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Exercise Tomographic Thallium-201 Imaging in Patients with Severe Coronary Artery Disease and Normal Electrocardiograms

Timothy F. Christian, MD; Todd D. Miller, MD; Kent R. Bailey, PhD; and Raymond J. Gibbons, MD
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From the Mayo Clinic, Rochester, Minnesota. Requests for Reprints: Timothy F. Christian, MD, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1994;121(11):825-832. doi:10.7326/0003-4819-121-11-199412010-00001
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Objective: To assess the incremental value and cost-effectiveness of exercise tomographic thallium-201 imaging compared with clinical and exercise electrocardiographic variables for detecting three-vessel or left main coronary artery disease in patients with normal at-rest electrocardiograms.

Design: Prospective cohort study.

Participants: 411 patients (77 [19%] had three-vessel or left main disease) with normal at-rest electrocardiograms who underwent exercise tomographic thallium-201 studies and subsequently had coronary angiography.

Measurements: Clinical, exercise, and thallium-201 variables; univariate followed by multivariate logistic regression analysis to determine predictors of three-vessel or left main disease (clinical variables; clinical and exercise electrocardiographic variables; and clinical, exercise, and thallium-201 variables). Patients were classified by each of these models into low-, intermediate-, and high-risk groups.

Setting: A tertiary referral center.

Results: Among the clinical variables, diabetes mellitus, sex, age, and typical angina were independently associated with severe coronary disease (46% of patients were correctly classified into low- or high-risk groups). The peak exercise heart rate-blood pressure product and the magnitude of the exercise-induced ST depression added independent information to clinical variables. Among the thallium variables, the change in the global thallium-201 score (a measure of redistribution) added independent information to clinical and exercise variables, resulting in only 3% of the patients being reclassified regarding their predicted risk for severe coronary disease. The cost per additional reclassification was estimated to be $20 550. Twenty-one cardiac events occurred (7 cardiac deaths and 14 myocardial infarctions) after thallium study (follow-up, 2.8 ±1.0 years). Event-free survival was 94% to 97% regardless of the predicted probability of developing three-vessel or left main coronary artery disease by any model.

Conclusions: When the at-rest electrocardiogram is normal, thallium-201 scintigraphy adds little information to clinical and exercise variables in identifying patients with severe coronary artery disease. The high cost of this information may not justify the routine use of sophisticated imaging for this purpose.


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Figure 1.
The anatomical results of patients classified as having a low, intermediate, or high probability of developing three-vessel or left main coronary artery disease by the use of multivariate models. Top.Middle.Bottom.

Clinical variables only (diabetes, history of typical angina, sex, and age). Clinical and exercise variables (heart rate-blood pressure product and the magnitude of exercise ST-segment depression were added independently). Clinical, exercise, and thallium-201 variables (the change in global score was added independently).

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Figure 2.
The receiver-operator characteristic curves of the three incremental multivariate models.P

The performance of the multivariate model significantly improved when exercise variables were added to the clinical model ( = 0.05), but the performance of the model did not significantly increase when thallium variables were added, as evident from the insignificant change in the area under the curve. The results were similar when data derived from the jack-knife cross-validation analysis were used.

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Figure 3.
The predicted probability of three-vessel or left main coronary artery disease for any patient as a function of cardiac work load based on clinical and exercise variables derived from the multivariate model shown inTable 3

( ). One point is given for the presence of each of the following variables: age >70 years, male sex, the presence of diabetes mellitus, the use of insulin, and a history of typical angina. One point is also given for each millimeter of exercise-induced ST-segment depression. The curve that applies to a particular patient is derived from the sum of points that apply to that patient. For example, a 60-year-old man with typical angina would be placed on curve 2. If he exercises to a peak heart rate x peak systolic blood pressure of 15 000, his predicted probability of severe coronary artery disease would be 20%.

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