ORIGINAL ARTICLE 
Annals of Nuclear Medicine Vol.15, No.4, 357-363, 2001 
Discordant iodine-123 metaiodobenzylguanidine uptake area reflects recovery time dispersion in acute myocardial infarction 
Miho MASAI,* Hitoshi NARUSE,* Masato MORITA,* Tohru ARII,* Keiko TAKAHASHI,* Mitsumasa OHYANAGI,* Tadaaki IWASAKI* and Minoru FUKUCHI** 
*Department of Internal Medicine, Cardiovascular Division, **Department of Nuclear Medicine, Hyogo College of Medicine 
Iodine-123_ metaiodobenzylgtianidine (MIBG) uptake was reported to be reduced compared to Tl-201 (Tl) in acute myocardial infarction (AMI). Within such an area, degrees of both sympathetic neural function and ischemic myocardial cell damage are considered to be greatly dispersed. These kinds of damage were reported to effect reporalization time in myocardial cells, and we evaluated our hypothesis that extension of the discordant MIBG uptake area correlates with recovery time (RT) dispersion and relate ventricular arrhythmias in AMI. MIBG and Tl images were obtained in AMI patients. Regional Tl or MIBG uptake was estimated in 9 segments of SPECT by using four-point scoring. The total score was the sum of scores in 9 SPECT segments. deltaTl-MIBG was calculated by subtracting the total MIBG score from the total Tl score. Corrected RT (RTc) was measured as a signal-averaged ECG. RTC dispersion was defined as the difference between maximal and minimal RTc. The patients were assigned to two groups (group A; <Lown 4a, group B; >Lown 4b) according to the results of 24-hour Holter monitoring. A positive correlation between RTC dispersion and deltaTl-MIBG was found. deltaTl-MIBG and RTC dispersion in group B were greater than those in group A. These results suggested that deltaTl-MIBG could be used to predict the development of malignant ventricular arrhythmias. 
Key words: iodine-123 metaiodobenzylguanidine, acute myocardial infarction, ventricular arrhythmia, recovery time dispersion 
INTRODUCTION 
MALIGNANT Ventricular arrhythmias represent a major complication of acute myocardial infarction. In addition, the development of ventricular tachycardia is an important predictor of prognosis I Although the mechanism responsible for ventricular tachycardia (VT) is not clear, experimental and clinical studies have suggested that VT caused by reentry is a result of the heterogeneity of repolarization 2 Furthermore, sympathetic activation3 and myocardial ischemias4,5 are important modulators of ventricular repolarization. Heterogeneity of both sympathetic 
Received January 22, 2001 , revision accepted May 21 , 2001. For reprint contact: Miho Masai, M.D., Department of Internal Medicine, Cardiovascular Division, Hyogo College of Medicine, 1-1 , Mukogawa-cho, Nishinomiya 663-8501, JAPAN. E-mail : miho@hyo-med.ac.jp 
activation and the degree of ischemia are thought to be risk factors for ventricular tachycardia.6-8 The periinfarct zone contains arrhythmogenic myocardium 9 and the presence of reentry circuits in this area has been reported by Kuo et al.10 Nevertheless, little has been reported concerning the relationship between myocardial ischemia and sympathetic function,]1 because no studies have previously evaluated sympathetic function. The accumulation of iodine-123 metaiodobenzylguanidine (MIBG), which is an analogue of norepinephrine, is believed to quantify sympathetic neuronal innervation.12 Furthermore, the corrected recovery time (RTc) obtained by surface electrocardiographic mapping, has provided an index of the heterogeneity of repolarization.13 If the results of these electrophysiologic and nuclear studies can be applied to patients with malignant arrhythmias after myocardial infarction, the results should represent an important predictor of prognosis. The aims of the present study were, 1) to evaluate the relationship between Tl-201 (Tl) uptake, MIBG uptake, and RTC dispersion, and 2) to determine the relationship between these indices and the development of malignant ventricular arrhythmias in the patients with acute myocardial infarction. 
