Myocardial
Imaging in the Noninvasive
Patients With Suspected
BERTRAM H.
WILLIAM
Baltimore,
PITT,
MD
STRAUSS,
MD
Maryland
From the Division of Cardiology, Department of Medicine, and the Division of Nuclear Medicine, Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Md. This work was supported by Grants GM-10548 and PH43-NHLI-67-1444 from the U. S. Public Health Service, Bethesda, Md. Address for reprints: Bertram Pitt, MD, Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, 601 N. Broadway, Baltimore, Md. 21205.
lschemic
Evaluation of
Heart Disease
Three noninvasive radioactive tracer techniques for evaluating patients with ischemic heart disease are described: (1) myocardial perfusion imaging, (2) acute infarct imaging, and (3) the gated blood pool scan. Myocardial perfusion imaging with tracers that distribute in the myocardium in relation to regional blood flow allows detection of patients with transmural and nontransmural infarction by the finding of decreased tracer concentration in the affected region of the myocardium. If these tracers are injected at the time of maximal stress to patients with significant coronary arterial stenosis but without infarction, areas of transient ischemia can be identified as zones of decreased tracer concentration not found when an examination is performed at rest. Acute infarct imaging with tracers that localize in acutely damaged tissue permits separation of patients with acute myocardial necrosis from those without infarction and those with more chronic damage. The gated blood pool scan permits assessment of left ventricular function and regional wall motion. The measurement of ventricular volumes, ejection fraction and regional wall motion adds significantly to the determination of hemodynamic variables in assessing patients with acute infarction. The technique also permits detection of right ventricular dysfunction. Performance of a combination of these radioactive tracer techniques is often advantageous, particularly in patients with suspected infarction. The techniques can establish whether infarction is present, whether it is acute, where the damage is located and how extensive it is; they can also provide a measure of the effect of this damage on left ventricular function.
The evaluation of a patient with suspected ischemic heart disease includes a consideration of the following questions: (1) Are the symptoms due to ischemic heart disease? (2) What is the extent of the disease and where is it located? (3) How does the lesion affect cardiac function? (4) Is therapy benefiting myocardial perfusion and function? Three noninvasive radioactive tracer techniques are currently available to answer these questions. The first is myocardial perfusion imaging with tracers such as potassium-43 or thallium-201 that concentrate in myocardial cells in proportion to blood flow. In this procedure areas of ischemia ‘or infarction appear as a zone of decreased tracer concentration. The second technique utilizes tracers such as technetium-99m-labeled pyrophosphate, tetracycline or glucoheptonate that concentrate in acutely damaged tissue. These procedures demonstrate areas of acute infarction as zones of increased tracer concentration. The third procedure is the gated cardiac blood pool scan, which permits the measurement of left ventricular ejection fraction and regional myocardial wall motion.
April 1976
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Myocardial
Perfusion
PITT AND STRAUSS
formed up to 1 hour after administration of potassium-43 (longer after thallium-201) and still reflect myocardial perfusion. Later scans reflect both perfusion and the regional rate of tracer loss. The longer the interval between injection and imaging the more important is the rate of regional loss as a determinant of tracer distribution.
