Preoperative Thallium Scanning, Selective Coronary Revascularization, and Long-Term Survival After Major Vascular Surgery

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1 Preoperative Thallium Scanning, Selective Coronary Revascularization, and Long-Term Survival After Major Vascular Surgery Giora Landesberg, MD, DSc; Morris Mosseri, MD; Yehuda G. Wolf, MD; Moshe Bocher, MD; Alon Basevitch, MD; Ehud Rudis, MD; Uzi Izhar, MD; Haim Anner, MD; Charles Weissman, MD; Yacov Berlatzky, MD Background Ischemia on thallium scanning is a strong predictor of long-term mortality in CAD patients. Whether coronary revascularization (CR) in patients with significant ischemia on preoperative thallium scanning (PTS) improves long-term survival after major vascular surgery has not been determined. Methods and Results The perioperative data, including PTS and subsequent CR in patients with moderate to severe reversible ischemia on PTS, and long-term survival of 502 consecutive patients who underwent 578 major vascular procedures were analyzed retrospectively. Patients with PTS who ultimately did not undergo the planned vascular operation were also studied. Cox regression and propensity score analyses were used to analyze survival. A total of 407 patients (81.1%) had PTS: 221 (54.3%) had no or mild defects (group I); 50 (12.3%) had moderate-severe fixed defects (group II); 62 (15.2%) had moderate-severe reversible ischemia yet did not undergo CR (group III); and 74 (18.2%) had moderate-severe reversible ischemia and subsequent CR by CABG (36) or PTCA (38; group IV). Patients who sustained major complications as a result of the preoperative cardiac workup were included in group IV. By multivariate analysis, age, type of vascular surgery, presence of diabetes, previous myocardial infarction, and moderate-severe ischemia on PTS independently predicted mortality (P 0.001, 0.009, 0.039, 0.006, and 0.029, respectively), and preoperative CR predicted improved survival (OR 0.52, P 0.018). Group IV had better survival than group III even when subdivided according to normal and reduced left ventricular function (OR 0.40 and 0.41, P and 0.021, respectively). Conclusions Long-term survival after major vascular surgery is significantly improved if patients with moderate-severe ischemia on PTS undergo selective CR. (Circulation. 2003;108: ) Key Words: radioisotopes imaging revascularization survival surgery Approximately 60% of patients undergoing major vascular surgery have significant ( 70% stenosis) symptomatic or asymptomatic coronary artery disease (CAD), 1 which leads to the majority (60%) of their perioperative and late mortality. 2,3 Preoperative thallium imaging predicts perioperative and long-term cardiac events 4,5 and survival after major vascular surgery. 6,7 In a meta-analysis, reversible myocardial perfusion defect on thallium imaging was the single independent predictor of perioperative cardiac death or infarction. 8 A small number of studies, none of which used preoperative noninvasive cardiac testing, suggested improved perioperative and long-term outcome after successful CABG in vascular surgery patients It was surmised, therefore, that a strategy of preoperative thallium scanning and subsequent coronary revascularization for high-risk patients would improve perioperative and long-term outcome. It was warned, however, that the periprocedural complication rate associated with CABG or PTCA might offset any apparent increase in safety of this strategy. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for preoperative cardiac assessment defined aortic and other major vascular surgery as high-risk surgery. 12 As such, the ACC/AHA guidelines stipulate that most of these patients undergo preoperative noninvasive testing and eventual coronary angiography and revascularization. No study, however, has examined the efficacy of noninvasive testing and subsequent coronary revascularization on perioperative and long-term outcome after major noncardiac surgery. The present study included the largest cohort of vascular surgery patients yet assembled, who were treated according to a strict protocol of routine preoperative thallium scanning, selective coronary angiography, and subsequent coronary revascularization by either CABG or PTCA for those suitable. Received March 20, 2003; accepted April 15, From the Departments of Anesthesiology and Critical Care Medicine (G.L., A.B., C.W.), Cardiology (M.M.), Vascular Surgery (Y.G.W., H.A., Y.B.), Cardio-thoracic Surgery (E.R., U.I.), and Nuclear Medicine (M.B.), Hebrew University Hadassah Medical Center, Jerusalem, Israel. Correspondence to Giora Landesberg, MD, DSc, Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, Ein-kerem, Kiryat-Hadassah, Jerusalem, Israel gio@cc.huji.ac.il 2003 American Heart Association, Inc. Circulation is available at DOI: /01.CIR FB 177

