Failure of right precordial electrocardiography during stress testing to identify coronary artery disease.

BACKGROUND: It has been reported that the use of right precordial leads results in the same diagnostic accuracy as thallium-201 exercise scintigraphy for the detection of coronary artery disease (CAD). The aim of this study was to evaluate the utility of right precordial leads in the detection of CAD. METHODS AND RESULTS: We evaluated 900 consecutive patients (514 men, 386 women) ranging in age from 39 to 84 years (mean +/- SD, 64 +/- 11 years). Seven hundred forty patients underwent treadmill exercise testing, and 160 underwent pharmacologic stress testing for the diagnosis of chest pain or dyspnea. All received either Tl-201 or technetium-99m sestamibi during stress. During stress testing, the ECG was recorded every minute with 12 limb and left precordial leads and 3 right precordial leads (V(3)R, V(4)R, and V(5)R). The electrocardiogram was considered positive when the ST segment was either elevated or depressed by at least 0.1 mV at 80 ms after the J point, and results were also compared with single photon emission computed tomography myocardial perfusion imaging results. Of the 900 patients, 158 had significant positive changes in the limb or left precordial leads. Only 4 patients had positive changes in the right precordial leads (Fisher exact test, P <.001). Of the patients who had positive electrocardiographic changes, 95 (60%) had abnormal myocardial perfusion scans, with 91 in patients with normal right precordial leads. All 4 patients with ischemic changes in the right precordial leads had abnormal scans, but the left leads were also positive. Three hundred seventy-three of 900 patients (41%) had abnormal scans with no electrocardiographic evidence of ischemia. CONCLUSIONS: Our experience is far different than that published and suggests that the use of right precordial leads during stress testing fails to provide the same diagnostic accuracy as either the standard left-sided electrocardiography or myocardial perfusion imaging for the detection of CAD.

Assessment of left ventricular function by real-time 3-dimensional echocardiography compared with conventional noninvasive methods.

Quantitative assessment of left ventricular ejection fraction is an essential component of cardiac evaluation. We performed real-time 3-dimensional echocardiography in 56 consecutive patients who underwent multigated radionuclide angiography. Thirteen patients were excluded for the following reasons: 5 for large size of left ventricle required for image acquisition, 5 for suboptimal image quality in real-time 3-dimensional echocardiography, and 3 for atrial fibrillation. Finally, we compared left ventricular ejection fraction assessed by real-time 3-dimensional echocardiography and conventional 2-dimensional echocardiography with that obtained by multigated radionuclide angiography in 43 patients. Left ventricular ejection fraction was determined by real-time 3-dimensional echocardiography with the use of parallel plane-disks and sector plane-disks summation methods. A good correlation was obtained between both real-time 3-dimensional echocardiography methods and multigated radionuclide angiography (r = 0.87 and 0.90, standard error of estimate = 3.7% and 4.2%), whereas the relation between the 2-dimensional echocardiography method and radionuclide angiography demonstrated a significant departure from the line of identity (P <.001). In addition, interobserver variability was significantly lower (P <.05) for the real-time 3-dimensional echocardiography methods than that by the 2-dimensional echocardiography method. Real-time 3-dimensional echocardiography may be used for quantification of left ventricular function as an alternative to conventional methods in patients with adequate image quality.

Feasibility of a two-dimensional echocardiographic method for the clinical assessment of right ventricular volume and function in children.

