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Comparison of thallium-201 single-photon emission computed tomographic scintigraphy with intravenous dipyridamole and arm exercise
Comparison of thallium-201 single-photon emission computed tomographic scintigraphy with intravenous dipyridamole and arm exercise In patients who cannot perform treadmill exercise, both intravenous dipyridamole and arm exercise have been used with thallium-201 scintigraphy to detect significant coronary artery disease. However, no study has directly evaluated the results of intravenous dipyridamole and arm exercise thallium scintigraphy as compared with coronary angiography. It was the purpose of this study to compare intravenous dipyridamole and arm exercise thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy for detection of significant coronary artery disease in patients who could not perform treadmill exercise. Data are presented for both intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy in 18 men who could not perform treadmill exercise, and results are compared with those of coronary angiography. Ten of 11 (91%) patients with significant coronary artery disease were identified correctly, and the results of intravenous dipyridamole and arm exercise thallium scintigraphy were comparable. In patients without significant coronary artery disease, intravenous dipyrfdamole thallium images were interpreted correctly. However, initial arm exercise thallium images demonstrated a fixed inferior wall defect in two of seven patients without significant coronary artery disease. Images in one of these patients could not be retrieved from tape for further analysis. Review of the images in the other patient demonstrated relatively high background radioactivity, and when the images were displayed without background subtraction, the inferior wall was correctly interpreted as normal. We conclude that results of intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy are comparable. (AM HEART J 1994;127:1516-20.)
Maleah Grover-McKay, MD, Norah Milne, MD, J. Edwin Atwood, MD, and Kenneth P. Lyons, MD Long Beach, Calif.
In patients who cannot perform treadmill exercise, both intravenous dipyridamole and arm exercise have been used with thallium-201 scintigraphy to detect significant coronary artery disease. The safety of intravenous dipyridamole thallium scintigraphy has been well estab1ished.l The sensitivity and specificity for detection of significant coronary artery disease were comparable for standard exercise and intravenous dipyridamole thallium scintigraphy in five studies comprising 215 patients who underwent From the Cardiology Long Beach Veterans
Section and Administration
the
Department of Nuclear Medical Center.
Medicine,
Supported in part by grants from the VA Research Advisory Group, University of California, Irvine-AHA Endowment Research Proposal, and by a University of California, Irvine Faculty Research Grant. Received Reprint Medicine,
for publication requests: University
Copyright @ 1994 0002-8703/94/$3.00
1516
July
8, 1993;
M&ah Grover-McKay, of Iowa Hospital, by Mosby-Year
+0
4/l/53790
Book,
accepted
Oct. 15, 1993.
MD, Department Iowa City, IA 52242. Inc.
of Internal
both studies.2 The average sensitivity was 79% for both techniques, and the average specificities were 92 % and 95 % , respectively. Comparison of intravenous dipyridamole and bicycle exercise thallium scintigraphy in 35 patients with coronary artery disease also demonstrated comparable sensitivity and specificity.3 In a review of 12 studies comprising 616 patients who underwent intravenous dipyridamole scintigraphy, the average sensitivity and specificity were similar to the preceding values (85 % and 90 o/o, respectively).4 Arm exercise thallium scintigraphy demonstrated a comparable sensitivity of 83 % and a specificity of 78% in 50 patients with leg impairment5 In 33 men with peripheral vascular disease who performed arm exercise, 25 (76 % ) had thallium defects, but coronary angiography was not performed routinely.6 However, no study has compared intravenous dipyridamole and arm exercise directly. Therefore, in patients who could not perform treadmill exercise, this study compared the results of intravenous
Volume 127, Number 6 American Heart Journal
