SHORT COMMUNICATION Annals of Nuclear Medicine Vol, 15, No, 1 , 65-68, 2001 Clinical significance of reverse redistribution on resting thallium-201 imaging in patients with vasospastic angina Akira NAKANO,* Jong-Dae LEE,* Hiromasa SHIMIZU,* Akiyoshi TSUBOKAWA,* Hiroyasu UZUI,* Tatsuro TSUCHIDA,** Norio TAKAHASHI,** Yoshiharu YONEKURA*** and Takanori UEDA* *First Department of Internal Medicine, **Department of Radiology and ***Biomedical Imaging Research Center, Fukui Medical University To evaluate the clinical signlficance of reverse redistributron (RR) of resting 201Tl single photon emission computed tomography (SPECT) in patients with vasospastic angina (VSA), we performed left ventriculography, coronary angiography and resting 201TI-SPECT in 22 patients with VSA. Left ventriculography showed abnormal wall motion in 17 of 22 patients (77%) and 37 of 154 segments. Thirty-one of these 37 segments (84%) were within the area perfused by coronary arteries showing acetylcholine-induced vasospasm. On 201Tl images, abnormal findings were observed in 11 of 22 patients (50%), and among them, 7 patients (32%) had RR. Seven of 37 segments (19%) having abnormal regional wall motion had RR of 201Tl, and in 6 of these 7 segments (86%), accumulation of 123I-BMIPP was found to be reduced. We conclude that repetitive brief myocardial ischemia may cause myocardial injuries in patients with VSA, and that thepresence of RR of 201Tl indicates the presence of myocardial injury in these patients. Key words : thallium-201 , reverse redistribution, vasospastic angina INTRODUCTION IT IS WELL KNOWN that patients with vasospastic angina (VSA) having normal coronary arteries often have abnormal left ventricular wall motion I abnormal myocardial free fatty acid utilization 2 and regional myocardial sympathetic dysinnervation3 even during attack-free periods, all suggesting myocardial stunning. In fact, some authors have described myocardial stunning after coronary vasospasm.4-6 Nevertheless, little is known about the relationship between abnormal left ventricular wall motion and reverse redistribution (RR) on resting 201Tl imaging in patients with VSA, although the latter is another impor- Received August 3, 2000, revision accepted November 20, 2000. For reprint contact: Jong-Dae Lee, M.D., First Department of Internal Medicine, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka-cho, Fukui 9 10-1193, JAPAN. E-mail : jdlee@fmsrsa.fukui-med.ac.jp tant phenomenon in cases of myocardial stunning.7-9 In this study, we performed resting single photon emission computed tomography (SPECT) with 201Tl and 123I-B methyl-p-iodophenyl pentadecanoic acid (BMIPP), and left ventriculography (LVG) to clarify the clinical implication of RR on resting 201Tl in patients with VSA. MATERIALS AND METHODS Recruitment of patients Twenty-two patients with VSA (19 men and 3 women; 46 to 80 years old, mean age 64+-9) were recruited (Table 1). All patients had chest pain which appeared at rest rather than on exertion. None showed an increase in the serum creatine kinase level after anginal attack or an abnormal Q wave on a 12-lead Electrocardiogram (ECG). Thirteen patients were current smokers, 4 had diabetes, 2 had hypertension and 2 had hypercholesterolemia. Patients with prior myocardial infarction, significant coronary stenosis (> 50%), left ventricular hypertrophy, right or left bundle-branch block or any other systemic disorder known@to affect left ventricular function or metabolism were excluded. Written informed consent was obtained from all subjects. LVG and coronary angiography Biplane LVG and coronary angiography were performed in all subjects prior to radionuclide studies after discontinuation of antianginal drugs for several days, except for sublingual nitroglycerin. The mean interval from the last anginal attack to angiography was 1 5.5 days (range 2 to 25 days). On LVG, left ventricular silhouette was divided into 7 segments (Fig. 1) and regional wall motion was visually scored on a 5-point scale (O: normal, 1: mild hypokinesis, 2: severe hypokinesis, 3: akinesis, 4: dyskinesis) by two experienced observers. 