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The treadmill exercise score revisited: Coronary arteriographic and thallium perfusion correlates
Abstract
The treadmill exercise score has been used to stratify patients into low-, moderate-, and high-risk groups. This score is derived from ST segment depression, angina, and exercise duration. To determine the coronary arteriographic and exercise thallium perfusion correlates of the score, we examined the extent of coronary artery disease and exercise single photon emission computed thallium-201 results in 834 patients for whom cardiac catheterization data were available. Of those, 174 had no coronary artery disease, 195 had one-vessel, 246 had two-vessel, and 219 had three-vessel disease. Based on the treadmill exercise score, 369 were in the low-risk, 384 in the moderate-risk, and 81 in the high-risk group. The extent of coronary artery disease was 2.1 +/- 1 diseased vessels in the high-risk, 1.7 +/- 1 in the moderate, and 1.4 +/- 1.1 in the low-risk group (p < 0.01). The extent of the thallium abnormality (maximum number of abnormal segments 120/patient) was 10 +/- 6 in the high-risk, 7 +/- 6 in the moderate, and 6 +/- 5 in the low-risk group (p < 0.05). Based on the extent of coronary artery disease and results of thallium imaging, patients were reclassified into three groups: group 1 had three-vessel disease and/or > or = 10 abnormal segments (n = 387), group 3 had no coronary artery disease or one-vessel disease and less than five abnormal segments (n = 212), and the remaining patients were in group 2 (n = 235).(ABSTRACT TRUNCATED AT 250 WORDS)
... Of those classified as low risk in our 3225-patient series, most had either no significant (Ն75% stenosis) lesions or single-vessel coronary disease. Similarly, Iskandrian and colleagues 15 reported that Ϸ50% of low-risk treadmill score patients had no or single-vessel coronary disease, whereas 75% of high-risk patients had multivessel disease in a series of 834 patients undergoing myocardial perfusion imaging. ...
... The exercise treadmill test is used for the identification of patients who are at increased risk of significant or severe disease and future coronary events. 14,15 Within the growth of managed care and capitated reimbursement schemes, management strategies that emphasize expensive stress imaging studies and cardiac catheterization are not likely to be favored in many practice environments. Although the treadmill test should not be considered to replace any imaging modality, if the efficient use of low-cost clinical data and risk stratification with a low-cost stress test are emphasized, evaluation costs may be reduced for many patients. ...
... Of the remaining moderate-risk patients, use of an imaging modality has been proposed to further risk-stratify these patients. 14,15 Thus, only Ϸ50% of our study population would require a stress imaging study before patient management is decided on. This provides a method for selective use of more expensive imaging or invasive testing. ...
Exercise testing is useful in the assessment of symptomatic patients for diagnosis of significant or extensive coronary disease and to predict their future risk of cardiac events. The Duke treadmill score (DTS) is a composite index that was designed to provide survival estimates based on results from the exercise test, including ST-segment depression, chest pain, and exercise duration. However, its usefulness for providing diagnostic estimates has yet to be determined.
A logistic regression model was used to predict significant (>/=75% stenosis) and severe (3-vessel or left main) coronary artery disease, and a Cox regression analysis was used to predict cardiac survival. After adjustment for baseline clinical risk, the DTS was effectively diagnostic for significant (P<0.0001) and severe (P<0.0001) coronary artery disease. For low-risk patients (score >/=+5), 60% had no coronary stenosis >/=75% and 16% had single-vessel >/=75% stenosis. By comparison, 74% of high-risk patients (score <-11) had 3-vessel or left main coronary disease. Five-year mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (P<0.0001).
The composite DTS provides accurate diagnostic and prognostic information for the evaluation of symptomatic patients evaluated for clinically suspected ischemic heart disease.
... DTS is most useful to guide downstream testing if it falls within the low-or high-risk category. However, as much as half of all patients undergoing exercise testing fall in the intermediate risk category (− 10 to 4) for DTS [55,58]. In such patients, MPI is very useful for further risk stratification [59,60]. ...
Purpose of Review
Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) has played a central role in the non-invasive evaluation of patients with obstructive coronary artery disease (CAD) for decades. In this review, we discuss the key differences and advantages of positron emission tomography (PET) MPI over SPECT MPI as it relates to the diagnosis, prognosis, as well as clinical decision-making in patients with suspected CAD.
Recent Findings
Stress-induced perfusion abnormalities on SPECT help estimate presence, extent, and location of ischemia and flow-limiting obstructive CAD, help with risk stratification, and serve as a gatekeeper to identify patients who will benefit from downstream revascularization versus medical management. Some of the major limitations of SPECT include soft-tissue attenuation artifacts, underestimation of ischemia due to reliance on relative perfusion assessment, and longer protocols with higher radiation dose when performed with traditional equipment. PET MPI addresses most of these limitations and offers better quality images, higher diagnostic accuracy along with shorter protocols and lower radiation dose to the patient. A special advantage of PET scanning lies in the ability to quantify absolute myocardial blood flow and assess true extent of epicardial involvement along with identifying non-obstructive phenotypes of CAD such as diffuse atherosclerosis and microvascular dysfunction. In addition, stress acquisition at/near peak stress with PET allows us to measure left ventricular ejection fraction reserve and myocardial blood flow reserve, which help with identifying patients at a higher risk of future cardiac events and optimally select candidates for revascularization.
Summary
The several technical advantages of PET MPI position as a superior method to diagnose obstructive and non-obstructive phenotypes of ischemic heart disease affecting the entirety of the coronary circulation offer incremental value for risk stratification and guide post-test management strategy for patients with suspected CAD.
... with high-risk DTS had multi-vessel disease patterns in a series of 834 patients undergoing MPI-SPECT. 18 The interesting aspect of doing SPECT in some high-risk DTS patients is to define, before anatomy is known, who indeed would benefit from revascularization based on ischemic burden, and of course identify patients where coronary angiography can be avoided. Nowadays, the coronary anatomy in some of these patients could be evaluated non-invasively using coronary-computed tomography. ...
Annual mortality rate can range from <1% for patients with normal myocardial perfusion by SPECT to >5% based on a high-risk Duke treadmill score (DTS). Information on the prognosis of patients with the combination of HRDTS and normal SPECT is limited and is the purpose of this study.
Data from a large nuclear cardiology registry (n = 17,972 patients) were reviewed. A total of 340 had HRDTS (score ≤ -11) while undergoing SPECT. Combined cardiovascular mortality and non-fatal myocardial infarction (MI) and cardiovascular mortality alone were available in 310 patients at a mean follow-up of 4.01 ± 1.5 years.
The majority of the patients had abnormal SPECT (n = 270, 71%). The abnormal SPECT patients compared to the normal were older (65.6 vs 62.8 years of age; P = .025), more likely to have abnormal left ventricular ejection fraction (26.1% vs 0%; P < .0001), known coronary artery disease (CAD, 35.9% vs 7.8%; P < .0001) and lower DTS (-14.5 vs -13.2; P = .0006), Kaplan-Meier survival analysis demonstrated a significantly lower cardiovascular mortality (5.4% vs 0%, P = .02) and combined outcome of MI and cardiovascular mortality (15% vs 4.4%, P = .009) in patients with normal versus abnormal SPECT.
High-risk DTS is associated with abnormal perfusion SPECT in most patients, but nearly one-third of the patients had normal perfusion. Patients with a normal SPECT had a lower cardiovascular event rates.