Imaging
Relation to myocardial blood flow: The tracers most freqtiently used for myocardial perfusion imaging are the monovalent cations, potassium-43, rubidium-81, cesium-129 and, recently, thallium-201 (Table I).‘-” The initial distribution of these tracers in the myocardium is a function of both coronary blood flow and myocardial sodium, potassium adenosine triphosphatase activity. To determine which of these factors is most important in defining the regional distribution of these tracers, Prokop et a1.4 compared the regional distribution of ionic potassium-43 with that of radioactive microspheres administered into the left atrium of dogs as an indicator of blood flo~.~ The regional myocardial distribution of potassium was similar to that of microspheres under normal conditions, during experimental ischemia and after complete coronary arterial occlusion (Fig. 1). These data suggest that the major determinant of ionic tracer distribution is blood flow although the relation to flow is not always linear. The extraction efficiency of the myocardium for cationic tracers decreases with marked increases in flow but increases when flow is less than 10 percent of norma1.5 Extraction efficiency may also be altered by drugs such as digitalis that affect sodium, potassium adenosine triphosphatase or by drugs such as insulin that affect membrane permeability.6 Despite these variations in total myocardial concentration the regional distribution of tracer appears to represent flow to a sufficient degree to be clinically useful. The ionic tracers, after initial concentration in the heart, begin to redistribute7 so that eventually they approximate the distribution of total body potassium. Their rate of leakage from the myocardium is relatively slow and differs for each tracer. Potassium has a clearance half-time in the heart between 1 l/2 and 3 hours whereas thallium has a clearance half-time from 7 to 24 hours. Myocardial imaging can therefore be per-
TABLE
Selection of tracer: The physical as well as the biologic properties of a tracer are important in its selection for myocardial perfusion imaging. The collimator and detector designs of currently available instruments optimize detection of photons within a range of 100 to 200 kev. Because potassium-43 and rubidium-81 have energy levels considerably above this range, effective collimation and good image resolution are difficult with a scintillation camera. Potassium-43 and rubidium-81 are best imaged with a rectilinear scanner7T8 which, because of its thicker crystal and high energy collimators,is more suitable for high energy tracers. Thallium-201 has gamma photons within the optimal range for imaging with a scintillation camera but they are only 10 percent abundant. During the course of its decay thallium201 becomes mercury and emits X-rays with an energy of 80 kev. These X-rays occur in 95 percent of disintegrations. Although the 80 kev energy is less than optimal, thallium-201 can be effectively imaged with both the rectilinear scanner and scintillation camera. In comparison with other cationic tracers thallium201 has a greater heart/blood and heart/liver ratio of activity.g This is important when considering a tracer for myocardial imaging since image quality will in part depend upon the contrast between activity in the myocardium and that in surrounding structures. The ratio of heart/liver activity levels is of particular importance in evaluating inferior myocardial lesions. The relatively large hepatic uptake of tracers such as rubidium-81g may obscure the inferior border of the myocardium, making interpretation of lesions in this
I
Physical and Biologic
Properties
of Tracers
Used for Myocardial
Perfusion
Imaging Biologic Properties
Physical Properties (Major Photon*)
Tracer
E?
Potassium-43
373 619 511 190 375 416 800
Rubidium-81 Cesium-129 Thallium-201
%
Half-Life (hours)
Extraction Efficiency Heart (%)
T l/2 Blood (set)
2.7
70
<30
9
700
12
100
% Heart
::
22
26 65 48 25 95
2.7
70
<30
32
1.6$
20
<138
74
2.9$
a5
<40
4.7
% Liver at 1 Hour+
170 7
l Greater than 25 percent abundance. + From Strauss et al .9 $ From Poe ND: Comparative myocardial uptake clearance of potassium and cesium. J Nucl Med 13: 557, 1972. From Bradley-Moore PR, Lebowtz E, Greene MW, et al: Thallium-201 for medical use. Il. Bidlogic behavior. J Nucl Med 16:156, 8 Mercury X-ray.
