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肿瘤治疗技术的进步使患者生存期延长,但伴随的不良反应也增加了其病死率[1]。其中肿瘤治疗相关心功能不全(cancer therapy-related cardiac dysfunction,CTRCD)是最严重的不良反应,可能会使治疗中断从而影响治疗效果;降低患者的生存质量甚至导致患者过早死亡[2-3]。蒽环类药物(anthracyclines,ANTs)自20世纪60年代问世以来,因其抗肿瘤作用强、抗肿瘤谱广而闻名,已作为淋巴瘤的一线治疗药物。多数淋巴瘤患者通过规范治疗,生存时间可显著延长,甚至终身治愈[4]。但ANTs造成的不可逆的心脏损伤会影响预后[5]。有研究结果表明,在给予ANTs多年后,超过50%的患者可发生左心室亚临床变化[6]。若能及早发现心肌损伤并予以干预治疗,患者通常恢复良好[7]。目前,CTRCD主要根据左心室射血分数(left ventricular ejection fraction,LVEF)进行诊断[3, 8-10],但尚无统一的诊断标准。欧洲肿瘤医学会提出,当超声心动图测量的LVEF>50%,但与治疗前相比LVEF下降>15%时,仍可诊断为CTRCD[8]。但是有研究结果表明,LVEF并不是一个灵敏指标,当心内膜活体组织病理学检查已经观察到心肌损伤时,LVEF并未下降[11]。因此,需要选择更加灵敏准确的技术方法对CTRCD进行早期检测,如超声心动图心肌应变成像、心脏磁共振(cardiac magnetic resonance,CMR)心肌应变成像和心肌组织定量成像以及PET/CT显像。本文就可能有助于早期检测ANTs心脏毒性的影像学新方法进行综述。
早期检测蒽环类药物心脏毒性的影像学研究进展
Advances in imaging research on the early detection of anthracycline cardiotoxicity
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摘要: 随着治疗手段的进步,肿瘤患者的生存率及生存时间明显改善,但肿瘤治疗相关心功能不全严重威胁着肿瘤幸存者的健康,其中蒽环类药物(ANTs)引起的心脏毒性极其常见,并可导致不可逆的心脏损伤。ANTs心脏毒性的早期发现和及时治疗对于心脏功能的恢复至关重要,因此早期检测心脏毒性具有重要的临床意义。笔者主要探讨有助于早期检测ANTs心脏毒性的影像学新方法,包括超声心动图心肌应变成像、心脏磁共振心肌应变成像和心肌组织定量成像以及PET/CT显像,以期为临床早期发现ANTs心脏毒性提供有价值的信息。
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关键词:
- 正电子发射断层显像术 /
- 体层摄影术,X线计算机 /
- 早期检测 /
- 心脏毒性 /
- 蒽环类药物 /
- 影像技术
Abstract: With the advancement of treating methods, the survival rate and survival time of tumor patients have improved significantly, but the cancer therapeutics-related cardiac dysfunction seriously threatens the health of tumor survivors, among which the cardiotoxicity caused by anthracyclines (ANTs) is extremely common and can lead to irreversible heart damage. Early detection and timely treatment of cardiotoxicity caused by ANTs are essential for the recovery of cardiac function, so early detection of cardiotoxicity is of great clinical importance. The author focuses on new imaging methods that may help to detect the cardiotoxicity caused by ANTs early, including myocardial strain imaging by echocardiography, myocardial strain imaging and quantification imaging of myocardial tissue by cardiac magnetic resonance and PET/CT imaging, in order to provide valuable information for early clinical detection of cardiotoxicity caused by ANTs. -
[1] Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016[J]. CA Cancer J Clin, 2016, 66(4): 271−289. DOI: 10.3322/caac.21349. [2] Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments[J]. Nat Rev Cardiol, 2015, 12(9): 547−558. DOI: 10.1038/nrcardio.2015.65. [3] Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline[J]. J Clin Oncol, 2017, 35(8): 893−911. DOI: 10.1200/JCO.2016.70.5400. [4] 中国临床肿瘤学会(CSCO)中国抗淋巴瘤联盟, 中国医师学会血液科医师分会. 中国淋巴瘤患者全程管理模式专家共识(2021年版)[J]. 中华血液学杂志, 2021, 42(5): 364−368. DOI: 10.3760/cma.j.issn.0253-2727.2021.05.003.
