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BACKGROUND: Recently published American College of Cardiology (ACC)/American Heart Association (AHA) guidelines state that patients with suspected coronary disease and an intermediate pretest probability are appropriate candidates for exercise ECG, while those with low or high pretest probability are not. METHODS: From 5,103 consecutive patients with symptoms of suspected coronary disease, we evaluated 872 patients who underwent coronary angiography following exercise ECG. Differences in test performance were determined using receiver operating characteristic curve area analysis. A score using age, gender, symptoms, and risk factors was used to classify patients into low, intermediate, and high pretest probability groups. RESULTS: When patients with inadequate exercise tests were excluded, overall sensitivity and specificity were 70% and 66%, respectively. Only the intermediate pretest probability group demonstrated significant incremental value: pretest vs posttest intermediate, 70 +/- 3 vs 79 +/- 3 (p < 0.0001); low, 71 +/- 6 vs 76 +/- 7 (p = 0.39); and high, 69 +/- 8 vs 75 +/- 7 (p = 0.12). From the low- to the high-probability groups, there was a progressive increase in positive predictive value (21%, 62%, and 92%) and decrease in negative predictive value (94%, 72%, and 28%), respectively. The frequencies of abnormal exercise ECGs were lower in the unselected groups compared with the angiography groups (low, 13% vs 36%; intermediate, 22% vs 53%; high, 36% vs 63%). CONCLUSIONS: Based on the information added by exercise testing to clinical data, these results confirm the ACC/AHA guideline assignments for test selection. However, despite these guidelines, patients with a low pretest probability can be selected for exercise testing with the knowledge that a positive result is infrequent and a negative result carries a very high negative predictive value. Intermediate-probability patients on average carry a significant false-negative rate, suggesting that exercise ECG alone may not be a sufficient screening test in all intermediate-probability patients. Because of poor negative predictive value and a large percentage of negative tests, high-probability patients should undergo coronary angiography as the initial strategy, unless the goal of exercise testing is to assess prognosis.

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OBJECTIVE: We compared the Diamond-Forrester (DF) tabular method to assess pretest probability of coronary artery disease to a new scoring method (NS). METHODS: We evaluated 544 patients with suspected coronary disease who underwent both exercise electrocardiography and coronary angiography. The prevalence of any coronary artery disease (CAD) (>/=1 vessel with a >/=50% stenosis) within low, intermediate, and high pretest probability groups defined by the 2 methods was compared. The DF method used age, sex, and symptoms. The NS used those 3 factors plus 7 other risk factors. RESULTS: Overall prevalence of CAD was 41%. We compared the respective prevalence of CAD within pretest probability groups. Low probability: DF 27% versus NS 17% (P <.03); intermediate probability: DF 42% versus NS 47%; high probability: DF 70% versus NS 72%. We evaluated results separately in men and women. In women, no significant differences were found. However, in men, a significant difference in the low probability group was found (DF 47% versus NS 22%; P <.03). When the 47 asymptomatic patients were removed from the analysis, there were no differences between the 2 methods. Men: low probability, DF 17% versus NS 21%; intermediate probability, DF 45% versus NS 49%; high probability, DF 67% versus NS 72%. Women: low probability, DF 17% versus NS 15%; intermediate probability, DF 38% versus NS 27%; high probability, DF 83% versus NS 70%. CONCLUSION: In symptomatic patients, the accuracy of the 2 methods was the same. In asymptomatic patients, further evaluation in larger populations will be needed.

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Primary angioplasty is a useful alternate treatment to open the occluded coronary arteries during the acute phase of a myocardial infarction associated with ST segment elevation. We describe our experience with 50 patients seen at West Virginia University Hospital in Morgantown over a period of one year.