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70
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area difficult. Hepatic activity can be decreased by measures that decrease hepatic blood flow-exercise, fasting or injection of tracer while the patient is standinglO- but these maneuvers are difficult or impractical in some situations such as the evaluation of patients with suspected acute infarction. Because of its relatively favorable biologic and physical properties thallium-201 appears to be the best of the currently available cationic tracers for myocardial perfusion imaging. Between 2 and 5 percent of an administered dose of thallium-201 localizes in the myocardium so that a high resolution image of the heart with a count density of 1,000 counts/cm* over the myocardium can be recorded in 10 minutes. Usually the activity in the heart is about twice that in the lung. This relatively low ratio makes it desirable to utilize some form of contrast enhancement to make small differences in myocardial tracer concentration apparent. Thallium-201 in detection of transmural myocardial infarction: In normal persons the concentration of thallium-201 is relatively uniform throughout the myocardium (Fig. 2). Perfusion distribution in each of the three major coronary arteries can be assessed by examining the uptake of thallium-201 in the area of myocardium supplied by each of the vessels. Areas of transmural myocardial infarction can be diagnosed by the finding of regional areas of absent to almost absent tracer uptake (“cold spot”). Examples from patients with an anterior and inferior myocardial infarction are shown in Figures 3 and 4, respectively. In a recent studyll 36 of 41 episodes of acute myocardial infarction were detected by visual inspection of the thallium-201 myocardial perfusion images. The detection of 14 of 16 episodes of inferior wall infarction in our study is of interest in view of previous difficulty in detecting lesions in this area with potassium-43.3 The reliability of the thallium201 myocardial perfusion scan in detecting areas of transmural infarction has also been assessed by comparing the presence and location of areas of akinesia or dyskinesia detected by left ventricular cineangiog-
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-E Hyperemia
K-43
ACTIVITY
RATIO
FIGURE 1. The ratios between ionic potassium-43 in the left anterior descending (LAD) coronary arterial region and that in the circumflex region plotted against the ratios of labeled microsphere activity in identical areas. One standard deviation is represented for each point. Reproduced from Prokop et al.,4 by permission of the American Heart Association, Inc.
raphy with areas of no thallium-201 uptake detected by myocardial perfusion imaging.l* Correlation between these two techniques has been excellent. However, correlation between the coronary arteriogram and the thallium scan in patients with infarction has been less good than that for patients with left ventricular akinesaa or dyskinesia, probably because of
FIGURE 2. Normal myocardial scan after intravenous administration of thallium-201 in the anterior (left), left anterior oblique (middle) and left lateral (right) positions. Tracer concentration is greatest in the left ventricular myocardium. The anterior wall, apex and inferior wall are clearly delineated in the anterior view; the septum and posterior wall are best seen in the left anterior oblique view. Tracer is also concentrated in the liver and spleen, which are seen as the bright areas below the region of the heart. Tracer concentration is relatively homogenous throughout the myocardium, decreasing slightly in the region of the apex. This is a normal variant.
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the biologic variation in coronary arterial distribution and the presence of collateral vessels. Thallium-201 in detection of nontransmural myocardial infarction: Although areas of transmural infarction are usually easy to appreciate from the resting thallium-201 myocardial perfusion scan, episodes of nontransmural infarction suspected by the finding of a relative decrease but not an absence of activity in a local area of myocardium (Fig. 5) are more difficult to detect. Three of 10 patients with electrocardiographic evidence of nontransmural infarction were considered to have normal scans by visual interpretation of perfusion images, whereas 2 of 6 patients with left ventricular hypertrophy without evidence of previous infarction were judged to have nontransmural infarcti0n.r’ Because of the difficulty in detecting nontransmural myocardial infarction by visual inspection of the myocardial perfusion scan, a technique for quantifying regional myocardial thallium-201 activity was developed in our laboratory. This method is independent of the dose administered, the contrast setting of the recording instrument, and the observer threshold for diagnosing the lesion. By this technique, the act.ivity in a reference area of lung adjacent to the heart is determined and compared with the activity in the myocardium. Regional myocardial thallium-201 activity (RMTA) is then calculated from the following equation:
1 standard deviation). Patients with electrocardiographic evidence of left ventricular hypertrophy have a significantly higher value than normal because of their increased muscle mass. Patients with nontransmural myocardial infarction have values, within at least one portion of myocardium, that are significantly less than normal and greater than those of patients with transmural infarction.ll The lowest values for regional myocardial thallium-201 activity are found in zones of transmural infarction. From these data it appears that quantification of the thallium201 scan provides an objective means of diagnosing both nontransmural and transmural infarction. However, a focal decrease in tracer uptake does not always indicate occlusive coronary artery disease. Recent studies’” have shown areas of myocardial scarring in patients with a primary cardiomyopathy without coronary arterial obstruction. Neither determination of regional myocardial thallium-201 activity nor visual inspection of the thallium-201 myocardial per-
RMTA = MTA - LTA MTA where MTA = myocardial thallium activity and LTA = the activity in the reference area over the lung.” This process is performed for the whole heart, and for 1 cm segments of the myocardium. In normal persons the value for segmental regional myocardial thallium-201 activity is 1.4 f 0.2 (mean f
FIGURE 3. Thallium myocardial perfusion scan in anterior (left) and Left anterior oblique (right) views in a patient with inferior wall myocardial infarction. A marked decrease in tracer concentration in the region of the inferior wall is seen in the anterior view and in the septum and posterior wall in the left anterior oblique view.
