18FDG和99mTc-MIBI双核素心肌显像对冠状动脉闭塞性缺血性心肌病治疗的临床价值

赵曼，徐予，朱中玉，安松涛，赵先锋，陈芳

（河南省人民医院心内科，河南 郑州 450000）

18FDG和99mTc-MIBI双核素心肌显像对冠状动脉闭塞性缺血性心肌病治疗的临床价值

赵曼，徐予，朱中玉，安松涛，赵先锋，陈芳

（河南省人民医院心内科，河南 郑州 450000）

目的对单支或多支冠状动脉完全闭塞性缺血性心肌病患者，进行99mTc-mibi/18F-FDG双核素心肌断层显像检测，以评价其对药物治疗或经皮冠状动脉介入治疗（PCI）术治疗冠状动脉闭塞性缺血性心肌病预测价值。方法139例冠状动脉造影证实为单支或多支冠状动脉完全闭塞缺血性心肌病患者行18F-FDG/99mTc-MIBI双核素心肌断层显像，根据其结果分为有存活心肌组及无存活心肌组。2组分别根据是否进行PCI治疗再分为2个亚组：PCI+优化药物治疗亚组和优化药物治疗亚组，治疗12个月。以治疗前、后超声左室射血分数（LVEF）、血浆NT-B型脑钠肽前体（NT-proBNP）水平评价治疗疗效。结果存活心肌组接受PCI+优化药物治疗亚组54例，优化药物治疗亚组24例。治疗前LVEF、NT-proBNP水平差异无统计学意义。与治疗前比较，两亚组治疗后LVEF均有增加，血NT-proBNP水平均显著下降，差异有统计学意义。但PCI+优化药物治疗组LVEF、NT-proBNP水平均较优化药物治疗组进一步改善，差异有统计学意义。无存活心肌组中PCI+优化药物治疗亚组27例，优化药物治疗亚组34例。与治疗前比较，两亚组治疗后LVEF、血NT-proBNP之间差异均无统计学意义；两亚组治疗后比较，差异无统计学意义。结论药物治疗或PCI术治疗仅对经双核素心肌断层显像证实有存活心肌的冠状动脉闭塞性缺血性心肌病患者有显著疗效。

双核素心肌灌注/代谢显像技术；经皮冠状动脉支架术；左心室射血分数；存活心肌；NT-proBNP

对冠状动脉闭塞性缺血性心肌病患者经皮冠状动脉介入治疗（percutaneous coronary intervention，PCI），仍有1/4～1/3的病例心功能和预后没有得到改善，但其部分病例仅经药物优化治疗，心功能却比较稳定，甚至得到一定程度的改善[1]。已有研究表明，药物治疗或PCI术治疗后心功能改善均与冠状动脉闭塞相应心室壁内是否有存活心肌有关[2-7]，目前国内相关报道甚少。本文对经冠状动脉造影（coronary angiography，CAG）证实为单支或多支冠状动脉完全闭塞性缺血性心肌病患者，进行99mTc-mibi/18F-FDG双核素心肌断层显像（dual imaging using isotope stimultaneous acquisition，DISA）检测，以评价其对药物治疗或PCI治疗术治疗冠状动脉闭塞性缺血性心肌病预测价值。

1 资料与方法

1.1 研究对象

选取2011年8月-2014年1月在河南省人民医院经CAG结果证实为单支或多支冠状动脉完全闭塞缺血性心肌病患者139例。入选标准：①至少一支冠状动脉完全闭塞，冠状动脉远端血流TIMI 0级；②心功能不全（NYHA分级Ⅱ～Ⅲ级）；③超声心动图显示左室舒末内径女性＞50 mm，男性＞55 mm，LVEF＜45%。排除标准：①急性ST段抬高型心肌梗死；②合并严重肺或肾脏疾病；③严重心脏瓣膜疾病；④6个月内脑血管疾病史。

1.2 研究方法

1.2.199mTc-MIBI/FDG双核素SPECT心肌显像所有患者检查日均晨起禁食，静脉注射99mTc-MIBI 740～1 110 MBq，20 min后进脂餐，30 min后测定患者的血糖浓度，将血糖浓度控制在7.9～8.8 mmol/L之间。如果患者血糖浓度低于7.8 mmol/L，则口服葡萄糖补充；如果血糖浓度高于8.9 mmol/L，则需要皮下注射胰岛素降低血糖浓度。在血糖控制10～15 min后，静脉注射18F-FDG 185～370 MBq，1 h后行DISA显像。获得短轴、垂直长轴、水平长轴的心肌灌注及心肌代谢对照图像。由2位以上医师盲法对灌注及代谢图像进行评价。灌注图像评分标准分为5级，分别为：正常；放射性分布轻度减低；中度减少；明显减低；放射性分布缺损。以放射性分布缺损存在是否分为相应闭塞血管心肌存活组和无心肌存活组。