dipyridamole and arm exercise thallium-201 singlephoton emission computed tomographic (SPECT) scintigraphy for detection of significant coronary artery disease determined by angiography. METHODS Patient selection. Between October 1987 and June 1988, patients who were referred for thallium scintigraphy and who could not walk on a treadmill were asked to participate in a study comparing intravenous dipyridamole and arm exercise thallium scintigraphy. The protocol WAS approved by the Veterans Administration Human Studies Subcommittee, and all patients signed informed consent forms. Exercise testing. Patients did not take xanthine-derivative medications for five half-lives and did not drink or eat any foods containing caffeine. In addition, patients took the same medications for the two thallium tests, which were performed on separate days. Exercise ECGs were interpreted as abnormal if ~1 mm flat or downsloping ST-segment depression occurred 80 msec after QRS cessation.7 Arm exercise. Patients cranked an arm ergometer starting at 25 W resistanceand increasingby 25 W at 3-minute intervaIs. Patients evaluated perceived exertion on a scale of 0 to 20 with 20 equal to maximum perceived exerti0n.s Patients exerciseduntil they were fatigued. Thallium was injected intravenously 1 minute before exercise was discontinued. Blood pressurewasobtained by having the patient stop cranking with one arm at the end of each level of exercise. Intravenous dipyridamole. Intravenous dipyridamole wasinjected with an infusion pump at 0.14 mg/kg/min for 4 minutes2 Thallium wasinjected 3 minutes after the end of the infusion. Blood pressureand a 12-leadECG were recorded every minute until imagingwasbegun.Intravenous aminophylline wasgiven for severechest pain or hypotension. Thallium scintigraphy. Thallium, 111 MBq, was injected as describedpreviously, and imageswere obtained approximately 5 minutes and 3 to 4 hours after injection. Data were acquired on a rotating, large field-of-view gamma camera (General Electric Starcam, Milwaukee, Wis). Standard protocols available from the manufacturer were used to acquire and process the images including bullseye images.gSpecifically a 30% window was centered on the low-energy x-ray peak of thallium, and 20% windowswere centered on the 135keV and 167keV photopeaks.Data acquisition beganfrom the 45-degreeright anterior oblique position and stopped at the 45degree left posterior oblique position. Imageswereobtained for 40 seconds at eachof 32 projections. Each projection wascorrected for nonuniformity. Backprojection wasperformed with a ramp Hanning filter with a cutoff value of 0.5 cycles/pixel. Axial filtration wasperformed perpendicular to the slice. No attenuation or scatter correction was performed. Three orthogonal projections were created by oblique-anglereconstruction and were photographed on x-ray film. Thallium uptake was evaluated in 20 myocardial segments on a scaleof 0 to 3 by three observersblinded to clinical data,
Grover-McKay
et al.
1517
with 0 indicating a normal segment and 3 identifying markedly decreasedthallium uptake with radioactivity equal to background.lO Coronary angiography. Images were obtained of the coronary arteries in multiple projections. Angiogramswere interpreted visually by an observerblinded to clinical data. Significant coronary artery diseasewas defined as ~50% stenosis. Statistics. Data are presentedasmean L SD. Data from intravenous dipyridamole and arm exercisewere compared by Student’s paired t test, and p < 0.05 was significant. RESULTS Patients. A total of 20 patients underwent thallium201 SPECT scintigraphy after both arm exercise and intravenous dipyridamole. In one patient medications were changed between the two thallium tests, and in another patient images obtained during arm exercise were suboptimal. Therefore data are presented for 18 men with an average age of 61 rt 7 years. Eight patients could not perform adequate exercise on a treadmill because of peripheral vascular disease, and 10 patients were confined to a wheelchair or had orthopedic problems. Sixteen patients were being evaluated for chest pain, and two had a history of congestive heart failure. Three patients had undergone prior coronary artery bypass graft surgery. Exercise testing. Intravenous dipyridamole and arm exercise studies were performed within 12 -t- 9 days. One patient had a left bundle branch block, and in another patient with an incomplete left bundle branch block, a complete left bundle branch block developed during both tests. The maximum heart rate during arm exercise wassignificantly higher than that during intravenous dipyridamole (116 -t 22 vs 77 k 13 beats/min; p < O.OOOl),aswas the maximum systolic blood pressure (149 f 24 vs 128 ~fr 16 mm Hg; p < 0.001). Arm exercise. Patients performed an average of 3.3 + 0.7 METS of activity, and the average perceived exertion was 18 f 1. Three patients had chest pain. Four of the 16 patients without a left bundle branch block had 11 mm ST depression, only one of whom had chest pain. Intravenous dipyridamole. Six patients had chest pain during or soon after the dipyridamole infusion, and one patient had atypical chest pain after thallium imaging was completed. Three patients had 2 1 mm ST depression, two of whom had chest pain. Six patients were given intravenous aminophylline for chest pain, one of whom had a 40 mm Hg decrease in systolic blood pressure. Coronary angiography. Eleven patients had significant coronary artery disease, six with three-vessel disease and five with one-vessel disease. Of the
1518
Grover-McKay
et al.
