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Discriminant function analysis using thallium-20 1 scintiscans and exercise stress test variables to predict the presence and extent of cornary artery disease
Abstract
The ability to predict the presence and extent (number of affected vessels) of coronary artery disease objectively from an exercise treadmill test and thallium-201 myocardial perfusion scintiscans was evaluated using linear discriminant function analysis. Exercise and redistribution scans in the 30 ° left anterior oblique view were characterized by their two dimensional Fourier transforms. The analysis was performed in 141 persons, including 110 patients with coronary artery disease (70 percent or greater stenosis of luminal diameter) and 31 control subjects. There were 43 patients with single vessel and 67 patients with multivessel disease.
... Measurement of redistribution or clearance does not improve sensitivity, but it improves specificity. Although thallium myocardial clearance is considered an important variable (J56789101112131415161720), in our study clearance had no added utility in detecting disease once redistribution was included. Only IO patients with coronary disease dem@BULLET onstrated abnormal thallium clearance by method A without having abnormal initial thallium uptake; none had three vessel or left main disease. ...
Although quantification of exercise thallium images has been previously reported, the relative value of different imaging variables for detection of coronary artery disease has not been analyzed in a large group of patients with cardiac catheterization data. Regional initial thallium uptake, redistribution and clearance on thallium study were measured in 325 patients also undergoing cardiac catheterization (281 patients with and 44 patients without coronary artery disease). Normal values were defined in 55 other clinically normal subjects. When five myocardial segments were analyzed in each view, the respective values for sensitivity and specificity were 95 and 50% for initial thallium uptake, 60 and 87% for redistribution and 74 and 66% for clearance. Initial thallium uptake was the most sensitive but least specific (p < 0.001), whereas redistribution was the least sensitive and most specific (p < 0.001).Using stepwise logistic regression analysis, the best correlate of coronary artery disease was initial thallium uptake. Addition of redistribution to a mathematical model of the probability of coronary artery disease did not alter sensitivity, but increased specificity from 50 to 70% (p < 0.001). Once initial uptake and redistribution were considered, myocardial thallium clearance provided no additional improvement in the correlation. Excluding the two basal segments in each view from the analysis increased the specificity from 70 to 80% (p < 0.001) without affecting sensitivity. Of the 15 patients (5%) with coronary disease not detected using this approach, none had left main disease and 10 (67%) had one vessel disease. A combination of variables derived from quantification of exercise thallium images provides a superior sensitivity and specificity for the detection of coronary artery disease compared with the use of a single variable.
Nuclear medicine is now recognized as an independent speciality in many countries including the German Federal Republic, where there are regulations for postgraduate training. It originated from the efforts of a few individuals and developed rapidly after the introduction of radionuclides with short physical halflives. Yet as long ago as 1927 Blumgartand Weisswere using natural radioisotopes for measuring circulation time (1927, 1928). The techniques of nuclear medicine thus had their beginnings in a test employed in cardiovascular research. Today, nuclear medicine is of major importance in cardiological diagnosis.
The new edition of Exercise and the Heart offers the essential clinical and scientific information on exercise testing and interpretation. Balancing the essential physiology with a problem based approach to cardiac problem management, this new edition provides the clinician with a resource for diagnosis and treatment with exercise. New material on exercise therapy and the effect of chronic exercise on the heart provide a clinical aide to the cardiologist and internist.
Value of exercise seismocardiography in the diagnosis of ischemic heart disease Introduction: Seismocardiography (SCG) is a non invasive method of detecting coronary artery disease. It combines technology from fields of seismology and signal analysis to accu-rately evaluate the biomechanical function of the heart. An exercise SCG test is performed in conjunction with standard exercise ECG test (EXT).
Coronary heart disease accounts for 250,000 deaths per year in American women. The presentation of this disease differs between men and women. The initial manifestations of coronary disease occur later in women. Pathologic and angiographic surveys suggest a tendency in men to earlier, more extensive, and more severe disease. While risk factors for coronary disease are probably independent of gender, three risk factors are particularly onerous in women: lack of ovarian estrogen, cigarette smoking, and diabetes mellitus. The initial presentation of coronary heart disease is more likely to be fatal in women. Further, women are more prone to suffer unrecognized, or "silent." coronary events. They are also more likely to develop Syndrome X. defined as angina with normal coronary angiograms. Noninvasive testing for coronary disease (exercise testing or alternative functional studies) appears to be less reliable in women than in men. Evidence suggests that women are offered the same antiischemic therapies as men once a diagnosis has been established. A growing body of data examines the relative efficacy and safety of certain therapies: blood pressure and lipid reduction as well as revascularization. While still debated, mounting evidence supports the use of estrogen replacement therapy in postmenopausal women for the prevention of coronary heart disease.
Exercise can be considered the most practical test of cardiac perfusion and function. Exercise testing is a noninvasive tool to evaluate the cardiovascular system’s response to exercise under carefully controlled conditions. Its main uses center around the diagnosis of coronary artery disease and the estimation of prognosis in a wide range of conditions. While there are important technological considerations and the need to be very knowledgable of the guidelines to insure its proper application, exercise testing remains one of the most widely used and valuable noninvasive tools to assess cardiovascular status.
Keywords:
exercise;
diagnostic;
prognostic;
ECG;
ventilatory oxygen;
consumption;
coronary artery disease;
scores;
clinical
Accurate use and interpretation of exercise test results depend on an understanding of physiologic principles, meticulous attention to proper methodlogy, and realization of the appropriate applications and limitations of testing.Understanding the relationship between myocardial and ventilatory oxygen consumption and exercise test variables will aid in the diagnosis and prognostic evaluation.Use of proper methodology in preparing the patient, performing the examination, and interpreting the results is critical to obtaining the maximum information with maximum safety for each individual patient. Improvements in methodology including the use of the Borg scale to estimate individual effort, abandonment of the predicted maximum heart rate, and the increased use of ventilatory oxygen uptake measurements should be applied. Exercise capacity should not be reported in total time but rather as the VO2 or MET equivalent of the workload achieved. This permits the comparison of the results of many different exercise testing protocols.The most useful exercise ECG variable for the diagnosis of coronary artery disease remains the ST segment shift. Unfortunately, it is not as helpful in localizing myocardial ischemia. Diagnostic accuracy can be improved by adjusting ST depressions for exercise-induced heart rate increase. Accuracy can be further increased by combining ECG, clinical, and radionuclide variables in probabilistic formulas that retain the independent diagnostic information from each variable and accurately predict disease probability. To avoid errors in clinical decision making, care must be used to insure that the mathematical formula used was derived from a population of patients that is similar to those being tested.The clinical applications for exercise testing include diagnosis of patients with chest pain syndromes, determination of disease severity, and prognosis in patients with known coronary artery disease, evaluation of arrhythmias, screening of asymptomatic patients, and evaluation of medical, surgical, and angioplastic therapy for coronary disease.In spite of studies involving thousands of patients, controversy exists regarding the diagnostic power of exercise testing. The large differences in reported accuracies are largely due to methodologic problems that have been encountered by various investigators. Clinicians should be made aware of these problems when reading the literature on ECG and radionuclide exercise testing. Such awareness will help them understand the limitations of these noninvasive procedures.Exercise testing can be used to predict coronary disease severity and prognosis. heart rate adjustment of ST depressions, exercise-induced hypotension, and reduced exercise capacity have been helpful in predicting critical coronary disease. Though exercise testing is helpful in evaluating the presence and severity of cardiac dysrhythmias, it is of little assistance in determining their prognostic significance. Careful evaluation of exercise testing as a screening device for asymptomatic patients reveals that it is somewhat disappointing in this application. Its use for evaluating the effects of therapy is also controversial, since studies evaluating antianginal agents have been greatly hampered by the increased in treadmill time that occurs merely by performing serial tests, and studies of bypass surgery and angioplasty are confounded by differences in medication states before and after intervention.
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 (≥1 vessel with a ≥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 any additional incremental accuracy attributed to its consideration virtually cancels its value as a diagnostic variable for assessing both coronary disease presence and extent.
Objectives:
Our goals were to develop and validate a multivariate algorithm for estimating the incremental probability of the presence of coronary artery disease.
Background:
Multivariate methods, including logistic regression analysis, have been extensively applied to diagnostic exercise testing. However, few previous studies have included both an incremental design and external validation.
Methods:
A retrospective collection of clinical, exercise test and catheterization data was performed involving four U.S. referral medical centers. All patients had no prior history of coronary disease and had undergone coronary angiography < or = 3 months after exercise stress testing. An algorithm was developed in one center (590 patients with a 41% prevalence of coronary artery disease) with the use of logistic regression analysis and was validated in the other three centers (1,234 patients, 70% prevalence). The algorithm incorporated pretest variables (age, gender, symptoms, diabetes, cholesterol), exercise electrocardiographic (ECG) variables (mm of ST segment depression, ST slope, peak heart rate, metabolic equivalents [METs], exercise angina) and one thallium variable. Discrimination was measured with receiver operating characteristic curve analysis. Calibration (that is, reliability) was assessed from a comparison of probability estimates and the actual prevalence of disease.
Results:
The overall incremental receiver operating characteristic curve areas for the validation group were pretest, -0.738 +/- 0.016; postexercise ECG, 0.78 (SE 0.017); and postthallium, 0.82 (SE 0.016); p < 0.01 for both increments. Within the three validation institutions, the institution with a disease prevalence closest to that of the derivation institution had the best incremental receiver operating characteristic curve areas. There was a stepwise incremental improvement in calibration especially from exercise ECG to thallium testing.
Conclusions:
An incremental multivariate algorithm derived in one center reliably estimated disease probability in patients from three other centers. The incremental value of testing was best demonstrated when the derivation and validation groups had a similar disease prevalence. This algorithm may be useful in decision making that relates to the diagnosis of coronary disease.
The ability of exercise thallium-201 tomographic imaging to predict the presence of left main or 3-vessel coronary artery disease (CAD) was examined in 688 patients who underwent both exercise thallium-201 testing and coronary angiography. Significant differences existed for multiple variables between patients with (n = 196) and without (n = 492) severe left main or 3-vessel CAD. Logistic regression analysis identified 4 variables as independently predictive of left main or 3-vessel CAD. These variables were the magnitude of ST-segment depression with exercise, the number of visually abnormal short-axis thallium-201 segments, the presence or absence of diabetes mellitus, and the change in systolic blood pressure with exercise. Using these variables, patients were classified by nomograms into low-, intermediate- and high-probability groups. Patients at high probability (n = 205) had a 52% prevalence of 3-vessel or left main CAD, whereas those at low probability (n = 170) had only a 12% prevalence. Only 53 patients (29%) with 3-vessel or left main CAD had perfusion abnormalities in all 3 coronary territories. Clinical and exercise parameters provide important independent information in the identification of left main or 3-vessel CAD by exercise thallium-201 tomographic imaging, because thallium scintigraphy alone is suggestive of extensive CAD in few patients.
