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Comparison of measurement of left ventricular ejection fraction by Tc-99m sestamibi first-pass angiography with electron beam computed tomography in patients with anterior wall acute myocardial infarction
Comparison of Measurement of Left Ventricular Ejection Fraction by Tc-99m Sestamibi First-Pass Angiography With Electron Beam Computed Tomography in Patients With Anterior Wall Acute Myocardial Infarction Thomas C. Gerber, MD, Thomas Behrenbeck, MD, PhD, Thomas Allison, PhD, Brian P. Mullan, MD, John A. Rumberger, MD, PhD, and Raymond J. Gibbons, MD The goal of this study was to compare measurements of left ventricular (LV) ejection fraction (EF) by first-pass radionuclide angiography (“first-pass angiography”) using technetium-99m (Tc-99m) sestamibi with those by contrast-enhanced electron beam computed tomography (“electron beam tomography”) as a reference technique in patients with an anterior wall acute myocardial infarction (AMI). Twenty-five patients with first Q-wave anterior wall AMI underwent paired electron beam tomographic and first-pass angiographic studies (mean, 1 day apart). Fourteen patients had 2 sets of measurements of the LVEF obtained by both methods (separated by at least 6 weeks), for a total of 39 paired measurements. LVEF by electron beam tomography was calculated from absolute systolic and diastolic LV chamber volumes. LV volumes by electron beam tomography were 199 6 51 ml at end-diastole and 111 6 42 ml at
end-systole. Mean LVEF was 45 6 11% by first-pass tomography and 46 6 9% by electron beam tomography. The linear correlation coefficient between both methods was 0.82 (p <0.0001), with slope 5 1.0, y-intercept 5 21.1, and SEE 5 6.1. The mean difference between the 2 methods was 20.7 6 6.0 EF units (p 5 0.75). The correlation between the differences and means of both methods was 0.34 (p 5 0.04), indicating a trend for first-pass angiography to overestimate LVEF in the higher range. LVEFs measured by first-pass angiography in patients with abnormal LV geometry and contraction patterns caused by anterior wall AMI agree well with those measured by electron beam tomography in the clinically relevant range. Q1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;83:1022–1026)
echnetium-99m-hexakis-2-methoxyisobutyl-isonitrile (Tc-99m sestamibi) is a radiopharmaceutical T that allows assessment of myocardial perfusion and
dial borders, without motion artifacts. Comprehensive assessment of cardiac muscle and chambers throughout the cardiac cycle at up to 17 frames/s is possible. Using well-validated methods for border definition,3 highly accurate measurements of right and LV volumes and global function4,5 as well as muscle mass3,6 have been reported. This quantitative imaging modality has not been used previously to validate LVEFs obtained by first-pass angiography. The goal of this study was to compare determinations of LVEF by Tc-99m sestamibi first-pass angiography and electron beam tomography.
function during a single diagnostic study.1 Perfusion imaging with Tc-99m sestamibi is established as an accurate method of quantifying left ventricular (LV) infarct size.2 Its introduction has led to renewed interest in first-pass radionuclide angiography (“first-pass angiography”) for measurement of LV ejection fraction (EF). Electron beam computed tomography (“electron beam tomography”) is an established imaging technique that allows rapid acquisition of closely spaced, parallel tomographic images of the heart at high frame rates. During an electron beam tomographic scan, a 3-dimensional image dataset is acquired. Intravenous administration of contrast agent provides superior definition of endocardial and epicarFrom the Division of Cardiovascular Diseases and Internal Medicine and the Department of Diagnostic Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. This study was supported in part by Grant MO1 RR00585 from Human Health Services, General Clinical Research Centers, Division of Research Resources, National Institutes of Health, Bethesda, Maryland. Manuscript received June 5, 1998; revised manuscript received November 17, 1998, and accepted November 20. Address for reprints: Thomas Behrenbeck, MD, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
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©1999 by Excerpta Medica, Inc. All rights reserved.
METHODS
Patients: Patients with first Q-wave anterior wall acute myocardial infarction (AMI) were eligible for the study. Anterior wall AMI was defined by the presence of at least 2 of the following criteria: (1) typical chest pain .20 minutes, (2) ST-segment elevation by $1 mV (lead I) or $1.5 mV in at least 2 precordial leads, (3) appearance of a new Q wave (width $0.03 second) in these leads, or (4) total creatine kinase and creatine kinase-muscle and brain fraction increased above normal. Exclusion criteria were (1) previous Q-wave or non–Q-wave AMI, (2) significant tricuspid regurgitation of greater than mild degree by physical examination or echocardiography, 0002-9149/99/$–see front matter PII S0002-9149(99)00008-9
The program assumed the valve plane to be constant throughout the cardiac cycle. LVEF was calculated from: LVEF 5
EDC~C! 2 ESC~C! 3 100 @%# EDC~C! (1)
where EDC(C) and ESC(C) are the background-corrected LV counts at end-diastole and end-systole, respectively.10 FIGURE 1. Electron beam computed tomographic image of a midventricular LV slice in diastole (left ) and systole (right ), with an area of anteroseptal dyskinesia (arrows). This patient had an infarct size of 61% of the left ventricle (LV) and an ejection fraction of 39% by Tc-99m sestamibi scanning. LVEF by electron beam computed tomography was 37%. A 5 anterior; L 5 lateral; P5 posterior; S 5 septal LV wall.