American
I. Comparison of thallium-201 arm exercise study, intravenous dipyridamole study, and coronary angiography Table
Patient
CAD
Arm
1 2 3 4 5 6 7 8 9 10
+ + + + + + + + + + + 0 0 0 0 0 0 0
+ + + + + + + + + + 0 0 0 0 0 0 +* 0
11
12 13 14 15
16 17 18
Arm, Arm exercise study; CAD, as >50% stenosis; Dipyridamole, not available to analyze without
significant intravenous background
Dipyridamole
June 1994 Heart Journal
retrieve the other study from tape). Therefore we photographed the images without background subtraction (Fig. l), and the inferior wall was interpreted as normal on the images without background subtraction. DISCUSSION
+ + + 0 0 0 0 0 0 0 0 coronary artery dipyridamole subtraction.
disease study.
defined *Images
patients without significant coronary artery disease, only one had peripheral vascular disease. During arm exercise two of the three patients who had chest pain had significant coronary artery disease, and all three patients who had ST depression had significant coronary artery disease. Of the six patients who had chest pain during or soon after the dipyridamole infusion, half had significant coronary artery disease. TWO of three patients with ST depression during the dipyridamole test had three-vessel disease, and two of these three had ST depression during arm exercise. Of the two patients who had chest pain during both tests, one had prior bypass surgery with stenosis in one graft, and the other had no significant coronary artery disease. Thallium scintigraphy (Table I). Among patients with significant coronary artery disease, the disease was detected in 10 of 11 (91%). Results of intravenous dipyridamole and arm exercise thallium tests were equivalent. Among patients without significant coronary artery disease, thallium scintigrams obtained after intravenous dipyridamole were interpreted as normal in all of them. However, thallium scintigrams obtained after arm exercise were initially interpreted as demonstrating a fixed defect in the inferior wall in two patients (scored as 3 and confirmed by the bullseye images). When images without background subtraction from one of these studies were reviewed on the computer, we noticed relatively high background radioactivity (it was not possible to
This study in men demonstrates that the results of intravenous dipyridamole and arm exercise thallium scintigraphy were comparable and correlated with the results of coronary angiography. All patients with significant coronary artery disease were identified correctly. In patients without sign :icant coronary artery disease, intravenous dipyridamole thallium images were interpreted correctly. Initial processing (with background subtraction) of thallium scintigrams obtained after arm exercise demonstrated a fixed inferior defect in two patients without significant coronary artery disease. When images from one of these patients were reprocessed without background subtraction, no poste: ior wall defect was detected (Fig. 1). Limitations of this study include the small number of subjects examined and the lack of women subjects. This study suggests that in men, an arm exercise study yields information comparable to coronary vasodilatation produced by intravenous dipyridamole if care is taken to not oversubtract background activity. A possible explanation for the increased background activity during arm exercise is increased blood flow to the muscles of the chest wall. Balady et al.ll compared arm and leg exercise in normal subjects and demonstrated that at a similar rate-pressure product, despite the lower work load performed with arm exercise, left ventricular wall stress and contractility were similar for arm and leg exercise. Balady et al. l2 also demonstrated that during arm exercise, men attained higher levels of absolute power output and oxygen consumption than women, and the chronotropic response to total body oxygen demand during arm exercise was greater among women than men. Because our study only examined men, whether the results of arm exercise and intravenous dipyridamole imaging are comparable in women will require further investigation. In addition, Balady et al. l2 found that during arm exercise, older subjects when compared with younger subjects reached a lower peak power output, despite similar peak oxygen consumption. Therefore the effect of age will also require further investigation. The pathophysiology of exercise and vasodilator imaging is different. The choice of whether to perform one type of testing over another is partially dependent on the type of patient who is to undergo the test. For example, in paraplegic patients the clinician
vd~me 127, Number 6 American Heart Journal
Grover-McKay
et al.