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FIGURE 4. Thallium-PO1 myocardial scan (top panels) in the anterior (left) and left anterior oblique (right) views in a patient with anterior wall myocardial infarction. The lower panels are technetium99m-labeled glucoheptonate scans in the same views in the same patient. The decreased region of tracer concentration in the anterior wall is best seen in the anterior thallium scan, indicating the presence of a transmural myocardial infarction. In the lower panels, technetium glucoheptonate is concentrated in the zone of acute damage in the anterior wall.
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fusion images allows separation of patients with acute and old infarction although this differentiation may be made by tracers that localize in acutely damaged myocardium. Myocardial Infarction myocardial
TABLE
II
Tracers
for
Imaging
The tracers suggested to image acute myocardial infarction are shown in Table II. Those currently advocated for the detection of acute myocardial infarction in man have an affinity for calcium, denatured protein or sulfhydry1 groups.14 Whether such affinity accounts for the localization of tracer in acutely infarcted tissue is uncertain at present. These agents are different from tracers such as potassium-43 or thallium-201 used to estimate myocardial perfusion since their distribution is not linearly related to perfusion but requires some residual vascular supply to the infarcted region to allow tracer uptake. Rossman et a1.,15 using technetium-99m glucoheptonate, have shown that maximal tracer concentration occurs in areas with flow rates of 40 to 60 percent of normal; concentration is greatly decreased in areas with more normal perfusion and in areas with almost absent perfusion. There are differences in the interval between acute infarction and the maximal concentration of these tracers. Technetium-99m pyrophosphate, for example, achieves maximal concentration in damaged tissue 24 to 48 hours after infarction. Tetracycline concentrates rapidly in acutely infarcted tissues but, since blood clearance of the tracer is slow, high quality images cannot be obtained for 12 to 24 hours after tracer administration. In contrast, glucoheptonate and pyrophosphate clear rapidly from the blood so that imaging may be performed 1 to 3 hours after tracer administration. Areas of acute damage will concentrate these tracers for only approximately 1 to 3 weeks after infarction; areas with old infarcts do not take up these tracers. Initial experience with infarct imaging has been encouraging. Most episodes of transmural infarction Acute
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infarction:
Imaging
Acute
Myocardial
1.
Chlormerodrin-Hg-197
2.
Tetracycline-Tc-99m
3.
Glucoheptonate-Tc-99m
4.
Dimercapto
5.
Mercurylhydroxy
6.