10 VSA was confirmed by coronary artery spasm, defined as total or subtotal coronary occlusion associated with chest pain and ischemic ST-segment deviations, induced by intracoronary injection of acetylcholine. 11 Fixed coronary stenosis was measured with quantitative cardiovascular angiographic software (Automated Coronary Analysis D.C.I. Philips, USA) after nitroglycerin administration. Significant stenosis was defined as luminal narrowing of > 50%. SPECT imaging and analysis In all subjects 201-Tl and 123-I-BMIPP dual SPECT imaging were performed within two weeks after coronary angiography and LVG. None had anginal attacks between anglography and SPECT studies. After overnight fasting, l23-I-BMIPP-SPECT images were acquired at rest, 20 min after administration of 111 MBq of 123-I-BMIPP. 111 MBq of 201-Tl was then injected, followed by SPECT acquisition 10 min (rest imaging) and 3 hours later (redistribution imaging).12 The reconstructed SPECT images of the left ventricular slice (1 vertical long axial slice and I horizontal long axial slice) were divided into 7 segments to compare the regional uptake of tracer to regional wall motion on LVG (Fig. 1 ). The myocardial accumulation of 123-I-BMIPP and 201-Tl were assessed visually by 2 independent observers using a 4-point defect score (O; normal uptake, 1 ; mildly reduced uptake, 2; moderately reduced uptake, 3; severely reduced uptake). The abnormal tracer uptake was a defect score of 2 or 3, and normal was O or 1. Furthermore, on rest and redistribution 201-Tl images, we defined 3 patterns of abnormal findings as follows. Redistribution (RD): abnormal uptake of 201-Tl on rest images altered normal uptake on redistribution images. Reverse redistribution (RR): normal uptake of 201-Tl on rest images altered abnormal uptake on redistribution images. Fixed defect (FD): abnormal uptake of 201-Tl is observed on both rest and redistribution images. In each patient, regional left ventricular wall motion and tracer uptake were compared. Statistical analysis All data are presented as the mean value +- SD. Fisher exact test was used to compare proportions. A p value < 0.05 was considered significant. RESULTS LVG and coronary angiography LVG showed abnormal wall motion in 17 of 22 patients (77%), although none showed signs of akinesis or dyskinesis on LVG. On segment-based analysis, abnormal wall motion was found in 37 of 154 segments consisting of 29 segments showing mild hypokinesis and 8 showing severe hypokinesis. Thirty-one of these 37 segments (84%) were within the area perfused by coronary arteries showing acetylcholine-induced vasospasm (Table 1 ). On ECG during acetylcholine-induced vasospasm, ST-segment elevation was found in 19 patients and ST-segment depression in 3 patients. 201-Tl images and left ventricular wall motion Abnormal 201-Tl images were found in ll of 22 VSA patients (50%) including 10 of 17 patients (59%) with abnormal left ventricular wall motion. RR of 201-Tl was observed in 6 of these 10 patients (Table 1, Fig. 2). In contrast, only 1 of 5 patients (20%) with normal left ventricular wall motion had abnormal findings in 201-Tl images. The incidence of abnormal 201-Tl images in patients with and without abnormal left ventricular wall motion was significantly different (p < 0.05). On segment-based analysis, abnormal 201-Tl images were found in 15 of 154 segments including 13 of 37 segments (35%) having abnormal left ventricular wall motion (including 7 segments showing RR; Table 1). On the other hand, only 2 of 117 segments (2%) with normal left ventricular wall motion showed signs of abnormal 201-Tl uptake. The incidence of abnormal 201-Tl findings for segments with and without abnormal left ventricular wall motion also differed significantly (p < 0.05). 