Anthony P. Morise

Development and Validation of a Clinical Score to Estimate the Probability of Coronary Artery Disease in Men and Women Presenting with Suspected Coronary Disease

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

Comparison of the sensitivity and specificity of exercise electrocardiography in biased and unbiased populations of men and women

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

Evaluation of pretest and exercise test scores to assess all-cause mortality in unselected patients presenting for exercise testing with symptoms of suspected coronary artery disease

OBJECTIVES To determine how well recently developed multivariables scores assess for all-cause mortality in patients with suspected coronary disease presenting for exercise electrocardiography (ExECG). BACKGROUND Recently revised American College of Cardiology/American Heart Association guidelines for ExECG have suggested that ExECG scores be used to assist in management decisions in patients with suspected coronary artery disease. Recently developed scores accurately stratify patients according to angiographic disease severity. METHODS To determine how well these scores assess for all-cause mortality, we utilized 4,640 patients without known coronary disease who underwent ExECG to evaluate symptoms of suspected coronary disease between 1995 and 2001. Previously validated pretest and exercise test scores as well as the Duke treadmill score were applied to each patient. All-cause mortality was our end point. RESULTS Overall mortality was 3.0% with 2.8 +/- 1.6 years of follow-up. All three scores stratified patients into low-, intermediate-, and high-risk groups (p < 0.00001). No differences were seen when patients were evaluated as subgroups according to gender, diabetes, beta-blockers, or inpatient status. Low-risk patients defined by the Duke treadmill score had consistently higher mortality and absolute number of deaths compared with low-risk patients using other scores. In addition, the Duke treadmill score had less incremental stratifying value than the new exercise score. CONCLUSIONS Simple pretest and exercise scores risk-stratified patients with suspected coronary disease in accordance with published guidelines and better than the Duke treadmill score. These results extend to diabetics, inpatients, women, and patients on beta-blockers.

Development and validation of a logistic regression-derived algorithm for estimating the incremental probability of coronary artery disease before and after exercise testing

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.

Value of a simple measure of estrogen status for improving the diagnosis of coronary artery disease in women

PURPOSE To determine the potential impact of estrogen status on the pretest and postexercise test diagnostic accuracy of exercise testing. PATIENTS AND METHODS The study comprised a total of 234 women and 326 men who underwent exercise testing followed by coronary angiography. We performed incremental logistic regression analysis of pretest (age, symptoms, smoking, diabetes, cholesterol level) with and without estrogen status (defined according to menopausal and oral estrogen status) and exercise test (two ST-segment and three non-ST-segment) variables separately for men and women. Outcomes were assessed by receiver operating characteristic (ROC) curve area analysis. RESULTS Estrogen status was an independent pretest predictor of angiographic coronary disease. Pretest ROC curve areas: women without estrogen status = 0.79, women with estrogen status = 0.85, men = 0.78 (women with estrogen status versus other groups, p < 0.001). Postexercise test ROC curve areas: women without estrogen status = 0.83, women with estrogen status = 0.87, men = 0.88 (women without estrogen status versus other groups, p < 0.001). CONCLUSION Consideration of estrogen status allowed for a significant improvement in the pretest clinical diagnosis of coronary disease in women. When these improvements were added to the results of exercise testing, the diagnostic accuracy of the combined clinical and exercise test data was similar for men and women. Estrogen status may be an important diagnostic clinical variable in women with suspected coronary disease.

Heart Rate Recovery Predictor of Risk Today and Target of Therapy Tomorrow

How quickly the heart rate recovers after treadmill exercise testing has been the subject of much interest over the last several years. The observations of Imai et al1 first prompted the clinical evaluation of heart rate recovery. In healthy subjects, athletes, and patients with heart failure, they demonstrated that early (within 1 minute) heart rate recovery was principally the result of vagal reactivation. The phenomenon was abolished by atropine, unaffected by β-blockers, independent of workload or age, blunted with heart failure, and accelerated in athletes. The hypothesis joining heart rate recovery and mortality arose from work that associated the autonomic nervous system with sudden cardiac death in the postinfarction setting.2 This hypothesis has developed to the point at which autonomic tone is considered a cardiovascular risk factor.3 Particular interest has focused on the ability of heart rate recovery to predict all-cause mortality.4–13 See p 2851 Michael Lauer’s group from The Cleveland Clinic has been the driving force behind this field of investigation. In this issue of Circulation , these investigators present a further, provocative analysis of data from their center that explores the question of whether heart rate recovery can predict who will survive after coronary revascularization. In their study, Chen et al14 address an issue that is typically dealt with via randomized controlled studies. In lieu of such a trial, they compiled observational data and applied a modified case-control study design. From a group of 8861 patients who underwent treadmill exercise tests with imaging, they found 552 patients who underwent early (ie, within 3 months of the exercise study) coronary revascularization. Using propensity matching, Chen and colleagues were able to match 508 patients from this group with 508 patients from the >8000 patients who did not undergo early revascularization. The final study group of …

Incremental value of exercise electrocardiography and thallium-201 testing in men and women for the presence and extent of coronary artery disease

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.

Review of studies using multivariable analysis of clinical and exercise test data to predict angiographic coronary artery disease.

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.

Frequency of oral estrogen replacement therapy in women with normal and abnormal exercise electrocardiograms and normal coronary arteries by angiogram

Abstract The specificity of the exercise electrocardiogram has been reported to be lower in women than in men. 1 Using different standards, other investigators have reported no difference. 2 Nevertheless, there exists a relative consensus in the practicing medical community that a positive exercise electrocardiogram is of inherently less value in women than in men. Although one cannot discount the role that a lower prevalence of coronary artery disease in women 3 may play in this false-positive predisposition (i.e., reduced positive predictive accuracy), several authorities have speculated on a possible role for estrogen as a direct contributor to the false-positive exercise electrocardiogram in women (i.e., reduced specificity). 1,4 This study reviews our experience with exercise electrocardiography in women without atherosclerotic coronary artery disease by angiogram and assesses whether estrogen was associated with (false)-positive ST-segment changes.

Diagnostic criteria for acute myocardial infarction in patients undergoing coronary artery bypass surgery.

Current techniques for diagnosing perioperative myocardial infarction were studied in 58 patients who underwent coronary bypass surgery. All patients had preoperative and postoperative ECGs and technetium-99m stannous pyrophosphate myocardial scintigrams; serum CK-MB was measured immediately after surgery and daily for 3 days. Postoperative bypass graft visualization and left ventriculography were performed before hospital discharge in every patient. Nine patients (16%) had new Q waves postoperatively. Five of these nine patients had positive pyrophosphate scintigrams, positive CK-MB and new wall motion abnormalities, and the remaining four had negative CK-MB, negative pyrophosphate scintigrams and no new wall motion abnormalities. Seven patients (12%) had newly positive postoperative pyrophosphate scintigrams, positive CK-MB and new wall motion abnormalities on postoperative ventriculography, but only four had new Q waves postoperatively. Eight patients (14%) had new wall motion abnormalities; seven had positive pyrophosphate scintigrams and all had positive CK-MB, but only five had new Q waves. Sixteen patients (28%) had positive CK-MB, including all patients with either positive pyrophosphate scintigrams or new wall motion abnormalities. Eight patients had positive CK-MB without other evidence of perioperative infarction. A newly positive postoperative pyrophosphate scintigram is more sensitive and specific than the development of new postoperative Q waves for the diagnosis of hemodynamically significant perioperative myocardial infarction. CK-MB is highly sensitive, but too nonspecific to be useful for the diagnosis of perioperative infarction.