... MPI adds incremental prognostic value to the score. In addition, Iskandrian and coauthors 26 showed that concordance between the Duke treadmill score and the information derived from coronary angiography and thallium scintigraphy was seen in only 33% of patients. In our series, the Duke treadmill score was generally high, including those patients with cardiac events, and did not improve the predictive value of EECG. ...
Although high exercise tolerance is associated with an excellent prognosis, the significance of abnormal myocardial perfusion imaging (MPI) in patients with high exercise tolerance has not been established. This study retrospectively compares the utility of MPI and exercise ECG (EECG) in these patients.
Of 388 consecutive patients who underwent exercise MPI and reached at least Bruce stage IV, 157 (40.5%) had abnormal results and 231 (59.5%) had normal results. Follow-up was performed at 18+/-2.7 months. Adverse events, including revascularization, myocardial infarction, and cardiac death, occurred in 40 patients. Nineteen patients had revascularization related to the MPI results or the patient's condition at the time of MPI and were not included in further analysis. Seventeen patients (12.2%) with abnormal MPI and 4 (1.7%) with normal MPI had adverse cardiac events (P<0.001). Cox proportional-hazards regression analysis showed that MPI was an excellent predictor of cardiac events (global chi2=13.2; P<0.001; relative risk=8; 95% CI=3 to 23) but EECG had no predictive power (global chi2=0.05; P=0.8; relative risk=1; 95% CI=0.4 to 3.0). The addition of Duke's treadmill score risk categories did not improve the predictive power of EECG (global chi2=0.17). The predictive power of the combination of EECG (including Duke score categories) and MPI was no better than that of MPI alone (global chi2=13.5).
Unlike EECG, MPI is an excellent prognostic indicator for adverse cardiac events in patients with known or suspected CAD and high exercise tolerance.
... This has been validated in both in-patients and out-patients. 19,20 Coronary angiography Coronary angiography was requested according to standard clinical criteria by the clinicians in charge of each case, and was not part of the protocol of this study. The standard Sones or Judkins techniques were used. ...
We have previously derived a chest pain score by comparing those with and without coronary artery disease on angiography, which was subsequently validated in patients attending coronary angiography.
To test the predictive validity of the score prospectively in a more varied out-patient population, and to determine whether it had predictive validity in addition to exercise testing.
Prospective clinical study.
The score was applied to 405 out-patients with chest pain who subsequently underwent coronary angiography. Framingham risk analysis and exercise testing were performed in 155.
The score had a sensitivity of 91.4% and specificity of 28% for coronary artery disease, which was found in 31.8%, 51%, 63%, and 82% of those with scores of 0, 1, 2, and 3, respectively. Gender (p < 0.001), age (p < 0.001), and chest pain score (p = 0.009) independently predicted coronary artery disease on multivariate Poisson regression analysis. The chest pain score had additive predictive value with Framingham risk analysis and Duke's score.
This simple chest pain score can predict coronary anatomy with similar sensitivity to exercise testing, and can be used in conjunction with exercise testing and other measures. Further validation of the chest pain score in the primary care setting will be useful.
Objective
To compare the sensitivity, the specificity, the positive and negative predictive value and the predictive accuracy of the Duke Treadmill Score, the Spanish Society of Cardiology (SEC) and American College of Cardiology/American Heart Association (ACC/AHA) highrisk criteria for exercise testing in the detection of left main disease, three vessel disease and two vessel disease involving the proximal left anterior descending artery.
Patients and method
A cohort of 199 patients (age ≤ 75 years) consecutively admitted to hospital for unstable angina was studied. All patients underwent an exercise stress test and coronariography.
Results
The SEC high-risk Criteria showed a sensitivity of 69.2% and a specificity of 49.0%. The ACC/AHA high-risk Criteria demonstrated a sensitivity of 98.1% and a specificity of 23.8% and the Duke Treadmill Score presented a sensitivity of 30.8% and a specificity of 90.5%. In patients with moderate risk in the Duke Treadmill Score we found a sensitivity of 62.9% and a specificity of 39.8% for the SEC high-risk criteria, while the ACC/AHA highrisk Criteria presented a sensitivity of 100.0% and a specificity of 5.8%.
Conclusions
: The ACC/AHA high-risk Criteria showed a higher sensitivity while the Duke Treadmill Score presented a higher specificity for the detection of left main disease, three vessel disease and two vessel disease involving the proximal left anterior descending artery. The ACC/AHA and SEC high-risk Criteria were found to be very useful in the group of patients with moderate risk in the Duke Treadmill Score.
The prognostic utility of an exercise ECG test depends upon having an adequate workload to stress the cardiac system. A negative stress test, in which there are no adverse clinical or ECG findings, and in which an adequate workload is achieved, stratifies patients into a low-risk group. The 1997 American Heart Association guidelines imply that any index of workload—heart rate, rate-pressure product, or exercise duration in multiples of resting O2 consumption (METS)—could be used to indicate that adequate stress was achieved. However, while there is considerable evidence supporting the use of METS as a strong independent prognostic variable, there is less support for the use of rate-pressure product or heart rate. Indeed, there is evidence that a high heart rate at a low workload carries an adverse prognosis. Further research is needed to identify the number of METS achieved that would define an adequate workload. In the meantime, a review of the literature suggests that 7 to 10 METS is a reasonable ballpark figure of the minimum workload in patients with a negative stress test that would imply a favorable outcome.
Abbreviations: ETT = exercise treadmill test; METS = multiples of resting O2 consumption
Background and Objectives:The recent data has revealed that the first 1 minute and 2 minutes of heart rate re- covery of patients who are being evaluated for chest pain and asymptomatic adults are associated with the overall mortality. However, the clinical significance of the heart rate recovery after exercise testing during the first 2 min- utes for predicting the presence or severity of coronary artery disease and the correlation with the Duke treadmill score (DTS) have not been fully evaluated. Subjects and Methods:The study population included 39 patients with significant coronary artery stenosis and 39 subjects with normal coronary arteries. All of them underwent a tread- mill exercise testing prior to coronary angiography. The differences in the heart rate recovery and the DTS between the two groups were investigated. The heart rate recovery and DTS between the multivessel disease group and single vessel disease group were also investigated. Results:The heart rate recovery during the second minute (calculated by the heart rate at 1 minute-the heart rate at 2 minute) after exercise and the DTS were significantly lower in the coronary artery disease group. These parameters were also significantly lower in the multivessel disease group than those in the single vessel disease group. The heart rate recovery during the second minute and the DTS had po- sitive linear correlation (R=0.281, p
As a general rule, clinicians should attempt to isolate those patient subsets whose posttest patient management may be optimally changed by the test referral. Use of testing in a heterogeneous population will lead to an increase in the false-positive rate with a resultant increase in the rate of normal catheterization and higher costs of care.14,16 By providing imprecise test results to the clinician, a higher rate of cardiac events may be observed as a result of lack of care for these patients. In addition, a high rate of normal coronary angiograms in patients with positive test results or admissions for subsequent myocardial infarctions in patients with normal test results may result in a lack of confidence in the imaging results leading to a change in referral to newer, untested modalities.
Thus to integrate our knowledge of the benefits to exercise electrocardiography within the context of clinical decision making and the appropriate selection of a noninvasive test, it is clear that physicians may use aggregate indexes such as the Duke treadmill score to guide patient care, but they should not be relied on to provide definitive evidence. Nor can one make the statement that because of the risk stratification ability of the Duke treadmill score this modality may be used to supplant stress myocardial perfusion imaging. In fact, exercise electrocardiography should be the test of choice for lower risk patient populations.17 However, in more intermediate-risk populations (e.g., known coronary disease or abnormal resting electrocardiogram), stress perfusion imaging is of established diagnostic and prognostic value. Further, from the exercise treadmill test, patients with an intermediate Duke treadmill score would benefit from additional noninvasive testing with stress myocardial perfusion imaging. This strategy provides substantial prognostic information on which to guide subsequent patient care.
