Kenneth G. Lehmann

Intravascular ultrasound imaging of human coronary arteries in vivo : analysis of tissue characterizations with comparison to in vitro histological specimens

BackgroundIntravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas. Methods and ResultsA 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 ± 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 ± 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 ± 3.2 mm2, which was a mean of 35 ± 23% of the available area bounded by the media. ConclusionsIntravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty. (Circulation 1991;83:913–926)

Cardiovascular abnormalities accompanying acute spinal cord injury in humans: Incidence, time course and severity

The frequency of cardiovascular abnormalities was evaluated in 71 consecutive patients with acute injury to the spinal cord. Persistent bradycardia was universal in all 31 patients with severe cervical cord injury and less common in milder cervical injury (6 of 17) or thoracolumbar injury (3 of 23) (p less than 0.00001). Marked sinus slowing (71 versus 12 versus 4%, respectively, p less than 0.00001), hypotension (68 versus 0 versus 0%, p less than 0.00001), supraventricular arrhythmias (19 versus 6 versus 0%, p = 0.05) and primary cardiac arrest (16 versus 0 versus 0%, p less than 0.05) were significantly more frequent in the severe cervical injury group. The frequency of bradyarrhythmias peaked on day 4 after injury and gradually declined thereafter. All observed abnormalities resolved spontaneously within 2 to 6 weeks. The primary mechanism underlying these observations appears to involve the acute autonomic imbalance created by the disruption of sympathetic pathways located in the cervical cord. Acute severe injury to the cervical spinal cord is regularly accompanied by arrhythmias and hemodynamic abnormalities not found with thoracolumbar cord trauma. These abnormalities are limited to the first 14 days after injury, a period in which life-threatening disturbances must be anticipated.

The Electrocardiographic Exercise Test in a Population with Reduced Workup Bias: Diagnostic Performance, Computerized Interpretation, and Multivariable Prediction