The additive prognostic value of tests done in a hierarchical order for the detection of coronary artery disease (CAD) is not always known. The principal goal of this study, therefore, was to assess the incremental prognostic value of data obtained in succession (clinical, exercise stress testing, 201Tl imaging, and coronary angiography) in patients with suspected CAD. A second goal was to develop models for determining prognosis based on results of these tests and to test the clinical validity of these models in unrelated patients.
Data from two groups of patients who had undergone such evaluation and had been followed for a mean of 4.4 years were analyzed. There were 204 patients from Massachusetts General Hospital (MGH) and 299 from the University of Virginia (UVA). There were 20 deaths and 21 nonfatal infarctions in the MGH group and 41 deaths and nine infarctions in the UVA group. Both univariate and multivariate Cox regression analyses were performed to assess the individual and incremental prognostic value of these tests. In both groups, 201Tl imaging provided significant additional prognostic information compared with clinical and exercise stress test data (p less than 0.05). At MGH, where the lung/heart 201Tl ratio had been analyzed, coronary angiography did not provide additional prognostic information. In this group of patients, the combination of clinical and exercise 201Tl variables provided greater prognostic information than the combination of clinical and angiographic data (p less than 0.001). In the UVA cohort, in which the lung/heart ratio had not been analyzed, coronary angiography provided incremental prognostic information compared with clinical and exercise 201Tl data alone (p less than 0.05). When models developed using data from either sample were applied to the other unrelated sample, there was often close agreement between the overall observed rates and those predicted by the models. This was also true for the low-risk and high-risk subgroups. Some models, however, did not perform as well as other models, which suggests that models that do well in one sample may not always be generalized to other groups.
Tests performed in hierarchical order for the evaluation of suspected CAD provide additional prognostic information. Models developed using clinically relevant combinations of test results obtained from different patient populations are frequently able to predict absolute levels of survival in unrelated but similar samples.
The aim of this study was to (1) determine whether nonimaging variables add to the diagnostic information available from exercise thallium-201 images for the detection of multivessel coronary artery disease; and (2) to develop a model based on the exercise thallium-201 stress test to predict the presence of multivessel disease.
The study populations included 383 patients referred to the University of Virginia and 325 patients referred to the Massachusetts General Hospital for evaluation of chest pain. All patients underwent both cardiac catheterization and exercise thallium-201 stress testing between 1978 and 1981.
In the University of Virginia cohort, at each level of thallium-201 abnormality (no defects, one defect, more than one defect), ST depression and patient age added significantly in the detection of multivessel disease. Logistic regression analysis using data from these patients identified three independent predictors of multivessel disease: initial thallium-201 defects, ST depression, and age. A model was developed to predict multivessel disease based on these variables. As might be expected, the risk of multivessel disease predicted by the model was similar to that actually observed in the University of Virginia population. More importantly, however, the model was accurate in predicting the occurrence of multivessel disease in the unrelated population studied at the Massachusetts General Hospital.
It is, therefore, concluded that (1) nonimaging variables (age and exercise-induced ST depression) add independent information to thallium-201 imaging data in the detection of multivessel disease; and (2) a model has been developed based on the exercise thallium-201 stress test that can accurately predict the probability of multivessel disease in other populations.
The aim was to evaluate discriminant analysis, performed in patients without prior myocardial infarction, in enhancing the diagnostic value of quantitative exercise 201thallium scintigraphy.
All clinical, electrocardiographic, and scintigraphic variables were first subjected to a univariate analysis. Afterwards a discriminant analysis was done.
135 patients (104 male) were studied. Age was 24-70 years, mean 55 years.
Two discriminant analyses were done. In the first analysis, the ability to detect the presence of coronary artery disease was tested. Significant variables were: (1) history of angina, (2) sex, (3) quantitative analysis of 201thallium scintigraphy, (4) age, (5) ischaemic ST response, (6) angina during the test, and (7) the pressure-rate product. The sensitivity, specificity, and accuracy of classification using the discriminant function were 91%, 87%, and 90%, respectively. The sensitivity was higher than when using only visual interpretation (sensitivity 70%; p less than 0.0002) or quantitative interpretation (sensitivity = 66%; p less than 0.0001) of thallium scans, without significant loss of specificity (p less than 0.5488; p less than 0.6875). In the second analysis, a discriminant function was calculated to detect multivessel disease. Five input variables were selected: (1) number of vessels with stenosis predicted by quantitative analysis, (2) number of vessels with stenosis predicted by visual analysis, (3) ischaemic ST response, (4) sex, (5) angina during the test. Multivariate analysis showed an increase in sensitivity when compared with visual interpretation (78% v 55%; p less than 0.0043) and quantitative analysis (66%; p less than 0.0156). Using the classification, the discriminant function was more accurate than visual analysis (81% v 69%) or quantitative analysis (77%).
The results show that multivariate analysis of non-invasive test results in quantitative thallium exercise testing allows convenient use for clinical purposes with improved results.
To determine the discriminant accuracy of exercise thallium-201 myocardial perfusion scintigraphy for the diagnosis and prognosis of patients with known or suspected coronary artery disease.
A survey of the National Library of Medicine MEDLINE database.
The key medical subject headings used were coronary disease, myocardial infarction, radionuclide imaging, and thallium. A total of 122 retrieved studies were considered relevant and were reviewed in depth.
Only studies reporting both the sensitivity and specificity of thallium scintigraphy were analyzed.
Discriminant accuracy for diagnosis and prognosis was summarized in terms of pooled sensitivity and specificity.
Exercise thallium scintigraphy is useful in the noninvasive diagnosis of coronary artery disease, especially in patients with abnormal resting electrocardiograms, restricted exercise tolerance, and intermediate probability of having disease at the time of testing as well as of defining the prognosis of patients with known or suspected coronary artery disease, especially in those with previous myocardial infarction. Because of various shortcomings in the published record, however, the marginal discriminant accuracy and cost effectiveness of thallium scintigraphy compared with conventional clinical assessment and exercise electrocardiography remain controversial.
Extensive experience has been accumulated over the past 15 years regarding planar thallium-201 imaging. Quantitation of technically superior images provides a high sensitivity and specificity for the detection of CAD. In addition, planar thallium-201 images provide very important prognostic information in different clinical situations. Although single photon emission computerized tomography offers potential theoretical advantages over planar imaging, because of the problems involved in reconstruction, specifically the creation of artifacts, it may not be the ideal imaging modality in all situations. Good quality planar thallium-201 imaging still has an important role in clinical cardiology today.
Receiver operating characteristic (ROC) curves have been frequently used to compare probability models applied to medical problems. Though the curves are a measure of the discriminatory power of a model, they do not reflect the model's accuracy. A supplementary accuracy curve is derived which will be coincident with the ROC curve if the model is reliable, will be above the ROC curve if the model's probabilities are too high or below if they are too low. A clinical example of this new graphical presentation is given.
Goals of exercise radionuclide imaging are to: enhance sensitivity, specificity and predictive value of coronary artery disease (CAD) detection; noninvasively assess extent and severity of functionally significant CAD; determine prognosis so that specific therapeutic strategies can be more rationally implemented; detect silent ischemia in asymptomatic subjects or in patients with known CAD with a higher degree of specificity than can be accomplished by electrocardiogram stress testing alone; evaluate the response to therapeutic interventions aimed at enhancing coronary blood flow. Two major radionuclide techniques are currently used in evaluating the total ischemic burden in patients with CAD. These are myocardial perfusion imaging with either thallium-201 or rubidium-82, and radionuclide angiography performed after administration of technetium-99m. Areas of diminished thallium-201 activity on early postexercise images are abnormal and represent either areas of stress-induced ischemia or myocardial scar. To differentiate between the two, delayed images are obtained to determine if the initial postexercise defect either persists or demonstrates redistribution (i.e., delayed defect disappearance or improvement). Defects demonstrating redistribution represent transient ischemia, whereas areas of previous infarction or scar usually appear as persistent defects. Patients with left main or 3-vessel CAD usually show multiple thallium-201 redistribution defects in more than 1 vascular supply region, a phenomenon often associated with abnormal lung thallium-201 uptake. In terms of radionuclide angiography, the normal ventricular response to exercise has been defined as an absolute increment of at least 5% in the left ventricular ejection fraction without the development of regional wall motion abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables--the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient--can provide practical estimates of the risk of having left main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful noninvasive estimate of the risk of having significant left main or three vessel disease.
The exercise electrocardiogram has been the subject of intense research over the last 50 years, as both a diagnostic and prognostic method to assess patients with chronic ischemic heart disease. In 1986, the strengths and limitations of the technique to predict coronary and multivessel disease in clinical patient subsets are understood. The diagnostic accuracy of the test is improved by consideration of Bayesian theory, multivariate models and new non-ST segment criteria. Post-test coronary disease risk estimates are best reported in terms of a conditional probability, rather than statements of "positive" or "negative." The value of exercise testing in prognostic risk stratification is considerably enhanced by recent reports of long-term follow-up data in asymptomatic and symptomatic patients. Powerful prognostic information can be obtained when the clinical, electrocardiographic and physiologic data from the exercise test are used to formulate the post-test risk of a cardiac event, even in patients whose coronary anatomy is known. The changing role of the exercise electrocardiogram as a diagnostic and prognostic test is reviewed, with emphasis on the strengths and limitations of the procedure.