(3) severe pulmonary hypertension by history or echocardiography, (4) hemodynamic instability, (5) creatinine .1.5 at baseline, or (6) atrial fibrillation or flutter by electrocardiography. The study group consisted of 25 patients (20 men and 5 women, mean age 57 6 12 years). All patients had a first anterior wall AMI 9 6 6 days before the first measurement of LVEF; infarct size determined by Tc-99m sestamibi perfusion scanning was 30 6 21% (range 0% to 76%) of LV muscle mass (Figure 1). In the 25 patients, 39 comparative determinations of LVEF were performed. The mean interval between electron beam tomography and first-pass angiography was 1 day (range 0 to 7). Fourteen patients had 2 sets of paired measurements of LVEF by both methods, separated by at least 6 weeks. Because of the expected changes in hemodynamic status and LV geometry in the weeks following an AMI,7 serial studies in these patients were considered independent sets of measurements. Tc-99m sestamibi first-pass angiography: IMAGE AC-
The technique of Tc-99m sestamibi (Cardiolite, DuPont Merck, Billerica, Massachusetts) firstpass angiography used at the authors’ institution is described in detail elsewhere.8 Bolus quality was evaluated from a time-activity curve from the superior vena cava. The first-pass study was used to calculate LVEF only if the following quality criteria for the bolus injection were met: (1) maximal count .100,000 counts/s, (2) time to half maximum of the time-activity curve ,1.5 second, and (3) adequate separation of the right ventricular and LV phases on the activity curve. The “lung-frame method” of background subtraction was used to eliminate background noise.9 All cycles with lengths varying .620% from the mean RR interval were rejected. The first and the last cycles of the LV phase were not used for calculation of LVEF. An example of a time-activity curve after a bolus injection of Tc-99m sestamibi is shown in Figure 2. IMAGE ANALYSIS: The observer for first-pass angiography was blinded to the electron beam tomographic data. Calculation of LVEF was performed with a semiautomatic interactive computer program. QUISITION:
Electron beam tomography: IMAGE AC-
For electron beam tomographic imaging, the Imatron C-100 scanner (Imatron Inc., San Francisco, California) was used. The technique of electron beam computed tomographic imaging of the heart used at the authors’ institution is described in detail elsewhere.7 During 2 scans, a total of 12 contiguous parallel short-axis tomograms (slices) of the heart were obtained. The scanning rate was 17 frames/s, the slice thickness was 0.8 cm, and the center-to-center distance of the slices was 1 cm. On average, 9 6 1 electron beam tomographic short-axis tomograms constitute LV volume of a patient. A 360 3 360 pixel matrix with a 350-mm field of view was used, yielding an image resolution of 0.94 mm2 per square pixel. If serial imaging was performed in the same patient, imaging angles and parameters from the previous scans were reproduced as accurately as possible. IMAGE ANALYSIS: The electron beam tomographic images were stored on optical disk for off-line analysis. Image analyses were performed on a workstation (Sun Microsystems, Silicon Valley, California) using custom software.11 The endocardial borders of the LV short-axis tomograms were traced by 1 of 2 observers using previously established criteria.3 The observers for electron beam tomography were blinded to firstpass angiographic and clinical data. The software allowed automatic detection of end-diastolic and endsystolic frames by selecting for each slice the frames coinciding with the R wave and the frame with the smallest traced LV area, respectively. From these, end-diastolic and end-systolic volumes were calculated based on Simpson’s rule using all available LV slices. LVEF was calculated from these data using a commercially available spreadsheet (Excel, Microsoft, Redmond, Washington) from the formula: QUISITION:
LVEF 5
~EDV 2 ESV! 3 100 @%# EDV
(2)
where EDV and ESV are the global end-diastolic and end-systolic LV chamber volumes, respectively. Statistical analysis: All statistical analyses were performed using SigmaStat for Windows 3.1, SPSS Inc., Chicago, Illinois. Data are presented as means 6 1 SD except where indicated. LVEFs obtained with either method were compared using paired t testing. A p value ,0.05 was considered significant. Linear regression analysis was performed to calculate the Pearson product-moment correlation coefficients between
CORONARY ARTERY DISEASE/MEASUREMENT OF LEFT VENTRICULAR EJECTION FRACTION
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FIGURE 2. Time-activity curves from left ventricle and lungs. Cycles 1 to 5 would be selected for analysis. S, start of left ventricular phase; E, end of left ventricular phase. The lower curve represents background activity.
first-pass angiographic and electron beam tomographic determinations of LVEF. A Bland-Altman method comparison12 was performed for each paired measurement of LVEF by electron beam tomography and first-pass angiography: the difference between the 2 methods (first-pass angiography minus electron beam tomography) was plotted on the y-axis against their mean on the x-axis together with the mean difference 6 2 SDs to assess (1) limits and degree of agreement between LVEF measurements obtained with each technique, (2) degree of bias of 1 method to yield systematically higher or lower results, and (3) relation between degree of under- or overestimation and mean value of the 2 techniques.
RESULTS In 27 patients, 45 comparative determinations of LVEF using first-pass angiographic and electron beam tomographic scanning of the heart were performed. Six first-pass angiographic studies from 5 patients were excluded because of poor bolus injection. Imaging studies: FIRST-PASS ANGIOGRAPHY AND
Table I shows mean 6 SDs, ranges, 25th and 75th percentiles, and 95% confidence intervals for end-diastolic and end-systolic background-corrected counts of first-pass angiography, end-diastolic and end-systolic LV chamber volumes by electron beam tomography, and LVEF measured by both methods. Method comparison: The correlation between the comparative EF measurements is shown in Figure 3A. The correlation coefficient was 0.82 (p ,0.0001) with slope 5 1.0, y-intercept 5 21.1, and SEE 5 6.1. Figure 3B shows the Bland-Altman plot. Mean LVEFs by both methods were not significantly different (p 5 0.75). Although the mean difference was low at 20.7 6 6.0% (range 29.9% to 10.8%), the scatter of data was relatively large, as indicated by the SD of the mean difference and the SEE (approximately 12% of the mean EF measured by electron beam tomography). However, the 95% confidence interval for the mean difference was narrow (22.6% to 1.2%). The correlation coefficient between differences and means of both methods was 0.34 (p 5 0.04), with slope 5 ELECTRON BEAM TOMOGRAPHY:
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0.22 and y-intercept 5 210.7, indicating a weak but significant trend for first-pass angiography to overestimate LVEF in the higher range. The number of studies with low LVEF (,40%) was small (n 5 11 [28%]), making validation of first-pass angiography for those patients difficult. Both electron beam tomography and first-pass angiography separated studies with EFs ,40% and .40% well (p ,0.001). There was no significant difference between electron beam tomography and first-pass angiography in the group with ,40% (35 6 5% vs 34 6 8%) or .40% LVEF (50 6 5% vs 49 6 8%). The mean difference between both methods showed a nonsignificant trend to be higher in patients with LVEF ,40% (21.0 6 5.0% vs 20.6 6 6.4%). The correlation coefficient between the 2 methods was lower in patients with EFs .40% (LVEF ,40%: r 5 0.79, slope 5 1.4, y-intercept 5 213.6, SEE 5 5.0; LVEF .40%: r 5 0.64, slope 5 0.9, y-intercept 5 4.5, SEE 5 6.5). In the 14 patients who had paired measurements by electron beam tomography and first-pass angiography at an early and a late time point after AMI, LVEF was 44 6 9% versus 44 6 9% early and 47 6 10% versus 47% 6 12% late (p 5 NS). The correlation coefficients and regression equations between the 2 methods early and late were similar (early: r 5 0.80, y-intercept 5 8.5, slope 5 0.8, SEE 5 5.4; late: r 5 0.85, y-intercept 5 21.2, slope 5 1.0, SEE 5 6.4). The increase in LVEF from early to late measured by electron beam tomography and first-pass angiography was 2.5 6 5.3% and 2.7 6 8.2% (p 5 NS), respectively. The correlation coefficient between changes in LVEF over time measured by the 2 methods was low at 0.37, with y-intercept 5 1.3 and slope 5 0.57.
