Myocardial imaging in myocardial infarction: technetium vs. thallium.
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Biomedical subjects
Publications and source records attributed to M C Gerson.
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After intravenous administration of Tc-99m DMPE the flow-dependent kinetics were studied in dogs during induced ischemia and during induced maximal reactive hyperemia. A control group was also studied. Mean time-activity curves obtained from the myocardial wall were compared within the same intervention group and also with other groups. During reactive hyperemia, there was a rapid and absolute increase in uptake followed by a rapid washout, whereas during ischemia there was a slow and decreased uptake followed by a slow washout. The magnitude of Tc-99m DMPE uptake during reactive hyperemia was slightly less than that of Tl-201, but the decreased uptake with ischemia was about equal for the two agents. Following maximal uptake in the myocardium the effective half-life of Tc-99m DMPE was one-third to one-fourth that of Tl-201. The similar kinetics of Tc-99m DMPE compared to Tl-201 suggests its usefulness in the evaluation of ischemic heart disease.
Newly synthesized Tc-99m dichlorobis(1,2-dimethylphosphino)ethane (DMPE) was investigated as a myocardial imaging agent with respect to its kinetics (dependent on both time and regional coronary blood flow), its percent organ uptake, and its imaging characteristics in the anesthetized dog. Most of these data are compared with those of Tl-201. Blood clearance of the two agents is essentially the same. Compared with Tl-201, Tc-99m DMPE shows faster overall kinetics, higher heart-to-lung ratio, equally good correlation with a wide range of regional blood flows, and higher liver uptake. At the time of peak myocardial uptake, the mean heart uptake of Tl-201 is 4.3%, compared with 2.9% for Tc-99m DMPE, yet only 0.9% uptake of Tc-99m DMPE is found in the lung as compared with 3.3% for Tl-201. These differences result in a heart-to-lung ratio of 2:1 for Tc-99m DMPE and 1:1 for Tl-201, based on the data obtained from the time-activity curve. The quantitative findings are supported by the superior quality of Tc-99m DMPE images of both normal and infarcted dog heart. The high hepatic uptake of Tc-99m DMPE is not a serious problem if images are obtained within 5-60 min after dose. These basic kinetic studies suggest that Tc-99m DMPE is a promising myocardial imaging agent.
Exercise electrocardiography was performed in 100 asymptomatic male volunteers with a mean age of 42.6 years. The R wave and total RS amplitude and the magnitude of physiologic S-T segment depression at the J junction were quantitated for a modified bipolar CC5 lead and a vertically oriented bipolar lead (VL) using computer-averaged groups of 25 consecutive QRS complexes from each of seven stages of rest and exercise. Computer-generated X-Y plots were used to examine the correlations between the magnitude of S-T depression and the R wave and total RS amplitudes. The magnitude of S-T depression and of the R wave amplitude were unrelated at standing rest but showed increasing correlation with progressive increases in exercise heart rate (correlation coefficient = 0.425, p < 0.00001 at maximal exercise). The total RS amplitude was also related to the magnitude of S-T depression during exercise, but the correlations did not improve progressively with increases in exercise heart rate. The magnitude of S-T depression was more closely related to R wave amplitude and total RS amplitude in the vertically oriented lead than in the CC5 lead. These data demonstrate a significant relation between the magnitude of R wave and total RS amplitudes and the magnitude of physiologic S-T segment depression in normal subjects during exercise. They suggest the need for evaluation of S-T depression corrected for R wave amplitude in an attempt to improve the diagnostic accuracy of the exercise electrocardiogram. The data also suggest that the criteria for abnormal S-T depression should take into consideration the different R wave voltages reflected by different types of recording leads.
Resting 12-lead electrocardiographic records from 849 patients who underwent coronary cineangiographic studies were reviewed for U wave negativity without knowledge of the clinical data or angiographic results. In order to evaluate U wave negativity as an independent electrocardiographic sign, patients with significant Q waves in the anterior leads were excluded from the final data analysis leaving 760 patients. Twenty-seven patients had U wave negativity in leads I, aVL or V4 through V6. For the study population, the prevalence of coronary artery disease was 64 percent (484 or 760); the prevalence of significant left anterior descending or left main coronary artery stenosis was 46 percent (350 of 760); and the prevalence of angiographic left ventricular dysfunction was 41 percent (309 of 754). Among 27 patients with resting U wave negativity the prevalence of coronary artery disease was 89 percent (24 of 27); the prevalence of left anterior descending or left main disease was 89 percent (24 of 27); and the prevalence of angiographic left ventricular dysfunction was 80 percent (20 of 25). Among patients selected for coronary cineangiographic study, U wave negativity was a significant predictor (p < 0.001) of greater than or equal to 75 percent stenosis of the left anterior descending or left main coronary artery and of left ventricular dysfunction (p < 0.001).