Both Bayesian analysis assuming independence and discriminant function analysis have been used to estimate probabilities of coronary disease. To compare their relative accuracy, we submitted 303 subjects referred for coronary angiography to stress electrocardiography, thallium scintigraphy, and cine fluoroscopy. Severe angiographic disease was defined as at least one greater than 50% occlusion of a major vessel. Four calculations were done: (1) Bayesian analysis using literature estimates of pretest probabilities, sensitivities, and specificities was applied to the clinical and test data of a randomly selected subgroup (group I, 151 patients) to calculate posttest probabilities. (2) Bayesian analysis using literature estimates of pretest probabilities (but with sensitivities and specificities derived from the remaining 152 subjects [group II]) was applied to group I data to estimate posttest probabilities. (3) A discriminant function with logistic regression coefficients derived from the clinical and test variables of group II was used to calculate posttest probabilities of group I. (4) A discriminant function derived with the use of test results from group II and pretest probabilities from the literature was used to calculate posttest probabilities of group I. Receiver operating characteristic curve analysis showed that all four calculations could equivalently rank the disease probabilities for our patients. A goodness-of-fit analysis suggested the following relationship between the accuracies of the four calculations: (1) less than (2) approximately equal to (4) less than (3). Our results suggest that data-based discriminant functions are more accurate than literature-based Bayesian analysis assuming independence in predicting severe coronary disease based on clinical and noninvasive test results.
A prospective cardiologic evaluation was performed in 83 consecutive patients with transient cerebral ischemia or mild stroke and without symptoms or electrocardiographic signs of ischemic heart disease. Patients were studied with an electrocardiographic exercise test; a positive test was followed by exercise Thallium-201 myocardial scintigraphy. Results were compared to those obtained in a group of 83 age and sex-matched healthy subjects submitted to the same study protocol. Asymptomatic coronary artery disease was detected in 28% of cerebrovascular patients with adequate electrocardiographic exercise test. A scintigraphic perfusion defect of variable extension was found in 19 of them. In the control group the electrocardiographic exercise test was positive in only 6% (p less than 0.01). Our results support the concept that: asymptomatic ischemic heart disease is often associated with cerebrovascular disease; therefore cerebral ischemic attacks may be a marker of coronary artery disease, an active investigation of the heart should be considered in cerebrovascular patients in order to plan optimal, comprehensive management.
The increase in Shannon information available from a diagnostic test associated with grading of the test results into many outcomes, rather than simply positive or negative, was examined to determine its upper limit as the number of test outcomes is increased indefinitely. Numerical methods were employed to find the optimal locations of outcome boundaries when a single normally distributed test variable is classified into 2, 3, 4, 5, 6, 8, 14, or 20 outcome categories. In each case Shannon information was computed for values of prior probability between 0.01 and 0.99 and for distances between the means in diseased and nondiseased populations ranging from 0.5 to 5.0 standard deviations. There is an important improvement in Shannon information as the number of outcomes defined is increased, but the increment in information diminishes rapidly with each additional category. A 20%-30% increment in information may be achieved with three outcomes instead of two. A further important increase in information occurs with four to seven outcomes, but beyond this the increment in inforation is negligible. The findings were similar over a wide range of prior probabilities and distances between the means. The analysis was extended to the case of multiple nonindependent tests by demonstrating their application to a Fisher discriminant function incorporating such tests. It was concluded that for normally distributed test variables: grading of test results significantly improves the information content of both single and multiple tests; the value of information content for 8-20 outcomes represents very nearly the maximum information content of a test; there is little value in using more than five to seven test outcomes; multiple grading should not be neglected for discriminant functions.
To evaluate the utility of exercise radionuclide angiography (RNA) and electrocardiography in assessing the severity of coronary artery disease (CAD), 185 patients undergoing coronary angiography were studied prospectively. To avoid work-up bias and to provide an appropriate control group, all patients were simultaneously scheduled for exercise RNA and electrocardiography and for coronary arteriography. All test results were interpreted blinded to other data. Of multiple exercise variables analyzed by stepwise linear discriminant analysis, the independent predictors of disease severity were exercise ejection fraction, ST segment change, and maximum heart rate. These three variables were used to create a set of four equations that determine probabilities of zero, one-, two-, or three-vessel disease (VD). The noninvasive estimate of number of VD in each patient was compared to the angiographic result. Patients without significant CAD were classified correctly 71% of the time, while those with three-VD were predicted correctly in 80%. Fully 90% of patients with predicted three-VD had two- or 3-VD. Conversely, 84% of patients predicted to have zero VD had zero or one-VD. Thus the combined use of exercise RNA and ECG data permits assessment of the presence and severity of CAD.
Alternative strategies using conditional probability analysis for the diagnosis of coronary artery disease (CAD) were examined in 93 infarct-free women presenting with chest pain. Another group of 42 consecutive female patients was prospectively analyzed. For this latter group, the physician had access to the pretest and posttest probability of CAD before coronary angiography. These 135 women all underwent stress electrocardiographic, thallium scintigraphic, and coronary angiographic examination. The pretest and posttest probabilities of coronary disease were derived from a computerized Bayesian algorithm. Probability estimates were calculated by the four following hypothetical strategies: SO, in which history, including risk factors, was considered; S1, in which history and stress electrocardiographic results were considered; S2, in which history and stress electrocardiographic and stress thallium scintigraphic results were considered; and S3, in which history and stress electrocardiographic results were used, but in which stress scintigraphic results were considered only if the poststress probability of CAD was between 10% and 90%, i.e., if a sufficient level of diagnostic certainty could not be obtained with the electrocardiographic results alone. The strategies were compared with respect to accuracy with the coronary angiogram as the standard. For both groups of women, S2 and S3 were found to be the most accurate in predicting the presence or absence of coronary disease (p less than .05). However, it was found with use of S3 that more than one-third of the thallium scintigrams could have been avoided without loss of accuracy. It was also found that diagnostic catheterization performed to exclude CAD as a diagnosis could have been avoided in half of the patients without loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)
There has been considerable interest in recent years in enhancing the accuracy of noninvasive tests in diagnosing coronary artery disease. The recognition that no currently available test is a perfect predictor has led to the use of probability analysis as a means of assessing the presence or absence of coronary disease. In this article we present a multivariate approach to the diagnosis of coronary disease. One hundred forty-seven patients undergoing coronary angiography, thallium-201 imaging, and exercise ECG were studied. Patients were classified according to age, sex, and typical vs atypical chest pain. Sequential stepwise logistic regression analysis was performed to develop probability statements prior to testing, after exercise ECG, and after exercise ECG and thallium-201. The results indicate that this sequential approach can be used to develop strategies for the diagnosis of coronary disease in the same way as Bayes' theorem, while permitting integration of multiple characteristics into one model.
The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy.
Current and future improvements in treatment to prevent cerebral infarction among patients with transient ischemic attacks may reduce neurological morbidity but may not lead to a proportional improvement in life expectancy. Because the long-term primary cause of death in these patients is myocardial infarction, it is most likely that the most important way to prolong survival may be the vigorous investigation of their cardiac status and the treatment of their coronary artery disease, even if asymptomatic.
Bayes' theorem of conditional probability was applied to the diagnosis of coronary artery disease (CAD) using thallium-201 scintigraphy as the testing procedure. Thallium-201 scintiscans were evaluated with a discriminant function previously developed using the amplitude coefficients of the Fourier transforms of the scans. The technique was applied prospectively to a population of 100 patients undergoing diagnostic coronary arteriography and thallium-201 scintigraphy, including 83 patients with CAD (70% or greater stenosis of luminal diameter) and 17 control subjects. A pretest probability of CAD was determined for each patient from the patient's age, sex and anginal symptoms. The pretest probability was combined with the patient's discriminant score to determine a posttest probability for CAD. For patients with CAD, the mean posttest probability was 0.85. Moreover, 57 of 83 patients (69%) had posttest probabilities exceeding 90%, including 40 patients (48%) with posttest probabilities exceeding 99%. For control subjects, the mean posttest probability was 0.19, with 11 of 17 (65%) having a posttest probability of less than 10%. Overall, 68 subjects had a posttest probability either less than 10% or more than 90% of which 63 were correctly classified (93%). Using a 50% posttest probability as a cutoff for classification, the technique has an 89% sensitivity, an 82% specificity and an overall accuracy of 88%. Therefore, this method objectively distinguishes patients with CAD from control subjects and provides a measure of the certainty of diagnosis. In addition, the discriminant function avoids the problem of inter- and intraobserver variability in visually interpreting thallium-201 scans.
We studied 83 men, who had a chest pain syndrome, no prior history of myocardial infarction, and exercise-induced horizontal or downsloping ST segment depression greater than or equal to 0.2 mV. The 38 patients unable to complete Bruce stage II had a significant increased risk of coronary (0.97 vs 0.71) and multivessel (0.88 vs 0.61) disease (p less than 0.01) compared to the pretest risk; data obtained from exercise-reperfusion thallium scintigraphy and cardiac fluoroscopy did not alter the risk of coronary or multivessel disease. The 45 patients who had ST depression greater than or equal to 0.2 mV and a peak work capacity greater than or equal to Bruce stage III did not have a significant increased risk of coronary (0.76) or multivessel disease (0.44). When both exercise-reperfusion thallium scintigraphy and cardiac fluoroscopy were abnormal in this latter patient subgroup, the post-test risk of multivessel disease was increased from 0.44 to 0.82 (p less than 0.03); when both tests were normal, none of the patients had multivessel disease (p less than 0.03) and only 0.18 had coronary artery disease. Thus, cardiac fluoroscopy and exercise thallium scintigraphy increase the diagnostic content of the strongly positive exercise ECG, particularly in men who have a peak work capacity greater than or equal to Bruce stage III.
The purpose of this study was to assess the relation between the extent of coronary artery disease (CAD) and size of exercise‐induced myocardial hypoperfusion in 79 patients with angiographically documented CAD. None of the patients had Q‐wave myocardial infarction. Fifty patients had one‐vessel disease, ten had two‐vessel disease, and 19 patients had three‐vessel or left main disease.
From a scintigraphic functional standpoint, patients were classified into two groups: 28 patients (35%) had large perfusion defects and 51 patients (65%) had small defects. The size of the thallium‐201 perfusion defect during exercise was assessed as the perimeter of the defect in each projection expressed as a percentage abnormality of the total left ventricular perimeter in that projection. The average abnormality from the three projections was used in the final analysis. Eleven patients with large defects (39%) had one‐vessel disease and 12 patients with small defects (24%) had multivessel disease. Stepwise multivariate discriminate analysis identified the number of diseased vessels (F = 13.9), the change in systolic blood pressure from rest to exercise (F = 10.8), the exercise heart rate (F = 9.1), and exercise electrocardiographic response (F = 7.8) as significant associates of the size of the perfusion defect (predictive accuracy = 70%).
