Methodologic problems in exercise testing research. Are we solving them?

To evaluate the comparative effects of methodologic factors on the reported accuracies of two standard exercise tests, 56 publications comparing the exercise thallium scintigram with the coronary angiogram were analyzed for conformation to five methodologic standards. Analyzed were adequate definition of study group, avoidance of a limited challenge group, avoidance of workup bias, and blinded analysis of the coronary angiogram and myocardial scintigram. Study group characteristics and technical factors were also reviewed. Better conformation with methodologic standards was found than has been reported previously for treadmill exercise testing. Furthermore, study group characteristics and technical factors were better predictors of sensitivity and specificity than were methodologic deficiencies. Only workup bias and test blinding were significantly associated with test accuracy. The percentage of patients with previous myocardial infarction had the highest correlation and was independently and directly related to sensitivity and inversely related to specificity.     

Methodological analysis of diagnostic dobutamine stress echocardiography studies

BACKGROUND: Dobutamine stress echocardiography (DSE) is an accepted test for the diagnosis of coronary artery disease (CAD), despite its wide diagnostic accuracy. AIM: Which factors cause test variability of DSE for the diagnosis of CAD. METHODS: In a retrospective analysis of 46 studies in 5,353 patients, the potential causes of diagnostic variability were systematically analyzed, including patient selection, definition of CAD, chest pain characteristics, confounding factors for DSE (left ventricular hypertrophy, left bundle branch block, female gender), work-up bias (present when patient's chance to undergo coronary angiography is influenced by the result of DSE), review bias (present when DSE is interpreted in relation to CAG), DSE protocol and definition of a positive DSE. RESULTS: Diagnostic variability was related to definition of a positive test, but not related to the definition of CAD or DSE protocol. However, only three of eight methodological standards for research design found general compliance. Differences in the selection of the study population (quality of echocardiographic window, angina pectoris), handling of confounding factors and analysis of disease in individual coronary arteries were observed. Lack of data on analysis of relevant chest pain syndromes and handling of nondiagnostic test results hampered further evaluation of these standards. CONCLUSION: Methodological problems may explain the wide range in diagnostic variability of DSE. An improvement of clinical relevance of DSE testing is possible by stronger adherence to common and new methodological standards.     

Value of early two dimensional echocardiography in patients with acute myocardial infarction

Seventy-five consecutive patients with acute myocardial infarction underwent two dimensional echocardiography 7.9 ±3.1 hours after admission (1) to determine if this procedure can detect regional left ventricular asynergy in an unselected series of patients; (2) to evaluate the relation of asynergy outside the electrocardiographic infarct zone to clinical events and coronary anatomic findings; and (3) to determine whether the procedure can identify patients at high risk for cardiogenic shock, before the onset of hemodynamic deterioration. For purposes of analysis, the left ventricle was divided into 11 segments; individual segments were evaluated for systolic wall motion and thickening, and a wall motion index was calculated as a measure of global left ventricular performance.Technically satisfactory two dimensional echographic studies were obtained in all 75 patients. Of 825 possible segments in the 75 patients, 795 (96 percent) or 10.6 segments per patient were deemed adequate for analysis. Akinesia or dyskinesia was detected in at least one segment in all patients, including 15 (20 percent) who underwent imaging within 4 hours of the onset of symptoms and 19 (25 percent) with nontransmural infarction. Severe wall motion abnormalities outside the infarct zone were observed in 47 percent of patients and correlated with a greater prevalence of death (p = 0.03), cardiogenic shock (p < 0.01), progression to a worse Killip class (p = 0.001), reinfarction (p = 0.01) and angina (p = 0.09). Echocardiographic findings were related to coronary anatomic findings in 26 patients; in 13 (93 percent) of 14 cases, remote asynergy occurred in the distribution of a second critically stenosed (90 percent or greater) coronary artery. Lastly, in 66 patients initially assigned to Killip class I to II, the wall motion index was highly predictive of later hemodynamic deterioration. If the numerical admission Killip class and wall motion index are introduced into a discriminant equation (1.44 [Killip class] + 2.11 [wall motion index]), and the discriminant result is 6.04 or greater, 78 percent of patients who had cardiogenic shock were identified. If the discriminant result is less than 6.04, 93 percent of patients without shock were correctly identified.Thus, two dimensional echocardiography performed soon after admission to the coronary care unit is technically feasible, provides useful information concerning regional and global left ventricular function and offers important predictive information about patients early in acute myocardial infarction.     

