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(Stroke. 1998;29:2541-2548.)
© 1998 American Heart Association, Inc.
Original Contributions |
Preoperative Thallium Scanning, Selective Coronary Revascularization, and Long-Term Survival After Carotid Endarterectomy
From the Departments of Anesthesiology and Critical Care Medicine (G.L., C.W.), Vascular Surgery (Y.W., H.A., Y.B.), Nuclear Medicine (D.S., R.C., N.K., M.B., J.E.), and Cardiology (M.M., M.H.L.), Hebrew University–Hadassah Medical Center, Jerusalem, Israel. Correspondence to Giora Landesberg, MD, DSc, Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, PO Box 12000, Jerusalem, Israel 91120.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—Long-term survival in patients after carotid endarterectomy (CEA) is determined mainly by their concomitant cardiac disease. We tested to determine whether preoperative thallium scanning (PTS) and subsequent selective coronary revascularization (CR), by either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG), improve long-term survival after CEA.
Methods—Two hundred twenty-six of 255 consecutive patients (88%) undergoing CEA from 1990 to 1996 had PTS. Those with significant reversible defects on PTS were referred for coronary angiography and possible CR. Patients who had undergone PTS were divided into the following 4 groups: group 1, normal or mild defects on PTS; group 2, moderate-severe fixed and/or reversible defects in patients who did not undergo CR; group 3, patients who had CR secondary to their PTS results; and group 4, patients who had CR in the past that was not related to the PTS. Perioperative data were prospectively recorded, and data on long-term survival and cardiac and neurological complications were collected.
Results—Seventy-seven patients (34%) had preoperative coronary angiography, and 42 (19%) had subsequent CR: preoperative PTCA or CABG in 24, combined CEA+CABG in 10, and post-CEA CABG in 8 patients. No deaths resulted from the coronary angiography, CR, or CEA. Six patients had perioperative nonfatal myocardial infarction and 8 had stroke. During the follow-up (40±23 months), 47 patients (18%) died, 31 (66%) from cardiac disease and 4 (8.5%) from stroke. Independent predictors of long-term overall mortality were diabetes mellitus, preoperative T-wave inversion on ECG, lower-extremity arterial disease, and history of neurological symptoms [exp(ß)=3.5, 3.4, 2.5, and 2.4; P=0.0003, 0.0004, 0.01, and 0.04, respectively]. In addition, preoperative moderate-severe thallium defect without CR (group 2) independently predicted long-term cardiac mortality [exp(ß)=2.8; P=0.04]. Patients with preoperative CR (group 3) had long-term survival rate similar to that of group 1 and significantly better than that of group 2 (P=0.02).
Conclusions—PTS predicts long-term survival, and selective CR based on the thallium results improves the survival rate of patients undergoing CEA.
Key Words: cardiac catheterization • carotid endarterectomy • coronary revascularization • survival • tomography, emission computed
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Since the publication of the multicenter, randomized studies demonstrating the superiority of carotid endarterectomy (CEA) over medical treatment in long-term stroke prevention in patients with carotid stenosis,1 2 3 the indications for CEA have increased and the number of patients referred for CEA has been growing. Although neurological outcome is markedly improved by CEA, long-term morbidity and mortality in patients with significant carotid stenosis are still heavily influenced by their concomitant cardiac disease. Candidates for CEA have >20% mortality from cardiac-related causes within 4 years, whether or not they undergo CEA.3 Patients with known or silent coronary artery disease (CAD) and those who are unable to exercise experience the worst long-term cardiac morbidity and mortality rates.4 Based on these data, several investigators have contended that candidates for CEA may benefit from an intensive preoperative cardiac workup to detect and treat high-risk cardiac patients.5 6 7 Until 1993, 50% to 75% of patients undergoing major vascular surgery in the United States had at least 1 of the following preoperative tests performed: exercise ECG testing, thallium scintigraphy, stress echocardiography, or ambulatory ischemia monitoring.8 In light of the current low perioperative complication rates (<3%) and the doubts raised about the accuracy of thallium testing in predicting perioperative cardiac complications, it has become difficult to demonstrate any significant beneficial effects from pre-CEA routine cardiac testing and coronary revascularization (CR) on perioperative outcome.9 In addition, cost-containment trends in medical care and the current guidelines of the American College of Cardiology/American Heart Association9 tend to reduce the use of preoperative cardiac testing. However, the question of whether patients who undergo CEA should have cardiac screening for the purpose of assessing their long-term outcome has been raised previously by authors10 11 but has failed to generate adequate answer. In the present study we examined the effect of preoperative thallium testing and selective perioperative CR on long-term survival after CEA.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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We studied 255 patients who underwent 288 consecutive CEA procedures at Hadassah University Hospital in Jerusalem, Israel, from 1990 to 1996. Two hundred forty-five patients had 278 CEA procedures (32 patients had bilateral CEAs, and 1 had bilateral CEAs and a repeat unilateral CEA); 10 patients were admitted for CEA, but because of the results of the preoperative cardiac evaluation were referred for combined CEA and coronary artery bypass grafting (CABG). The indications for CEA were (1) an angiographic finding of >70% stenosis (diameter reduction on angiography) of the internal carotid artery in patients with ipsilateral neurological symptoms, ie, cerebrovascular accident, transient ischemic attack, or amaurosis fugax during the last 6 months before surgery, or (2) an angiographic finding of >80% internal carotid artery stenosis in patients who were neurologically asymptomatic in the previous 6 months.
