Ann Thorac Surg 1997;64:473-477
© 1997 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Impact of Early Exercise Radionuclide Cineangiography on Long-Term Prognosis After CABG
Itzhak Shapira, MD,
Israel Heller, MD,
Aharon Isakov, MD,
Jacob Gurevitch, MD,
Vladimir Yakirevich, MD,
Marcel Topilsky, MD,
Yael Villa, PhD,
Amos Pines, MD
Departments of Cardiology, Internal Medicine "H," Cardiothoracic Surgery, Medical Statistics, and Internal Medicine "T," Tel Aviv E. Sourasky Medical Center affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Accepted for publication March 4, 1997.
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Abstract
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Background. The immediate benefits of coronary artery bypass grafting might be only transient. This prospective study examined the capability of exercise radionuclide cineangiography done shortly after coronary artery bypass grafting to predict outcome and long-term prognosis.
Methods. Results of exercise radionuclide cineangiography at 5.5 ± 0.7 months (range, 4 to 8 months) postoperatively were correlated with mortality, major surgical and nonsurgical cardiac events, and cardiac event–free survival in 100 consecutive patients who underwent coronary artery bypass grafting. Stepwise logistic regression analysis was used to evaluate the incremental value of radionuclide cineangiography beyond the commonly used variables.
Results. Left ventricular ejection fraction at rest was normal (
0.45) in 72 patients and increased on exercise in 58. The exercise radionuclide variables that correlated with future cardiac events were change and fractional change in heart rate, ST segment changes, anginal pain and congestive heart symptoms during exercise, rest ejection fraction, and change and fractional changes in ejection fraction. Predictors of event-free survival were exercise heart rate, rest ejection fraction, and change and fractional change in ejection fraction during exercise. Logistic regression analysis revealed that change in ejection fraction was an independent predictor of cardiac death and surgical interventions, whereas resting ejection fraction was a predictor of nonsurgical cardiac events.
Conclusions. Postoperative exercise radionuclide cineangiography carried out soon after coronary artery bypass grafting had definite independent prognostic value and should be performed routinely to help decide treatment protocol.
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Introduction
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In patients undergoing coronary artery bypass grafting (CABG), the initial symptoms and signs of angina and coronary ischemia may recur soon after operation to as long as a decade later [1, 2]. Beyond this period, survival rates of surgically and medically treated patients become similar [3]. Objective determination of risk for adverse events after operation bears enormous clinical importance. Reappearance of symptoms and resting and exercise electrocardiographic results have poor prognostic value [4, 5], and serial coronary angiographic studies are impractical and expensive. Several studies have shown the results of radionuclide cineangiography have prognostic significance in both medically and surgically treated patients with coronary artery disease [6–8]. However, the contribution of exercise radionuclide cineangiography done soon after operation in determining the prognosis of patients after CABG has not been adequately assessed. This study prospectively evaluates a cohort of 100 patients in whom an exercise radionuclide study was performed a short time (4 to 8 months) after CABG. The aim of the study was to find out whether ejection fraction (EF) has an incremental value on prognosis, in addition to the known clinical parameters long used for this purpose.
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Material and Methods
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The study population comprised 100 consecutive patients who underwent CABG. Since June 1987, patients have been referred to the post–cardiac surgery follow-up clinic of a 1,000-bed municipal medical center 3 months after discharge from hospital. These patients were prospectively evaluated. Exclusion criteria from the study included the following: unstable angina, myocardial infarction (MI) occurring postoperatively but preceding commencement of the study, prior heart operation (including congenital heart disease correction, valve replacement, aneurysmectomy, or implantable cardioverter defibrillator insertion), evidence of cardiomyopathy, repeat CABG or angioplasty 2 months or less after radionuclide cineangiography, left ventricular (LV) EF (LVEF) of 0.30 or lower during study at rest, and any life-threatening noncardiac disease.
Clinical Variables
Age at CABG, sex, history of MI, functional class of angina, and evidence of congestive heart failure on radionuclide examination were obtained from direct interviews with the patients and were supplemented by hospital discharge files (available for all patients). Eighty-three patients were men, the mean age at operation was 57.4 ± 9.6 years (range, 39 to 87 years), and 33 of the patients had sustained an MI prior to operation. The New York Heart Association [9] functional class for angina was 1.6 ± 0.8, and The Canadian Cardiovascular Society [10] congestive heart failure class was 1.2 ± 0.6.
