| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Nuclear Medicine |
1 From the Departments of Cardiology (A.F.L.S., A.E. R.T.v.D., J.R.T.C.R., D.P.) and Nuclear Medicine (R.V.), Erasmus Medical Center Rotterdam, Dr Molewaterplein 40, Thoraxcenter Rm Ba 300, 3015 GD Rotterdam, the Netherlands, and the Department of Cardiology, Leiden University Medical Center, the Netherlands (J.J.B.). Received February 14, 2002; revision requested March 7; revision received May 6; accepted June 25. Address correspondence to D.P. (e-mail: poldermans@hlkd.azr.nl).
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
MATERIALS AND METHODS: Clinical data and SPECT results were analyzed in 531 consecutive patients. Follow-up was successful in 528 (99.4%) patients; 55 underwent early revascularization and were excluded. Normal or abnormal findings were considered in the absence or presence of fixed and/or reversible perfusion defects. A summed stress score was calculated to estimate the extent and severity of perfusion defects. Univariate and multivariate Cox proportional hazards regression models were used to identify independent predictors of late cardiac events. The incremental value of myocardial perfusion scintigraphy over clinical variables in predicting events was determined according to two models. The probability of survival was calculated by using the Kaplan-Meier method.
RESULTS: Findings were abnormal in 312 patients. During 8.0 years ± 1.5 of follow-up (range, 4.5–10.6 years), cardiac death occurred in 67 patients (total deaths, 165); nonfatal myocardial infarction, in 34; and late revascularization, in 49. The annual rates for cardiac death, cardiac death or infarction, and all events were 0.9%, 1.2%, and 1.5%, respectively, after normal findings and 2.7%, 3.4%, and 4.4%, respectively, after abnormal findings (P < .05). In a multivariable Cox proportional hazards model, not only an abnormal finding but also the summed stress score provided incremental prognostic information in addition to clinical data. The hazard ratio for cardiac death was 1.09 (95% CI: 1.01, 1.18) per 1-unit increment of the summed stress score.
CONCLUSION: The incremental prognostic value of dobutamine stress 99mTc-sestamibi SPECT over clinical data was maintained over an 8-year follow-up in patients with limited exercise capacity.
© RSNA, 2002
Index terms: Heart, abnormalities, 51.771 • Heart, SPECT, 51.12119
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
However, it is important to note that to our knowledge, no findings of long-term prognostic studies involving 99mTc-sestamibi myocardial perfusion imaging are currently available (1–7). The purpose of our study was to determine the long-term prognostic value of dobutamine stress 99mTc-sestamibi SPECT findings in patients with limited exercise capacity.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
In all patients, a structured interview was performed and a clinical history obtained, including assessment of cardiac risk factors, prior to dobutamine stress testing. Hypertension was defined as blood pressure of 140/90 mm Hg or greater or treatment with antihypertensive medication. Diabetes mellitus was defined as a fasting glucose level of 7.8 mmol/L or higher or the need for insulin or oral hypoglycemic agents. Hypercholesterolemia was defined as a total cholesterol level of 6.4 mmol/L or higher or as treatment with lipid-lowering medication.
Dobutamine Stress Protocol
Stress testing after dobutamine administration was performed as described previously (8). Dobutamine hydrochloride (Dobutamine; Centrafarm Services, Etten-Leur, the Netherlands) was injected intravenously, first at a dose of 10 µg per kilogram of body weight per minute for 3 minutes; the dose was then increased by 10 µg/kg/min every 3 minutes up to a maximum dose of 40 µg/kg/min. If the test end point was not reached at a dobutamine dose of 40 µg/kg/min, up to 1 mg of atropine sulfate (Atropine; Centrafarm Services) was administered intravenously. Blood pressure, heart rate, and electrocardiographic (ECG) findings were continuously monitored. Test end points were achievement of target heart rate (85% of maximum age and sex-predicted heart rate); horizontal or downsloping ST segment depression of more than 2 mm at an interval of 80 msec after the J point, as compared with the baseline measurement; ST segment elevation greater than 1 mm in patients without previous myocardial infarction (MI); severe angina; systolic blood pressure decrease greater than 40 mm Hg, as compared with the baseline measurement; blood pressure higher than 240/120 mm Hg; or clinically important cardiac arrhythmias. Intravenously administered metoprolol tartrate (Metoprolol, Selokeen IV; AstraZeneca, Zoetermeer, the Netherlands) was available to reverse the side effects of dobutamine, and atropine was used if the effects did not revert spontaneously after termination of dobutamine infusion. Side effects were registered, and the relationship between cardiac arrhythmias during testing and subsequent cardiac events was evaluated.
