Cardiac Assessment Prior to Vascular Surgery: Is Dipyridamole-Sestamibi Necessary?

Papers Presented at the Southern California

Vascular Surgical Society Cardiac Assessment Prior to Vascular Surgery: Is Dipyridamole- Sestamibi Necessary? Christian de Virgilio, MD, Sang Pak, MD, Tracey Arnell, MD, Carlos Donayre, MD, Roger J. Lewis, MD, PhD, Bruce E. Stabile, MD, and Rodney White, MD, Torrance, California

Dipyridamole-sestamibi (PMIBI) is recommended prior to vascular surgery in patients with ->1 Eagle criteria (Q waves, history of ventricular ectopy, diabetes, advanced age, and/or angina). To review our cardiac morbidity and mortality and the need for preoperative PMIBI, we reviewed 109 consecutive patients with a mean age of 59 years who underwent 145 elective major vascular procedures over a 1-year period. Seventy patients (with a mean of 0.8 Eagle criteria) underwent 92 vascular procedures without preoperative PMIBI and without coronary revascularization. Thirty-one patients (with a mean of 1.1 Eagle criteria) underwent 39 procedures without coronary revascularization following PMIBI, which showed reversible ischemia in seven and a fixed defect in 10; findings were normal in 14. Preoperative coronary bypass or angioptasty was limited to eight patients (14 procedures, mean of 1.6 Eagle criteria) who had unstable angina with (2 patients) or without (6 patients) acute myocardial infarction. There were four perioperative myocardial infarctions (2.8%), seven cardiac events overall (4.8%), and one cardiac death (0.7%). Three (43%) of the seven cardiac events occurred in patients with a normal scan or fixed defect on PMIBI imaging. In the absence of unstable angina, PMIBI had a sensitivity of only 25% and a specificity of 80% for cardiac events. We conclude that among patients without severe cardiac symptoms (1) PMIBI has a very limited ability to identify patients at risk for cardiac complications, and (2) preoperative PMIBI is neither necessary nor cost-effective. (Ann Vasc Surg 1996; 10:325-329.)

The role of nuclear cardiac imaging prior to major elective vascular surgery remains controversial. The use of dipyridamole-thallium (PTHAL) or dipyridamole-sestamibi (PMIBI) to detect and correct coronary artery disease prior to vascular sur-

From the Departments of Surgery (C,d.V., S.P., T.A., C.D. B.E.S., and R.W.) and Emergency Medicine (R.J.L.), HarborUCLA Medical Center, Torrance, Calif. Supported in part by a grant from the Harbor-UCLA Medical Center Research and Education Institute. Presented at the Fourteenth Annual Meeting of the Southern California Vascular Surgical Society, September 15-17, 1995, La JolIa, Calif. Reprint requests: Chrktian de Virgilio, MD, Harbor-UCLA Medical Center, Department of Surgery, Division of Vascular Surgery, Box 25, I000 W. Carson St., Torrance, CA 90509.

gery is theoretically appealing, inasmuch as cardiac complications are the cause of significant morbidity and mortality. Numerous studies have recommended PTHAL or PMIBI as the best noninvasive screening test to detect coronary artery disease. ~-5 However, others have questioned the predictive potential of PTHAL, 6'7 as well as its costeffectiveness.8 The purpose of this study was to evaluate the efficacy of PMIBI prior to vascular surgery in relation to perioperative cardiac morbidity and mortality during a l-year period.

PATIENTS AND METHODS MI patients who underwent elective major vascular reconstruction at Harbor-UCLA Medical Cen325

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T a b l e I. Distribution of vascular procedures Type of procedure

Group 1

Group 2

Group 3

Total

Femorodistal Aortoiliac occlusive Carotid Aortic aneurysm Extra-anatomic Renal

57 9 10 7 6 3

19 6 5 4 4 1

6 5 3 0 0 0

82 20 t8 11 l0 4

92

39

14

145

Table II. Cardiac risk factors Risk factor Tobacco Hypertension Male sex Diabetes History of myocardial infarction Q wave on ECG Age >70 yr Angina Congestive heart failure

Renal insufficiency Ventricular arrhythmia

No. (%) 79 70 63 54 27 20 15 14 7

(72) (64) (58) (50) (25) (18) (14) (13) (6)