Relation of graded exercise test findings after myocardial infarction to extent of coronary artery disease and left ventricular dysfunction

To evaluate the effectiveness of the graded exercise test in predicting the extent of coronary artery disease and the degree of left ventricular dysfunction in patients with prior myocardial infarction, 100 consecutive patients underwent both graded exercise testing and coronary and left ventricular angiography at a median of 4 months after infarction. The studies caused no complications. An equal number of patients had anterior and inferior infarction. Coronary artery disease, defined as 70 percent or greater stenosis of luminal diameter, was present in three vessels in 31 patients, in two vessels in 35 patients, in one vessel in 33 patients and in no vessel in one patient. With “diagnostic” electrocardiographic criteria of 1 mm or greater J point depression plus a flat or downsloping S-T segment, 31 patients had an electrocardiographically positive exercise test; 27 of these (87 percent) had two or three vessel coronary artery disease. Of the 21 patients with a negative exercise test, 62 percent had coronary artery disease in no more than one vessel, 33 percent in two vessels and 5 percent in three vessels. Fourteen patients had S-T segment elevation during exercise; these patients had a lower ejection fraction and larger angiographic scar size than the remaining 86 patients. Patients terminating exercise because of symptoms of left ventricular dysfunction (fatigue or dyspnea) showed correlation between duration of exercise and ejection fraction (r = 0.65) and between duration of exercise and angiographic scar size (r = ?0.62). Thus, several months after infarction, the graded exercise test can be performed safely and can be utilized to predict the extent of coronary artery disease and left ventricular dysfunction in selected groups of patients.     

Can exercise electrocardiography and thallium-201 myocardial imaging exclude the diagnosis of coronary artery disease?: Bayesian analysis of the clinical limits of exclusion and indications for coronary angiography

The objective of this study was to determine whether exercise electrocardiography can be combined with thallium-201 myocardial imaging and the clinical history to exclude the diagnosis of coronary artery disease. All 96 patients in this study were referred for coronary angiography because of chest pain but did not have prior myocardial infarction; 52 percent had coronary artery disease. Each patient's chest pain was classified as either typical or not typical of angina pectoris. Negative tests with inadequate exercise stress (less than 85 percent of the age-predicted maximal heart rate) and combined tests with discordant results (either exercise electrocardiography or thallium imaging positive and the other test negative) were judged nondiagnostic. Nondiagnostic tests that contributed most to the uncertainty of results were classified separately: exercise electrocardiogram, 35 patients; thallium imaging, 9 patients; and combined exercise electrocardiogram and thallium imaging, 50 patients. The ability of each test to rule out coronary artery disease was defined by its predictive error (probability of coronary disease despite a negative test): history of chest pain not typical of angina, 26 percent (11 of 42); exercise electrocardiogram, 22 percent (5 of 23); thallium imaging, 27 percent (6 of 35); and negative findings on both exercise electrocardiogram and thallium imaging, 6 percent (1 of 17). Finally, when only the patients with atypical chest pain were considered, there was zero (0 of 15) predictive error if both tests were negative.Negative exercise electrocardiography and thallium imaging during adequate stress ruled out any coronary artery disease in these patients with considerable reliability (94 percent) and excluded multivessel disease with even greater reliability. These exclusion tests for coronary artery disease were most reliable in patients in whom the clinical diagnosis of coronary artery disease was least likely, as defined by Bayes' theorem. It is concluded that there is no perfect noninvasive test to exclude coronary disease in all patient populations; however, coronary angiography is not necessary to rule out the diagnosis of coronary artery disease in patients who'have (1) no clinical indicators of a very high probability of coronary disease, such as typical angina, (2) adequate exercise stress, (3) negative exercise electrocardiogram and (4) negative exercise thallium images.     