2 178 Circulation July 15, 2003 Methods In compliance with the standards of the hospital s Ethics Committee, all consecutive patients who underwent elective peripheral vascular operations at the Hadassah University Hospital during the decade of 1990 to 1999 were studied retrospectively. During this period, preoperative thallium scanning was performed routinely in our institution on patients scheduled for major vascular surgery. Patients were excluded from the preoperative thallium regimen if they had coronary angiography within the last year before surgery with no subsequent change in symptoms, negative exercise stress test and no history of CAD, or no clinical evidence or history of CAD and a delay of the vascular surgery was perceived to be detrimental in terms of their leg ischemia. Perioperative Management Except for a minority of the patients who were able to perform an adequate exercise stress test by upright treadmill according to the Bruce protocol, all patients received dipyridamole infusion followed by 3 minutes of isometric hand-grip exercise. Two millicuries of 201 Tl was given at peak exercise. Immediate and 4-hour delayed single photon emission computed tomography (SPECT) images were obtained. An additional 1.0 mci of thallium was given before the delayed images. Thallium defects were defined as either fixed or reversible. Defect size was determined on the basis of a 9-sector model of the heart: anterior, lateral, inferior, and posterior walls, each divided into basal and apical regions, plus the apex. A defect larger than 2 sectors was defined as large, 1 to 2 sectors as moderate, and 1 sector as a small defect. Defect severity was evaluated on the basis of the ratio of defect intensity to presumed normal myocardial area: a mild defect was a reduction of 15% to 40% in counts; moderate, a reduction of 40% to 50%; and severe, a reduction of 50% in counts. 13 Reversibility of perfusion defect was defined as an improvement of at least 10% in counts during rest as compared with stress images. Patients with moderate or severe reversible defects, including partially reversible defects, or large areas ( 2 sectors) of even mild but reversible defects on thallium imaging were defined as having moderate-severe reversible ischemia and were referred for coronary angiography and possible revascularization by either PTCA or CABG before the vascular surgery. Patients who had serious clinical predictors of outcome according to the criteria of Eagle et al 4 were referred for coronary angiography even if they had mild-moderate reversible defects on thallium scanning. Preoperative PTCA was performed for technically accessible, 70% coronary stenosis. CABG was preferred in patients with significant ( 50%) left main coronary stenosis, diabetic patients with multivessel disease, or patients with 2- or 3-vessel disease unsuitable for PTCA. None of the patients had unstable coronary syndrome in the 3 months preceding surgery. Preoperative cardiovascular medications were continued perioperatively. Data Collection The perioperative data were collected from the hospital s computerized information system and patient files by investigators who were blinded to the process of data analysis. All preoperative thallium results, coronary angiograms, PTCA data, and CABG data were reviewed. Long-term survival was recorded from the hospital s information system, which was updated monthly by the Israeli Ministry of Interior to include all newly deceased individuals. Patients who had preoperative thallium scanning were divided into 4 nonoverlapping groups: Group I included patients with no or mild (fixed or reversible) defects; group II, patients with moderate-severe fixed defects; group III, patients with moderate-severe reversible ischemia who did not undergo preoperative coronary revascularization, despite their thallium