The relative ease of acquisition and safety of two-dimensional echocardiography has established it as the mainstay for routine cardiac imaging. Translation of imaging data into useful quantitative information, however, requires fitting the ventricle to a specific geometric model. Because of its complex shape and anterior position, many attempts at right ventricular quantitation by two-dimensional echocardiography have been criticized as impractical and not reproducible. A simple method incorporating subcostal and apical imaging was introduced in 1984. This approach appeared to combine accuracy and practicability but was never validated in a clinical setting because of the difficulties of subcostal imaging in adults. This study assessed the feasibility and accuracy of this technique in the pediatric population. Results of volume comparison to values derived by magnetic resonance imaging were r = 0.96, standard error of the estimate (SEE) = 19.3 ml, and mean difference = 15 +/- 19.4 ml and r = 0.97, SEE = 12.3 ml, and bias = 5 +/- 11.8 ml for diastolic and systolic volumes, respectively. Comparison of estimates of ejection fraction with magnetic resonance imaging demonstrated r = 0.90, SEE = 5.9%, and bias = 3% +/- 5.7%. Interobserver and intraobserver variability was 9.9% and 8.2%, respectively, for systolic volumes and 11.5% and 8.9%, respectively, for diastolic volumes. Evaluation of right ventricular size and function by this approach is comparable to determinations by magnetic resonance imaging and may be clinically useful in the management of pediatric patients.

Assessment of cardiac function by three-dimensional echocardiography compared with conventional noninvasive methods.

BACKGROUND: Reliable, serial, noninvasive quantitative estimation of left ventricular ejection fraction is essential for selecting and timing therapeutic interventions in patients with heart disease. Equilibrium radionuclide angiography is widely used for this purpose but has well-recognized limitations. Advantages of echocardiography over equilibrium radionuclide angiography include assessment of wall motion, valvular pathology, and cardiac hemodynamics, in addition to portability, lack of radiation exposure, and substantially lower cost. However, conventional echocardiographic techniques are limited by geometric assumptions, image positioning errors, and use of subjective visual methods. To overcome these limitations, a three-dimensional echocardiographic method was developed. This study compares ejection fraction by three-dimensional echocardiography, quantitative two-dimensional echocardiography, and subjective two-dimensional echocardiographic visual estimation with that by equilibrium radionuclide angiography. METHODS AND RESULTS: Fifty-one unselected patients with suspected heart disease underwent left ventricular ejection fraction determination by equilibrium radionuclide angiography and three-dimensional echocardiography using an interactive line-of-intersection display and a new algorithm, ventricular surface reconstruction, for volume computation. In 44 patients, ejection fractions were also estimated visually by experienced observers from two-dimensional echocardiography and by quantitative two-dimensional echocardiography using an apical biplane summation-of-disks algorithm. An excellent correlation was obtained between three-dimensional echocardiography and equilibrium radionuclide angiography (r = .94 to .97, SEE = 3.64% to 5.35%; limits of agreement, 10.3% to 13.3%) without significant underestimation or overestimation. SEE values and limits of agreement were twofold to threefold lower than corresponding values for all two-dimensional echocardiographic techniques. In addition, interobserver variability was significantly lower for the three-dimensional echocardiographic method (10.2%) than for the apical biplane summation-of-disks method (26.1%) and subjective visual estimation (33.3%). CONCLUSIONS: Determination of ejection fraction by three-dimensional echocardiography yields results comparable to those obtained by equilibrium radionuclide angiography and is substantially superior to all two-dimensional echocardiographic methods. Therefore, three-dimensional echocardiography may be used for accurate serial quantification of left ventricular function as an alternative to equilibrium radionuclide angiography.

Thallium-201 lung uptake and peak treadmill exercise first-pass ejection fraction.

Increased thallium-201 lung uptake immediately after exercise has been shown (1) to be a marker for extensive coronary artery disease, (2) to correlate with low rest and exercise left ventricular ejection fraction by supine gated blood pool scintigraphy, and (3) to be a powerful independent predictor of future cardiac events. Exercise left ventricular ejection fraction measured during upright exercise by the first-pass technique has also been shown to be a powerful independent prognostic variable. Combined perfusion and exercise left ventricular ejection fraction can be acquired by using the technetium 99m-based myocardial perfusion agents and offers an alternative protocol to stress/redistribution thallium imaging. It is therefore clinically important to understand the relation between exercise lung heart thallium uptake and exercise left ventricular ejection fraction. Accordingly, both these measurements were acquired in 38 patients with documented coronary artery disease who underwent two treadmill exercise studies. Parameters obtained from the first-pass study that are known to affect lung thallium uptake were correlated with exercise lung/heart thallium ratios; lung/heart ratios were used in a model to predict exercise left ventricular ejection fraction values. Exercise left ventricular ejection fraction and peak filling rate showed significant negative correlations with thallium lung/heart ratio, but the first-pass variables examined were not independently predictive of thallium lung uptake. The chance of finding an abnormal thallium lung/heart ratio at exercise LVEF of 40% is only 52%, whereas the chance of finding an abnormal ratio at exercise LVEF of 30% is 74%.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion scintigraphy in heart transplant recipients with and without allograft atherosclerosis: a comparison of thallium-201 and technetium 99m sestamibi.