1519
1. Effect of background subtraction on arm exercisethallium-201 images.Immediate (left) and delayed (right) thallium-201 SPECT imagesare shownfor arm exercisestudy. Imageswith background subtraction are at the top; imageswith no background subtraction are at the bottom. Midventricular shortaxis imagesare shown at the top of each set of images;midventricular vertical long-axis imagesare shown at the bottom. On imageswith background subtraction, decreasedthallium-201 uptake is seenin the inferoposterior wall. On imageswith no background subtraction, decreasedthallium-201 uptake in the inferoposterior wall is not as evident.
Fig.
may want to know whether the patient can safely perform a given amount of arm work. In addition, arm exercise testing can be performed in patients with bronchospastic lung disease, who cannot be taken off xanthine-derivative medications such as theophylline. Intravenous adenosine has also been used safely to evaluate regional myocardial perfusion after maximum vasodilatation,13* l4 and results are comparable to those of exercise testing.15-l7 Because results of intravenous dipyridamole testing are also comparable to those of exercise testing, it is not clear whether adenosine studies have higher specificity. Data obtained by measuring coronary flow reserve with an
intracoronary Doppler catheter concluded that intravenous adenosine is a more potent vasodilator than the dose of intravenous dipyridamole used in this study.18 However, investigators who performed a recent study in which myocardial blood flow was quantitated by means of dynamici N-ammonia imaging and positron emission tomography concluded that the two drugs produced comparable increases in coronary flow reserve. lg Each vasodilator has advantages and disadvantages20 In conclusion, results of thallium-201 SPECT scintigraphy in men with either intravenous dipyridamole or arm exercise were comparable for the detection of the presence or absence of significant
1520
Grover-McKay et al.
coronary artery disease, if care was taken not to oversubtract background radioactivity on thallium images obtained after arm exercise. We thank Mr. Victor Smith for expert assistance and Dr. Victor Froelicher for providing the environment that helped make this study possible. We also thank Dr. Sheila Robinson for assistance with patient identification and recruitment and Ms. Marlene Blakley for help with preparation of the manuscript. REFERENCES
1. Ranhosky A, Kempthorne-Rawson J, and the Intravenous Dipyridamole Thallium Imaging Study Group. The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Circulation 1990$1:1205-9. 2. Leppo JA. Dipyridamole-thallium imaging: the lazy man’s stress test. J Nucl Med 1989;30:281-7. 3. Huikuri HV, Korhonen UR, Airaksinen KEJ, Iaheimo MJ, Heikkila J, Takkunen JT. Comparison of dipyridamolehandgrip test and bicycle exercise test for thallium tomoimaeine. Am J Cardiol 1988:61:264-8. o-aranhic -~A- ~~~ 4. Beller GA.” Pharmacologic stress imaging. JAMA 1991; 265~633-8. 5. Balady GJ, Weiner DA, Rothendler JA, Ryan TJ. Arm exercise-thallium imaging testing for the detection of coronary artery disease. J Am Co11 Cardiol 1987;9:84-8. S, Rubler S, Bryk H, Sklar B, Glasser L. Arm exer6. Goodman cise testing with myocardial scintigraphy in asymptomatic patients with peripheral vascular disease. Chest 1989;95:740-6. 7. Froelicher VF. Exercise and the heart. 2nd ed. Chicago: Year Book Medical Publishers, 1987:120. basis of perceived exertion. Med Sci 8. Borg GA. Psychophysical Sports Exert 1982;14:377. 9. De Pasquale EE, Nody AC, DePuey EG, Garcia EV, Pilcher G, Bredlau C, Roubin G, Gober A, Gruentzig A, DaMato P, Berger A. Quantitative rotational thallium-201 tomography for identifying and localizing coronary artery disease. Circulation 1988;77:316-27. L. Kiat H. Friedman JD. Van Train K, Maddahi J, 10. Matzer Berman DF. A new approach to the assessment oftomographic thallium-201 scintigraphy in patients with left bundle branch block. J Am Co11 Cardiol 1991;17:1309-17.