7 (6) 1 ( 1)

ter from January 1994 to January 1995 were retrospectively reviewed. Patients needing emergency surgery (i.e., required immediately to prevent loss of life or limb) were excluded from the study, as were trauma patients. Procedures performed under local anesthesia (e.g., arterial embolectomy) were excluded as well. There were 109 patients (68 men and 41 women) with a m e a n age of 59 years who underwent 145 elective vascular procedures (Table I). Cardiac risk factors for each patient were recorded (Table II) including the Eagle criteria (diabetes, age >70 years, Q wave on ECG, angina, and ventricular dysrhythmia requiring treatment). Each patient was given a score ranging from 0 to 5 based on how m a n y Eagle criteria they met. PMIBI imaging was performed as previously described. 8 For the purpose of analysis, patients were divided into three groups. Patients in group 1 (n = 70, 64%) underwent vascular reconstruction without preoperative PMIBI and without preoperative coronary revascularization. Patients in group 2 (n = 31, 28%) underwent preoperative PMIBI imaging but did not undergo coronary revascularization, even if the PMIBI scan showed reversible ischemia. None of the patients in group 1

or 2 had severe, recent-onset cardiac symptoms (unstable angina or myocardial infarction [MI] within 6 months). Patients in group 3 (n = 8, 7%) all underwent preoperative percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) within 6 months prior to vascular surgery for unstable angina with (2 patients) or without (6 patients) acute MI. Postoperative MI was defined as a creatinine kinase MB fraction that was elevated to >5%, the development of a new Q wave on ECG, or persistent changes in the ST-T wave. 6 A cardiac arrest was considered to be of primary cardiac origin if it was the result of a primary cardiac event (acute MI, dysrhythmia, or congestive heart failure). Cardiac death was defined as death from dysrhythmia or congestive heart failure caused primarily by a cardiac complication. 6 Categorical variables were examined for associations by means of chi-square or Fisher's exact tests where appropriate. Continuous variables were compared using the Wilcoxon rank-sum test or the Kmskal-Wallis test where appropriate. A m a x i m u m p value of 0.05 was considered statistically significant and no adjustment was made for multiple comparisons. M1 statistical comparisons were performed using the SAS statistical software package (SAS Institute, Cary, N.C.).

RESULTS Patient risk factors are summarized in Table II. The Eagle criteria that were present, in descending order of frequency, included diabetes (50%), Q wave on ECG (18%), advanced age (14%), angina (13%), and ventricular arrhythmia (1%). Overall, the patients had a mean of 0.96 (median 1.0) Eagle criteria. Group 1 (70 patients, 92 vascular procedures) did not undergo preoperative PMIBI imaging. They had a mean of 0.8 Eagle criteria. Group 2 (31 patients, 38 procedures) had a mean of 1.1 Eagle

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Table III. Perioperative myocardial infarction and cardiac event rate by group Group

No. of procedures

Mean No. of Eagle criteria

No. of MIs (%)

1

92 39 14

0.8 1.1 1.6

2 (2.2)

3 (3.3)

2 (5.1) 0

3 (7.7%) 1 (7.1%)

2 3

Table IV. Predictive value of PMIBI for cardiac events

( + ) CE ( - ) CE

( + ) PMIBI

( - ) PMIBI

1 9

3 36

CE = cardiac events. Sensitivity, 25%; specificity, 80%; ( + ) predictive value, 10%; ( - ) predictive value, 92%.

T a b l e V. Predictive value of PMIBI for myocardial infarction

(+) MI ( - ) MI

( + ) PMIBI

( - ) PMIBI

0 10

2 37

Sensitivity, 0%; specificity, 79%; ( + ) predictive value, 0%; ( - ) predictive value, 95%.

criteria. Preoperative PMIBI scans were normal in 16 but showed reversible ischemia in eight and a fixed defect in seven. Of the eight patients in group 2 with reversible ischemia, three underwent preoperative coronary arteriography, which showed >50% coronary artery stenosis in one, two, and four vessels, respectively. None of the patients in group 1 or 2 underwent preoperative PTCA or CABG, and none had unstable angina or a recent MI. Group 3 (8 patients, 14 procedures) had a mean of 1.6 Eagle criteria. All patients in group 3 underwent preoperative CABG (6 patients) or PTCA (2 patients) for unstable angina with (2 patients) or without (6 patients) acute MI. Three patients in group 3 underwent PMIBI imaging prior to CABG or PTCA, and the scans demonstrated reversible ischemia in all of them. Following coronary revascularization, five patients in group 3 underwent PMIBI imaging, and all demonstrated fixed defects. In comparing groups I, 2, and 3 with regard to the various clinical risk factors, statistical differences were noted in the mean number of Eagle criteria (0.8, 1.1, and 1.6,