Pyrophosphate-Tc-99m
PITT AND STRAUSS
Infarction
Succinic Acid-Tc-99m Fluorescin-Hg-197
can be detected with pyrophosphate;16 nontransmural infarctions, especially small lesions, are not detected with nearly the same frequency.17 Glucoheptonate and tetracycline appear to be as sensitive as pyrophosphate in detecting areas of transmural myocardial infarction but the quality of the image produced is less good; experience with these two agents is still too limited to allow an accurate estimation of their sensitivity in detecting episodes of nontransmural infarction. Conditions other than acute infarction have been associated with myocardial pyrophosphate concentration: unstable angina pectoris without electrocardiographic or serum enzyme evidence of necrosis, left ventricular aneurysms, and some instances of primary cardiomyopathy. Is Whether the uptake of tracer in these cases represents subclinical myocardial necrosis or ischemia without necrosis remains to be determined. Estimation of infarct size: Because of the recent introduction of therapeutic agents designed to limit the size of acute myocardial infarcts there has been interest in techniques to measure infarct size. Infarct size appears to correlate best with the extent of tracer localization rather than with activity of the tracer in the heart. This finding is probably related to the complex interrelations between the residual flow required to allow delivery of tracer and the cell damage that permits entry of the tracer into the cell. Although initial correlations between extent of gluco-
FIGURE 5. Thallium myocardial Scan in the anterior (left), left anterior oblique (middle) and left lateral (right) views in a patient with left ventricular hypertrophy. Increased thickness of the walls is particularly prevalent in the anterior and left anterior oblique positions. The slight decrease in the region of the apex could be related to normal thinning but is also seen in some patients with nontransmural myocardial infarction.
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heptonate concentration with infarct size, as estimated from peak creatinine phosphokinase values, have: been good, data are insufficient to reach a final conclusion on the reliability of this technique. A problem in applying these tracers for clinical use is that optimal imaging may not be possible on admission of the patient to the coronary care unit, when the information would be most useful. For example, optimal images are not obtained with pyrophosphate during the first 12 to 24 hours of infarction. In addition, these tracers do not yield information about the perfusion and function of the residual noninfarcted areas of myocardium, two important factors in determining long-term survival. Gated Cardiac
physiologic markers such as the electrocardiogram, phonocardiogram or arterial pressure wave recording. In practice, the most commonly used signal is the electrocardiogram. Ejection
fraction
and left ventricular
volumes:
Gated end-systolic and end-diastolic images should be recorded in two positions, either the right anterior oblique or anterior projection and the left anterior oblique projection. To calculate left ventricular volumes and ejection fraction, an outline of the left ventricle is obtained by projecting the images to life size and tracing the borders of the ventricular chambers from the gated images. The mitral and aortic valve planes may be difficult to assess from the gated images. To facilitate localization of the valve planes a nuclear angiocardiogram is recorded during the initial passage of tracer through the heart. The left ventricular outline is then completed by combining data about the valve planes from the nuclear angiocardiogram with the outline of the ventricle obtained from the gated examination. Ventricular volumes and ejection fraction are obtained by applying standard angiographic equations to the traced images; regional myocardial wall motion can be assessed by superimposing the end-systolic and end-diastolic images. Values for left ventricular ejection fraction and regional myocardial wall motion determined from the gated cardiac blood pool scan correlate closely with values obtained by left ventricular contrast cineangiography.1g120
Blood Pool Scanning
The gated cardiac blood pool scan permits calculation of left ventricular ejection fraction and regional myocardial wall motion from a single examination.1g*20 After intravenous administration of a blood pool tracer such as technetium-99m-labeled human serum albumin or red blood cells, a scintillation camera is triggered (“gated”) by the patient’s cardiac cycle and the data from many cycles are summed on a single film to produce a high resolution image of at least 300,000 counts, all recorded during a specific portion of the cardiac cycle. To permit calculation of left ventricular ejection fraction, images are recorded at end-systole and end-diastole. The signal used to trigger the scintillation camera may be any of several GATED BLOOD POOL SCANS
NORMAL
RIGHT VENTRICULAR ENLARGEMENT
LEFT VENTRICULAR ENLARGEMENT
RIGHT AND LEFT VENTRICULAR ENLARGEMEN
FIGURE 6. Gated blood pool scans in the left anterior oblique projection performed in a normal subject (top), and a patient with right ventricular dysfunction (bottomleft), left ventricular dysfunction (middle) and combined right and left ventricular dysfunction (bottom right). The normal ratio of right ventricular area to left ventricular area is 1.1:1. In right ventricular dysfunction, the ratio is increased: in left ventricular dysfunction it is decreased. When both ventricles are involved, the ratio may remain 1.1: 1, but the volume of the left ventricle is in-. creased. Ao = aorta: LV = left ventricle; PA = pulmonary artery; RV = right ventricle. Reprinted from Rigo et al., 25 by permission of the American Heart Association, Inc.