We conclude that the size of hypoperfused myocardium during exercise is variable in patients with CAD. Discriminate analysis identified the extent of CAD, exercise heart rate, change in systolic pressure from rest to exercise, and exercise electrocardiographic response as significant associates of the size of the defect.
We applied logistic regression analysis to a group of 736 patients with chest pain to determine which radionuclide angiographic (RNA) parameters were most useful in the diagnosis of significant coronary artery disease. The most useful parameters were exercise ejection fraction, exercise heart rate, "ischemia score," and the presence of a regional wall motion abnormality at exercise. Ten clinical variables were used in one logistic regression model to estimate each patient's pretest probability of disease. A second logistic regression model considered these clinical variables and the four important RNA parameters to estimate each patient's posttest probability. These models were applied prospectively to a group of 76 patients with chest pain who did not have a high pretest probability of disease. Twenty-four patients (32%) could be diagnosed with 90% probability; 32 patients (42%) could be diagnosed with 85% probability. RNA testing is therefore helpful in the noninvasive diagnosis of coronary artery disease. However, a majority of patients who do have a low or intermediate pretest probability of disease will require additional testing for a definitive diagnosis.
This study determines whether a mathematical model can be used to assess noninvasively the extent of coronary artery disease (CAD). The model was based on stepwise multivariate discriminant analysis of data obtained in 99 patients from clinical and nonhemodynamic exercise variables, or from radionuclide determination of left ventricular function at rest or during exercise, or both. The extent of CAD was assessed by a scoring system and by the number of diseased vessels. The variables selected by this method (Q-wave infarction, exercise LV ejection fraction, change in systolic blood pressure from rest to exercise, sex and diabetes mellitus) yielded a predictive accuracy of 82% for the identification of patients with extensive CAD (score greater than or equal to 35). Slightly better results were achieved by a subgroup of 77 patients who had adequate exercise end points (exercise heart rate greater than or equal to 120 beats/min, or angina or ST depression during exercise). In these patients, the predictive accuracy was 84%. The model also identified patients with "light" CAD (score less than or equal to 10) with a predictive accuracy of 82%. Thus, noninvasive assessment of the extent of CAD is possible with a stepwise multivariate discriminant analysis of clinical, electrocardiographic and left ventricular function assessed by radionuclide ventriculography at rest and during exercise. The scoring system was superior to the conventional method of classifying patients according to the number of diseased vessels.
One hundred fifty-four patients referred for coronary arteriography were prospectively studied with stress electrocardiography, stress thallium scintigraphy, cine fluoroscopy (for coronary calcifications), and coronary angiography. Pretest probabilities of coronary disease were determined based on age, sex, and type of chest pain. These and pooled literature values for the conditional probabilities of test results based on disease state were used in Bayes' theorem to calculate posttest probabilities of disease. The results of the three noninvasive tests were compared for statistical independence, a necessary condition for their simultaneous use in Bayes' theorem. The test results were found to demonstrate pairwise independence in patients with and those without disease. Some dependencies that were observed between the test results and the clinical variables of age and sex were not sufficient to invalidate application of the theorem. Sixty-eight of the study patients had at least one major coronary artery obstruction of greater than 50%. When these patients were divided into low-, intermediate-, and high-probability subgroups according to their pretest probabilities, noninvasive test results analyzed by Bayesian probability analysis appropriately advanced 17 of them by at least one probability subgroup while only seven were moved backward. Of the 76 patients without disease, 34 were appropriately moved into a lower probability subgroup while 10 were incorrectly moved up. We conclude that posttest probabilities calculated from Bayes' theorem more accurately classified patients with and without disease than did pretest probabilities, thus demonstrating the utility of the theorem in this application.
Several diagnostic noninvasive tests to detect coronary and multivessel coronary disease are available for women. However, all are imperfect and it is not yet clear whether one particular test provides substantially more information than others. The aim of this study was to evaluate clinical findings, exercise electrocardiography, exercise thallium myocardial scintigraphy and cardiac fluoroscopy in 92 symptomatic women without previous infarction and determine which tests were most useful in determining the presence of coronary disease and its severity. Univariate analysis revealed two clinical, eight exercise electrocardiographic, seven myocardial scintigraphic and seven fluoroscopic variables predictive of coronary or multivessel disease with 70% or greater stenosis. The multivariate discriminant function analysis selected a reversible thallium defect, coronary calcification and character of chest pain syndrome (p less than 0.05) as the variables most predictive of presence or absence of coronary disease. The ranked order of variables most predictive of multivessel disease were cardiac fluoroscopy score, thallium score and extent of ST segment depression in 14 electrocardiographic leads. Each provided statistically significant information to the model. The estimate of predictive accuracy was 89% for coronary disease and 97% for multivessel coronary disease. The results suggest that cardiac fluoroscopy or thallium scintigraphy provide significantly more diagnostic information than exercise electrocardiography in women over a wide range of clinical patient subsets.
We assessed the effect of gender on the electrocardiographic changes and thallium-201 myocardial perfusion during exercise in patients with coronary artery disease. Eighty-nine patients with coronary artery disease (50% or greater diameter narrowing of one or more major coronary arteries) who had undergone exercise thallium scintigraphy were retrospectively studied. There were 29 women and 60 men. Fifty-six patients had one-vessel disease, 11 patients had two-vessel disease, and 22 patients had three-vessel disease or left main disease. The extent of coronary artery disease was assessed by the Gensini score. There was no difference between men and women in age, medications, number of diseased vessels and the coronary artery disease score. Exercise tolerance was lower, although insignificantly in women compared to men. However, exercise heart rate, double product, and the electrocardiographic response were similar in men and women. Also, both the presence and size of exercise-induced perfusion defects were similar in men and women. Thus, the electrocardiographic response to exercise is not influenced by gender in patients with similar extent of coronary artery disease and comparable manifestations of myocardial ischemia.
We have evaluated the clinical value of new electrocardiographic criteria in exercise testing. In this study, we compared both ST-segment and R-wave amplitude criteria, separately and in combination with the findings from coronary arteriography in 122 patients. In these selected patients application of conventional ST-segment criteria gave a sensitivity of 31% and a specificity of 100%; with application of the slow upsloping ST-segment criteria the sensitivity was 51% and the specificity 82%. Analysis of R-wave amplitude changes alone led to a sensitivity of 50% and a specificity of 61%. In combined interpretation of ST-segment and R-wave amplitude changes the sensitivity was 51% and the specificity 93%. We conclude that slow upsloping ST-segment criteria constitute the most important recent improvement in interpreting exercise test results and that the value of R-wave amplitude changes during exercise in diagnosing significant coronary artery disease is rather low in the individual patient. R-wave amplitude changes, however, may have value in patients with a previous myocardial infarction and in reducing false-negative and false-positive responses according to ST-segment criteria. Combined interpretation of ST-segment and R-wave amplitude criteria is useful but not very efficient.
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.
To evaluate the clinical utility of perfusion scintigraphy in patients with markedly positive exercise ECGs, we studied 94 consecutive patients with markedly positive exercise ECGs; 74 of them were also studied with scintigraphy. Patients undergoing scintigraphy had an intermediate pretest likelihood of coronary disease and were divided into two groups: those with reversible defects involving one complete area or aspects of multiple vascular areas (group 1, 38 patients), and those with normal scintigrams and reversible defects in a limited aspect of one vascular area, isolated fixed defects, or both (group 2, 36 patients). Among all demographic and exercise variables, only a hypotensive or blunted blood pressure response and scintigraphic lung uptake or cavitary dilation, although insensitive, were more frequent in group 1 (all p < 0.05). All 36 patients in group 1 and 14 of 18 in group 2 who underwent coronary angiography had significant coronary lesions; 31 in group 1 but only seven in group 2 had multivessel disease (p < 0.05). Subsequently 32 patients in group 1 had revascularization compared with only two patients in group 2. Only one cardiac event was noted among 34 patients in group 2 who were followed for a mean of 38 months while they were being treated medically. However, four of nine patients in group 1 initially treated medically required late revascularization because of clinical progression of disease, and one patient died (p < 0.05). Compared with patients having scintigraphy, patients not imaged had a higher pretest likelihood of coronary disease, a higher incidence of angina, unstable angina, and induced angina, with a lower exercise time and time to ST depression (p < 0.05). All underwent angiography, and 16 had multivessel disease. Not all patients with markedly positive exercise ECGs were at similarly high coronary risk. Some with high-risk coronary anatomy were identified without the use of scintigraphy. In others, where diagnosis and prognosis were less clear, scintigraphy aided in the diagnosis and accurately identified a low-risk subgroup as did no other parameter.
This study evaluates the incremental prognostic value of qualitative thallium-201 imaging and coronary angiography in patients with suspected or known coronary artery disease.
Within 1 month, 150 patients underwent diagnostic symptom-limited ECG stress test, thallium imaging, and coronary angiography. The incremental power of sequentially performed tests was evaluated by the overall likelihood ratio statistic.
At 3-year follow-up, 16 patients had died from a cardiac cause, 12 had suffered a nonfatal myocardial infarction, and 34 had undergone revascularization procedures more than 60 days after testing. Considering hard events, thallium imaging did not improve the prognostic information provided by clinical exercise stress test data, while coronary angiography increased the predictive power of the combined, exercise stress test, and scintigraphic data (P < 0.001). Moreover, when thallium results were added to clinical, exercise, and coronary angiographic data, the predictive power was unchanged. When the analysis was repeated including the occurrence of late revascularization procedures, each test showed additional prognostic information to that obtained by the other combined tests (P < 0.001).
This study demonstrates that in patients with a symptom-limited ECG stress test, coronary angiography adds prognostic information to combined clinical, exercise ECG, and thallium imaging data. The incremental prognostic value of qualitative thallium imaging is demonstrable only when late revascularization procedures are included as events.