1.2.2 病例分组与治疗所有患者均行优化药物治疗，如ACEI类药物、β受体阻滞剂、螺内酯、他汀类药物、阿司匹林肠溶片等，必要时加服地高辛等。2组分别根据是否进行PCI治疗再分为2个亚组：PCI+优化药物治疗亚组和优化药物治疗亚组。PCI+优化药物治疗组行相应闭塞血管PCI治疗，PCI术后TIMI血流均达Ⅲ级。治疗后1、3、6和12个月定期门诊随访，观察12个月。

1.2.3 超声心功能及NT-proBNP测定入组前和治疗12个月分别进行常规心脏超声心动图（ultrasonic cardiography，UCG）及NT-proBNP检测。在左侧卧位下，应用彩色超声检测仪（飞利浦IE33）经胸行心脏彩超检查，超声二维左室长轴切面检测左室舒张末内径（LVEDD）和左室收缩末内径（LVESD），左室射血分数（left ventricular ejection fraction，LVEF），取5个心动周期均值。经肘静脉采血，静脉血注入预先加入乙二胺四乙酸（EDTA）的试管中，应用罗氏Cobas E601诊断仪检测NT-proBNP。

1.3 统计学方法

采用SPSS 16.0统计软件进行数据分析，计量资料用均数±标准差（±s）表示，心肌存活组及无心肌存活组包括LVEF、NT-proBNP比较用t检验，P＜0.05为差异有统计学意义。

2 结果

2.1 心肌存活组和无心肌存活组一般临床资料

心肌存活组78例，非心肌存活组61例，两组除PCI手术比例有明显差异外，其他各指标之间差异均无统计学意义（P＞0.05），见表1。

表1 心肌存活组和非心肌存活组治疗前一般临床资料例（%）

2.2 存活心肌组PCI+优化药物治疗与优化药物治疗疗效比较

存活心肌组中接受PCI+优化药物治疗亚组54例、优化药物治疗亚组24例。两个亚组心血管危险因素和冠状动脉病变无明显差异（P＞0.05），比较治疗前LVEF、NT-proBNP水平，差异均无统计学意义。2个亚组随访12个月后，与治疗前比较，LVEF均有增加，血NT-proBNP水平均显著下降，差异有统计学意义。但治疗后12个月后，PCI+优化药物治疗组LVEF、NT-proBNP水平均较优化药物治疗组进一步改善，差异有统计学意义（P＜0.05），见表2。

表2 存活心肌组PCI+优化药物治疗与优化药物治疗疗效比较（±s）

表2 存活心肌组PCI+优化药物治疗与优化药物治疗疗效比较（±s）

注：1）与治疗12个月后2组比较，P=0.038；2）与治疗组比较，P=0.003

LVEF/%NT-proBNP/（ng/L）治疗前治疗12个月治疗前治疗12个月P值PCI术+优化药物治疗（n=54）40.16±6.0243.16±5.241）0.0234 586.48±514.62421.34±92.052）0.001优化药物治疗（n=24）40.08±5.3642.97±5.480.0314 492±483.591015±95.120.001组别P值

2.3 无存活心肌组PCI+优化药物治疗与优化药物治疗疗效比较

无存活心肌组中PCI+优化药物治疗亚组27例、优化药物治疗亚组34例。与治疗前比较，2个亚组随访12个月后LVEF、血NT-proBNP差异均无统计学意义；2个亚组治疗后比较，差异亦无统计学意义，见表3。

表3 无存活心肌组PCI+优化药物治疗与优化药物治疗疗效比较（±s）

表3 无存活心肌组PCI+优化药物治疗与优化药物治疗疗效比较（±s）

LVEF/%NT-proBNP/（ng/L）基线（CAG术前）基线（CAG术前）12个月PCI术+优化药物治疗（n=27）40.05±3.3641.28±4.054 387.68±357.924 054.32±189.65优化药物治疗（n=34）40.11±6.0241.16±5.654 693.24±93.814 427.53±82.69组别12个月