findings; and group IV, patients with moderate-severe reversible ischemia who therefore underwent preoperative coronary revascularization by CABG or PTCA. Patients in Whom Vascular Surgery Was Canceled All patients who had thallium scans but ultimately did not undergo the planned surgery were also investigated. Their thallium scans, angiography findings, reasons for cancellation of surgery, and long-term survival were reviewed. Patients who had complications during preoperative cardiac catheterization or revascularization were added to group IV on the basis of an intention-to-treat analysis. Statistical Analyses Student t test and 2 analysis were used to compare continuous and dichotomous variables. Kaplan-Meier log-rank test and Cox (univariate and multivariate) regression models were used to compare survival and identify predictors of survival. All preoperative predictors were included in the analysis, and a backward conditional method was used for variable selection by the Cox multivariate regression model. Propensity score analysis 14 was performed with regard to the use of preoperative coronary revascularization. For each patient, a propensity score indicating the likelihood of obtaining coronary revascularization was calculated by backward logistic regression analysis, which included all the preoperative demographic, clinical, and thallium imaging data. Goodness of fit of the propensity score was evaluated by the Hosmer-Lemeshow test. Survival was compared in 5 subgroups (quintiles) based on their propensity scores. P 0.05 defined statistical significance. All statistical analyses were performed with SPSS version 10.0 software (SPSS Inc). Results A cohort of 502 consecutive patients who underwent 578 vascular operations was studied. The 76 patients with more than 1 operation were included once, at the time of their first vascular surgery. Preoperative thallium scanning was performed in 407 patients (81.1%), 32 (7.9%) with adequate exercise stress testing and the rest with intravenous dipyridamole injection. Group I included 221 (54.2%) patients; Group II, 50 (12.3%); Group III, 62 (15.2%); and Group IV, 74 (18.2%) (Table 1). Moderate-Severe Reversible Ischemia Group III included 62 patients who did not undergo coronary revascularization despite moderate-severe ischemia on thallium scanning; 31 (50%) also had moderate-severe fixed defects. In 28 patients, coronary angiography was not performed because they were asymptomatic, had no history of CAD, and lacked significant risk factors. The other 34 patients did undergo coronary angiography but not revascularization for the following reasons: 17 had progressive leg ischemia with coronary findings not severe or not easily treatable; 8 had significant CAD not technically amenable to either PTCA or CABG; 5 had total occlusion of 1 or 2 coronary arteries unsuitable for PTCA and not severe enough to warrant CABG; 4 patients had nonsignificant coronary stenoses; and 4 patients with previous CABG had patent grafts, and no additional revascularization was necessary. Group IV included 74 patients who underwent PTCA (38 patients) or CABG (36 patients) after moderate-severe ischemia on thallium scanning; 33 (44.6%) also had moderatesevere fixed defects. The preoperative coronary angiography and left ventricular (LV) function data from angiography or echocardiography are depicted in Table 2. In 42 patients who had moderate-severe ischemia, the planned vascular surgery was canceled. Thirty-eight of them had severe CAD based on thallium scanning and/or coronary angiography findings that posed a prohibitive risk for surgery. Four patients had major cardiovascular complications: 1 death after CABG, 2 cerebrovascular accidents, and 1 myo-