Depressed heart rate variability (HRV) is associated with increased mortality and morbidity with various forms of heart disease, and the Duke treadmill score (DTS) provides diagnostic and prognostic information for the evaluation of patients with coronary artery disease (CAD). Our study was aimed at assessing any possible correlation between HRV and DTS in stable CAD. We evaluated the correlation between the HRV assessed by using 24 hour ambulatory ECG monitoring, and treadmill exercise score in 37 patients with angiographically proven and clinically stable CAD. In univariate analysis, DTS showed a significant negative correlation with age (r=–0.89, p50 ms (PNN50) (r=0.69, P
OBJECTIVE: To develop a hierarchical approach to cardiac risk stratification after treadmill testing.
PATIENTS: Clinical and treadmill test data were used to identify a patient population that may be candidates for further risk stratification with stress tomographic myocardial perfusion imaging. A prospective series of 3,620 medically treated patients (42% female, mean age 63 years) with a 2.5% mortality was identified (follow-up 2.5±SD 1.5 years).
MEASUREMENTS AND MAIN RESULTS: A Cox proportional hazards model was used to estimate a patient’s likelihood of cardiac death. Kaplan-Meier survival curves were used to estimate time to cardiac death by nuclear test results. Annual rates of cardiac death were 0.4% (n=921), 1% (n=2,498), and 1% (n=201) for patients with low, intermediate, and high Duke treadmill scores (DTS). For patients with an intermediate DTS, multivariate estimators of cardiac death included the number of ischemic vascular territories (relative risk per defect 1.4, p=.01), the number of infarcted vascular territories (relative risk per defect 2.4, p=.00001), and the DTS (relative risk per unit 0.97, p=.00001), following adjustment for a patient’s pretest risk of coronary disease. For patients with an intermediate DTS, the presence of no, one or two, and three vascular territories with defects was associated with annual rates of cardiac death of 0.5%, 1.4%, and 2.5%, respectively (p<.0001). Kaplan-Meier survival curves exhibited a statistically worsening survival for patients with defects by 1 year after treadmill exercise.
CONCLUSIONS: For symptomatic patients with an intermediate treadmill test score, the exercise myocardial perfusion scan may be used to stratify their risk of cardiac death over 3 years of follow-up. Patient management may be efficiently guided by further outcome assessment, with an exercise nuclear scan for patients whose treadmill test score is intermediate.
Exercise stress testing is the most commonly used noninvasive method to evaluate for coronary artery disease in men and women. Although emphasis has been placed on the diagnostic value of ST-segment depression, the exercise stress test provides other valuable diagnostic and prognostic data, beyond ST-segment depression. The value of these variables, which include exercise capacity, chronotropic response, heart rate recovery, blood pressure response, and the Duke Treadmill Score, are reviewed in this article. In addition, the gender differences seen with these exercise testing variables are reviewed. In this modern era of exercise stress testing, making use of all the information from a stress test and creating a comprehensive stress testing report are recommended in the evaluation of patients with suspected coronary artery disease who undergo exercise stress testing.
Objectives:
This study assessed the incremental value of technetium-99m myocardial single-photon emission computed tomography (SPECT) and simultaneous first-pass radionuclide angiography, when added to treadmill exercise, for prediction of the extent of coronary artery disease.
Background:
Technetium-99m count statistics permit the simultaneous assessment of myocardial perfusion and function. However, whether this characteristic improves prediction of the extent of coronary artery disease remains unknown.
Methods:
We studied 70 consecutive patients who had coronary angiography within 6 months of the scintigraphic study. All patients underwent a symptom-limited treadmill exercise test. Treadmill data were summarized using a previously validated score. Left ventricular ejection fraction and regional wall motion were evaluated from a first-pass radionuclide angiogram acquired at peak treadmill exercise in the anterior view. Perfusion was assessed visually. Extent of angiographic disease was expressed as the presence or absence of multivessel disease (more than two coronary artery territories with > 50% stenosis) and as a score that reflects the location of severe (> 75%) stenosis.
Results:
Stepwise addition of scintigraphic data (perfusion first, followed by function) to the treadmill score showed significant incremental value for prediction of the angiographic score at each step; exercise ejection fraction alone was the strongest independent predictor. Discriminant accuracy for detection of multivessel disease was also improved by the addition of perfusion information to the treadmill score and addition of regional wall motion analysis to both of them. In this case, ejection fraction failed to show independent value.
Conclusions:
The addition of simultaneously performed sestamibi perfusion SPECT and first-pass radionuclide angiography to the treadmill exercise test significantly improved prediction of the extent of coronary artery disease.
The appropriate management of patients with an intermediate Duke treadmill score (DTS) is not well established.The aim of this study is to compare several treadmill indexes (American College of Cardiology/American Heart Association (ACC/AHA) High-Risk Criteria for exercise testing,Veterans Affairs and West Virginia Prognostic Score, ST/Heart Rate Index, Failure to attain 85% of age-predicted maximum Heart Rate) with ST-segment depression in detecting significant or severe coronary artery disease as determined by coronary angiography in patients with an intermediate DTS.
144 consecutive patients admitted to the hospital for unstable angina were studied.
The sensitivities of the ACC/AHA High-Risk Criteria and West Virginia Prognostic Score were greater than 95% for the detection of significant coronary artery disease and 96.67% for the detection of severe coronary artery disease. The sensitivity of I mm ST depression for the detection of significant and severe coronary disease was 74.74% and 86.67%, respectively. The combined evaluation of ST-segment depression > or =1 mm and exercise-induced angina could efficiently identify a population with a high prevalence of significant coronary artery disease (specificity of 95.92%, positive predictive value of 94.29%).
The ACC/AHA High-Risk Criteria was West Virginia Prognostic Score provided relevant diagnostic information in patients with an intermediate DTS. A coronary angiography is to be recommended in patients with an intermediate DTS who also present ST-segment depression > or =1 mm and exercise-induced angina.
Wide variations in the sensitivity and specificity of the exercise ECG for the diagnosis of coronary artery disease (CAD) have been reported. The aim of this study was to reexamine the sensitivity and specificity of the stress ECG and stress myocardial perfusion imaging (MPI) relative to cardiac catheterization in an era of aggressive screening.
We evaluated 218 patients [mean age: 62+/-13 (SD) years; 69% males] with symptoms of chest pain or dyspnea, normal resting ECGs, and no earlier myocardial infarction. All patients exercised to age-corrected and sex-corrected Bruce protocol times and achieved >or=85% of predicted maximum heart rate. Coronary angiography was performed within 3 months of stress testing. Sixty-six percent of patients had significant CAD by angiography. The overall sensitivity of the exercise ECG (36%) was significantly lower than that of exercise MPI (81%) (P<0.001). In addition, the specificity of the exercise ECG was higher in men than in women (94% men, 74% women; P<0.01), whereas there were no significant differences in sensitivity or specificity (79%) of MPI between men and women. In patients with multivessel CAD or proximal left anterior descending stenosis >or=70%, the sensitivity of the exercise ECG was higher (58%), but still less than MPI (88%) (P<0.01).