The standard exercise test is still the first step in the evaluation of the stable patient with chest pain that may be due to coronary artery disease. This is because simple ST-segment measurements are as diagnostic as other tests that can be performed by the clinician [1, 2]. Although studies suggest that the discrimination of multivariable equations [3], heart rate adjustment [4], and scores [5] is superior to that of ST-segment measurements, failure to validate this superiority has impeded acceptance of these tools. Even in correlation studies that have appropriately enrolled consecutive patients who have had both exercise testing and coronary angiography, workup bias has been a limitation. Patients in these studies were selected for angiography if a physician judged that the likelihood of coronary disease was high enough to warrant this invasive procedure. This selection process makes patients with abnormal exercise test results more likely to be chosen and excludes patients with normal test results and high exercise capacity; this results in a higher prevalence of disease than would be seen in a clinical population. Prediction equations, scores, and heart rate adjustment algorithms have been derived from population with extensive workup bias and are unlikely to be applicable to patients who present with chest pain [6]. Our study reduced workup bias prospectively by following a protocol that required patients to agree to undergo both exercise testing and coronary angiography. A pilot study that did not avoid workup bias was done in 687 patients at two sites from October 1990 to August 1994. The main study, Quantitative Exercise Testing and Angiography (QUEXTA), enrolled 1274 patients at 12 sites from August 1994 to September 1995. Methods Patients To be included in QUEXTA, patients had to be men 18 years of age or older with probable or definite stable angina. Standard exclusion criteria were used, and patients with previous myocardial infarction or previous abnormal angiograms were excluded. To further minimize workup bias, the study allowed no more than 25% of the patients at any one site to have had a recent treadmill test. The preferred entry point was the clinic, but less than 25% of patients could come from either the exercise or angiography laboratories. Of 1274 consecutive male patients who were enrolled at 12 Veterans Affairs Medical Centers between 22 August 1994 and 15 September 1995, 814 had no myocardial infarction on electrocardiography or history, underwent both coronary angiography and treadmill testing, and had complete data. Institutional review was done centrally and at each study site, and all patients signed a consent form approved for this study. Coronary angiography and treadmill testing had to be done within 30 days of each other. For validation purposes, the 814 patients were divided into a training set of 543 patients (two thirds of the total sample) and a test set of 271 patients (one third of the total sample). Approximately 7000 patients had exercise testing, and 1328 patients were enrolled during the recruitment period. Clinical variables obtained at the initial evaluation were recorded on a standard form. Chest pain was coded as 1 for definite angina, 2 for probable angina, 3 for nonanginal pain, and 4 for no pain. All other clinical variables, except age, body mass index, resting ST-segment depression, hemodynamic variables, and pack-years of cigarette smoking, were coded as present or absent. Exercise Testing All patients had exercise testing done with a ramp treadmill protocol [7]. ST-segment depression was measured at the J junction to the nearest quarter millimeter, and ST slope, measured over the following 60 milliseconds of the ST segment, was classified as upsloping, horizontal, or downsloping. ST slope was coded as 1 for abnormal (horizontal or downsloping and at least 1 mm of depression) or 0 for normal slope. The 12-lead electrocardiograms were read by two cardiologists at each site on separate days, once by using raw signals and once by using the device averages. The cardiologists were blinded to patient identity and test results. Maximal and delta values for hemodynamic variables, along with exercise-induced hypotension, exercise-induced angina, and exercise capacity estimated in metabolic equivalents (METs) from the final treadmill speed and grade, were recorded. Angina during testing was classified according to the Duke Angina Index (2 if angina required that the test be stopped, 1 if angina occurred during or after the test, and 0 if no angina occurred) [8]. No test result was classified as indeterminate [9]. Medications were withheld only on the day of testing, and no maximal heart rate targets were applied [10]. Computer Analysis Electrocardiographic devices were used at all sites to simultaneously record in digital format all 12 electrocardiographic leads through exercise and recovery at 500 samples per second (Mortara Instrument, Milwaukee, Wisconsin) on