SPECT Image Acquisition and Interpretation
A dose of 370 MBq of 99mTc-sestamibi (Cardiolite; Bristol-Myers Squibb Pharma Belgium, Brussels, Belgium) was administered intravenously approximately 1 minute prior to termination of the stress test. For studies performed with the patient at rest, 370 MBq of sestamibi was injected at least 24 hours after the stress test. Images were acquired with a Gammasonics single-head Rota camera (Orbiter; Siemens, Iselin, NJ) without attenuation or scatter correction, by using a low-energy all-purpose collimator. Thirty-two projections were obtained over a 180° arc, from left posterior oblique to right anterior oblique, with an acquisition time of 45 seconds per projection. Data were collected in a 64 x 64 matrix (word mode), and images were reconstructed by using a filtered backprojection algorithm and a ramp reconstruction filter. Transverse images were reconstructed by using a software package (SPETS; Nuclear Diagnostics, Hägersten, Sweden). From the three-dimensional data, oblique (short-axis) and sagittal (vertical long-axis) images obtained perpendicular and parallel to the long axis, respectively, were reconstructed. For each study, six oblique sections were defined from the apex to the base, and three sagittal sections were defined. Each of the six short-axis sections was divided into eight equal segments. The septal part of the two basal sections was excluded from analysis because this region corresponds to the fibrous portion of the interventricular septum and normally exhibits reduced uptake. Therefore, a total of 47 segments were identified (three long axis and 44 short axis). Scans were semiquantitatively interpreted by using visual analysis assisted by circumferential profile analysis. Profile curves 2.5 SDs below normal perfusion were considered abnormal.
Images obtained at stress and rest were reviewed side by side at a computer display with consensus reading by two experienced observers who were unaware of the patients’ clinical data. In case of disagreement, a majority decision was achieved by consulting a third observer. In this study, the original interpretations of the images were used. A reversible perfusion defect was defined as a perfusion defect on stress images that partially or completely resolved at rest on two or more contiguous segments or sections in the 47-segment model. A fixed perfusion defect was defined as a perfusion defect on stress images on two or more contiguous segments or sections that persisted on rest images in the 47-segment model. Findings were designated as abnormal in the presence of a fixed and/or reversible perfusion defect.
To assess the severity of perfusion abnormalities, the left ventricular myocardium was divided into six segments: anterior, inferior, septal anterior, septal posterior, posterolateral, and apical. Each of the six major left ventricular segments was assigned a score by using a four-point system: 0, normal (100% 
tracer activity > 75%); 1, slightly reduced (75% tracer activity > 50%); 2, moderately reduced (50% tracer activity > 25%); or 3, severely reduced or absent uptake (25% tracer activity 0%). A summed stress score (SSS) was obtained by adding the scores of the six myocardial segments during stress. The SSS incorporates the extent and severity of a perfusion defect.
Follow-up
Follow-up data were collected in 2001. One author (A.F.L.S.) contacted patients’ general practitioners and/or reviewed hospital records. This author was blinded to scanning results. The date of the last examination or consultation was used to determine follow-up. The mean follow-up was 8.0 years ± 1.4 (range, 4.5–10.6 years). End points were overall deaths (death from all causes), cardiac death, nonfatal MI, or late (>60 days) coronary revascularization. Cardiac death was defined as death caused by acute MI, clinically important cardiac arrhythmias, or refractory congestive heart failure, together with ECG and autopsy results, when available. Sudden death occurring without another explanation was included as cardiac death. Cardiac enzyme levels and ECG changes were used to define nonfatal MI. Patients were censored at the time of late coronary revascularization.
