Value of ECG-gated Thallium-201 Dipyridamole SPECT in ...

Original ArticleECG-gated SPECT and Thallium-201 Myocardial PerfusionActa Cardiol Sin 2006;22:2430Nuclear MedicineValue of ECG-gated Thallium-201 DipyridamoleSPECT in Borderline Cases of MyocardialPerfusion ScanYueh-Chung Chen, 1 Kun-Chou Chin 2 and Jing Tang Ko 3Background: Thallium-201 myocardial perfusion scan is a commonly utilized method for detection of coronaryartery disease. Although this technique is generally reliable, results can be inconclusive in some cases. The purposeof this study was to assess whether candidates for coronary angiogram could be better identified with the addition ofan electrocardiographic (ECG)-gated myocardial perfusion scan to a thallium scan.Method: A total of 512 patients with suspected coronary artery disease were included in this study and received athallium scan. In 69 patients, the results were borderline, and 32 of these 69 patients also received an ECG-gatedscan and underwent coronary angiogram within one month.Results: We found that 21 of the 32 patients who underwent coronary angiogram had significant coronary arterydisease. However, when an ECG-gated perfusion scan was also performed, 25 of the 32 patients had abnormalregional wall motion following the stress test. Twenty-one of these 25 patients were found to have significantcoronary artery disease. Statistical analysis revealed that the ECG-gated perfusion scan in combination with thethallium scan was significantly more accurate than the thallium scan alone in borderline cases of myocardial perfusionscan (p = 0.0166), with 100% sensitivity, 63.6% specificity, an 84% positive predictive rate, and a 100% negativepredictive rate.Conclusions: The ECG-gated perfusion scan in combination with a thallium scan was more accurate in predictingthe presence of coronary artery disease than a thallium scan alone in borderline cases of myocardial perfusion scan.Key Words:Gated myocardial SPECT Thallium-201 Myocardial perfusion scan Stunning Coronary artery diseaseINTRODUCTIONThallium-201 myocardial perfusion single-photonemission computed tomography (SPECT) is a commonlyReceived: November 29, 2005 Accepted: February 10, 20061Division of Cardiology, Department of Internal Medicine, Taipei CityHospital, Ren-Ai Branch, 2 Department of Nuclear Medicine, Min-ShengGeneral Hospital, and 3 Division of Cardiology, De- partment of InternalMedicine,Taipei City Hospital, Zhong-Xiao Branch.Address correspondence and reprint requests to: Dr. Yueh-ChungChen, Division of Cardiology, Department of Internal Medicine,Taipei City Hospital, Ren-Ai Branch, No. 10, Section 4, Ren-AiRoad, Taipei 106, Taiwan. Tel: 886-2-2709-3600 ext. 3741; Fax:886-2-2704-9399; E-mail: chenyuehchung.tw@yahoo.com.twutilized method to detect coronary artery disease. 1 Althoughthis technique is generally reliable, inconclusiveresults can be obtained when trying to detect perfusiondefects involving a small territory, 2 reverse redistribution,3 or fixed defects caused by an attenuation effect 4,5(e.g. a diaphragm shadow in males or a breast shadow infemales). The electrocardiographic (ECG) gated myocardialperfusion scan is utilized for assessment of regionaland global motion of the left ventricular wall. This testmay also be useful in differentiating attenuation artifactsfrom myocardial scars.The purpose of this study was to assess the efficacyof performing an ECG-gated perfusion scan in combinationwith a thallium scan. We hypothesized that theActa Cardiol Sin 2006;22:2430 24

