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心力衰竭(简称心衰)的发病率和病死率较高,严重影响患者的生活质量,且治疗费用昂贵。目前全球约有6 400万心衰患者,发展中国家占比较高[1]。心脏移植是终末期心衰患者最有效的治疗手段,但供体紧缺且需求庞大的特点极大地限制了心脏移植的临床应用。左心室辅助装置(left ventricular assist device,LVAD)植入术缓解了这一紧迫的医疗状况。LVAD研制之初是作为心衰患者心脏移植前的“桥梁”,但已有越来越多的患者,尤其是不适合做心脏移植的患者,选择将LVAD作为治疗心衰的终点治疗手段[2]。患者植入LVAD后1~2年的生存率与心脏移植相当,4年生存率稍低于心脏移植[3]。与其他人工植入物一样,患者植入LVAD也会导致诸多并发症,其中术后感染最常见,而术后感染的早期诊断、定性、定位和程度评估,对临床指导(抗生素治疗、外科清创、拆除泵或紧急心脏移植)和预后预测等具有十分重要的意义[4]。
PET/CT是集解剖和功能显像于一身的融合显像技术,可在CT的清晰解剖背景上融合显示功能信息,其在肿瘤、心脏和脑疾病中的临床应用价值已得到公认,在感染诊断中的应用价值也越来越受到重视。2015年欧洲心脏病学会指南[5]推荐将18F-FDG PET/CT应用于心脏植入性电子装置相关感染、人工瓣膜感染和心内膜感染的评估。18F-FDG PET/CT显像在诊断LVAD植入术后的感染方面亦有着重要的临床价值。我们对18F-FDG PET/CT在LVAD植入术后感染中的临床应用进展进行综述。
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虽然超声心动图检查便捷、成本低,但是其过分依赖于操作者的个人经验,如泵体金属伪影等干扰因素会导致较差的显影声窗,且早中期感染很可能无明显形态学改变,这会造成较高比例的假阴性,因此超声心动图较少应用于LVAD植入术后感染的诊断,但通常可作为渗出液抽吸引流时的影像指导。CT显像受伪影影响更大,虽然注射造影剂后的门控采集可在一定程度上改善此问题,但更高的辐射剂量和碘造影剂会对患者的肾功能造成损伤。MRI因有绝对禁忌而不能使用。PET/CT的优势是在感染早期,即形态学损伤发生之前就能检测到炎症细胞聚集,其还可同时检查LVAD和其他部位,从而检测容易被忽略的远处感染部位,这对LVAD植入术后相关感染早期处理策略的制定和预后均有重要意义。
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18F-FDG结构与葡萄糖相似,可由细胞膜上的葡萄糖转运蛋白(glucose transporter,GLUT)转运至细胞内,在己糖激酶作用下磷酸化,形成6-磷酸-18F-FDG,但不能再进一步参与三羧酸循环而滞留于细胞内,因此葡萄糖代谢增高的组织细胞对18F-FDG的摄取也会增高。因此,18F-FDG PET/CT通常被应用于肿瘤和心肌代谢显像。对炎症过程而言,以活化的白细胞为主的炎症细胞,如中性粒细胞、单核或巨噬细胞家族的细胞和淋巴细胞等能高水平表达GLUT,尤其是GLUT1和GLUT3,其可提高己糖激酶活性,增加自身葡萄糖的摄取并以此为主要能量来源。因此,在感染所致的炎症病灶中会有18F-FDG摄取的异常增高,18F-FDG PET/CT也被应用于感染所致的炎症显像[12]。
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LVAD植入术后感染的炎症病灶在18F-FDG PET/CT中表现为18F-FDG异常高摄取,在图像上形成“热点”,判读时需要先鉴别组织生理性摄取与非感染性病灶。目前推荐显像前1 d高脂低碳化合物饮食,检查前禁食12 h以上,以调动心肌脂肪酸代谢、抑制糖代谢,从而减少心肌摄取18F-FDG对周边判读的干扰[13]。LVAD植入本身会产生一定的反应性炎症,需要与感染性炎症相鉴别。因此,术后18F-FDG PET/CT显像时间十分关键,但目前尚无统一定论。一般认为最快在植入术后1个月,反应性炎症就会完全消失,如有需要可行18F-FDG PET/CT[14],但还是以术后3个月为最佳显像时间[15]。
在对LVAD植入术后感染的图像进行判读时应注意与装置相关的重点部位:(1)导线传动系统出口处;(2)导线传动系统皮下段;(3)泵和(或)泵袋;(4)泵流入口及周围;(5)流出管道周围,即沿人工血管路径;(6)胸骨切口及其周围;(7)术区远端的其他区域。人体免疫组织和器官,如淋巴结、脾脏和骨髓的异常摄取,通常反映人体对感染的反应性免疫细胞活化和动员。目前尚无LVAD植入术后感染的18F-FDG PET/CT图像判读的统一标准。de Vaugelade等[16]将心脏LVAD部位(套管、泵袋和泵)摄取分为3级:Ⅰ级,无摄取或仅在流入套管周围区域的环形区域摄取;Ⅱ级,局灶性18F-FDG摄取但不延伸到软组织;Ⅲ级,局灶性或节段性18F-FDG摄取延伸到软组织或纵隔系统。将外周导线传动系统摄取(近、中和远段)分为3级:Ⅰ级,无18F-FDG摄取;Ⅱ级,局灶性或节段性18F-FDG摄取而不延伸到软组织;Ⅲ级,局灶性或节段性18F-FDG摄取并延伸到软组织。Ⅰ级为感染阴性,Ⅱ、Ⅲ级为感染阳性。不同于传统判读标准,考虑到LVAD植入术后短期内会产生非感染性的局部炎症反应,该研究将泵体周边呈环形、均匀一致的18F-FDG摄取也判定为感染阴性。有研究者采用4点评分法(0为无摄取;1为略高但低于肺摄取;2为中度摄取,但低于或等于肝摄取;3为高于肝摄取)进行视觉分析[17]。Kanapinn等[18]将导线传动系统感染在18F-FDG PET/CT上的表现分为3类:(1)浅表导线感染直到腹筋膜(筋膜上);(2)感染扩散超过腹筋膜(筋膜下);(3)皮下导线感染,沿着术后额外的腹部切口,而导线出口处无感染。
18F-FDG PET/CT亦能提供半定量分析指标,如SUV或SUVmax。目前尚未有统一的SUVmax临界值来对所有的感染病灶进行判读。有研究结果显示,在LVAD核心感染部位使用半定量分析的诊断效能较差[17-18]。Avramovic等[19]的研究结果显示,18F-FDG PET/CT对可疑LVAD导线传动系统感染的视觉判读与半定量分析之间的诊断效能并无明显差异。但应注意,病灶若在衰减校正模式下和非衰减校正模式下均表现为18F-FDG摄取程度比本底明显升高,才会被判定为感染阳性,避免因衰减校正过度而造成的假阳性[16-17]。