DISCUSSION
Measurement of LVEF with electron beam tomography: Electron beam tomography allows simultaneous
assessment of the structure and function of the heart with 1 scan. Contrast-enhanced electron beam tomography provides high-resolution images with excellent endocardial and epicardial border definition. It has been shown to determine right and LV muscle mass and volumes accurately,3,5,6 and derived variables such as stroke volume or LVEF,4 with very low interand intraobserver variability (,3%).3 The disadvantages of using electron beam tomography in clinical practice include the cost of the scanners, the need for intravenous contrast agent, and the fairly complex postprocessing of images. Measurement of cardiac chamber volumes and LVEF using proprietary software supplied with the scanner takes approximately 10 minutes. Measurement of LVEF with Tc-99m sestamibi firstpass angiography: First-pass angiography was one of
the first noninvasive methods to assess ventricular function.13 It has shown to correlate well with equilibrium radionuclide angiography14 and contrast ventriculography.15 Tc-99m sestamibi has gained wide acceptance as a myocardial perfusion single-photon emission computed tomographic imaging agent,2,16 because of its advantages of higher photon energy and APRIL 1, 1999
TABLE I Tc-99m Sestamibi First-Pass Angiography and Electron Beam Computed Tomography Measurements FPRNA Variable Mean 6 SD Range 25th Percentile 75th Percentile 95% CI
EBCT
LVEF (%)
ED Counts
ES Counts
EDV (ml)
ESV (ml)
FPRNA
EBCT
3,345 6 996 1,863–5,781 2,709 3,886 3,013–3,677
1,926 6 818 712–4,179 1,270 2,535 1,653–2,198
199 6 51 103–318 156 231 182–215
111 6 42 39–230 80 134 98–125
45 6 11 22–63 38 52 41–48
46 6 9 28–62 40 54 43–48
CI 5 confidence interval of mean; EBCT 5 electron beam computed tomography; ED Counts, ES Counts 5 end-diastolic and end-systolic background-corrected counts, respectively; EDV 5 end-diastolic volume; ESV 5 end-systolic volume; FPRNA 5 first-pass radionuclide angiography.
higher injectable dose compared with thallium-201.17 Extremely high count rates (150 to 600 kcps) can be achieved because of the high activity and concentration of Tc-99m in the bolus dose. The possibility and convenience of assessing both myocardial perfusion and function with a 1-dose injection of a radionuclide, eliminating the need for additional radiation exposure,1 has led to renewed interest in first-pass technology. The advantages of first-pass angiography over equilibrium radionuclide angiography include a very short acquisition time and lower background activity. The inter- and intraobserver variability is low (approximately 3%).18 Accurate measurement of LVEF with first-pass angiography is highly dependent on the quality of the bolus injection. The presence of severe pulmonary hypertension, tricuspid regurgitation, or dysrhythmia may invalidate the study. LVEF has been measured with good success from electrocardiographically gated single-photon emission computed tomographic perfusion images, obviating bolus injection and specialized equipment.19,20 However, definition of the LV cavity border by manual tracing or automated edge-detection algorithms may be difficult in the presence of a large perfusion defect, particularly when it involves the base of the heart.19 The data acquisition time is longer than for first-pass angiography, and the count statistics can be poor (approximately 1/8 of nongated single-photon emission computed tomographic images). A sampling rate high enough to allow reliable identification of end-diastolic and endsystolic frames (16/s) consumes considerable processing time and computer memory.19,20 Sources of error in measuring LVEF with first-pass angiography: Most planar techniques for measuring
LVEF, including equilibrium and first-pass angiography, require manual drawing of a region of interest (usually at end-diastole). This in practice frequently includes counts superior to the valve plane during end-systole as a result of motion of the cardiac base toward the apex, causing underestimation of the LVEF.19 The use of an inappropriate image projection can lead to errors in measurement of EF by radionuclide angiography, particularly in patients with anterior wall motion abnormalities.21,22 Factors influencing the accuracy of count-based methods to estimate LV cavity volumes have been described in detail elsewhere.23,24 Inaccuracies related to image projec-
FIGURE 3. A, correlation between measurements of LVEF by electron beam computed tomography (EBCT) and Tc-99m sestamibi first-pass radionuclide angiography (FPRNA). There is excellent agreement between both methods, even in distorted left ventricles with altered contraction patterns. B, Bland-Altman plot showing the relation between the differences and means of the LVEF measurements by EBCT and Tc-99m sestamibi FPRNA. The significant correlation with positive slope indicates overestimation of EF by FPRNA at values >55% to 60%.
CORONARY ARTERY DISEASE/MEASUREMENT OF LEFT VENTRICULAR EJECTION FRACTION
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tion can be overcome with the use of scintillation cameras with perpendicular biplane detectors.25 Discussion of study results: Exclusion criteria in our study were patient conditions known to adversely affect the bolus quality and studies not satisfying commonly accepted technical criteria. Good counts statistics are an important requirement for reliable first-pass studies. It has been suggested that background-corrected end-diastolic counts should be .2 kcounts.26 In the present study, the mean end-diastolic count far exceeded this threshold, indicating satisfactory image quality. Therefore, high-quality first-pass angiographic studies were available for comparison with electron beam tomography. The high end-diastolic volumes and low LVEFs in the present study are explained by large infarctions. The correlation of firstpass angiography with electron beam tomography was very good and probably would be improved more with the use of a multicrystal gamma camera. The BlandAltman method of comparison showed a positive correlation between the difference and mean of both methods, indicating an overestimation of the LVEF by first-pass angiography at higher values. This tendency should be acceptable because the crucial threshold for clinical decision making is around 40%.27 In previous comparative studies,28,29 first-pass angiography underestimated LVEF by 12% to 25% compared with LV angiography. This may be due to decreased LV preload in the upright position during first-pass study as opposed to higher preload during contrast injection in the supine position, resulting in a higher angiographic EF secondary to the Frank-Starling mechanism. In the present study, the study subjects were supine during both first-pass angiography and electron beam tomography, eliminating this source of error. For scientific purposes, methods such as magnetic resonance imaging or electron beam computed tomography that make no assumptions about LV geometry and contraction patterns are most valuable for the measurement of LVEF. The method a physician uses in the clinical setting should depend on the situation and the local availability of a specific technique. Firstpass angiography using Tc-99m sestamibi is a valuable adjunct to the assessment of patients undergoing stress perfusion imaging. When absolute measures of right and LV volumes and EF are needed, magnetic resonance imaging and electron beam tomography are the most quantitative and reproducible methods.30 1. Baillet GY, Mena IG, Kuperus JH, Robertson JM, French WJ. Simultaneous technetium-99m MIBI angiography and myocardial perfusion imaging. J Nucl Med 1989;30:38 – 44. 2. Gibbons RJ, Verani MS, Behrenbeck T, Pellikka PA, O’Connor MK, Mahmarian JJ, Chesebro JH, Wackers FJ. Feasibility of tomographic 99mTc-hexakis2-methoxy-2-methylpropyl-isonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute myocardial infarction. Circulation 1989;80:1277–1286. 3. Feiring AJ, Rumberger JA, Reiter SJ, Skorton DJ, Collins SM, Lipton MJ, Higgins CB, Ell S, Marcus ML. Determination of left ventricular mass in dogs with rapid-acquisition cardiac computed tomographic scanning. Circulation 1985;72:1355–1364. 4. Reiter SJ, Rumberger JA, Feiring AJ, Stanford W, Marcus ML. Precision of measurements of right and left ventricular volume by cine computed tomography. Circulation 1986;74:890 –900.