It was our policy during these years to perform preoperative thallium scanning (PTS) on patients scheduled for CEA, in addition to the routine testing, clinical history, physical examination, 12-lead ECG and chest x-ray. Thallium scanning was performed in all patients except: 1) Patients with previously known coronary lesions, ie, those who had coronary angiography within the last year and who had no subsequent change in cardiac symptoms; 2) Patients who were referred from other institutions with a negative regular exercise stress test and no history of ischemic heart disease 3) patients who required urgent CEA due to crescendo transient ischemic attacks.
Depending on their ability to exercise, patients were stressed by
upright treadmill exercise according to the Bruce protocol, or by
dipyridamole infusion (0.56 mg/Kg BW over 4 minutes)
immediately followed by 3 min of isometric hand grip exercise. Two mCi
of thallium-201 were given at peak exercise, and immediate, and 4 hours
delayed SPECT images were obtained.12 An additional 1.0
mCi of thallium was given prior to the delayed images. Thallium defects
were defined as either fixed or reversible, depending on whether they
persisted on the delayed images or improved, respectively. Defect size
was determined based on a 9 sector model of the heart: the anterior,
lateral, inferior and posterior walls each divided in to
basal and apical regions, plus the apex. A defect larger than 2 sectors
was defined as large, 1 to 2 sectors was moderate size and < 1
was small size defect. Defect severity was evaluated based on the ratio
of defect intensity to presumed normal myocardial area: mild defect –a
reduction of
25 to 40% in counts, moderate –40% to 50% reduction,
and severe –
50% reduction in counts at the defect compared with
the normal area. Patients with moderate to severe reversible defects or
multiple areas of reversible defects on thallium images were referred
to coronary angiography and possible CR by either
percutaneous transluminal coronary angioplasty
(PTCA) or CABG prior to the CEA, combined CEA+CABG or CABG after the
CEA (staged procedure). Preoperative PTCA was performed for technically
accessible significant (>70%) coronary lesions. CABG was
preferred in patients with severe triple-vessel CAD or a left main
coronary lesion. CABG prior to CEA was done only during the
years 1990 to 1992 since combined CEA+CABG procedures were initiated at
our institution during 1992 and were the preferred mode of treatment
for patients with severe combined disease thereafter. None of the
patients admitted for CEA during the study period was excluded from
surgery due to the cardiac disease.
All preoperative clinical findings and perioperative data, including postoperative cardiac or neurological complications were recorded prospectively. Preoperative history of ischemic heart disease (IHD) was defined as clinical evidence of myocardial infarction, angina pectoris, or CR at any time in the past. History of neurological symptoms was recorded if the patient had experienced a cerebrovascular accident, transient ischemic attack, or amaurosis fugax at any time in the past (on any side). Lower-extremity arterial disease was considered present if a patient had intermittent claudication, ischemic pain at rest, or a foot ulcer or gangrene due to peripheral arterial disease.
Patients were monitored perioperatively for any sign or symptom of a cardiac or neurological event. Routine 12-lead ECG and serum creatine kinase–MB isoenzymes were obtained on the first, second, and third postoperative days, and later if clinically indicated.
All preoperative 12-lead ECGs were analyzed retrospectively by
2 independent investigators for signs of pathological Q waves, voltage
criteria for left ventricular hypertrophy,
baseline ST depression (0.5 mm), or T-wave inversion, based on
the Sokolow-Lyon Criteria for left ventricular
hypertrophy,13 as previously
published.14 All preoperative thallium results,
coronary angiograms, or PTCA and CABG data were retrieved from
the hospital's computerized registry.