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目前关于LVAD植入术后感染的影像诊断尚无公认的“金标准”,然而越来越多的研究结果表明,相比于传统影像,18F-FDG PET/CT对LVAD植入术后感染诊断的应用价值更高[18, 20-22]。有研究者认为18F-FDG PET/CT对LVAD植入术后感染诊断效能的灵敏度和特异度较高,但也有研究者得出了特异度较低的结论[16,21, 23-24]。Tam等[25]的Meta分析中,18F-FDG PET/CT诊断LVAD植入术后感染的灵敏度和特异度分别为92%(95%CI:0.82~0.97)和83%(95%CI:0.24~0.99)。ten Hove等[15]的Meta分析中,18F-FDG PET/CT诊断LVAD植入术后感染的灵敏度和特异度分别为95%(95%CI:0.89~0.97)和91%(95%CI:0.54~0.99);诊断泵和(或)泵袋感染的灵敏度和特异度分别为97%(95%CI:0.69~1.00)和93%(95%CI:0.64~0.99);诊断导线传动系统感染的灵敏度和特异度分别为96%(95%CI:0.88~0.99)和99%(95%CI:0.13~1.00)。目前,18F-FDG PET/CT是最具前途的诊断和评估LVAD植入术后感染的成像技术。近年来关于18F-FDG PET/CT对LVAD植入术后感染诊断效能研究的主要文献见表1。
作者 发表年份 例数 图像判断方法 灵敏度(%) 特异度(%) 诊断标准 Akin等[14] 2018 9 视觉判断 100 100 a de Vaugelade等[16] 2019 22 视觉判断、SUVmax 95.2、90 66.7、66.7 a、b、c Kanapinn等[18] 2019 30 SUVmax 100 100 a、b Avramovic等[19] 2017 48 视觉判断、SUVmax、代谢容积 87.5、87.5、96 79、87.5、87.5 a、b Kim等[20] 2019 35 视觉判断 100 100 a、b Bernhardt等[21] 2017 21 视觉判断 87.5 100 a Dell'Aquila等[22] 2018 47 视觉判断 90 71.4 a、b Dell'Aquila等[24] 2016 31 视觉判断 100 80 a、b Friedman等[26] 2020 25 视觉判断 100 100 a、b Sommerlath等[27] 2019 57 视觉判断、SUVpeak(传动系统) 100、87 25、59 a 注:FDG为氟脱氧葡萄糖;PET为正电子发射断层显像术;CT为计算机体层摄影术;a表示微生物学,包括血培养、拭子检测、渗出液培养及设备表面微生物培养等;b表示临床证据,包括疼痛、反复发热、C反应蛋白水平升高、白细胞水平升高及随访结果等;c表示其他影像,包括CT、超声等 表 1 18F-FDG PET/CT对左心室辅助装置植入术后感染的诊断效能
Table 1. Diagnostic efficacy of 18F-FDG PET/CT in infection after implantation of left ventricular assist device
18F-FDG PET/CT在左心室辅助装置植入术后感染诊断中的临床应用进展
Clinical application progress of 18F-FDG PET/CT in the diagnosis of infection after left ventricular assist device implantation
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摘要: 左心室辅助装置(LVAD)植入术是治疗终末期心力衰竭患者重要且有效的手段,感染是其最常见的并发症,诊断延误或评估不足将导致生存预后降低等严重后果。近年来,18F-氟脱氧葡萄糖(FDG)PET/CT在LVAD植入术后感染诊断的定性、定位、分型、程度评估、治疗指导和预后预测方面发挥着独特且重要的临床作用。笔者对18F-FDG PET/CT在LVAD植入术后感染中的临床应用进展进行综述。
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关键词:
- 病灶感染 /
- 左心室辅助装置 /
- 正电子发射断层显像术 /
- 体层摄影术,X线计算机 /
- 氟脱氧葡萄糖F18
Abstract: Left ventricular assist device (LVAD) implantation is an important and effective method for the treatment of patients with end-stage heart failure. Infection is the most common complication. Delayed diagnosis or inadequate evaluation will lead to reduced survival and other serious consequences. In recent years, 18F-fluorodeoxyglucose(FDG) PET/CT plays an unique and important clinical effect in the diagnosis, location, classification, degree evaluation, treatment guidance and prognosis prediction of infection after LVAD implantation. The paper reviews the progress of clinical application of 18F-FDG PET/CT in infection after LVAD implantation. -
表 1 18F-FDG PET/CT对左心室辅助装置植入术后感染的诊断效能