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5. Roig E, Georgiou D, Chomka EV, Wolfkiel C, LoGalbo-Zak C, Rich S, Brundage BH. Reproducibility of left ventricular myocardial volume and mass measurements by ultrafast computed tomography. J Am Coll Cardiol 1991;18: 990 –996. 6. Hajduczok ZD, Weiss RM, Stanford W, Marcus ML. Determination of right ventricular mass in humans and dogs with ultrafast cardiac computed tomography. Circulation 1990;82:202–212. 7. Hirose K, Reed JE, Rumberger JA. Serial changes in left and right ventricular systolic and diastolic dynamics during the first year after an index left ventricular Q wave myocardial infarction. J Am Coll Cardiol 1995;25:1097–1104. 8. O’Connor MK, Miller TD, Christian TF, Gibbons RJ. 99mTc sestamibi firstpass radionuclide angiogram. In: O’Connor MK, ed. The Mayo Clinic Manual of Nuclear Medicine. New York: Churchill Livingstone, 1996:197–203. 9. Gal R, Grenier RP, Schmidt DH, Port SC. Background correction in first-pass radionuclide angiography: comparison of several approaches. J Nucl Med 1986; 27:1480 –1486. 10. Wackers FJT. First-pass radionuclide angiocardiography. In: Gerson MC, ed. Cardiac Nuclear Medicine. New York: McGraw-Hill, 1987:53– 66 11. Rumberger JA, Reed JE, Behrenbeck T, Davitt PJ, Sheedy PF. Development and application of image processing, data processing, database and data query tools to study post-infarction cardiac remodeling in man. In: Hoffman EA, Acharya RS, eds. Medical Imaging 1994: Physiology and Function From Multidimensional Images. Bellingham, WA: Proceedings SPIE, 1994;2168:131–140. 12. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–310. 13. Van Dyke D, Anger HO, Sullivan RW, Vetter WR, Yano Y, Parker HG. Cardiac evaluation from radioisotope dynamics. J Nucl Med 1972;13:585–592. 14. Wackers FJ, Berger HJ, Johnstone DE, Goldman L, Reduto LA, Langou RA, Gottschalk A, Zaret BL. Multiple gated cardiac blood pool imaging for left ventricular ejection fraction: validation of the technique and assessment of variability. Am J Cardiol 1979;43:1159 –1166. 15. Jengo JA, Mena I, Blaufuss A, Criley JM. Evaluation of left ventricular function (ejection fraction and segmental wall motion) by single pass radioisotope angiography. Circulation 1978;57:326 –332. 16. Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993;328:685– 691. 17. Berman DS. Introduction—technetium-99m myocardial perfusion imaging agents and their relation to thallium-201. Am J Cardiol 1990;66:1E– 4E. 18. Jones RH, McEwan P, Newman GE, Port S, Rerych SK, Scholz PM, Upton MT, Peter CA, Austin EH, Leong KH, Gibbons RJ, Cobb FR, Coleman RE, Sabiston DC Jr. Accuracy of diagnosis of coronary artery disease by radionuclide management of left ventricular function during rest and exercise. Circulation 1981;64:586 – 601. 19. Williams KA, Taillon LA. Left ventricular function in patients with coronary artery disease assessed by gated tomographic myocardial perfusion images. Comparison with assessment by contrast ventriculography and first-pass radionuclide angiography. J Am Coll Cardiol 1996;27:173–181. 20. DePuey EG, Nichols K, Dobrinsky C. Left ventricular ejection fraction assessed from gated technetium-99m-sestamibi SPECT. J Nucl Med 1993;34: 1871–1876. 21. Esquerre JP, Coca FJ, Gantet P, Ouhayoun E. Feasibility of first-pass radionuclide angiography with a 10-mCi technetium bolus using a single-crystal digital gamma camera: implications for technetium-sestamibi single-day protocols. Eur J Nucl Med 1995;22:521–527. 22. Schneider RM, Jaszczak RJ, Coleman RE, Cobb FR. Disproportionate effects of regional hypokinesis on radionuclide ejection fraction: compensation using attenuation-corrected ventricular volumes. J Nucl Med 1984;25:747–754. 23. Levy WC, Cerqueira MD, Matsuoka DT, Harp GD, Sheehan FH, Stratton JR. Four radionuclide methods for left ventricular volume determination: comparison of a manual and an automated technique. J Nucl Med 1992;33:763-770. 24. Levy WC, Jacobson AF, Cerqueira MD, Matsuoka DT, Sheehan FH, Stratton JR. Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor. J Nucl Med 1992;33:1642– 1647. 25. DePuey EG, Salensky H, Melancon S, Nichols KJ. Simultaneous biplane first-pass radionuclide angiocardiography using a scintillation camera with two perpendicular detectors. J Nucl Med 1994;35:1593–1601. 26. Wackers FJ, Sinusas AJ, Saari MA, Mattera JA. Is list mode ECG-gated first pass LVEF accurate using a single crystal gamma camera? Implications for Tc-99m labeled perfusion imaging agents (abstr). J Nucl Med 1991;32:939. 27. The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309:331–336. 28. Folland ED, Hamilton GW, Larson SM, Kennedy JW, Williams DL, Ritchie JL. The radionuclide ejection fraction: a comparison of three radionuclide techniques with contrast angiography. J Nucl Med 1977;18:1159 –1166. 29. Nusynowitz ML, Benedetto AR, Walsh RA, Starling MR. First-pass Anger camera radiocardiography: biventricular ejection fraction, flow, and volume measurements. J Nucl Med 1987:28:950 –959. 30. Rumberger JA, Behrenbeck T, Bell MR, Breen JF, Johnston DL, Holmes DR Jr, Enriquez-Sarano M. Determination of ventricular ejection fraction: a comparison of available imaging methods. Mayo Clin Proc 1997;72:860 – 870.