Catheterization and Coronary Artery Bypass Grafting
Results of left ventriculography, selective coronary angiography, and CABG were retrieved from the original hospital discharge reports. A lesion was considered to be angiographically significant if a reduction of 50% or more in the diameter of the respective artery was observed. Proximal coronary artery disease was defined as such if the major lesion occurred proximal to the origin of the first septal perforator or the first obtuse marginal branch or in the first half of the right coronary artery.
All the operations were performed at the same medical center. A revascularization index [6] was used for reporting the surgical results in this study and was computed by dividing the number of graft anastomoses performed by the number of major vessels or major branches with angiographically significant lesions. On catheterization, 10% of the study patients were shown to have one-vessel disease, 32% had two-vessel disease, and 58% had three-vessel disease. Left main coronary artery disease was found in 15 patients, proximal three-vessel disease in 18, and proximal left anterior descending coronary artery disease in 33. The number of diseased coronary arteries (the major branches also being counted) per patient was 2.8 ± 0.9; 10 patients had one diseased coronary artery, 24 had two diseased coronary arteries, 43 had three, 22 had four, and 1 patient had five. The number of implanted grafts per patient was 2.7 ± 0.9; 8% of patients had one anastomosis, 36% had two anastomoses, 37% had three, 18% had four, and 1% had five anastomoses. The internal mammary artery was used in 26% of the patients, and the revascularization index was 0.98 ± 0.22.
Radionuclide Cineangiography
Gated equilibrium radionuclide cineangiography was done in all patients for routine assessment shortly after bypass grafting, ie, 5.5 ± 0.7 months (mean ± standard deviation) (range, 4 to 8 months) postoperatively. All the patients were evaluated by exercise radionuclide cineangiography before their second visit to the clinic. The procedure was performed using standard guidelines, similar to those previously described [11, 12]. ß-Blockers and angiotensin-converting enzyme inhibitors were stopped 48 hours prior to the examination. The LVEF was considered normal at 0.45 or greater, and an increase of 0.05 or more was an adequate exercise response. The exercise test was performed at an initial load of 25 W, and this was gradually increased by 25 W at 3-minute intervals until the target heart rate (according to age) was achieved or until angina, dyspnea, or severe fatigue developed. The tests were interpreted by qualified readers who were blinded to patient characteristics. The results are shown in Table 1
. The following variables were screened for prognostic importance: LVEF (resting, exercise, difference [
]) systolic blood pressure (resting, exercise, ), diastolic blood pressure (resting, exercise, ), heart rate (resting, exercise, ), heart rate–blood pressure double product, ST segment variation with exercise, presence of pain or congestive heart failure or both during exercise, and fractional change ( divided by initial value) in heart rate, blood pressure, and LVEF.
After the initial follow-up at the Cardiothoracic Surgery Department, the patients were referred to the post–cardiac surgery follow-up clinic and underwent clinical evaluations four times a year during the first 2 postoperative years, two times a year in the next 2 years, and subsequently once annually unless cardiac events occurred or there were cardiac complaints. This follow-up schedule was also observed by the study cohort, the end point being 6 years of follow-up or death. The periodic assessment of the study population included the registration of cardiac symptoms, occurrence of MI, repeat CABG, or coronary angioplasty. The anamnestic data were always supplemented by a review of the data recorded in hospital records. Drug regimens and intervention procedures were determined by the clinic's physicians and were based on the patient's clinical status and the results of the radionuclide cineangiographic study. Categorization of the cause of death was established by information contained in the medical charts or death certificates. Deaths were considered "cardiac" if they resulted from cardiac arrhythmias, congestive heart failure, or MI. No patient was lost to follow-up.
Statistical Analysis
All data are expressed as the mean ± the standard deviation or as a percentage, when appropriate. The univariate analysis was performed using the 
2 test for discrete variables, the t test for continuous variables normally distributed, and the nonparametric Mann-Whitney test for ordinal variables. To evaluate the incremental contribution of EF to prediction of cardiac death and cardiac events, stepwise multivariate logistic regression analysis was performed after adjusting for clinical variables found to be significant in the univariate analysis.