MPI is vastly superior to the stress ECG for the diagnosis of CAD, especially in patients with single-vessel CAD. Older literature reporting higher sensitivity for the stress ECG was likely biased by patients with more severe CAD and must be reexamined in the era of earlier diagnosis and intervention.
This study compared the diagnostic accuracy of exercise thallium-201 single-photon emission computed tomography (SPECT) with the exercise electrocardiographic (ECG) response in patients with normal baseline ECG results.
Previous studies comparing exercise thallium imaging with exercise electrocardiography have included patients with abnormal rest ECG results that may have biased the results in favor of thallium imaging.
Of 321 patients with a pretest likelihood of coronary artery disease of 70 +/- 29% (mean +/- SD) who underwent exercise stress testing and coronary angiography, 68 had no coronary artery disease; 94 had one-vessel disease; 79 had two-vessel disease; and 80 had three-vessel or left main coronary artery disease.
The diagnostic accuracy of SPECT was higher than that of the ECG response (79% vs. 49%, p < 0.0001). Patients with extensive (left main or three-vessel) coronary artery disease were older and had a lower work load, lower heart rate, greater ST segment depression and more extensive perfusion abnormalities than patients with no disease or one- or two-vessel disease. Multivariate discriminant analysis of exercise and thallium variables identified multivessel thallium abnormalities (F = 35), exercise heart rate (F = 18) and extent of ST segment depression (F = 6) as independent predictors of extensive disease. Of the 80 patients with left main or three-vessel disease, 37 (46%) had > or = 2-mm ST segment depression, 44 (55%) had multivessel SPECT abnormalities, and 61 (76%) had either > or = 2-mm ST depression or multivessel SPECT abnormalities (p = 0.0005 vs. the ECG response; p = 0.01 vs. SPECT).
In patients with an intermediate to high pretest probability of coronary artery disease and normal baseline ECG results, SPECT is superior to the ECG response in detecting coronary disease. Further, SPECT provides incremental power in identifying patients with extensive (left main or three-vessel) coronary disease.
For more than two decades, conventional radionuclide techniques have been employed for the noninvasive evaluation of cardiac function. Standardized techniques have been developed and are widely available. Extensive clinical experience has confirmed the reliability of these techniques and has established important roles in providing diagnostic and prognostic information. Conventional radionuclide cardiac imaging currently emphasizes the demonstration of abnormalities in myocardial perfusion and ventricular function. Myocardial and radionuclide studies are infrequently employed but can offer helpful information in specific clinical situations.
The diagnostic value and incremental contribution of different noninvasive tests to the identification of coronary artery disease in 128 patients from a general population with intermediate pretest likelihood (48.0%) were determined by ordered logistic regression analysis and receiver-operating characteristic (ROC) curves.
Patients referred for suspicion of coronary heart disease were submitted to bicycle exercise testing under clinical and electrocardiographic control. AT peak exercise, first-pass radionuclide angiography was performed after injection of 99mTc-labeled sestamibi, followed by single-photon emission computed tomographic (SPECT) acquisition. A comparative rest study was obtained within 1 week, and qualitative and quantitative analysis was applied to assess the presence and extent of disease. With coronary angiography and 50% stenosis used as a standard, the discriminative accuracy of each test was calculated. The accuracies to diagnose coronary heart disease were 71.3% +/- 4.7% for the bicycle test, 66.7% +/- 5.3% for radionuclide angiography, and 81.6% +/- 3.9% for the SPECT data. By ROC curves, the optimal criteria for positivity were determined for the visual and quantitative analysis for both presence and extent of coronary artery disease. Results of visual and quantitative SPECT were compared in terms of area under the ROC curves. The diagnostic performances showed no significant difference, ranging from 74.3% to 81.6%. The first-pass radionuclide angiographic and SPECT data were added progressively to the stress testing to evaluate their incremental diagnostic contribution. Only the addition of SPECT results significantly increased the accuracy to 85.6% +/- 3.3% (p < 0.0001).
Exercise electrocardiography and first-pass radionuclide angiography showed comparable accuracy to detect coronary artery disease. However, the combination of exercise testing and visual SPECT analytic data sufficed to ensure diagnostic accuracy, without significant benefit from the addition of other tests or the application of quantification.
Previous studies have examined the predictors of outcome in medically treated patients with coronary artery disease (CAD). There is limited information on predictors of outcome after coronary artery bypass grafting (CABG). This study examined the predictors of outcome of 255 patients with CAD, at a mean time of 5 years after CABG for angina pectoris. The 255 patients underwent coronary angiography and stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging after CABG. During a mean follow-up of 41 +/- 28 months after stress testing, there were 34 hard events (24 cardiac deaths and 10 nonfatal myocardial infarctions). The hemodynamics during stress testing, and age and gender were not predictors of events. The SPECT variables of multivessel perfusion abnormality, perfusion deficit size, and increased lung thallium uptake were predictors of death and total events by uni- and multivariate survival analysis. There were 14 events in 45 patients (31%) with multivessel abnormality and increased lung thallium uptake, 14 events in 101 patients (14%) with either multivessel abnormality or increased lung uptake, and 6 events in 109 patients (6%) with neither of these 2 variables (p = 0.0001). The annual mortality and total event rates were 7.5% and 9.5% with both variables, 3.4% and 4.3% with either variable, and 0.6% and 1.7% with neither of the variables (p = 0.01). Thus, stress SPECT perfusion imaging is useful to stratify patients after CABG into low, intermediate, and high risk groups for future cardiac events.
Stress perfusion imaging is useful in risk stratification of patients with known or suspected coronary artery disease. In the current era of managed health care, there is a need to provide data on patient outcome.
This study examined the impact of exercise single-photon emission computed tomographic (SPECT) thallium imaging on patient management (the subsequent need for coronary angiography and revascularization) and outcome (the occurrence of hard cardiac events defined as cardiac death or nonfatal acute myocardial infarction) in 2700 patients who were being evaluated for diagnostic purposes. None of the patients had previous coronary angiography, coronary revascularization, or Q-wave myocardial infarction. The SPECT images were normal in 2027 patients (group 1) and abnormal in 673 patients (group 2). Within 6 months after thallium imaging 53 patients in group 1 (3%) and 242 patients in group 2 (36%) underwent coronary angiography (p = 0.0001). The patients who underwent coronary angiography had higher pretest probability of coronary disease (group 1) or more perfusion defects (group 2) than patients who did not (p = 0.0001 each). Coronary revascularization within 3 months of coronary angiography was performed in 1 of the 53 patients (2%) in group 1 and in 87 of 242 patients (30%) in group 2 (p = 0.0001). Among the remaining patients who had coronary angiography but were medically treated there were no hard cardiac events in group 1 but there were 15 events in group 2 (p = 0.02).
The results of exercise SPECT thallium imaging are important in patient management and outcome. Coronary angiography, coronary revascularization and events are rare in patients with normal exercise SPECT thallium images.
This study compared the prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging with that of treadmill exercise score in medically treated patients with coronary artery disease (CAD).
The treadmill exercise score was derived from exercise duration, degree of ST segment depression, and the treadmill anginal index. There were 121 patients with no CAD and 316 patients with angiographically defined CAD (> or = 50% diameter stenosis of one or more vessels). During a mean follow-up of 29 months, there were 35 cardiac deaths or nonfatal myocardial infarctions. Multivariate Cox survival analysis showed the extent of thallium imaging abnormality and CAD to be independent predictors of prognosis. On the other hand, the treadmill exercise score was not a significant predictor even on univariate analysis. The results of thallium uptake were the strongest independent predictors of prognosis and in addition provided incremental prognostic power to coronary angiography (chi 2 = 29 for SPECT, 27 for coronary angiography, and 37 for both).