The objective of the study was to optimize the accuracy of the exercise test for predicting the presence of significant angiographic coronary artery disease. A retrospective analysis of stored digital exercise electrocardiographic data on 147 men who had undergone exercise testing and cardiac catheterization was performed. With significant coronary artery disease defined as > or = 70% stenosis, 95 patients had one or more vessel(s) diseased. None were receiving digoxin, had a myocardial infarction or previous coronary artery bypass graft, or exhibited left bundle branch block, left ventricular hypertrophy, Q waves, or ST depression on their resting electrocardiogram. Analysis was performed using the authors' averaging and measurement software at rest and at each 30 seconds throughout the exercise and recovery in leads II, V2, and V5. Discriminant function analysis was used to analyze pretest variables, as well as hemodynamic and electrocardiographic changes and symptoms during exercise. A discriminant function score was developed and compared to other treadmill scores. The setting was a 1,000 bed Veterans Affairs Medical Center (Long Beach, CA). Discriminant function analysis chose age, smoking status, presenting chest pain characteristics, and lead V5 ST slope in recovery to have independent power for separating those with and without coronary artery disease. A discriminant function score using these four variables was used to form a receiver operating characteristics curve (and derive receiver operating characteristics curve areas) for comparison to other exercise test methods and scores: (discriminant function score = .81; slope 3.5 minutes into recovery in lead V5 = .73; traditional ST amplitude method = .72; ST60/HR index (amplitude of ST depression 60 ms after the J point/delta heart rate) = .66; traditional ST amplitude/HR index (traditional method/delta heart rate) = .75; Hollenberg score = .68; Hollenberg areas only = .66; and ST integral = .66. Receiver operating characteristics curve analysis revealed a trend for the discriminant function score to be superior to all other measurements and scores. Recovery ST slope in lead V5 performed as well as or better than all other electrocardiographic criteria or treadmill scores except for the authors' discriminant function score.
The additional diagnostic yield of exercise 201Tl scintigraphy using both visual and quantitative analysis was determined in 221 patients with known or suspected coronary artery disease (CAD). The coronary arteriogram was adopted as the gold standard. After pretest clinical and exercise electrocardiographic data were taken into consideration, scintigraphy added diagnostic accuracy both in the diagnosis of CAD and of multivessel disease. The diagnostic yield of the scintigraphy in terms of sensitivity and specificity was, however, not significant. In 79% (121/153) of the patients, the diagnosis of the presence, or exclusion, of CAD was highly probable (P > 0.80 or P < 0.20) when considering clinical and exercise data. The diagnosis was, however, not significantly improved by the scintigraphic result. Twenty-seven per cent (20/73) returned a negative scintigraphic results with a high (P > 0.80) prescintigraphic probability for CAD and a positive arteriogram. It was concluded that 201Tl scintigraphy has additional diagnostic value after clinical and exercise parameters were taken into consideration in the diagnosis of coronary artery and multiple vessel disease. It is not recommended to refer patients with either a low or high probability of CAD for screening and diagnosis as in a high proportion of patients the diagnosis of CAD could have been made using clinical or exercise data alone.
Multivariable analysis of clinical and exercise test variables has the potential to become both a useful tool for assisting in the diagnosis of coronary artery disease and reducing the cost of evaluating patients with suspected coronary disease. Managed care and capitation require that tests such as the exercise test or its replacements, be used only when they can accurately and reliably identify which patients need medications, counseling, or further evaluation or intervention. The replacements for the standard exercise electrocardiogram test require expensive equipment and personnel, and their incremental value is currently being evaluated. Because general practitioners are to function as gatekeepers and decide which patients must be referred to the cardiologist, they will need to use the basic tools they have available (ie, history, physical exam, and the exercise test) in an optimal fashion. However, the discriminating power of the variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. There is a need for further evaluation of these routinely obtained variables to improve the accuracy of prediction algorithms especially in women. Of paramount concern is the need to avoid workup bias by having patients agree to testing before the decision for angiography is made. The portability and reliability of these equations must be shown because access to specialized care must be safeguarded. By reviewing the available studies considering clinical and exercise test variables to predict coronary angiographic findings, we have attempted to provide guidelines and recommendations for a more uniform approach to this endeavor in future investigations. Hopefully, the next generation of multivariable equations will be robust and portable, and empower the clinician to assure the cardiac patient access to appropriate cardiac care.
To demonstrate that an agreement approach to applying equations on the basis of clinical and exercise test variables is an accurate, self-calibrating, and cost-efficient method for predicting severe coronary artery disease in clinical populations.
Retrospective analysis of consecutive patients with complete data from exercise testing and coronary angiography referred for evaluation of possible coronary artery disease. After developing an equation in a training set, this equation and two other equations developed by other investigators were validated in a test set. The study was performed at two university-affiliated Veteran's Affairs medical centers.
1080 consecutive men studied between 1985 and 1995 who had coronary angiography within 3 months of the treadmill test. The population was randomly divided into a training set of 701 patients and a test set of 379 patients. Patients with previous coronary artery bypass surgery, valvular heart disease, marked degrees of resting ST depression, and left bundle branch block were excluded.
Recording of clinical and exercise test data along with visual interpretation of the electrocardiogram recordings on standardized forms and abstraction of visually interpreted angiographic data from clinical catheterization reports.
Simple clinical and exercise test variables improved the standard application of exercise-induced ST criteria for predicting severe coronary artery disease. By setting probability thresholds for severe disease of <20% and >40% for the three prediction equations, the agreement approach divided the test set into three groups: low risk (patients with all three equations predicting <21% probability of severe coronary disease), no agreement, and high risk (all three equations with >39% probability) for severe coronary artery disease. Because the patients in the no agreement group would be sent for further testing and would eventually be correctly classified, the sensitivity of the agreement approach was 89% and the specificity was 96%. The agreement approach appeared to be unaffected by disease prevalence, missing data, variable definitions, or even angiographic criteria.
Requiring diagnosis of severe coronary disease to be dependent on agreement between these three equations has made them likely to function in all clinical populations. The agreement approach should be an efficient method for the evaluation of populations with varying prevalence of coronary artery disease, limiting the use of more expensive noninvasive and invasive testing to patients with a higher probability of left main or triple-vessel coronary artery disease. This approach provides a strategy that can be applied by inputting the results of basic clinical assessment into a programmable calculator or a computer to assist the practitioner in deciding when further evaluation is appropriate, thus assuring patients access to subspecialty care.
We evaluated the prognostic value of exercise 201Tl indexes of myocardial hypoperfusion in patients with suspected or known coronary artery disease.
Patients were divided into two groups: group I consisted of 332 patients with diagnostic electrocardiographic stress test results and group II consisted of 144 patients with nondiagnostic (inadequate or uninterpretable) stress electrocardiograms. At the 2-year follow-up, 20 hard events (16 cardiac deaths and 4 nonfatal myocardial infarctions) and 80 soft events (coronary revascularization procedures) occurred in group I. Considering total events, thallium imaging provided significant prognostic information in addition to clinical and exercise stress test data in the total study population (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, thallium imaging added incremental prognostic value only in those with positive electrocardiographic stress test results (p < 0.01). When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). In group II at the end of follow-up, 15 hard and 39 soft events had occurred. In these patients occurrence of total (p < 0.001), hard (p < 0.05), and soft (p < 0.001) events was higher in those with abnormal thallium scintigraphic results than in those without. Moreover, no clinical and exercise variable, except history of myocardial infarction, was significantly related to outcome, whereas both indexes of extent and severity of hypoperfusion were significant.
The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give unique prognostic information in patients with nondiagnostic electrocardiographic stress test results. Thallium imaging provides incremental prognostic information even in patients with diagnostic electrocardiographic stress test results but not in the low-risk subset of patients without previous infarction who have negative electrocardiographic stress test results.
To assess whether inotropic stress myocardial perfusion imaging, echocardiography, or a combination of the two could enhance the detection of multivessel disease, over and above clinical and exercise electrocardiographic data.
100 consecutive patients investigated by exercise electrocardiography and diagnostic coronary arteriography underwent simultaneous inotropic stress Tc-99m sestamibi SPECT (MIBI) imaging and echocardiography. MIBI imaging and echocardiographic data were analysed using a 12 segment left ventricular model, and each segment was ascribed to a particular coronary artery territory. The presence of perfusion defects with MIBI imaging or of wall thickening abnormality with echocardiography in at least two coronary artery territories at peak stress was taken as diagnostic of multivessel disease. Arteriographic evidence of > or = 50% stenosis was considered significant.
56 patients had multivessel disease. The sensitivity of the combination of MIBI imaging and echocardiography for detecting this was greater than either MIBI imaging or echocardiography alone (82%, 68%, and 68%, respectively; p = 0.005). Clinical and exercise electrocardiographic variables gave an R2 value of 18.2% for predicting multivessel disease. The addition of either MIBI imaging (R2 = 29.2%; p = 0.002) or echocardiography (R2 = 28.8%; p < 0.001) enhanced the detection of multivessel disease, and the inclusion of both had further incremental value (R2 = 34.8%; p = 0.003). Age (p = 0.03), MIBI imaging (p = 0.007), and echocardiography (p = 0.001) were independent predictors of multivessel disease.
The assessment of both myocardial perfusion and contractile function by simultaneous inotropic stress MIBI imaging and echocardiography optimises the non-invasive detection of multivessel disease.
The aim of this study was to determine which clinical, exercise and thallium variables can aid in the identification of three-vessel or left main coronary artery disease (3VLMD) in patients with one abnormal coronary territory (either a reversible or fixed defect) on exercise thallium testing and to test the prognostic value of these variables.
Although the sensitivity of detection of coronary artery disease by thallium-201 imaging is high, the actual detection of 3VLMD by thallium tomographic images alone is not optimal.
A multivariate model for prediction of 3VLMD was developed from several clinical, exercise and thallium-201 variables in a training population of 264 patients who had one abnormal coronary artery territory on exercise thallium testing and had undergone coronary angiography. Using this model, patients were stratified into risk groups for prediction of 3VLMD. A separate validation cohort of 474 consecutive patients who were treated initially with medical therapy and who had one abnormal coronary territory were divided into identical risk groupings by the variables derived from the training population, and they were followed for a median of 7.0 years to evaluate the prognostic value of this model.
The prevalence of 3VLMD was 26% in the training population despite one abnormal thallium coronary territory. Four clinical and exercise variables--diabetes, hypertension, magnitude of ST segment depression, and exercise rate-pressure product-were found to be independent predictors of 3VLMD. In the training population, the prevalence of 3VLMD in low-, intermediate- and high-risk groups was 15%, 22% and 51%, respectively. When the multivariate model was applied to the validation population, the eight-year overall survival rates in the low-, intermediate- and high-risk groups were 89%, 73% and 75%, respectively (p < 0.001).
A substantial proportion of patients with one abnormal thallium coronary territory have 3VLMD with subsequent divergent outcomes based upon risk stratification by clinical and exercise variables. Consequently, the finding of only a single abnormal coronary territory by thallium-201 perfusion imaging does not necessarily confer a benign prognosis in the absence of consideration of nonimaging variables.