optical disks [11]. Optical disk recordings were processed off-line by using a microcomputer at the exercise electrocardiography core laboratory. After the raw data were averaged, QRS measurement landmarks were determined by using software developed by Sunny-side Biomedical (Vista, California) [12]. Coronary Angiography Coronary angiography was done with standard techniques after administration of nitroglycerin. Trained observers at each site made blinded quantitative measurements. All stenoses with visual percentage narrowing greater than 30% were measured. Raw measurements were sent to the core angiography laboratory in Seattle, where they were converted to true diameters after correction for distortion. In a randomized selection, the mean difference per stenosis between the measurement in the core laboratory and measurements at participating sites was 0.9%, with a mean absolute value of 11.4%. Patients were categorized as having significant coronary artery disease if at least one stenosis with narrowing of 50% or more by quantitative measurement was present in any artery or branch with a reference diameter of at least 1 mm. Statistical Analysis The summary statistics were examined, and several variables were eliminated from the model building because of their low prevalence or low variance. Examination of the distribution of the visual ST-segment measurements and their relation to the angiographic results led to the choice to use raw visual interpretation of the maximal abnormal ST-segment depression in either exercise or recovery. On the basis of these results, 20 variables were chosen for multivariate analyses (Table 1 and Table 2). The training set for diagnosis of any coronary artery disease was divided into two groups, one with and one without significant angiographic coronary artery disease. After a logistic regression Equation was developed for predicting pre-exercise test probability for coronary artery disease, the exercise test hemodynamic and nonelectrocardiographic variables were added to the pre-exercise test variables as candidates. This allowed variable selection for three additional models to predict post-exercise test probability for coronary artery disease and to compare the discriminating power of computerized and visual measurements. Table 1. Clinical Characteristics of Patients in the QUEXTA Study (n = 814)* Table 2. Hemodynamic and Visual Electrocardiographic Characteristics of Patients in the QUEXTA Study* On the basis of the protocol and previous publications, the computer variables considered for the equations were 1) ST/HR [heart rate] index calculated at ST0 and ST60, 2) the Hollenberg score, 3) depression at ST60 [ST amplitude 60 milliseconds after J junction] in V5 at a heart rate of 100 beats/min, 4) ST integral in V5 at 3.5 minutes of recovery, 5) ST slope in V5 at maximal exercise, 6) ST slope in V5 at 3.5 minutes of recovery, 7) ST amplitude at J junction with a horizontal ST slope in V5 at maximal exercise, 8) ST amplitude at J junction with a horizontal ST slope in V5 at 3.5 minutes of recovery, 9) ST60 in V5 at 3.5 minutes of recovery, and 10) ST60 in II at 3.5 minutes of recovery. The most ST60 depression and the sum of ST60 depression in the three major perpendicular leads (II, V2, and V5) at maximal exercise and 3.5 minutes of recovery, as well as ST60, ST0, and ST integral in V2 and II, were considered individually. Comparisons were based on the area under the receiver-operating characteristic (ROC) curve and on sensitivity at the fixed specificity for visual ST-segment depression. Table 3 shows the results obtained by comparing visual ST-segment depression separately with every other model. Table 3. Results from the QUEXTA Test Set Obtained by Using Unsimplified Multivariable Equations* Comparison with the pilot population (Appendix Table 2), which had a prevalence of disease similar to that of the study population and was tested by using the same methods, showed how effective the protocol was in reducing workup bias. Appendix Table 2. Values in Pilot Study Group Derived by Using Unsimplified Equations at the Specificity Matching Visual Analysis (69%) in the Pilot Group and the Specificity Matching Visual Analysis in the QUEXTA Test Set (85%)* Results Clinical and Resting Electrocardiographic Variables Table 1 shows summary statistics for clinical variables in the full diagnostic group. According to the angiographic criteria, 276 patients in the training set and 135 patients in the test set had coronary disease. We noted that in our patients, all of whom had stable chest pain, the probability of coronary artery disease was almost halved if the pain ever occurred at rest. Thus, pain at rest was included as a candidate variable. The pre-exercise test variables chosen by the logistic model for the pre-exercise test Equation included age (explaining 60% of total variance), chest pain type (explaining 30% of total variance), diabetes, and pack-years of smoking. Exerc