American
June 1994 Heart Journal
11. Balady GJ, Schick EC, Weiner DA, Ryan TJ. Comparison of determinants of myocardial oxygen consumption during arm and leg exercise in normal persons. Am J Cardiol 1986; 57:1385-7. GJ, Weiner DA, Rose L, Ryan TJ. Physiologic re12. Balady sponses to arm ergometry exercise relative to age and gender. i Am Co11 Cardiol 199O;i6:130-5. 13. Verani MS. Mahmarian JJ. Hixson JB. Bovce TM. Staudacher RA. ‘Diagnosis of coronary artery disease by controlled coronary vasodilation with adenosine and thallium-201 scintigraphy in patients unable to exercise. Circulation 1990;82: 80-7. 14. Abreu A, Mahmarian JJ, Nishimura S, Boyce TM, Verani MS. Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease. J Am Co11 Cardiol 1991;18:730-5. 15. Nguyen T, Heo J, Ogilby JD, Iskandrian AS. Single photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia: correlation with coronary arteriography, exercise thallium imaging and two-dimensional echocardiography. J Am Co11 Cardiol 1990;16:1375-83. 16. Coyne EP, Belvedere DA, Vande Streek PR, Weiland FL, Evans RB, Spaccavento LJ. Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease. J Am Co11 Cardiol 1991;17:1289-94. 17. Gupta NC, Esterbrooks DJ, Hilleman DE, Mohiuddin SM. Comparison of adenosine and exercise thallium-201 singlephoton emission computed tomography (SPECT) myocardial oerfusion imaeina. J Am Co11 Cardiol 1992:19:248-57. 18. kossen JD, Quillen JE, Lopez JAG, Stenberg RB, Talman CL, Winniford MD. Comparison of coronary vasodilation with intravenous dipyridamole and adenosine. J Am Coil Cardiol 1991;18:485-91. 19. Chan SY, Brunken RC, Czernin J, Porenta G, Kuhle W, Krivokapich J, Phelps ME, Schelbert HR. Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men. J Am Co11 Cardiol 1992;20:979-85. 20. Wackers FJ. Adenosine or dipyridamole: which is preferred for myocardial perfusion imaging? J Am Co11 Cardiol 1991;17: 1295-6.
Maleah Grover-McKay, MD, Norah Milne, MD, J. Edwin Atwood, MD, and Kenneth P. Lyons, MD Long Beach, Calif.
In patients who cannot perform treadmill exercise, both intravenous dipyridamole and arm exercise have been used with thallium-201 scintigraphy to detect significant coronary artery disease. The safety of intravenous dipyridamole thallium scintigraphy has been well estab1ished.l The sensitivity and specificity for detection of significant coronary artery disease were comparable for standard exercise and intravenous dipyridamole thallium scintigraphy in five studies comprising 215 patients who underwent From the Cardiology Long Beach Veterans
Section and Administration
the
Department of Nuclear Medical Center.
Medicine,
Supported in part by grants from the VA Research Advisory Group, University of California, Irvine-AHA Endowment Research Proposal, and by a University of California, Irvine Faculty Research Grant. Received Reprint Medicine,
for publication requests: University
Copyright @ 1994 0002-8703/94/$3.00
1516
July
8, 1993;
M&ah Grover-McKay, of Iowa Hospital, by Mosby-Year
+0
4/l/53790
Book,
accepted
Oct. 15, 1993.