A comprehensive method is described for quantitation of the spatial distribution of TI-201 in the myocardium and its changes with time. The method, applied here to 51 patients, uses bilinear interpolative background subtraction to compensate for tissue crosstalk, and circumferential profiles to quantitate the relative radionuclide activity in the myocardium as an angular function with origin at the center of the left-ventricular cavity. In addition, washout circumferential profiles are calculated as percent washout from the stress circumferential profiles. Abnormal thallium distribution or washout is identified by automatic computer comparison of each patient's profiles with the corresponding limits of normal profiles, determined from the pooled profiles of 31 normal patients. In these 31, the computer output was normal in all cases. In 20 patients with angiographically documented coronary artery disease, 19 were determined to be abnormal by this method. This new computerized treatment provides accurate objective assessment of the presence of coronary artery disease.
A computer method has been developed to determine the relative initial uptake and segmental washout rates of thallium-201 from sequential myocardial images. Initial images in multiple projections are obtained at 10 min after thallium-201 injection, and delayed images 2-3 hr after injection. A modified interpolative method was used to construct a background reference plane, and net myocardial counts was used to construct a background reference plane, and net myocardial counts above this reference plane were determined from multiple count profiles. Washout rates were determined by linear regression of time-activity curves constructed from the sequential images. In this approach, both relative temporal as well as relative spatial quantitation is performed. Data from 25 normal subjects were used to establish numerical criteria and normal ranges for relative focal defects and abnormal segmental washout slopes. Normal ranges were set to include the 90-percentile limits of the distribution of values obtained from the normal population. From these values we derived a quantitative criterion for thallium scan interpretation that can be used for analysis and interpretation of scintigrams in clinical situations.
This study correlates the presence of exercise-related ventricular premature complexes with both exercise-induced ST-segment depression and coronary arteriographic and ventriculographic findings in 60 patients evaluated for chest pain. Of 38 patients in whom ventricular premature complexes were either precipitated or increased with exercise, 22 had coronary disease, 10 showed a cardiomyopathy, and 6 were normal. Twelve of the 22 coronary patients had 3-vessel disease, 6 had 2-vessel disease and 4 had 1-vessel disease. Sixteen of these 22 also showed coronary collaterals and left ventricular contraction abnormalities (asynergy). Twenty of the 22 showed ≥2 mm ST-segment depression with exercise, in addition to the ventricular premature complexes (P < 0.001). Twenty-two patients showed a decrease in ventricular premature complexes with exercise. Six had coronary disease, eight had a cardiomyopathy, and eight were normal. None of the six with coronary disease had 3-vessel disease, two had 2-vessel disease, and four had disease of 1 vessel. Collaterals and asynergy were found in one of the six patients. None of the patients in this group showed ST-segment depression with exercise.
This paper summarizes work in discriminant analysis. Normal theory and discrete results are discussed. Estimation of error rates and variable selection problems are indicated. Current research problems are considered: robustness, nonparametric rules, contamination, density estimation, mixtures of variables.
Seven hundred and ninety-five consecutive patients with the diagnosis of angina pectoris were studied by coronary angiography and followed for 2–7 years. The prognosis is greatly determined by the extent of coronary artery involvement. Concomitant mitral insufficiency or ventricular aneurysm influence the prognosis adversely. There was no significant difference in prognosis between men and women. As regards patients with three-vessel disease and elevated left ventricular end-diastolic pressure, the prognosis was better in operated than in non-operated patients. The prognosis seems to have improved when angina pectoris materials collected in the 70s are compared with materials from the 60s.
The incidence of decreases in peak systolic blood pressure during treadmill exercise was investigated in 460 patients with definite or suspected coronary heart disease. All patients were studied with coronary cineangiography. Exercise was continued to one of the following end points: chest pain, 85 to 90 percent of the patient's age-predicted maximal heart rate, ventricular tachycardia or a sustained decrease of 10 mm Hg or more below the peak level of systolic blood pressure. Twenty-two patients with 75 percent or greater stenosis of one or more major coronary arteries manifested a decrease in systolic pressure 10 mm Hg or more during exercise. These included 15 (17 percent) of 88 patients with three vessel, 7 (7 percent) of 101 with two vessel and 0 of 90 with single vessel disease. The decrease in pressure was reproducible in the seven patients who underwent a second exercise test before alteration of therapy; this decrease was abolished in the six patients who exercised again after coronary bypass graft surgery.A decrease in systolic pressure of 10 mm Hg or more also occurred during exercise testing in 3 of 23 patients with noncoronary organic heart disease; all 3 had an obstructive cardlomyopathy that had not been suspected clinically. Only 1 of 158 subjects with chest pain and no demonstrable heart disease had a decrease in systolic blood pressure with exercise. Declines in blood pressure were not observed during 650 maximal exercise tests performed on 560 clinically normal men.In conclusion, if one excludes subjects with cardiomyopathy or significant heart valve disease, a sustained exercise-induced decrease in peak systolic blood pressure of 10 mm Hg or more is a highly specific sign of multiple vessel coronary artery disease. This phenomenon is best explained by acute left ventricular pump failure secondary to extensive myocardial ischemia.
The rote of the single dose technique of myocardial perfusion imaging with thallium-201 in evaluating patients with suspected coronary artery disease was studied in 128 patients undergoing diagnostic coronary arteriography. Significant coronary disease (70 percent or more luminal stenosis) was present in 95 patients. Exercise scans were compared with 4 hour redistribution scans for the presence of new defects with exercise. Myocardial perfusion imaging was significantly more sensitive (85 versus 64 percent, P < 0.01) and more accurate (84 versus 71 percent, P < 0.05) than stress electrocardiography in detecting coronary disease.The patients were classified into two groups: group I,89 patients with diagnostically adequate stress electrocardiograms (that is, positive for ischemia or negative at 85 percent or more predicted maximal heart rate), and group II, 39 patients with nondiagnostic stress electrocardiograms (that is, uninterpretable because of intraventricular conduction disturbance or inadequate because of absence of ischemic S-T depression but failure to achieve 85 percent of predicted maximal heart rate). The sensitivity (87 percent), specificity (85 percent) and accuracy (87 percent) of myocardial perfusion imaging in detecting coronary disease in group I were not significantly different from the results of stress electrocardiography alone (88 percent sensitivity, 85 percent specificity and 88 percent accuracy). in group II scintigraphy was 81 percent sensitive, 69 percent specific and 77 percent accurate in detecting coronary disease; these results were not significantly different from those in group I.These data indicate that myocardial perfusion imaging with thallium-201 is more sensitive and more accurate than stress electrocardiography in detecting coronary artery disease but offers no advantage for this purpose in patients with diagnostically adequate stress electrocardiograms.
A cohort of 1472 patients who underwent both exercise stress testing and coronary angiography within six weeks was examined. The data indicated that a combination of exercise parameters is both diagnostically and prognostically important. Almost all patients (greater than 97%) who had positive exercise tests at Stage I or Stage II had significant coronary artery disease. More than half of these (greater than 60%) had three vessel disease and over 25% had significant narrowing (greater than 50%) of the left main coronary artery. Patients who achieved Stage IV or greater exercise durations with either negative or indeterminate ST-segment response had less than a 15% prevalence of three vessel disease and less than a 1% prevalence of left main coronary artery disease. A low risk subgroup (75% of all non-operated patients) was identified with a twelve month survival greater than 99%. A high risk subgroup (11% of all nonoperated patients) was identified with a twelve month survival of less than 85%. The exercise test is a noninvasive, reproducible method to assess the presence and extent of anatomic disease and the prognosis when significant disease has been defined. It should be used in conjunction with other noninvasive tests to determine optimal management in patients evaluated for ischemic heart disease.
Sixty-five patients were studied with stress electrocardiography and thallium-20 1 relative myocardial perfusion scintigraphy. Results were correlated with selective coronary angiography. Scintigraphy was more sensitive (85 versus 67 percent), more specific (89 versus 63 percent) and significantly more accurate (87 versus 65 percent) than stress electrocardiography for the diagnosis of significant coronary arterial lesions in patients with isoelectric S-T segments at rest. Stress scintigraphy helped clarify the equivocal stress test due to left bundle branch block, left ventricular hypertrophy, drugs, hyperventilation and other conditions and was more accurate than the stress electrocardiogram (89 versus 53 percent) even in the presence of a depressed S-t segment at rest. Thallium-20 1 scintigraphy is a safe and simple noninvasive method for identifying abnormal myocardial perfusion, stress-induced ischemia and, indirectly, significant coronary arterial lesions.
In order to evaluate hemodynamic predictors of myocardial oxygen consumption (MVO2), 27 normotensive men with angina pectoris were studied at rest and during a steady state at sympton-tolerated maximal exercise (STME). Myocardial blood flow (MBF) was measured by the nitrous oxide method using gas chromatography. MBF increased by 71% from a resting value of 57.4 +/- 10.2 to 98.3 +/- 15.6 ml/100 g LV/min (P less than 0.001) during STME while MVO2 increased by 81% from a resting value of 6.7 +/- 1.3 to 12.1 +/- 2.8 ml O2/100 g LV/min (P less than 0.001). MVO2 correlated well with heart rate (HR) (r = 0.79), with HR x blood pressure (BP) (r = 0.83), and, adding end-diastolic pressure and peak LV dp/dt as independent variables, slightly improved this correlation (r = .86). Including the ejection period (tension-time index) did not improve the correlation (r = 0.80). Thus, HR and HR x BP, both easily measured hemodynamic variables, are good predictors of MVO2 during exercise in normotensive patients with ischemic heart disease. Including variables reflecting the contractile state of the heart and ventricular volume may further improve the predictability.
The sensitivity of myocardial imaging with thallium-201 for detection of infarction and ischemia depends on reproducible image interpretation. Agreement in interpretation among four experienced readers at two institutions was studied in 100 consecutive patients, 50 from each center. Studies were performed at rest following a 2-mCi injection of Tl-201 on similar scintillation cameras with high-resolution collimation. Each study (three views: ANT, 45° LAO, LLAT) was read independently from trilens Polaroid scintiphotos. All observers were unaware of other clinical information. Each study was interpreted as normal (N), borderline (B), or abnormal (AB) and quality graded as poor, adequate, or excellent. Complete agreement among all possible observer pairs (six) was similar: 67% (range: 61-73%); complete disagreement (e.g. N/AB) was 4% (range: 2-8%). For all four readers combined, there was complete or essential (e.g. NNNB) agreement in 79, minor disagreement in 8, and major disagreement (e.g. at least 1 N and 1 AB) in 13. Poor-quality scans (as judged by two or more observers) were nearly equally divided between the two centers: nine in Seattle, and seven in Amsterdam. The interobserver agreement found is similar to that reported for other images and for coronary arteriography. This study defines interobserver limitations on Tl-201 sensitivity in detecting infarction and ischemia.
