光学相干断层成像技术在冠脉支架植入术后随访中的价值

   早在1977年,Andrea Gruntzig即开创了经皮冠状动脉腔内成形术(percutaneous transluminal coronary angioplasty,PTCA),随后在上世纪80年代,金属裸支架(bare-metal stents,BMS)开始在临床中使用,2000年后,药物洗脱支架(drug-eluting stents,DES)的时代正式到来[1,2]。作为冠状动脉粥样硬化性心脏病(coronary artery disease,CAD)介入治疗发展史中的里程碑,PTCA、BMS、DES的支架内再狭窄和靶病变再次血运重建发生率逐步下降[3,4]。如今,生物可降解支架(bioresorbable scaffold,BRS)成为介入心脏病学最重要的新进展之一 [5]。我们需要积累更多、更长时间的研究数据来证明哪种类型的支架能给患者带来更多临床获益,并寻找不同类型支架的最佳适用人群。因此,对冠状动脉支架植入术后的随访结果评判尤为关键。光学相干断层成像技术(optical coherence tomography,OCT)作为一种新型的应用光学成像技术,通过光源发射近红外光,使干涉仪记录不同厚度生物组织的反射光,应用计算机重建反射光信号,最终形成能够被简单识别的图像[6]。其综合了半导体、光学技术、共焦显微技术、超灵敏探测技术与计算机图像处理技术,被称为“光学活检”,空间分辨率可高达10-15um,已经被广泛应用于冠心病诊疗与随访的各个领域之中。
一 常规影像学技术在冠脉支架植入术后随访中的不足
   冠状动脉造影(coronary artery angiograghy,CAG)与血管内超声(intravascular ultrasound,IVUS)为冠状动脉支架植入术后结果评判的常用的影像学方法。冠状动脉造影为二维成像,不能有效地识别支架内再狭窄、支架断裂、支架贴壁不良、支架内血栓等介入术后中远期并发症并阐明其原因。IVUS可以有效地识别支架相关的中远期并发症,但由于其分辨率不高(仅为80-120um),在评价内膜覆盖以及支架内新生内膜组织等现象时还不够精确。尤其是新一代DES植入后的平均管腔丢失仅为0.1-0.2mm,使得IVUS对新一代支架植入术后评估更为受限。OCT空间分辨率高达10-15um,在检测少量支架内新生内膜(小于支架面积30%)上敏感性明显高于IVUS[7,8],在评估血管愈合程度方面具有相当的优势,能在横截面水平准确观察各种类型支架植入后的情况,特别在支架小梁贴壁不良、支架内新生内膜增生、新生动脉粥样硬化和血栓形成等方面优势更为明显。
二 OCT对冠脉支架植入术后的评价内容
   在冠脉介入治疗的不同阶段,OCT不仅可以评估术前斑块稳定性,还可以指导术中冠脉支架植入,并能够评价支架植入后的远期效果。在冠脉支架植入术后的随访过程中,OCT主要对术后血管修复情况进行评价,包括支架小梁贴壁、内皮化以及新生粥样斑块等。
   2012年OCT国际工作组专家共识指出[9]:若支架小梁表面到管腔表面的轴向距离小于支架小梁厚度(包括聚合物涂层厚度),则认为支架贴壁;反之,若大于支架小梁厚度,则认为支架贴壁不良。OCT成像能够清楚地显示管腔和血管壁的边界、节段血管的病变特征以及复杂程度。OCT对冠状动脉支架置入术后的随访研究发现,支架小梁贴壁不良可逐渐被内皮细胞覆盖,并与血管壁融合[10,11];晚期获得性支架贴壁不良可能增加血栓事件的发生风险[12-14]。