Electrocardiographic responses to atrial pacing and multistage treadmill exercise testing. Correlation with coronary arteriography

Atrial pacing was compared with multistage treadmill exercise testing in 50 patients undergoing diagnostic cardiac catheterization to determine the diagnostic sensitivity of atrial pacing. Coronary artery disease was considered significant if luminal narrowing greater than 75 percent was present. Twenty-one subjects (Group I) had no significant coronary artery disease with vessel narrowing of less than 50 percent. Twelve (Group II) had single vessel disease and 17 (Group III) had disease of two or more vessels.The mean maximal heart rate during atrial pacing was 140/min and during exercise testing was 131/min. A positive atrial pacing test result was obtained in 5 percent of patients in Group I, 17 percent of patients in Group II and 24 percent of patients in Group III. A positive multistage treadmill exercise test result was obtained in 10 percent of patients in Group I, 67 percent of patients in Group II and 94 percent of patients in Group III. These differences are statistically significant (P < 0.001). The sensitivity of atrial pacing was 20 percent compared with 83 percent for multistage treadmill exercise testing. The specificity of atrial pacing was 95 percent compared with 90 percent for multistage treadmill exercise testing. Thus, atrial pacing is an insensitive test in the diagnosis of ischemic heart disease and does not improve the diagnostic value of multistage treadmill exercise testing.     

Cardiac fluoroscopy for the diagnosis of coronary artery disease: a meta analytic review

To evaluate variability in the reported accuracy of fluoroscopically detected coronary calcific deposits for predicting angiographic coronary disease, we applied meta analysis to 13 consecutively published reports comparing the results of cardiac fluoroscopy with coronary angiography. Population characteristics and technical and methodologic factors were analyzed. Sensitivity and specificity for predicting serious coronary disease compare quite well with those from the literature on the exercise ECG and the exercise thallium scintigram. Sensitivity increases and specificity decreases more significantly with patient age, and sensitivity is paradoxically lower in laboratories testing patients with more severe disease, as well as when 70% rather than 50% diameter narrowing is used to define angiographic disease. Work-up and test review bias were also significantly related to reported accuracy.     

Prognosis of asymptomatic or mildly symptomatic patients with coronary artery disease

One hundred forty-seven asymptomatic or mildly symptomatic patients with coronary artery disease, who did not have significant left main coronary occlusion and had an ejection fraction greater than 20 percent, were followed up prospectively for 6 to 67 months (average 25). Significant obstruction of one coronary artery was present in 28 percent of patients, of two coronary arteries in 31 percent and of three coronary arteries in 41 percent. Ejection fraction was 55 percent or greater in 69 percent of patients. During the follow-up period there were eight deaths (annual mortality rate 3 percent for the entire group, 1.5 percent for patients with single and double vessel disease but 6 percent for those with triple vessel disease). Better definition of high and low risk subgroups of patients with three vessel disease was accomplished with exercise testing. Despite a history of mild symptoms, 25 percent of the patients with triple vessel disease exhibited poor exercise capacity on exercise testing after administration of beta adrenoceptor blocking agents and nitrates was discontinued; of these, 40 percent either died (20 percent) or had progressive symptoms requiring operation (20 percent) (annual mortality rate 9 percent). Of the patients with good exercise capacity, only 22 percent either died (7 percent) or had progressive symptoms (15 percent) (annual mortality rate 4 percent).

Thus, prognosis is excellent in patients with no or mild symptoms who have one or two vessel coronary disease. Patients with three vessel disease who have good exercise capacity documented by objective testing have an annual mortality rate of 4 percent. However, because patients with three vessel disease and poor exercise capacity have an extremely grave prognosis, it would appear reasonable to recommend coronary bypass surgery for this subgroup, even in the absence of supporting data derived from a definitive randomized study.     