Thus exercise SPECT thallium imaging is significantly better than the treadmill exercise score in risk assessment. The size of the perfusion abnormality is an important predicator of prognosis.
This study showed that quantitative analysis of SPECT perfusion images provide comparable prognostic information to summed stress score in medically treated patients with coronary artery disease.
This study compared qualitative assessment of exercise thallium imaging to quantitative assessment in predicting outcome in 713 patients with 78% prevalence of coronary artery disease by coronary angiography; during a mean follow-up of 52 months, there were 106 hard cardiac events (death or nonfatal myocardial infarction). The qualitative method provided important prognostic information; however, unlike the quantitative technique, less patients were assigned to either the low- or high-risk group and proportionally more patients into the intermediate-risk group, which may limit the clinical usefulness of the technique.
Several studies show that patients, especially those with low to intermediate pretest probability of coronary artery disease (CAD) and normal stress single-photon emission computed tomography (SPECT) perfusion imaging, have an annual event rate of death or nonfatal myocardial infarction of <1%/year.(1-3) It is unlikely that coronary interventions can improve survival in this cohort of patients. In 1 study the utilization rate of coronary angiography and coronary revascularization was directly related to the use of stress imaging (more imaging studies resulted in more coronary angiography and coronary revascularization).(4) In other studies, however, the rate of coronary angiography was deemed appropriate based on SPECT results: very low rate in patients with normal or near-normal images, intermediate rate in patients with intermediate abnormality, and high rate in patients with severe abnormality.(5,6) This study examined the downstream utilization rate in 2 cohorts of patients with intermediate pretest probability of CAD. In 1 group, coronary angiography was used as an initial screening test and in the second group stress SPECT perfusion imaging was the initial screening test and coronary angiography was subsequently performed if deemed necessary. Medicare reimbursements were used to calculate the cost savings.
The appropriate management of patients with intermediate-risk Duke treadmill scores is not established. The purpose of this study was to determine the long-term risk of subsequent cardiovascular events in patients with an intermediate-risk treadmill score who do not have myocardial perfusion defects on radionuclide imaging.
The existing databases of the nuclear cardiology laboratories of 4 academic institutions were searched retrospectively. A total of 4649 patients were identified who had intermediate-risk Duke treadmill scores (-10 to 4), normal or near-normal exercise single photon-emission computed tomographic myocardial perfusion images using either thallium-201 or technetium-99m sestamibi, and no previous coronary revascularization. Follow-up was 95% complete. Cardiovascular survival was 99.8% at 1 year, 99.0% at 5 years, and 98.5% at 7 years. Cardiac survival free of myocardial infarction was similarly high at 96.6% at 7 years. Cardiac survival free of myocardial infarction or revascularization was 87.1% at 7 years. Near-normal scans and cardiac enlargement were independent predictors of time to cardiac death. Seven-year cardiac survival was still high at 97.0% in the 357 patients with near-normal scans and normal cardiac size and somewhat lower, at 89.0%, in the 167 patients with cardiac enlargement.
Patients with an intermediate-risk treadmill score but with normal or near-normal exercise myocardial perfusion images and normal cardiac sizes are at low risk for subsequent cardiac death and can be safely managed medically until their symptoms warrant revascularization. The appropriate management of patients with cardiac enlargement will remain a matter of clinical judgment.
Evaluation and treatment of stable angina pectoris is based on invasive diagnostic and therapeutic procedures focused on identification and treatment of coronary artery stenoses, instead of myocardial ischaemia which is considered the cause of symptoms. Thus, coronary angiography should possibly be preceded routinely by myocardial perfusion imaging, which can provide the diagnosis of ischaemia and determine if the patient will benefit from invasive therapy. As a consequence, treatment of patients without ischaemia and patients with ischaemia so serious that invasive therapy is futile might be avoided. It is unknown exactly how many angiographies and treatments with angioplasty or bypass surgery that could be spared in this way. It is estimated that a patient pathway based on the diagnosis of myocardial ischaemia including the type of ischaemia may render approximately half of the present angiographies and a number of invasive revascularisations redundant. This pathway implies substantial economic savings.
Multivariable analysis of clinical and exercise test data has the potential to become a useful tool for assisting in the diagnosis of coronary artery disease, assessing prognosis, and reducing the cost of evaluating patients with suspected coronary disease. Since general practitioners are functioning as gatekeepers and decide which patients must be referred to the cardiologist, they need to use the basic tools they have available (i.e. history, physical examination and the exercise test), in an optimal fashion. Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power compared with simple classification of the ST response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a management strategy. While computers, as part of information management systems, can run complicated equations and derive these scores, physicians are reluctant to trust them. Thus, these scores have been represented as nomograms or simple additive tables so physicians are comfortable with their application. Their results have also been compared with physician judgment and found to estimate the presence of coronary disease and prognosis as well as expert cardiologists and often better than nonspecialists.
To compare the sensitivity, the specificity, the positive and negative predictive value and the predictive accuracy of the Duke Treadmill Score, the Spanish Society of Cardiology (SEC) and American College of Cardiology/American Heart Association (ACC/AHA) high-risk criteria for exercise testing in the detection of left main disease, three vessel disease and two vessel disease involving the proximal left anterior descending artery.
A cohort of 199 patients (age 75 years) consecutively admitted to hospital for unstable angina was studied. All patients underwent an exercise stress test and coronariography.
The SEC high-risk Criteria showed a sensitivity of 69.2% and a specificity of 49.0%. The ACC/AHA high-risk Criteria demonstrated a sensitivity of 98.1% and a specificity of 23.8% and the Duke Treadmill Score presented a sensitivity of 30.8% and a specificity of 90.5%. In patients with moderate risk in the Duke Treadmill Score we found a sensitivity of 62.9% and a specificity of 39.8% for the SEC high-risk criteria, while the ACC/AHA high-risk Criteria presented a sensitivity of 100.0% and a specificity of 5.8%.
The ACC/AHA high-risk Criteria showed a higher sensitivity while the Duke Treadmill Score presented a higher specificity for the detection of left main disease, three vessel disease and two vessel disease involving the proximal left anterior descending artery. The ACC/AHA and SEC high-risk Criteria were found to be very useful in the group of patients with moderate risk in the Duke Treadmill Score.
Statistical tools can be used to create scores for assisting in the diagnosis of coronary artery disease and assessing prognosis. General practitioners and internists frequently function as gatekeepers, deciding which patients must be referred to the cardiologist. Therefore, they need to use the basic tools they have available (ie, history, physical examination and the exercise test) in an optimal fashion. Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power compared with diagnosis only using the ST segment response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a more practical management strategy than a response of normal or abnormal. Although computers, as part of information management systems, can calculate complicated equations and derive these scores, physicians are reluctant to trust them. However, when represented as nomograms or simple additive discrete pieces of information, scores are more readily accepted. The scores have been compared with physician judgment and have been found to estimate the presence of coronary disease and prognosis as well as expert cardiologists and often better than nonspecialists. However, the discriminating power of specific variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. Should expired gases be substituted for estimated METs? Should ST/heart rate index be used instead of putting ST depression and heart rate separately into the models? Should right-sided chest leads and heart rate in recovery be considered? There is a need for further evaluation of these easily obtained variables to improve the accuracy of prediction algorithms, especially in women. The portability and reliability of scores must be ensured because access to specialized care must be safeguarded. Assessment of the clinical and exercise test data and application of the newer scores can empower the clinician to assure the cardiac patient access to appropriate and cost-effective cardiologic care.