   支架植入后,新生内膜生长分为炎症期、肉芽期及基质重构期三个阶段,为血管局部损伤后内皮修复的关键。OCT可对支架小梁覆盖情况进行定量分析,精确评估新生内膜增生程度,并可识别血管修复增生组织的特征[15,16]。但与组织学检查相比,其对支架小梁未覆盖现象的敏感性较低,且不能区分不同组织[17]。OCT对支架植入后随访研究发现,支架小梁未覆盖率与远期不良心脏事件风险显著相关[18],而其对支架小梁覆盖程度的评估可成为临床工作中预测不良心血管事件的替代指标之一。
   新生动脉粥样硬化为内膜组织内发生动脉粥样硬化改变,即内膜含有吞噬脂质的泡沫样巨噬细胞[19]。OCT可对支架植入术后不同时间间隔新生内膜及新生动脉粥样硬化特点进行评估[20],并对比不同支架植入后新生动脉粥样硬化发生的差别[21]。在研究传统心血管危险因素如高血压、糖尿病、高血脂等与支架植入术后新生动脉粥样硬化斑块发生的相关性,OCT作为有效的影像学手段不仅可以定性、还可以做出定量的比较和相关性评价。
三 OCT在冠脉支架植入术后随访中的作用研究
   OCT对支架小梁是否完全覆盖及是否贴壁,支架位置是否合适,支架边缘有无夹层,支架内有无组织脱垂、组织撕裂、新生粥样硬化斑块、再狭窄及血栓等的随访观察具有重要价值,尤其在支架小梁水平的定量测定中具有明显优势。
   OCT可在支架置入后不同随访时间对血管情况进行评估。在术后早期,Xie等研究发现患者支架置入3个月后,与BMS组比较,西罗莫司药物洗脱支架(sirolimus-eluting stents,SES)组OCT显示的支架小梁覆盖率明显升高(15%比0.1%,P<0.0001)[22]。Miyoshi等发现,紫杉醇洗脱支架(paclitaxel-eluting stents,PES)及SES植入术后6个月,前者新生内膜覆盖率明显高于后者(92.6%比85.8%,p<0.01)[23]。OCT随访研究亦提示新一代DES置入术后血管修复程度显著优于第一代DES[24]。Takumi等发现,在支架置入术后8个月,新一代DES组较第一代DES组新生内膜覆盖率情况显著改善[28]。Ishibashi等研究对比置入BMS、SES、PES患者术后9个月的OCT影像,结果显示PES组支架小梁周围低密度区域(提示新生内膜粥样硬化)厚度较BMS、SES更大(77±5%比53±9%比57±8%,p<0.01)[26]。这些观察性研究均表明,OCT随访可对血管修复情况进行评估,从而预测不良事件的发生风险,指导高危患者的早期干预。在术后中晚期、极晚期,OCT仍然可以对支架置入情况进行有效评价。Kitabata等对支架置入患者随访4年,结果发现支架小梁厚度与新生内膜动脉粥样硬化有关,支架小梁更薄的BMS较支架小梁厚的BMS不易产生新生内膜动脉粥样硬化性改变[25]。Raber等研究发现,支架置入术后5年SES与PES两组支架小梁未覆盖率及贴壁不良率基本相同[27]。 因此,OCT在不同类型支架置入术后、不同时间点(短期、中期和长期)的疗效评估中都具有重要的临床意义。
   OCT还可对不同临床表现的患者支架置入术后的血管修复情况进行评估。急性冠脉综合症(acute coronary syndrome,ACS)患者富含易损斑块,支架植入术后血管修复易受影响,支架小梁贴壁不良、支架边缘夹层、支架内组织脱垂等不良现象多见,晚期支架内血栓形成的发生风险亦增加,。在ACS患者支架置入术后早期(3个月),Takano[29]应用OCT观察到,与稳定型心绞痛(stable angina pectoris,SAP)患者比较,ACS患者中支架小梁未覆盖(18% vs 13%,p<0.0001)和支架梁贴壁不良的发生率(8% vs 5%,p<0.005)更高。