Total cardiac events (%)

respectively; p < 0.005) and in the percentage with a history of MI ( 11%, 33%, and 64%, respectively; p < 0.001). There were four cases of acute perioperative MI (2.8%) among the 145 vascular procedures, all of which were nonfatal. Three MIs were non-Q wave (2.1%) and one was Q wave (0.7%). Three patients suffered cardiac arrest as a result of primary dysrhythmias (2.1%), and one of them died. It should be noted that two of the MIs occurred in association with other physiologic abnormalities (acute gastrointestinal bleeding and acute hypoxia) and two of the cardiac arrests occurred while the patients were under anesthesia. The overall cardiac event rate (including MI, cardiac arrest, and cardiac death) was 4.9% (0% for 0 Eagle criteria, 7.5% for _1 Eagle criteria, p = 0.05). The cardiac death rate was 0.7%. The cardiac event rates by group are shown in Table III. There was no statistical difference in cardiac event rates between the groups. However, because the groups differed with regard to the mean number of Eagle criteria and the percentage with a history of MI, this finding must be interpreted with caution. Three (43%) of the seven cardiac events occurred in patients with a normal or fixed defect on PMIBI imaging. The sensitivity and specificity of PMIBI (in the absence of unstable angina) for perioperative cardiac events was 25% and 80%, respectively. The positive and negative predictive values were 10% and 92%, respectively (Table IV). The predictive value of PMIBI for MI is shown in Table V. On univariate analysis, none of the cardiac risk factors listed in Table II, including the individual Eagle criteria, were predictive of adverse cardiac events.

DISCUSSION The role of preoperative PTHAL/PMIBI prior to major vascular surgery remains debatable. Controversy exists as to which patients, if any, should be screened. Eagle et al. 2 recommend using PTHAL in patients with one or two clinical risk factors (advanced age, angina, Q waves, diabetes, and/or ventricular arrhythmias). In patients without clinical

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risk factors they recommend proceeding with surgery without PTHAL, inasmuch as the cardiac event rate is low. Conversely, in patients with three or more risk factors the incidence of adverse cardiac events in their series was high, regardless of the PTHAL results, so the decision to perform preoperative coronary revascularization was made independent of PTHAL scans. Taylor et al. 9 recommend limiting invasive cardiac testing to patients with severe symptomatic coronary disease. In their series of 492 patients, only three (0.5%) underwent prophylactic CABG. They reported an MI rate of 3.9%, while limiting invasive cardiac testing to 31 patients (5.8%). Our study confirms the low rate of cardiac events (0% in the present series) in patients with no Eagle criteria. Thus further cardiac testing in this group is not warranted. Additionally, the low overall cardiac event rate in our series (4.9%), in which coronary revascularization was limited to patients with severe cardiac symptoms, supports restricting invasive cardiac testing to this small subgroup as proposed by Taylor et al. Another matter of controversy involves the ability of PTHAL/PMIBI to predict adverse cardiac events following vascular surgery. Boucher et al. ' noted a 50% cardiac event rate w h e n PTHAL demonstrated reversible ischemia and a 0% event rate with a normal scan or a persistent defect. Eagle et al. 2 noted a 30% cardiac event rate w h e n the PTHAL scan demonstrated reversible ischemia compared to a 3% event rate w h e n the PTHAL scan was normal. In contradistinction, Mangano et al. 6 noted no difference in adverse cardiac events (27% with abnormal PTHAL scans vs. 18% with normal PTHAL scans; p -- NS). Fifty-eight percent of severe ischemia episodes occurred in patients w i t h o u t reversible ischemia. The sensitivity and specificity of PTHAL for adverse cardiac events were 27% and 82%, respectively. Positive and negative predictive values were 27% and 82%, respectively. The predictive value of PMIBI in our series (sensitivity, 25%; specificity, 80%; positive predictive value, 10%; and negative predictive value, 92%) mirrors that of the Mangano report. Likewise, the high incidence of adverse cardiac events (43%) in patients without reversible ischemia in our series adds support to the Mangano series. Others have also noted no difference in adverse cardiac event rates between patients with abnormal and normal PTHAL scans. 7 PMIBI differs from PTHAL in that technetium99m is used as the perfusion tracer instead of thallium-201. The shorter half-life of technetium99m permits injection of higher doses, providing higher image count density. '° M t h o u g h PMIBI

compares favorably with PTHAL in detecting coronary artery disease, 1' the literature is sparse with regard to the ability of PMIBI to predict adverse perioperative cardiac events following vascular surgery. ~ The inability of PMIBI to predict adverse events in our series may be explained in several ways. First, unexpected physiologic changes during the perioperative period (e.g., sudden hypoxia or acute gastrointestinal blood loss in our series) are not necessarily predictable by preoperative criteria. Second, although the patients in our series had a m e a n of 0.96 Eagle criteria, the most frequent risk factor was diabetes (50%), and only 14% had active angina. It is possible that PMIBI loses its predictive ability in the absence of symptoms. Third, this was a retrospective review and the number of patients involved was small. Some subtle ischemic changes may have been missed, although the importance of such transient ischemic episodes is questionable. Finall]~; although PMIBI imaging was performed by means of standard techniques, there is always the potential for differences in the interpretation of PMIBI scans. In weighing the decision to perform preoperative PTHAL/PMIBI, followed by coronary artery revascularization, the costs and risks of further invasive interventions should be considered, as well as the risks of delaying the vascular procedure. The risk of major complications resulting from cardiac catheterization is 1.8%. 12The risks of PTCA include a 1% mortality and a 4.3% MI rate, whereas CABG carries a 2% risk of MI and a 5% mortality rate) 3 In the series of Hertzer et al., 14 0.9% of patients with infrarenal aortic aneurysms sustained aneurysm rupture after CABG and died. Mason et al., 15using a base case analysis, found that proceeding directly to vascular surgery without coronary revascularization led to decreased morbidity and lower cost in patients with no angina or mild angina. Using a PTHAL/PMIBI screening program, Bry et al. s calculated a cost-effectiveness ratio of $181,039 per MI averted and $392,253 per life saved. Whether the cost and risks of preoperative coronary revascularization will decrease with the advent of coronary artery stenting remains to be seen.