MD, Department Iowa City, IA 52242. Inc.
of Internal
both studies.2 The average sensitivity was 79% for both techniques, and the average specificities were 92 % and 95 % , respectively. Comparison of intravenous dipyridamole and bicycle exercise thallium scintigraphy in 35 patients with coronary artery disease also demonstrated comparable sensitivity and specificity.3 In a review of 12 studies comprising 616 patients who underwent intravenous dipyridamole scintigraphy, the average sensitivity and specificity were similar to the preceding values (85 % and 90 o/o, respectively).4 Arm exercise thallium scintigraphy demonstrated a comparable sensitivity of 83 % and a specificity of 78% in 50 patients with leg impairment5 In 33 men with peripheral vascular disease who performed arm exercise, 25 (76 % ) had thallium defects, but coronary angiography was not performed routinely.6 However, no study has compared intravenous dipyridamole and arm exercise directly. Therefore, in patients who could not perform treadmill exercise, this study compared the results of intravenous
Volume 127, Number 6 American Heart Journal
dipyridamole and arm exercise thallium-201 singlephoton emission computed tomographic (SPECT) scintigraphy for detection of significant coronary artery disease determined by angiography. METHODS Patient selection. Between October 1987 and June 1988, patients who were referred for thallium scintigraphy and who could not walk on a treadmill were asked to participate in a study comparing intravenous dipyridamole and arm exercise thallium scintigraphy. The protocol WAS approved by the Veterans Administration Human Studies Subcommittee, and all patients signed informed consent forms. Exercise testing. Patients did not take xanthine-derivative medications for five half-lives and did not drink or eat any foods containing caffeine. In addition, patients took the same medications for the two thallium tests, which were performed on separate days. Exercise ECGs were interpreted as abnormal if ~1 mm flat or downsloping ST-segment depression occurred 80 msec after QRS cessation.7 Arm exercise. Patients cranked an arm ergometer starting at 25 W resistanceand increasingby 25 W at 3-minute intervaIs. Patients evaluated perceived exertion on a scale of 0 to 20 with 20 equal to maximum perceived exerti0n.s Patients exerciseduntil they were fatigued. Thallium was injected intravenously 1 minute before exercise was discontinued. Blood pressurewasobtained by having the patient stop cranking with one arm at the end of each level of exercise. Intravenous dipyridamole. Intravenous dipyridamole wasinjected with an infusion pump at 0.14 mg/kg/min for 4 minutes2 Thallium wasinjected 3 minutes after the end of the infusion. Blood pressureand a 12-leadECG were recorded every minute until imagingwasbegun.Intravenous aminophylline wasgiven for severechest pain or hypotension. Thallium scintigraphy. Thallium, 111 MBq, was injected as describedpreviously, and imageswere obtained approximately 5 minutes and 3 to 4 hours after injection. Data were acquired on a rotating, large field-of-view gamma camera (General Electric Starcam, Milwaukee, Wis). Standard protocols available from the manufacturer were used to acquire and process the images including bullseye images.gSpecifically a 30% window was centered on the low-energy x-ray peak of thallium, and 20% windowswere centered on the 135keV and 167keV photopeaks.Data acquisition beganfrom the 45-degreeright anterior oblique position and stopped at the 45degree left posterior oblique position. Imageswereobtained for 40 seconds at eachof 32 projections. Each projection wascorrected for nonuniformity. Backprojection wasperformed with a ramp Hanning filter with a cutoff value of 0.5 cycles/pixel. Axial filtration wasperformed perpendicular to the slice. No attenuation or scatter correction was performed. Three orthogonal projections were created by oblique-anglereconstruction and were photographed on x-ray film. Thallium uptake was evaluated in 20 myocardial segments on a scaleof 0 to 3 by three observersblinded to clinical data,
Grover-McKay
et al.
