Methods. Yoshiaki Maruyama, MD; Toru Kato, MD; Hiroyuki Ito, MD; Shugo Tanaka, MD; Nobuo Yoshimoto, MD; Yukio Kishi, MD*; Fujio Numano, MD*

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1 Jpn Circ J 1999; 63: New Method of Estimating Myocardial Infarct Size Using Technetium-99m Pyrophosphate and Thallium-201 Dual Single Photon Emission Computed Tomography Imaging Yoshiaki Maruyama, MD; Toru Kato, MD; Hiroyuki Ito, MD; Shugo Tanaka, MD; Nobuo Yoshimoto, MD; Yukio Kishi, MD*; Fujio Numano, MD* A new method was devised to estimate infarct size using dual single photon emission computed tomography with thallium-201 and technetium-99m pyrophosphate. Designating the ratio of infarct area to whole myocardial volume as %MI, the correlation of %MI with other markers of left ventricular dysfunction was examined: peak creatine kinase, ejection fraction and left ventricular asynergy. As %MI correlated well with these markers, it is considered that %MI will be useful for estimating infarct size and predicting the severity of left ventricular dysfunction in the early stage of acute myocardial infarction. (Jpn Circ J 1999; 63: ) Key Words: Dual SPECT; Infarct size; Left ventricular dysfunction; %MI Left ventricular (LV) dysfunction and residual ischemia are useful prognostic indicators in acute myocardial infarction (AMI). Successful reperfusion therapy clearly reduces infarct size and prevents left ventricular expansion. Early estimation of infarct size is necessary for predicting the severity of infarction and planning the rehabilitation program. Infarct size is usually determined using creatine kinase (CK) 1,2 or thallium-201 ( 201 T1) polar map display. But these data are not clinically reliable, because reperfusion therapy causes a washout of CK, and 201 T1 is not appropriate for determining infarct size. We devised a new method to estimate infarct size using dual single photon emission computed tomography (dual SPECT) with 201 T1 and technetium-99m pyrophosphate ( 99m Tc pyp), and designated the result as %MI. To evaluate the usefulness of %MI as a predictor of LV dysfunction, we investigated the correlations between %MI and other markers of LV dysfunction: peak CK, ejection fraction (EF) and LV asynergy. Methods Subjects The subjects for this study were 78 AMI patients (61 males and 17 females, aged years). Their clinical features are shown in Table 1. All subjects underwent dual SPECT and left ventriculography (LVG) within 4 weeks of onset. (Received August 13, 1998; revised manuscript received December 7, 1998; accepted December 8, 1998) Third Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama and*third Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan Mailing address: Yoshiaki Maruyama, MD, Third Department of Internal Medicine, Saitama Medical Center, Saitama Medical School Kamodatsujimichi-machi, Kawagoe city, Saitama , Japan Dual SPECT Dual SPECT with 201 T1 and 99m Tc pyp was performed at 3 5 days from onset. Three hours after intravenous injection of 740 MBq of 99m Tc pyp, 111 MBq of 201 T1 was injected. Simultaneous dual SPECT was performed 5 min after injection of 201 T1. Thirty-two 30-s projection images were obtained, from 45 right-anterior oblique to 45 leftposterior oblique, using a rotating large field of view gamma camera (GE Starcam 3000) equipped with a low-energy, high resolution, parallel- hole-collimator. The camera was interfaced with a dedicated computer. Each image was obtained at a digital resolution of Energy discriminations were set at 75 KeV with a 20% window for 201 T1 images, and at 140 KeV with a 15% window for Table 1 Clinical Characteristics of Patients PTCA PTCR Conservative (n=36) (n=11) (n=31) Age (years) 60.6± ± ±9.6 Gender (M/F) 28/8 10/1 23/8 Infarct-related artery LAD RCA LCx Peak CK (IU/L) 963± ± ±913 Time to SPECT (days) 3.9± ± ±0.7 %MI (%) 17.2± ± ±11.8 Tl-uptake (%) 34.9± ± ±13.4 Time to LVG (days) 19.1± ± ±4.4 EF (%) 63.6± ± ±15.9 Wall motion Normal Hypokinesis Akinesis Dyskinesis PCTA, percutaneous transluminal coronary angioplasty; PTCR, percutaneous transluminal coronary reperfusion; LAD, left anterior descending; RCA, right coronary artery; LCX, left circumflex coronary artery; LVG, left ventriculography; EF, ejection fraction.