A 57 year old women with substernal nonexertional chest pain and angiographically patent coronary arteries was evaluated with two dimensional echocardiography and myocardial perfusion scintigraphy after provocation of pain with methacholine. Simultaneous with the development of angina pectoris, the electrocardiogram demonstrated S-T segment elevation in leads II, III and aVF, followed by atrioventricular block. The echocardiogram revealed akinesia of the previously normally contracting left ventricular posterior wall during pain followed by hyperkinesia after the administration of nitroglycerin. Perfusion imaging suggested reversible inferior wall hypoperfusion. Thus, these studies provided noninvasive documentation of segmental left ventricular dysfunction and hypoperfusion during variant angina.
The prevalence and cineangiographic correlates of exercise-induced inversion of U waves were studied in 248 patients. Exercise-induced U-wave inversion was observed in 36 patients (15%), of whom 35 had greater than or equal to 75% stenosis in one or more of the major coronary arteries. The proximal left anterior descending or left main coronary artery was involved in 33 of these patients, including 24 patients with no electrocardiographic evidence of anterior myocardial infarction. Exercise-induced U-wave inversion was observed in the absence of an abnormal resting 12-lead ECG. Only one of the 82 patients (1.2%) without significant coronary artery disease demonstrated exercise-induced U-wave inversion, and this patient had a primary cardiomyopathy. We conclude that exercise-induced inversion of the U-wave is highly predictiveof significant coronary artery disease and, more specifically, of disease of the proximal left anterior descending coronary artery.
BACKGROUND: 99mTc-labeled Q12 (99mTc-Q12) is a new imaging agent that produces myocardial visualization in humans. This study examined the hypothesis that a 100-minute rest-exercise tomographic imaging protocol after injection of 99mTc-Q12 can be used to detect the presence or absence of coronary artery stenoses. METHODS AND RESULTS: Imaging with 201Tl and 99mTc-Q12 was performed in 20 patients with angiographically documented coronary artery disease and 10 "normal" subjects including two patients with chest pain and normal coronary arteriograms and eight subjects with a very low likelihood of occlusive coronary disease. 99mTc-Q12 was imaged beginning 15 minutes after injection at rest and with exercise. In the 20 patients, a corresponding myocardial defect was detected in blinded fashion in 18 with 201Tl and 17 with 99mTc-Q12 (difference not significant). Of 10 patients without evidence of coronary disease, nine had a normal 201Tl scan and eight had a normal 99mTc-Q12 scan (difference not significant). Agreement of 99mTc-Q12 and 201Tl imaging for detection of regional myocardial perfusion defects was excellent (kappa = 0.88). Identification of the presence or absence of angiographically documented coronary disease in individual coronary artery distributions was 80% and 82% for 201Tl imaging and 73% and 87% for 99mTc-Q12 (difference not significant). CONCLUSION: 99mTc-Q12, used in a rest-exercise sequence that can be completed in 100 minutes, provided identification of regional myocardial perfusion defects similar to that of 201Tl.
BACKGROUND: Trans (N,N'-ethylene bis(acetylacetoneimine)) bis(tris(3-methoxy-1-propyl) phosphine) 99mTc(III) (99mTc-Q3) has been developed for myocardial perfusion imaging. Biokinetic studies and dosimetry analysis have been completed for six healthy volunteers. METHODS AND RESULTS: The same-day two-injection protocol involved (1) an average rest injection of 241 MBq of 99mTc-Q3 followed by myocardial single-photon emission computed tomography (SPECT) at 15.0 minutes and a whole body (WB) scan at 1.5 hours; and (2) an average stress injection during treadmill exercise of 744 MBq of 99mTc-Q3 at 2.4 hours (postrest injection) followed by myocardial SPECT and additional WB scans at 1.5, 3.5, 6.5, and 21 hours poststress injection. Total urine was collected over 24 hours. Absolute organ activities were determined by conjugate counting methods. The two-injection data were simplified to a one-injection equivalent data set to facilitate dosimetry analysis. Decay corrected average percentage uptake values, plus or minus one standard deviation, for the myocardium were 1.4% +/- 0.2% at approximately 1.5 hours for both the postrest and poststress injections. The average biologic half-time for the myocardium was 26.4 hours. The highest organ uptake values included the gallbladder with 5.5% +/- 1.9% and the liver with 4.1% +/- 1.0% at the 1.5 hours poststress scan time. The sum of all gastrointestinal (GI) tract components was 18.8% +/- 9.4% at approximately 6.5 hours poststress injection (before any fecal elimination). The total 24 hour urine clearance was 17.1% +/- 2.4%. The gallbladder wall and upper large intestine wall received the highest doses at 0.024 and 0.023 mGy/MBq, respectively. CONCLUSION: The effective dose equivalent is estimated to be 0.01 mSv/MBq, which for an administration of 1110 MBq (30 mCi) is less than half that of a standard imaging protocol using 111 MBq (3 mCi) of 201Tl, and comparable to the published estimates for 99mTc-labeled sestamibi and 99mTc-labeled tetrofosmin (also normalized to 1110 MBq of administered activity). The 99mTc-Q3 exhibits myocardium uptake similar to that for these other two 99mTc agents.