Statistical Analysis
Values were expressed as means ± SDs or numbers and were compared by using the Student t test or 
2 test. Univariate and multivariate Cox proportional hazards regression models (BMDP Statistical Software, Los Angeles, Calif) were used to identify independent predictors of late cardiac events (9). Variables were selected in a stepwise forward selection manner, with entry and retention set with a P value of .05 considered to indicate a significant difference. A variable’s risk was expressed as a hazard ratio with a corresponding 95% CI. The incremental value of myocardial perfusion scintigraphy over the clinical variables in the prediction of events was calculated according to two models. In model 1, the only scanning variable entered was an abnormal finding. In model 2, scanning variables, including SSS and the presence of a fixed or reversible defect, were entered. The probability of survival was calculated by using the Kaplan-Meier method, and survival curves were compared by using the log-rank test. A P value less than .05 was considered to indicate a statistically significant difference.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
|
Predictive Value of Clinical Data and Test Results
Univariate and multivariate predictors of cardiac events are presented in Tables 2 and 3. The annual event rates for cardiac death, cardiac death or nonfatal MI, and all events were 0.9%, 1.2%, and 1.5%, respectively, for patients with normal findings and 2.7%, 3.4%, and 4.4% for patients with abnormal findings. Kaplan-Meier survival curves are presented in Figures 1–3. The survival curves indicate that patients with normal sestamibi SPECT findings after induced stress maintained a low event rate up to 8 years after stress testing. Figure 4 demonstrates the incremental prognostic value of dobutamine stress sestamibi SPECT findings over clinical data. An abnormal perfusion pattern, as well as the SSS, provided additional incremental prognostic information. The hazard ratio for cardiac death was 1.09 (range, 1.01–1.18) per 1-unit increment of the SSS. There was no further increase of the hazard ratio if the SSS was greater than 9.
|
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
Long-term Prognostic Value
Although the findings of long-term prognostic studies are currently not available, the medium-term prognostic value of dobutamine stress sestamibi SPECT has been reported in several studies (4–7). Geleijnse et al (4) examined 392 patients, with a median follow-up of 22 months ± 13. Twenty-seven (7%) patients died of cardiac-related causes during follow-up, 17 (4%) had nonfatal MIs, and 34 (9%) underwent late coronary revascularization. The hard cardiac event (cardiac death or nonfatal MI) rates were 0.8% per year in patients with normal examination findings and 9.2% per year in those with abnormal dobutamine stress sestamibi SPECT scintigraphic findings.
The medium-term prognosis of women with chest pain and normal dobutamine stress sestamibi SPECT images is excellent (5). None of the study population of 80 women died or had a nonfatal MI during the follow-up of 23 months ± 13. Senior et al (6) followed up 61 patients undergoing coronary angiography and dobutamine stress sestamibi SPECT for 19 months ± 11. There were two (3%) deaths, two (3%) nonfatal MIs, 13 (21%) cases of unstable angina, and three (5%) cases of congestive heart failure during follow-up. The event rate was 3% in patients with normal results and 44% in patients with abnormal results. Recently, Calnon et al (7) studied 308 patients at high risk for cardiac events who underwent dobutamine stress sestamibi SPECT. During an average follow-up of 1.9 years ± 1.1, 15 patients died of cardiac causes and 18 had MIs. Event rates were 10.0% in patients with abnormal SPECT images and 2.3% in those with normal results.
The findings of the present study extend the conclusions drawn from the four medium-term prognostic studies (4–7). In the current study population of 473 patients, the prognostic value of dobutamine stress sestamibi SPECT imaging was maintained over an 8-year period. The event rates for cardiac death, cardiac death or nonfatal MI, and all events were, respectively, 0.9%, 1.2%, and 1.5% per year for patients with normal results and 2.7%, 3.4%, and 4.4% per year for those with abnormal results. Moreover, Kaplan-Meier survival curves continued to diverge over time, whereas the curve for patients with normal SPECT findings showed favorable event-free survival, indicating that the prognostic value was maintained during the entire follow-up period. This is particularly relevant, since some investigators have recently suggested that the "warranty" period for normal findings of sestamibi imaging after stress appears to be 2 years (2). In contrast, findings of the present study indicate that patients with normal findings of sestamibi imaging after stress have a durable good prognosis up to 8 years after index stress testing. The annual event rate for cardiac death or nonfatal MI in patients with normal scintigraphic results was comparable with the event rate in the general population. Hence, patients with normal SPECT images can be spared further invasive evaluation of their coronary anatomy. However, the clinical value and optimal intervals of periodic stress testing in these patients deserve further investigation.