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BACKGROUND: Left ventricular hypertrophy (LVH) on the electrocardiogram (ECG) may be masked in the presence of complete right bundle-branch block (RBBB). Left bundle-branch block on the ECG is associated with LVH at autopsy in 93% of hearts studied. However, RBBB does not predict LVH and the usual ECG criteria applied for LVH may not be reliable in the presence of RBBB. HYPOTHESIS: The study was undertaken to evaluate left atrial (LA) abnormality as a criterion for the diagnosis of LVH in the presence of RBBB. METHODS: Left atrial abnormality in the ECG was assessed by two independent observers as a criterion of LVH in the presence of RBBB in 100 patients, and data were compared with those of 50 patients without LA abnormality. RESULTS: Left ventricular hypertrophy was confirmed by echocardiographic determination of left ventricular (LV) mass in both groups. Observers reliably differentiated between hypertrophied and normal-sized LV in the presence of RBBB by using LA abnormality as an ECG criterion when correlated with LV mass determined by echocardiography. Observer 1 correctly detected LVH in 88% and Observer 2 in 82% of patients. False positive diagnosis was made in 12 and 18% of patients by Observers 1 and 2, respectively. Observers' performance of recognition of LA abnormality in the present study was 94%. Results showed sensitivity of 76 and 70% and specificity of 84 and 92% for Observers 1 and 2, respectively. Left ventricular mass increased significantly and was diagnostic of LVH in 92% of patients with LA abnormality. Left ventricular mass was high in 84% of patients when corrected by body surface area. LVH in the presence of RBBB by the ECG was found in only seven patients (5%) when six commonly used conventional criteria of diagnosis of LVH by ECG were employed. Regression analysis found LA abnormality to be a strong independent predictor of increased LV mass. Multiple regression analysis revealed that age, body mass index, body surface area, and frontal axis are also significant predictors of LV mass. CONCLUSION: The results obtained by the correlation of LA abnormality by ECG and LVH by echocardiography conclude that LA abnormality by ECG was significantly diagnostic of LV hypertrophy in the presence of RBBB.

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We compared the accuracy of the ST segment/heart rate (STHR) index and slope to standard criteria (> or =1 mm horizontal/downsloping ST-segment depression at J + 60 msec) in 1358 patients (152 underwent angiography). All exercise tests used the Cornell protocol and computer measurements of maximum ST-segment depression at J + 60 msec. Test accuracy was determined for the entire group with a probability-based method. Thresholds with equal specificity to standard criteria were determined. By using only patients who underwent angiography, neither STHR index nor slope was more accurate than standard criteria (maximum sensitivity: standard criteria, 42%; STHR index, 51%; STHR slope, 40%). However, by using the entire group, both STHR index and slope were more accurate than standard criteria, but only STHR index achieved statistical significance (maximum sensitivity: standard criteria, 31%; STHR index, 60%; STHR slope, 47%). We conclude that heart rate-adjusted ST-segment criteria are more accurate than standard ST-segment criteria. A lack of demonstration of improved accuracy of STHR index and slope only occurs in patients affected by posttest referral bias.

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We compared the specificity of exercise electrocardiography in 1880 men and 1818 women with women grouped by menopausal and estrogen replacement status. Specificity for > or = 1 mm horizontal or downsloping ST-segment depression was determined using angiography in 781 patients and using two other nonangiography-based methods (a pretest probability-based method and a predictive accuracy-based method) in all patients. Using angiography, the specificities+/-SE were 84 +/- 2 for men, 79 +/- 3 for women, 81 +/- 5 for premenopausal women, 81 +/- 4 for postmenopausal women without estrogen replacement, and 77 +/- 5 for women on estrogen replacement. None of these were significantly different. For all patients, the respective specificities using the probability and predictive accuracy-based methods were 97 +/- 1 and 94 +/- 1 for men, 90 +/- 1 and 88 +/- 1 for women, 97 +/- 1 and 92 +/- 2 for premenopausal women, 92 +/- 4 and 88 +/- 3 for postmenopausal women without estrogen replacement, and 85 +/- 4 and 81 +/- 3 for women on estrogen replacement. (Men vs. all women groups except premenopausal women-P < 0.05). Therefore, the premenopausal women had significantly greater specificity than women on estrogen replacement (P < 0.001) and no difference in specificity with men. Women on estrogen replacement had a significantly lower specificity than postmenopausal women not on estrogen replacement (P < 0.05). These results suggest that estrogen replacement therapy and not naturally occurring estrogen has a role in producing false positive exercise electrocardiograms in women.

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PURPOSE: Guidelines for the management of patients with suspected coronary disease have emphasized stratification into groups with low, intermediate, and high probability of significant coronary disease. Previously derived clinical prediction rules have been difficult to apply in clinical settings. The purpose of this study was to develop and validate a clinical score that facilitates this stratification process. PATIENTS AND METHODS: We performed a retrospective analysis of prospectively acquired data from 915 patients with suspected coronary disease and normal resting electrocardiograms who presented for exercise testing at a university hospital. All patients subsequently underwent coronary angiography. Analysis included logistic regression with significant coronary disease (> or = 1 vessel with a > or = 50% lesion) presence as the dependent variable and clinical variables as independent variables. From this analysis, a coronary disease score was developed to estimate prevalence of coronary disease from clinical variables. Validation of this score was performed in a separate prospectively acquired cohort of 348 patients. RESULTS: For the entire validation group, the prevalence of significant coronary disease was 16% (10/63) in the low probability group, 44% (86/195) in the intermediate probability group, and 69% (62/90) in the high probability group. Both men and women were stratified equally well into the 3 probability groups. CONCLUSION: The clinical score is an easily memorized and accurate method for categorizing patients with suspected but not proven coronary disease and normal resting electrocardiograms into clinically meaningful probability groups upon which decisions concerning appropriate diagnostic test selection could potentially be based.