Prediction of Cardiovascular Death in Men Undergoing Noninvasive Evaluation for Coronary Artery Disease

Clinical evaluation, exercise testing, and coronary angiography are used routinely by physicians to decide whether interventions are needed in patients with coronary artery disease [1, 2]. Various conflicting clinical prediction rules have been proposed [3]. In a first report, we described our method of outcome assessment in patients who had undergone exercise testing and coronary angiography within a 3-month period and compared our prediction rules with those from other samples [4]. Our two main findings were that the results of coronary angiography and exercise-induced ST depression were not independently associated with cardiovascular death or infarct-free survival. The purpose of this investigation was to predict cardiovascular death using variables available from a standard noninvasive work-up of patients with known or suspected coronary artery disease. The use of this larger cohort, uninfluenced by selection for cardiac catheterization, allowed assessment of work-up bias. Methods Patients Patients were selected from a consecutive series of 3609 persons who underwent routine clinical exercise testing between 1984 and 1990; 30% of this group had coronary angiography within 3 months of testing and were excluded from the analysis. Also excluded were women (who constituted less than 2% of the sample), patients with significant valvular disease, and those who had previous coronary artery bypass surgery. Most of the remaining 2456 (84%) patients had been referred for testing because of chest pain or for the evaluation of exercise capacity. Clinical Definitions Myocardial infarction was defined by the presence of two or more of the following factors: 1) serial electrocardiographic changes; 2) typical chest pain; and 3) myocardial enzyme increase. Congestive heart failure was defined by typical symptoms and signs, plus echocardiographic or radiographic confirmation of cardiomegaly and pulmonary edema. Before treadmill testing, angina pectoris was classified as typical if the patient described substernal pressure, tightness, or pain that was brought on by exertion or emotions, lasted several minutes, and was relieved by nitroglycerin or rest. Angina was considered atypical in the absence of one or more of these features if the pain was thought to be cardiac in origin. Exercise Testing The exercise test was done using a standard progressive treadmill protocol [5]. Except for patients undergoing testing before discharge after myocardial infarction, each test was sign or symptom limited using standard recommended criteria for termination [2]; fatigue or chest pain was the reason for termination in most patients. In addition to the maximal systolic blood pressure achieved, the blood pressure response during exercise was coded as a score reflecting exercise-associated changes in systolic blood pressure (0 points = increase > 40 mm Hg; 1 point = 31 to 40 mm Hg; 2 points = 21 to 30 mm Hg; 3 points = 11 to 20 mm Hg; 4 points = 0 to 11 mm Hg; and 5 points = decrease below standing systolic blood pressure taken before testing) [6]. The treadmill was stopped abruptly at the completion of exercise, and the patient was placed in the supine position within 1 minute [7]. Exercise capacity was estimated in multiples of resting oxygen consumption (METs) and was also analyzed as a percentage of normal for age according to an equation derived from a normal subset of our referral group [8]. Electrocardiographic Measurements Left ventricular hypertrophy was coded according to Romhilt and Estes criteria [9]. Patients lacking left ventricular hypertrophy with more than 0.5 mm ST depression in any lead were coded as having resting ST depression. The exercise electrocardiogram was interpreted as previously described [7]. Measurement of Outcome Variable Since 1984, the Department of Veterans Affairs Health Care System has developed a series of programs to support Veterans Affairs Medical Center clinical functions as part of the Decentralized Hospital Computer Project (DHCP). Death certificates are routinely completed by Veterans Affairs Medical Center physicians for inpatient and outpatient deaths. Information on care received elsewhere is routinely requested for clinical purposes, and all patients were scheduled for routine appointments at 6-month intervals after testing. Data on hospitalizations and deaths are entered, and retrieval programs are available to obtain dates and information regarding the most recent clinical visit and prescription received as well as those regarding hospitalization or death. To avoid bias, the coding of death certificates and other outcome variables was blinded to the predictor (exposure) variables. Although not designed for research purposes, this administrative and clinical database helped us obtain complete follow-up information. Data Analysis All data were entered into R:Base (Microrim, Redmond, Washington) and were analyzed using