3 Landesberg et al Coronary Revascularization in Vascular Patients 179 TABLE 1. Preoperative Demographic and Clinical Data Patients With Preoperative Thallium Scanning (n 407; 81.1%) All Patients (n 502) Group I (n 221) cardial infarction after coronary angiography. These 4 patients were added to group IV for all long-term survival analyses. Propensity Score Analysis Variables most strongly associated with the performance of preoperative angiography and revascularization by logistic regression were moderate-severe reversible ischemia on thallium scanning, history of CAD, hypertension, and male gender. The goodness of fit of the propensity score as evaluated by the Hosmer-Lemeshow test was (P 0.027). The propensity scores within each quintile were comparable between groups III and IV (Table 3). Group II (n 50) Group III (n 62) Group IV (n 74) P Age, y NS Male gender 382 (76.1) 163 (74.4) 44 (89.8) 54 (72.6) 68 (73.9) NS Surgery Infrainguinal bypass 301 (59.9) 131 (59.3) 29 (60.4) 38 (61.3) 42 (56.8) NS AAA 189 (37.6) 88 (39.8) 17 (34.0) 21 (33.9) 31 (41.9) NS Axillofemoral bypass 12 (2.4) 2 (0.9) 3 (6.0) 3 (4.8) 1 (1.4) NS Diabetes mellitus 150 (29.9) 56 (25.3) 15 (30.0) 28 (45.2) 28 (37.8) 0.02 Hypertension 247 (49.2) 127 (57.5) 29 (60.0) 34 (54.8) 32 (43.2) Hyperlipidemia 105 (20.9) 51 (23.3) 8 (16.3) 11 (17.7) 19 (25.7) NS Smoking history 265 (52.8) 121 (54.8) 38 (76.0) 33 (53.2) 39 (52.7) History of IHD 210 (41.8) 50 (22.6) 40 (80.0) 34 (54.8)* 58 (78.4)* S/A MI 119 (23.7) 24 (10.9) 28 (56.0) 22 (35.5) 31 (41.9) Angina pectoris 83 (16.5) 20 (9.0) 14 (28.0) 16 (25.8) 24 (32.4) Congestive heart failure 28 (5.6) 2 (0.9) 3 (6.0) 9 (14.5) 11 (14.9) Kidney disease (creatinine 2 mg/dl) 16 (3.2) 10 (4.5) 4 (8.0) Preoperative thallium scanning 412 (82.1) 221 (100) 50 (100) 62 (100) 74 (100) Moderate-severe fixed defect 0 (0) 50 (100) 31 (50.0) 33 (44.6) Moderate-severe reversible defect 0 (0) 0 (0) 62 (100) 74 (100) Patients medications Calcium blockers 161 (32.1) 71 (31.7) 19 (38.0) 19 (30.6)* 36 (48.6)* Blockers 75 (14.9) 33 (14.9) 13 (26.0) 6 (9.7) 11 (14.9) ACE inhibitors 112 (22.3) 42 (19.0) 17 (34.0) 18 (29.0) 23 (31.1) 0.08 Diuretics 65 (12.9) 26 (11.8) 10 (20.0) 9 (14.5) 15 (20.3) Digoxin 18 (3.6) 2 (0.9) 5 (10.0) 3 (4.8) 6 (8.1) Oral hypoglycemic agents 85 (16.9) 29 (13.1) 9 (18.0) 16 (25.8) 15 (20.3) 0.16 Insulin 39 (7.8) 15 (6.8) 1 (2.0) 6 (9.7) 9 (12.2) 0.37 Hypolipidemic agents 62 (12.3) 26 (11.8) 10 (20.0) 8 (12.9) 14 (18.9) AAA indicates abdominal aortic aneurysm; IHD, ischemic heart disease; and S/A MI, state after myocardial infarction. Values are n (%), except for age. *Variables with significant differences between groups III and IV (P and 0.014, respectively). Long-Term Survival Patients were followed up for a period of months (range 18 to 138 months). Age, type of surgery (lowerextremity bypass versus aortic surgery), presence of diabetes mellitus, history of CAD, previous myocardial infarction, congestive heart failure, creatinine 2 mg/dl, moderatesevere reversible defects on thallium scanning, and use of diuretic drugs and digoxin were significant predictors of long-term mortality, and the use of hypolipidemic agents was the only predictor of improved survival by univariate analysis (OR 0.49, P 0.04; Table 4). By Cox multivariate analysis, age, type of surgery, presence of diabetes mellitus, previous myocardial infarction, and moderate-severe reversible ischemia predicted worse survival. Preoperative coronary revascularization, however, independently predicted improved longterm survival (OR 0.52, P 0.018; Table 4). By Kaplan-Meier analysis, group III had worse long-term survival than either of the other groups (P 0.001, , and for group III versus groups I, II, and IV, respectively; Figure 1). Survival in group III became significantly worse than that in group I 10 months after surgery (P 0.05), and this difference increased thereafter (P ). Group IV had better long-term survival than group III even when the propensity score was included in the multivariate analysis (Table 3). The 5-year survival of group IV was better than that of group III in each of the propensity score quintiles,

4 180 Circulation July 15, 2003 TABLE 2. Preoperative Coronary Angiography and LV Function Results Group III Group IV P Preoperative coronary angiography 38 (61.3) 74 (100) Left main coronary stenosis ( 50%) 3 (7.3) 15 (20.3) 0.058* Triple-vessel disease ( 70% stenosis) 15 (39.4) 41 (55.4) 0.11* Double-vessel disease ( 70% stenosis) 13 (34.2) 26 (35.1) NS Single-vessel disease ( 70% stenosis) 6 (15.8) 7 (9.5) NS No significant coronary stenosis 4 (10.5) 0 NS Preoperative LV function (by angiography or 60 (96.7) 74 (100) echocardiogram) Normal LV function 35 (58.3) 42 (56.8) NS Mildly reduced LV function 6 (10) 11 (14.9) NS Moderately reduced LV function 13 (21.7) 8 (10.8) NS Severely reduced LV function 6 (10) 13 (17.6) NS Values are n (%). *P for left main and triple-vessel disease combined. although it was