1517
with 0 indicating a normal segment and 3 identifying markedly decreasedthallium uptake with radioactivity equal to background.lO Coronary angiography. Images were obtained of the coronary arteries in multiple projections. Angiogramswere interpreted visually by an observerblinded to clinical data. Significant coronary artery diseasewas defined as ~50% stenosis. Statistics. Data are presentedasmean L SD. Data from intravenous dipyridamole and arm exercisewere compared by Student’s paired t test, and p < 0.05 was significant. RESULTS Patients. A total of 20 patients underwent thallium201 SPECT scintigraphy after both arm exercise and intravenous dipyridamole. In one patient medications were changed between the two thallium tests, and in another patient images obtained during arm exercise were suboptimal. Therefore data are presented for 18 men with an average age of 61 rt 7 years. Eight patients could not perform adequate exercise on a treadmill because of peripheral vascular disease, and 10 patients were confined to a wheelchair or had orthopedic problems. Sixteen patients were being evaluated for chest pain, and two had a history of congestive heart failure. Three patients had undergone prior coronary artery bypass graft surgery. Exercise testing. Intravenous dipyridamole and arm exercise studies were performed within 12 -t- 9 days. One patient had a left bundle branch block, and in another patient with an incomplete left bundle branch block, a complete left bundle branch block developed during both tests. The maximum heart rate during arm exercise wassignificantly higher than that during intravenous dipyridamole (116 -t 22 vs 77 k 13 beats/min; p < O.OOOl),aswas the maximum systolic blood pressure (149 f 24 vs 128 ~fr 16 mm Hg; p < 0.001). Arm exercise. Patients performed an average of 3.3 + 0.7 METS of activity, and the average perceived exertion was 18 f 1. Three patients had chest pain. Four of the 16 patients without a left bundle branch block had 11 mm ST depression, only one of whom had chest pain. Intravenous dipyridamole. Six patients had chest pain during or soon after the dipyridamole infusion, and one patient had atypical chest pain after thallium imaging was completed. Three patients had 2 1 mm ST depression, two of whom had chest pain. Six patients were given intravenous aminophylline for chest pain, one of whom had a 40 mm Hg decrease in systolic blood pressure. Coronary angiography. Eleven patients had significant coronary artery disease, six with three-vessel disease and five with one-vessel disease. Of the
1518
Grover-McKay
et al.
American
I. Comparison of thallium-201 arm exercise study, intravenous dipyridamole study, and coronary angiography Table
Patient
CAD
Arm
1 2 3 4 5 6 7 8 9 10
+ + + + + + + + + + + 0 0 0 0 0 0 0
+ + + + + + + + + + 0 0 0 0 0 0 +* 0
11
12 13 14 15
16 17 18
Arm, Arm exercise study; CAD, as >50% stenosis; Dipyridamole, not available to analyze without
significant intravenous background
Dipyridamole
June 1994 Heart Journal
retrieve the other study from tape). Therefore we photographed the images without background subtraction (Fig. l), and the inferior wall was interpreted as normal on the images without background subtraction. DISCUSSION
+ + + 0 0 0 0 0 0 0 0 coronary artery dipyridamole subtraction.
disease study.
