Myocardial contrast echocardiography in human beings: correlation of resting perfusion defects to sestamibi single photon emission computed tomography.

The presence of myocardial perfusion abnormalities is generally accepted to suggest underlying coronary artery disease. In previous animal studies, myocardial contrast echocardiography (MCE) has been shown to be useful in delineating areas at risk after coronary occlusions. We sought to compare the presence or absence, size, and location of perfusion defects detected in human beings by MCE and sestamibi single photon emission computed tomography (SPECT). Regional wall motion was qualitatively assessed in the parasternal and apical views of a resting two-dimensional echocardiogram. Coronary angiography was performed in all patients and myocardial contrast echocardiography performed with 2 ml of intracoronary sonicated meglumine (Nycomed). A cine loop of the digitized contrast echocardiograms was used to analyze perfusion defects. Gated SPECT resting images in standard views were obtained after technetium 99m sestamibi (20 mCi) was administered. Visually perceived perfusion defects were established at 30% of maximal counts at end diastole. Perfusion defects by both techniques were planimetered, assigned to one of three perfusion artery territories, and expressed as a percentage of the perfusion territory studied. Comparison was made by linear regression analysis. Forty-one patients were studied. Perfusion defects were observed in 12 (29%) patients by MCE, 19 (46%) patients by SPECT, and 11 (27%) patients by both techniques. No perfusion defects were detected by MCE in 29 (70%) patients, by SPECT in 22 (53%) patients, or by either technique in 21 (51%) patients. The two techniques agreed in 78% of the patients. In 67 matching orthogonal views suitable for comparison between the two techniques, an 82% concordance for the presence or absence of defects was observed. The location of the defects matched in 86% of the cases. A significant correlation (p < 0.001; r = 0.62) between these techniques was observed in assessing the size of perfusion defects. In conclusion, our results suggest that MCE and sestamibi SPECT are comparable techniques for detecting severely underperfused myocardium in human beings.

Immunoassays for quantifying choriogonadotropin compared for assay performance and clinical application.

We examined calibration and accuracy, precision, sensitivity, specificity, and "hook" effects for recently revised automated choriogonadotropin (hCG) immunoassay systems (Baxter-Dade Stratus II, Abbott IMx intact hCG and total beta hCG) and compared them with a widely used immunoradiometric assay (Hybritech). We estimated hCG in pregnant women, women with trophoblastic disease, nonpregnant young and menopausal women, normal men, and men with testicular tumors. We found clinically unimportant differences in calibration (all calibrated to the 3rd International Standard). Detection of hCG by all four assays was limited by their responses in serum from nonpregnant women and men. Precision within-run was best for the automated instruments, but all four assays had similar between-run precision. The Hybritech, Stratus, and IMx intact assays are specific for intact hCG. The IMx total beta assay quantifies both free beta subunit and beta subunit present in intact hCG. There is a clinically important hook effect in the Hybritech assay but not the Stratus or IMx assays (to 1.2 x 10(6) int. units/L). Results for pregnant women were similar by all four assays. We measured "hCG" to 8 int. units/L in menopausal women, which weakly correlated with concentrations of lutropin and follitropin and was, in part, explained by crossreactivity. There was no sample-probe carryover in either instrument. We found the IMx diluting module as well as results at the extremes of the IMx calibration curves (less than 10, 800-1200 int. units/L) unreliable but encountered no such problems with the Stratus system. Both automated systems involve batch analyzers with limited throughput but provide hCG concentration estimates much more quickly than the Hybritech assay can.

Quantification of the reversibility of stress-induced thallium-201 myocardial perfusion defects: a multicenter trial using bull's-eye polar maps and standard normal limits.

A multicenter trial was performed on 140 patients from four centers to determine the accuracy of quantitative analysis of stress/delayed thallium-201 myocardial tomograms using normal limits to assess the relative amount of reversibility of stress-induced defects. The patients were found to have 85 fixed and 124 reversible defects, as determined by visual interpretation. Reversibility bull's-eye polar maps were compared to gender-matched normal limits from 36 normals. Regions were identified as reversible if their normalized difference between stress and 4 hr greater than 1.5 s.d.s. from the mean normal limits. Overall agreement between experts at multicenter sites and reversibility maps was 73% for reversible defects and 80% of fixed defects. Sensitivity in detecting reversibility was highest for the left circumflex (88%) and lowest for the right coronary (60%). These results indicate that reversibility polar maps and normal limits offer an objective, accurate technique for determining the reversibility of stress-induced perfusion defects.

Radionuclide bone/joint imaging in children with rheumatic complaints.