另有研究显示,支架置入术后9个月,不稳定型心绞痛(unstable angina pectoris,UAP)患者残留破裂斑块(28% vs 4%,p=0.031),支架小梁壁不良(33%比4%,p=0.012)及内膜不完全覆盖发生率(72% vs 37%,p=0.019)均明显高于SAP患者[30] ;此外,Kim等对ACS及SAP患者DES置入术后9个月的血管修复情况进行了OCT随访,结果发现ACS患者血管修复程度较SAP患者明显减低[31]。急性ST段抬高型心肌梗死(ST-elevated myocardial infarction,STEMI)患者的罪犯病变斑块脂质核心较大,易发生血管正性重构,斑块破裂与血栓形成的发生风险更高。Mizoguchi等采用OCT分析了STEMI及SAP患者置入第二代依维莫司涂层支架(everolimus-eluting stents,EES)术后12个月的支架内影像,结果发现STEMI患者支架小梁贴壁不良发生率(0.4%±0.6% vs 0.1%±0.4%,p=0.04)与新生内膜不均匀指数(1.74±0.2vs 1.64±0.16,p=0.04)均明显升高,而内膜覆盖程度与SAP组基本相同[32]。OCT研究发现,不同类型支架置入后血管愈合情况表现各异。HORIZONS-AMI研究对STEMI患者随访13个月,结果发现, PES组较BMS组支架小梁未覆盖率(5.7% vs 1.1%,p<0.0001)及支架贴壁不良率(0.9% vs 0.1%,p=0.0003)均升高[33]。Sawada等研究发现,STEMI患者支架置入术后7个月EES组较SES组新生内膜厚度更高,支架丝未覆盖率更低,支架丝贴壁不良更少[34]。新近BRS已逐步应用于临床,BRS的优势在于支架降解后能完成金属支架不能完成的任务,如恢复血管正常的生理功能、缓解血管壁炎症、可在同一病变部位反复介入治疗等。随着BRS的推广应用,其安全性备受关注。OCT可以清楚地显示BRS置入后支架小梁降解、支架内膜覆盖以及支架内血栓发生情况。Abbott BRS的First-in-Human研究对BRS置入术后患者进行OCT随访,结果显示术后2年34.5%的支架小梁已不可见[35]。ABSORB Cohort B研究在BRS置入后不同时间点分别进行血管影像学检查(冠状动脉造影、IVUS、OCT),术后6个月,OCT显示96.8%的支架小梁已经被内膜覆盖,术后2年OCT发现的新生内膜面积为0.68±0.43mm2,99%的支架小梁已被内膜覆盖[36,37]。尽管从理论上讲,BRS血栓事件会明显减少,但是OCT研究发现BRS术后1年的血栓发生率约为3%,与支架扩张不全、支架贴壁不良以及双联抗血小板治疗有关,采用特定置入方案,支架血栓发生率可降低70%[38]。 总之,不同临床表现的患者支架置入后的血管愈合程度有所不同,不同类型支架置入后的血管愈合程度也存在差异,OCT腔内影像学评估可为不同患者制定诊疗策略提供有力的证据支持。。
四 小结
   OCT技术利用光学相干原理进行成像,其成像速度、分辨率等较传统腔内成像技术有了明显的提升。OCT能够凭借其超高的空间分辨率能够准确测量斑块的表面形态和组成,评价支架置入术后支架小梁贴壁状况及术后新生内膜覆盖情况等。支架置入术后的OCT随访研究探索了不同时期血管修复情况及其影响因素,成为不同类型支架置入术后效果的重要评估方法,为支架设计的优化以及精准药物治疗提供在体影像学依据。但OCT在冠脉支架植入术后随访中仍存在不足。其组织穿透力有限,在组织分辨方面尚存在一定不足。随着OCT工艺和技术的不断完善,OCT最终会成为临床研究特别是支架术后随访研究的重要手段,为优化支架置入效果、改善患者预后提供重要的策略支持。