Long-term follow-up data, including death, cause of death, and neurological and cardiac complications, were collected using 3 complementary methods. (1) Patient charts were reviewed for hospitalizations and visits to outpatient clinics. Two hundred five of the patients (80.3%) had visited Hadassah's outpatient clinics during the 6 months preceding the end of the follow-up period. (2) All but 6 surviving patients (97.1%) were interviewed by phone for their cardiac and neurological symptoms. (3) For patients who died, date and cause of death were obtained by reviewing death certificates from the Ministry of Interior Affairs. Cardiac death was defined as death following myocardial infarction, congestive heart failure, or fatal arrhythmia. Late cardiac event was defined as hospitalization for myocardial infarction, congestive heart failure, unstable angina, PTCA, or CABG.
To examine the effect of selective perioperative CR on long-term survival, patients were divided into 4 non-overlapping groups: group 1, patients with normal scans or mild (fixed or reversible) thallium defects, with no CR in their past; group 2, patients with moderate-severe (fixed or reversible) thallium defects who did not undergo CR; group 3, patients with moderate-severe thallium defects who had perioperative CR based on their thallium findings; and group 4), patients with moderate-severe thallium defects who had CR at any time in the past, not related to the preoperative thallium testing.
Statistical Analyses
Student's t test and 
2
analyses were used to compare continuous and dichotomous
variables between groups of patients, respectively. The
Kaplan-Meier method, log-rank test, and Cox (univariate and
multivariate) regression model were used to identify
predictors for long-term survival. The forced-entry method was used for
variable selection by the Cox regression model to get the maximal
number of predictors of long-term survival.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Preoperative demographic and clinical details of all patients are found in Table 1
. The results of
preoperative thallium testing and subsequent coronary
angiography and revascularization procedures are
summarized in Table 2. Of the 102
(45.1%) patients who had moderate to severe reversible defects or
partially redistributing multiple fixed defects on thallium scanning,
77 (75.5%) had findings considered significant enough to require
preoperative coronary angiography. After coronary
angiography, 42 patients had perioperative CR.
Preoperative cardiac catheterizations and CRs in the
entire group were not associated with periprocedural mortality. There
were no major perioperative complications from either
the PTCA or the CABG procedures. After combined CEA+CABG, 1 patient had
a prolonged ICU stay because of sepsis and multiorgan failure, and
another patient underwent re-exploration because of bleeding and
cardiac tamponade.
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Intraoperative carotid shunting was used in 28% of the patients, and a
synthetic patch was used for carotid closure in 72% of the patients.
Table 3 shows the
perioperative and late morbidity and mortality rates.
Follow-up duration of all survivors was 40.6±23.5 months (range, 2 to
103 months; interquartile,: 19 to 59 months).
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Predictors of Long-Term Outcome
Diabetes mellitus, abnormal preoperative 12-lead ECG results (in
particular, inverted T waves), preoperative neurological symptoms,
lower-extremity vascular disease, and history of IHD were the
independent predictors of long-term survival (Tables 4 and 5 and
Figure 1). Diabetes mellitus, history of
IHD, and lower-extremity arterial disease were the only
independent predictors of long-term cardiac morbidity (myocardial
infarction, congestive heart failure, unstable angina pectoris, PTCA,
or CABG) by multivariate analysis
[exp(ß)=2.54, 2.50, and 1.91; P=0.0004, 0.01 and 0.03,
respectively].
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Thallium Testing and Perioperative Coronary
Revascularization
The 226 patients who had preoperative thallium testing were
divided into the following 4 groups: group 1, 117 patients with normal
or mild defects on preoperative thallium testing and no previous
revascularization; group 2, 41 patients with
moderate-to-severe fixed and/or reversible defects who did not
undergo CR; group 3, 42 patients who had perioperative
CR as a result of the thallium testing; and group 4, 26 patients who
had undergone CR in the past that was not related to the preoperative
thallium testing. Nineteen of these patients had moderate-to-severe
(mostly fixed) thallium defects, and 7 had either normal scans or mild
perfusion defects.
Using Kaplan-Meier life-table analysis (Figure 2) patients in group 2 had significantly
worse overall and cardiac long-term survival compared with group 1,
(Log-rank=6.97 and 11.5, and P=0.008 and 0.0008,
respectively). Moreover, group 2 had a worse long-term overall and
cardiac survival than group 3 (log rank=4.97 and 5.41 and
P=0.02 and 0.06, respectively). group 4 had worse cardiac
survival than group 1 (P=0.04). By adding this grouping into
the multivariate Cox regression analysis
together with other independent predictors of survival (except for
preoperative ECG), only group 2 was independently associated with
long-term cardiac mortality (Table 5
).