Union for China Lymphoma Invesingators, Chinese Medical Doctor Association, Hematology Branch. Expert consensus on the whole-process management model of lymphoma patients in China (2021)[J]. Chin J Hematol, 2021, 42(5): 364−368. DOI: 10.3760/cma.j.issn.0253-2727.2021.05.003.[5] Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy[J]. N Engl J Med, 2000, 342(15): 1077−1084. DOI: 10.1056/NEJM200004133421502. [6] 石远凯, 巴一, 冯继锋, 等. 中国蒽环类药物特性专家共识[J]. 中国肿瘤临床, 2018, 45(3): 109−112. DOI: 10.3969/j.issn.1000-8179.2018.03.955.
Shi YK, Ba Y, Feng JF, et al. Expert consensus on the characteristics of anthracyclines in China[J]. Chin J Clin Oncol, 2018, 45(3): 109−112. DOI: 10.3969/j.issn.1000-8179.2018.03.955.[7] Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy[J]. Circulation, 2015, 131(22): 1981−1988. DOI: 10.1161/CIRCULATIONAHA.114.013777. [8] Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations[J]. Ann Oncol, 2020, 31(2): 171−190. DOI: 10.1016/j.annonc.2019.10.023. [9] Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging[J]. J Am Soc Echocardiogr, 2014, 27(9): 911−939. DOI: 10.1016/j.echo.2014.07.012. [10] Zamorano JL, Lancellotti P, Muñoz DR, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines[J]. Eur Heart J, 2016, 37(36): 2768−2801. DOI: 10.1093/eurheartj/ehw211. [11] Ewer MS, Ali MK, Mackay B, et al. A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving adriamycin[J]. J Clin Oncol, 1984, 2(2): 112−117. DOI: 10.1200/JCO.1984.2.2.112. [12] Oikonomou EK, Kokkinidis DG, Kampaktsis PN, et al. Assessment of prognostic value of left ventricular global longitudinal strain for early prediction of chemotherapy-induced cardiotoxicity: a systematic review and meta-analysis[J]. JAMA Cardiol, 2019, 4(10): 1007-1018. DOI: 10.1001/jamacardio.2019.2952. [13] Biswas AK, Haque T, Banik D, et al. Identification of significant coronary artery disease in patients with non-ST segment elevation acute coronary syndrome by myocardial strain analyses using three dimensional speckle tracking echocardiography[J]. Echocardiography, 2018, 35(12): 1988-1996. DOI: 10.1111/echo.14181. [14] Xu L, Huang XM, Ma J, et al. Value of three-dimensional strain parameters for predicting left ventricular remodeling after ST-elevation myocardial infarction[J]. Int J Cardiovasc Imaging, 2017, 33(5): 663−673. DOI: 10.1007/s10554-016-1053-3. [15] Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging[J]. J Am Soc Echocardiogr, 2015, 28(1): 1−39.e14. DOI: 10.1016/j.echo.2014.10.003. [16] Fallah-Rad N, Walker JR, Wassef A, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor Ⅱ-positive breast cancer treated with adjuvant trastuzumab therapy[J]. J Am Coll Cardiol, 2011, 57(22): 2263−2270. DOI: 10.1016/j.jacc.2010.11.063. [17] Tahir E, Azar M, Shihada S, et al. Myocardial injury detected by T1 and T2 mapping on CMR predicts subsequent cancer therapy-related cardiac dysfunction in patients with breast cancer treated by epirubicin-based chemotherapy or left-sided RT[J]. Eur Radiol, 2022, 32(3): 1853−1865. DOI: 10.1007/s00330-021-08260-7. [18] Khan JN, Singh A, Nazir SA, et al. Comparison of cardiovascular magnetic resonance feature tracking and tagging for the assessment of left ventricular systolic strain in acute myocardial infarction[J]. Eur J Radiol, 2015, 84(5): 840−848. DOI: 10.1016/j.ejrad.2015.02.002. [19] Pedrizzetti G, Claus P, Kilner PJ, et al. Principles of cardiovascular magnetic resonance feature tracking and echocardiographic speckle tracking for informed clinical use[J]. J Cardiovasc Magn Reson, 2016, 18(1): 51. DOI: 10.1186/s12968-016-0269-7. [20] Wang R, Zhou Z, Schoepf UJ, et al. Monitoring of anthracycline-induced myocardial injury using serial cardiac magnetic resonance: An animal study[J]. Int J Cardiol, 2021, 328: 111−116. DOI: 10.1016/j.ijcard.2020.12.040. [21] Harries I, Berlot B, Ffrench-Constant N, et al. Cardiovascular magnetic resonance characterisation of anthracycline cardiotoxicity in adults with normal left ventricular ejection fraction[J]. Int J Cardiol, 2021, 343: 180−186. DOI: 10.1016/j.ijcard.2021.08.037. [22] Galán-Arriola C, Lobo M, Vílchez-Tschischke JP, et al. Serial magnetic resonance imaging to identify early stages of anthracycline-induced cardiotoxicity[J]. J Am Coll Cardiol, 2019, 73(7): 779−791. DOI: 10.1016/j.jacc.2018.11.046. [23] 赵世华. 迎接心脏磁共振成像新技术挑战[J]. 中国医学影像技术, 2017, 33(8): 1125−1128. DOI: 10.13929/j.1003-3289.201707120.