The application of common statistical techniques to clinical and exercise test data has the potential to become a useful tool for assisting in the diagnosis of coronary artery disease, assessing prognosis, and reducing the cost of evaluating patients with suspected coronary disease. Since general practitioners function as gatekeepers and decide which patients must be referred to the cardiologist, they need to optimally use the basic tools they have available (i.e., history, physical exam, and the exercise test).
Review of the literature with a focus on the scientific techniques for aiding the decision-making process.
Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power when compared using receiver-operating-characteristic curves with the ST segment response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a management strategy. While computers as part of information management systems can calculate complicated equations to provide scores, physicians are reluctant to trust them. Thus, these scores have been represented as nomograms or simple additive tables so physicians are comfortable with their application. Scores have also been compared with physician judgment and been found to estimate the presence of coronary disease and prognosis as well as expert cardiologists, and often better than nonspecialists.
Multivariate scores can empower the clinician to assure the cardiac patient with access to appropriate and cost-effective cardiological care.
In 1214 symptomatic medically treated patients with coronary artery disease, 57 noninvasive baseline clinical characteristics and 24 catheterization descriptors were analyzed by a multivariable analysis technique to determine the characteristics that were independent predictors of survival and, in particular, to determine whether noninvasive characteristics contributed prognostic information in addition to catheterization findings. When the noninvasive characteristics were analyzed, 31 characteristics were significant (p<0.05) univariate predictors of survival, but only 12 contained significant independent prognostic information. Five- and 7-year survival rates in 197 patients who had none of the independently significant noninvasive characteristics were both 90%. Nineteen variables were significant when the catheterization descriptors were analyzed individually. Only seven were independently significant when they were analyzed jointly. When all 81 baseline characteristics were analyzed jointly, seven noninvasive characteristics (history of peripheral vascular disease, New York Heart Association class IV heart failure, nonspecific intraventricular conduction defect, progressive chest pain, nocturnal pain, premature ventricular complexes on the resting ECG, and left bundle branch block) and six invasive characteristics (left-main stenosis, arteriovenous oxygen difference, number of diseased vessels, abnormal left ventricular contraction, left ventricular end-diastolic pressure and anterior asynergy) were independently significant. Different survival rates may occur in subsets that are uniform with respect to only one or two important characteristics (e.g., coronary anatomy and ventricular function) because of differences in other important baseline characteristics. Both noninvasive and invasive characteristics must be taken into account to define prognosis in coronary disease fully.
Hypotension during exercise testing has been considered a marker of extensive coronary artery disease (CAD) and poor prognosis. The mechanism of hypotension was examined in 25 CAD patients who developed hypotension during treadmill exercise testing (mean decrease in systolic blood pressure [BP] 33 +/- 13 mm Hg) (group 1) and was compared with the results of 25 CAD patients who had a normal systolic BP response to exercise (mean increase 53 +/- 15 mm Hg) (group 2). The 2 groups were comparable in age, sex, extent of CAD, previous myocardial infarction, left ventricular ejection fraction, history of hypertension and cardiac medications. Exercise heart rate (121 +/- 23 vs 133 +/- 25 beats/min; p = not significant [NS]) and duration (6 +/- 2 vs 7 +/- 3 minutes; p = NS) were comparable. ST-segment depression occurred in 44% of patients in group 1 and in 52% in group 2 (p = NS), and angina during exercise occurred in 60% of both groups. Single-photon emission computed tomographic thallium images were abnormal in 24 patients (96%) in group 1 and in 20 patients (80%) in group 2 (p = NS). Percent thallium abnormality was 19 +/- 12% in group 1, and 18 +/- 14% in group 2 (p = NS), and the severity of thallium abnormality was 710 +/- 510 in group 1, and 510 +/- 500 in group 2 (p = NS). Ischemia involving the inferior/posterior segments was seen in 68% of patients in group 1 and in 60% in group 2 (p = NS). Increased lung thallium uptake was seen in 48% of both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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 treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients.
We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk).
Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent).
The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment.
To assess the extent of jeopardized myocardium in patients with single vessel coronary artery disease of variable severity and location, quantitative exercise thallium-201 single photon emission computed tomography was performed in 158 consecutive patients with angiographically proved single vessel coronary artery disease. The extent of abnormal left ventricular perfusion was quantified from computer-generated polar maps of three-dimensional myocardial radioactivity. Patients with only a moderate (51% to 69%) stenosis tended to have a small perfusion defect irrespective of the coronary artery involved. Whereas a perfusion defect measuring greater than or equal to 10% of the left ventricle was found in 78% of patients with no prior infarction and severe (greater than or equal to 70%) stenosis, this was observed in only 24% of patients with moderate stenosis. Perfusion defect size increased with increasing severity of stenosis for the entire group without infarction and for those with left anterior descending, right and circumflex coronary artery stenosis. However, the correlation between stenosis severity and perfusion defect size was at best only modest (r = 0.38, p = 0.0001). The left anterior descending artery was shown to be the most important of the three coronary arteries for providing left ventricular perfusion. Proximal stenosis of this artery produced a perfusion defect approximately twice as large as that found in patients with a proximal right or circumflex artery stenosis. However, marked heterogeneity in perfusion defect size existed among all three vessels despite comparable stenosis severity. This was most apparent for the left anterior descending coronary artery, where mid vessel stenosis commonly produced a perfusion defect similar in size to that found in proximally stenosed vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available.
To evaluate the variability in the reported diagnostic accuracy of the exercise electrocardiogram, we applied meta-analysis to 147 consecutively published reports comparing exercise-induced ST depression with coronary angiography. These reports involved 24,074 patients who underwent both tests. Population characteristics and technical and methodologic factors, including publication year, number of electrocardiographic leads, exercise protocol, use of hyperventilation, definition of an abnormal ST response, exclusion of certain subgroups, and blinding of test interpretation were analyzed. Wide variability in sensitivity and specificity was found (mean sensitivity, 68%; range, 23-100%; SD, 16%; and mean specificity, 77%; range, 17-100%; SD, 17%). The four study characteristics found to be significantly and independently related to sensitivity were the treatment of equivocal test results, comparison with a "better" test such as thallium scintigraphy, exclusion of patients on digitalis, and publication year. The four variables found to be significantly and independently related to specificity were the treatment of upsloping ST depressions, the exclusion of subjects with prior infarction or left bundle branch block, and the use of preexercise hyperventilation. Stepwise linear regression explained less than 35% of the variance in sensitivities and specificities reported in the 147 publications. There is wide variability in the reported accuracy of the exercise electrocardiogram. This variability is not explained by information reported in the medical literature.
This study examined the effect of the level of exercise on the ability of thallium-201 imaging with single photon emission computed tomography (SPECT) to detect coronary artery disease. Patients in group 1 (n = 164) achieved adequate exercise end points, defined as positive exercise electrocardiograms or greater than or equal to 85% of maximal predicted heart rate. Patients in group 2 (n = 108) had submaximal exercise. The SPECT thallium-201 images showed perfusion defects in 74%, 88%, and 98%, respectively, of patients with one, two and three vessel coronary artery disease in group 1, compared with 52%, 84% and 79%, respectively, of such patients in group 2 (p less than 0.05). Perfusion defects showed partial or complete redistribution consistent with ischemia in 56%, 80% and 88%, respectively, of patients with one, two and three vessel coronary artery disease in group 1 compared with 35%, 58% and 56%, respectively, of such patients in group 2 (p = 0.08, less than 0.03 and less than 0.001, respectively). Of 58 patients with normal coronary angiograms or less than 50% diameter stenosis, 36 (62%) had normal SPECT images. In a separate group of 131 patients with less than 5% pretest probability of coronary artery disease, the specificity was 93%. The sensitivity of exercise SPECT imaging in group 1 was higher than that of ST segment depression (p less than 0.001). Thus, the level of exercise affects the results of SPECT thallium imaging in the localization and evaluation of the extent of coronary artery disease and the detection of ischemia.
