et al: Oxygen uptake, plasma catecholamines,

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Address reprint requests to Sumita D. Paul, MD, MPH Massachusetts General Hospital Cardiac Unit, Ellison Room #908 Boston, MA 02114