ECG-gated SPECT and Thallium-201 Myocardial Perfusioncombination of the two tests could help to clarify inconclusiveresults from a thallium scan, 6,7 and be useful indetermining if an invasive coronary angiogram wasneeded.METHODSPatient PopulationFrom January to November of 2004, 512 patients inRen-Ai Hospital with suspected coronary artery diseasewere included in the study and underwent stress thallium-201myocardial perfusion SPECT. Exclusion criteriaincluded a history of documented myocardial infarction,coronary bypass surgery, or percutaneous coronary intervention.A positive result was defined as a perfusiondefect in an area larger than 6% of the total left ventriclewith the exception of the inferior wall in male patients,the anterior wall in female patients, or areas with uptakereduced by 65%. A negative result was defined as nopre- or post-stress perfusion defect. Borderline resultswere defined as areas of reversible redistribution smallerthan 6% of the total left ventricle, or areas of the inferiorwall in male patients and anterior wall in female patientswith 65% to 75% reduced uptake. According to thesedefinitions, 191 patients had a positive result, 252 patientshad a negative result, and 69 patients had a borderlineresult. All borderline case received ECG-gated scansimultaneously. Of the 69 cases with a borderline result,32 patients received a coronary angiogram within onemonth of the scan. Of the 32 cases received angiogram,there were 44% women and 56% men with a mean bodyweight of 64 16 kilogram and a mean age of 61 14years. Of the 69 cases with a borderline result, therewere 41% women and 59% men with a mean bodyweight of 62 14 kilogram and a mean age of 62 15years.We selected 32 patients who underwent a coronaryangiogram for further evaluation in order to assess if useof an ECG-gated scan was useful in clarifying inconclusiveresults of a thallium scan and identifying patientsfor an invasive coronary angiogram in clinical practice(Figure 1).ProcedureAll patients were scanned in the supine position.Figure 1. Algorithm of the examination procedure.25 Acta Cardiol Sin 2006;22:2430

Yueh-Chung Chen et al.Dipyridamole 0.56 mg/kg was intravenously injected,and patients were instructed to raise each leg or do ahandgrip maneuver as the adjuvant stress exercise. Thiswas followed by injection of 2.5-3.0 mCi of thallium-201 followed by SPECT imaging. Imaging at rest wasconducted after 3-4 hours.The scintigraphic imagines were acquired with anADAC dual-head SPECT camera (ADAC Laboratories,Milpitas,CA) equipped with a low-energy, high-resolusioncollimator. Thirty-two projections (40 secondsperprojection) were obtained over a 180 semicircular arc(45 right anterior oblique to 45 left posterior oblique).Image resolution was 64 64 pixels. Filtered back projectionwas performed by use of a low-pass Butterworthfilter with a frequency cutoff of 4 and an order of 5.An ECG R wave gating detector was used to acquire8 frames of each cardiac cycle. No attenuation or scattercorrection was used. ECG-gated SPECT images were visuallyscored for motion using a 20-segment model ofthe left ventricle (Figure 2). Five representative slices (3distal, middle and basal short-axis slices and 1 verticaland 1 horizontal mid-ventricular long axis slice) wereautomatically selected for this purpose.All images were processed and interpreted by thesame experienced technologist. All stress and rest imageswere displayed simultaneously on an ADAC Pegasysworkstation (ADAC Laboratories) through use ofthe commercially available Autoquant QGS (QuantitativeGated SPECT) software program. 