Zhao SH. Cardiac MRI techniques: new challenges[J]. Chin J Med Imaging Technol, 2017, 33(8): 1125−1128. DOI: 10.13929/j.1003-3289.201707120.[24] Park HS, Hong YJ, Han K, et al. Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic changes[J]. J Cardiovasc Magn Reson, 2021, 23(1): 76. DOI: 10.1186/s12968-021-00767-8. [25] Podyacheva EY, Kushnareva EA, Karpov AA, et al. Analysis of models of doxorubicin-induced cardiomyopathy in rats and mice. A modern view from the perspective of the pathophysiologist and the clinician[J/OL]. Front Pharmacol, 2021, 12: 670479[2022-01-08]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209419. DOI: 10.3389/fphar.2021.670479. [26] Bauckneht M, Ferrarazzo G, Fiz F, et al. Doxorubicin effect on myocardial metabolism as a prerequisite for subsequent development of cardiac toxicity: a translational 18F-FDG PET/CT observation[J]. J Nucl Med, 2017, 58(10): 1638−1645. DOI: 10.2967/jnumed.117.191122. [27] Seiffert AP, Gómez-Grande A, Castro-Leal G, et al. An image processing tool for the detection of anthracycline-induced cardiotoxicity by evaluating the myocardial metabolic activity in [18F]FDG PET/CT[J]. Int J Comput Assist Radiol Surg, 2022, 17(2): 373−383. DOI: 10.1007/s11548-021-02508-9. [28] Sarocchi M, Bauckneht M, Arboscello E, et al. An increase in myocardial 18-fluorodeoxyglucose uptake is associated with left ventricular ejection fraction decline in Hodgkin lymphoma patients treated with anthracycline[J/OL]. J Transl Med, 2018, 16(1): 295[2022-01-08]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202821. DOI: 10.1186/s12967-018-1670-9. [29] 卫毛毛, 刘卫平, 袁婷婷, 等. 18F-FDG PET/CT早期诊断淋巴瘤治疗相关心脏毒性的应用[J]. 中华核医学与分子影像杂志, 2021, 41(11): 653−659. DOI: 10.3760/cma.j.cn321828-20200722-00291.
Wei MM, Liu WP, Yuan TT, et al. Application of 18F-FDG PET/CT in early detection of therapy-associated cardiotoxicity in patients with lymphoma[J]. Chin J Nucl Med Mol Imaging, 2021, 41(11): 653−659. DOI: 10.3760/cma.j.cn321828-20200722-00291.[30] 隋秀莉, 石洪成. SUV测量准确性的影响因素及其解决对策[J]. 国际放射医学核医学杂志, 2021, 45(8): 521−526. DOI: 10.3760/cma.j.cn121381-202007041-00080.