参考文献
1. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: utive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons[J]. Circulation. 2012 Dec 18;126(25):3097-137.
2. Nakazawa G, Otsuka F, Nakano M, et al. The Pathology of Neoatherosclerosis in Human Coronary Implants[J]. Jacc, 2011(11):1314-1322.
3. Lupi A, Rognoni A, Secco G G, et al. Biodegradable versus durable polymer drug eluting stents in coronary artery disease: insights from a meta-analysis of 5,834 patients.[J]. European Journal of Preventive Cardiology, 2014, 21(4):411-424.
4. Montalescot G, Sechtem U, Achenbach S, et al. Corrigendum to: ‘2013 ESC guidelines on the management of stable coronary artery disease’[J]. Perceptual & Motor Skills, 2013, 16(8):457-470.
5. Wiebe J, Nef H M, Hamm C W. Current Status of Bioresorbable Scaffoldsin the Treatment of CoronaryArtery Disease[J]. Journal of the American College of Cardiology, 2014, 64(23):2541-51.
6. Prati F, Jenkins M W, Giorgio A D, et al. Intracoronary optical coherence tomography, basic theory and image acquisition techniques.[J]. International Journal of Cardiovascular Imaging, 2011, 27(2):251-8.
7. Suzuki Y, Ikeno F, Koizumi T, et al. In Vivo Comparison Between Optical Coherence Tomography and Intravascular Ultrasound for Detecting Small Degrees of In-Stent Neointima After Stent Implantation[J]. Jacc Cardiovascular Interventions, 2008, 1(2):168-73.
8. Kwon S W, Kim B K, Kim T H, et al. Qualitative assessment of neointimal tissue after drug-eluting stent implantation: Comparison between follow-up optical coherence tomography and intravascular ultrasound[J]. American Heart Journal, 2011, 161(2):367–372.
9. Tearney G J, Regar E, Akasaka T, et al. Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies: A Report From the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation (vol 59, pg 1[J]. Journal of the American College of Cardiology, 2012, 59(12):1058-72.
10. Gutiérrez-Chico J L, Wykrzykowska J, Koch K, et al. Vascular tissue reaction to acute malapposition in human coronary arteries: sequential assessment with optical coherence tomography[J]. Circulation Cardiovascular Interventions, 2012, 60(17):B82.
11. Kawamori H, Shite J, Shinke T, et al. Natural consequence of post-intervention stent malapposition, thrombus, tissue prolapse, and dissection assessed by optical coherence tomography at mid-term follow-up[J]. European Heart Journal Cardiovascular Imaging, 2013, 14(9):865-875.
12. Kume T, Okura H, Miyamoto Y, et al. Natural history of stent edge dissection, tissue protrusion and incomplete stent apposition detectable only on optical coherence tomography after stent implantation – preliminary observation –. [J]. Circulation Journal Official Journal of the Japanese Circulation Society, 2012, 76(3):698-703.
13. Miyazaki S, Hiasa Y, Takahashi T, et al. In vivo optical coherence tomography assessment of very late drug-eluting stent thrombosis compared with late in-stent restenosis[J]. Circulation Journal, 2012, 76(2):390-8.
14. Kang S J, Lee C W, Song H, et al. OCT Analysis in Patients With Very Late Stent Thrombosis[J]. Jacc Cardiovascular Imaging, 2013, 6(6):695-703.
15. Gonzalo N, Serruys P W, Okamura T, et al. Optical coherence tomography assessment of the acute effects of stent implantation on the vessel wall: a systematic quantitative approach.[J]. Heart, 2009, 95(23):1913-1919.
16. Hou J, Jia H, Liu H, et al. Neointimal tissue characteristics following sirolimus-eluting stent implantation: OCT quantitative tissue property analysis[J]. International Journal of Cardiovascular Imaging, 2012, 28(8):1879-1886.
17. Seifarth H, Schlett C L, Nakano M, et al. Histopathological correlates of the napkin-ring sign plaque in coronary CT angiography[J]. Atherosclerosis, 2012, 224(1):90-96.
18. Won H, Shin D H, Kim B K, et al. Optical coherence tomography derived cut-off value of uncovered stent struts to predict adverse clinical outcomes after drug-eluting stent implantation[J]. International Journal of Cardiovascular Imaging, 2013, 29(6):1255-63.
19. Nakazawa G, Otsuka F, Nakano M, et al. The Pathology of Neoatherosclerosis in Human Coronary Implants[J]. Jacc, 2011(11):1314-1322.
20. Takano M, Yamamoto M, Shigenobu Inami, et al. Appearance of Lipid-Laden Intima and Neovascularization After Implantation of Bare-Metal Stents[J]. Journal of the American College of Cardiology, 2009, 55(1):26-32.
21. Yonetsu T, Kim J S, Kato K, et al. Comparison of Incidence and Time Course of Neoatherosclerosis Between Bare Metal Stents and Drug-Eluting Stents Using Optical Coherence Tomography[J]. American Journal of Cardiology, 2012, 110(7):933-9.
22. Yong X, Takano M, Murakami D, et al. Comparison of Neointimal Coverage by Optical Coherence Tomography of a Sirolimus-Eluting Stent Versus a Bare-Metal Stent Three Months After Implantation[J]. American Journal of Cardiology, 2008, 102(1):27-31.