3 讨论

99mTc-MIBI/18F-FDG双核素同步心肌显像可同时获得心肌血流灌注及代谢图像，可较准确地估价心肌灌注及代谢水平，判断存活心肌的部位及范围，克服单纯应用FDG显像无法区分正常和缺血心肌的局限性。其他学者应用99mTc/18F-FDG双核素同步心肌显像检测存活心肌，证明DISA法SPECT显像对检测心肌存活性有重要价值，能有效地识别存活心肌且方法简便[5]。国外进一步相关研究亦说明双核素心肌显像可以无创、快捷而又准确地观察PCI后心肌的灌注及代谢变化[8-12]。

本研究结果显示，单支或多支冠状动脉完全闭塞的缺血性心肌病患者中，经18F-FDG/99mTc-MIBI双核素心肌断层显像检测，证实仅有存活心肌的患者接受PCI+优化药物治疗或单纯优化药物治疗，均可显著提高LVEF、降低血NT-proBNP水平，且联合治疗疗效进一步提高；反之，PCI+优化药物治疗或单纯优化药物治疗对无存活心肌的患者，上述心功能指标均无显著性改善。本研究结果提示，对单支或多支冠状动脉完全闭塞的缺血性心肌病患者，应进行双核素心肌断层显像检测评估存活心肌；对有存活心肌的患者推荐PCI+优化药物治疗，对无存活心肌的患者，基于PCI+优化药物治疗效果比较差异无统计学意义，仅推荐优化药物治疗。本研究支持近期国外研究结果，VAN等[13]研究证实，仅具有存活心肌的患者经血运重建后LVEF值明显提高，而无心肌存活患者虽经血运重建，LVEF却无明显改善。COURAGE核素亚组研究[14]中，105例轻度缺血的患者在随访1年后再次接受核素检查，结果显示PCI+药物治疗组较单独优化药物治疗组有更多的显著缺血降低。随后COURAGE核素亚组对心肌灌注显像中度以上缺血的468例患者的分析显示与单独药物治疗相比，PCI+药物治疗组并未降低死亡[15]。另外，国外已有研究显示冠心病患者存活心肌数量越多，心功能改善越显著，反之亦然[16-18]。

本研究结果有一定的局限性，入选病例数偏少，观察时间仅限12个月，故需要大样本的多中心研究、且更长时间随访进一步证实。

总之，合理应用双核素心肌显像不仅可以指导患者治疗方案，而且可以节约大量医疗费用，这在我国目前情况下尤为迫切和必要。

[1]ZHANG XL,LIU XJ,HU SS,et al.Impact of viable myocardium assessed by99Tcm-MIBI SPECT and 18F-FDG PET imaging on clinical outcome of patients with left ventricular aneurysm underwent revascularization[J].Chinese Journal of Cardiology,2008, 36(11):999-1003.

[2]BELLER GA,HEEDE RC.SPECT imaging for detecting coronary artery disease and determining prognosis by noninvasive assessment of myocardial perfusion and myocardial viability[J].Cardiovasc Transl Res,2011,4(4):416-424.

[3]HOLLY TA,BONOW RO,ARNOLD JM,et al.Myocardial viability and impact of surgical ventricular reconstruction on outcomes of patients with severe left ventricular dysfunction undergoing coronary artery bypass surgery:Results of the Surgical Treatment for Ischemic Heart Failure trial[J].2014,148(6):2677-2684.

[4]YAP J,TAN RS.Myocardial viability in ischemic left ventricular dysfunction[J].N Engl J Med,2011,365(5):472.

[5]BONOW RO,MAURER G,LEE KL,et al.Myocardial viability and survival in ischaemic left ventricular dysfunction[J].NEJM, 2011,69(10):1095-1096.

[6]MYLONAS I,BEANLANDS RS.Radionuclide Imaging of Viable Myocardium:is it Underutilized[J].Curr Cardiovasc Imaging Rep, 2011,4(3):251-261.

[7]LI LQ,LIU XH,ZHANG J,et al.Influences of percutaneous coronary intervention on myocardial activity in myocardial infarction patients with different viable myocardium[J].Chinese Journal of Department of Internal Medicine,2013,52(10):811-814.

[8]HUANG ZK,LOU C,SHI GH,et al.Value of(99m)Tc-MIBI/(18) F-FDG dual-isotope simultaneous acquisition in diagnosis and treatment of myocardial infarction[J].Journal of Zhejiang University,2010,39(5):530-533.

[9]ALLMAN KC.Noninvasive assessment myocardial viability:current status and future directions[J].Nucl Cardiol,2013,20(4):618-637.