Table 1. Diagnostic efficacy of 18F-FDG PET/CT in infection after implantation of left ventricular assist device
作者 发表年份 例数 图像判断方法 灵敏度(%) 特异度(%) 诊断标准 Akin等[14] 2018 9 视觉判断 100 100 a de Vaugelade等[16] 2019 22 视觉判断、SUVmax 95.2、90 66.7、66.7 a、b、c Kanapinn等[18] 2019 30 SUVmax 100 100 a、b Avramovic等[19] 2017 48 视觉判断、SUVmax、代谢容积 87.5、87.5、96 79、87.5、87.5 a、b Kim等[20] 2019 35 视觉判断 100 100 a、b Bernhardt等[21] 2017 21 视觉判断 87.5 100 a Dell'Aquila等[22] 2018 47 视觉判断 90 71.4 a、b Dell'Aquila等[24] 2016 31 视觉判断 100 80 a、b Friedman等[26] 2020 25 视觉判断 100 100 a、b Sommerlath等[27] 2019 57 视觉判断、SUVpeak(传动系统) 100、87 25、59 a 注:FDG为氟脱氧葡萄糖;PET为正电子发射断层显像术;CT为计算机体层摄影术;a表示微生物学,包括血培养、拭子检测、渗出液培养及设备表面微生物培养等;b表示临床证据,包括疼痛、反复发热、C反应蛋白水平升高、白细胞水平升高及随访结果等;c表示其他影像,包括CT、超声等 -
[1] Bragazzi NL, Zhong W, Shu JX, et al. Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017[J]. Eur J Prev Cardiol, 2021, 28(15): 1682−1690. DOI: 10.1093/eurjpc/zwaa147. [2] Qu Y, Peleg AY, McGiffin D. Ventricular assist device-specific infections[J/OL]. J Clin Med, 2021, 10(3): 453[2022-04-19]. https://www.mdpi.com/2077-0383/10/3/453. DOI: 10.3390/jcm10030453. [3] Goldstein DJ, Meyns B, Xie RB, et al. Third annual report from the ISHLT mechanically assisted circulatory support registry: a comparison of centrifugal and axial continuous-flow left ventricular assist devices[J]. J Heart Lung Transplant, 2019, 38(4): 352−363. DOI: 10.1016/j.healun.2019.02.004. [4] Teoh TK, Hannan MM. Ventricular assist device-associated infection[J]. Infect Dis Clin North Am, 2018, 32(4): 827−841. DOI: 10.1016/j.idc.2018.07.001. [5] Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM)[J]. Eur Heart J, 2015, 36(44): 3075−3128. DOI: 10.1093/eurheartj/ehv319. [6] Kormos RL, Cowger J, Pagani FD, et al. The society of thoracic surgeons intermacs database annual report: evolving indications, outcomes, and scientific partnerships[J]. J Heart Lung Transplant, 2019, 38(2): 114−126. DOI: 10.1016/j.healun.2018.11.013. [7] Hannan MM, Xie RB, Cowger J, et al. Epidemiology of infection in mechanical circulatory support: a global analysis from the ISHLT mechanically assisted circulatory support registry[J]. J Heart Lung Transplant, 2019, 38(4): 364−373. DOI: 10.1016/j.healun.2019.01.007. [8] Chahal D, Sepehry AA, Nazzari H, et al. The impact of left ventricular assist device infections on postcardiac transplant outcomes: a systematic review and meta-analysis[J]. ASAIO J, 2019, 65(8): 827−836. DOI: 10.1097/MAT.0000000000000921. [9] Aburjania N, Hay CM, Sohail MR. Continuous-flow left ventricular assist device systems infections: current outcomes and management strategies[J]. Ann Cardiothorac Surg, 2021, 10(2): 233−239. DOI: 10.21037/acs-2020-cfmcs-26. [10] Zierer A, Melby SJ, Voeller RK, et al. Late-onset