R:Base, Statgraphics (Statistical Graphics Corporation, Rockville, Maryland), True Epistat (Epistat Services, Richardson, Texas), Confidence Interval Analysis (American College of Physicians, Philadelphia, Pennsylvania), and EGRET (SERC, Seattle, Washington) on a standard 80386-SX-based personal computer (Vectra RS/20C, Hewlett Packard, Palo Alto, California). Survival time in person-days was measured from the time of the exercise test and was censored at the time of noncardiac death, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty. Survival Analysis Analysis was done to predict cardiovascular deaths and infarct-free survival (that is, cardiovascular death and nonfatal myocardial infarction). Kaplan-Meier survival curves were evaluated stratifying one or more variables to explore the data for interactions. The Cox proportional-hazard model was then applied to clinical and resting electrocardiographic variables, hemodynamic variables from treadmill testing, and electrocardiographic changes and angina during the treadmill test. Each variable grouping was also analyzed independently and by combining the strongest or most logical variables. Analysis was also done on the total group, including those who underwent catheterization (588 patients) because they were seen before the decision to catheterize. Results Follow-up Computed clinical information was available for all 2546 patients, and follow-up was initiated in February 1991. Of these, 85% were confirmed to be alive by a clinic visit or prescription filled at a minimum of 1 year after their treadmill date, and 187 (7.5%) had died after a mean follow-up period of 45 17 months. Contact either by telephone or letter led to follow-up and verification of vital status in 99%. After review of autopsy, death certificate, or hospital charts, 119 of the deaths (63%) were classified as cardiovascular. Forty-four patients had nonfatal myocardial infarctions, 34 developed congestive heart failure, 46 underwent coronary bypass surgery, and 18 received one or more angioplasties. The average annual cardiac mortality rate was 1.5%. Clinical Characteristics Table 1 shows the clinical characteristics of the study cohort grouped by end point. The mean age (SD) was 59 10 years. One fifth of the patients had typical angina pectoris, and one fifth had a history of previous myocardial infarction or electrocardiograms with diagnostic Q waves. Medications were not changed or withheld before exercise testing; 22% were taking -blockers, and 8% were taking digoxin. Statistically significant differences between the no cardiovascular event and cardiovascular death groups were observed for age, congestive heart failure, myocardial infarction, digoxin use, and most resting electrocardiographic abnormalities (P < 0.01). Table 1. Clinical Features of the Total Study Population and Number and Percentage with a Given End Point Hemodynamic and Electrocardiographic Responses Group averages for pre-exercise standing heart rate, systolic blood pressure, and double product were 76 beats per minute, 130 mm Hg, and 9800 (heart rate times systolic blood pressure), respectively. Table 2 shows the hemodynamic and electrocardiographic responses during the exercise test. No significant differences were found among end point groups for perceived exertion and occurrence of premature ventricular contractions. Table 2. Hemodynamic and Exercise Electrocardiographic Features of the Total Study Population* Cox Proportional Hazards Model The univariate scores and P values for the variables are listed in Appendix Table. No significant interactions were discovered, and thus none are included. Similar results were obtained both when infarct-free survival was considered as an end point (variable order, coefficients, and level of significance) and when the entire cohort was analyzed. The score test statistic listed is the relative weight or importance assigned the variables in the Cox model. Using stepwise selection, the Cox model was allowed to build on each variable group (clinical variables alone entered first with subsequent addition of other variables) to arrive at the final model that chose history of congestive heart failure or digoxin use, the change in systolic blood pressure score, exercise capacity (METs), and exercise-induced ST depression. A score was then formed using the coefficients from the Cox model with only these four variables entered as follows: 5 x (congestive heart failure or digoxin use [yes = 1; no = 0]) + exercise-induced ST depression in millimeters + change in systolic blood pressure score METs. Three groups were formed using a scoring system in which 2 indicated low risk, 2 to 2 indicated moderate risk, and greater than 2 indicated high risk. The hazard ratios, confidence intervals (CIs), and P values for these groups are shown in Table 3, and the Kaplan-Meier survival curves are shown in Figure 1. This score enabled identification of a low-risk group (77% of the cohort) with an annual cardiovascular mortality rate of less th