<---“\
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Other tracer techniques allow calculation of left ventricular ejection fraction directly from the activity in the chamber at end-systole and end-diastole. These techniques have the advantage of freedom from an assumed geometric shape. Measurements can be made either at equilibrium, by the method of Seeker-Walker et a1.,21 or from the initial passage of tracer through the heart.22 Steele et a1.23have developed a simple bedside counter for serial measurement of ventricular ejection fraction, cardiac output and pulmonary blood volume.23 However, this bedside technique does not allow determination of regional myocardial wall motion. Abnormalities in regional myocardial wall motion and left ventricular dysfunction: In an initial study 24 of 36 patients with acute myocardial infarction evaluated by gated cardiac blood pool scanning, abnormalities in regional myocardial wall motion could be detected in all. Thirty-four patients had an area of akinesia and two an area of hypokinesia. The gated cardiac blood pool scan appears to be a more sensitive means of detecting left ventricular dysfunction in patients with acute myocardial infarction than the determination of routine hemodynamic variables including left ventricular filling pressure and cardiac output. The left anterior oblique gated cardiac blood pool scan has been of particular help in detecting patients with cardiogenic shock due to right ventricular infarction.25 In normal patients the ratio of right ventricular to left ventricular area in the left anterior oblique scan is approximately l.l:l. In patients with cardiogenic shock due to left ventricular dysfunction the left ventricle dilates and the ratio decreases whereas in patients with the syndrome of right ventricular infarction and cardiogenic shock the ratio is significantly greater than normal (Fig. 6). Lesser degrees of right ventricular enlargement have been found in patients with inferior myocardial infarction but without cardiogenic shock. The left anterior oblique scan may also be useful in detecting patients with cardiogenic shock due to rupture of the interventricular septum. Injection of the tracer through a Swan-Ganz catheter in the left anterior oblique projection reveals almost simultaneous filling of the right and left ventricles in this situation.
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PITT AND STRAUSS
Left ventricular aneurysm: Another situation in which gated cardiac blood pool scanning has proved to be of value is the evaluation of patients with congestive heart failure after convalescence from myocardial infarction.26 It is important to separate patients with congestive heart failure and localized left
FIGURE 7. Thallium scan in the anterior (top left) and left anterior oblique (top right) views and a gated blood pool scan at end-diastole (bottom left) and end-systole (bottom right) in the left anterior oblique view. In the thallium scan there is a focal region of decreased perfusion in the inferior wall of the myocardium. In the gated scan the right ventricle, septum and left ventricle are visualized. Comparison of the left ventricle at end-systole and end-diastole reveals paradoxical movement of the inferior border with poor motion of the remainder of the chamber.
FIGURE 8. Thallium scan in the left anterior oblique view (left) and gated blood pool scans in the same view at enddiastole (middle) and end-systole (right). In the thallium scan a marked decrease of tracer distribution involves most of the septum and posterior wall. In the gated blood pool scan wall motion is absent in the septum and posterior wall of most of the myocardium. The patient has severe ischemic heart disease with diffuse ventricular involvement and diffuse hypokinesia.
