Sanjiv Kaul

Superiority of quantitative exercise thallium-201 variables in determining long-term prognosis in ambulatory patients with chest pain: A comparison with cardiac catheterization

The purpose of this study was to determine the prognostic utility of quantitative exercise thallium-201 imaging and compare it with that of cardiac catheterization in ambulatory patients. Accordingly, long-term (4 to 9 years) follow-up was obtained in 293 patients who underwent both tests for the evaluation of chest pain: 89 had undergone coronary artery bypass graft surgery within 3 months of testing and were excluded from analysis, 119 experienced no cardiac events and 91 had an event (death in 20, nonfatal myocardial infarction in 21 and coronary artery bypass operations performed greater than 3 months after cardiac catheterization in 50). When all variables were analyzed using Cox regression analysis, the quantitatively assessed lung/heart ratio of thallium-201 activity was the most important predictor of a future cardiac event (chi 2 = 40.21). Other significant predictors were the number of diseased vessels (chi 2 = 17.11), patient gender (chi 2 = 9.43) and change in heart rate from rest to exercise (chi 2 = 4.19). Whereas the number of diseased vessels was an important independent predictor of cardiac events, it did not add significantly to the overall ability of the exercise thallium-201 test to predict events. Furthermore, information obtained from thallium-201 imaging alone was marginally superior to that obtained from cardiac catheterization alone (p = 0.04) and significantly superior to that obtained from exercise testing alone (p = 0.02) in determining the occurrence of events. In addition, unlike the exercise thallium-201 test, which could predict the occurrence of all categories of events, catheterization data were not able to predict the occurrence of nonfatal myocardial infarction. The exclusion of bypass surgery and previous myocardial infarction did not alter the results. In conclusion, data from this study demonstrate that exercise thallium-201 imaging may be superior to data from both exercise testing alone and cardiac catheterization data alone for predicting future events in ambulatory patients who have undergone both exercise thallium-201 imaging and catheterization for the evaluation of chest pain.

Contrast echocardiography in acute myocardial ischemia. III: An in vivo comparison of the extent of abnormal wall motion with the area at risk for necrosis

To define the in vivo relation between abnormal wall motion and the area at risk for necrosis after acute coronary occlusion, 11 open chest dogs were studied. Five dogs underwent left anterior descending coronary artery occlusion and six underwent left circumflex artery occlusion. Area at risk was defined at five short-axis levels (mitral valve, chordal, high and low papillary muscle and apex) using myocardial contrast echocardiography. Wall motion was measured in the cycles preceding injection of contrast medium. Two observers used two different methods to measure wall motion. In method A, end-diastolic to end-systolic fractional radial change for each of 32 endocardial targets was determined. The extent of abnormal wall motion was then calculated using three definitions of wall motion abnormality: akinesia/dyskinesia, fractional inward endocardial excursion of less than 10%, and fractional inward endocardial excursion of less than 20%. In method B, the information from the entire systolic contraction sequence was analyzed and correlated with a normal contraction pattern. The best linear correlation between area at risk (AR) and abnormal wall motion (AWM) was achieved using method B and expressed by the following linear regression: AWM = 0.92 AR + 3.0 (r = 0.92, p less than 0.0001, SEE = 1.7%). Of the three definitions of abnormality used in method A, the best correlation was achieved between area at risk and less than 10% inward endocardial excursion and was expressed by the following polynomial regression: AWM = -0.01 AR2 + 1.5 AR -0.14 (r = 0.92, p less than 0.001, SEE = 1.7%). These data demonstrate that there is a definite relation between area at risk and abnormal wall motion but that this relation varies depending on the method used to analyze wall motion. However, wall motion during acute ischemia is also influenced by the loading conditions of the heart. Because these may vary in a manner that is independent of the ischemic process, measurement of both risk area and abnormal motion may provide a more comprehensive assessment of cardiac function in myocardial ischemia than is provided by the measurement of either alone.