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Patients in group 3 were not significantly different from those in
group 2 in terms of preoperative clinical predictors except for higher
incidences of history of ischemic heart disease (mainly history
of angina pectoris), left bundle-branch block by ECG, and a higher rate
of preoperative coronary angiography in group 3 (Table 6). Twenty-one patients in group 2
underwent preoperative coronary catheterization
without subsequent intervention. The reasons for not intervening were
as follows: mild coronary lesions with <70% stenosis
in 4 patients, double-vessel coronary disease with total
occlusion of at least 1 artery and <70% stenosis in 3
patients; significant coronary lesions unfavorable for PTCA and
not severe enough to warrant CABG in 8 patients; diffuse triple-vessel
disease not localized enough for PTCA and unsuitable for CABG because
of small vessels and/or poor runoff in 4 patients; and severe
triple-vessel disease in 2 patients in whom CABG was not recommended
because of aortic calcifications judged too hazardous for
coronary bypass. The other patients in group 2 were
asymptomatic and had mainly moderate-to-severe fixed
defects, with only mild or no redistributing defects on thallium
scanning, and they were therefore not referred for coronary
angiography by our cardiology consultant
(M.M.). Group 3 included 20 patients who had significant triple-vessel
disease and underwent CABG either before surgery (reversed staged; 2
patients), during the same surgery (combined CEA+CABG; 10 patients) or
a short time after CEA (staged; 8 patients). The other 22 patients in
group 3 had preoperative PTCA; 1 vessel in 15 patients and 2 vessels in
7 patients were dilated.
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Clinical Features Associated With Perioperative CR
Of the 42 patients in group 3, 29 (69.0%) had history of
ischemic heart disease (angina pectoris or myocardial
infarction anytime in their past), 25 (59.5%) had preoperative ECG
abnormality (T-wave inversion, ST-segment depression, pathological Q
waves, or left ventricular hypertrophy), 13
(31.0%) had symptomatic lower-extremity vascular disease,
and 15 (35.7%) had diabetes mellitus. Thirty-eight of the patients in
group 3 (92.9%) had at least 1 of the those preoperative features.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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This study shows that the main negative predictors of long-term survival after CEA are diabetes mellitus, preoperative 12-lead ECG abnormalities (T-wave inversion in particular), lower-extremity vascular disease, and preoperative neurological symptoms. In addition, PTS independently predicts long-term cardiac survival. Moderate-to-severe (fixed and/or reversible) defects are associated with a 2.8-fold increase in cardiac mortality if not treated by CR. Finally, long-term survival of patients who undergo CR based on PTS is similar to that of patients with normal scans or mild preoperative thallium defects and significantly better than that of patients with moderate-to-severe thallium defects who do not undergo CR.
Hertzer et al15 were the first to establish that cardiac disease plays a central role in morbidity and mortality of CEA patients. They routinely performed preoperative coronary angiography and showed that 37% of patients suspected of having CAD and 16% of those with no history of CAD had surgically correctable coronary lesions. Cardiac complications accounted for most early, as well as late, deaths following CEA, and long-term survival in their study was significantly improved in patients who underwent CABG based on preoperative coronary angiograms.16 Subsequent investigations confirmed that CAD rather than cerebrovascular disease is the most frequent cause of morbidity and mortality after CEA.6 17 Subgroups of patients without overt CAD but with diabetes mellitus, peripheral vascular disease, abnormal preoperative ECG, or coexisting intracranial occlusive disease also exhibit long-term cardiac survival as reduced as that of patients with overt CAD.9 18
In accordance with the findings of Hertzer et al, 29 (25%: 15 CABG and 14 PTCA) of our patients with and 13 (11.8%: 5 CABG and 8 PTCA) of those without symptomatic IHD had CR, although in our series these were based on preoperative thallium testing rather than routine coronary angiography. Our data also agree with the reports showing that preoperative clinical factors other than overt IHD, such as diabetes mellitus, ECG abnormality, and symptomatic lower-extremity vascular disease, are stronger predictors of long-term outcome than a clinical history of IHD, despite the fact that most (66%) late deaths are of cardiac origin. Our study, however, expands previous observations by underscoring the impact of PTS and selective CR on long-term survival following CEA.