Exercise cross-sectional echocardiographic diagnosis of coronary artery disease

To test the feasibility of detecting transient left ventricular regional wall motion abnormalities during exercise-induced myocardial ischemia, 55 patients undergoing diagnostic coronary arteriography were studied in a prospective blinded manner with wide angle cross-sectional echocardiography. The ultrasonic studies were obtained with the patients at rest and during exercise in the supine position using a bicycle ergometer. Cross-sectional echocardiographic studies during exercise were adequate for analysis in 43 (78 percent) of the 55 patients. Forty-one of the 43 manifested either a new regional wall motion abnormality during exercise (20 subjects) or wall motion that remained entirely normal during exercise (21 subjects); In two subjects an abnormal wall motion abnormality at rest did not change with exercise. Nineteen of the 20 patients with a new regional wall motion abnormality had significant coronary artery disease and 15 of these 19 had S-T segment depression during bicycle ergometry. The one patient with a normal coronary arteriogram had an early cardiomyopathy. Ten of the 21 subjects with normal wall motion at rest and during exercise had a normal coronary arteriogram, whereas 11 had evidence of important anatomic coronary artery disease and thus had a false negative echocardlographic findings. Six of these 11 patients had S-T segment depression during exercise. The usefulness of exercise echocardlography to predict coronary artery disease was not altered even when only 26 patients without previous myocardial infarction and with a normal cross-sectional echocardiogram at rest were considered. Thus, new regional wall motion abnormalities during exercise as identified with cross-sectional echocardiography represent a specific finding for the presence of coronary artery disease. However, normal regional wall motion during exercise does not exclude the presence of important anatomic coronary artery disease.     

Implications of probability analysis on the strategy used for noninvasive detection of coronary artery disease: Role of single or combined use of exercise electrocardiographic testing,radionuclide Cineangiography and myocardial perfusion imaging

The accuracy of any less than perfect noninvasive test in detecting coronary artery disease is critically dependent not only oh its sensitivity and specificity, but also on the prevalence or pretest likelihood of disease in the population under study. Thus, an abnormal test result in a patient with a low pretest probability of disease (for example, an asymptomatic subject) is considerably more likely to be falsely indicative of disease than an identical result in a patient with a high pretest probability (for example, a patient with angina). On the basis of both theoretical considerations and clinical studies, it is now clear that diagnostic information derived from electrocardiographic exercise testing, radionuclide cineangiography or thalium perfusion imaging of persons with a low pretest probability of the disease is limited. However, by applying easily obtained clinical information, one can change estimates of the pretest likelihood of coronary artery disease and thereby greatly improve diagnostic information derived from a normal or an abnormal test result. Thus, the probability of coronary artery disease in a middle-aged man with hypertension and hypercho-lesterolemia who has an abnormal noninvasive test result is much greater than the probability of disease when the same abnormal result occurs in a younger man without such risk factors. Probability analysis can further enhance diagnostic accuracy if one applies the principle that when the results of two test procedures are independent of one another, the post-test likelihood of disease derived from the first test can be used as the pretest likelihood of disease for the second. Thus, if an electrocardiographic exercise test result is abnormal and the resulting probability of coronary artery disease is estimated at 70 percent, the diagnosis is still uncertain. However, the postelectrocardiographic test probability of 70 percent can be used as the pretest likelihood of coronary artery disease for radionuclide testing. If the radionuclide study result is abnormal, the probability of disease increases to nearly 100 percent. Thus, (1) nonin-vasive testing procedures yield probability estimates of disease, rather than simple “yes or no” diagnostic statements; (2) a working knowledge of probability analysis will make it easier for the physician to decide which patients might benefit from noninvasive diagnostic studies and whether more than one test should be employed; (3) this approach can provide reliable estimates of the probability that coronary artery disease is present or absent in an individual patient.     

Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease

There has been only modest clinical interest in exercise echocardiography because of the technical limitations of the procedure. Recognizing that there have been recent technical advances in the echocardiographic instruments and that echocardiography should, in theory, be an ideal technique for evaluating exercise-induced wall motion abnormalities, a clinically practical method of performing exercise echocardiograms was developed. By obtaining the echocardiograms immediately after treadmill exercise, with the patient sitting at the treadmill, a high percent of studies adequate for interpretation was obtained (92%). The addition of echocardiography to the treadmill exercise test significantly enhanced the diagnostic yield. In addition, in cases of one and three vessel disease, exercise echocardiography identified stenosis in specific coronary arteries. In patients with two vessel disease and left circumflex obstruction, specific vessel identification was less reliable. A high percent of patients with multivessel disease developed wall motion abnormalities with exercise that persisted for at least 30 minutes. It is concluded that echocardiography performed immediately after exercise with the new generation of echocardiographs can be a practical and useful clinical tool.     

Non-invasive diagnostic and prognostic assessment of single-vessel coronary artery disease: focus on stress echocardiography.