defined *Images
patients without significant coronary artery disease, only one had peripheral vascular disease. During arm exercise two of the three patients who had chest pain had significant coronary artery disease, and all three patients who had ST depression had significant coronary artery disease. Of the six patients who had chest pain during or soon after the dipyridamole infusion, half had significant coronary artery disease. TWO of three patients with ST depression during the dipyridamole test had three-vessel disease, and two of these three had ST depression during arm exercise. Of the two patients who had chest pain during both tests, one had prior bypass surgery with stenosis in one graft, and the other had no significant coronary artery disease. Thallium scintigraphy (Table I). Among patients with significant coronary artery disease, the disease was detected in 10 of 11 (91%). Results of intravenous dipyridamole and arm exercise thallium tests were equivalent. Among patients without significant coronary artery disease, thallium scintigrams obtained after intravenous dipyridamole were interpreted as normal in all of them. However, thallium scintigrams obtained after arm exercise were initially interpreted as demonstrating a fixed defect in the inferior wall in two patients (scored as 3 and confirmed by the bullseye images). When images without background subtraction from one of these studies were reviewed on the computer, we noticed relatively high background radioactivity (it was not possible to
This study in men demonstrates that the results of intravenous dipyridamole and arm exercise thallium scintigraphy were comparable and correlated with the results of coronary angiography. All patients with significant coronary artery disease were identified correctly. In patients without sign :icant coronary artery disease, intravenous dipyridamole thallium images were interpreted correctly. Initial processing (with background subtraction) of thallium scintigrams obtained after arm exercise demonstrated a fixed inferior defect in two patients without significant coronary artery disease. When images from one of these patients were reprocessed without background subtraction, no poste: ior wall defect was detected (Fig. 1). Limitations of this study include the small number of subjects examined and the lack of women subjects. This study suggests that in men, an arm exercise study yields information comparable to coronary vasodilatation produced by intravenous dipyridamole if care is taken to not oversubtract background activity. A possible explanation for the increased background activity during arm exercise is increased blood flow to the muscles of the chest wall. Balady et al.ll compared arm and leg exercise in normal subjects and demonstrated that at a similar rate-pressure product, despite the lower work load performed with arm exercise, left ventricular wall stress and contractility were similar for arm and leg exercise. Balady et al. l2 also demonstrated that during arm exercise, men attained higher levels of absolute power output and oxygen consumption than women, and the chronotropic response to total body oxygen demand during arm exercise was greater among women than men. Because our study only examined men, whether the results of arm exercise and intravenous dipyridamole imaging are comparable in women will require further investigation. In addition, Balady et al. l2 found that during arm exercise, older subjects when compared with younger subjects reached a lower peak power output, despite similar peak oxygen consumption. Therefore the effect of age will also require further investigation. The pathophysiology of exercise and vasodilator imaging is different. The choice of whether to perform one type of testing over another is partially dependent on the type of patient who is to undergo the test. For example, in paraplegic patients the clinician
vd~me 127, Number 6 American Heart Journal
Grover-McKay
et al.
1519
1. Effect of background subtraction on arm exercisethallium-201 images.Immediate (left) and delayed (right) thallium-201 SPECT imagesare shownfor arm exercisestudy. Imageswith background subtraction are at the top; imageswith no background subtraction are at the bottom. Midventricular shortaxis imagesare shown at the top of each set of images;midventricular vertical long-axis imagesare shown at the bottom. On imageswith background subtraction, decreasedthallium-201 uptake is seenin the inferoposterior wall. On imageswith no background subtraction, decreasedthallium-201 uptake in the inferoposterior wall is not as evident.
Fig.
may want to know whether the patient can safely perform a given amount of arm work. In addition, arm exercise testing can be performed in patients with bronchospastic lung disease, who cannot be taken off xanthine-derivative medications such as theophylline. Intravenous adenosine has also been used safely to evaluate regional myocardial perfusion after maximum vasodilatation,13* l4 and results are comparable to those of exercise testing.15-l7 Because results of intravenous dipyridamole testing are also comparable to those of exercise testing, it is not clear whether adenosine studies have higher specificity. Data obtained by measuring coronary flow reserve with an
intracoronary Doppler catheter concluded that intravenous adenosine is a more potent vasodilator than the dose of intravenous dipyridamole used in this study.18 However, investigators who performed a recent study in which myocardial blood flow was quantitated by means of dynamici N-ammonia imaging and positron emission tomography concluded that the two drugs produced comparable increases in coronary flow reserve. lg Each vasodilator has advantages and disadvantages20 In conclusion, results of thallium-201 SPECT scintigraphy in men with either intravenous dipyridamole or arm exercise were comparable for the detection of the presence or absence of significant
1520
Grover-McKay et al.
coronary artery disease, if care was taken not to oversubtract background radioactivity on thallium images obtained after arm exercise. We thank Mr. Victor Smith for expert assistance and Dr. Victor Froelicher for providing the environment that helped make this study possible. We also thank Dr. Sheila Robinson for assistance with patient identification and recruitment and Ms. Marlene Blakley for help with preparation of the manuscript. REFERENCES
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