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OBJECTIVE: To validate the independent nature and incremental value of estrogen status concerning the diagnostic evaluation of women with suspected coronary artery disease. DESIGN AND METHODS: The study comprised a total of 1,168 patients, the first 915 of whom served as a training or derivation population. Data from the subsequent 253 patients were prospectively collected and used to validate observations from the derivation group. We performed logistic regression analysis of age, sex, symptoms, smoking habits, diabetes, hypertension, and other variables with and without estrogen status (defined according to menopausal and estrogen replacement status). Diagnostic outcomes were assessed by receiver-operating characteristic curve area analysis. RESULTS: Within the derivation group, estrogen status was an independent predictor of both significant (> or = 1 lesion > or = 50% stenosis) and serve (at least two vessels with > or = 70% stenosis) coronary disease on angiography. Receiver-operating characteristic curve areas for models applied to the validation group were as follows: women without estrogen status, 77 +/- 4 for significant disease and 76 +/- 5 for severe disease; women with estrogen status, 80 +/- 4 for significant disease and 80 +/- 5 for severe disease; men, 72 +/- 4 for significant disease and 74 +/- 4 for severe disease (women with versus women without estrogen status; P < 0.05). CONCLUSION: Estrogen status has significant incremental value for enhancing the diagnostic discrimination of significant and severe coronary disease in women. Estrogen status, as defined in this study, is an important and independent diagnostic clinical variable in women with suspected coronary disease.

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The accuracy of a logistic prediction model is degraded when it is transported to populations with outcome prevalences different from that of the population used to derive the model. The resultant errors can have major clinical implications. Accordingly, the authors developed a logistic prediction model with respect to the noninvasive diagnosis of coronary disease based on 1,824 patients who underwent exercise testing and coronary angiography, varied the prevalence of disease in various "test" populations by random sampling of the original "derivation" population, and determined the accuracy of the logistic prediction model before and after the application of a mathematical algorithm designed to adjust only for these differences in prevalence. The accuracy of each prediction model was quantified in terms of receiver operating characteristic (ROC) curve area (discrimination) and chi-square goodness-of-fit (calibration). As the prevalence of the test population diverged from the prevalence of the derivation population, discrimination improved (ROC-curve areas increased from 0.82 +/- 0.02 to 0.87 +/- 0.03; p < 0.05), and calibration deteriorated (chi-square goodness-of-fit statistics increased from 9 to 154; p < 0.05). Following adjustment of the logistic intercept for differences in prevalence, discrimination was unchanged and calibration improved (maximum chi-square goodness-of-fit fell from 154 to 16). When the adjusted algorithm was applied to three geographically remote populations with prevalences that differed from that of the derivation population, calibration improved 87%, while discrimination fell by 1%. Thus, prevalence differences produce statistically significant and potentially clinically important errors in the accuracy of logistic prediction models. These errors can potentially be mitigated by use of a relatively simple mathematical correction algorithm.

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The application of myocardial perfusion scintigraphy to patient care in the era of health care cost containment is a difficult issue. The traditional diagnosis based approach to testing, although effective, is incompletely applied, as evidenced by the number of low likelihood of coronary artery disease patients referred for testing. A prognosis- or risk-based testing approach may be applied to both patients with or without known coronary artery disease by utilizing clinical and scan information to estimate the projected risk of adverse outcomes (cardiac death or myocardial infarction) and planning subsequent patient strategy based upon this estimate. Patients at high risk for these events are more likely to benefit from referral to catheterization while those patients at lower risk may benefit from medical therapy alone. Irrespective of the approach utilized to evaluate testing, consideration of patient population selection and its implications must be considered when reviewing the results of testing or published literature. Further, scrutiny of both the statistical methods used for evaluation of the value of testing and the economic implications of testing in particular patient subgroups are of importance.