We reviewed the medical records and technetium bone/joint scans of 160 children presenting to the inpatient Pediatric Rheumatology service over a 3-year period. When the scan result (normal versus abnormal) was considered for each patient as a whole, scan sensitivity and specificity were both approximately 75%. However, when each joint was considered individually, sensitivity decreased to 37%, while specificity rose to more than 95% when compared to clinical examination. Reasons for these variations and their clinical correlation are discussed. Overall, radionuclide bone/joint scanning was found to be very useful in the evaluation of monoarticular and nonrheumatic disorders, but it did not alter therapy in children with known connective tissue disorders or other polyarticular diseases.

Chemically blocked analog assays for free thyronines. II. Use of equilibrium dialysis to optimize the displacement by chemical blockers of T4 analog and T3 analog from albumin while avoiding displacement of T4 and T3 from thyroxin-binding globulin.

Chemical blockers used to displace thyronine analog from albumin in analog kits for assay of free thyroxin (FT4) or free triiodothyronine (FT3) may also displace thyroxin (T4) or triiodothyronine (T3) from thyroxin-binding globulin (TBG), resulting in an apparent TBG dependence of results of free hormone estimates. We used equilibrium dialysis and antibody binding to assess the displacement of thyronine analogs and thyronines from albumin and TBG by use of chemical blockers. We chose a combination of two chemical blockers, which eliminated thyronine analog-albumin binding but minimized thyronine displacement from TBG for use in FT4 and FT3 assays. These blocked-analog free-hormone assays yielded accurate clinical results in euthyroid patients, hypo- and hyperthyroid patients, and in pregnant women. FT4 results were not entirely normalized in all nonthyroidally ill patients, indicating that decreased analog-albumin binding is not the only factor resulting in low FT4 results. In current Diagnostic Products Corp. (DPC) FT4 and FT3 blocked-analog kits, the blocker concentrations are the same as we used in these assays.

Chemically blocked analog assays for free thyronines. I. The effect of chemical blockers on T4 analog and T4 binding by albumin and by thyroxin-binding globulin.

Analog assays for free thyroxin (FT4) produce inaccurate results because the T4 analog is sequestered by albumin. Diagnostic Products Corp. (DPC) introduced the concept of chemically blocking analog-albumin binding in 1982. While DPC succeeded in eliminating albumin dependence, their 1985 version of chemically blocked FT4 assay appeared to be "thyroxin-binding globulin" (TBG) dependent, producing inappropriately low FT4 results with low TBG concentrations and high results with high TBG concentrations. We examined the effects of chemical blockers on albumin and TBG binding, using equilibrium dialysis to measure free fractions of T4 analog and T4. We then created FT4 assays in which various concentrations of chemical blockers were used to demonstrate their effects on FT4 estimates in patients with low or increased TBG concentrations or who were pregnant. We found that chemical blockers do displace T4 analog from albumin, but also displace T4 from albumin and, in high concentrations, from TBG as well. It is this displacement of T4 from TBG by chemical blockers that resulted in "TBG dependence" of DPC FT4 estimates. This problem has been corrected in currently available versions of the DPC FT4 kit.

Integration of database capabilities into a patient reporting system.

A database design is described which automatically archives computer-generated patient imaging and radioassay reports. Selected phrases are condensed so that data storage will be efficient without sacrificing a prose style of report. An indexed file structure has been used to facilitate rapid record retrieval even when several hundred thousand records are stored. Personnel time is considerably reduced for recalling patient records, preparing periodic summaries of studies completed, and performing administrative functions such as billing and keeping track of checked out images. Complex queries, such as "list all the patients between the ages of 50 and 60 on digitalis referred for a stress cardiac study, with left ventricular ejection fraction less than 40% and apical dyskinesis," become feasible. A system for data backup is described to protect against catastrophic data loss.

Advantages of list-mode data acquisition in gated blood-pool studies.

Because of physiologic R-R interval variability and arrhythmia, frame-mode acquisition of gated images may produce erroneous left ventricular volume curves, particularly in the diastolic filling phase. Eighteen patients in sinus rhythm underwent gated imaging in which both frame-mode and list-mode acquisitions were used. The systolic portions of the volume curves were similar in both studies, and the ejection fractions correlated well (R = 0.97). "Dropout" of data in the late diastolic phase, noted in 15 patients in whom frame mode was used, was not present in list mode, in which the atrial kick was clearly delineated. In additional patients with various arrhythmias, separate volume curves were obtained with list mode for premature, post-premature, and sinus beats. In patients with atrial fibrillation, a prominent peak mid-range on the R-R histogram was selected, and a complete volume curve was obtained. It was concluded that list-mode acquisition provided improved volume curves, with particular applicability in arrhythmic patients.