Our objectives were to assess the comparative value of thallium-201 and technetium 99m sestamibi for the detection of cardiac allograft atherosclerosis and the left ventricular ejection fraction response to exercise in heart transplant recipients with and without allograft atherosclerosis. Allograft atherosclerosis is the critical factor limiting long-term survival in heart transplant recipients. Annual coronary angiography is invasive and expensive. A noninvasive test to detect allograft atherosclerosis would be clinically useful. Treadmill exercise testing followed by myocardial perfusion single-photon computed tomographic imaging was performed in 25 heart transplant recipients. All patients underwent coronary angiography. Group 1 (13 patients) had angiographic coronary artery disease; group 2 (12 patients) did not. Eighteen patients underwent two exercise tests to equivalent work loads with thallium-201 and technetium 99m sestamibi; seven patients underwent only thallium-201 imaging. First-pass left ventricular ejection fraction was measured during injection of technetium 99m sestamibi. In group 1, 10 of 13 patients had abnormal thallium-201 scans. There was no significant difference in the number of patients who had abnormal thallium-201 (7/10) and technetium 99m sestamibi scans (6/10). Fifty-two percent (12/23) of discordantly scored segments were reversible on thallium-201 and fixed on technetium 99m sestamibi imaging compared with the opposite (0%; 0/23) (p < 0.01). All patients in group 2 had normal perfusion scans. There were no false-positive scans.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of silent myocardial ischemia on a thallium stress test.

The clinical significance of silent ischemia is not fully known. The purpose of this study was to determine whether the presence or absence of angina during a thallium stress test positive for ischemia was independently predictive of an adverse outcome. Two hundred thirty-four consecutive patients with ischemia on a thallium stress test were identified. Ischemia was defined as the presence of defect(s) on the immediate postexercise scans not in the distribution of prior infarctions that redistributed on 4-hour scans. During the test 129 patients had angina, defined as characteristic neck, jaw, arm, back or chest discomfort, while the remaining 105 patients had no angina. Follow-up ranged from 2 to 8.2 years (mean 5.2 +/- 2.1) and was successfully obtained in 156 patients. Eighty-two of the 156 patients had angina (group A) and 74 had silent ischemia (group S). Group A patients were significantly older (62 +/- 8 vs 59 +/- 8 years, p less than 0.05). There was no significant difference between the 2 groups in terms of sex, history of prior infarction or presence of left main/3-vessel disease. A larger percentage of patients in group A were receiving beta blockers (60 vs 41%, p less than 0.05) and nitrates (52 vs 36%, 0.05 less than p less than 0.10). There was a large number of cardiac events (myocardial infarction, revascularization and death) in both groups (37 of 82 [45%] in group A; 28 of 72 [38%] in group S) but no statistically significant difference between the groups. Similarly, life-table analysis revealed no difference in mortality between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy.