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To assess for sex-related differences in posttest referral bias, we compared the accuracy of exercise electrocardiography in biased (coronary angiography only) and unbiased (all unselected) populations with possible coronary disease. A retrospective analysis of clinical and exercise test data from 4467 patients (788 who underwent angiography) was performed (2824 men and 1643 women). The accuracy of a positive exercise test result was assessed in the entire unbiased group with a method that used disease probability (derived with a logistic algorithm) rather than angiography results. We found that the sensitivity and specificity were significantly greater in men than in women with use of the biased or unbiased groups. When the results for the unbiased and biased groups were compared, the sensitivities for the unbiased group were significantly lower and the specificities were significantly higher than those of the biased group. These differences reflect the effects of posttest referral bias. The amounts that sensitivity decreased and specificity increased, however, was not different for men and women. Therefore, we conclude that the accuracy of exercise electrocardiography is lower in women than men irrespective of whether a biased or an unbiased group is used. However, these differences cannot be explained on the basis of sex-related differences in posttest referral bias.

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Our goal was to assess the incremental value of exercise testing in men and women for the diagnosis and extent of coronary artery disease. With data from one center, incremental logistic algorithms were developed and evaluated in a separate set of 865 patients from four centers. Variables included were pretest (age, sex, symptoms, diabetes, smoking, and cholesterol concentration); exercise electrocardiogram (ECG) (ST-segment depression [millimeters], ST-segment slope, peak heart rate, and change in systolic blood pressure); and thallium-201 scintigram (defect presence, reversibility, and intensity of hypoperfusion). End points were coronary disease presence (50% diameter stenosis) and extent (multivessel disease). Accuracy and incremental value were assessed by receiver operating characteristic (ROC) curve analysis. Incremental ROC curve areas for disease presence were pretest 0.75 +/- 0.02, post-exercise ECG 0.82 +/- 0.01, and post-thallium scintigram 0.85 +/- 0.01 and for disease extent were pretest 0.71 +/- 0.02, post-exercise ECG 0.76 +/- 0.02, and post-thallium scintigram 0.78 +/- 0.02 (p < 0.005 for all increments). Incremental increases in accuracy were similar for men and women. We conclude that when multivariable algorithms derived from one center were applied to a separate group, there was a significant incremental increase in accuracy associated with exercise testing for the presence and extent of coronary disease. This increase in accuracy was similar for men and women.

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BACKGROUND: The goal was to assess the incremental diagnostic value of thallium single-photon emission computed tomographic (SPECT) imaging and lung/heart ratio (LHR) over other clinical and exercise electrocardiographic (ECG) variables concerning the presence and extent (three vessel/left main) of coronary artery disease. METHODS AND RESULTS: Multivariable logistic regression analysis that used an incremental study design was applied to clinical, exercise test, SPECT, LHR, and catheterization data from 323 patients with suspected coronary disease. The following variables were evaluated as predictors of presence and extent of disease: clinical (age, sex, symptoms, diabetes, and smoking), exercise ECG (millimeters of ST segment depression, slope of ST segment depression, peak heart rate, change in systolic blood pressure, and metabolic equivalents of the task), and thallium (defect reversibility and intensity of hypoperfusion and LHR). Discrimination and incremental value were assessed by receiver operating characteristic (ROC) curve analysis. SPECT imaging (segment hypoperfusion score) was an independent predictor of both presence and extent of disease (p < 0.0001) irrespective of the percent stenosis criterion used. However, it added significant incremental diagnostic information over clinical and exercise ECG data only concerning presence (e.g., ROC curve areas: presence of disease-clinical plus exercise ECG = 83 +/- 2 vs clinical, exercise ECG, plus SPECT = 87 +/- 2, p < 0.001; extent of disease-clinical plus exercise ECG = 83 + 4 vs clinical, exercise ECG, plus SPECT = 85 +/- 3, p = 0.11). Thallium LHR was an independent predictor of both presence and extent of disease (p < 0.05), but the incremental information added to SPECT data did not reach statistical significance (e.g., ROC curve areas: presence of disease--SPECT = 87 +/- 2 vs SPECT plus LHR = 88 +/- 2, p = 0.24; disease extent--SPECT = 85 +/- 2 vs SPECT plus LHR = 86 +/- 2, p = 0.24). However, when combined, LHR and SPECT data had significant incremental value over clinical and exercise ECG data alone concerning extent of disease (e.g., ROC curve areas: clinical plus exercise ECG = 83 +/- 4 vs clinical, exercise ECG, SPECT and LHR = 86 +/- 3, p = 0.04). CONCLUSION: SPECT thallium imaging variables are independent predictors of both presence and extent of coronary disease. However, they have significant incremental value over clinical and exercise ECG data concerning only presence of disease. Thallium LHR is an independent predictor of both presence and extent of disease but adds only a small insignificant amount of incremental diagnostic information over SPECT data. However, there was significant incremental value to the addition of LHR to SPECT data concerning extent of disease.