123-I-BMIPP images and left ventricular wall motion 123-I-BMIPP images were abnormal in 13 of 22 patients (59%) including 12 of 17 patients (71%) with abnormal left ventricular wall motion, but only 1 of 5 patients (20%) with normal left ventricular wall motion had abnormal 123-I-BMIPP images (Table 1). The incidence of reduced 123-I-BMIPP uptake in patients with and without abnormal left ventricular wall motion differed significantly (p < 0.05). On segment-based analysis, 24 of 154 segments including 19 of 37 segments (5l%) with abnormal wall motion had reduced 123-I-BMIPP uptake, but only 5 of 117 segments (4%) with normal left ventricular wall motion had reduced accumulation of 123-I-BMIPP. The incidence of reduced 123-I-BMIPP uptake in segments with and without abnormal left ventricular wall motion also differed significantly (p < 0.05). Relation between 201-Tl and 123-I-BMIPP images Accumulation of 123-I-BMIPP was reduced in 12 of 15 segments (80%) showing abnormal findings in 201-Tl-SPECT. Moderately reduced 123-I-BMIPP uptake was observed in 6 of 9 RR segments (Table 1), but 12 segments without abnormal findings in 201-Tl images also showed reduced accumulation of 123-I-BMIPP. Of these, 7 segments showed signs of mild hypokinesis and 5 showed normal wall motion. DISCUSSION Previous reports have well documented that RR pattern on resting 201-Tl image is often observed in patients with acute myocardial infarction, and that the phenomenon is related to myocardial stunning after successful reperfusion. 7-9 Nevertheless, the relationship between abnormal left ventricular wall motion and RR on resting 201-Tl-SPECT has not been examined systematically in patients with VSA, although several authors have suggested a close relation between repetitive brief periods of myocardial ischemia in patients with VSA and myocardial stunning.4-6 In this study, 17 of 22 (77%) VSA patients and 37 of 154 segments showed signs of abnormal left ventricular wall motion, in agreement with the findings of Nakajima et al.1 Thirteen of these 37 segments (35%) had abnormal uptake in resting 201Tl-SPECT, suggesting that they were caused by repetitive myocardial ischemia with vasoconstriction. In these 13 segments, FD was observed in 4 segments, RD in 2 segments and RR in 7 segments. Geft et al. reported that brief intermittent periods of myocardial ischemia, which when single did not cause necrosis, had a cumulative effect and caused myocardial necrosis 13 Since this mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes, FD of 201Tl is considered to reflect myocardial necrosis. On the other hand, Weiss et al.7 reported that the pattern of RR in resting 201Tl images represented an admixture of viable and nonviable myocardium. Therefore, both necrotic and stunned (viable) myocardium might exist in the region threatened by repeated transient ischemia in patients with VSA. Reduced 123I-BMIPP accumulations were also found in 13 of 22 (59%) patients and in 19 of 37 segments (51 %) showing signs of abnormal left ventricular wall motion. Reduced 123I-BMIPP accumulation was observed in segments showing not only FD and RD, but also in segments showing RR of 201Tl. Since Nakajima et al. observed serial improvement in 123I-BMIPP uptake in VSA patients whose anginal attacks were controlled completely by medical treatment,1 it is quite likely that RR of 201Tl in our patients also represented stunned but viable segments. Our point of view was also supported by the fact that 6 of 7 segments exhibiting both abnormal left ventricular wall motion and RR of 201Tl showed signs of discordant uptake between 201Tl and 123I-BMIPP (reduced uptake of 123I-BMIPP relative to 201Tl) that has been reported to reflect ischemic but viable myocardium. We therefore conclude that repetitive brief periods of myocardial ischemia due to coronary spasm could cause myocardial necrosis 1 3 as well as myocardial injury (stunned but viable), and that RR on 201Tl-SPECT indicates regions with myocardial injury in patients with VSA. REFERENCES l. 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