AIMS: Revascularization procedures are increasingly applied in patients with single-vessel coronary artery disease in spite of the fact that a prognostic benefit has been proved only for soft end-points. This review summarizes the results of stress echocardiography in the diagnostic and prognostic assessment of these patients. METHODS AND RESULTS: The diagnostic and prognostic assessment of patients with single-vessel disease using stress (exercise, dobutamine, adenosine and dipyridamole) echocardiography are focused upon in the light of pathophysiological considerations and the results of clinical studies. Factors affecting test accuracy are individually addressed and comparisons made with different stress testing modalities, including exercise electrocardiography and nuclear techniques. Finally, therapeutic options are discussed and the superior accuracy of the physiological assessment of coronary stenosis as compared to the simple anatomic evaluation emphasized. CONCLUSIONS: Patients with single-vessel disease represent an anatomically heterogeneous group. Although the suboptimal performance of any technique in their evaluation has to be acknowledged, stress echocardiography can effectively contribute to selection of the management strategy.     

Comparison of ambulatory electrocardiography and exercise testing

Ambulatory electrocardiography and exercise testing are two noninvasive diagnostic procedures widely employed to evaluate patients for cardiac arrhythmias and S-T segment changes. This review addresses the differences and similarities of the two techniques, and examines the relative diagnostic and prognostic merit of the arrhythmia and S-T segment changes detected with each method.

Ambulatory electrocardiography is more sensitive than exercise testing in detecting cardiac arrhythmias. The recording of ventricular arrhythmia is of value in predicting sudden death in survivors of myocardial infarction, whereas exercise-induced ventricular arrhythmia has limited predictive value. Nevertheless, exercise-induced S-T depression is of great prognostic value in predicting mortaliy and sudden death in patients wlth acute and chronic coronary heart disease.     

Predicting the extent and location of coronary artery disease during the early postinfarction period by quantitative thallium-201 scintigraphy

The ability of quantitative thallium-201 scintigraphy to predict the extent and location of coronary artery disease before hospital discharge after acute myocardial infarction was evaluated in 52 patients. All patients underwent coronary angiography and serial thallium-201 imaging either at rest (10 patients) or after submaximal exercise stress (42 patients; target heart rate 120 beats/min). Two or three vessel disease was designated if abnormal thallium-201 uptake or washout patterns, or both, were seen in two or three vascular segments, respectively. Of 156 vessels analyzed in the 52 patients, 91 stenoses of 70 percent or greater were found by angiography. Seventy-four (81 percent) of these were predicted by scintigraphy. The specificity of scintigraphy for identifying vessel stenoses was 92 percent. Sensitivity for detecting and localizing stenoses supplying an infarct zone was 96 percent compared with 62 percent for stenoses supplying myocardium remote from the acute infarct. Perfusion abnormalities were more frequently seen in the distribution of vessels with severe (90 percent or greater) stenoses than in those with moderate (70 to 90 percent) stenoses (87 versus 53 percent, p <0.01). Scintigraphy detected a greater proportion of left anterior descending and right coronary arterial stenoses than circumflex stenoses (91 and 87 versus 63 percent, respectively, p <0.006).In the 42 patients who underwent submaximal exercise testing, multivariate analysis of 23 clinical and laboratory variables identified multiple thallium-201 defects as the best predictor of multivessel disease. The predictive accuracy of exercise-induced S-T segment depression was only 45 percent compared with 88 percent (p <0.05) for thallium-201 scintigraphy. Thus, 2 weeks after myocardial infarction, exercise thallium-201 scintigraphy is useful for predicting the extent and location of coronary artery disease, particularly stenoses in the left anterior descending and right coronary arteries. Moreover, thallium-201 imaging at rest is reliable in assessing the extent of coronary disease in hospitalized patients who cannot undergo exercise testing because of unstable angina, uncompensated heart failure, poorly controlled arrhythmias or physical limitations.     

Role of exercise stress testing in healthy subjects and patients with coronary heart disease. Controversies in cardiology--I.