APRIL 1, 1999
end-systole. Mean LVEF was 45 6 11% by first-pass tomography and 46 6 9% by electron beam tomography. The linear correlation coefficient between both methods was 0.82 (p <0.0001), with slope 5 1.0, y-intercept 5 21.1, and SEE 5 6.1. The mean difference between the 2 methods was 20.7 6 6.0 EF units (p 5 0.75). The correlation between the differences and means of both methods was 0.34 (p 5 0.04), indicating a trend for first-pass angiography to overestimate LVEF in the higher range. LVEFs measured by first-pass angiography in patients with abnormal LV geometry and contraction patterns caused by anterior wall AMI agree well with those measured by electron beam tomography in the clinically relevant range. Q1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;83:1022–1026)
echnetium-99m-hexakis-2-methoxyisobutyl-isonitrile (Tc-99m sestamibi) is a radiopharmaceutical T that allows assessment of myocardial perfusion and
dial borders, without motion artifacts. Comprehensive assessment of cardiac muscle and chambers throughout the cardiac cycle at up to 17 frames/s is possible. Using well-validated methods for border definition,3 highly accurate measurements of right and LV volumes and global function4,5 as well as muscle mass3,6 have been reported. This quantitative imaging modality has not been used previously to validate LVEFs obtained by first-pass angiography. The goal of this study was to compare determinations of LVEF by Tc-99m sestamibi first-pass angiography and electron beam tomography.
function during a single diagnostic study.1 Perfusion imaging with Tc-99m sestamibi is established as an accurate method of quantifying left ventricular (LV) infarct size.2 Its introduction has led to renewed interest in first-pass radionuclide angiography (“first-pass angiography”) for measurement of LV ejection fraction (EF). Electron beam computed tomography (“electron beam tomography”) is an established imaging technique that allows rapid acquisition of closely spaced, parallel tomographic images of the heart at high frame rates. During an electron beam tomographic scan, a 3-dimensional image dataset is acquired. Intravenous administration of contrast agent provides superior definition of endocardial and epicarFrom the Division of Cardiovascular Diseases and Internal Medicine and the Department of Diagnostic Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. This study was supported in part by Grant MO1 RR00585 from Human Health Services, General Clinical Research Centers, Division of Research Resources, National Institutes of Health, Bethesda, Maryland. Manuscript received June 5, 1998; revised manuscript received November 17, 1998, and accepted November 20. Address for reprints: Thomas Behrenbeck, MD, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
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©1999 by Excerpta Medica, Inc. All rights reserved.
METHODS
Patients: Patients with first Q-wave anterior wall acute myocardial infarction (AMI) were eligible for the study. Anterior wall AMI was defined by the presence of at least 2 of the following criteria: (1) typical chest pain .20 minutes, (2) ST-segment elevation by $1 mV (lead I) or $1.5 mV in at least 2 precordial leads, (3) appearance of a new Q wave (width $0.03 second) in these leads, or (4) total creatine kinase and creatine kinase-muscle and brain fraction increased above normal. Exclusion criteria were (1) previous Q-wave or non–Q-wave AMI, (2) significant tricuspid regurgitation of greater than mild degree by physical examination or echocardiography, 0002-9149/99/$–see front matter PII S0002-9149(99)00008-9
The program assumed the valve plane to be constant throughout the cardiac cycle. LVEF was calculated from: LVEF 5
EDC~C! 2 ESC~C! 3 100 @%# EDC~C! (1)
where EDC(C) and ESC(C) are the background-corrected LV counts at end-diastole and end-systole, respectively.10 FIGURE 1. Electron beam computed tomographic image of a midventricular LV slice in diastole (left ) and systole (right ), with an area of anteroseptal dyskinesia (arrows). This patient had an infarct size of 61% of the left ventricle (LV) and an ejection fraction of 39% by Tc-99m sestamibi scanning. LVEF by electron beam computed tomography was 37%. A 5 anterior; L 5 lateral; P5 posterior; S 5 septal LV wall.