23. Miyoshi N, Shite J, Shinke T, et al. Comparison by optical coherence tomography of paclitaxel-eluting stents with sirolimus-eluting stents implanted in one coronary artery in one procedure. - 6-month follow-up -.[J]. Circulation Journal Official Journal of the Japanese Circulation Society, 2010, 74(5):903-908.
24. Kim B K, Shin D H, Kim J S, et al. Randomized comparison of acute stent malapposition between platinum–chromium versus cobalt–chromium everolimus-eluting stents[J]. International Journal of Cardiovascular Imaging, 2015, 64(11):B170.
25. Inoue T, Shite J, Yoon J, et al. Optical coherence evaluation of everolimus-eluting stents 8 months after implantation[J]. Heart, 2010, 97(17):1379-84.
26. Ishibashi K, Tanaka A, Kitabata H, et al. Clinical significance of low signal intensity area surrounding stent struts identified by optical coherence tomography.[J]. International Heart Journal, 2013, 54(1):7-10.
27. Kitabata H, Kubo T, Komukai K, et al. Effect of strut thickness on neointimal atherosclerotic change over an extended follow-up period (≥4 years) after bare-metal stent implantation: Intracoronary optical coherence tomography examination[J]. American Heart Journal, 2012, 164(2):275-275.
28. Räber L, Baumgartner S, Garcia H M G, et al. Long-Term Vascular Healing in Response to Sirolimus- and Paclitaxel-Eluting Stents : An Optical Coherence Tomography Study[J]. Jacc Cardiovascular Interventions, 2012, 5(9):946-957.
29. Takano M; Inami S; Jang IK; Yamamoto M; Murakami D; Seimiya K; Ohba T; Mizuno K. Evaluation by Optical Coherence Tomography of Neointimal Coverage of Sirolimus -Eluting Stent Three Months After Implantation[J]. American Journal of Cardiology, 2007, 99(8):1033-8.
30. Kubo T; Imanishi T; Kitabata H; Kuroi A; Ueno S; Yamano T; Tanimoto T; Matsuo Y; Masho T; Takarada S; Tanaka A; Nakamura N; Mizukoshi M; Tomobuchi Y; Akasaka T. Comparison of Vascular Response After Sirolimus-Eluting Stent Implantation Between Patients With Unstable and Stable Angina Pectoris : A Serial Optical Coherence Tomography Study[J]. Jacc Cardiovascular Imaging, 2008, 1(4):475-84.
31. Kim J S, Fan C, Choi D, et al. Different patterns of neointimal coverage between acute coronary syndrome and stable angina after various types of drug-eluting stents implantation; 9-month follow-up optical coherence tomography study ☆[J]. International Journal of Cardiology, 2009, 146(3):341-6.
32. Mizoguchi T, Sawada T, Shinke T, et al. Detailed comparison of intra-stent conditions 12 months after implantation of everolimus-eluting stents in patients with ST-segment elevation myocardial infarction or stable angina pectoris[J]. International Journal of Cardiology, 2013, 171(2):224-230.
33. Guagliumi G, Costa MA, Sirbu V, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Inf[J]. Circulation, 2011, 123(3):274-281.
34. Sawada T, Shinke T, Otake H, et al. Comparisons of detailed arterial healing response at seven months following implantation of an everolimus- or sirolimus-eluting stent in patients with ST-segment elevation myocardial infarction.[J]. International Journal of Cardiology, 2013, 168(2):960–966.
35. Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, Garcia-Garcia HM, Nieman K, Bruining N, Dorange C, Miquel-Hébert K, Veldhof S, Webster M,Thuesen L, Dudek D. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results frommultiple imaging methods. Lancet. 2009; 373(9667): 897-910.
36. Serruys PW, Onuma Y, Ormiston JA, de Bruyne B, Regar E, Dudek D, Thuesen L, Smits PC, Chevalier B, McClean D, Koolen J, Windecker S, Whitbourn R, Meredith I, Dorange C, Veldhof S, Miquel-Hebert K, Rapoza R, García-García HM. Evaluation of the second generation of a bioresorbable everolimus drug-eluting vascular scaffold for treatment of de novo coronary artery stenosis: six-month clinical and imaging outcomes. Circulation. 2010; 122(22):2301-12.
37. Serruys PW, Onuma Y, Dudek D, Smits PC, Koolen J, Chevalier B, de Bruyne B, Thuesen L, McClean D, van Geuns RJ, Windecker S, Whitbourn R, Meredith I, Dorange C, Veldhof S, Hebert KM, Sudhir K, Garcia-Garcia HM, Ormiston JA. Evaluation of the second generation of a bioresorbable everolimus-eluting vascular scaffold for the treatment of de novo coronary artery stenosis: 12-month clinical and imaging outcomes. J Am Coll Cardiol. 2011; 58(15): 1578-88.
38. Puricel S, Cuculi F, Weissner M, Schmermund A, Jamshidi P, Nyffenegger T, Binder H, Eggebrecht H, Münzel T, Cook S, Gori T. Bioresorbable Coronary Scaffold Thrombosis: Multicenter Comprehensive Analysis of Clinical Presentation, Mechanisms, and Predictors. J Am Coll Cardiol 2016; 67(8): 921-31.


    2016/7/10 12:34:53     访问数:939
    转载请注明:内容转载自365医学网

文内提及

大家都在说       发表留言

客服中心 4000680365  service@365yixue.com
编辑部   editor@365yixue.com

365医学网 版权所有 © 365heart All Rights Reserved.

京ICP备12009013号-1
京卫网审[2013]第0056号
京公网安备110106006462号
京ICP证041347号
互联网药品信息服务资格证书(京)-经营性-2018-0016  
搜专家
搜医院
搜会议
搜资源
 
先点击
再选择添加到主屏