The value of the exercise stress test in the evaluation of clinically healthy subjects and patients with coronary heart disease is not limited to the isolated interpretation of abnormalities of the S-T segment. Other measurable parameters which are of diagnostic and prognostic importance include: (1) a decrease in systolic blood pressure during exercise; (2) the appearance of complex ventricular arrhythmias of low exercise heart rates; (3) the appearance of inverted U waves during or after exercise; (4) the patient's maximal exercise capacity; and (5) new auscultatory findings postexercise. The reliability of the exercise test as a diagnostic tool is futher enhanced by proper patient selection and careful attention to exercise techniques. Subjects with labile ST-T wave changes during standing hyperventilation, fixed ST-T changes at rest, and intraventricular conduction defects are not ideal candidates for "diagnostic" stress testing and the examining physician must rely more heavily on nonelectrocardiographic findings. The criteria used to define an abnormal S-T response will vary according to the lead system used. However, in both symptomatic and asymptomatic subjects the appearance of marked degrees of S-T depression at low exercise heart rates significantly increases the probability of finding advanced coronary disease, particularly if the S-T depression is seen in multiple monitoring leads and is of prolonged duration postexercise.     

Magnetic resonance imaging of the brain and spine. Is clinical efficacy established after the first decade?

STUDY OBJECTIVE: Evaluation of demonstrated clinical efficacy of magnetic resonance (MR) imaging in the central nervous system. DESIGN: Information synthesis of studies before January 1987. SETTING: Reports were classified by the level of clinical efficacy studied (technical capacity, diagnostic impacts, and therapeutic or patient outcome impacts) and were judged by the validity of their methods, especially avoidance of diagnosis review, test review, and work-up biases. MAIN RESULTS: Magnetic resonance imaging probably is superior to computed tomography for detection and characterization of posterior fossa lesions and spinal cord myelopathies, imaging in multiple sclerosis, detecting lesions in patients with refractory partial seizures, and detailed display for guiding complex therapy, as for brain tumors. In other diseases, the efficacy of MR imaging is similar to that of computed tomography (cerebrovascular, radiculopathy, and infection). Magnetic resonance imaging is less invasive than intrathecal or intravenous contrast-enhanced computed tomography and costs 20% to 300% more than computed tomography, although avoidance of hospital stays may offset some costs. Generally, the quality of MR images probably exceeds that of computed tomographic (CT) scans. However, published evidence does not show that the clinical efficacy of MR imaging is generally superior to that of existing imaging modalities such as computed tomography. Only six studies avoided major methodologic biases, and lower true-positive rates for MR imaging were reported in these studies than reported in multiply biased studies. Few studies of the potential of MR imaging for false-positive diagnosis have been done. CONCLUSIONS: Use of standards for quality of evidence leads to more conservative conclusions than those of reports describing the clinical potential of MR imaging. Some applications of MR imaging were confirmed by rigorous studies, whereas others were not well supported by reports free of methodologic biases. If the diagnostic alternative is invasive (for example, myelography and cisternography), MR imaging is preferred, but adequate diagnosis for many conditions (head trauma, simple stroke, and dementia) may not require the detail of an MR imaging study. In general, more rigorous clinical research studies are needed for new technologies such as MR imaging. Because the field of MR imaging is changing, review of its clinical efficacy will need to be revised frequently.     

Evaluation of abnormal exercise electrocardiogram in apparently healthy subjects: Labile repolarization (ST-T) abnormalities as a cause of false positive responses

Long-term follow-up studies were carried out in 121 apparently healthy men with an abnormal S-T segment response to exercise—49 Indiana State policemen and 72 subjects from a large occupational health center. The mean follow-up periods were 66 months and 43 months, respectively, for the two groups of subjects. A tendency toward labile S-T or T wave abnormalities were documented during standing rest or with hyperventilation in 61 of these 121 subjects and there was only one new coronary event in this subgroup. The labile ST-T wave changes and the abnormal S-T segment responses to exercise were not consistently reproducible in these subjects, and it was not unusual to see an abnormal S-T segment response at a time when the labile repolarization changes could not be demonstrated. Many of the subjects exhibited labile ST-T wave changes only after oral glucose loading. Significant coronary artery disease was documented in 34 (57 percent) of the remaining 60 subjects during the follow-up period.Coronary cineangiographic studies, obtained in 21 of the 35 subjects from the health center who had had no evidence of labile ST-T wave abnormalities, revealed coronary arterial stenoses of 75 percent or greater in 19. A statistical analysis was carried out in the 35 subjects without labile ST-T abnormalities to determine if there were exercise test variables that would differentiate the true positive from the false positive responses. A set of criteria were identified that yielded a specificity of 92 percent, a sensitivity of 82 percent and a predictive value of 95 percent. The entire group of 72 from the health center subjects had undergone an average of 3.8 exercise tests before their referral to the authors' laboratory. A review of these records revealed that a serial conversion from a normal to an abnormal S-T segment response was not more predictive of underlying coronary artery disease than an initially abnormal test result.     