[10]EL-MAGHRABY T.The use of nuclear imaging to assess the myocardial viability[J].Saudi Heart Assoc,2010,22(3):157-158.

[11]CHOPRA HK,SAMBI RS,KRISHNA CK,et al.Techniques to assess myocardial viability[J].Indian Heart J,2011,63(1):39-44.

[12]WEI H1,TIAN C,SCHINDLER TH,et al.The impacts of severe perfusion defects,akinetic/dyskinetic segments,and viable myocardium on the accuracy of volumes and LVEF measured by gated mTc-MIBI SPECT and gated F-FDG PET in patients withleftventricularaneurysm:cardiacmagneticresonance imaging as the reference[J].J Nucl Cardiol,2014,21(6):1230-1244.

[13]VAN LOON RBI,VEEN G,BAUR LH,et al.Improved clinical outcome after invasive management of patients with recent myocardial infarction and provenmyocardial viability:primary results of a randomized controlled trial(VIAMI-trial)[J].Trials,2012,3 (13):1.

[14]SHAW LJ,BERMAN DS,MARON DJ,et al.COURAGE Investigators.Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden:results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation(COURAGE)trial nuclear substudy[J]. Circulation,2008,117(10):1283-1291.

[15]SHAW LJ,WEINTRAUB WS,MARON DJ,et al.Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention[J].Am Heart J,2012,164(2):243-250.

[16]BAX J,EROEN J,FRANS C,et al.Relationship between preoperative viability and postoperative improvement in LVEF and heart failure symptoms[J].Nucl Med,2001,42(2):79.

[17]PEOVSKA I,MAKSIMOVIC J,VAVLUKIS M,et al.Relationship between myocardial viability and improvement in left ventricular function and heart failure symptoms after coronary artery bypass surgery[J].Prilozi,2007,28(1):97-112.

[18]UEBLEIS C,HELLWEGER S,LAUBENDER RP,et al.The amount of dysfunctional but viable myocardium predicts long term survival in patients with ischemic cardiomyopathy and left ventricular dysfunction[J].Int J Cardiovasc Imaging,2013,29(7): 1645-1653.

（张蕾 编辑）

Predictive value of radionuclide myocardial perfusion/ metabolic imaging technology(99mTc-MIBI/18F-fluorodeoxyglucose)in treatment for coronary artery occlusive ischemic cardiomyopathy

Man ZHAO,Yu XU,Zhong-yu ZHU,Song-tao AN,Xian-feng ZHAO,Fang CHEN
(Department of Cardiology,Henan Provincial People's Hospital,Zhengzhou, Henan 450000,P.R.China)

【Objective】To evaluate the predictive value of radionuclide myocardial perfusion/metabolic imaging technology[99mTc-MIBI/18F-fluorodeoxyglucose(18F-FDG)]in the treatment for coronary artery occlusive ischemic cardiomyopathy.【Methods】Totally 139 patients with ischemic cardiomyopathy associated with single or multiple coronary artery occlusion confirmed by coronary artery angiography were enrolled in this study.These patients were divided into survival myocardium and non-survival myocardium groups according to the99mTc-MIBI/18F-FDG dual isotope SPECT myocardial imaging.According to whether receiving percutaneous coronary intervention(PCI)treatment,both groups were further divided into two subgroups:PCI+optimal medical therapy and simple optimal medical therapy subgroups.The course of treatment lasted for 12 months.Left ventricular ejection fraction(LVEF)and plasma level of N-terminal probrain natriuretic peptide(NT-proBNP)before and after treatment were used to evaluate the treatment efficacy.【Results】In the survival myocardium group,LVEF was increased and the NT-proBNP level decreasedsignificantly after treatment in both subgroups.However,compared with the patients only receiving optimal medical therapy,LVEF and NT-proBNP level were further significantly improved after treatment in the patients receiving optimal medical therapy combined with PCI.In the non-survival myocardium group,no significant difference was found in LVEF or NT-proBNP level in both subgroups after treatment compared to thatbeforetreatment,therewasnosignificantdifferencebetweenbothsubgroupsaftertreatment.【Conclusions】DrugtreatmentorPCItreatmentisobviouslyeffectiveonlyforthesubjectswiththe myocardial viability among the patients with ischemic cardiomyopathy associated with single or multiple coronary artery occlusion.

radionuclide myocardial perfusion/metabolic imaging examination；PCI；left ventricular ejection fraction；viable myocardium；N-terminal pro-brain natriuretic peptide

R541.4

B

1005-8982（2015）30-0053-04

2015-06-14