Exercise electrocardiography has relatively poor specificity and predictive accuracy for 3-vessel coronary artery disease (CAD) when conventional diagnostic criteria are used. However, electrocardiographic evaluation using linear regression analysis of the heart-rate (HR)-related change in ST-segment depression (ST/HR slope) is reported to accurately distinguish patients with from those without CAD, and to accurately separate patients with 1-, 2- and 3-vessel CAD. To assess the applicability of this method and to compare it with conventional interpretation, retrospective evaluation of 50 patients in whom exercise electrocardiography and coronary cineangiography had been performed for suspected CAD was conducted using a modified ST/HR slope analysis limited to leads V5, V6 and aVF. Eighteen patients had 3-vessel, 22 had 2-vessel, 6 had 1-vessel and 4 had no CAD. Standard electrocardiographic criteria (1 mm or more of horizontal or downsloping ST depression) identified 3-vessel CAD with a sensitivity of 78%, specificity of 56% and positive predictive value of only 50%. Peak ST/HR slope criteria (greater than or equal to 6.0 microV/beat/min) identified 3-vessel CAD with a sensitivity of 78%, specificity of 97% and positive predictive value of 93%. The overall test accuracy using measured peak ST/HR slope was 90%, compared with 64% for standard ST-depression criteria. In conclusion, analysis of the peak ST/HR slope can greatly improve the diagnostic accuracy of exercise electrocardiography, and further prospective study of this method is indicated.
The study objective was to assess the widespread applicability of ST/HR slope for the modified Bruce exercise test using a computerized electrocardiogram (ECG); compare the usefulness of the ST/HR slope with standard ECG criteria in detection of coronary artery disease (CAD) and identification of three-vessel or left main CAD; and then develop a new, modified ST/HR score (MSHS) for improving the diagnostic accuracy of ST/HR slope. The studies were retrospective and prospective in design, conducted in referral-based cardiology clinics at a national cardiovascular center. A selected sample of 142 patients underwent exercise ECG and coronary angiography, as did a normal control group of 402 patients who were apparently free from CAD. Sixty three other patients who underwent coronary angiography were also studied prospectively. No limitations of medical treatment were exacted for the test except digitalis treatment. Linear regression analysis, from which ST/HR slope was derived, was done with seven measurements of HR and ST displacement at 60 ms from J point in leads a VF and V5 during 6 min before the end of exercise. MSHS was derived from a multiple regression model with peak HR (% maximum HR), ST index (ST depression + ST slope), and ST/HR slope. Although the usual ST criteria (sensitivity = 63 percent, specificity = 73 percent), ST index (71 percent, 80 percent), and ST/HR slope (70 percent, 97 percent) were equally accurate in detection of CAD, MSHS showed significantly improved sensitivity (88 percent) with similar specificity (81 percent). In identification of three-vessel or left main CAD, when compared with other criteria, ST/HR slope and MSHS provided improved diagnostic accuracy: sensitivity (74 and 78 percent, respectively), specificity (88 and 93 percent) and overall test accuracy (85 and 89 percent). The improved accuracy of ST/HR slope and MSHS was prospectively validated in 63 other patients. ST/HR slope was applicable to computerized ECG data for the standard treadmill test, and showed improved accuracy in detection of three-vessel or left main CAD. The new, modified ST/HR score more accurately predicted not only the presence but also the severity of CAD.
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 present study was planned to investigate whether the sum of ST segment depression in 12-lead electrocardiogram (sigma STD) in relation to change in heart rate (delta HR) during exercise, sigma STD/delta HR index, could be utilized to predict the extent of underlying coronary artery disease. Two hundred and twenty-six consecutive patients were included in this study, 191 men and 35 women, aged 28-74 years (mean 56). Patients were classified into two groups. Group I consisted of 165 patients with either no coronary disease, single or double vessel disease. Group II included 61 patients with triple vessel or left main stem stenosis. It was found that the sigma STD/delta HR index at 25 mm. beat-1 X min. 10(2) provided the best separation between Groups I and II patients. All but 3 of the 61 patients in Group II had a sigma STD/delta HR index greater than 25. In contrast, all but 4 of the 165 patients in Group I had an index less than 25. The sensitivity, specificity and positive predictive value in the identification of Group II patients by using the index were 95%, 98% and 94% respectively. Utilization of ST segment depression of greater than or equal to 2 mm in a VF alone as a test criterion for the recognition of Group II patients had a low sensitivity (41%), specificity (88%) and positive predictive value (56%).(ABSTRACT TRUNCATED AT 250 WORDS)
To compare four recently proposed methods of analyzing the exercise electrocardiogram with the conventional analysis of ST segment depression, 303 consecutive patients without myocardial infarction who had been referred for coronary arteriography underwent stress electrocardiography and stress thallium imaging. The specificity for the prediction of a greater than 50% coronary obstruction of 0.5, 1.0, 1.5 and 2.0 mm ST segment depression measured in the conventional way was 0.59, 0.73, 0.88 and 0.94, respectively. The specificity of a thallium perfusion defect was 0.79. Sensitivities of the conventional ST depressions, thallium defect, the change in the sum of the R amplitudes and the slope adjusted for heart rate increase were calculated and compared at the cited levels of specificity. R wave changes had a significantly lower sensitivity than did the conventionally analyzed ST depression at each level of specificity. Slope-adjusted ST depression had a slightly higher sensitivity than that of conventional ST depression only at a specificity of 0.73 (0.68 versus 0.65, p = 0.07). R wave-adjusted ST depression was significantly more sensitive than conventional ST depression only at a specificity of 0.94 (0.45 versus 0.36, p = 0.01). Heart rate-adjusted ST depression was more sensitive than conventional ST depression at all of the specificities except 0.59. This pattern of superior accuracy of heart rate-adjusted ST depressions was preserved for the prediction of multivessel coronary disease. Heart rate adjustment is a simpler and more accurate modification of the conventional electrocardiographic analysis than are the other three methods studied.
The study examined the value of rest and exercise radionuclide ventriculography in risk stratification in patients with suspected coronary artery disease. There were 604 patients, 474 men and 130 women, aged 55 +/- 11 years (mean +/- standard deviation). At a follow-up of 18 +/- 10 months, there were 43 hard cardiac events: 27 patients died of cardiac causes and 16 had nonfatal acute myocardial infarctions. Univariate and multivariate survival analysis of the 10 most important clinical and exercise variables identified the exercise left ventricular ejection fraction as the most important predictor of death and total cardiac events (chi 2 = 18.1 and 29.6, respectively). The exercise heart rate was a significant, independent, but much weaker predictor of cardiac death and total events (chi 2 = 8.4 and 3.9, respectively), while exercise tolerance was a significant independent predictor of cardiac death only (chi 2 = 6.4). Actuarial life table analysis showed that the risk for future cardiac events increased in stepwise fashion as the exercise ejection fraction decreased. Thus, the exercise left ventricular ejection fraction is a useful prognosticator in patients with suspected coronary artery disease. This finding has important implications in patient management.