In the present cohort study, 88% of the patients had preoperative thallium testing. One third of them had subsequent coronary angiography, and 54.5% of those who had coronary angiography were treated perioperatively by either PTCA (52.4%) or CABG (47.6%). Few studies report data on selective coronary angiography and revascularization after PTS. Most of the data are derived from patients undergoing a variety of vascular surgical procedures rather than only CEA.19 20 21 In those studies, coronary angiography was performed in 7.5% to 35% of the patients studied by thallium imaging. Coronary revascularization, however, was performed in only 15% to 36% of those who had coronary angiography. Massie et al20 contended that coronary angiography did not provide any additional useful information for most peripheral vascular surgery patients with abnormal thallium scanning; this was due to their poor coronary anatomy, which was not suitable for revascularization. In contrast, in our study a relatively high proportion of the patients had CRs. This proportion is almost identical to that (55%) predicted on theoretical grounds by Mason et al22 from the high sensitivity and specificity of thallium testing in detecting CAD and the estimated feasibility of CR in vascular surgery patients. Mason et al also predicted that 50% of the patients could be revascularized by PTCA. The difference between our data and those of Massie et al20 may reflect the fact that the prevalence of correctable CAD is different in CEA and lower-extremity arterial bypass patients,23 although other factors, such as differences in views of the treating clinicians about which coronary vessels can be revascularized, could contribute to the difference between the 2 studies.
Thallium SPECT scanning has a high sensitivity (87% to 98%) and a
good specificity (56% to 91%) for detection of CAD24 and
is a well known predictor of long-term cardiac morbidity and
mortality.25 In our study also, thallium scanning was an
independent predictor of long-term cardiac mortality in patients not
treated by CR (Table 5). Furthermore, our study is the first to
show that selective CR guided by routine thallium testing significantly
improves long-term survival in patients undergoing CEA. Survival after
perioperative CR resembled that of patients with normal
or mild thallium abnormality and was significantly better than that of
patients with moderate-to-severe thallium defects who did not undergo
such revascularization (Figure 2).
CABG is known to improve long-term survival in both moderate- and high-risk cardiac patients (risk defined by number of diseased vessels and presence of left ventricular dysfunction).26 PTCA and CABG confer similar long-term survival rates in patients with multivessel coronary disease, although PTCA requires more subsequent coronary interventions than CABG.27 28 In the present study, CR based on routine thallium testing in CEA patients improved long-term survival even though the CR group (group 3) included patients with single- and double-vessel as well as multivessel coronary disease. It is possible, therefore, that preoperative thallium testing and CR initiated a track of better cardiac follow-up and repeated CRs in patients in whom revascularizations were feasible, which then contributed to the better survival of these patients.
Should all patients undergoing CEA have PTS? Our data agree with those
of previous publications that routine preoperative thallium testing is
not indicated solely for the purpose of stratifying and lowering
perioperative cardiac risk. We do show, however, that
the mere fact that a patient is a candidate for carotid surgery is an
indication for more intensive cardiac screening, such as thallium
scanning, because CR based on such testing can improve the patient's
long-term survival. Thallium scanning may be performed preoperatively
whereas CR, if indicated, can be done before, after, or even during the
same surgery, according to each patient's risks and benefits.
Moreover, 93% of the patients who underwent
perioperative CR (group 3) had at least 1 of the
following findings: history of ischemic heart disease, abnormal
preoperative ECG abnormality, diabetes mellitus, and
symptomatic lower-extremity vascular disease. Patients
without these findings (26% of all our patients) had an excellent
long-term survival (Figure 1) and could probably be spared the
preoperative thallium testing. The remaining 74% of the patients are
those who benefited most from the preoperative cardiac screening. In
contrast, testing only patients with a history of ischemic
heart disease (47% of our patients) would result in the detection of
only 69% of the cases with correctable CAD.
Study Limitations
PTS was used as part of our routine cardiac assessment
strategy and not as a study protocol. This investigation is therefore a
case series and not a case-control study. Consequently, groups 2 and 3,
which form the core of the study, may not be entirely comparable
because patients were not randomly assigned to either group but rather
selected by the cardiology consultants on the
basis of on their thallium imaging and angiography results. Group 3
contained the highest-risk patients who were selected for
revascularization. Group 2 also included patients
with mainly fixed defects but also patients in whom CR was
theoretically indicated but not performed because of technical
considerations of feasibility of the procedures. Both groups were
comparable, however, in terms of their other preoperative clinical
predictors, except for the higher incidence of overt ischemic
heart disease in group 3.
We conclude that coronary angiography and revascularization based on preoperative thallium dipyridamole scanning can be safely performed in CEA patients by tailoring the right type and timing of revascularization to each patient's coronary anatomy and overall risk. Such CR, if performed before, during, or after operation, significantly improves patients' long-term survival. Further prospective randomized studies are needed to confirm our findings.
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Acknowledgments |
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We are deeply indebted to our colleague, Dr Oz Tibon, who started this work as part of his MD thesis and died as a medical officer in the IDF on January 16, 1996.
Received June 12, 1998; revision received September 10, 1998; accepted September 10, 1998.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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