Comparison of two-dimensional echocardiography, radionuclide ventriculography and cineangiography in detecting surgically documented left ventricular thrombi.

To assess the diagnostic value of various imaging techniques for identifying left ventricular thrombi, we studied 35 patients who underwent left ventricular aneurysm repair and inspection of the ventricular cavity for the presence of a thrombus. All patients underwent preoperative two-dimensional echocardiography and left ventricular cineangiography; radionuclide ventriculography was also performed in 19 of these patients. Data from these procedures were analyzed as in a blind study, and were interpreted as either positive or negative for thrombus. A left ventricular thrombus was present in 22 of the 35 patients at surgery (63%). Two-dimensional echocardiography showed a sensitivity of 95%, specificity of 92% and overall predictive accuracy of 94% for the detection or exclusion of thrombi. In comparison, cineangiography yielded a sensitivity of 73%, specificity of 92% and predictive accuracy of 80%. The sensitivity of radionuclide ventriculography was 60%, specificity was 100%, and predictive accuracy was 79%. Our data, based on a surgical-pathological standard, shows that two-dimensional echocardiography is a highly accurate technique for the diagnosis of left ventricular thrombi, and may be the procedure of choice for this purpose.

Tc-99m glucoheptonate estimation of glomerular filtration rate. Correlation with endogenous creatinine clearance.

Estimation of GFR using radioisotope techniques has been successfully accomplished with I-125 iothalamate, Cr-51 EDTA, and Tc-99m DTPA. However, the techniques have required up to several hours to complete with blood and/or urine sampling. A method introduced by Schlegel and modified by Gates provides a simple and rapid technique of GFR quantitation that obviates the need for blood and urine sampling. In the present study an evaluation of Tc-99m GHA was undertaken to assess its ability to reflect GRF using a modification of Gates' technique. When the GFR determinations were compared with a current 24-hour CrC1, a correlation coefficient of 0.91 was obtained. Tc-99m GHA-derived GFR appears to closely correlate with endogenous CrC1 over a wide range of renal function.

Clinical utility of a two-site immunoradiometric assay for creatine kinase-MB in the detection of perioperative myocardial infarction.

In 144 patients, creatine kinase MB was measured serially at 0, 8, 16, 24, 48, and 72 hr using a two-site immunoradiometric assay (IRMA). Cardiac enzymes were also measured, including SGOT, LDH, total CPK, and CK-MB by electrophoresis. The presence of perioperative myocardial infarction (poMI) was established in 24 patients by the appearance of new electrocardiographic Q waves and/or new wall motion abnormalities detected by radionuclide ventriculography. In patients without poMI, CK-MB (IRMA) was elevated (6.4 +/- 4.9 equivalent units per liter) at 0-8 hr but decreased to 3.4 +/- 1.3 EU/l by 16 hr. In patients with poMI, peak values occurred at 16-24 hr (21.0 +/- 19.8 EU/l). Using a threshold value of 8.5 EU/l, patients with poMI could be distinguished from those without with 97% accuracy (sensitivity = 88%, specificity = 99%). The CK-MB (IRMA) was more reliable than the other enzyme assays, for which we used both empirically elevated threshold values based upon previous experience, and also threshold values retrospectively optimized for the study population. We conclude that the CK-MB (IRMA) can serve as a valuable postoperative screening test for poMI.

Effects of stress management training and dietary changes in treating ischemic heart disease.

To evaluate the short-term effects of an intervention that consists of stress management training and dietary changes in patients with ischemic heart disease (IHD), we compared the cardiovascular status of 23 patients who received this intervention with a randomized control group of 23 patient who did not. After 24 days, patients in the experimental group demonstrated a 44% mean increase in duration of exercise, a 55% mean increase in total work performed, somewhat improved left ventricular regional wall motion during peak exercise, and a net change in the left ventricular ejection fraction from rest to maximum exercise of +6.4%. Also, we measured a 20.5% mean decrease in plasma cholesterol levels and a 91.0% mean reduction in frequency of anginal episodes. In this selected sample, short-term improvements in cardiovascular status seem to result from these adjuncts to conventional treatments of IHD.

Exercise radionuclide ventriculography in evaluating successful transluminal coronary angioplasty.