8,21 Images wereanalyzed using a linear color scale, with each color transitionrepresenting a 10% difference in uptake activity.Regional wall motion in the left ventricle was scored usinga 20-segment model following the stress test.Statistical AnalysisDifferences in data among two protocols were testedusing analysis of standard deviation. The hypothesis testabout the difference between two population propositionswas used to evaluate the significance of successfulexaminations, using thallium scan alone or with the additionof the ECG-gated scan for detection of coronaryartery disease. The level for statistical significance waspredetermined at p < 0.05. All comparisons were onetailed.RESULTSWe identified 69 patients with a borderline result onthe thallium scan, and 32 of these patients underwent acoronary angiogram within one month following thescan. Of the patients undergoing a coronary angiogram,21 of 32 patient exhibited significant coronary artery disease(> 50% stenosis of one or more vessels) and theremaining 11 patients showed normal or insignificantcoronary artery disease. However, if ECG-gated perfusionscan was used simultaneously, 25 of the 32 patientsexhibited abnormal regional wall motion following thestress test. Furthermore, 21 of these 25 patients exhibitedsignificant coronary artery disease, with the remaining 4patients exhibiting no coronary artery disease. Finally, 7of the 32 patients with normal regional wall motion followingthe stress test exhibited normal or insignificantcoronary artery disease.Statistical analysis revealed that the ECG-gated perfusionscan in combination with the thallium scan wassignificantly more accurate than the thallium scan alonein borderline cases of myocardial perfusion scan (p =0.0166), with 100% sensitivity, 63.6% specificity, an84% positive predictive rate, and a 100% negative predictiverate. Patient data and characteristics are presentedin Table 1.DISCUSSIONFigure 2.ventricle.Schematic representation of the 20-segment model of the leftThe post-stress perfusion defects caused by myocardialischemia are similar to the so-called phenomena oftransient ischemia stunning (TIS), indicating that thedefects may be both transient and reversible. 9 The techniqueof technetium-99m SPECT offers a superior imagequality compared to thallium-201 SPECT due to a higherActa Cardiol Sin 2006;22:2430 26

Yueh-Chung Chen et al.other hand, is better suited for TIS detection 12 but has ahigher rate of borderline results. 13,14 Reverse redistributionin a resting thallium scan in patients with coronaryartery disease also has a close relationship with coronaryanatomy and ventricular function. 15 However, the anatomiccorrelation in our study seemed not very identical.We believed this is not uncommon in clinical practice.The addition of an ECG-gated scan to technetium-99m scan can clarify the uncertainty of borderline resultsand increase the success rate of diagnosing coronary arterydisease. 16 Gated SPECT imaging is also of value inrecognizing questionable perfusion defects, 4 includingattenuation artifacts, which are ubiquitous, particularlywhen persistent defects raise the question of myocardialscar versus defect. The presence of corresponding normalor abnormal wall motion before and after stressimaging with an ECG-gated scan may resolve this problem,and may be even more accurate than the treadmillexercise test (The change of regional wall motion observedby echocardiography pre- and post-stress may bemore accurate than treadmill exercise test 22 for the diagnosisof coronary artery disease). The complementaryinformation can also be useful to evaluate the severity ofTIS and the extent of myocardial viability. Furthermore,the ejection fraction of the left ventricle can be accuratelyassessed by gated SPECT with either technetium-99m or thallium scan in properly selected patients (e.g.patients who are not overweight) with normal or depressedleft ventricular function. 17,18 Assessment of globalfunction is useful for determing prognosis and in differentiatingischemic from non-ischemic cardiomyopathy. 