Incidence and significance of decreases in systolic blood pressure during graded treadmill exercise testing.

The incidence of decreases in peak systolic blood pressure during treadmill exercise was investigated in 460 patients with definite or suspected coronary heart disease. All patients were studied with coronary cineangiography. Exercise was continued to one of the following end points: chest pain, 85 to 90 percent of the patient's age-predicted maximal heart rate, ventricular tachycardia or a sustained decrease of 10 mm Hg or more below the peak level of systolic blood pressure. Twenty-two patients with 75 percent or greater stenosis of one or more major coronary arteries manifested a decrease in systolic pressure 10 mm Hg or more during exercise. These included 15 (17 percent) of 88 patients with three vessel, 7 (7 percent) of 101 with two vessel and 0 of 90 with single vessel disease. The decrease in pressure was reproducible in the seven patients who underwent a second exercise test before alteration of therapy; this decrease was abolished in the six patients who exercised again after coronary bypass graft surgery.A decrease in systolic pressure of 10 mm Hg or more also occurred during exercise testing in 3 of 23 patients with noncoronary organic heart disease; all 3 had an obstructive cardlomyopathy that had not been suspected clinically. Only 1 of 158 subjects with chest pain and no demonstrable heart disease had a decrease in systolic blood pressure with exercise. Declines in blood pressure were not observed during 650 maximal exercise tests performed on 560 clinically normal men.In conclusion, if one excludes subjects with cardiomyopathy or significant heart valve disease, a sustained exercise-induced decrease in peak systolic blood pressure of 10 mm Hg or more is a highly specific sign of multiple vessel coronary artery disease. This phenomenon is best explained by acute left ventricular pump failure secondary to extensive myocardial ischemia.     

Pharmacologic radionuclide myocardial perfusion imaging

Pharmacologic stress testing with myocardial perfusion imaging has enabled patients who cannot complete adequate exercise to undergo diagnostic and prognostic evaluation for coronary artery disease. Pharmacologic stress agents belong to two groups: vasodilators (such as adenosine and dipyridamole), and inotropes (such as dobutamine). All have similar sensitivity (89%-91%) and specificity (78%-86%) for the diagnosis of coronary disease. For risk stratification, the risk of future cardiac events is related to the extent and severity of perfusion abnormalities. Pharmacologic stress testing permits risk stratification as early as 1 to 4 days following an acute myocardial infarction, and is superior to exercise stress testing in this regard. Similarly, it identifies patients at high risk for perioperative cardiac events prior to noncardiac surgery. This review summarizes the current evidence available regarding the diagnostic and prognostic use of pharmacologic stress testing.     

Heart rate recovery: validation and methodologic issues

OBJECTIVES: The goal of this study was to validate the prognostic value of the drop in heart rate (HR) after exercise, compare it to other test responses, evaluate its diagnostic value and clarify some of the methodologic issues surrounding its use. BACKGROUND: Studies have highlighted the value of a new prognostic feature of the treadmill test-rate of recovery of HR after exercise. These studies have had differing as well as controversial results and did not consider diagnostic test characteristics. METHODS: All patients were referred for evaluation of chest pain at two university-affiliated Veterans Affairs Medical Centers who underwent treadmill tests and coronary angiography between 1987 and 1999 as predicted after a mean seven years of follow-up. All-cause mortality was the end point for follow-up, and coronary angiography was the diagnostic gold standard. RESULTS: There were 2,193 male patients who had treadmill tests and coronary angiography. Heart rate recovery at 2 min after exercise outperformed other time points in prediction of death; a decrease of <22 beats/min had a hazard ratio of 2.6 (2.4 to 2.8 95% confidence interval). This new measurement was ranked similarly to traditional variables including age and metabolic equivalents but failed to have diagnostic power for discriminating those who had angiographic disease. CONCLUSIONS: Heart rate at 1 or 2 min of recovery has been validated as a prognostic measurement and should be recorded as part of all treadmill tests. This new measurement does not replace, but is supplemental to, established scores.