Comparison of ST segment/heart rate index to standard ST criteria for analysis of exercise electrocardiogram.

The objective of our study was to compare the discriminating power of a proposed ST segment/heart rate index with that of a standard method of assessing exercise-induced ST segment depression for diagnosing coronary artery disease. We used a cross-sectional retrospective analysis of exercise test and coronary angiographic data. The study took place in a 1,200-bed Veterans Affairs Medical Center; participants were 328 male patients who had undergone both a sign and symptom-limited treadmill test and coronary angiography. The sensitivity of the ST segment/heart rate index was 54% at a cut point of 0.021 mm/(beats/min), corresponding to a specificity of 73%. The standard visual ST segment analysis had a sensitivity of 58% at this same specificity, which corresponded to an ST segment cut point of 1-mm depression relative to rest (p = NS). Similarly, for diagnosing three-vessel or left main coronary disease, no significant difference was found between the sensitivities or the two measurements at cut points of equivalent specificity. In this consecutive series of patients presenting for routine clinical testing, the ST segment/heart rate index did not improve the diagnostic accuracy of the exercise test for identifying the presence or severity of coronary artery disease relative to standard visual criteria.

Correlation between resting ST segment depression, exercise testing, coronary angiography, and long-term prognosis

Resting ST segment depression has been identified as a marker for adverse cardiac events in patients with and without known coronary artery disease. To correlate this with exercise testing, coronary angiography, and how it impacts on long-term prognosis, a retrospective study was performed on 476 patients, of whom 223 had no clinical or electrocardiographic evidence of prior myocardial infarction while 253 were survivors of an infarction. All patients performed a standard exercise test and underwent diagnostic coronary angiography within an average of 32 days of their exercise test (range 0 to 90 days). Exclusions were women, those with left bundle branch block, left ventricular hypertrophy, use of digoxin, previous revascularization procedures, or significant valvular or congenital heart disease. Long-term follow-up was carried out for an average of 45 months (+/- 17). Of the patients without prior infarction, 23 (10%) had persistent resting ST segment depression, and of those with a prior history of infarction, 37 (15%) also had resting ST segment depression. Patients with resting ST segment depression and no prior myocardial infarction had a higher prevalence of severe coronary disease (three-vessel and/or left main) (30%) than those without resting ST segment depression (16%) (95% confidence interval [CI] for observed difference -5.0% to 33.9%, p = 0.12). The criterion of greater than or equal to 2 mm of additional exercise-induced ST segment depression was a particularly useful marker in these patients for the diagnosis of any coronary disease (likelihood ratio 3.35, 95% CI 0.56 to 19.93, p = 0.06). Patients with resting ST segment depression and a prior myocardial infarction had a 2.5 times higher prevalence of severe coronary artery disease compared with patients without resting ST segment depression (43% versus 17% prevalence, respectively, 95% CI for observed difference 9.38% to 42.8%, p less than 0.001) and also had larger left ventricles postinfarction (left ventricular end-diastolic volume index 102 ml/m2 compared with 96 ml/m2, p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Usefulness of exercise-induced ST-segment depression in the inferior leads during exercise testing as a marker for coronary artery disease.

Multiple lead systems are shown to have a higher sensitivity than that of single leads for detecting coronary artery disease (CAD) during exercise testing, but the value of ST-segment depression isolated to the inferior leads is questionable. To ascertain the diagnostic accuracy of inferior limb lead II compared with that of precordial lead V5, a retrospective analysis of 173 men was performed (108 in a training population and 65 in a validation cohort). All patients had a standard exercise test and underwent diagnostic coronary angiography within 15 days of the exercise test (range 1 to 65). Sixty-three patients had greater than or equal to 1 coronary stenoses greater than or equal to 70%, or left main lesion greater than or equal to 50%, whereas 45 patients in the training population did not. Exclusion criteria were female sex, left ventricular hypertrophy, left bundle branch block or resting ST-segment depression on the baseline electrocardiogram, previous myocardial infarction or revascularization procedures, and any significant valvular or congenital heart disease. Lead V5 had a better combination of sensitivity (65%) and specificity (84%) (chi-square = 24.11; p less than 0.001) than that of lead II (sensitivity 71%, specificity 44%) (chi-square = 2.25; p = 0.13) at a single cut point, and this improved specificity was substantial (95% confidence interval for observed difference 22 to 58%). Receiver-operating characteristic curve analysis also revealed that lead V5 (area = 0.759) was markedly superior to lead II (area = 0.582) over multiple cut points (z = 3.032; 2p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Altered ventricular repolarization in central sympathetic dysfunction associated with spinal cord injury

Complete injury to the cervical spinal cord results in total disruption of central sympathetic outflow. Although ventricular repolarization can be significantly influenced by disorders of autonomic function, the effects of cervical sympathectomy are unknown. Therefore, 40 subjects with complete chronic spinal cord injury were prospectively divided into 2 groups, half with total disruption of central sympathetic outflow (level of injury C5 to C8) known as the high level injury group, and half with nearly intact sympathetic innervation (T10 to L1) serving as controls. The completeness of autonomic dysfunction was verified by the cold pressor response. ST-segment analysis of the resting surface electrocardiogram revealed multilead ST elevation in the high level injury group, with maximum ST height significantly higher than the control group (131 +/- 21 [standard error] vs 47 +/- 8 microV; p = 0.0005). Unlike the control subjects, maximal arm ergometry exercise in the high level injury subjects failed to decrease ST-segment height (delta ST = -3 +/- 6 vs -43 +/- 14 microV in controls; p = 0.02). This difference persisted even after matching for exercise capacity. However, during exogenous stimulation with the sympathomimetic amine isoproterenol, ST-segment height in the high level injury group markedly decreased (mean delta ST = -84 +/- 26 vs -17 +/- 18 microV in controls; p = 0.04). Thus, central sympathetic dysfunction regularly results in multilead ST-segment elevation that decreases to or below isoelectric baseline during low dose isoproterenol infusion. Unlike normal subjects and individuals with normal variant ST-segment elevation, ST height is not altered by exercise. These findings document that ST-segment height in man is greatly influenced by central sympathetic nervous activity both at baseline and during physiologic and pharmacologic stress.