Myocardial perfusion in ten normal volunteers and 20 patients with coronary artery disease documented by recent coronary arteriography was studied with 99mTc-labeled SQ30217 and 201TI. Plantar 201TI imaging followed standard treadmill exercise and planar SQ30217 imaging followed upright bicycle exercise, performed to angina, or the same double product achieved on the treadmill test. Upright anterior, 30 degrees left anterior oblique, and 60 degrees left anterior oblique images were obtained for 3, 6, and 9 min, respectively, starting 2 min after injection of 15 mCi of 99mTc SQ30217. A second 15-mCi dose was injected at rest approximately 2 hr later, and the same imaging protocol was followed. No adverse reactions or laboratory abnormalities attributable to SQ30217 were observed. All scans on the normal volunteers were interpreted as normal. Qualitative readings of both tests were equally sensitive for detecting patients with coronary disease (SQ30217 - 16/20, TI - 17/20, p = NS) and identifying abnormal vessels (SQ30217 - 19/45, TI - 21/45, p = NS). Both agents were falsely positive in 1/15 vessels. Ten vascular regions showed persistent abnormalities on resting SQ30217 scans; eight of these were distal to stenoses of at least 90% and three were also abnormal on thallium redistribution images. Hepatic uptake of SQ30217 obscured inferoapical segments in some views in 14/20 patients but did not interfere with abnormal vessel identification.

Effect of isolated proximal coronary stenotic lesions on distal myocardial perfusion during exercise.

This study tested the hypothesis that the absolute dimension of a coronary stenotic lesion is a more important determinant of its hemodynamic effect on regional myocardial perfusion during exercise than is relative percent stenosis. In 31 patients with an isolated lesion of the left anterior descending coronary artery, regional myocardial perfusion was determined from thallium-201 scans recorded in the left anterior oblique projection after symptom-limited treadmill exercise. Thallium-201 uptake in the distribution of the left anterior descending coronary artery was expressed as a ratio of thallium-201 uptake in the left circumflex artery distribution. Percent area stenosis, minimal cross-sectional area and mean diameter of each stenotic lesion were measured by computer-assisted cinevideodensitometric analysis of projected coronary arteriograms digitized in a 512 X 512 pixel matrix with 256 gray levels. Thallium-201 uptake in the left anterior descending coronary artery distribution, expressed as a ratio, correlated poorly (r = 0.65) with relative percent stenosis, but correlated significantly (r = 0.83; p less than 0.05) with absolute lesion area. For all 16 patients with reduced regional perfusion in the left anterior descending coronary artery distribution during exercise, lesion cross-sectional area was less than 1.8 mm2 (mean 0.9 +/- 0.6); for 13 of the 15 patients with normal distal perfusion, the area of the stenotic lesion was greater than 1.8 mm2 (mean 2.7 +/- 0.7; p less than 0.001). Percent coronary stenosis failed to predict flow-limiting lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of the electrocardiographic effects of phenelzine, tricyclic antidepressants, mianserin, and placebo.

Although the electrocardiographic effects of the tricyclic antidepressants have been extensively investigated, there are fewer data on the effects of monoamine oxidase inhibitors and tetracyclics on cardiac conduction. This study used high speed recordings of the electrocardiogram to investigate the cardiographic effects of phenelzine and mianserin and to compare these to the effects of imipramine, amitriptyline, and placebo. Phenelzine caused significant slowing of the heart rate, while mianserin showed little effect on heart rate compared to the increases in rate seen with tricyclics. In clinically effective doses, neither phenelzine nor mianserin caused changes in conduction, while both tricyclics studied caused the expected prolongation of conduction. These data suggest that phenelzine and mianserin deserve further study in patients with disease of the cardiac system as they may be less likely to cause heart block in these patients.

Plasma lactate and ventilation thresholds in trained and untrained cyclists.