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We compared the accuracy of ST segment/heart rate (ST/HR) index with that of standard criteria (> or = 0.1 mV horizontal/downsloping ST depression 80 ms after the J point) in 121 patients who had undergone angiography (49 with > or = 1 lesion with > or = 50% stenosis) and 50 clinically normal subjects. All exercise tests used the Cornell protocol and computer measurements of maximal ST depression 80 ms after the J point. Thresholds with equal specificity to standard criteria were determined for ST/HR index using each of the 2 normal groups (those who were normal by angiography and those who were clinically normal). In using only patients who underwent angiography, we found that the ST/HR index had a sensitivity that was not significantly greater than that of standard criteria (standard criteria 51%, ST/HR index 59%; p = 0.21). However, the receiver-operating characteristic curve area increased from 64 +/- 4 to 68 +/- 4 (p < 0.02). When clinically normal subjects were used instead of patients without angiographic disease, there was a clearly discernible improvement in sensitivity of ST/HR index over standard criteria (standard criteria 51%, ST/HR index 69%; p < 0.05). The associated curve areas were 69 +/- 4 and 79 +/- 3 (p < 0.001). Therefore, accuracy of the ST/HR index was marginally better than standard criteria only in patients who underwent angiography. When clinically normal subjects were used, the accuracy of the ST/HR index was definitely better than standard criteria. We conclude that the demonstration of improved accuracy of the ST/HR index depends on the population being tested.

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Although the diagnostic accuracy of myocardial perfusion scintigraphy can be improved by additional consideration of clinical and exercise information, multivariate prediction models are infrequently used for this purpose in the clinical setting. We therefore developed a Bayesian algorithm that instead transforms the scintigraphic image itself, modifying defect contrast as a function of the pretest likelihood of coronary artery disease. The algorithm was tested in computer simulations of myocardial perfusion scintigraphy with data from 378 patients (166 from California and 212 from West Virginia) who underwent planar exercise thallium-201 scintigraphy and coronary angiography. Images were interpreted before and after enhancement by eight readers (four at each medical center) with different training orientations (internist, radiologist, cardiologist, nuclear cardiologist, and nuclear medicine technologist) who used a four-point score (from 0, normal to 3, severe defect). Accuracy was quantified as area under a receiver-operating characteristic (ROC) curve. Improvements in accuracy obtained by the algorithm were compared to those provided by multiple logistic regression. Overall, Bayesian enhancement increased ROC area from 0.63 +/- 0.04 to 0.71 +/- 0.04 (p < 0.01). The improvement was consistent for all 16 reading sets (eight readers multiplied by two patient populations; p < 0.05). In comparison, multiple logistic regression increased ROC area from 0.63 +/- 0.04 to 0.79 +/- 0.03 (p < 0.01), outperforming interpretation of the enhanced images in 13 of the 16 reading sets. Bayesian enhancement improves diagnostic accuracy of conventional scintigraphic image interpretation. The improvement is stable across individuals, training orientations, and patient populations. Although this approach is not as accurate as multiple logistic regression, it may be more practical for widespread clinical application.

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To determine the independent incremental value of exercise capacity (METS) concerning the presence and extent of coronary artery disease, we analyzed data from 800 patients with suspected coronary disease who underwent both exercise testing and coronary angiography. We performed logistic regression analysis of clinical and exercise test data with an incremental design to mimic the usual flow of data acquisition. Separate analyses were performed concerning coronary disease presence (> or = 1 vessel with a > or = 50% lesion) and extent (three-vessel/left main disease). Diagnostic accuracy was determined by calculating receiver operating characteristic (ROC) curve areas. When considered alone, METS was a significant predictor of both presence and extent of disease. Multivariate analysis revealed that METS was an independent predictor of disease extent but not presence. However, comparison of ROC curve areas failed to show any loss of accuracy when METS was removed from the coronary disease extent analysis. Despite the strong univariate relationship between exercise capacity and coronary disease presence and extent and the independence of exercise capacity as a predictor of coronary disease extent, the lack of an additional incremental accuracy attributed to its consideration virtually cancels its value as a diagnostic variable for assessing both coronary disease presence and extent.

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