(3) severe pulmonary hypertension by history or echocardiography, (4) hemodynamic instability, (5) creatinine .1.5 at baseline, or (6) atrial fibrillation or flutter by electrocardiography. The study group consisted of 25 patients (20 men and 5 women, mean age 57 6 12 years). All patients had a first anterior wall AMI 9 6 6 days before the first measurement of LVEF; infarct size determined by Tc-99m sestamibi perfusion scanning was 30 6 21% (range 0% to 76%) of LV muscle mass (Figure 1). In the 25 patients, 39 comparative determinations of LVEF were performed. The mean interval between electron beam tomography and first-pass angiography was 1 day (range 0 to 7). Fourteen patients had 2 sets of paired measurements of LVEF by both methods, separated by at least 6 weeks. Because of the expected changes in hemodynamic status and LV geometry in the weeks following an AMI,7 serial studies in these patients were considered independent sets of measurements. Tc-99m sestamibi first-pass angiography: IMAGE AC-
The technique of Tc-99m sestamibi (Cardiolite, DuPont Merck, Billerica, Massachusetts) firstpass angiography used at the authors’ institution is described in detail elsewhere.8 Bolus quality was evaluated from a time-activity curve from the superior vena cava. The first-pass study was used to calculate LVEF only if the following quality criteria for the bolus injection were met: (1) maximal count .100,000 counts/s, (2) time to half maximum of the time-activity curve ,1.5 second, and (3) adequate separation of the right ventricular and LV phases on the activity curve. The “lung-frame method” of background subtraction was used to eliminate background noise.9 All cycles with lengths varying .620% from the mean RR interval were rejected. The first and the last cycles of the LV phase were not used for calculation of LVEF. An example of a time-activity curve after a bolus injection of Tc-99m sestamibi is shown in Figure 2. IMAGE ANALYSIS: The observer for first-pass angiography was blinded to the electron beam tomographic data. Calculation of LVEF was performed with a semiautomatic interactive computer program. QUISITION:
Electron beam tomography: IMAGE AC-
For electron beam tomographic imaging, the Imatron C-100 scanner (Imatron Inc., San Francisco, California) was used. The technique of electron beam computed tomographic imaging of the heart used at the authors’ institution is described in detail elsewhere.7 During 2 scans, a total of 12 contiguous parallel short-axis tomograms (slices) of the heart were obtained. The scanning rate was 17 frames/s, the slice thickness was 0.8 cm, and the center-to-center distance of the slices was 1 cm. On average, 9 6 1 electron beam tomographic short-axis tomograms constitute LV volume of a patient. A 360 3 360 pixel matrix with a 350-mm field of view was used, yielding an image resolution of 0.94 mm2 per square pixel. If serial imaging was performed in the same patient, imaging angles and parameters from the previous scans were reproduced as accurately as possible. IMAGE ANALYSIS: The electron beam tomographic images were stored on optical disk for off-line analysis. Image analyses were performed on a workstation (Sun Microsystems, Silicon Valley, California) using custom software.11 The endocardial borders of the LV short-axis tomograms were traced by 1 of 2 observers using previously established criteria.3 The observers for electron beam tomography were blinded to firstpass angiographic and clinical data. The software allowed automatic detection of end-diastolic and endsystolic frames by selecting for each slice the frames coinciding with the R wave and the frame with the smallest traced LV area, respectively. From these, end-diastolic and end-systolic volumes were calculated based on Simpson’s rule using all available LV slices. LVEF was calculated from these data using a commercially available spreadsheet (Excel, Microsoft, Redmond, Washington) from the formula: QUISITION:
LVEF 5
~EDV 2 ESV! 3 100 @%# EDV
(2)
where EDV and ESV are the global end-diastolic and end-systolic LV chamber volumes, respectively. Statistical analysis: All statistical analyses were performed using SigmaStat for Windows 3.1, SPSS Inc., Chicago, Illinois. Data are presented as means 6 1 SD except where indicated. LVEFs obtained with either method were compared using paired t testing. A p value ,0.05 was considered significant. Linear regression analysis was performed to calculate the Pearson product-moment correlation coefficients between
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FIGURE 2. Time-activity curves from left ventricle and lungs. Cycles 1 to 5 would be selected for analysis. S, start of left ventricular phase; E, end of left ventricular phase. The lower curve represents background activity.
first-pass angiographic and electron beam tomographic determinations of LVEF. A Bland-Altman method comparison12 was performed for each paired measurement of LVEF by electron beam tomography and first-pass angiography: the difference between the 2 methods (first-pass angiography minus electron beam tomography) was plotted on the y-axis against their mean on the x-axis together with the mean difference 6 2 SDs to assess (1) limits and degree of agreement between LVEF measurements obtained with each technique, (2) degree of bias of 1 method to yield systematically higher or lower results, and (3) relation between degree of under- or overestimation and mean value of the 2 techniques.
RESULTS In 27 patients, 45 comparative determinations of LVEF using first-pass angiographic and electron beam tomographic scanning of the heart were performed. Six first-pass angiographic studies from 5 patients were excluded because of poor bolus injection. Imaging studies: FIRST-PASS ANGIOGRAPHY AND
Table I shows mean 6 SDs, ranges, 25th and 75th percentiles, and 95% confidence intervals for end-diastolic and end-systolic background-corrected counts of first-pass angiography, end-diastolic and end-systolic LV chamber volumes by electron beam tomography, and LVEF measured by both methods. Method comparison: The correlation between the comparative EF measurements is shown in Figure 3A. The correlation coefficient was 0.82 (p ,0.0001) with slope 5 1.0, y-intercept 5 21.1, and SEE 5 6.1. Figure 3B shows the Bland-Altman plot. Mean LVEFs by both methods were not significantly different (p 5 0.75). Although the mean difference was low at 20.7 6 6.0% (range 29.9% to 10.8%), the scatter of data was relatively large, as indicated by the SD of the mean difference and the SEE (approximately 12% of the mean EF measured by electron beam tomography). However, the 95% confidence interval for the mean difference was narrow (22.6% to 1.2%). The correlation coefficient between differences and means of both methods was 0.34 (p 5 0.04), with slope 5 ELECTRON BEAM TOMOGRAPHY:
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0.22 and y-intercept 5 210.7, indicating a weak but significant trend for first-pass angiography to overestimate LVEF in the higher range. The number of studies with low LVEF (,40%) was small (n 5 11 [28%]), making validation of first-pass angiography for those patients difficult. Both electron beam tomography and first-pass angiography separated studies with EFs ,40% and .40% well (p ,0.001). There was no significant difference between electron beam tomography and first-pass angiography in the group with ,40% (35 6 5% vs 34 6 8%) or .40% LVEF (50 6 5% vs 49 6 8%). The mean difference between both methods showed a nonsignificant trend to be higher in patients with LVEF ,40% (21.0 6 5.0% vs 20.6 6 6.4%). The correlation coefficient between the 2 methods was lower in patients with EFs .40% (LVEF ,40%: r 5 0.79, slope 5 1.4, y-intercept 5 213.6, SEE 5 5.0; LVEF .40%: r 5 0.64, slope 5 0.9, y-intercept 5 4.5, SEE 5 6.5). In the 14 patients who had paired measurements by electron beam tomography and first-pass angiography at an early and a late time point after AMI, LVEF was 44 6 9% versus 44 6 9% early and 47 6 10% versus 47% 6 12% late (p 5 NS). The correlation coefficients and regression equations between the 2 methods early and late were similar (early: r 5 0.80, y-intercept 5 8.5, slope 5 0.8, SEE 5 5.4; late: r 5 0.85, y-intercept 5 21.2, slope 5 1.0, SEE 5 6.4). The increase in LVEF from early to late measured by electron beam tomography and first-pass angiography was 2.5 6 5.3% and 2.7 6 8.2% (p 5 NS), respectively. The correlation coefficient between changes in LVEF over time measured by the 2 methods was low at 0.37, with y-intercept 5 1.3 and slope 5 0.57.