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ventricular aneurysms from those with diffuse left ventricular hypokinesia since the former may be helped by surgery and the latter often cannot be operated on. The history, physical examination, electrocardiogram and routine chest X-ray film often do not allow this differentiation. Although we previously admitted patients to the hospital for left ventricular cineangiography when left ventricular aneurysm was suspected, we now obtain a gated cardiac blood pool scan on an outpatient basis. Patients with a localized left ventricular aneurysm are admitted to the hospital for further diagnostic studies including coronary and left ventricular cineangiography if surgery is indicated; those with diffuse left ventricular hypokinesis (Fig. 7 and 8) are followed up on an outpatient basis, thereby avoiding unnecessary risk and expense. Clinical evaluation of patient with myocardial infarction: In evaluating a patient with acute myocardial infarction, a combination of tracer techniques is often advantageous. In patients with a first myocardial infarction we perform an initial myocardial perfusion scan with thallium-201. This provides immediate information about the presence, location and extent of the infarction as well as the perfusion of the remaining myocardium. Immediately after the thallium-201 myocardial perfusion image we obtain a gated cardiac blood pool scan. The relatively low energy photons from thallium-201 do not interfere with the imaging of technetium-99m-labeled human serum albumin. The gated cardiac blood pool scan serves as an independent measure to detect infarction and provides information about left ventricular function. In patients with questionable areas of decreased perfusion the finding of a corresponding regional myocardial wall motion abnormality adds to the certainty of the diagnosis of myocardial infarction. In patients whose evidence for infarction is unclear because of a previous episode of infarction or equivocal electrocardiographic or serum enzyme changes, the myocardial perfusion scan may be fol-
lowed by infarct scanning with an agent such as technetium-99m pyrophosphate to determine whether there are areas of fresh damage. Evaluation
of Patients with Suspected Heart Disease
lschemic
Myocardial perfusion during exercise stress: Although myocardial perfusion imaging at rest is useful in detecting areas of myocardial infarction and severe ischemia, it is often inadequate in detecting narrowing of the coronary arteries without infarction. Physiologic studies have shown that a coronary artery may be occluded to 50 to 70 percent of its diameter without altering resting flow; however, patients with this degree of coronary arterial narrowing may be detected by administering tracer during stress.10 Areas of myocardium served by normal coronary arteries can sustain a doubling of blood flow, whereas areas of myocardium supplied by a critically narrowed coronary artery cannot sustain such increases in flow or may actually have a decrease in flow during stress. A cationic tracer with rapid blood clearance such as potassium-43, rubidium-81 or thallium-201 administered during the peak of stress will reflect the myocardial perfusion at the time of tracer administration. Since the distribution of tracer during the first hour after administration primarily reflects the initial flow-related distribution rather than cell loss, imaging may be performed after termination of exercise. Zaret and his co-workers3J0J7 have used potassium-43 during stress to detect patients with subclinical coronary arterial lesions and to separate patients with ischemic heart disease from those with normal coronary arteries and false positive exercise tests. If a myocardial perfusion defect is detected during stress the scan should be repeated at a later date during rest. Persistence of a perfusion defect at rest suggests myocardial scarring, whereas a normal resting scan
FIGURE 9. Thallium-201 myocardial scan in anterior view with injection performed at rest (left), during maximal exercise (middle) and after saphenous vein bypass grafting (right). In the initial scan at rest, there is a normal distribution of tracer throughout the myocardium. The scan during exercise reveals a focal region of decreased tracer concentration in the inferoapical portion of the myocardium, suggesting the presence of transient ischemia. A coronary arteriogram revealed a 75 percent occlusion of the right coronary artery. After saphenous vein bypass grafting the perfusion scan performed at rest reveals normal perfusion to the inferior wall but a new defect of tracer concentration in the anterior wall, suggesting a possible myocardial infarction.