Exercise ECGs and coronary angiograms were reviewed in 266 patients (81 normals and 185 with significant coronary artery disease). Thirty-three false positive and 96 false negative ST responses to stress testing were purposely chosen to determine if the R wave could reduce the number of false ST responses. R wave amplitude changes were measured in the control and in the immediate postexercise period. An increase or no change in R wave was taken as evidence of an abnormal response, while a decrease in the R wave was a normal response. The sensitivity by ST segment was 48% and the specificity was 59%. These values were low because of the large number of false positive and negative ST responses in the study. It was our purpose to determine if these lowered values could be significantly improved by the R wave. Using R wave criteria, the sensitivity was 63% (P is less than 0.01) while the specificity was 79% (P is less than 0.01). The sensitivity and specificity of stress testing can be significantly improved using R wave changes.
Coronary angiograms and treadmill stress tests were reviewed in 89 patients. Changes in R wave amplitude were measured in the control and immediate postexercise periods. Of 45 patients with normal coronary arteries, 41 (91 percent) had a decrease in R wave amplitude (P less than 0.01); 3 (7 percent) had an increase in amplitude, including 2 with abnormal left ventriculograms. The remaining patient (2 percent) had abnormal wall motion but no change in R wave amplitude. Among the 44 patients with significant coronary artery disease (70 percent or greater luminal narrowing in one or more vessels), R wave amplitude increased after exercise in 26 (59 percent) with more severe coronary artery disease. R wave amplitude decreased in 18 patients (41 percent) with normal or minimally abnormal resting ventriculograms and less severe coronary artery disease (P less than 0.01). Changes in R wave amplitude reflect ventricular function, an increase in R wave amplitude reflecting more severe dysfunction and severe coronary narrowing. A decreased R wave amplitude indicates normal or minimal dysfunction and is strongly associated with normal coronary angiograms.
The specificity and sensitivity of thallium-201 myocardial perfusion imaging (MPI), under exercise, in patients with suspected coronary-obstructive disease was compared with graded exercise ECG tests (GTX) in patients with angiographically normal (N = 34) and obstructed (N = 48) coronary arteries. Of the 34 patients with normal coronaries, only one had a perfusion defect on the MPI (specificity 97%). Of the 48 patients with coronary obstructive disease (>50% obstruction of at least one coronary vessel), MPI was positive in 38 (sensitivity 79%). In contrast, the GTX had a specificity of 62% and sensitivity of 88% if nondiagnostic GTX tests are excluded. When the MPI and the GTX were used in combination, however, the sensitivity of detecting patients with coronary obstructive disease was increased to 94% (p < 0.01). The MPI was particularly useful in the evaluation of the 26 patients with nondiagnostic GTX. In this group, 24 of the 26 patients were correctly identified by the MPI with respect to the presence or absence of coronary-obstructive disease. In the 14 patients with a history of classical angina but with normal coronaries, the MPI was negative in 13 and positive in one, thus suggesting that in the majority of these patients transient transmural myocardial ischemia probably does not occur during exercise. The presence or absence of angiographically demonstrable coronary collateral vessels did not seem to influence the exercise MPI in patients with coronary-obstructive disease. Thus, although the MPI does not correctly identify all patients with either coronary-obstructive disease or normal coronary arteries, it is helpful in patients who have a nondiagnostic GTX. Furthermore, when used in combination with the GTX, the MPI significantly increases the likelihood that significant coronary-obstructive disease is present when both tests are positive, and that coronary disease is absent when both tests are negative.
To determine the value of a multivariate approach for the analysis of the treadmill exercise tolerance test (ETT), 237 patients referred for evaluation of chest pain who underwent a standard Bruce protocol ETT and coronary arteriography were studied. Predictive value of a positive ETT was 0.78 (43/55) using 1.0--1.9 mm ST segment depression criterion, 0.97 (59/61) using greater than or equal to 2.0 mm ST segment depression. When the 1.0--1.9 mm ST criterion was combined with peak systolic blood pressure-heart rate product (double product) less than or smaller than 23,000, exercise duration less than 6 minutes, and ST depression for greater than 3 minutes into recovery, predictive value improved to 0.89 in 18 patients with any two of the above. Predictive value for multivessel disease was also improved using non-ST criteria. Predictive value of a negative ETT for absence of coronary artery disease was 0.60 (29/48), and was 0.86 (12/14) if double product was greater than or equal to 30,000. Presence of chest pain during ETT did not improve predictive value of any type of test. Digitalis ingestion in 33 patients was not associated with decreased predictive value of a positive test. These data suggest that the predictive value of both positive and negative ETT in a symptomatic population can be improved with a multivariate approach.
Thallium-201 myocardial perfusion scintigraphy was performed after exercise, 4 hours after exercise (redistribution) and after a separate rest injection in 87 patients undergoing coronary arteriography. Significant coronary lesions were present in 62 of the patients. Interpretation of the rest and redistribution scintiscans was the same in 69 patients, 45 of whom had coronary artery disease (CAD). In 16 of the 17 patients with CAD and differing interpretations, defects were present on redistribution scintiscans but not on rest scintiscans; 11 of these patients had evidence of prior transmural myocardial infarction and the other five had an occluded coronary artery supplying the region of the defect. Redistribution scintiscans were more sensitive than rest scintiscans for the detection of prior myocardial infarction (93% vs 54%; P less than 0.01). The increased sensitivity was confined to the detection of prior inferior myocardial infarctions. In 36 of 38 patients with persistent perfusion defects on 4-hour redistribution scintiscans, either a prior infarction or an occluded coronary vessel was present. Exercise scintiscans were compared with rest scintiscans or with redistribution scintiscans for the detection of CAD. The sensitivity was not significantly different with either technique (90% and 89%, respectively), but both scintigraphic techniques were more sensitive than exercise electrocardiography (66%, P less than 0.01). These data demonstrate that redistribution thallium-201 scintiscans may be substituted for conventional rest scintiscans, resulting in reduced cost and radiation exposure to the patient.
Methods have been developed for on-line computer enhancement of a scintillation camera's myocardial images and for a graphical presentation showing relative thallium-201 activity in the myocardium. Enhancement uses fast Fourier transform techniques. The methods have been applied to multiple images obtained after stress and 4--5 hr rest. Patients with myocardial infarction and/or transient ischemia were evaluated and typical examples are presented.
The sensitivity of myocardial perfusion imaging (MPI) using thallium-201 injected both at rest and during peak exercise was compared to simultaneously recorded 12 lead electrocardiography (ECG) for the detection of transient ischemia in 20 normal subjects and 63 patients with coronary artery disease (CAD). No significant perfusion defects or ECG changes were seen on either the rest or exercise studies in any of the normal subjects. Fifty-six percent of patients with CAD developed new perfusion defects with exercise compared to 38% who developed ischemic ST-segment depression (P less than 0.02). However, when chest pain and/or ST depression were considered indices of ischemia, the sensitivity of exercise testing and thallium-201 MPI was similar. The increased sensitivity of MPI compared to ST-segment depression on the ECG was due to patients with baseline ECG abnormalities and those who failed to achieve 85% of predicted maximum heart rate with exercise. Analysis of the exercise results according to the extent of coronary artery disease revealed a progressive increase in both positive ECGs and MPI with the number of vessels involved. In patients with single vessel disease the MPI was more sensitive than the ECG (P less than 0.02). The combination of the rest and exercise ECG, MPI and chest pain during exercise failed to identify 11% of patients with CAD. Exercise thallium-201 MPI is a useful adjunct to conventional exercise testing particularly when evaluating patients with abnormal resting ECGs, those who develop ventricular conduction defects of arrhythmias during exercise, and those who fail to achieve their predicted heart rate because of fatigue or breathlessness.
Myocardial imaging with intravenous thallium-201 (201Tl) was performed at rest and following maximal treadmill exercise in 101 patients with suspected coronary artery disease. Results were interpreted from Polaroid scintiphotos by three independent observers with complete interobserver agreement in 79%. Of 25 patients with no or insignificant coronary artery disease (less than 50% diameter stenosis), one (4%) had a resting 201Tl image defect, one (4%) had an exercise 201Tl defect, none had an ECG Q wave, and four (16%) had exercise ST-segment depression. Among 76 patients with coronary artery disease (greater than or equal to 50% diameter stenosis), 58 (76%) had a defect on either the rest or exercise 201Tl image. The proportion of patients with an exercise image defect (50/76, 66%) was greater than the proportion with exercise ST depression alone (34/76, 45%; P less than 0.02). Overall, 69 of the 76 (91%) patients with coronary artery disease had either a positive rest or exercise myocardial image and/or a positive rest (ECG Q waves) or exercise (ST depression) electrocardiogram. This exceeded the proportion with only rest or exercise electrocardiographic abnormalities (50/76, 65%; P less than 0.001). We conclude that rest and exercise myocardial imaging with 201Tl is easily accomplished with readily available imaging equipment. The image data enhanced the diagnostic sensitivity of stress electrocardiography, and provided spatial identification of the abnormal segment(s) of myocardium.
The configuration, time of onset, and duration of depressed ST segments during and after treadmill exercise testing were evaluated in 269 patients with angiographically proven coronary artery disease and 141 normal subjects. The test specificity was 93% and sensitivity 64%, the latter being influenced by the type of ST response; false-positive responses were rare with depressed, downsloping STs (1 of 123, 1%), occurred more frequently with horizontal ST depression (9 of 60, 15%), and occurred commonly with slowly upsloping STs (15 of 47, 32%). Depressed downsloping STs, ischemic changes appearing in the first 3 minutes of exercise, and those persisting past 8 minutes in recovery were associated with 91%, 86%, and 90% prevalences of two- to three-vessel or main left coronary disease, respectively. It is concluded that attention to configuration, time of onset, and duration of ischemic ST depression aids both in assessing the validity of exercise responses in diagnosing coronary artery disease and in delineating patients with advanced coronary obstruction.