significantly different only in the 5th quintile. There were no differences between groups III and IV in mean propensity scores within each quintile. The 30-day, 1-year, and 5-year survival rates of group IV versus group III were 98.7% versus 97.8% (P NS), 89.7% versus 83.9% (P NS), and 74.3% versus 53.2% (P 0.006), respectively. Patients without preoperative thallium scanning had a biphasic survival curve, starting with worse than group I 2 months after surgery (P 0.019), yet this difference disappeared 16 months after surgery. After separation of group IV patients into 2 subgroups, those with PTCA versus CABG, analysis showed that patients who underwent CABG had a tendency toward better survival than those who had PTCA, and each subgroup independently had better survival than group III (P and 0.05, respectively; Figure 2). Alternatively, when group III was divided into 2 subgroups, those who underwent preoperative coronary angiography and those who did not, both subgroups had worse long-term survival than group IV (P and 0.036, respectively), with the former having a trend toward worse prognosis than the latter. Finally, separation of patients according to their LV function showed that group IV had significantly better long-term survival than group III even when only patients with normal LV function were included (OR 0.40, P 0.035) and also when only patients with reduced (mild, moderate, or severe) LV function were analyzed (OR 0.41, P 0.021; Figure 3). Discussion Coronary revascularization with either CABG or PTCA has been shown to improve long-term survival in selected patient groups. CABG improves survival in patients with left main CAD, LV dysfunction, and those having 2- or 3-vessel disease involving the proximal left anterior descending coronary artery 15,16 and in severely symptomatic patients with triple-vessel disease regardless of their ventricular function or the presence of proximal coronary stenoses. 17 PTCA and intracoronary stenting confer long-term survival that is similar to that after CABG in symptomatic patients with multivessel CAD, 18,19 with the exception of diabetic patients, who benefit more from CABG. 18 One trial, the Asymptomatic Cardiac Ischemia Pilot (ACIP), showed improved survival after revascularization by CABG or PTCA compared with medical treatment in both symptomatic and asymptomatic patients with proven CAD and ischemia on ambulatory ECG or exercise stress testing. 20 In the present study, selective coronary revascularization before major vascular surgery in patients who had moderate-severe ischemia on routine preoperative thallium scanning was associated with improved long-term survival. Furthermore, revascularization improved long-term survival in both patients with normal and those with impaired LV function. Only 2 cohort studies compared long-term survival with and without coronary revascularization before major vascular surgery. 9,10 In both studies performed in the 1980s, successful revascularization by CABG improved perioperative and 5-year survival after lower-extremity bypass and infrarenal aortic surgical procedures. CABG in these studies, however, was prompted by routine preoperative coronary angiography before major vascular surgery, an approach no longer recommended. Other studies examined the effect of successful coronary revascularization on perioperative (30 day) outcome only after noncardiac surgery. 11,21,22 One retrospective study using administrative data (Medicare) found reduced perioperative and 1-year mortality in aortic surgery patients who had preoperative stress testing followed by coronary revascularization. 23 None of the above studies examined the TABLE 3. Propensity Score Analysis Comparing Revascularization in Patients With Moderate-Severe Reversible Defects on PTS Number of Patients Mean (SD) PS 5-Year Survival (Cumulative), % Cox Multivariate Analysis Quintile Group III Group IV* Group III Group IV* Group III Group IV OR (95% CI) P All (PS included) (0.45) 0.47 (0.50) ( ) PS quintile (0.028) (0.023) ( ) 0.26 PS quintile (0.03) 0.18 (0.02) ( ) 0.34 PS quintile (0.03) 0.34 (0.03) (0.21 2,77) 0.69 PS quintile (0.03) 0.53 (0.03) ( ) 0.09 PS quintile (0.08) 0.74 (0.07) ( ) PS indicates propensity score. *Group IV includes the 4 patients in whom preoperative cardiac catheterization and revascularization ended with complications.

