A B S T R A C T Analysis of multiple noninvasive tests offers the promise of more accurate diagnosis of coronary artery disease, but discordant test responses can occur frequently and, when observed, result in diagnostic uncertainty. Accordingly, 43 patients undergoing diagnostic coronary angiography were evaluated by noninvasive testing and the results subjected to analysis using Bayes' theorem of conditional probability. The procedures used included electrocardiographic stress testing for detection of exercise-induced ST segment depression, cardiokymographic stress testing for detection of exercise-induced precordial dyskinesis, myocardial perfusion scintigraphy for detection of exerciseinduced relative regional hypoperfusion, and cardiac fluoroscopy for detection of coronary artery calcification.The probability for coronary artery disease was estimated by Bayes' theorem from each patient's age, sex, and symptom classification, and from the observed test responses. This analysis revealed a significant linear correlation between the predicted probability for coronary artery disease and the observed prevalence of angiographic disease over the entire range of probability from 0 to 100% (P < 0.001 by linear regression). The 12 patients without angiographic disease had a mean posttest likelihood of only 7.0+±2.6% despite the fact that 13 of the 60 historical and test responses were falsely "positive." In contrast, the mean posttest likelihood was 94.1±2.8% in the 31 patients with angiographic coronary artery disease, although 45 of the 155 historical and test responses were falsely "negative." In 8 of the 12 normal patients, the final posttest likelihood was under 10% and in 26 ofthe 31 coronary artery disease patients, it was over 90%. These estimates also correlated well with the pooled clinical judgment of five experienced cardiologists (P < 0.001 by linear reReceivedfor publication 13 August 1979 and in revisedform 30 November 1979. 1210 gression). The observed change in probability for disease for each of the 15 different test combinations correlated with their information content predicted according to Shannon's theorem (P < 0.001 by linear regression).These results support the use of probability analysis in the clinical diagnosis of coronary artery disease and provide a formal basis for comparing the relative diagnostic effectiveness and cost-effectiveness of different test combinations.

SUMMARY The inherent imperfection of clinical diagnostic tests introduces uncertainty into their interpretation. The magnitude of diagnostic uncertainty after any test result may be quantified by information theory. The information content of the electrocardiographic ST-segment response to exercise, relative to the diagnosis of angiographic coronary artery disease, was determined using literature-based pooled estimates of the true-and false-positive rates for various magnitudes of ST depression from < 0.5 mm to 2 2.5 mm. This analysis allows three conclusions of clinical relevance. First, the diagnostic information content of exercise-induced ST-segment depression, interpreted by the standard 1.0-mm criterion, averages only 15% of that of coronary angiography. Second, there is a 41% increase in information content when the specific magnitude of STsegment depression is analyzed, as opposed to the single, categorical 1-mm criterion. Third, the information obtained from ECG stress testing is markedly influenced by the prevalence of disease in the population tested, being low in the asymptomatic and typical angina groups and substantially greater in groups with nonanginal chest pain and atypical angina.The quantitation of information has broad relevance to selection and use of diagnostic tests, because one can analyze objectively the value of different interpretation criteria, compare one test with another and evaluate the cost-effectiveness of both a single test and potential testing combinations.INFORMATION THEORY was developed as a means for quantifying the information content and the noise content in the audio signal transmitted over telephone channels.' Because the general theory provides a formal mathematical basis for quantifying information and uncertainty, it has been widely applied in other sciences as diverse as economics and engineering, but has been little used in clinical medicine,2' 3 presumably because its relevance was not apparent.The application of information analysis to diagnostic testing in medicine derives from the recognition that all clinical tests are imperfect. This imperfection introduces uncertainty (or "noise") into the interpretation of the test. The information (and, conversely, the uncertainty existing before and after a diagnostic test) can be quantified if one knows its three determinants. These are the pretest probability of disease in the individual being tested (prevalence), the conditional probability of the test response observed in a diseased population (the true-positive rate), and the conditional probability of this same response in a nondiseased population (the false-positive rate). The change in diagnostic uncertainty that occurs as a result of testing, then, is a measure of the test's effectiveness ( fig. 1 where N is the number of patients from which the value of P is derived. The complete bibliography for the literature review from which these data were obtained is given in reference 5.where a = p(Tj D+) = true positive rate, b = p(TjThe derivation of this equation is ...

Stress-induced abnormalities of regional left ventricular wall motion were assessed by cardiokymography (CKG) during the course of maximal treadmill exercise tests in 157 patients, of whom 122 subsequently underwent coronary angiography. Seventy patients had significant angiographic coronary artery disease and 52 were normal. Forty-one of the 70 patients developed greater than 0.1 mV ST-segment depression (ECG sensitivity 59%) and 52 of 70 patients developed abnormal systolic outward motion by CKG (CKG sensitivity 74%). Among the 52 normals, 36 had negative ECG stress tests (ECG specificity 69%) and 49 had normally sustained systolic inward motion by CKG (CKG specificity 94%). The stress CKG was normal in 15 of the 16 false-positive stress ECGs; the stress ECG was correctly normal in two of the three false-positive stress CKG tests. Only one normal patient had concordantly false-positive ECG and CKG tests. The predictive accuracy of concordant ECG and CKG interpretations was, therefore, higher than either test alone. These data suggest that regional wall motion abnormalities, which are sensitive and specific markers of myocardial ischemia, may be detected noninvasively by CKG. We concluded that CKG helps identify false-positive and false-negative ECG stress tests and improves the diagnostic accuracy of stress testing for detection of coronary artery disease.

Fibrinolytic therapy is an alternative to urgent reoperation for patients with St. Jude prosthetic valve thrombosis, but requires an accurate method for repeated assessment of prosthetic function. Since the St. Jude valve is not well visualized by conventional cinefluoroscopy, digital subtraction techniques were developed that improved visualization of the value and allowed assessment of leaflet separation and velocity. A 74 year old woman with prosthetic valve thrombosis 5 years after St. Jude aortic valve placement had an opening angle of 58 degrees (normal range 10 to 13; n = 8) with a maximal opening velocity of 1.37 degrees/ms (normal range 2.46 to 2.93). The closing angle was 125 degrees (normal range 120 to 127) with a maximal closing velocity of 1.38 degrees/ms (normal range 2.24 to 3.60). The patient received 250,000 U of streptokinase intravenously, then 100,000 U/h for 72 hours. Improvement in auscultatory findings occurred at 12 hours; repeat digital cinefluoroscopy showed an opening angle of 20 degrees with a maximal velocity of 2.77 degrees/ms, and a closing angle of 126 degrees with a maximal velocity of 1.91 degrees/ms. Digital cinefluoroscopy 4 weeks after discharge on warfarin and dipyridamole therapy was unchanged. There have been no thromboembolic complications after 6 months of follow-up. Thus, digital cinefluoroscopy is a new noninvasive technique that permits accurate measurement of normal and abnormal St. Jude leaflet function. Intravenous streptokinase dissolution of prosthetic valve thrombosis under digital cinefluoroscopic guidance may be an acceptable alternative to emergency reoperation. The frequency and significance of residual subclinical leaflet dysfunction after fibrinolytic therapy and the indications for elective reoperation require further evaluation.

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