METHODS 
Subjects
Twenty patients presenting with their first acute myocardial infarction (AMI) were enrolled in the present study. The study group consisted of 19 men and 1 woman (mean age +- standard deviation, 60 +- 10 years). Patients who met all of the following criteria were included in the study: chest pain lasting at least 30 minutes, abnormal q waves in 12-lead electrocardiogram, and serum CPK value > 500 IU/l. The infarct affected the anterior wall in 11 patients and the inferior wall in 9 patients. All patients had undergone successful coronary reperfusion therapy during the acute phase. Twenty-four-hour ambulatory Holter monitoring, Tl and MIBG scintigraphy, and RT measurement were performed during the subacute phase (1 to 3 weeks). Patients were divided into two groups: group A (n = 11) developed no life-threatening ventricular arrhythmias, (Lown grade arrhythmias 1 to 4a), whereas group B (n = 9) experienced severe ventricular arrhythmias (Lown grade arrhythmias 4b to 5), including 2 patients who had ventricular tachycardia. The clinical profiles of groups A and B are summarized in Table 1.
Nuclear studies
Doses of MIBG and Tl (111 MBq each) were administered intravenously with the patients in a resting state. A StarCam 3000XCT (General Electric, Milwaukee, WI) was used for data acquisition and analysis. Thirty-two planar acquisitions were performed for 30 seconds each over a 180-degree arc extending from the 45-degree right anterior oblique projection to the 45-degree left posterior oblique projection. By means of filtered back projection, transaxial slices were reconstructed parallel to the vertical and horizontal long axis and the short axis of the left ventricle. SPECT images were evaluated visually in each of 9 segments, and the severity of the perfusion defect was quantified on a 4-grade scale: grade 0, severe defect; grade 1, moderate defect; grade 2, mild defect; grade 3, normal. The sum of the scores in the 9 segments was defined as the total Tl or total MIBG score. deltaTl-MIBG was calculated as the total Tl score minus the MIBG score (Fig. 1). 
RTC measurement
The dV/dt of the T wave was obtained by the filtering technique and recorded as a signal-averaged ECG with a Multicardiner VCM-3000 (Fukuda Denshi Co., Tokyo, Japan). The ECGS from each of 16 leads were amplified, digitized and passed through a low pass filter (300 Hz; slope, 18 dB/octave) and a high pass filter (20 Hz; slope, 6 dB/octave). Signals from 20 beats were averaged. The recovery time (RT) was defined as the interval between the QRS onset and the time of the maximum dV/dt for the T-wave. The RT was calculatcd manually for each lead. Each RT value was corrected (RTc) for heart rate by Bazett's formula: RTC = RT x RR1/2. The RTC dispersion was dcfined as the difference between the maximum RTC and the minimum RTC Values (Fig. 2).
24-hour ambulatory Holter monitoring
All patients underwent 24-hour Holter monitoring 7 days after the onset of infarction to detect premature ventricular contractions (VPC). Holter recordings consisted of continuous 2-channel recordings analyzed with a Holter analyzer DMW-9000H (Fukuda Denshi).
Statistics
Correlations between RTC dispersion and total Tl, total MIBG and deltaTl-MIBG were assessed by linear regression analysis. Comparisons between the two groups were made by Student's unpaired t test or Fisher's exact probability test. Data are expressed as the mean +- standard deviation. A value of p < 0.05 was considered statistically significant. 
RESULTS 
Clinical characteristics of groups A and B
There were no significant differences in age, gender, heart rate, left ventricular ejection fraction, peak CPK value or left ventricular ejection fraction between groups A and B (Table 1). All patients received nitrate and calcium-channel antagonist. No patient received b-blocking agents or major tranquilizing agents. One patient was treated with a loop diuretic drug, and one patient was treated with a group lb anti-arrhythmia drug. Three patients in group A and 4 patients in group B had diabetes. No patient had any electrolytic abnormalities. Table 2 summarized subject characteristics and the results in this study. Nuclear studies and RTC dispersion RTC dispersion did not correlate with either the total Tl score (r = 0.25, Fig. 3a) or the total MIBG score (r = 0.35, Fig. 3b), but a significant correlation was found with deltaTl-MIBG (r = 0.75, p < 0.0001 , Fig. 3c).
Ventricular arrhythmias and nuclear studies
There were no significant differences between groups A and B in the total Tl score and the total MIBG score (Table 1). The mean deltaTl-MIBG was 9.7 +- 3.2 in group B and 6.3 +- 2.5 in group A. The dletaTl-MIBG in group B was greater than that in group A (p = 0.02, Fig. 4a).