5 Landesberg et al Coronary Revascularization in Vascular Patients 181 TABLE 4. Univariate and Multivariate (Backward Conditional Selection) Cox Regression Survival Analyses Univariate Analysis Multivariate Analysis* OR (95% CI) P OR (95% CI) P Age 1.04 ( ) ( ) Gender 1.03 ( ) 0.87 Type of surgery Distal bypass vs aorta 1.63 ( ) ( ) Axillofemoral bypass vs aorta 3.71 ( ) ( ) Diabetes mellitus 1.72 ( ) ( ) Hypertension 1.33 ( ) Smoking history 0.76 ( ) 0.11 Ischemic heart disease 1.22 ( ) 0.21 History of MI 1.22 ( ) ( ) History of angina pectoris 1.27 ( ) 0.21 Congestive heart failure 1.79 ( ) Kidney disease (creatinine 2 mg/dl) 2.26 ( ) ( ) Preoperative thallium scanning Moderate-severe fixed defect 1.31 ( ) Moderate-severe reversible defect 1.38 ( ) ( ) Preoperative revascularization 0.81 ( ) ( ) (PTCA/CABG) Medications Calcium blockers 1.08 ( ) Blockers 1.13 ( ) 0.58 ACE inhibitors 0.94 ( ) 0.94 Diuretics 1.52 ( ) Digoxin 1.87 ( ) Oral hypoglycemic agents 1.19 ( ) 0.37 Insulin 1.00 ( ) 0.99 Hypolipidemic agents 0.49 ( ) ( ) *All preoperative variables were included in the multivariate analysis, and only those identified by the stepwise Cox regression model as independently associated with survival were included in the table. long-term efficacy of preoperative noninvasive testing and subsequent revascularization. In addition, none of them included the hazards of preoperative revascularization in their analyses. The few studies that investigated the effect of coronary revascularization subsequent to positive preoperative thallium scanning also focused predominantly on perioperative outcome and not on long-term outcome Younis et al 24 showed reduced perioperative death and infarction by preoperative change in medical therapy or coronary revascularization in patients with abnormal preoperative thallium studies. Massie et al 25 studied the short-term effect of preoperative coronary angiography after abnormal thallium scanning and concluded that it did not provide useful information because of the poor coronary anatomy of most patients, who were unsuitable for revascularization. However, the effect of coronary revascularization, performed in only 35% of their patients with coronary angiography, was not reported. Schueppert et al 26 reported that 4-year survival after coronary revascularization was similar to that of patients with a normal thallium study; however, no statistical data were provided to support this statement. Previous studies from our institution showed improved outcome after preoperative thallium scanning and selective revascularization in patients undergoing carotid endarterectomy 7 or surgery for critical leg ischemia. 28 The pooled 30-day and 5-year survival rates in groups I, II, and IV were 97.2% and 74.4%, respectively, compared with 96.8% and 53.2%, respectively, in group III. These findings corroborate other studies performed on similar patients. 3,29,30 Four patients (5.1%) had major cardiovascular complications as a result of the preoperative cardiac investigation and revascularization and were added to group IV on the basis of intention-to-treat analysis. This periprocedural complication rate was lower than the 12% major complication rate in peripheral vascular disease patients in the Bypass Angioplasty Revascularization Investigation study. 31 The difference may be explained by the fact that most patients in the latter study were severely symptomatic, with high rates of unstable angina pectoris ( 63%), history of myocardial infarction, and congestive heart failure, and all had multivessel CAD, in

6 182 Circulation July 15, 2003 Figure 1. Kaplan-Meier survival curves of all groups. No PTS indicates patients without preoperative thallium scanning; group I, patients with no or mild defects on thallium scanning; group II, patients with only moderate-severe fixed defects; group III, patients with moderate-severe reversible defects who did not undergo preoperative coronary revascularization; and group IV, patients with moderate-severe reversible defects who underwent preoperative coronary revascularization by CABG or PTCA. Group III had significantly worse long-term survival than the other groups. contrast to the stable or asymptomatic CAD in patients in the present study. Moreover, on the basis of the present data, even if 10 patients died during revascularization before vascular surgery, group IV would still maintain a long-term survival benefit over group III (P 0.037). Only a small minority (4 of 38) of the patients treated by PTCA in the present study received intracoronary stents, because such treatment was not frequently used during most of the study period. Modern therapeutic modalities, such as platelet IIb/IIIa receptor antagonists and drug-eluting stents shown to improve the results of coronary interventions, were Figure 2. Kaplan-Meier survival curves of group III compared with group IV divided into 2 subgroups: those who had CABG, and those who had PTCA. Both CABG and PTCA were associated with better long-term survival than group III (P and 0.05, respectively). Figure 3. Kaplan-Meier survival curves of group III versus group IV, each divided into 2 subgroups: patients with normal LV function (LVF) and those with reduced LVF. Group IV patients had better long-term