CONCLUSION The role of preoperative nuclear cardiac imaging prior to elective vascular surgery remains controversial. In patients with no Eagle criteria, the incidence of adverse perioperative cardiac events is so low that further cardiac testing is unnecessary. Patients with _>1 Eagle criteria have a sta-

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tistically greater incidence of adverse cardiac events. In the absence of severe cardiac symptoms (unstable angina or recent [within 6 months] MI), PMIBI is not predictive of these events and is thus not indicated. In deciding whether to perform preoperative invasive cardiac testing, one must bear in mind the low cardiac morbidity and mortality associated with the absence of Eagle criteria, the poor predictive value of PMIBI, and the risks of invasive cardiac intervention, Future prospective, randomized trials will be needed to determine whether preoperative cardiac testing will benefit patients with one or more Eagle criteria. REFERENCES 1. Boucher CA, Brewster DC, Darling RC, et al. Determination of cardiac risk by dipyridamole-thallium imaging before peripheral vascular surgery. N Engl J Med 1985;312:389-394. 2. Eagle KA, Cotey CM, Newell JB, et al. Combining climcal and thallium data optimizes preoperative assessment of cardiac risk before major vascular surgery. Ann Intem Med 1989; 110: 859-866. 3. Sachs RN, Tellier P, Larmignat P, et al. Assessment of dipyridamole-thallium-201 myocardial scintigraphy of coronary risk before peripheral vascular surgery. Surgery 1988;103: 584-587. 4. Cutler BS, Leppo JA, Dipyridamole thallium-201 scintigraphy to detect coronary artery disease before abdominal aortic surgery. J Vasc Surg 1987;5:91-100. 5. Eagle KA, Singer DE, Brewster DC, et al. Dipyridamolethallium scanning in patients undergoing vascular surgery: Optimizing preoperative evaluation of cardiac risk. JAMA 1987;257:2185-2189.

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6. Mangano DT, London MJ, Tubau JF, et aL Dipyridamole thallium-201 scintigraphy as a preoperative screening test: A reexamination of its predictive potential. Circulation 1991;84: 493-502. 7. Baron J, Mundler O, Bertrand M, et al. Dipyridamole-thallium scintigraphy and gated radionuclide angiography to assess cardiac risk before abdominal aortic surgery. N Engl J Med 1994;330:663-669. 8. Bry JD, Belkin M, O'Donnell TF, et al. An assessment of the positive predictive value and cost-effectiveness of dipyridarnole myocardial scintigraphy in patients undergoing vascular surgery. J Vasc Surg 1994;19:112-124. 9. Taylor IDA, Yeager RA, Moneta GL, et al. The incidence of perioperative myocardial infarction in general vascular surgery. J Vasc Surg 1991;15:52-61. 10. Parodi O, Marcassa C, Casucci R, et al. Accuracy and safety of technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile ( sestamibi) myocardial scintigraphy with high-dose dipyridamole test in patients with effort angina pectoris: A multicenter study. J Am Coll Cardiol 1991;18:1439-1444. 11. Wackers FJ, Berman DS, Maddahi J, et al. Technetium-99m hexakis 2-methoxyisobutyl isonitrile: Human biodistribution, dosimetry, safety, and preliminary comparisons to thallium201 for myocardial perfusion imaging. J Nud Med 1989;30: 301-311. 12. Detre K, Holubkow R, Kelsey S, et al. Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. N Engl J Med 1988;318:265-270. 13. Bredlau C, Roubin G, Leimgruber P, et al. In-hospital morbidity and mortality in patients undergoing coronary angioplasty. Circulation 1985;72:1044-1052. 14. Hertzer NR, Beven EG, Young JR, et al. Coronary artery disease in peripheral vascular patients: A classification of 1000 coronary angiograms and results of surgical management. Ann Surg 1984;199:223-233. 15. Mason J J, Owens DK, Harris RA, et al. The role of coronary angiography and coronary revascularization before noncardiac surgery. JAMA 1995;273:1919-1925.