driveline infections: the Achilles' heel of prolonged left ventricular assist device support[J]. Ann Thorac Surg, 2007, 84(2): 515−520. DOI: 10.1016/j.athoracsur.2007.03.085. [11] Tattevin P, Flécher E, Auffret V, et al. Risk factors and prognostic impact of left ventricular assist device–associated infections[J]. Am Heart J, 2019, 214: 69−76. DOI: 10.1016/j.ahj.2019.04.021. [12] Martineau P, Grégoire J, Harel F, et al. Assessing cardiovascular infection and inflammation with FDG-PET[J/OL]. Am J Nucl Med Mol Imaging, 2021, 11(1): 46−58[2022-04-19]. https://pubmed.ncbi.nlm.nih.gov/33688455. [13] Legallois D, Manrique A. Diagnosis of infection in patients with left ventricular assist device: PET or SPECT?[J]. J Nucl Cardiol, 2019, 26(1): 56−58. DOI: 10.1007/s12350-018-1324-6. [14] Akin S, Muslem R, Constantinescu AA, et al. 18F-FDG PET/CT in the diagnosis and management of continuous flow left ventricular assist device infections: a case series and review of the literature[J]. ASAIO J, 2018, 64(2): e11−e19. DOI: 10.1097/MAT.0000000000000552. [15] ten Hove D, Treglia G, Slart RHJA, et al. The value of 18F-FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device: a systematic review and meta-analysis[J]. Eur J Nucl Med Mol Imaging, 2021, 48(1): 241−253. DOI: 10.1007/s00259-020-04930-8. [16] de Vaugelade C, Mesguich C, Nubret K, et al. Infections in patients using ventricular-assist devices: comparison of the diagnostic performance of 18F-FDG PET/CT scan and leucocyte-labeled scintigraphy[J]. J Nucl Cardiol, 2019, 26(1): 42−55. DOI: 10.1007/s12350-018-1323-7. [17] Dell'Aquila AM, Sindermann JR. 18F-FDG positron emission tomography/computed tomography for diagnosis of pump housing infections in patients on left ventricular assist devices: should we contain our initial enthusiasm?[J]. Eur J Cardiothorac Surg, 2018, 53(4): 892−896. DOI: 10.1093/ejcts/ezx445. [18] Kanapinn P, Burchert W, Körperich H, et al. 18F-FDG PET/CT imaging of left ventricular assist device infection: a retrospective quantitative intrapatient analysis[J]. J Nucl Cardiol, 2019, 26(4): 1212−1221. DOI: 10.1007/s12350-017-1161-z. [19] Avramovic N, Dell'Aquila AM, Weckesser M, et al. Metabolic volume performs better than SUVmax in the detection of left ventricular assist device driveline infection[J]. Eur J Nucl Med Mol Imaging, 2017, 44(11): 1870−1877. DOI: 10.1007/s00259-017-3732-2. [20] Kim J, Feller ED, Chen W, et al. FDG PET/CT for early detection and localization of left ventricular assist device infection: impact on patient management and outcome[J]. JACC Cardiovasc Imaging, 2019, 12(4): 722−729. DOI: 10.1016/j.jcmg.2018.01.024. [21] Bernhardt AM, Pamirsad MA, Brand C, et al. The value of fluorine-18 deoxyglucose positron