survival both in patients with normal LVF and in patients with reduced LVF. not yet in use during the study and might have further improved the long-term outcome after revascularization. Study Limitations The main limitation of the present study is its retrospective nature. Because clinical decisions dictated whether patients with moderate-severe ischemia were revascularized (group IV) or not (group III), we included the propensity score analysis to control for the possible differences in background characteristics between the 2 groups. Although the propensity score compensates only for background factors included in the study (Table 4) and not for other factors that may have influenced the clinical decision, it nevertheless decreases the probability that the improved survival of group IV was related to causes other than coronary revascularization. Group III was heterogeneous and included patients with and without preoperative coronary angiography, although all of them had positive thallium results. Nevertheless, both subgroups had worse survival than group IV and patients without preoperative angiography. The fact that revascularization improved long-term survival both in patients with normal LV function and those with reduced LV function further strengthens these results. Recently, improved understanding of the pathophysiology of perioperative myocardial ischemia and infarction 32,33 and methods to prevent it, such as perioperative -blockers, 34 decreased perioperative cardiac morbidity and mortality. Only a minority of patients in the present study received -blockers because such treatment was not yet a state-of-theart therapy in the perioperative period at that time. However, many vascular patients do not tolerate -blockers because of slow resting heart rate or other side effects. 35 Additionally, in the present study, hypolipidemic medications, not -blockers, were associated with improved long-term survival. Moreover, -blocker therapy is less effective than revascularization in preventing long-term cardiac events in patients with significant CAD suitable for revascularization. 20

7 Landesberg et al Coronary Revascularization in Vascular Patients 183 Conclusions A significant proportion of patients undergoing major vascular surgery have moderate-severe CAD, which is detectable by preoperative thallium scanning and treatable by coronary revascularization. Selective coronary revascularization in these patients is associated with improved long-term survival. Further investigation is needed to better define patient subgroups who deserve thallium scanning and subsequent revascularization versus other treatment modalities, such as -blockers, to improve prognosis after major vascular surgery. References 1. 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: L Italian GJ, Cambria RP, Cutler BS, et al. Comparative early and late cardiac morbidity among patients requiring different vascular surgery procedures. J Vasc Surg. 1995;21: Norman PE, Semmens JB, Lawrence-Brown MM. Long-term relative survival following surgery for abdominal aortic aneurysm: a review. Cardiovasc Surg. 2001;9: Eagle KA, Coley CM, Newell JB, et al. Combining clinical and thallium data optimizes preoperative assessment of cardiac risk before major vascular surgery. Ann Intern Med. 1989;110: Brown KA, Rowen M. Extent of jeopardized viable myocardium determined by myocardial perfusion imaging best predicts perioperative cardiac events in patients undergoing noncardiac surgery. J Am Coll Cardiol. 1993;21: Darbar D, Gillespie N, Main G, et al. Prediction of late cardiac events by dipyridamole thallium scintigraphy in patients with intermittent claudication and occult coronary artery disease. Am J Cardiol. 1996;78: Landesberg G, Wolf Y, Schechter D, et al. Preoperative thallium scanning, selective coronary revascularization, and long-term survival after carotid endarterectomy. Stroke. 1998;29: Shaw LJ, Eagle KA, Gersh BJ, et al. Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery. J Am Coll Cardiol. 1996;27: Hertzer NR, Young JR, Beven EG, et al. Late results of coronary bypass in patients presenting with lower extremity ischemia: the Cleveland Clinic Study. Ann Vasc Surg. 1987;1: Hertzer NR, Young JR, Beven EG, et al. Late results of coronary bypass in patients with infrarenal aortic aneurysms: the Cleveland Clinic Study. Ann Surg. 1987;205: Eagle KA, Rihal CS, Mickel MC, et al. Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations. CASS Investigators and University of Michigan Heart Care Program: Coronary Artery Surgery Study. Circulation. 1997;96: Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation. 2002;105: Kitsiou AN, Srinivasan G, Quyyumi AA, et al. Stress-induced reversible and mild-to-moderate irreversible thallium defects: are they equally accurate for predicting recovery of regional left ventricular function after revascularization? Circulation. 1998;98: Joffe MM, Rosenbaum PR. Propensity scores. Am J Epidemiol. 1999; 150: The VA Coronary Artery Bypass Surgery Cooperative Study Group. Eighteen-year follow-up in the Veterans Affairs cooperative study of coronary artery bypass surgery for stable angina. Circulation. 1992;86: Yusuf S, Zucker D, Peduzzi P, et al. 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