Six trained male cyclists and six untrained sedentary men were studied to determine whether the plasma lactate threshold (PLT) and ventilation threshold (VT) occur at the same work rate in both fit and unfit populations. The PLT was determined from a marked increase in plasma lactate concentration ([La]) and VT from a nonlinear increase in expired minute ventilation (VE) during incremental leg-cycling tests; work rate was increased 30 W every 2 min until volitional exhaustion. The trained subjects' mean VO2 max (63.8 ml O2 X kg-1 X min-1) and VT (65.8% VO2 max) were significantly higher (P less than 0.05) than the untrained subjects' mean VO2max (35.5 ml O2 X kg-1 X min-1) and VT (51.4% VO2 max). The trained subjects' mean PLT (68.8% VO2 max) and VT did not differ significantly, but the untrained subjects' mean PLT (61.6% VO2 max) was significantly higher than their VT. The trained subjects' mean peak [La] (10.5 mmol X l-1) did not differ significantly from the untrained subjects' mean peak [La] (11.5 mmol X l-1). However, the time of appearance of the peak [La] during passive recovery was inversely related to VO2 max. These results suggest that variance in lactate diffusion and/or removal processes between the trained and untrained subjects may account in part for the different relationships between the VT and PLT in each population.

Bayesian analysis using Fourier transforms of thallium-201 scintiscans to predict the presence of coronary artery disease.

Bayes' theorem of conditional probability was applied to the diagnosis of coronary artery disease (CAD) using thallium-201 scintigraphy as the testing procedure. Thallium-201 scintiscans were evaluated with a discriminant function previously developed using the amplitude coefficients of the Fourier transforms of the scans. The technique was applied prospectively to a population of 100 patients undergoing diagnostic coronary arteriography and thallium-201 scintigraphy, including 83 patients with CAD (70% or greater stenosis of luminal diameter) and 17 control subjects. A pretest probability of CAD was determined for each patient from the patient's age, sex and anginal symptoms. The pretest probability was combined with the patient's discriminant score to determine a posttest probability for CAD. For patients with CAD, the mean posttest probability was 0.85. Moreover, 57 of 83 patients (69%) had posttest probabilities exceeding 90%, including 40 patients (48%) with posttest probabilities exceeding 99%. For control subjects, the mean posttest probability was 0.19, with 11 of 17 (65%) having a posttest probability of less than 10%. Overall, 68 subjects had a posttest probability either less than 10% or more than 90% of which 63 were correctly classified (93%). Using a 50% posttest probability as a cutoff for classification, the technique has an 89% sensitivity, an 82% specificity and an overall accuracy of 88%. Therefore, this method objectively distinguishes patients with CAD from control subjects and provides a measure of the certainty of diagnosis. In addition, the discriminant function avoids the problem of inter- and intraobserver variability in visually interpreting thallium-201 scans.

Relationship between segmental thallium-201 uptake and regional myocardial blood flow in patients with coronary artery disease.

The relationship between the spatial distribution of thallium-201 in myocardial perfusion scintigrams and the distribution of left ventricular regional myocardial blood flow was examined in 25 patients undergoing coronary arteriography. Thallium-201 myocardial scintigrams were obtained after symptom-limited exercise and after a 4 hr delay. Regional myocardial blood flow was measured by the xenon-133 clearance method in patients at rest and during rapid atrial pacing to a double product comparable with that achieved during exercise stress testing. Patterns of regional thallium-201 activity and regional myocardial blood flow, recorded in similar left anterior oblique projections, were compared for left ventricular segments supplied by the left anterior descending (LAD) and left circumflex (CIRC) arteries. In 11 patients without significant lesions of the left coronary artery (group 1), thallium-201 was homogeneously distributed in the LAD and CIRC distributions in scintigrams taken during peak exercise; these scintigrams correspond to homogeneous regional myocardial blood flow in the LAD and CIRC regions during pacing-induced stress. In 14 patients with significant lesions of the left coronary artery (group 2), ratios of regional thallium-201 activity in the LAD and CIRC distributions of exercise scintigrams correlated well (r = .84) with ratios of regional myocardial blood flow measured during rapid pacing. Background subtraction altered the relationship between relative thallium-201 uptake and regional myocardial blood flow, causing overestimation of the magnitude of flow reduction on exercise scintigrams. These data indicate that: (1) in patients with normal left coronary arteries, thallium-201 is homogeneously distributed to the left ventricle, reflecting the homogeneous distribution of regional myocardial blood flow over a wide range of mean left ventricular flow rates and (2) in patients with significant lesions of the left coronary artery, the relative spatial distribution of thallium-201 activity in exercise perfusion scintigrams reflects the distribution of regional myocardial blood flow.

