Published online before print June 30, 2003, doi: 10.1161/01.CIR.0000080292.11186.FB
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(Circulation. 2003;108:177.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Preoperative Thallium Scanning, Selective Coronary Revascularization, and Long-Term Survival After Major Vascular Surgery
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 91120. E-mail gio{at}cc.huji.ac.il
Received March 20, 2003; accepted April 15, 2003.
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Abstract |
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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=0.035 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.
Key Words: radioisotopes • imaging • revascularization • survival • surgery
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Introduction |
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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 events4,5 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.9–11 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.
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Methods |
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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 201Tl 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 al4 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 analysis14 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).
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Results |
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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).
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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 moderate-severe fixed defects. The preoperative coronary angiography and left ventricular (LV) function data from angiography or echocardiography are depicted in Table 2.
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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 myocardial 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 2=12.64 (P=0.027). The propensity scores within each quintile were comparable between groups III and IV (Table 3).
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Long-Term Survival
Patients were followed up for a period of 55.3±32.3 months (range 18 to 138 months). Age, type of surgery (lower-extremity bypass versus aortic surgery), presence of diabetes mellitus, history of CAD, previous myocardial infarction, congestive heart failure, creatinine >2 mg/dL, moderate-severe 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 long-term survival (OR 0.52, P=0.018; Table 4).
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By Kaplan-Meier analysis, group III had worse long-term survival than either of the other groups (P=0.001, 0.0098, and 0.003 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=0.0001). 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, 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.
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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=0.016 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=0.003 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).
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Discussion |
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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 artery15,16 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 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.24–27 Younis et al24 showed reduced perioperative death and infarction by preoperative change in medical therapy or coronary revascularization in patients with abnormal preoperative thallium studies. Massie et al25 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 al26 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 endarterectomy7 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 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 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 infarction32,33 and methods to prevent it, such as perioperative ß-blockers,34 decreased perioperative cardiac morbidity and mortality. Only a minority of patients in the present study received ß-blockers because such treatment was not yet a state-of-the-art therapy in the perioperative period at that time. However, many vascular patients do not tolerate ß-blockers because of slow resting heart rate or other side effects.35 Additionally, in the present study, hypolipidemic medications, not ß-blockers, were associated with improved long-term survival. Moreover, ß-blocker therapy is less effective than revascularization in preventing long-term cardiac events in patients with significant CAD suitable for revascularization.20
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Conclusions |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
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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 ß-blockers, to improve prognosis after major vascular surgery.
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Footnotes |
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The preoperative thallium scanning (PTS), coronary revascularization (CR), and long-term survival (up to 10 years) data of 502 consecutive patients who underwent major vascular procedures were analyzed retrospectively. Preoperative CR independently predicted improved survival (OR 0.52, P=0.018). Long-term survival after CR was similar to that of patients with no or mild defects on PTS and better than that of patients with moderate to severe ischemia who did not undergo CR (OR 0.38, P=0.001).
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References |
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