19In the current study, we evaluated the efficacy ofcoronary artery disease detection by using the same QGS(Quantitative Gated SPECT) method in combinationwith a thallium scan. Based on the findings of the coronaryangiograms, more than half of the borderline casesidentified by thallium scan revealed significant coronaryartery disease, indicating the value of following the borderlinecases with a coronary angiogram. However, ourstudy showed, if QGS (e.g. ECG-gated scan) was addedin these borderline cases, the coronary artery disease detectionrate by coronary angiogram increased. Thesefindings suggest that borderline patients with abnormalpresentation following QGS should receive an angiogram.There remains a number of issues that require furtherclarification, including the diagnostic value of QGSwhen the thallium scan is positive or when the thalliumscan is negative. We believe that ECG-gated SPECTalso improves diagnosis in those populations, and thatwill be the subject of further investigation.Finally, we should note that our study has some limitation.Minimal bias may still exist in the interpretationeven though we used the same experienced technologist.Besides, there was no absolute standard for determiningthe contribution of collateral flow to regions with an anatomicobstruction. Furthermore, these catheterized patientswere not randomly selected, and the total numberof cases examined was relatively small.CONCLUSIONThe addition of an ECG-gated perfusion scan mayreduce the uncertainty in interpreting results of a thalliumscan alone, especially with respect to interpretationof borderline results. Measuring resting and post-stressleft ventricular ejection fraction and changes in regionalwall motion, 7,20 can make it possible to detect coronaryartery disease more precisely in clinical practice.REFERENCES1. Chen ML, Chao IM, Chen CH. Diagnostic accuracy and safety ofdipyridamole thallium-201 single photon emission computedtomography in coronary artery disease. Acta Cardiol Sin 1996;12:126-133.2. Van Train KF, Maddahi J, Berman DS, et al. Quantitative analysisof tomographic stress thallium-201 myocardial scintigraphy: amulticenter trial. J Nucl Med 1990;31:1168-1179.3. Popma JJ, Smitherman TC, Walker BS, et al. Reverse redistributionof thallium-201 detected by SPECT imaging afterdypiridamole in angina pectoris. Am J Cardiol 1990;65:1176-1180.4. DePuey EG, Rozanski A. Using gated technetium-99m sestamibiSPECT to characterize fixed myocardial defects as infarct orartifact. J Nucl Med 1995;36;952-955.5. Wacker FJ, Bodenheimer M, Fleiss JL, Brown M. Factorsaffecting uniformity in interpretation of planar thallium-201imaging in a multicenter trial. J Am Coll Cardiol 1993;21:1064-1074.6. Maddahi J, Van Train K, Prigent F, et al. Quantitative singlephoton emission computed thallium-201 tomography for detectionand localized of coronary artery disease: optimization andprospective validation of a new technique. J Am Coll CardiolActa Cardiol Sin 2006;22:2430 28

ECG-gated SPECT and Thallium-201 Myocardial Perfusion1989;14:1689-1699.7. Germano G, Kavanagh PB, Waechter PB, et al. A new algorithmfor the quantitation of myocardial perfusion SPECT. I. Theoreticalaspects. J Nucl Med. 2000;41:712-719.8. Achter AD, King MA, Dahlberg ST, Hendrick P, LaCroix KJ,Tsui BMW. An investigation of the estimation of ejectionfractions and cardiac volumes by quantitative gated SPECTsoftware package in simulated gated SPECT images. J NuclCardiol 1998;5:144-152.9. He ZX, Cwaig E, Preslar JS, et al. Accuracy of left ventricularejection fraction determined by gated myocardial perfusionSPECT with Tl-201 and Tc-99m sestamibi: comparison withfirst-pass radionuclide angiography. J Nucl Cardiol 1999;6:412-417.10. Manrique A, Fraggi M, Verra P, et al. Tl-201 and Tc99m MIBIgated SPECT in patients with large perfusion defects and leftventricular dysfunction: comparison with equilibrium radionuclideangiography. J Nucl Med 1999;40:805-809.11. Johnson LL, Verdesca SA, Aude WY, et al. Postischemic stunningcan affect left ventricular ejection fraction and regional