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.

Quality improvement on an academic autopsy service.

CONTEXT: Autopsy rates continue to decline in the United States. OBJECTIVE: Although many of the causes of this decline are external to pathology departments, we hypothesized that intradepartmental efforts to improve the quality of the service we provide to our clinical colleagues could increase our autopsy rate. METHOD: We developed a multifaceted quality improvement program for our autopsy service aimed at increasing the visibility of the service, improving the service's reporting, and increasing the amount and quality of data available from the service. SETTING: A large academic medical center that performs approximately 250 autopsies each year. RESULTS: After implementation of our quality improvement program, the decline in our autopsy rate has not only stopped, but rates have even begun to increase. Additionally, physician satisfaction surveys conducted before and after implementation of our quality improvement initiatives showed an across-the-board improvement in clinician perception of the service. CONCLUSION: Pathologists can and should be proactive in addressing the declining autopsy rate, rather than viewing it as someone else's problem or hoping that someone else will protect this important quality assurance tool for medical care.

Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.

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.

Association of postprandial triglyceride and retinyl palmitate responses with newly diagnosed exercise-induced myocardial ischemia in middle-aged men and women.

Although strong evidence exists linking fasting plasma levels of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) to risk for development of coronary artery disease (CAD), the data in support of an independent role for fasting triglyceride (TG) concentrations are weak. Humans are in the postprandial state most of the day, however, and results from both basic and clinical studies suggest that postprandial TG levels may be atherogenic. Previous studies have not, however, attempted to determine if postprandial TG levels are associated with CAD independent of other traditional risk factors or plasma lipid levels, particularly fasting plasma concentrations of TG and HDL-C. Ninety-two men and 113 women (mean age, 51.6 and 53.6 years, respectively) were recruited from populations undergoing diagnostic exercise electrocardiographic or thallium stress tests at our medical centers. Twenty-six men and 24 women had positive tests. We chose exercise-induced myocardial ischemia (EIM) as the criterion for defining case and control subjects because we wanted participants who did not have a prior diagnosis of CAD. Blood samples were obtained for measurement of plasma TG, TG-rich lipoprotein TG, and retinyl palmitate (RP) levels 2, 3.5, 5, and 8 hours after the subjects had consumed a fatty test meal. Logistic regression models were developed to test for associations between each variable and case-control status. Among men but not women postprandial TG and RP responses were associated with EIMI independent of age, race, and smoking status. In the male group, the odds ratio (OR) for an increase in postprandial TG response of approximately 1 SD was 1.69 (P = .007); the OR for an increase in RP response of 1 SD was 2.47 (P = .011). However, when fasting TG was added to the model, the OR for postprandial TG area in the men was reduced to 1.44 (P = .17); the OR postprandial RP area in the men was reduced to 1.88 (P = .12). There was no effect of adding other risk factors, including LDL-C and HDL-C, to the model. Significant effect modification by body mass index (BMI) on the relationship between postprandial responses and case-control status was observed. In men with BMI < 30, the OR was 1.83 for postprandial TG (P = .041) and 2.77 for postprandial RP (P = .032) in models that included fasting TG, LDL-C, and hypertension.

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)

Effects of Title X "gag rule" upon women's attitudes towards their healthcare providers.

79 women were randomly assigned to conditions in which they received pregnancy counseling including abortion information or excluding abortion information (with or without a reminder of the "gag rule"). Subjects not given abortion information viewed their caregivers as more biased, less competent, less empathetic, and holding anti-abortion views compared to those receiving such information. Those not given abortion information but reminded of the "gag rule" viewed their caregivers with relative dislike and mistrust.

PIP: Before the lifting of the Title X gag rule in 1993, health caregivers from federally funded clinics were prohibited from providing abortion information to clients. In February 1992, 79 undergraduate women in business classes at the University of Connecticut were randomly assigned to one of three conditions (age range 18 to 29 years, M= 19.4 yrs, SD=2.1). Subjects read a written scenario, imagining they were pregnant and receiving information from a nurse at a health clinic. In the first condition, the nurse described all pregnancy options, including abortion (n=26). In the second condition, information on abortion was omitted (n=27). In the third condition, information on abortion was omitted and attributed to the gag rule (n=26). Subjects rated their attitudes toward abortion and the health caregiver on 7-point agree-disagree scales. Reliable composite scales measured attitudes toward the health caregiver in terms of credibility, perceived views on abortion, and empathy. Subjects held pro-abortion views, and the conservative Scheffe multiple-comparison test on one-way analyses was employed. Subjects in both groups for whom information on abortion was omitted viewed the healthcare provider as less credible than the group given information (p .01); however, the effect of the gag rule reminder was to reduce the likability and trustworthiness of the health caregiver (p .01). The group without information on abortion was more likely to infer the healthcare provider held anti-abortion views, but the gag rule reminder mediated this perception (p .01). Subjects from whom information on abortion was withheld perceived their health caregivers as less empathetic to their situation than the fully informed group (p .01). These findings suggest that women who are pro-abortion and who do not receive information on abortion during pregnancy counseling may view their health caregivers as incompetent or biased. The Title X gag rule may have adversely affected the quality of patient-caregiver relationships.

Effects of background music on anxiety, satisfaction with communication, and productivity.

Previous research on music's influences has often been nonconclusive, partly because subjective measures have been used for testing opposite conditions such as sedative versus stimulative music or happy versus sad music. Here, background music's influence upon 104 conversants was explored by manipulating the presence of music, and when present, by the more objectively assessed structural elements of mode and speed. Conversations taking place in the presence of background music were rated as more satisfying. Major mode music elicited higher ratings of satisfaction with communication than minor mode. Modality and speed interacted, illustrating the importance of not confounding music's structural elements when testing opposite conditions in studies of the effects of music. While background music did not affect productivity relative to no music, those hearing background music achieved greater productivity when music was in the major mode.

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.