DISCUSSION
Measurement of LVEF with electron beam tomography: Electron beam tomography allows simultaneous
assessment of the structure and function of the heart with 1 scan. Contrast-enhanced electron beam tomography provides high-resolution images with excellent endocardial and epicardial border definition. It has been shown to determine right and LV muscle mass and volumes accurately,3,5,6 and derived variables such as stroke volume or LVEF,4 with very low interand intraobserver variability (,3%).3 The disadvantages of using electron beam tomography in clinical practice include the cost of the scanners, the need for intravenous contrast agent, and the fairly complex postprocessing of images. Measurement of cardiac chamber volumes and LVEF using proprietary software supplied with the scanner takes approximately 10 minutes. Measurement of LVEF with Tc-99m sestamibi firstpass angiography: First-pass angiography was one of
the first noninvasive methods to assess ventricular function.13 It has shown to correlate well with equilibrium radionuclide angiography14 and contrast ventriculography.15 Tc-99m sestamibi has gained wide acceptance as a myocardial perfusion single-photon emission computed tomographic imaging agent,2,16 because of its advantages of higher photon energy and APRIL 1, 1999
TABLE I Tc-99m Sestamibi First-Pass Angiography and Electron Beam Computed Tomography Measurements FPRNA Variable Mean 6 SD Range 25th Percentile 75th Percentile 95% CI
EBCT
LVEF (%)
ED Counts
ES Counts
EDV (ml)
ESV (ml)
FPRNA
EBCT
3,345 6 996 1,863–5,781 2,709 3,886 3,013–3,677
1,926 6 818 712–4,179 1,270 2,535 1,653–2,198
199 6 51 103–318 156 231 182–215
111 6 42 39–230 80 134 98–125
45 6 11 22–63 38 52 41–48
46 6 9 28–62 40 54 43–48
CI 5 confidence interval of mean; EBCT 5 electron beam computed tomography; ED Counts, ES Counts 5 end-diastolic and end-systolic background-corrected counts, respectively; EDV 5 end-diastolic volume; ESV 5 end-systolic volume; FPRNA 5 first-pass radionuclide angiography.
higher injectable dose compared with thallium-201.17 Extremely high count rates (150 to 600 kcps) can be achieved because of the high activity and concentration of Tc-99m in the bolus dose. The possibility and convenience of assessing both myocardial perfusion and function with a 1-dose injection of a radionuclide, eliminating the need for additional radiation exposure,1 has led to renewed interest in first-pass technology. The advantages of first-pass angiography over equilibrium radionuclide angiography include a very short acquisition time and lower background activity. The inter- and intraobserver variability is low (approximately 3%).18 Accurate measurement of LVEF with first-pass angiography is highly dependent on the quality of the bolus injection. The presence of severe pulmonary hypertension, tricuspid regurgitation, or dysrhythmia may invalidate the study. LVEF has been measured with good success from electrocardiographically gated single-photon emission computed tomographic perfusion images, obviating bolus injection and specialized equipment.19,20 However, definition of the LV cavity border by manual tracing or automated edge-detection algorithms may be difficult in the presence of a large perfusion defect, particularly when it involves the base of the heart.19 The data acquisition time is longer than for first-pass angiography, and the count statistics can be poor (approximately 1/8 of nongated single-photon emission computed tomographic images). A sampling rate high enough to allow reliable identification of end-diastolic and endsystolic frames (16/s) consumes considerable processing time and computer memory.19,20 Sources of error in measuring LVEF with first-pass angiography: Most planar techniques for measuring
LVEF, including equilibrium and first-pass angiography, require manual drawing of a region of interest (usually at end-diastole). This in practice frequently includes counts superior to the valve plane during end-systole as a result of motion of the cardiac base toward the apex, causing underestimation of the LVEF.19 The use of an inappropriate image projection can lead to errors in measurement of EF by radionuclide angiography, particularly in patients with anterior wall motion abnormalities.21,22 Factors influencing the accuracy of count-based methods to estimate LV cavity volumes have been described in detail elsewhere.23,24 Inaccuracies related to image projec-
FIGURE 3. A, correlation between measurements of LVEF by electron beam computed tomography (EBCT) and Tc-99m sestamibi first-pass radionuclide angiography (FPRNA). There is excellent agreement between both methods, even in distorted left ventricles with altered contraction patterns. B, Bland-Altman plot showing the relation between the differences and means of the LVEF measurements by EBCT and Tc-99m sestamibi FPRNA. The significant correlation with positive slope indicates overestimation of EF by FPRNA at values >55% to 60%.
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tion can be overcome with the use of scintillation cameras with perpendicular biplane detectors.25 Discussion of study results: Exclusion criteria in our study were patient conditions known to adversely affect the bolus quality and studies not satisfying commonly accepted technical criteria. Good counts statistics are an important requirement for reliable first-pass studies. It has been suggested that background-corrected end-diastolic counts should be .2 kcounts.26 In the present study, the mean end-diastolic count far exceeded this threshold, indicating satisfactory image quality. Therefore, high-quality first-pass angiographic studies were available for comparison with electron beam tomography. The high end-diastolic volumes and low LVEFs in the present study are explained by large infarctions. The correlation of firstpass angiography with electron beam tomography was very good and probably would be improved more with the use of a multicrystal gamma camera. The BlandAltman method of comparison showed a positive correlation between the difference and mean of both methods, indicating an overestimation of the LVEF by first-pass angiography at higher values. This tendency should be acceptable because the crucial threshold for clinical decision making is around 40%.27 In previous comparative studies,28,29 first-pass angiography underestimated LVEF by 12% to 25% compared with LV angiography. This may be due to decreased LV preload in the upright position during first-pass study as opposed to higher preload during contrast injection in the supine position, resulting in a higher angiographic EF secondary to the Frank-Starling mechanism. In the present study, the study subjects were supine during both first-pass angiography and electron beam tomography, eliminating this source of error. For scientific purposes, methods such as magnetic resonance imaging or electron beam computed tomography that make no assumptions about LV geometry and contraction patterns are most valuable for the measurement of LVEF. The method a physician uses in the clinical setting should depend on the situation and the local availability of a specific technique. Firstpass angiography using Tc-99m sestamibi is a valuable adjunct to the assessment of patients undergoing stress perfusion imaging. When absolute measures of right and LV volumes and EF are needed, magnetic resonance imaging and electron beam tomography are the most quantitative and reproducible methods.30 1. Baillet GY, Mena IG, Kuperus JH, Robertson JM, French WJ. Simultaneous technetium-99m MIBI angiography and myocardial perfusion imaging. J Nucl Med 1989;30:38 – 44. 2. Gibbons RJ, Verani MS, Behrenbeck T, Pellikka PA, O’Connor MK, Mahmarian JJ, Chesebro JH, Wackers FJ. Feasibility of tomographic 99mTc-hexakis2-methoxy-2-methylpropyl-isonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute myocardial infarction. Circulation 1989;80:1277–1286. 3. Feiring AJ, Rumberger JA, Reiter SJ, Skorton DJ, Collins SM, Lipton MJ, Higgins CB, Ell S, Marcus ML. Determination of left ventricular mass in dogs with rapid-acquisition cardiac computed tomographic scanning. Circulation 1985;72:1355–1364. 4. Reiter SJ, Rumberger JA, Feiring AJ, Stanford W, Marcus ML. Precision of measurements of right and left ventricular volume by cine computed tomography. Circulation 1986;74:890 –900.