Determination of the quantitative thallium imaging variables that optimize detection of coronary artery disease

Although quantification of exercise thallium images has been previously reported, the relative value of different imaging variables for detection of coronary artery disease has not been analyzed in a large group of patients with cardiac catheterization data. Regional initial thallium uptake, redistribution and clearance on thallium study were measured in 325 patients also undergoing cardiac catheterization (281 patients with and 44 patients without coronary artery disease). Normal values were defined in 55 other clinically normal subjects. When five myocardial segments were analyzed in each view, the respective values for sensitivity and specificity were 95 and 50% for initial thallium uptake, 60 and 87% for redistribution and 74 and 66% for clearance. Initial thallium uptake was the most sensitive but least specific (p less than 0.001), whereas redistribution was the least sensitive and most specific (p less than 0.001). Using stepwise logistic regression analysis, the best correlate of coronary artery disease was initial thallium uptake. Addition of redistribution to a mathematical model of the probability of coronary artery disease did not alter sensitivity, but increased specificity from 50 to 70% (p less than 0.001). Once initial uptake and redistribution were considered, myocardial thallium clearance provided no additional improvement in the correlation. Excluding the two basal segments in each view from the analysis increased the specificity from 70 to 80% (p less than 0.001) without affecting sensitivity. Of the 15 patients (5%) with coronary disease not detected using this approach, none had left main disease and 10 (67%) had one vessel disease. A combination of variables derived from quantification of exercise thallium images provides a superior sensitivity and specificity for the detection of coronary artery disease compared with the use of a single variable.

Functional and pathologic effects of multiple echocardiographic contrast injections on the myocardium, brain and kidney

Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast echocardiography in acute myocardial ischemia. II. The effect of site of injection of contrast agent on the estimation of area at risk for necrosis after coronary occlusion

Myocardial contrast echocardiography has been shown to accurately assess the area at risk for necrosis after acute coronary occlusion in the experimental model. The area at risk as determined by this method, however, has been defined in different ways depending on the model used. Some investigators have injected the contrast agent proximal to the site of coronary occlusion (left main coronary artery or aorta) and defined the area at risk as the segment of myocardium not showing a contrast effect (negative risk area). Others have injected the contrast agent directly into the occluded vessel and have defined the area at risk as that showing contrast enhancement (positive risk area). To evaluate whether the areas at risk determined by these two techniques are identical, six open chest dogs were studied using both methods. The area at risk was slightly but significantly larger when the contrast agent was injected into the occluded vessel than when it was injected proximally into the left main coronary artery (4.98 +/- 1.69 versus 3.97 +/- 1.27 cm2, p less than 0.01). It is concluded that the site of injection of the contrast agent significantly influences the determination of area at risk. Therefore, data obtained by the two techniques should not be used interchangeably, and in a given study the area at risk should be measured consistently using one technique.

Magnetic resonance imaging during acute myocardial infarction

Experimental canine studies have demonstrated the potential of magnetic resonance imaging (MRI) for detecting and characterizing acute myocardial infarction (AMI) in humans. Accordingly, electrocardiographic-gated spin-echo MR images of the left ventricular short axis were obtained in 34 patients a mean of 11 +/- 6 days (range 3 to 30) after AMI. This imaging technique allowed division of the left ventricle into segments corresponding to the left ventricular segments on angiography. Patients were separated into 2 groups; the first 16 patients (group I) were examined using a variety of imaging techniques. Information derived from this experience resulted in a standard imaging protocol and development of criteria for the presence of AMI. The imaging protocol and interpretation criteria were used in the assessment of a subsequent group of 18 patients (group II). Of the 14 patients in group II with satisfactory image quality, all showed an increase in myocardial signal intensity consistent with an AMI. In addition, the anterior or inferior location of the abnormal MR segments corresponded to the electrocardiographic infarct location. MR segments showing increased signal intensity corresponded with severely hypokinetic or akinetic segments on the left ventriculogram in 8 patients having both procedures. In a group of volunteers who underwent imaging and whose images were interpreted in the same manner as those of the patients with AMI, 1 of 9 subjects had regional variation in myocardial signal intensity compatible with an AMI. In summary, AMI is readily detected, located and characterized by electrocardiographic-gated MRI. These findings suggest that MRI techniques may have a role in the evaluation of AMI in humans.

Quantitative thallium imaging findings in patients with normal coronary angiographic findings and in clinically normal subjects.

Computer-quantified exercise thallium images in 45 clinically normal subjects (group I) and in 44 patients with chest pain and no significant coronary artery disease by angiography (group II) were compared. Group II patients were older and more frequently female, had ST-segment depression by electrocardiography, and included 8 with subcritical (0 to 49%) stenoses. When normality was defined by the range of thallium imaging values in the clinically normal subjects, and after correcting clearance for peak exercise heart rate, 20 of 44 patients (45%) in group II had abnormal findings. The only difference between the 20 patients with abnormal findings and the 24 with normal findings in group II was a greater frequency of subcritical (less than 50%) coronary stenoses in the abnormal group, 7 (35%) vs 1 (4%) (p less than 0.05). However, this does not explain most of the abnormalities of thallium imaging in group II. Thus, abnormal thallium findings in subjects with normal angiographic findings are frequently seen and are partially related to the presence of subcritical coronary stenoses, suggesting an underestimation of coronary obstruction. Furthermore, clinically and angiographically normal subjects may differ substantially, and both sets of normal subjects should be considered when establishing criteria for abnormality in exercise thallium imaging.

Sources of variability in the radionuclide angiographic assessment of ejection fraction: A comparison of first-pass and gated equilibrium techniques

Measurements of ejection fractions (EF) determined by first-pass and gated equilibrium radionuclide angiography are widely believed to be equivalent. To compare these measurements in a large group of patients over a wide range of EF values, left ventricular (LV) and right ventricular (RV) EFs at rest were measured in 135 consecutive patients who underwent the 2 methods of radionuclide angiography within 1 hour: first-pass upright with a multi-crystal camera in the anterior projection and gated equilibrium supine with a single-crystal camera in the left anterior oblique projection. The population included 18 normal patients and 117 patients with various cardiac and pulmonary disorders. First-pass and gated equilibrium LVEF correlated well (r = 0.83, p less than 0.001), but the slope of the regression line was different from unity, with the first-pass values lower than the gated equilibrium values (0.51 +/- 0.16 vs 0.56 +/- 0.15, p less than 0.05 [mean +/- standard deviation] ). Among the 45 patients with a gated equilibrium LVEF of less than or equal to 0.50, the correlation (r = 0.84) was better than that for the 90 patients with a LVEF greater than 0.50 (r = 0.44, p less than 0.05). However, in the latter group, the correlation remained good in the 15 patients with cardiomegaly due to aortic or mitral regurgitation (r = 0.80). Inter- and intraobserver error was similar for both methods. In contrast, there was a poor correlation between first-pass and gated equilibrium RVEF, with the first-pass values higher than the gated equilibrium values (0.51 +/- 0.11 vs 0.43 +/- 0.11, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of exercise electrocardiography and quantitative thallium imaging for one-vessel coronary artery disease

The relative value of exercise electrocardiography and computer analyzed thallium-201 imaging was compared in 124 patients with 1-vessel coronary artery disease (CAD). Of these, 78 had left anterior descending (LAD), 32 right and 14 left circumflex (LC) CAD. In patients with no previous myocardial infarction (MI), thallium imaging was more sensitive than the electrocardiogram (78% vs 64%, p less than 0.01), but in patients with previous MI, sensitivity was similar. Further, thallium imaging was more sensitive only in LAD and LC disease. Redistribution was compared with ST-segment depression as a marker of ischemia. Only in patients with prior MI (76% vs 44%, p less than 0.01) and only in LC and right CAD did redistribution occur more often than ST depression. Thallium imaging was more accurate in localizing stenoses than the electrocardiogram (p less than 0.001), but did not always correctly predict coronary anatomy. Septal thallium defects were associated with LAD disease in 84%, inferior defects with right CAD in 40% and posterolateral lesion defects with LC CAD in 22%. The results indicate the overall superiority of thallium imaging in 1-vessel CAD compared with exercise electrocardiography; however, there is a wide spectrum of extent and location of perfusion defects associated with each coronary artery. Thallium imaging complements coronary angiography by demonstrating the functional impact of CAD on myocardial perfusion.

Quantitative aspects of myocardial perfusion imaging

Computer quantitation of myocardial perfusion images has enhanced the detection of thallium perfusion abnormalities compared to visual analysis. Computer analysis is more specific than visual analysis for detection of initial defects and more sensitive for detection of redistribution. Computer analysis is equally good for detecting thallium abnormalities in the distribution of the three major coronary arteries. Measurement of absolute clearance of thallium results in an unacceptable high false-positive rate. However, when clearance in a myocardial segment is compared to the fastest clearing segment in the heart, the specificity of clearance improves significantly. Quantitation of lung:heart ratio is very useful. Increased lung:heart ratio reflects exercise induced left ventricular dysfunction and is a strong marker of prognosis. Single photon emission computerized tomography (SPECT) offers the potential of more precisely sizing the risk area. The question of whether this technique offers a significant advantage over planar thallium imaging has to be answered.