Sui XL, Shi HC. The influencing factors on the accuracy of SUV measurement and their solutions[J]. Int J Radiat Med Nucl Med, 2021, 45(8): 521−526. DOI: 10.3760/cma.j.cn121381-202007041-00080.[31] Bauckneht M, Morbelli S, Fiz F, et al. A score-based approach to 18F-FDG PET images as a tool to describe metabolic predictors of myocardial doxorubicin susceptibility[J/OL]. Diagnostics (Basel), 2017, 7(4): 57[2022-01-08]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745393/. DOI: 10.3390/diagnostics7040057. [32] Borde C, Kand P, Basu S. Enhanced myocardial fluorodeoxyglucose uptake following Adriamycin-based therapy: evidence of early chemotherapeutic cardiotoxicity?[J]. World J Radiol, 2012, 4(5): 220−223. DOI: 10.4329/wjr.v4.i5.220. [33] Gorla AKR, Sood A, Prakash G, et al. Substantial increase in myocardial FDG uptake on interim PET/CT may be an early sign of Adriamycin-induced cardiotoxicity[J]. Clin Nucl Med, 2016, 41(6): 462−463. DOI: 10.1097/rlu.0000000000001194. [34] 姜婧晨, 王雪梅, 张凯秀. 18F-FDG PET/CT心肌代谢显像图像质量影响因素的研究进展[J]. 国际放射医学核医学杂志, 2020, 44(2): 114−118. DOI: 10.3760/cma.j.issn.1673-4114.2020.02.008.
Jiang JC, Wang XM, Zhang KX. Current status of studies on factors affecting myocardial metabolism imaging quality of 18F-FDG PET/CT[J]. Int J Radiat Med Nucl Med, 2020, 44(2): 114−118. DOI: 10.3760/cma.j.issn.1673-4114.2020.02.008.[35] Yan R, Song JB, Wu ZF, et al. Detection of myocardial metabolic abnormalities by 18F-FDG PET/CT and corresponding pathological changes in beagles with local heart irradiation[J]. Korean J Radiol, 2015, 16(4): 919−928. DOI: 10.3348/kjr.2015.16.4.919. [36] Varricchi G, Ameri P, Cadeddu C, et al. Antineoplastic drug-induced cardiotoxicity: a redox perspective[J/OL]. Front Physiol, 2018, 9: 167[2022-01-08]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846016. DOI: 10.3389/fphys.2018.00167. [37] Varga ZV, Ferdinandy P, Liaudet L, et al. Drug-induced mitochondrial dysfunction and cardiotoxicity[J]. Am J Physiol Heart Circ Physiol, 2015, 309(9): H1453−H1467. DOI: 10.1152/ajpheart.00554.2015. [38] Sivapackiam J, Sharma M, Schindler TH, et al. PET radiopharmaceuticals for imaging chemotherapy-induced cardiotoxicity[J]. Curr Cardiol Rep, 2020, 22(8): 62. DOI: 10.1007/s11886-020-01315-z. [39] Boutagy NE, Wu J, Cai ZX, et al. In vivo reactive oxygen species detection with a novel positron emission tomography tracer, 18F-DHMT, allows for early detection of anthracycline-induced cardiotoxicity in rodents[J]. JACC Basic Transl Sci, 2018, 3(3): 378−390. DOI: 10.1016/j.jacbts.2018.02.003. [40] Sivapackiam J, Kabra S, Speidel S, et al. 68Ga-Galmydar: a PET imaging tracer for noninvasive detection of Doxorubicin-induced cardiotoxicity[J/OL]. PLoS One, 2019, 14(5): e0215579[2022-01-08]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532866. DOI: 10.1371/journal.pone.0215579. [41] McCluskey SP, Haslop A, Coello C, et al. Imaging of chemotherapy-induced acute cardiotoxicity with 18F-labeled lipophilic cations[J]. J Nucl Med, 2019, 60(12): 1750−1756. DOI: 10.2967/jnumed.119.226787. [42] Wu J, Boutagy NE, Cai ZX, et al. Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals[J]. J Nucl Cardiol, 2022, 29(1): 216-225. DOI: 10.1007/s12350-020-02184-3. [43] Su H, Gorodny N, Gomez LF, et al. Noninvasive molecular imaging of apoptosis in a mouse model of anthracycline-induced cardiotoxicity[J]. Circ Cardiovasc Imaging, 2015, 8(2): e001952. DOI: 10.1161/CIRCIMAGING.114.001952. [44] 石琴, 孙玉云, 曹升, 等. 18F-ML-10 PET/CT早期评价阿霉素诱导心脏毒性的实验研究[J]. 中华核医学与分子影像杂志, 2019, 39(10): 581−586. DOI: 10.3760/cma.j.issn.2095-2848.2019.10.002.
Shi Q, Sun YY, Cao S, et al. 18F-ML-10 PET/CT imaging in early evaluation of doxorubicin-induced cardiotoxicity[J]. Chin J Nucl Med Mol Imaging, 2019, 39(10): 581−586. DOI: 10.3760/cma.j.issn.2095-2848.2019.10.002.
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