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Results
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Exercise Radionuclide Cineangiography
The LVEF at rest was normal (0.45) in 72 patients, and the exercise LVEF exceeded the lower normal limit in 74 patients. The LVEF increased during exercise in 58 patients. When the EF failed to rise during exercise, the distribution of the EF was as follows: -0.01 to -0.05 in 34 patients, -0.06 to -0.10 in 5, and -0.11 or more in 3. Table 1
shows the data from exercise radionuclide cineangiography.
Mortality
Twenty-one patients died during follow-up: 14 had a documented cardiac death, and 7 died of noncardiac disease (6 of cancer, 1 of stroke) (Tables 2, 3). Resting and exercise LVEFs were similar for patients who sustained a cardiac death and for survivors (0.54 ± 0.08 versus 0.50 ± 0.1, 0.52 ± 0.09 versus 0.51 ± 0.09, respectively). However, the mean rest-to-peak exercise differences in LVEF were -0.021 ± 0.04 in those who died versus 0.013 ± 0.045 (p = 0.01) in those who were alive at the end of follow-up. Stepwise logistic regression showed that EF had a significant independent prognostic value (p = 0.03), ie, the larger the rest-to-peak exercise difference, the better the prognosis. The rest-to-peak exercise differences in heart rate and systolic blood pressure were similar for patients who died and survivors, whereas the diastolic blood pressure difference was larger in the latter group (15.8 ± 12.8 mm Hg versus 6.7 ± 4.8 mm Hg; p < 0.01).
Nonfatal Events
Among the survivors, there were seven nonfatal MIs and 16 revascularization interventions (see Table 2). The results of early postoperative radionuclide angiography correlated with the later need of revascularization procedures. Patients who eventually required and underwent such an intervention demonstrated a decrease in LVEF on exercise in contrast with those who had no need of an additional procedure (-0.05 ± 0.04 versus 0.03 ± 0.03; p < 0.001). Stepwise logistic regression analysis demonstrated an independent positive correlation between EF at rest and future nonsurgical cardiac events (p = 0.05); a similar association was found for EF and surgical events (p = 0.01). As for all events, EF and resting EF were both independent prognostic variables (p = 0.009 and p = 0.02, respectively). The rest-to-peak exercise difference in heart rate was larger in patients who completed 6 years of an uneventful follow-up compared with those who required an intervention (65 ± 22 versus 45 ± 16 beats/min; p < 0.001). Similar findings were observed for the rest-to-exercise difference in diastolic blood pressure (17.9 ± 13 mm Hg versus 10.6 ± 9 mm Hg; p = 0.035). The multivariate analysis showed that the difference in LVEF just discussed predicted future interventions at a p value of less than 0.002, and the difference in diastolic blood pressure had a marginal (p = 0.05) predictive significance.
Exercise-Induced Anginal Pain
The classic exercise-related symptom for myocardial ischemia, ie, angina pectoris, was also found to have important prognostic significance. Nine (64%) of 14 patients who died of cardiac disease had complained of anginal pain during radionuclide angiography compared with only 23 (27%) of the 86 others (p = 0.005). Also, pain was present in all 16 patients who underwent some type of cardiac intervention versus only 7 (11%) of 63 patients who needed no therapeutic procedure (p = 0.001).
Total Event-Free Survival
Fifty-six patients survived without any major cardiac event and required no cardiac surgical intervention during follow-up. The most significant predictors of event-free survival in this subgroup were exercise heart rate, resting LVEF, and change and fractional change in LVEF during exercise. Other significant predictors are shown in Table 3.