Ventricular arrhythmias and RTC dispersion
RTC dispersion was 117.0 +- 20.4 msec in group B and 93.4 +- 19.0 msec in group A. RTC dispersion in group B was longer than that in group A (p = 0.02, Fig. 4b). Case presentation (Fig. 5) Figure 5 shows representative scintigraphic images and the RTC dispersion in a patient with acute anterior wall myocardial infarction. The Tl images demonstrate mild hypoperfusion in the anterior wall (total Tl score = 25), whereas the MIBG images show severe hypoperfusion in the anterior and septal walls (total MIBG score = 9). This is a typical case of Tl-MIBG mismatch (deltaTl-MIBG = 16). The RTC dispersion was increased to 149.2 msec in this patient and the ventricular tachycardia occurred 7 days after infarction. 
DISCUSSION
Previous studies have shown that prolongation of the QT interval is a risk factor for ventricular arrhythmia in the patients with myocardial infarction.14-18 The relationship between QT dispersion and susceptibility to arrhythmias has also been reported in patients with acute myocardial infarction.19 Zabel et al. have reported that QT dispersion correlates both with the dispersion of the monophasic action potential recorded from the left ventricular endocardium (APD 90) and RT.20 Sasaki et al. have reported that the APD 90 correlates with RT obtained by surface electrocardiography.21 We therefore used RTC dispersion in the present study. Lekakis et al. and Dae et al . have reported that the defect in MIBG uptake is larger than the defect in TI uptake in the patients with acute myocardial infarction.22 This type of mismatch is believed to represent denervated but viable myocardium.23 Our results demonstrate that RTC dispersion does not correlate with either the total Tl score or the total MIBG score, but a significant correlation was found between RTC dispersion and deltaTl-MIBG. This suggests that denervated but viable myocardium could be responsible for to the heterogeneity of repolarization, and such myocardium is believed to be the reentrant focus. Increased catecholamine release after myocardial infarction is thought to change the conduction pathway and to induce a unidirectional block.24 Microscopic examination has demonstrated a discontinuous structure (border zone) during recovery from infarction in animal studies.25,26 Furthermore, unidirectional block has been shown to induce reentrant arrhythmias in this area.27 Denervated but viable myocardium in the present study represents a border zone. Our results therefore suggest that the reentrant circuit is located in an area with reduced MIBG uptake compared with Tl uptake. Fu et al. reported that QT dispersion prolongation has been associated with poor cardiac function and ventricular arrhythmias.28 In our study, since there were no significant differences between groups A and B in the ejection fraction, we did not investigate the relationship between the degree of cardiac function and RT dispersion. Our data demonstrated that both RTC dispersion and deltaTl-MIBG were greater in group B than in group A. The presence of denervated but viable myocardium is dependent on whether the myocardium had been salvaged by acute coronary reperfusion. Dae et al. has reported that arrhythmias other than reperfusion arrthythmias occur less frequently in patients who have undergone successful reperfusion therapy.29 Previous studies have reported that there is less QT dispersion in patients with successful reperfusion therapy.30,31 Theoretically, deltaTl-MIBG should be greater in patients who receive reperfusion therapy, because of the presence of greater amounts of viable tissue, but the present study demonstrated a higher frequency of arrhythmias in such patients. The reason for this finding is unknown, but the increase in deltaTl-MIBG may be dependent not on the amount of viable tissue (Tl) but rather on the amount of denervated tissue (MIBG). Therefore, both deltaTl-MIBG and RTC dispersion are useful predictors of the development of malignant arrhythmias. Study limitation. In this study, arrhythmia was evaluated for only 24 hours by Holter monitoring 7 days after the onset of acute myocardial infarction, but arrhythmia after acute myocardial infarction changes by the day, and it is difficult to evaluate these changes based on data for only 24 hours. If the occurrence of arrhythmia had been evaluated for several days, we speculate that more accurate results may have been obtained. 
CONCLUSIONS 
1. RTC dispersion did not correlate with either the total Tl score or the total MIBG score, but there was a good correlation between RTC dispersion and deltaTl-MIBG.
2. Both RTC dispersion and deltaTl-MIBG were greater in patients with severe ventricular arrhythmias than in patients without life threatening arrhythmias.
3. deltaTl-MIBGCould be used to predict the development of malignant ventricular arrhythmias. 
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