2 156 MARUYAMA Y et al. Fig 1. (Upper) Short axis image of 99m Tc (left) and 201 T1 (right). (Middle) Circumferential profile curve curve of 99m Tc (red) and 201 T1 (green) in same patients. (Lower) Schema for calculation of %MI in Slice X (%MIx). 99m Tc pyp images. Orthogonal images were generated by oblique angle reconstruction, producing short-axis (base, middle, apex), vertical long-axis, and horizontal long-axis slices, each 6mm thick. In this study, we selected 3 shortaxis image slices to calculate %MI (Fig 1). All images were analyzed using the circumferential profile method. Calculation of %MI Fig1 shows the 201 T1 circumferential profile curve and the 99m Tc pyp count curve for the same slice. The ratio of infarct area to myocardial volume in slice X is designated %MIx. The area enclosed by the accumulation of 99m Tc pyp and the circumferential profile curve of 201 T1 (area A in blue) was regarded as the infarct area. Fig1 also shows the formula for calculating %MI. After calculating %MI in each short-axis slice (base, middle, apex), we designated these as %MIB, %MIM and %MIA, respectively. The middle slice means the center of the left ventricle. The basal slice means the most basal slice including septal wall. The apical slice means the most apical slice including left ventricular lumen. The distance from the center point to the maximum count site in slice x (Lx) was also measured in the 3 slices and designated LB, LM and LA respectively. Using %MIx and Lx in each slice, %MI of the whole myocardium was calculated using the formula in Fig 2. In the calculation of %MI, the Tl defect was thought to be the depth and the Tc-pyp uptake the width of the myocardial infarction. Correlation of %MI With Other Markers of LV Dysfunction Serum CK was measured every 3h following admission. Peak CK corresponds to the maximum count of serum CK obtained. EF was calculated from LVG using Simpson s method. We investigated the correlation between %MI and these markers. Wall motion of the infarct area was classified as normal, hypokinesis, akinesis or dyskinesis according to the LVG by 2 experienced cardiologists. The mean %MI of these 4 asynergy groups were compared with each other. Analysis of Data Data are presented as mean±sd values. Simple linear regression was calculated using the least-squares method for %MI with peak CK and EF. Correlation was tested

3 New Method of Estimating Infarct Size 157 Fig2. Formula for calculation of %MI. Fig3. Correlation between %MI and peak CK. Fig4. Correlation between %MI and EF (ejection fraction).

4 158 MARUYAMA Y et al. Fig5. Bar graph of %MI (mean ±SD) in 4 groups. using Pearson s correlation coefficient. In asynergy analysis, the %MI of each group was analysed using the analysis of variance (ANOVA), and significant differences were determined by the multiple comparison test (Scheff test). Statistical significance was defined as p<0.05. Results In all patients, %MI was readily calculated. The regression coefficient between %MI (x) and peak CK (y) was y= x and r=0.731 in percutaneous transluminol coronary angioplasty (PTCA) patients, y= x and r=0.724 in percutaneous transluminol coronary reperfusion (PTCR) patients, and y= x and r=0.728 in conservatively treated patients. A statistically significant (p<0.05) correlation was seen in each individual patient, and also for all patients as a whole (y= x, r=0.729) (Fig 3). The regression coefficient between %MI (x) and EF (y) was y= x and r= 0.53 in PTCA patients, y= x and r= 0.63 in PTCR patients, and y= x and r= 0.68 in conservative patients. A statistically significant (p<0.05) correlation was seen in each individual patient, and also for all patients as a whole (y= x, r= 0.605) (Fig 4). A statistically significant correlation was seen between %MI and both peak CK and EF irrespective of whether reperfusion therapy was performed. Asynergy analysis showed that %MI for the akinesis group was significantly larger than that of the normal (p<0.01) and hypokinesis (p<0.05) groups (Fig5). Discussion Residual ischemia and LV dysfunction determine the patient s prognosis in cases of AMI. Because prevention of LV dysfunction is the main object of reperfusion therapy, an early estimate of infarct size is desirable. There are several clinical methods of calculating infarct size. Sobel et al estimated infarct size by washout of CK. However, reperfusion washes out CK sooner, causes it to peak earlier, and decreases the total CK, 3 so following reperfusion therapy CK is not appropriate for estimating infarct size by Sobel s formula. The same problem exists for CK-MB. 4 Currently, nuclear imaging methods with 99m Tc pyp, 5 8 Tl and 99m Tc isonitrile are used to measure infarct size. With 99m Tc pyp, one can demonstrate infarct area, but not whole myocardial volume, so it is impossible to express the ratio of infarct area to myocardial volume. With 201 T1, one can show the severity of myocardial damage and whole myocardium volume. However, because of its poor sensitivity and resolution, 201 T1 cannot precisely define the area of infarction. Defining the infarct area with 99m Tc pyp and the severity with 201 T1, using dual SPECT with 99m Tc pyp and 201 T1 we can readily calculate the ratio of infarct area to whole myocardial volume. In cases of recurrent AMI, with 201 T1 and 99m Tc isonitrile, fresh infarct area cannot be differentiated from old myocardial infarction. Only 99m Tc pyp can clearly demonstrate the area of AMI, if dual SPECT is performed within 7 days of onset. Some clinicians use the 201 T1 Bull s eye imaging polar map to estimate infarct size, but since the Bull s eye map does not take LV shape into account, it usually underestimates the infarct area at the LV apex. In contrast, in our method, %MI is calculated directly from LV dimensions, and the ratio is therefore more accurate than Bulls eye imaging. As is widely known, 99m Tc pyp also accumulates in stunned myocardium. The %MI in our method may therefore include both infarct area and area at risk. A new way to differentiate stunned myocardium from infarct area requires further investigation. Conclusions Our study showed that we can readily calculate infarct size, expressed as %MI, using 99m Tc pyp and 201 T1 dual SPECT imaging in the early stage of AMI. Good correlation was also showed between %MI and other markers of LV dysfunction. We consider %MI to be useful in predicting the severity of myocardial damage and planning rehabilitation programs, with or without reperfusion therapy, in AMI patients.

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