Comparison of Silent and Symptomatic Ischemia during Exercise Testing in Men

OBJECTIVE To compare angina and ST-segment depression during exercise testing, as markers for coronary artery disease. DESIGN Retrospective analysis of exercise test responses and cardiac catheterization results. SETTING A U.S. Veterans Affairs medical center. PATIENTS Four hundred and sixteen men who were referred for the evaluation of symptoms, postmyocardial infarction testing, or both. Two hundred patients had no clinical or electrocardiographic evidence of previous myocardial infarction, whereas 216 were survivors of a previous myocardial infarction. INTERVENTIONS All patients did a standard exercise test and had diagnostic coronary angiography with ventriculography within an average of 32 days (range, 0 to 90 days) of their exercise test. RESULTS Two hundred patients without a previous myocardial infarction were divided into four groups: the no ischemia group had 80 patients; the angina pectoris only group had 23 patients; the silent ischemia group had 40 patients; and the ST-segment depression and angina pectoris group had 57 patients. In patients without a previous myocardial infarction, exercise-induced ST-segment depression was a better marker than exercise-induced angina for the presence of any coronary artery disease (P less than 0.005). Patients with symptomatic exercise-induced ischemia had a higher prevalence of severe coronary artery disease than did those with only silent ischemia (30% compared with 20%; 95% CI, - 7.3% to 27.0%; P = 0.005). For the 216 survivors of a myocardial infarction, divided into the same four groups, ST-segment depression again was a better marker for the presence of severe coronary artery disease compared with angina alone (P = 0.08). The prevalence rates of severe coronary artery disease in the no ischemia plus myocardial infarction group, the angina pectoris only plus myocardial infarction group, the silent ischemia plus myocardial infarction group, and the ST-segment depression and angina pectoris plus myocardial infarction group were 10%, 9%, 23%, and 32%, respectively (P less than 0.01). CONCLUSIONS Exercise-induced ST-segment depression is a better marker for coronary artery disease than is exercise-induced angina. Symptomatic ischemia during the exercise test is a better marker for severe coronary artery disease than is silent ischemia.

Exercise-induced ST depression and ST/heart rate index to predict triple-vessel or left main coronary disease: A multicenter analysis

The aim of this investigation was to determine the difference in accuracy between two frequently published noninvasive indicators of severity of coronary artery disease (exercise-induced ST segment depression and heart rate-adjusted ST depression [ST/HR index]). The study was designed as a survey of consecutive patients undergoing exercise electrocardiography and coronary angiography. There were a total of 2,270 patients without prior myocardial infarction or cardiac valvular disease referred for angiography from eight institutions in three countries; 401 of these patients had triple-vessel or left main coronary artery disease. The sensitivities of ST depression and ST/HR index in detecting triple-vessel or left main coronary artery disease were, respectively, 75% and 78% (p = 0.08) at cut point values where their specificities were equal (64%). This small increase in the accuracy of the ST/HR index was evident only at peak exercise heart rates below the median value of 132 beats/min, where the sensitivities of ST depression and ST/HR index were 73% and 76% (p = 0.03), respectively, at cut point values corresponding to a specificity of 60%. These results were consistent at all eight participating institutions. The increase in accuracy achieved by dividing exercise-induced ST depression by heart rate is small and confined exclusively to a low exercise heart rate. This lack of superiority cannot be generalized to all methods of heart rate adjustment.