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suggests that the perfusion defect seen during stress is due to transient myocardial ischemia. If the myocardial perfusion scan is normal during stress the probability of a significant coronary arterial lesion is relatively small. Myocardial perfusion imaging during stress may be of special importance in detecting ischemia in patients with previous myocardial infarction and an abnormal resting electrocardiogram and in those with an abnormal resting electrocardiogram due to left ventricular hypertrophy or an interventricular conduction defect. In a recent study of patients with a previous myocardial infarction and an abnormal resting electrocardiogram, Bailey et a1.28 found that the thallium-201 myocardial perfusion scan during stress was almost twice as sensitive as electrocardiographic stress testing in detecting myocardial ischemia. Berman et a1.2g made a similar finding using rubidium-81. Evaluation of patients undergoing coronary bypass surgery: The thallium-201 myocardial perfusion scan has proved to be of value in patients undergoing coronary arterial bypass graft surgery. Zaret et a1.30 using potassium-43 myocardial perfusion imaging were able to detect postoperative myocardial infarction in 3 of 16 patients undergoing bypass graft surgery, whereas 9 of the patients demonstrated improvement during stress. 3o In some patients with unstable angina pectoris and severely narrowed coronary arteries a perfusion defect may be detected at rest and may diminish after successful bypass graft
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surgery. In other patients the perfusion scan may reveal new defects suggestive of postoperative infarction (Fig. 9). The thallium-201 myocardial perfusion scan appears to be twice as sensitive as the electrocardiogram in detecting patients with postoperative infarction. Evaluation of triple vessel coronary disease: A major problem with myocardial imaging in patients with suspected ischemic heart disease has been the inability of the technique to detect patients with severe triple vessel disease. Myocardial scans in these patients are often interpreted as normal because tracer uptake, although reduced, is uniform throughout the myocardium. The presence of a focal decrease of tracer uptake, the hallmark of ischemic heart disease, may not be seen. Quantification of the thallium201 myocardial perfusion image in a few of these patients has demonstrated that thallium-201 concentration is significantly reduced in all segments of the myocardium. Thus, quantification of the myocardial perfusion scan may provide a means of detecting patients whose disease affects the myocardium uniformly. The tracer techniques described in this review are still relatively new and require further assessment and verification. It is likely,‘however, that with further advances in radiopharmaceutical agents and instrumentation they will play an increasingly important role in the assessment of patients with ischemic heart disease.
References 1. Rhodes BA: Radiopharmaceuticals. In, Cardiovascular Nuclear Medicine (Strauss HW, Pitt B, James AE, eds). St. Louis, CV Mosby, 1974, p 35-51 2. Cooper M: Myocardial imaging-an overview. In Ref 1, p 149-162 3. Zaret BL, Martin ND, Flamm MD: Myocardial imaging for the noninvasive evaluation of regional perfusion at rest and after exercise. In Ref 1. p 181-210 4. Prokop EK, Strauss HW, Shaw J, et al: Comparison of regional myocardial perfusion determined by ionic potassium-43 to that determined by microspheres. Circulation 50:978-984, 1974 5. Becker L, Ferreira R, Thomas M: Comparison of s%b and microsphere estimates of left ventricular blood flow distribution. J Nucl Med 15:969-973, 1974 6. Schelbert HR. Ashburn WL, Chauncey DM, et al: Comparative myocardial uptake of intravenously administered radionuclides. J Nucl Med 15:1092-1100, 1974 7. Strauss HW, Zaret BL, Martin ND, et al: Non-invasive evaluation of regional myocardial perfusion with potassium-43: technique in patients with exercise-induced transient myocardial ischemia. Radiology 108:85-90. 1973 8. Martin ND, Zaret BL, McGowan RL, et al: Rubidium-81: a new myocardial scanning agent. Radiology 111:651-656, 1974 9. Strauss HW, Harrison K, Langan JK, et al: Thallium-201 for myocardial imaging: relation of thallium-201 to regional myocardial perfusion. Circulation 51:641-645, 1975 10. Zaret BL, Strauss HW, Martin ND, et al: Noninvasive regional myocardial perfusion with radioactive potassium. N Engl J Med 288:809-812, 1973 11. Rouleau J, Strauss HW, Pitt B: Thallium-201 for myocardial imaging: evaluation of patients with acute myocardial infarction.
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