BACKGROUND: An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease. METHODS AND RESULTS: The time constant of isovolumic relaxation (T) and the left atrioventricular gradient were measured with micromanometer catheters and diastolic left ventricular filling variables were measured with radionuclide ventriculography in nine anesthetized, open-chest dogs with an acute coronary artery occlusion. Infusion of the positive inotropic drug dobutamine hydrochloride (5 to 10 micrograms/kg/min) resulted in a 35% shortening of T and a 37% increase in the radionuclide first-half filling fraction (both p < 0.05), but no change in the left atrioventricular gradient. Conversely, infusion of the alpha-adrenergic vasoconstrictor phenylephrine hydrochloride (20 to 40 micrograms/min) augmented left ventricular load, increasing the atrioventricular gradient by 45%, but had no significant effect on T or the first-half filling fraction. Infusion of the direct-acting vasodilator, sodium nitroprusside (80 to 120 micrograms/min), was accompanied by a 14% lengthening of T with a corresponding 28% decrease in the first-half filling fraction (both p < 0.05). CONCLUSION: In an anesthetized, open-chest canine model of acute myocardial ischemia, the radionuclide first-half filling fraction reflects pharmacologically induced changes in the lusitropic state of the left ventricle with relative independence of loading conditions.
BACKGROUND: This study was a direct comparison of the imaging characteristics of 99mTc-labeled Q12 (99mTc-Q12) and 99mTc-labeled Q3 (99mTc-Q3) in the same patients. METHODS AND RESULTS: In 10 patients with known angiographic coronary artery anatomy, 99mTc-Q12 and 99mTc-Q3 myocardial imaging were performed. Tomographic myocardial imaging was started 15 minutes after tracer injection at rest and with treadmill exercise. Ratios of heart-to-lung and heart-to-liver activity were calculated from the anterior plane projections of the tomograms at 20 minutes after tracer injection. The presence or absence of angiographic coronary artery disease was correctly determined from 99mTc-Q12 images in 10 of 10 patients with 99mTc-Q12 and in 9 of 10 patients with 99mTc-Q3. The presence or absence of a greater than 50% stenosis in an individual coronary vessel was correctly predicted for 26 of 30 vessels with 99mTc-Q12 (87%) and in 27 of 30 vessels with 99mTc-Q3 (90%, p = NS vs 99mTc-Q12). Mean heart-to-lung activity ratio at rest was 1.50 for 99mTc-Q12 and 1.93 for 99mTc-Q3 (p < 0.01). Mean heart-to-liver activity ratio at rest for 99mTc-Q12 was 0.78 versus 0.54 for 99mTc-Q3 (p < 0.0001). CONCLUSIONS: In 10 patients with chest pain and angiographically defined coronary anatomy, 99mTc-Q12 and 99mTc-Q3 provided similar detection of coronary artery stenoses. At 20 minutes after tracer injection, heart-to-liver activity ratios were more favorable for 99mTc-Q12 than for 99mTc-Q3, but 99mTc-Q3 resulted in a more favorable ratio of heart-to-lung activity.
BACKGROUND: Based on physical properties, 99mTc-labeled perfusion agents offer several advantages over 201Tl for myocardial perfusion imaging. The results of in vivo and experimental studies, along with preliminary experience in human subjects, have shown 99mTc-labeled furifosmin to be a promising new perfusion tracer. The purpose of this study was to evaluate the safety of a new myocardial perfusion agent, 99mTc-labeled furifosmin (Q12), and determine the concordance of furifosmin perfusion scintigraphy to 201Tl imaging. In addition, we sought to determine the normalcy rate of myocardial scintigraphy with furifosmin. METHODS AND RESULTS: One hundred fifty patients constituted the study group in this multicenter trial. Patients underwent exercise testing with furifosmin injected at peak exercise, and tomographic imaging was begun 15 to 30 minutes afterward. After a separate injection, resting images were obtained 3 to 4 hours later. Thallium scintigraphy was performed within 2 weeks of the furifosmin scans, after a similar exercise workload. Patients with a low likelihood of coronary artery disease (n = 39) also underwent furifosmin imaging. All images were processed and displayed in uniform manner and interpreted by a panel of readers. No adverse effects or clinically important laboratory alterations were related to furifosmin imaging. Image quality was slightly better with furifosmin than with thallium. The overall concordance between the perfusion studies was 86% (kappa value = 0.669). The normalcy rate for furifosmin scintigraphy was 100%. CONCLUSIONS: 99mTc-labeled furifosmin is a promising new 99mTc-labeled myocardial perfusion agent, providing diagnostic results similar to those obtained with 201Tl.
With publication of the studies by Khaw et al. and Beanlands et al. in this issue of the Journal, there is mounting evidence that 99mTc glucarate is taken up by infarcted but not by ischemic myocardium. The early myocardial distribution and rapid blood-pool clearance of 99mTc glucarate suggest important diagnostic potential in the very early detection of acute myocardial infarction and for the identification of successful acute revascularization therapy. To understand the full diagnostic implications of 99mTc glucarate accumulation in the myocardium, larger human trials are now needed. It will be critically important to document the capabilities of 99mTc glucarate to identify, early on, acute myocardial infarction in the presence of a persistently occluded infarct-related coronary artery in human beings.