To evaluate the ability of transluminal coronary angioplasty (TCA) to relieve myocardial ischemia, 44 patients with single vessel disease underwent exercise gated radionuclide ventriculography (GRNV) before and 2.8 +/- 1.3 days following angiographically successful TCA. Pre-TCA GRNV was abnormal in 11 of 14 patients with right coronary artery (RCA) stenosis and 24 of 30 with left anterior descending (LAD) stenosis. Following TCA there was an increase in exercise duration from 500 +/- 288 sec to 625 +/- 273 sec (P less than 0.001), and in maximum double product from (209 +/- 69) x 10(2) to (263 +/- 70) x 10(2) (P less than 0.001). The number of patients with stress-induced ST-T abnormalities decreased from 13 to 4 (P less than 0.05), and the number with chest pain during exercise decreased from 18 to one (P less than 0.001). Whereas resting ejection fraction was unchanged (0.58 +/- 0.10 vs 0.59 +/- 0.11) following TCA, the ejection fraction at peak exercise increased from 0.61 +/- 0.13 to 0.66 +/- 0.12 (P less than 0.001). Of 24 patients with resting abnormalities, regional wall motion improved in 13. In 22 of 31 patients with stress-induced asynergy, the wall motion response to exercise improved (P less than 0.001). Of 19 patients restudied angiographically and with exercise GRNV at 6-12 months, restenosis of greater than or equal to 50% had occurred in six, four of whom had abnormal studies. In six of whom the degree of stenosis of the dilated artery had remained less than or equal to 20% the exercise GRNV study remained normal. It is concluded that GRNV is helpful in documenting the improvement in resting left ventricular function and functional reserve in patients with angiographically successful TCA. In the limited number of patients with late follow-up studies, data suggest that GRNV may be a valuable test to detect restenosis.

Left ventricular performance during exercise in patients with left bundle branch block: evaluation by gated radionuclide ventriculography.

To investigate changes in left ventricular (LV) function during exercise in patients with left bundle branch block (LBBB), 22 patients without a history or physical findings of previous myocardial infarction or LV dysfunction were studied by gated radionuclide ventriculography (GRNV) at rest and during bicycle exercise. Coronary arteriography demonstrated greater than 75% diameter narrowing of at least one coronary artery in nine patients. Of the remaining 13 patients, GRNV demonstrated wall motion abnormalities in seven patients either at rest or with exercise. During exercise, mean ejection fraction (EF) did not increase in patients without coronary artery disease (CAD). Patients with CAD had a 12-point fall in mean EF with exercise. We conclude that LV reserve, as demonstrated by ability to increase EF with exercise, is impaired in patients with LBBB even in the absence of CAD or other underlying cardiac disease and that standard GRNV criteria to exclude the presence of CAD (a greater than five-point increase in EF with exercise and normal wall motion) are not strictly applicable in screening patients with LBBB.

Post-exercise potentiation of wall motion to identify myocardial viability.

Resting left ventricular wall motion abnormalities may represent myocardial scars or areas of viable muscle which are ischemic and may thus benefit from revascularization surgery. Improvement in wall motion in the 3-6 minute post-exercise recovery period as compared to the resting state was investigated as a possible criterion to predict myocardial viability in 168 patients with coronary artery disease. Of 125 patients with abnormal resting wall motion, 14 of 14 who improved regional function post-exercise also improved following coronary bypass surgery. However, wall motion improved postoperatively in an additional 55 patients who had not demonstrated post-exercise improvement. An increase in ejection fraction post-exercise occurred in patients with coronary disease as well as an additional group of 24 normal subjects. Thus in the post-exercise period, improvement in resting wall motion is a highly specific but insensitive predictor of myocardial viability.

Probe radiocardiography: validation of a technique to routinely determine left ventricular ejection fraction.

We investigated the probability of obtaining a valid radiocardiogram with the first commercially available cardiac probe and a peripheral injection of the radiopharmaceutical. Measurements of left ventricular ejection fraction (LVEF) were obtained in a series of 15 patients undergoing cardiac catheterization. Probe LVEF determinations using central, peripheral and rapid sequential injections correlated well with each other and with ventriculography (r = .88--.98). By documenting its accuracy and precision, this study confirms the validity of a new technique for measuring LVEF.

Single injection thallium-201 stress and redistribution myocardial perfusion imaging: comparison with stress electrocardiography and coronary arteriography.

The efficacy of single injection thallium-201 exercise stress and rest redistribution imaging in the evaluation of myocardiacl ischemia was compared with stress electrocardiography and coronary arteriography. Thallium-201 imaging was interpreted at two levels of sensitivity in order to define the circumstances under which it best serves as a screening modality for coronary arteriography. With the prevalence of coronary disease usually found in patients referred for coronary arteriography (75%), unprocessed thallium-201 imaging is as good as stress electrocardiography in identifying patients apt to show coronary artery abnormalities, but not much better than stress electrocardiography in delineating those patients unlikely to show coronary artery disease. In contrast, processed lesion enhanced images showing normal results virtually eliminate the possibility of significant arteriographic findings. With this screening technique, many patients may be spared unnecessary coronary arteriography.