Incremental Prognostic Value
In this study, a multivariate Cox regression model demonstrated that dobutamine stress sestamibi SPECT had an incremental prognostic value in addition to prognostic information from clinical data and stress testing. This is in agreement with the findings obtained in long-term follow-up studies in which thallium 201 SPECT was used to stratify patients (10–14). Independent clinical predictors of cardiac events were age, male sex, diabetes mellitus, and congestive heart failure. Typical angina was not independently predictive of events, perhaps because of diminished physical activity in a population with a limited exercise capacity. The incremental value of myocardial perfusion scintigraphy over the clinical variables in the prediction of events was determined according to two models: In the first model, abnormal findings were a powerful independent scintigraphic predictor of future cardiac events. The second model demonstrated that the SSS was additive to clinical parameters and to hemodynamic and ECG parameters. This indicates that the long-term prognosis is related not only to the presence but also to the extent and severity of perfusion defects on dobutamine stress sestamibi SPECT scans.
Limitations
The diagnostic value of dobutamine stress sestamibi SPECT was high; however, 9% of patients had inconclusive findings (failure to achieve the target heart rate or to demonstrate a perfusion abnormality). Therefore, the diagnostic and perhaps the prognostic value could have been even higher if beta-blocker medication had been routinely withheld before stress testing.
In conclusion, the incremental prognostic value of dobutamine stress 99mTc-sestamibi SPECT findings over clinical data is maintained at long-term follow-up. Patients with normal test results have a good long-term prognosis and thus may not require further invasive evaluation.
|
FOOTNOTES |
|---|
Author contributions: Guarantors of integrity of entire study, A.F.L.S., J.R.T.C.R., D.P.; study concepts, all authors; study design, A.F.L.S., A.E., R.T.v.D., J.R.T.C.R., D.P., R.V.; literature research, A.F.L.S., A.E.; clinical studies, A.F.L.S., A.E., D.P., R.V.; data acquisition, R.T.v.D., R.V.; data analysis/interpretation, A.F.L.S., A.E., R.T.v.D., D.P., R.V.; statistical analysis, R.T.v.D.; manuscript preparation, A.F.L.S., A.E., D.P.; manuscript definition of intellectual content, all authors; manuscript editing, J.R.T.C.R., D.P., A.E., R.V.; manuscript revision/review, A.E., J.J.B., J.R.T.C.R., D.P., R.V.; manuscript final version approval, all authors.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  B. A. Herzog, L. Husmann, I. Valenta, O. Gaemperli, P. T. Siegrist, F. M. Tay, N. Burkhard, C. A. Wyss, and P. A. Kaufmann Long-Term Prognostic Value of (13)N-Ammonia Myocardial Perfusion Positron Emission Tomography Added Value of Coronary Flow Reserve. J. Am. Coll. Cardiol., July 7, 2009; 54(2): 150 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Bax, S. E. Inzucchi, R. O. Bonow, J. D. Schuijf, M. R. Freeman, E. J. Barrett, and on behalf of the Global Dialogue Group for the Eva Cardiac Imaging for Risk Stratification in Diabetes Diabetes Care, May 1, 2007; 30(5): 1295 - 1304. [Full Text] [PDF]
|
|
|
|
 |
|
 J. J Bax, R. O Bonow, D. Tschoepe, S. E Inzucchi, and E. J Barrett Early detection of coronary heart disease in diabetic patients without symptoms of coronary artery disease: implications for expanded use of myocardial perfusion imaging The British Journal of Diabetes & Vascular Disease, September 1, 2005; 5(5): 283 - 288. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |
