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This report reviews the applications of tomographic imaging with current and new tracers in assessing myocardial perfusion and viability. Multiple studies with thallium-201 (TI-201) single photon emission computed tomography (SPECT) imaging for the detection of coronary artery disease (CAD) have demonstrated high sensitivity, high rates of normalcy and high reproducibility. In assessing viability, fixed defects are frequently detected in viable zones in 4-hour studies with TI-201 imaging. Redistribution imaging performed 18 to 72 hours after injection or reinjection of TI-201 before 4-hour redistribution imaging has been shown to improve accuracy of viability assessment. TI-201 SPECT studies are limited by the suboptimal physical properties of TI-201, which result in variable image quality. The 2 new technetium-99m (Tc-99m) - labeled myocardial perfusion tracers offer the ability to inject much higher amounts of radioactivity, making it possible to assess ventricular function as well as myocardial perfusion from the same injection of radiotracer. Tc-99m sestamibi has very slow myocardial clearance, which allows for prolonged imaging time and results in image quality superior to that obtained with TI-201 and Tc-99m teboroxime. The combination of minimal redistribution of Tc-99m sestamibi and high count rates makes gated SPECT imaging feasible, and also permits assessment of patients with acute ischemic syndromes by uncoupling the time of injection from the time of imaging. The combination of high image quality and first-pass exercise capabilities may lead to a choice of this agent over TI-201 for assessment of chronic CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m (Tc-99m) sestamibi is a new myocardial perfusion imaging agent that offers significant advantages over thallium-201 (Tl-201) for myocardial perfusion imaging. The results of the current clinical trials using acquisition and processing parameters similar to those for Tl-201 and a separate (2-day) injection protocol suggest that Tc-99m sestamibi and Tl-201 single photon emission computed tomography (SPECT) provide similar information with respect to detection of myocardial perfusion defects, assessment of the pattern of defect reversibility, overall detection of coronary artery disease (CAD) and detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m sestamibi planar imaging because the former provides a higher defect contrast and is more accurate for detection of disease in individual coronary arteries. Research is currently under way addressing optimization of acquisition and processing of Tc-99m sestamibi studies and development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which in turn will further increase the confidence in image interpretation. Development of algorithms for analysis of end-diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion and wall thickening. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the occurrence of attenuation-related image artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

The occurrence and significance of transient dilation of the left ventricle during dipyridamole stress-redistribution thallium-201 scintigraphy was studied in 73 patients who underwent both dipyridamole thallium-201 study and coronary angiography. Transient dilation ratio was calculated from planar anterior images by dividing the computer-derived left ventricular area on the initial image by that of the 4-hour image. In 11 patients with normal coronary arteriograms or less than 50% coronary stenosis, the transient dilation ratio was 0.98 +/- 0.046. An abnormal transient dilation ratio was defined as greater than or equal to 1.12, representing greater than or equal to 3 standard deviations above the mean normal value. When the 15 patients with an abnormal ratio were compared with the 58 with a normal ratio, the former group had a significantly higher frequency of 3 critical (greater than or equal to 90%) coronary stenoses (33 vs 5%), higher prevalence of collaterals (67 vs 24%), more extensive myocardial reversible defects by planar (71 vs 10%) or by single-photon emission computed tomography (87.5 vs 35%) imaging and a higher incidence of dipyridamole-induced anginal chest pain (53 vs 22%). No significant difference between the 2 groups was noted with respect to age, gender, prior myocardial infarction, single or double critical coronary stenosis, dipyridamole-induced ischemic electrocardiographic response and increased lung uptake. An abnormal transient dilation ratio of greater than or equal to 1.12 was a specific marker of multivessel (87%) or 3-vessel (85%) critical coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

The utility of stress-redistribution thallium-201 myocardial perfusion single-photon emission computed tomography (SPECT) in patients with a prior single myocardial infarction was studied in 66 patients who were tested by both SPECT and coronary angiography. SPECT was quantified by comparing the patients' circumferential count profiles to a previously established normal data base and by plotting the results onto a polar coordinate map that localized defects to the 3 major coronary artery territories. The pattern of reversibility of the quantitatively detected defects was assessed by consensus visual analysis. SPECT thallium-201 detected myocardial infarction in 62 of 66 patients (sensitivity = 94%). Sixty-five percent of the infarct zones showed some reversibility at 4-hour imaging which corresponded with angiographic evidence of flow to the infarct zones in 95.5% of cases. Late (18 to 24 hours) imaging, done in 26 patients, showed complete or partial reversibility of 29% of infarct zone segments which were nonreversible on 4-hour images. To improve specificity for detection of disease in coronary arteries supplying the non-infarct territories, new quantitative criteria were developed that took into consideration contiguity of defects with the infarct zone. Accuracy for detection of patients with multivessel coronary disease by quantitative thallium-201 SPECT was 86%, which was significantly higher than those of the clinical response to exercise (48%), the exercise electrocardiographic response (56%) or their combination (65%).(ABSTRACT TRUNCATED AT 250 WORDS)

The accuracy of the previously developed and validated Cedars-Sinai Medical Center (CSMC) computer program for quantitative analysis of thallium-201 (201TI) stress myocardial tomograms was assessed in a multicenter trial consisting of 242 patients with coronary angiography and 76 with a low likelihood (LL) of coronary artery disease (CAD) involving various cameras, computers, and operators. The program utilized gender-matched normal limits developed from 35 LL patients at CSMC. The multicenter results as compared to those of 168 patients from CSMC were not significantly different with respect to the overall sensitivities (94% versus 95%) and specificities (44% versus 56%) for identification of CAD and normalcy rates which were determined in LL patients (82% for both) and with respect to identification of individual diseased arteries. The results indicate that our method for quantifying tomographic 201TI stress scintigrams utilizing standard normal limits can be applied at other institutions by different operators, using a variety of cameras and computers, with similar accuracy to that currently obtained at our institution.

The frequency of thallium-201 late reversibility was prospectively assessed in 118 patients who had stress-redistribution thallium-201 studies by single photon emission computed tomography (SPECT). These patients demonstrated two or more segments with nonreversible defects at 4 h imaging and underwent late (18 to 72 h) redistribution imaging. When the criterion of late reversibility was defined as greater than or equal to 1 segment with 4 h nonreversible defects demonstrating late reversibility, it was present in 62 (53%) of the 118 patients and 164 (22%) of 762 segments. When the criterion of greater than or equal to 2 segments was used, late reversibility was found in 41 (35%) of 118 patients and 143 (19%) of 762 segments. The frequency of detected reversible defects increased from 27% at 4 h imaging to 43% at combined 4 h and late imaging (p less than 0.0001) and was significantly increased in all myocardial regions. In comparing the efficacy of initial and late imaging alone versus performing initial, 4 h and late imaging for the identification of reversible defects, 421 (94%) of 449 segments classified as reversible by the latter protocol were also correctly identified by the early and late imaging only approach, with the remaining 6% (28 segments) comprising those segments demonstrating the reversible pattern at 4 h and the nonreversible pattern at late imaging. No major differences were noted with respect to clinical, stress electrocardiographic and scintigraphic variables between the 118 patients undergoing late imaging and 98 additional randomly selected patients with two or more nonreversible defects at 4 h, who did not have late imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty-one patients with inferior acute myocardial infarction (AMI) and no evidence of prior AMI were studied to determine which factors influence the magnitude of precordial ST-segment depression. In the total study group, there was a significant but weak correlation between the magnitude of precordial ST-segment depression and the magnitude of inferior ST-segment elevation (r = -0.46, p less than 0.001). In the 29 patients with evidence of concomitant right ventricular (RV) involvement, precordial ST-segment depression was significantly smaller both in absolute terms (-1.3 +/- 1.8 vs -2.8 +/- 1.9 mm, p less than 0.01) and relative to the magnitude of inferior ST-segment elevation (ratio of -0.2 +/- 1.0 vs -1.1 +/- 0.5, p less than 0.01), whereas in the 15 patients with lateral ST-segment elevation (greater than or equal to 1 mm in lead V6), precordial ST-segment depression was significantly greater both in absolute terms (-3.5 +/- 2.3 vs -1.6 +/- 1.7 mm, p less than 0.01) and relative to the magnitude of inferior ST-segment elevation (ratio of -1.1 +/- 0.8 vs -0.5 +/- 0.9, p less than 0.02). Consistent with these findings, the correlation between the magnitudes of precordial and inferior ST-segment deviations was considerably improved when only the 24 patients with neither evidence of RV involvement nor lateral ST-segment elevation were analyzed (r = 0.89, p less than 0.001, n = 24). These data suggest that in patients with inferior AMI, there is a reciprocal relation between precordial and inferior ST-segment deviations, which is distorted by concomitant RV involvement and by concomitant lateral left ventricular wall involvement.

The capabilities of visual and quantitative analysis of stress redistribution thallium-201 scintigrams, exercise electrocardiography and exercise blood pressure response were compared for correct identification of extensive coronary disease, defined as left main or triple vessel coronary artery disease, or both (50% or more luminal diameter coronary narrowing), in 105 consecutive patients with suspected coronary artery disease. Extensive disease was present in 56 patients and the remaining 49 had either less extensive coronary artery disease (n = 34) or normal coronary arteriograms (n = 15). Although exercise blood pressure response, exercise electrocardiography and visual thallium-201 analysis were highly specific (98, 88 and 96%, respectively), they were insensitive for identification of patients with extensive disease (14, 45 and 16%, respectively). Quantitative thallium-201 analysis significantly improved the sensitivity of visual thallium-201 analysis for identification of patients with extensive disease (from 16 to 63%, p less than 0.001) without a significant loss of specificity (96 versus 86%, p = NS). Eighteen (64%) of the 28 patients who were misclassified by visual analysis as having less extensive disease were correctly classified as having extensive disease by virtue of quantitative analysis of regional myocardial thallium-201 washout. When the results of quantitative thallium-201 analysis were combined with those of blood pressure and electrocardiographic response to exercise, the sensitivity and specificity for identification of patients with extensive disease was 86 and 76%, respectively, and the highest overall accuracy (0.82) was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

The validity of cardiac nuclear magnetic resonance imaging for determination of left ventricular myocardial mass was evaluated in nine dogs. A gated spin echo-pulsing sequence was used for in vivo imaging, obtaining 0.7 cm thick slices of the heart spaced by 1 cm. On each imaged slice, the left ventricular surface area was reproducibly determined by planimetry and was multiplied by slice spacing and specific gravity of the myocardium (1.05) to obtain slice mass. Total left ventricular mass was calculated by adding slice masses in short-axis (method I), transaxial (method II) and vertical long-axis (method III) orientations using Simpson's rule. With each method, masses of the portions of the left ventricle subject to partial volume effect either were not accounted for or alternatively were estimated from the same or an orthogonal imaging plane. Calculated left ventricular mass was compared with the actual excised left ventricular weight. With NMR imaging of in situ nonbeating hearts, best results were obtained when either method I or method II was used and partial volume effect was estimated either from the same or an orthogonal plane. With in vivo NMR imaging, best results were noted when method I was used and mass of the partial volume apex was calculated from transaxial slices: Y (in vivo NMR image) = 8.3 + 0.99X, r = 0.996, SEE = 3.14. For this method, the interobserver reliability coefficient and standard error of the measurement were 0.97 and 5.4, respectively. Compared with method I, in vivo methods II and III were associated with larger errors (SEE ranging from 13.03 to 19.03) regardless of the approach used to estimate partial volume effect. It is concluded that NMR imaging is a highly accurate noninvasive method for in vivo measurement of left ventricular mass in dogs and offers promise for accurate measurement of left ventricular mass in patients.

Conventional anterior and 45-degree left anterior oblique (LAO) views are limited in the evaluation of inferior segmental wall motion by multiple gated equilibrium cardiac blood pool scintigraphy. This study evaluated the addition of a 70-degree LAO view by comparing scintigraphic and contrast ventriculography in 25 patients, of whom 17 demonstrated abnormal inferior wall motion. Abnormal inferior wall motion was correctly identified in only 10 of 17 patients in the anterior view, but in 16 of 17 patients in the 70-degree LAO view. The number of assessable inferior segments was improved from 58% in the anterior view to 98% in the 70-degree LAO view. When the inferior segments could be visualized in the anterior view, inferior wall motion was accurately assessed. The addition of the 70-degree LAO view aids in the multiple gated equilibrium scintigraphic detection of inferior wall motion abnormalities with a minor loss in specificity.

Occlusive intracoronary (IC) thrombosis was produced experimentally in dogs by placement of a copper coil. The thrombus was consistently lysed by application of Thrombolysin (streptokinase and plasminogen) at the site of occlusion, 1 to 6 hours after thrombosis. Thrombolysin has no toxic effect on the coronary artery wall or the myocardium. Reperfusion after 30 to 60 minutes of occlusion frequently resulted in ventricular fibrillation, but gradual reperfusion reduced the probability of ventricular fibrillation. Intramyocardial bleeding was noted after reperfusion in areas of advanced necrosis and was shown to be the consequence, rather than the cause, of necrosis. The reperfused myocardium remained hypocontractile, but in contrast to the occlusion period, its mechanical function could be enhanced by inotropic stimulation. After experimental studies confirmed the feasibility and safety of IC thrombolysis, the technique was applied within 3 hours of onset of pain in 29 patients with evolving acute myocardial infarction (AMI) and showing ST elevations without pathologic Q waves. Nitroglycerin (NTG), 0.1 mg, was injected into the occluded coronary artery to rule out spasm; NTG failed to open the occluded artery. A special, very flexible, radiopaque No. 2 French catheter was advanced through the angiography catheter to the site of occlusion. Thrombolysin was infused at a rate of 4000 to 6000 IU/min until patency was achieved, followed by 2000 IU/min for 60 minutes. Lysis of clot was achieved in 27 of 29 patients. The single death (unrelated to the procedure) occurred subsequently in a patient in whom the artery was not reopened. After successful thrombolysis, 12 patients underwent elective coronary bypass surgery because of multiple stenoses. The need for early reperfusion is emphasized for effective IC thrombolysis therapy in evolving AMI.

Maximum-count circumferential profile analysis of 201TI single photon emission computed tomograms (SPECT) was employed to quantify infarct size (15) in ten dogs with acute closed chest coronary occlusion (seven left anterior descending coronary artery and three left circumflex coronary artery) who underwent rest-redistribution 201TI SPECT. The extent of hypoperfused myocardium was calculated as a percentage of slice mass on rest-redistribution 201TI SPECT. Pathologic IS was determined by triphenyl tetrazolium chloride (TTC) staining. On each tomogram, SPECT IS was defined as the % of the maximum-count circumferential profile points falling below normal. To calculate total LV infarct size, slice ISs were added to one another after each was multiplied by a coefficient K that reflected the contribution of that slice to the total left ventricular mass. K was derived from an observed relationship in normal dogs between slice fractional distance from the apex and either its actual weight, its geometric SPECT area, or its count-based SPECT area, the assessment of which was independent of edge detection. Using any of these algorithms, there was a high linear correlation between the tomographic and TTC IS. A similar algorithm was also developed from tomograms of eight normal patients. These data offer promise for the clinical noninvasive assessment of the extent of hypoperfused myocardium.

The relationship between the severity of coronary artery stenosis and the time to completed redistribution of thallium 201 (TI-201) defects following maximal exercise was investigated in 59 patients undergoing stress-redistribution TI-201 scintigraphy, coronary angiography, and contrast ventriculography. Multiple view TI-201 scintigrams were obtained, beginning 6 minutes (immediately post stress), less than 1 hour (early), 3 to 5 hours (average), and 18 to 24 hours (late) following intravenous TI-201 injection at peak exercise. Angiographic lesions were grouped into five levels of severity by percent stenosis. In the 107 defects which were seen on the immediate post stress images, early redistribution was noted in 15 (14%) and late redistribution was found in 23 (21%). In addition, there was a correlation (r = 0.56) between the time to completed redistribution and the severity of the coronary artery stenosis (p = 0.001). In comparison to defects with early and average redistribution, the segments contralateral to those with defects showing late redistribution more often had a critical stenosis supplying that segment. The frequency of myocardial infarction on ECG and the number of segments with akinetic and dyskinetic wall motion were less in defects undergoing late rather than no redistribution. Thus the time to completed TI-201 redistribution following stress appears to be related to the severity of stenosis in the coronary artery supplying the defect. Also, late redistribution is associated with the presence and early redistribution with the absence of a significant stenosis in the coronary artery to the contralateral segment.

The ability of NMRI to assess LV mass was studied in 20 normal males. By means of a 1.5 Tesla GE superconducting magnet and a standard spin-echo pulse sequence, multiple gated short-axis and axial slices of the entire left ventricle were obtained. LV mass was determined by Simpson's rule with the use of a previous experimentally validated method. The weight of the LV apex (subject to partial volume effect in the short-axis images) was derived from axial slices and that of the remaining left ventricle from short-axis slices. The weight of each slice was calculated by multiplying the planimetered surface area of the LV myocardium by slice thickness and by myocardial specific gravity (1.05). Mean +/- standard deviation of LV mass and LV mass index were 146 +/- 23.1 gm (range 92.3 to 190.4 gm) and 78.4 +/- 7.8 gm/m2 (range 57.7 to 89.4 gm/m2), respectively. Interobserver agreement as assessed by ICC was high for determining 161 individual slice masses (ICC = 0.99) and for total LV mass (ICC = 0.97). Intraobserver agreement for total LV mass was also high (ICC = 0.96). NMRI-determined LV mass correlated with body surface area: LV mass = 55 + 108 body surface area, r = 0.83; with body weight: LV mass = 26 + 0.77 body weight, r = 0.82; and with body height: LV mass = 262 +/- 5.9 body height, r = 0.75. Normal limits were developed for these relationships. NMRI-determined LV mass as related to body weight was in agreement with normal limits derived from autopsy literature data.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the functional significance of residual stenosis at the site of the thrombolysed infarct-related coronary artery, 37 patients underwent exercise radionuclide ventriculography or stress-redistribution thallium-201 scintigraphy at an average of 7 weeks following streptokinase therapy during evolving myocardial infarction. The size of the initially jeopardized myocardium and the salvaged myocardium were quantitated on thallium-201 studies obtained immediately before and 10 days after streptokinase infusion. Exercise-induced ischemia (defined by reversible thallium-201 perfusion defects or stress-induced deterioration of regional wall motion) in the reperfused myocardium was absent in 46% of patients and was present in different degrees in the remaining 54%. A significantly lower proportion of patients, however, showed exercise-induced chest pain and/or ST segment depression (10% and 20%, respectively). By stepwise multiple logistic regression analysis, the quantitatively determined size of the salvaged myocardium (398 units versus 65 units, p less than 0.01) and the ratio of the salvaged myocardium/extent of initially jeopardized myocardium (70% versus 28%, p less than 0.01) were both independent predictors of stress-induced ischemia, whereas the extent of initially jeopardized myocardium (585 units versus 407 units, p = NS), incidence of greater than or equal to 99% coronary stenosis (37% versus 46%, p = NS), and ischemic time (160 versus 196 minutes, p = NS) did not provide additional predictive information. We conclude that exercise-induced ischemia, which is frequently present in the streptokinase-reperfused myocardium, cannot be detected accurately by exercise-induced chest pain or ST segment depression, nor can it be predicted by the severity of residual coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The myocardial washout rate of thallium-201 was studied in 85 subjects with a less than 5% likelihood of coronary artery disease undergoing rest (group I, n = 12), dipyridamole (group II, n = 24) and exercise (group III, n = 49) stress thallium-201 scintigraphy. Subjects receiving dipyridamole were subdivided into group IIA (n = 11), who received an aminophylline injection 10 minutes after dipyridamole infusion, and group IIB (n = 13), who did not. The mean and highest washout rate values in each of 3 segments in the anterior, 45 degrees and 85 degrees left anterior oblique views were calculated. In group II the mean washout rate of thallium-201 was similar in all segments of each view and the overall mean washout rate did not differ between the 3 views studied. There was a good correlation between the mean and highest washout rate values in individual subjects (r = 0.98, p less than 0.001). The mean +/- standard deviation myocardial 4-hour washout rate of thallium-201 (anterior view) was 10 +/- 6% in group I compared with 40 +/- 14% in group IIA (p less than 0.05 vs group I), 31 +/- 13% in group IIB (p less than 0.05 vs group I) and 54 +/- 11% in group III (p less than 0.05 each vs group IIA and group IIB, respectively). There was a wide variation in mean washout rate values in group II (range 12 to 58%), and this variation was not altered by aminophylline administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Technical advances in radionuclide imaging have important implications for the management of patients with acute myocardial infarction. Single-photon emission computerized tomography with thallium 201 (TI-201) offers greater accuracy than planar imaging in detecting, localizing and sizing myocardial perfusion defects. Use of single-photon emission computerized tomography with TI-201 should allow for a more accurate assessment of prognosis after myocardial infarction. A new radiopharmaceutical, technetium 99-m methoxyisobutyl isonitrile, provides a number of advantages over TI-201, including higher quality images, lack of redistribution, and the ability to assess first-pass ventricular function. Applications of TI-201 and technetium 99-m methoxyisobutyl isonitrile include assessment of arterial patency and myocardial salvage immediately after thrombolytic therapy, detection of resting ischemia after thrombolytic therapy, targeting of subsets of patients for further intervention, and predischarge assessment to predict the future course of patients after an acute myocardial infarction.

To determine the spectrum and prognostic implications of left and right ventricular (LV and RV) ejection fractions (EFs) in acute myocardial infarction (AMI), radionuclide ventriculography was performed in 114 consecutive patients, admitted without (Killip class I, 78 patients) or with (killip class II, 36 patients) clinical signs of pulmonary congestion within 24 hours of onset of symptoms of a transmural AMI. Mean LVEF was significantly lower in patients in Killip class II than in those in class I (0.32 +/- 0.11 vs 0.46 +/- 0.15, p less than 0.001) and in patients with anterior than inferior AMI (0.34 +/- 0.11 vs 0.52 +/- 0.14, p less than 0.001). Of the 36 patients with a severely depressed (0.30 or less) LVEF, 15 (42%) were in Killip class I. Mean RVEF did not differ significantly between Killip class I and II patients (0.42 +/- 0.11 vs 0.40 +/- 0.12, difference not significant) but was significantly lower in patients with inferior than anterior AMI (0.38 +/- 0.09 vs 0.44 +/- 0.11, p = 0.005). In patients with inferior AMI, a depressed RVEF (0.38 or less) was associated with a normal LVEF in 30% and a depressed LVEF in 20%, whereas in those with anterior AMI, a depressed RVEF, observed in 25% of patients, occurred only in association with a depressed LVEF.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous quantitation of exercise-redistribution planar 201TI scintigraphy has shown high sensitivity and specificity in the detection of coronary artery disease and improved detection of individual coronary stenoses over visual analysis. By using similar methodology based on the circumferential profile method, we studied 133 patients to quantitatively assess the extent, depth, and severity of thallium defects compared with consensus visual analysis. These quantitative measurements are objective, requiring only three operator interactions. In comparing quantitative and visual results, a close correlation was found for measurement of extent of thallium defect (r = 0.73) and severity of defect (r = 0.79). In detecting patients with the high-risk scintigraphic pattern of a severe stress thallium defect, a quantitative depth score of greater than or equal to 36 had an 81% sensitivity and an 82% specificity. Thus, this nearly automatic, computerized quantitative method allows objective determination of extent, severity, and depth of planar 201TI defects.

The potential value of the ratio of precordial ST-segment depression to inferior ST-segment elevation as a sign of concomitant right ventricular (RV) ischemia was examined. The study group consisted of 68 patients, admitted within 3 hours of the onset of inferior acute myocardial infarction (AMI), in whom there was no evidence of prior AMI. In 27 of the 34 patients in whom inferior AMI was the result of right coronary artery occlusion proximal to the RV branch, the magnitude of ST-segment depression in lead V2 was 50% or less of the magnitude of ST-segment elevation in lead aVF, whereas in only 3 of the 34 patients in whom the site of occlusion was either distal to the RV branch (n = 23) or in the left circumflex artery (n = 11) was this ratio 50%; in no patient was it less than 50% (p less than 0.001). All 34 patients with occlusion of the right coronary artery proximal to the RV branch also had regional or global ischemic RV dysfunction by radionuclide ventriculography, with a mean RV ejection fraction of 30 +/- 10% compared with 42 +/- 6% in patients with occlusion distal to the RV branch or in the left circumflex artery (p less than 0.001). In conclusion, in patients with evolving inferior AMI, ST-segment depression in lead V2 of 50% or less of the magnitude of ST-segment elevation in lead aVF may be a useful sign (sensitivity 79%, specificity 91%, positive predictive value 90% and negative predictive value 82%) for identifying patients with concomitant RV ischemia.

A new cause of artifactual 201Tl defects on single photon emission computed tomography (SPECT) termed "upward creep" of the heart is described. In 102 consecutive patients undergoing 201Tl SPECT, 30 (29%) demonstrated upward creep defined by an upward movement of the heart of greater than or equal to 2 pixels during acquisition. In 45 consecutive patients with a less than 5% likelihood of coronary artery disease, 17 (38%) had upward creep. Of these nine had reversible 201Tl defects localized to the inferior and basal inferoseptal walls, while none of the 28 without upward creep had defects. The 17 low likelihood patients with upward creep had longer exercise duration and higher peak heart rate than those without upward creep. In five additional low likelihood patients with upward creep in whom imaging was immediately repeated, the upward creep pattern disappeared on the repeated images. After we changed our test protocol to begin imaging 15 min postexercise, only five (14%) of 36 low likelihood patients tested demonstrated upward creep. Upward creep is probably related to a transient increase in mean total lung volume early following exhaustive exercise, resulting in a mean lower position of the diaphragm (and thus the heart) at the beginning of imaging. The frequency of this source of false-positive 201Tl studies can be reduced by delaying SPECT acquisition until 15 min postexercise.

Ventricular function was assessed at rest and during exercise by multiple gated cardiac blood pool scintigraphy before and after coronary artery bypass surgery in 21 patients. Resting left and right ventricular ejection fraction and segmental wall motion were unchanged by surgery. However, the postoperative exercise response of left ventricular ejection fraction (-1 +/- 12% vs 6 +/- 9%) and segmental wall motion score (medium -2.7 [range -8 to 2] vs -0.4 [range -6 to 2]) were significantly improved (p less than 0.05). The normal right ventricular ejection fraction exercise response was maintained after surgery. Previous myocardial infarction in 15 patients did not attenuate the observed improvement in ventricular function. In addition, normal postoperative left ventricular ejection fraction response to exercise was associated with symptomatic improvement. In three of six patients a normal preoperative left ventricular ejection fraction response to exercise was not maintained. Therefore, global and regional left ventricular reserve is improved by coronary bypass surgery and this improvement is not affected by previous myocardial infarction.

Myocardial asynergy is sometimes reversed by coronary bypass, and a noninvasive method of predicting which assess are reversible would be desirable. To assess whether changes in myocardial wall motion observed immediately after exercise can differentiate reversible from nonreversible myocardial asynergy, we evaluated 53 patients by radionuclide ventriculography before and after exercise and again at rest after coronary bypass surgery. Preoperative improvement in wall motion immediately after exercise was highly predictive of the surgical outcome (average chance-corrected agreement, 91 per cent). At surgery the asynergic segments that had improved after exercise were free of grossly apparent epicardial scarring. The accuracy of these predictions for postoperative improvement was significantly greater (P less than 0.01) than that of analysis of Q waves on resting electrocardiography (average chance-corrected agreement, 40 per cent). In contrast, preoperative changes in left ventricular ejection fraction after exercise were not predictive of postoperative resting ejection fraction. We conclude that postexercise radionuclide ventriculography can be used to identify reversible resting myocardial asynergy. This test should prove effective in predicting which patients with myocardial asynergy are most likely to benefit from aortocoronary revascularization.

Left ventricular dysfunction has been implicated in the pathogenesis of septic shock, but little is known about its natural history, cause, and prognostic significance. Left ventricular performance was assessed by serial radionuclide and hemodynamic studies in 35 patients with culture-proven septic shock. The mean age (+/- S.D.) of the group was 64 +/- 18 years; 16 of the subjects were women, and 15 had antecedent heart disease. On the first study, the left ventricular stroke work index was depressed in 33 (94%) patients, and nineteen (54%) had a left ventricular ejection fraction less than 0.48. Twenty-two (63%) of the patients had segmental and four had generalized wall motion abnormalities. Conventional hemodynamic parameters were of no value in predicting the patients who had a depressed left ventricular ejection fraction or segmental abnormalities. Patients with underlying heart disease had a much higher frequency (87%) of segmental dysfunction than those without underlying heart disease (45%; p = 0.016), but no differences were noted in the left ventricular ejection fraction or left ventricular stroke work index of these two groups. Segmental abnormalities and low ejection fractions were seen more often in patients with a large left ventricular end-diastolic volume index. Only five subjects had a systemic vascular resistance index greater than 2580 dynes X sec X cm-5 per m2, and the correlation between systemic vascular resistance index and left ventricular ejection fraction was poor. No difference was found in the mean coronary perfusion pressure of those with segmental abnormalities and those with normal wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

A comprehensive method is described for quantitation of the spatial distribution of TI-201 in the myocardium and its changes with time. The method, applied here to 51 patients, uses bilinear interpolative background subtraction to compensate for tissue crosstalk, and circumferential profiles to quantitate the relative radionuclide activity in the myocardium as an angular function with origin at the center of the left-ventricular cavity. In addition, washout circumferential profiles are calculated as percent washout from the stress circumferential profiles. Abnormal thallium distribution or washout is identified by automatic computer comparison of each patient's profiles with the corresponding limits of normal profiles, determined from the pooled profiles of 31 normal patients. In these 31, the computer output was normal in all cases. In 20 patients with angiographically documented coronary artery disease, 19 were determined to be abnormal by this method. This new computerized treatment provides accurate objective assessment of the presence of coronary artery disease.

To determine the clinical and hemodynamic correlates as well as therapeutic and prognostic implications of predominant right ventricular dysfunction complicating acute myocardial infarction, 43 consecutive patients with scintigraphic evidence of right ventricular dyssynergy and a depressed right ventricular ejection fraction (less than 0.39) in association with normal or near normal left ventricular ejection fraction (greater than or equal to 0.45) were prospectively evaluated. All 43 patients had acute inferior infarction, forming 40% of patients with acute inferior infarction, and only eight (24%) had elevated jugular venous pressure on admission. On hemodynamic monitoring, 74% of patients had a depressed cardiac index (less than or equal to 2.5 liters/min per m2), averaging 2.0 +/- 0.05 for the group. Of these, 30% did not demonstrate previously described hemodynamic criteria of predominant right ventricular infarction (right atrial pressure greater than or equal to 10 mm Hg or right atrial to pulmonary capillary wedge pressure ratio greater than or equal to 0.8, or both). The left ventricular end-diastolic volume was reduced to 49 +/- 11 ml/m2 (n = 22) and correlated significantly with the stroke volume index (r = 0.82; p less than 0.0001) and cardiac index (r = 0.57; p = 0.005). The follow-up right ventricular ejection fraction, determined in 33 patients, showed an increase of 10% or greater in 26 (79%), increasing from a mean value of 0.30 +/- 0.06 to 0.40 +/- 0.09 (p less than 0.0001) without a significant overall change in the mean left ventricular ejection fraction (0.56 +/- 0.10 to 0.56 +/- 0.11, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Eighty-one consecutive patients presenting within 3 hours of the onset of acute myocardial infarction (AMI) and without contraindications to thrombolytic or anticoagulant therapy received a 15- to 30-minute intravenous infusion of 750,000 or 1.5 million units of streptokinase (STK) followed by anticoagulation. Treatment was instituted 130 +/- 41 minutes after the onset of symptoms and reperfusion was achieved 36 +/- 26 minutes later. Reperfusion of the "infarct artery" was recognized by indirect clinical criteria in 78 patients (96%). In all 66 patients who underwent coronary angiography 3 to 7 days later, there was complete concordance between indirect and angiographic evidence of reperfusion. In 6 patients there was early reocclusion within 24 hours of treatment; in 4 of these patients, the artery was reopened with an additional dose of STK. Two elderly patients suffered an intracranial hemorrhage and there were 8 other major hemorrhagic complications, of which 7 were related to procedural trauma. Five patients (6.2%) died in the hospital. The results of intravenous STK thrombolytic therapy are compared with those of our previous study using intracoronary STK.

The effects of aerobic and anaerobic exercise on ventricular performance were studied in 13 normal subjects who underwent simultaneous pulmonary gas exchange evaluation and exercise radionuclide ventriculography in the supine and upright postures. Right and left ventricular ejection fraction was measured serially at 2-minute intervals during exercise. The anaerobic threshold occurred at 74% and 80% of maximum heart rate, respectively, during upright and supine exercise. Left and right ventricular ejection fractions rose from rest to the anaerobic threshold (p less than 0.01, p less than 0.01, respectively) and there was a further increase between the anaerobic threshold and maximum exercise (p less than 0.01, p less than 0.01, respectively). The rate of rise of ejection fraction beyond the anaerobic threshold was slightly blunted compared with the rise prior to attaining the anaerobic threshold. There was no significant difference in ventricular performance between supine and upright exercise. The data demonstrate that ventricular performance increases steadily during exercise and is not limited by the conversion of aerobic to anaerobic metabolism.

Patients with a history of typical angina but negative exercise electrocardiography represent a subgroup with an intermediate likelihood of having coronary artery disease and future cardiac events. A retrospective study of the prognostic utility of stress-redistribution thallium-201 scintigraphy was performed in 190 such patients. A second group of 203 patients with typical angina and a positive exercise electrocardiogram were analyzed for comparative scintigraphic purposes. The cardiac event rate for the 144 negative exercise electrocardiogram patients with normal thallium results was 5 vs 15% in the 46 patients with abnormal thallium results (p = 0.01). These patients were further stratified into high (14 to 18%), intermediate (9%) and low (less than 2%) risk groups for future cardiac events based on combining the thallium results with the percentage of maximal predicted heart rate achieved. A multivariate analysis revealed that an abnormal thallium result was the only significant correlate of future cardiac events. Mechanisms responsible for the discordant finding of a negative exercise electrocardiogram in patients with typical angina include (1) false-positive angina symptomatology in low prevalence coronary artery disease groups in whom the thallium test is negative, and (2) "electrocardiographically silent" ischemia in patients in whom the thallium test is positive. These findings reveal that thallium stress-redistribution scintigraphy can be used to stratify 1-year prognosis in this subgroup of patients with typical angina and negative exercise electrocardiograms.

We studied the relationship between the heart rate at the time of onset of exercise-induced wall motion abnormality and the severity of coronary artery disease in 89 patients who underwent exercise equilibrium radionuclide ventriculography as part of their evaluation for coronary artery disease. Segmental wall motion was scored with a five-point system (3 = normal; -1 = dyskinesis); a decrease of one score defined the onset of wall motion abnormality. The onset of wall motion abnormality at less than or equal to 70% of maximal predicted heart rate had 100% predictive accuracy for coronary artery disease and higher sensitivity than the onset of ischemic ST segment depression at similar heart rate during exercise: 36% (25 of 69 patients with coronary disease) vs 19% (13 of 69 patients), p = 0.01. Wall motion abnormality occurring at less than or equal to 70% of maximal predicted heart rate was present in 49% of patients (23 of 47) with critical stenosis (greater than or equal to 90% luminal diameter narrowing), and in only 5% of patients (2 of 42) without such severe stenosis, p less than 0.001. The sensitivity of exercise-induced wall motion abnormality occurring at a low heart rate for the presence of severe coronary artery disease was similar to that of a deterioration in wall motion by more than two scores during exercise (49% vs 53%) or an absolute decrease of greater than or equal to 5% in exercise left ventricular ejection fraction (49% vs 45%).(ABSTRACT TRUNCATED AT 250 WORDS)

The pattern of reverse redistribution on the day 10 poststreptokinase resting thallium-201 myocardial scintigrams is a common finding in patients who have undergone streptokinase therapy in evolving myocardial infarction. To investigate this phenomenon, 67 patients who underwent streptokinase therapy were studied pre- and 10 days poststreptokinase therapy resting thallium-201 studies, poststreptokinase therapy resting radionuclide ventriculography and coronary arteriography (60 of the 67 patients). Of the 67 patients, 50 (75%) showed the reverse redistribution pattern on the day 10 thallium-201 study (Group I), 9 (13%) had a nonreversible defect (Group II) and the remaining 8 (12%) had a normal study or showed a reversible defect (Group III). The reverse redistribution pattern was associated with patency of the infarct-related artery (100%), quantitative improvement in resting thallium-201 defect size from day 1 to day 10 study (94%) and normal or near normal wall motion on day 10 radionuclide ventriculography (80% of segments with marked and 54% of those with mild reverse redistribution). In contrast, nonreversible defects were associated with significantly less frequent patency of the infarct-related artery (67%, p = 0.01), improvement in defect size (11%, p less than 0.001) and normal or near normal wall motion (21%, p less than 0.05). Group III patients were similar to Group I with respect to these variables. The quantitated thallium-201 percent washout was higher in the regions with the reverse redistribution pattern (49 +/- 15%) compared with the contralateral normal zone (24 +/- 15%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Thallium imaging in conjunction with electrocardiographic stress testing has become a widely utilized method for evaluating the presence and location of coronary artery disease. The literature has emphasized the appearance of the left ventricle with little mention of the right ventricle. This report presents the initial demonstration of abnormal right ventricular myocardial radionuclide visualization due to right coronary artery stenosis, as exemplified in two patients. In both patients a perfusion defect was documented in the free wall of the right ventricle with early redistribution imaging showing reversibility of these defects. Both patients were found to have proximal stenosis of the right coronary artery at cardiac catheterization. Thereby, the appearance of the free right ventricular wall on thallium imaging may provide useful additional information regarding presence and location of right coronary artery stenosis.

The development of quantitative techniques to assist in the analysis of planar thallium-201 stress-redistribution scintigrams has led to improved abilities of this modality to detect the presence of and to localize significant coronary artery disease (CAD). This fact has encouraged the reevaluation of its capabilities relative to other types of scintigraphic data collection, including seven-pinhole tomography. We have undertaken a comparison of planar scintigraphy and seven-pinhole tomography to detect in 40 exercised patients (23 with angiographically demonstrated CAD, eight with normal coronary angiograms, and nine with less than or equal to 1% likelihood of having CAD) the presence of significant CAD and to localize it correctly to an individual coronary artery. Emphasis was placed on similar imaging conditions and on analysis of images by the same quantitative program of TI-201 distribution and washout. Both techniques were found to be highly sensitive and specific for disease detection and localization. Importantly, seven-pinhole tomography did not significantly improve results.

A comprehensive method is described for quantification of the relative 3-dimensional distribution of Tl-201 in the myocardium, following stress and subsequent washout. The method uses maximal-count circumferential profiles of well-defined long- and short-axis tomograms to determine the 3-dimensional distribution of Tl-201; it then maps this distribution onto a 2-dimensional polar representation. Abnormal thallium distribution or washout is identified by automatic computer comparison of each patient's profile with the corresponding lower limits of normal profiles. Abnormality is expressed as a percentage of the entire myocardium by use of polar maps for extent and severity. The binary extent map expresses the degree of abnormality. Preliminary criteria for abnormality were derived from the tomographic results of 25 normals and 28 patients with documented coronary artery disease. The results were normal in 23 of the 25 normals and were abnormal in 25 of the 28 CAD patients. In addition, the computer output correctly localized the presence or absence of disease in 46 of 56 coronary circulations.

Because Tl-201 SPECT requires that patients remain in an awkward position for a prolonged time, patient motion is a potentially serious source of artifactual defects on tomographic reconstructions. Thus, a simple method was developed for detection and correction of motion from SPECT images using a Co-57 point source placed on the lower anterior chest, an area remaining in the camera's field of view throughout imaging. In the absence of motion, this point source inscribes a straight line on planar summation of the 32 projections over 180 degrees. Movement is detected by deviation from this line. The number of pixels of motion is used to shift images so that the resultant images of the point source are linear. The method of motion detection and correction was tested in 48 consecutive patients undergoing Tl-201 SPECT. The corrected and uncorrected images were reconstructed and long and short axis tomographic cuts were quantitatively analyzed using circumferential profiles of maximal counts with comparison to the lower limits of normal. Motion was detected in eight of 48 patients (17%). The amount of motion was 2 pixels in three patients and 1 pixel in five patients. Quantitative defect extent was less after correction in seven of eight patients, with a mean decrease of 71% in patients with 2 pixel motion and 44% in patients with 1 pixel motion. This corresponded with a definite reduction in the size of the tomographic defect by visual analysis, and closer resemblance to quantitatively analyzed planar images performed either before or after tomography in the same patient.(ABSTRACT TRUNCATED AT 250 WORDS)

When coronary artery disease is extensive and of relatively uniform severity, regional myocardial hypoperfusion may be balanced during stress, precluding development of spatially relative perfusion defects. Assessment of the washout of thallium-201 from myocardial regions may provide diagnostic assistance in these cases because washout analysis is spatially nonrelative and hypoperfused myocardial regions manifest a slow thallium-201 washout rate. In 1,265 consecutive patients having quantitatively analyzed stress-redistribution scintigraphy, 46 had a diffuse slow washout pattern with no or a maximum of one regional perfusion defect. Thirty-two underwent clinically indicated coronary angiography, and 23 (72%) of these were found to have three vessel or left main disease. Of 30 similar patients without a diffuse slow washout pattern and with no or a maximum of one perfusion defect, only 5 (17%) had extensive coronary disease. An independent relation between diffuse slow washout and extensive coronary disease was demonstrated by a Mantel- Haentzel chi-square analysis of a wide variety of other indexes of extensive disease. A diffuse washout abnormality, even in the absence of other scintigraphic, clinical or electrocardiographic indicators, carries a high predictive value for three vessel or left main coronary artery disease. The predictive value is maintained when the exercise level achieved is submaximal. Although an infrequent occurrence (3.6% of tested patients), a diffuse slow washout pattern without other scintigraphic indications of extensive coronary disease should lead to further diagnostic testing.

Twenty-one patients were studied who underwent thallium-201 stress-redistribution single photon emission computed tomography (SPECT) both before and after coronary artery bypass grafting (n = 15) or transluminal coronary angioplasty (n = 6). All patients underwent thallium imaging 15 min, 4 h and late (18 to 72 h) after stress as part of the preintervention thallium-201 scintigram. In a total of 201 tomographic myocardial segments with definite post-stress thallium-201 perfusion defects in which the relevant coronary arteries were subsequently successfully reperfused, the 4 h redistribution images did not predict the postintervention scintigraphic improvement: 67 (85%) of the 79 4 h reversible as well as 88 (72%) of the 122 4 h nonreversible segments improved (p = NS). The 18 to 72 h late redistribution images effectively subcategorized the 4 h nonreversible segments with respect to postintervention scintigraphic improvement: 70 (95%) of the 74 late reversible segments improved after intervention, whereas only 18 (37%) of the 48 late nonreversible segments improved (p less than 0.0001). The frequency of late reversible defects and the frequency of postrevascularization improvement of late nonreversible defects are probably overestimated by this study because of referral biases. The cardiac counts and target to background ratios from late redistribution studies resulted in satisfactory cardiac images for visual interpretation. For optimal assessment of the extent of viable myocardium by thallium-201 scintigraphic studies, late redistribution imaging should be performed when nonreversible defects are observed on 4 h redistribution images.

In 22 patients with single-vessel coronary artery disease and no history of infarction, stress Tl-201 rotational tomography was used to quantify the extent of jeopardized myocardium. The vertical long- and short-axis tomograms were quantified by means of maximum-count circumferential profile analysis. The scintigraphic extent of jeopardized myocardium was expressed as the percentage of profile points falling 2.5 standard deviations below a previously established mean normal profile and was correlated to a quantitatively expressed angiographic extent of jeopardized myocardium. The extent of jeopardized myocardium varied from 1% to 55% by tomography and 8% to 50% by angiography and correlated with an r = 0.79 and a 10% standard error of the estimate. Defect intensity, reflecting the mean depth by which the abnormal points fell below the normal value of greater than or equal to 10%, was 100% specific for a coronary stenosis of greater than or equal to 70%. In conclusion, this study demonstrates that: patients with single-vessel disease have highly variable extents of hypoperfused myocardium defined by Tl-201 tomography and coronary arteriography, there is a fair relationship between angiographic jeopardy score and perfusion defects by Tl-201 tomography during exercise, and Tl-201 tomography may be used to noninvasively determine the extent of hypoperfused myocardium in coronary artery disease.

The biodistribution, dosimetry, and safety of a new myocardial imaging agent, 99mTc-hexakis-2-methoxyisobutyl isonitrile (HEXAMIBI), was evaluated in 17 normal volunteers at rest and exercise (Phase I studies). Technetium-99m HEXAMIBI clears rapidly from the blood with good myocardial uptake and favorable myocardial-to-background ratios for myocardial imaging. Dosimetry allows for administration of up to 30 mCi (1, 110 Bq) of [99mTc]HEXAMIBI. The myocardial images were of good quality and appeared less granular with sharper myocardial walls compared to 201T1 images. The clinical efficacy of [99mTc]HEXAMIBI planar stress and rest imaging was evaluated in a multicenter Phase II clinical trial involving 38 patients. Of 36 patients with significant coronary artery disease, 35 patients (97%) had abnormal 201T1 stress images, and 32 (89%) had abnormal [99mTc]HEXAMIBI stress images (P = N.S.). Technetium-99m HEXAMIBI images correlated in 31/35 patients (86%) who had either scar or ischemia on 201T1 images. By segmental myocardial analysis, exact concordance was obtained in 463/570 myocardial segments (81%). This multicenter Phase I and II study indicates that planar [99mTc]HEXAMIBI stress imaging is safe and compares well with 201T1 stress imaging for detection of coronary artery disease.

One hundred eight-three men underwent stress-redistribution thallium-201 myocardial perfusion tomography. After evaluation of various preprocessing filters in a phantom study, the Butterworth filter with a frequency cutoff of 0.2 cycles/pixel, order 5 (which provided optimal filter power) was used in the back projection algorithm of the patient studies. All short-axis and apical portions of vertical long-axis images were quantified by dividing each myocardial slice into 60 equal sectors and displaying the maximal count per sector as a linear profile. In a pilot group consisting of 20 normal men (less than 5% likelihood of coronary artery disease) and 25 men with coronary artery disease (greater than or equal to 50% coronary stenosis by angiography), profiles representing the lowest observed value below the mean normal profiles provided the best threshold for defining normal limits. Abnormal portions of the patient profiles were plotted on a two-dimensional polar map. The polar map was divided into 102 sectors, and sectors with a probability of greater than or equal to 80% for disease of each one of the three major coronary arteries were clustered to represent specific coronary artery territories. Receiver operating characteristic curve analysis for defect size showed that the optimal threshold for defining a definite perfusion defect was 12% for the left anterior descending and left circumflex and 8% for the right coronary artery territories. These criteria were prospectively applied to an additional 92 patients with angiographic coronary artery disease, 18 patients with normal coronary arteriograms and 28 patients with less than 5% likelihood of coronary disease. Sensitivity, specificity (in patients with normal coronary arteriograms) and normalcy rate (in patients with less than 5% likelihood of coronary artery disease) for overall detection of coronary disease were 96%, 56% and 86%, respectively. Sensitivity and specificity for identification of individual diseased vessels were, respectively, 78% and 85% for the left anterior descending, 79% and 60% for the left circumflex and 81% and 71% for the right coronary artery. These results were not significantly different from those of the pilot group. An optimized quantitative method for interpretation of stress thallium-201 myocardial perfusion tomography has been developed. Prospective application of this method indicates that the technique is accurate for the overall detection of coronary artery disease and identification of disease in individual arteries.