emission tomography scans in patients with ventricular assist device specific infections[J]. Eur J Cardiothorac Surg, 2017, 51(6): 1072−1077. DOI: 10.1093/ejcts/ezx016. [22] Dell'Aquila AM, Avramovic N, Mastrobuoni S, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for improving diagnosis of infection in patients on CF-LVAD: longing for more 'insights'[J]. Eur Heart J Cardiovasc Imaging, 2018, 19(5): 532−543. DOI: 10.1093/ehjci/jex158. [23] Juneau D, Golfam M, Hazra S, et al. Positron emission tomography and single-photon emission computed tomography imaging in the diagnosis of cardiac implantable electronic device infection: a systematic review and meta-analysis[J]. Circ Cardiovasc Imaging, 2017, 10(4): e005772. DOI: 10.1161/CIRCIMAGING.116.005772. [24] Dell'Aquila AM, Mastrobuoni S, Alles S, et al. Contributory role of fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis and clinical management of infections in patients supported with a continuous-flow left ventricular assist device[J]. Ann Thorac Surg, 2016, 101(1): 87−94. DOI: 10.1016/j.athoracsur.2015.06.066. [25] Tam MC, Patel VN, Weinberg RL, et al. Diagnostic accuracy of FDG PET/CT in suspected LVAD infections: a case series, systematic review, and meta-analysis[J]. JACC Cardiovasc Imaging, 2020, 13(5): 1191−1202. DOI: 10.1016/j.jcmg.2019.04.024. [26] Friedman SN, Mahmood M, Geske JR, et al. Positron emission tomography objective parameters for assessment of left ventricular assist device infection using 18F-FDG PET/CT[J/OL]. Am J Nucl Med Mol Imaging, 2020, 10(6): 301−311[2022-04-19]. https://pubmed.ncbi.nlm.nih.gov/33329932. [27] Sommerlath Sohns JM, Kröhn H, Schöde A, et al. 18F-FDG PET/CT in left-ventricular assist device infection: initial results supporting the usefulness of image-guided therapy[J]. J Nucl Med, 2020, 61(7): 971−976. DOI: 10.2967/jnumed.119.237628. [28] Chen W, Dilsizian V. Diagnosis and image-guided therapy of cardiac left ventricular assist device infections[J]. Semin Nucl Med, 2021, 51(4): 357−363. DOI: 10.1053/j.semnuclmed.2020.11.002. [29] Filsoufi F, Castillo JG, Rahmanian PB, et al. Epidemiology of deep sternal wound infection in cardiac surgery[J]. J Cardiothorac Vasc Anesth, 2009, 23(4): 488−494. DOI: 10.1053/j.jvca.2009.02.007. [30] Zhang RF, Feng ZH, Zhang Y, et al. Diagnostic value of fluorine-18 deoxyglucose positron emission tomography/computed tomography in deep sternal wound infection[J]. J Plast Reconstr Aesthet Surg, 2018, 71(12): 1768−1776. DOI: 10.1016/j.bjps.2018.07.017. [31] Liu SW, Zhang J, Yin HY, et al. The value of 18F-FDG PET/CT in diagnosing and localising deep sternal wound infection to guide surgical debridement[J]. Int Wound J, 2020, 17(4): 1019−1027. DOI: 10.1111/iwj.13368.