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5. Roig E, Georgiou D, Chomka EV, Wolfkiel C, LoGalbo-Zak C, Rich S, Brundage BH. Reproducibility of left ventricular myocardial volume and mass measurements by ultrafast computed tomography. J Am Coll Cardiol 1991;18: 990 –996. 6. Hajduczok ZD, Weiss RM, Stanford W, Marcus ML. Determination of right ventricular mass in humans and dogs with ultrafast cardiac computed tomography. Circulation 1990;82:202–212. 7. Hirose K, Reed JE, Rumberger JA. Serial changes in left and right ventricular systolic and diastolic dynamics during the first year after an index left ventricular Q wave myocardial infarction. J Am Coll Cardiol 1995;25:1097–1104. 8. O’Connor MK, Miller TD, Christian TF, Gibbons RJ. 99mTc sestamibi firstpass radionuclide angiogram. In: O’Connor MK, ed. The Mayo Clinic Manual of Nuclear Medicine. New York: Churchill Livingstone, 1996:197–203. 9. Gal R, Grenier RP, Schmidt DH, Port SC. Background correction in first-pass radionuclide angiography: comparison of several approaches. J Nucl Med 1986; 27:1480 –1486. 10. Wackers FJT. First-pass radionuclide angiocardiography. In: Gerson MC, ed. Cardiac Nuclear Medicine. New York: McGraw-Hill, 1987:53– 66 11. Rumberger JA, Reed JE, Behrenbeck T, Davitt PJ, Sheedy PF. Development and application of image processing, data processing, database and data query tools to study post-infarction cardiac remodeling in man. In: Hoffman EA, Acharya RS, eds. Medical Imaging 1994: Physiology and Function From Multidimensional Images. Bellingham, WA: Proceedings SPIE, 1994;2168:131–140. 12. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–310. 13. Van Dyke D, Anger HO, Sullivan RW, Vetter WR, Yano Y, Parker HG. Cardiac evaluation from radioisotope dynamics. J Nucl Med 1972;13:585–592. 14. Wackers FJ, Berger HJ, Johnstone DE, Goldman L, Reduto LA, Langou RA, Gottschalk A, Zaret BL. Multiple gated cardiac blood pool imaging for left ventricular ejection fraction: validation of the technique and assessment of variability. Am J Cardiol 1979;43:1159 –1166. 15. Jengo JA, Mena I, Blaufuss A, Criley JM. Evaluation of left ventricular function (ejection fraction and segmental wall motion) by single pass radioisotope angiography. Circulation 1978;57:326 –332. 16. Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993;328:685– 691. 17. Berman DS. Introduction—technetium-99m myocardial perfusion imaging agents and their relation to thallium-201. Am J Cardiol 1990;66:1E– 4E. 18. Jones RH, McEwan P, Newman GE, Port S, Rerych SK, Scholz PM, Upton MT, Peter CA, Austin EH, Leong KH, Gibbons RJ, Cobb FR, Coleman RE, Sabiston DC Jr. Accuracy of diagnosis of coronary artery disease by radionuclide management of left ventricular function during rest and exercise. Circulation 1981;64:586 – 601. 19. Williams KA, Taillon LA. Left ventricular function in patients with coronary artery disease assessed by gated tomographic myocardial perfusion images. Comparison with assessment by contrast ventriculography and first-pass radionuclide angiography. J Am Coll Cardiol 1996;27:173–181. 20. DePuey EG, Nichols K, Dobrinsky C. Left ventricular ejection fraction assessed from gated technetium-99m-sestamibi SPECT. J Nucl Med 1993;34: 1871–1876. 21. Esquerre JP, Coca FJ, Gantet P, Ouhayoun E. Feasibility of first-pass radionuclide angiography with a 10-mCi technetium bolus using a single-crystal digital gamma camera: implications for technetium-sestamibi single-day protocols. Eur J Nucl Med 1995;22:521–527. 22. Schneider RM, Jaszczak RJ, Coleman RE, Cobb FR. Disproportionate effects of regional hypokinesis on radionuclide ejection fraction: compensation using attenuation-corrected ventricular volumes. J Nucl Med 1984;25:747–754. 23. Levy WC, Cerqueira MD, Matsuoka DT, Harp GD, Sheehan FH, Stratton JR. Four radionuclide methods for left ventricular volume determination: comparison of a manual and an automated technique. J Nucl Med 1992;33:763-770. 24. Levy WC, Jacobson AF, Cerqueira MD, Matsuoka DT, Sheehan FH, Stratton JR. Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor. J Nucl Med 1992;33:1642– 1647. 25. DePuey EG, Salensky H, Melancon S, Nichols KJ. Simultaneous biplane first-pass radionuclide angiocardiography using a scintillation camera with two perpendicular detectors. J Nucl Med 1994;35:1593–1601. 26. Wackers FJ, Sinusas AJ, Saari MA, Mattera JA. Is list mode ECG-gated first pass LVEF accurate using a single crystal gamma camera? Implications for Tc-99m labeled perfusion imaging agents (abstr). J Nucl Med 1991;32:939. 27. The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309:331–336. 28. Folland ED, Hamilton GW, Larson SM, Kennedy JW, Williams DL, Ritchie JL. The radionuclide ejection fraction: a comparison of three radionuclide techniques with contrast angiography. J Nucl Med 1977;18:1159 –1166. 29. Nusynowitz ML, Benedetto AR, Walsh RA, Starling MR. First-pass Anger camera radiocardiography: biventricular ejection fraction, flow, and volume measurements. J Nucl Med 1987:28:950 –959. 30. Rumberger JA, Behrenbeck T, Bell MR, Breen JF, Johnston DL, Holmes DR Jr, Enriquez-Sarano M. Determination of ventricular ejection fraction: a comparison of available imaging methods. Mayo Clin Proc 1997;72:860 – 870.
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