Serious obstructive coronary artery disease was found in all patients who developed hypotension accompanying the onset of angina during multistage exercise testing. Seventeen exercising patients demonstrated a fall in systolic pressure to below resting levels as chest pain and ST-segment depression appeared. Two patients died suddenly six weeks after treadmill testing and prior to arteriography. The remaining fifteen were studied with coronary arteriography and all except one exhibited greater than or equal to 90% stenosis of the left anterior descending artery (LAD). The remaining patient demonstrated two 75% LAD stenoses in series. Five exhibited significant (greater than or equal 75%) narrowing of the main left coronary artery (MLCA) and thirteen of fifteen had significant stenosis of proximal LAD and circumflex arteries. The two patients without significant circumflex disease exhibited greater than or equal to 90% stenosis of the dominant right coronaryartery (RCA) circulation. Six of six patients had restoration of a normal blood pressure response following coronary bypass surgery, which also relieved angina and reversed ST-segment depression. Conditions essential for proper interpretation of this sign are discussed. If these conditions are met, then a fall in systolic pressure during treadmill-induced angina pectoris is a reliable sign of severe compromise of left ventricular blood supply.
The incidence, types and patterns of emergence of treadmill exercise induced ventricular arrhythmias were studied in 482 subjects with and without coronary heart disease. All subjects were free of premature ventricular complexes at rest and were classified into groups on the basis of their clinical status. In Group 1A were 141 patients with chest pain and normal coronary arteriograms and in Group IB 144 age-matched subjects free of clinical evidence of heart disease. Group II consisted of 197 patients with chest pain and arteriographically documented coronary artery disease. Patients in Group IA and II exercised to at least 85% of their predicted maximal heart rate or until chest pain occurred. Subjects in Group IB underwent maximal exercise testing. The total incidence of exercise-induced ventricular arrhythmias was 16% in Group IA, 44% in Group IB and 29% in Group II. However, when exercise heart rate at the time of appearance of ventricular arrhythmias was taken into account the incidence of exercise-induced ventricular arrhythmias up to a heart rate of 130/min was 27% in the patients with documented coronary artery disease (Group II) compared with rates of 9 and 6%, respectively, for Groups IA and IB (P less than 0.001). The incidence rates of multifocal ventricular premature complexes, ventricular tachycardia and ventricular premature complexes at a rate of more than 10/min were also significantly greater at submaximal heart rates in the patients with coronary disease. Patients with three vessel coronary artery disease and abnormal left ventricular wall motion had a significantly greater incidence of exercise-induced ventricular arrhythmias. The incidence of exercise-induced ventricular arrhythmias in patients with coronary disease and a positive S-T segment response was not significantly increased.
Ventricular extrasystoles occurring before, during or after graded exercise testing were related to extent of coronary artery disease and to ventricular motion disorders in 81 symptomatic patients undergoing selective coronary and left ventricular angiography; the results were compared with data in 89 similar age-matched patients without arrhythmias. Compared with arrhythmia-free patients, 67 patients with exercise-induced arrhythmias had a significantly greater incidence of prior myocardial infarction, double or triple vessel disease and overall abnormal ventricular contractile patterns. Exercise induced extrasystoles occurred in only 11 percent of patients with insignificant coronary disease. Abolition of resting extrasystoles by exercise was not associated with less extensive coronary disease. Our study suggests that exercise-precipitated arrhythmias may represent a form of subclinical ischemia, signify more advanced degrees of coronary and left ventricular disease, and serve as an aid in detecting potentially high-risk patients.
The clinical progress was studied in a series of 590 consecutive nonsurgical patients with coronary disease documented by selective coronary arteriography. All had 50% or more obstruction in at least one major artery. Patients who were operated on within 5 years were excluded. Observations of the survivors ranged from 5 to 9 yrs. During the total observation period 263 patients died; only 19 deaths were not due to coronary disease. The 5 yr cardiac mortality rate was 34.4% for the entire population, 14.6% for patients with one vessel involvement, 37.8% for patients with 2 vessel involvement, 53.8% for patients with 3 vessel involvement, and 56.8% for those with at least 50% narrowing of the left main coronary artery. In patients with single vessel disease the presence or absence of additional lesions causing less than 50% narrowing was of significant prognostic influence.
Graded exercise stress tests performed on 650 consecutive patients with proven or suspected coronary disease undergoing evaluation by cardiac catheterization were correlated with clinical, hemodynamic, and angiographic findings. Among 451 patients with significant coronary stenosis, 332 (74%) had interpretable stress tests and 65% of these were positive (sensitivity). The rate of "false positives" was 8%.
The clinical syndrome of typical angina identified significant coronary disease in 89% of the patients, and 58% of that group had a positive exercise test defined by objective electrocardiographic criteria.
Patients were not eliminated from this study because of recent digitalis ingestion. Although a higher frequency of uninterpretable exercise tests was found in this group (40%), the test results reflected more severe coronary disease. None of the patients with "false positive" tests were taking digitalis. It is concluded that recent digitalis ingestion should not be considered a contraindication for exercise stress testing.
Among the patients with interpretable exercise tests, the angiographic severity of coronary artery disease correlates strongly with the frequency of positive tests (40%, 66%, and 76%, with 70% or greater occlusion of one, two or three vessels respectively). Left main coronary stenosis of 70% or greater was associated with more severe ST segment changes, inability to achieve target heart rate during stress, and a lower maximum heart rate during exercise. The angiographic occurrence of collateral vessels was related to the extent of coronary disease and was associated with a higher percentage of positive exercise tests; no protective effect of collateral circulation could be demonstrated. Patients with abnormal resting hemodynamics or left ventricular asynergy had no significant difference in the frequency of positive tests after adjustment for the angiographic severity of disease.
This study correlates the presence of exercise related ventricular premature complexes with both exercise induced ST segment depression and coronary arteriographic and ventriculographic findings in 60 patients evaluated for chest pain. Of 38 patients in whom ventricular premature complexes were either precipitated or increased with exercise, 22 had coronary disease, 10 showed a cardiomyopathy, and 6 were normal. Twelve of the 22 coronary patients had 3-vessel disease, 6 had 2-vessel disease and 4 had 1-vessel disease. Sixteen of these 22 also showed coronary collaterals and left ventricular contraction abnormalities (asynergy). Twenty of the 22 showed ≥2 mm ST segment depression with exercise, in addition to the ventricular premature complexes (P< 0.001). Twenty two patients showed a decrease in ventricular premature complexes with exercise. Six had coronary disease, 8 had a cardiomyopathy, and 8 were normal. None of the 6 with coronary disease had 3-vessel disease, 2 had 2-vessel disease, and 4 had disease of 1 vessel. Collaterals and asynergy were found in 1 of the 6 patients. None of the patients in this group showed ST segment depression with exercise.
1.1. An electrode placement system is described which permits the recording of 12-lead electrocardiograms of excellent quality during exercise as well as at rest which closely resemble records derived from the standard peripheral position for limb lead electrodes. These records are essentially free of interference from muscle potential.2.2. A light-weight, disposable, inexpensive, stainless steel and plastic electrode has been developed which obviates virtually all sources of electrode interference, even during strenuous exercise.3.3. A means is described whereby stress as external work in graded increments may be administered. Thus, work can be adapted to the state of disease and physical fitness of the individual at any level.
A system of multiple-lead exercise electrocardiography has been applied to the study of 107 normal subjects and 67 patients with angina pectoris. The results of this test are compared to those of coronary cinearteriography in 84 patients. In-exercise ECGs gave useful additional information in 59% of the angina patients but were essential for interpretation in 9%. It added considerably to the safety of the test. The value of each individual lead and of the multiple lead system was assessed. Lead V6 was the most often positive, but each made a contribution in some cases. Test-retest reproducibility survey indicated that five of 65 tests on 25 subjects failed to conform. Evidence has been presented that 1.0 mm of ischemic S-T segment shift was the best criterion for a positive test in the subjects studied. The test was positive in 84% of 67 patients with angina pectoris and 3.7% of 107 normal subjects (excluding vasoregulatory hyperreactors). The double two-step test given to the first 41 of the same angina patients for comparison was found to give 61% positive reactions despite the use of multiple leads and in-exercise recording. The test was administered to 84 subjects who were studied concurrently by selective coronary cinearteriograms and these two parameters were compared with the clinical diagnosis of angina in each patient. Since each of these parameters represents a different facet of coronary arterial disease, the agreement among them is very instructive.
A method is presented which enables one to obtain confidence intervals for the probability of misclassification for a given discriminant function using the observations from which it is computed. It is similar to Smith's [1947] method in that it re-uses all of the data, but dissimilar in that the estimates one obtains are unbiased for the probability of misclassification for a discriminant function based on n1 - 1 and n2 observations or n1 and n2 - 1 observations.
Comparison of submaximal exercise ECG test with coronary cineangiocardiogram
- Rohman D Jones
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- Sheffield
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RoHman D, Jones WB, Sheffield LT. Comparison of submaximal exercise ECG test with coronary cineangiocardiogram. Ann Intern Med 1970;71:841-7.
A new system of multiple-lead exercise elec-trocardiography Bruce RA. Exercise testing of patients with coronary heart disease: principles and normal standards for evaluation
- Mason Re Llkar
Mason RE, Llkar I. A new system of multiple-lead exercise elec-trocardiography. Am Heart J 1966;71:196-205. Bruce RA. Exercise testing of patients with coronary heart disease: principles and normal standards for evaluation. Ann Clin Res 1971;3:323-32.
Quantitative methods in the evaluation of thallium-201 myocardial perfusion images.
- Meade RC
- Bamrah RS
- Horgan JD
- Ruetz PP
- Kroneneetter C
- Yen E-L
The rate-pressure products as an index of myocardial oxygen consumption during exercise in patients with angina pectoris.
- Globel FL
- Nordstrom LA
- Nelson RR
- Jorgensen CR
- Wang Y
Hypotension accompanying the onset of exertional angina
- Thomson
A multivariate approach for interpreting treadmill exercise tests in coronary artery disease.
- Berman JL
- Wynne J
- Conn PF
Comparison of submaximal exercise ECG test with coronary cineangiocardiogram.
- Roltman D
- Jones WB
- Sheffield LT
A multivariate approach for interpreting treadmill exercise tests in coronary artery disease
- Berman