We studied 42 symptomatic patients with coronary artery disease involving two or three vessels using exercise thallium-201 myocardial scintigraphy. Qualitative analysis of the images predicted multivessel disease in 75% of the patients with two-vessel disease and in 82% of the patients with three-vessel disease. Quantitative analysis of the size of the perfusion defect indicated that approximately 40% of the left ventricular perimeter showed abnormal perfusion pattern during stress in these patients, and there was no significant difference in the size of the defect in patients with two-vessel disease or three-vessel disease (41 +/- 17% vs 42 +/- 14%, respectively, mean +/- SD). The exercise heart rate, exercise ECG response, and severity of narrowing did not correlate with the size of the perfusion defect. Patients with anterior infarction had larger defects in the distribution of the left anterior descending artery than those without infarction. Collaterals offered partial protection during exercise only when they were not jeopardized. This study confirms the value of qualitative analysis of exercise thallium-201 imaging in predicting multivessel disease, and describes a simple method of assessing the extent of perfusion abnormalities during stress in patients with multivessel disease. The results may be important in patient management and prognosis.
The purpose of this investigation was to determine which variables obtained when performing radionuclide angiography predict subsequent survival or total events (cardiovascular death or nonfatal myocardial infarction) in stable patients with symptomatic coronary artery disease (CAD). Univariable and multivariable analyses of 6 variables, including ejection fraction (EF) at rest and exercise, change in EF with exercise, development of ischemic chest pain or electrocardiographic changes, left ventricular (LV) wall motion abnormalities and exercise time were examined in 386 patients followed up to 4.5 years. Univariate analyses revealed that the exercise EF was the variable most closely associated with future events (p less than 0.01), followed by EF at rest, wall motion abnormalities and exercise time. Multivariable analyses revealed that once the exercise EF was known, no other radionuclide variables contributed independent information about the likelihood of future events. Multivariable analyses also revealed that the exercise EF describes much of the prognostic information of coronary anatomy. Our findings suggest that the radionuclide angiogram is useful in predicting future events in patients with stable CAD, although examination in conjunction with other clinical descriptors will be necessary to further quantify this contribution.
Previous studies show considerable variation in the perfusion and function of the left ventricle at rest and during stress in patients with disease of the isolated left anterior descending coronary artery. In search of mechanisms, we obtained exercise thallium-201 images in 35 such patients. None of the patients had had infarction. The exercise-induced perfusion defect size was measured as the average of the percentage of abnormal perimeter from the three standard projections. The perfusion defect size was smaller in the nine patients with 50-69% stenosis than in the 26 patients with ≥ 70% stenosis (10 ± 9% vs 27 ± 15%, mean ± SD, p < 0.01). Among the 26 patients with ≥ 70% stenosis, the perfusion defect was ≤ 30% in 14 and > 30% in 12. All 14 patients with perfusion defects ≤ 30% were older than 50 years; eight of the 12 with perfusion defects > 30% were 50 years of younger (p = 0.0003). The severity and site of stenosis, collaterals, exercise heart rate and double product, propranolol therapy and results of exercise ECG were similar in patients with perfusion defects ≤ 30% and in patients with perfusion defects > 30%. Using a stepwise regression analysis of 30 clinical, anatomic and exercise variables, only age showed a significant correlation with perfusion defect size (r = -0.58, p < 0.005). In patients with effective collaterals, the perfusion defect was smaller in patients older than 50 years than in patients age 50 years or younger (14 ± 7% vs 41 ± 8%, p < 0.001). We conclude that the perfusion defect is small in patients with < 70% stenosis of the left anterior descending coronary artery, but varies considerably in patients with ≥ 70% stenosis. Age is the chief determinant of perfusion defect size in patients with similar left anterior descending coronary artery anatomy and exercise variables. Age and, conceivably, the duration of disease may affect the functional maturity of collaterals. The data indicate that left anterior descending coronary artery lesions may well put into risk more than 30% of the heart muscle in a great number of patients. This phenomenon is significantly more common in patients younger than age 50 years.
To determine the relation between left ventricular performance during exercise and the extent of coronary artery disease, the results of exercise radionuclide ventriculography were analyzed in 65 patients who also underwent cardiac catheterization. A scoring system was used to quantitate the extent of coronary artery disease. This system takes into account the number and site of stenoses of the major coronary vessels and their secondary branches. The conventional method of interpreting the coronary angiograms indicated that 26 patients had significant coronary artery disease (defined as 70% or more narrowing of luminal diameter) of one vessel, 21 had multivessel disease and 18 had no significant coronary artery disease. Although the exercise left ventricular ejection fraction was significantly higher in patients with no coronary artery disease than in patients with one or multivessel disease (probability [p] less than 0.001), there was considerable overlap among the three groups. With the scoring system, a good correlation was found between the coronary artery disease score and the exercise left ventricular ejection fraction (r = -0.70; p less than 0.001). If the exercise heart rate was 130 beats/min or greater or the age of the patient was 50 years or less, an even better correlation was found (r = -0.73 and r = -0.82, respectively). The exercise ejection fraction (but not the change in ejection fraction, end-diastolic volume and end-systolic volume from rest to exercise) correlated with the extent of coronary artery disease. The exercise ejection fraction is the most important exercise variable that correlates with the extent of coronary artery disease when the latter is assessed quantitatively by a scoring system rather than the conventional method of reporting coronary angiograms. Young age and greater exercise heart rate strengthened the correlation. The change in ejection fraction from rest to exercise is useful in the diagnosis of coronary artery disease, but it was the absolute level of exercise ejection fraction that predicted the extent of disease.
A new exercise electrocardiography test has been examined in patients with angina pectoris; the rate of development of ST segment depression with respect to increases in heart rate during exercise on a bicycle ergometer was measured during exercise using 13 leads in 64 patients. The steepest slope of regression lines relating displacement of ST segment to increases in heart rate (maximal ST/HR slope) was used as an index of myocardial ischaemia and was compared with the results of coronary angiography which were determined by the radiologists and the cardiologist responsible for the management of these patients.
The maximal ST/HR slope could be derived consistently from a linear ST/HR relationship (r≥0.95) only in 50 patients with significant coronary artery disease (≥75% luminal narrowing). The ranges of the maximal ST/HR slope in 17 patients with single-vessel disease, in 18 patients with double-vessel disease and in 15 patients with triple-vessel disease were different from each other and the differences between the means were statistically significant (P <0.0005). The maximal ST/HR slopes for the patients with single-vessel disease were also different from those in the 14 patients in whom significant coronary disease could not be demonstrated.
In contrast, the criteria of heart rate at which ST segment depression began, maximum ST segment depression, rate-pressure product and heart rate attained at the end of the test showed an overlap between the groups of the patients studied; using the usual exercise test criteria in the same population, there were three false negative results, one false positive result and the results in eight of the patients were indeterminate.
It is concluded that the maximal ST/HR slope, used as an index of myocardial ischaemia, reliably predicted the presence and severity of coronary artery disease, as determined by coronary arteriography in each of the patients with anginal pain.
The prognostic value of exercise thallium imaging in patients with positive exercise electrocardiograms [Abstract]
- Cox
Assessment of jeopardized myocardium in patients with multivessel disease
- Iskandrian
What is the significance of a strongly positive exercise electrocardiogram associated with a normal thallium-201 tomogram?
- Smith