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Comment
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This study assessed the prognostic contribution of radionuclide angiography performed early after CABG during a 6-year follow-up. Major end points were death or the occurrence of an MI or the need of another cardiac intervention in survivors. The results of our study suggest that the LVEF response to exercise is valuable for long-term prediction of outcome. These findings not only support the results of two previous studies [6, 8], but also amplify and extend them. Iskandrian and associates [8] found that LVEF at peak exercise provided the best independent predictive information, which was not significantly improved when LVEF was also taken into consideration. We found a significant association between the prognosis and LVEF at peak exercise in patients studied by radionuclide cineangiography 4 to 8 months postoperatively and followed up for a further 78 months. Wallis and co-workers [6] suggested that LVEF response to exercise had a long-lasting predictive value even many years after the initial cardiac evaluation. Moreover, the predictive value could be inferred even when LVEF response was obtained 2 or 3 years after the operation.
The present study demonstrates that the rest-to-peak exercise difference in LVEF, rather than the peak exercise value, is of prognostic significance in patients who have undergone CABG. These findings are consistent with data on patients with coronary artery disease who did not undergo a bypass operation [8]: the evaluation of LVEF during exercise in this population bears decided prognostic value, as these changes in patients with preserved LV function were predictors of death and progressive anginal symptoms requiring revascularization [13]. In the present study, the radionuclide cineangiography was performed 5.5 ± 0.7 months postoperatively (range, 4 to 8 months) in 100 consecutive patients who fulfilled the inclusion criteria of the study.
The patients in our study were followed for a relatively long time, with emphasis on data collection regarding survival, major cardiac events, and revascularization procedures. The uniform timing of radionuclide studies carried out in our study was lacking in the study reported by Wallis and colleagues [6], and our patients were followed up to 6 years in contrast with the study of Iskandrian and co-workers [8] in which the follow-up was relatively brief.
In the present study, as in that of Wallis and associates [6], the patients with severely depressed LVEF at rest (
0.30) were excluded. The variation in LVEF changes was shown to influence the value of LVEF at rest [14]: this variation decreases as LVEF at rest decreases. However, more than 90% of patients with known or suspected coronary artery disease referred for radionuclide testing were found to be in the group with an LVEF of 0.30 or higher [15].
Study Limitations
The study group consisted of patients with an LVEF of 0.30 or more at rest. Among patients with relatively well preserved LV function, the prognostic value was related only to the LVEF at peak exercise and not to the LVEF changes [15]. Thus, inclusion of patients with severe LV ventricular dysfunction may be expected to add weight to the predictive value of absolute LVEF at exercise. Consequently, the present study design means that our conclusions are based only on patients with relatively well preserved ventricular performance, similar to those reported by Wallis and co-workers [6] and in randomized surgical trials [16, 17].
The study was carried out at a follow-up clinic, and the results of radionuclide cineangiography were among the considerations in deciding therapeutic recommendations. For this reason, patients whose LVEF decreased significantly during the study were detected at a comparatively earlier phase, and these same patients had undergone a larger number of revascularization procedures at an earlier stage. This finding does not diminish the clinical importance of early routine radionuclide cineangiography. The results of the European Coronary Surgery Study Group [3] indicate that survival benefits, although significant in the early postsurgical period, are not maintained throughout a very long follow-up. Our findings may indicate that early postoperative LVEF response to exercise can serve to stratify those patients at risk of loss of bypass benefits. Subsequent referral of such patients to invasive evaluation and revascularization, when deemed necessary, could have far-reaching advantage.
The internal mammary artery was used as a conduit graft in 26% of the patients in the present study; the use of this artery has since become more widespread. Because of the relatively small number of internal mammary arteries employed, we were unable to demonstrate its potential value as a predictive tool. As a bypass conduit, it has been shown to improve the prognosis in patients undergoing CABG [18]; therefore, had it been used more frequently in our series, the rate of adverse events would probably have been lower.
Clinical Implications
Exercise radionuclide cineangiography performed at an early postoperative interval in patients who have undergone CABG has clear prognostic significance. Routine performance of this examination throughout the postoperative workup is advisable, and the results should be taken into consideration when treating these patients.
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Acknowledgments
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We thank Ms Esther Lior for her secretarial assistance in running the post–cardiac surgery follow-up clinic and Ms Esther Eshkol for manuscript preparation.
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Footnotes
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Address reprint requests to Dr Shapira, Tel Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv 64239, Israel (e-mail: shapiraiz{at}tasmc.health.gov.il).
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References
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Abstract
Introduction