wallmotion on post-stress gated sestamibi tomograms. J Am CollCardiol 1997;30:1641-1648.12. Paul AK, Hasegawa S, Yoshioka J, Tsujimura E, Yamaguchi H,Tokita N, et al. Exercise-induced stunning continues for at leastone hour: evaluation with quantitative gated sinple-photon emissiontomography. Eur J Nucl Med 1999;26:410-415.13. Hendel RC, Parker M, Wackers FJ, Ragio P, Lahiri A, Zaret BL.Reduced variability of interpretation and improved image qualitywith a technetium-99m myocardial perfusion agent: comparisonof thallium-201 and technetium-99m-labelled tetrofosmin. J NuclCardiol 1994;1:509-514.14. Tailefer R, Depurey EG, Udelson JE, Beller GA, Latour Y,Reeves F. Comparative diagnostic accurancy of Tl-201 and Tc-99m sestamibi SPECT imaging (perfusion and ECG-gated SPECT)in detecting coronary artery disease in women. J Am Coll Cardiol1997;29:69-77.15. Pace L, Cuocolo A, Maurea S, et al. Reverse redistribution inresting thallium-201 myocardial scintigraphy in patients withcoronary artery disease: relation to coronary anatomy and ventricularfunction. J Nucl Med 1993;34:1688-1692.16. Sharir T, Berman DS, Waechter PB, et al. Quantitative analysis ofregional motion and thickening by gated myocardial perfusionSPECT: normal heterogeneity and criteria for abnormality. J NuclMed 2001;42:1630-1638.17. Bolli R, Marban E. Molecular and cellular mechanisms of myocardialstunning. Physiol Rev 1999;79:609-634.18. Ambrosio G, Betocchi S, Pace L, et al. Prolonged impairment ofregional contractile function after resolution of exercise-inducedangina: evidence of myocardial stunning in patients with coronarydisease. Circulation 1996;94:2455-2464.19. Danias PG, Ahlberg AW, Clark BA, Messineo F, Levine MG,Mcgill CC, et al. Combined assessment of myocardial perfusionand left ventricular function with exercise technetium-99msestamibi gated single-photon emission computed tomographycan differentiate ischemic and non-ischemic dilated cardiomyopathy.Am J Cardiol 1998;82:1253-1258.20. Vallejo E, Dione DP, Bruni WL, Constable RT, Borek PP, SoaresJP, et al. Reproducibility and ccuracy of gated SPECT for determinationof left ventricular volumes and ejection fraction:experimental validation using MRI. J Nucl Med 2000;41:874- 882.21. Germano G, Kavanagh P, Su HT, et al. Automatic reorientation ofthree-dimensional transaxial myocardial perfusion SPECT images.J Nucl Med 1995;36:1107-1114.22. Severi S, Picano E, Michelassi C, et al. Diagnostic and prognosticvalue of dipyridamole echocardiography in patients with suspectedcoronary artery disease. Circulation 1994;89:1160-1173.29 Acta Cardiol Sin 2006;22:2430

Original ArticleActa Cardiol Sin 2006;22:24−30心 節 律 門 閥 鉈 壓 力 攝 影 對 傳 統 造 影 邊 緣 型 病 例 之 價 值1陳 鉞 忠2秦 公 焯3柯 景 塘1台 北 市 市 立 聯 合 醫 院 仁 愛 分 院 心 臟 內 科2桃 園 縣 敏 盛 醫 院 核 子 醫 學 科3台 北 市 市 立 聯 合 醫 院 忠 孝 分 院 心 臟 內 科背 景 鉈 -201 心 肌 灌 注 攝 影 為 一 常 用 於 冠 心 症 診 斷 之 工 具 , 然 而 常 有 一 些 情 形 , 例 如 小 區域 之 缺 氧 、 可 逆 性 再 分 佈 及 衰 減 效 應 造 成 之 灌 流 不 足 , 均 可 能 使 判 讀 發 生 困 難 。方 法 我 們 希 望 使 用 心 節 律 門 閥 鉈 壓 力 攝 影 加 入 原 來 檢 查 顯 示 邊 緣 性 結 果 之 病 例 中 , 看 是否 可 以 增 加 冠 心 症 之 正 確 診 斷 。2004 年 1 月 至 11 月 共 512 位 受 檢 病 人 中 , 有 69 位 呈 現 邊緣 性 結 果 , 其 中 32 位 接 受 了 心 導 管 檢 查 , 本 實 驗 即 取 此 32 名 病 例 做 分 析 。結 果 鉈 -201 心 肌 灌 注 攝 影 32 名 邊 緣 性 病 例 中 ,21 位 有 顯 著 冠 心 症 ,11 位 無 ; 此 32 名病 例 若 再 加 上 心 節 律 門 閥 鉈 壓 力 攝 影 檢 查 後 , 不 正 常 變 化 之 病 例 共 25 位 , 當 中 21 位 有 顯著 冠 心 症 ,4 位 無 , 而 無 不 正 常 變 化 之 7 名 病 例 中 均 無 冠 心 症 ; 換 言 之 , 本 研 究 從 邊 緣 病例 中 , 找 出 32 名 , 將 這 32 名 病 例 皆 實 施 心 導 管 手 術 , 其 中 有 11 名 將 被 誤 作 心 導 管 手 術 ,但 多 加 了 一 套 檢 驗 手 續 , 此 32 名 病 例 中 僅 4 名 可 能 被 誤 作 心 導 管 手 術 , 可 見 後 者 比 前 者 更能 降 低 誤 判 的 機 率 。 我 們 使 用 兩 母 體 比 率 差 異 之 假 設 檢 驗 來 測 試 此 一 結 果 , 顯 示 假 設 有 意義 ,p 值 = 0.0166 (p < 0.05)。結 論 心 節 律 門 閥 鉈 壓 力 攝 影 對 鉈 -201 心 肌 灌 注 攝 影 邊 緣 性 結 果 之 病 人 , 於 冠 心 症 之 診 斷上 有 極 佳 的 參 考 效 果 。關 鍵 詞 : 心 節 律 門 閥 鉈 壓 力 攝 影 、 鉈 -201、 心 肌 灌 注 攝 影 、 心 肌 昏 迷 、 冠 心 症 。30