Lactate accumulation relative to the anaerobic and respiratory compensation thresholds.

Anaerobic thresholds of five male subjects were determined invasively (ATi), from a marked increase in plasma lactate above resting levels (delta La), and noninvasively (ATn), from a nonlinear increase in minute ventilation (VE) during incremental work (IW) leg cycling tests; work rate was increased 30 W every 2 min. Each subject also performed four constant-load work (CLW) tasks just above and just below their ATn and respiratory compensation threshold (RCT), i.e., the point expressed as O2 consumption (VO2) or work rate, at which VE increases disproportionally to CO2 output during IW. In four of the five subjects the ATn preceded the ATi during IW. Yet the ATn delineated the CLW in which marked lactate accumulation did or did not occur. During CLW just above the ATn in these same four subjects, VE/VO2 and fractional expired O2 (FEO2) peaked well before delta La plateaued. These findings suggest that exercise hyperventilation is not necessarily proportional to increases in plasma lactate.

Type A behavior and the thallium stress test.

Several recent studies have examined the association between Type A personality and coronary artery disease (CAD) by coronary angiography. Most of these studies have reported a significant association. The present study is an attempt at further confirmation, using a new non-invasive technique for measuring CAD. Subjects were 53 patients undergoing routine exercise stress tests with concomitant thallium-201 myocardial perfusion studies. Five aspects of Type A behavior were assessed by the use of the Rosenman-Friedman Semistructured Interview, and each was rated on a three-point scale. Severity of CAD was independently estimated on a four-point scale. Pearson correlation coefficients were separately computed for patients with and without reported history of myocardial infarction (MI). For 37 patients without reported MI, CAD severity was significantly correlated with Overall Type A (r = -0.53), Vocal Characteristics (r = -0.53), Job Involvement (r = -0.36) and Aggressiveness (r = -0.48), but not Time Urgency (r = -0.25). For 16 patients with reported MI, CAD severity was significantly correlated with Job Involvement only (r = +0.49). The data are consistent with the association of Type A personality and coronary atherogenesis, but may also reflect Type A psychological and physiological characteristics. Future studies may be able to examine these and other aspects of Type A behavior using this noninvasive technique in more diverse patient populations.

Comparison of two radionuclide techniques for detecting disease of right and left coronary arteries.

Radionuclide angiography and thallium-201 myocardial perfusion scintigraphy were compared in 31 patients with coronary artery disease studied at rest and during exercise. Seventeen of the 31 patients had perfusion defects on thallium-201 redistribution scans (61%); 16 of these had prior transmural infarction. Six other patients with prior inferior infarction had no defects on thallium-201 redistribution scans. During treadmill exercise, 28 of 31 patients (90%) developed new or larger thallium-201 perfusion defects, a significantly higher percentage of patients than those that developed ST segment abnormalities during exercise (74%). During bicycle exercise left ventricular ejection fraction decreased in 27 of the 31 patients (87%); the average change in left ventricular ejection fraction was from 54 +/- 16+ to 48 +/- 14% (p less than 0.1). Twenty-three of the 31 patients had abnormalities of regional ejection fraction at rest (74%), while 30 of the 31 had abnormalities during exercise (97%). The number of patients who developed new regional ejection fraction abnormalities during exercise (28 of 31) was not significantly different from the number of patients who developed new or larger thallium-201 myocardial perfusion defects during exercise. In order to compare the two radionuclide techniques with respect to identification of vessel involvement, the patients were separated into those with disease of the right coronary system, disease of the left coronary system, or both. Thallium-201 scintigraphy correctly identified ten of 14 patients with involvement of only the right or left system; radionuclide angiography correctly identified six of 14. However, radionuclide angiography identified more patients with right and left system involvement (15/17) than did thallium-201 scintigraphy (6/17), p less than .01. These data suggest radionuclide angiography is more useful for identifying patients with disease of both the right and left coronary arteries.