Hara Tetsuya, Ughi Giovanni J, McCarthy Jason R, Erdem S Sibel, Mauskapf Adam, Lyon Samantha C, Fard Ali M, Edelman Elazer R, Tearney Guillermo J, Jaffer Farouc A
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Eur Heart J. 2017 Feb 7;38(6):447-455. doi: 10.1093/eurheartj/ehv677. Epub 2015 Dec 18.
Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage.
Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001).
Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing.
纤维蛋白沉积和内皮缺失是未愈合支架的特征,这类支架发生支架血栓形成的风险较高。光学相干断层扫描(OCT)越来越多地用于评估支架组织覆盖情况,以此作为支架愈合的一项指标,但无法精确识别覆盖组织是否代表生理性新生内膜。在此,我们采用近红外荧光(NIRF)分子成像技术在体内评估并比较了裸金属支架(BMS)和药物洗脱支架(DES)上的纤维蛋白沉积及持续存在情况,并结合同步进行的OCT支架覆盖情况评估。
对兔肾下主动脉植入一枚BMS和一枚DES,两者不重叠(N = 20;3.5×12 mm)。在第7天和/或第28天,注射靶向纤维蛋白的NIRF分子成像剂FTP11-CyAm7后进行血管内NIRF-OCT检查。血管内NIRF-OCT能够在体内对覆盖于支架支柱上的纤维蛋白进行高分辨率成像,这已通过组织病理学得到验证。与BMS相比,DES在第7天和第28天显示出更多的纤维蛋白沉积和纤维蛋白持续存在情况(与BMS相比,P < 0.01)。值得注意的是,对于在第7天被OCT判定为已覆盖的边缘支架支柱,DES的92.8±9.5%和BMS的55.8±23.6%的支柱NIRF纤维蛋白呈阳性(P < 0.001)。在第28天,OCT覆盖的支柱中,18.6±10.6%(DES)和5.1±8.7%(BMS)仍为纤维蛋白阳性(P < 0.001)。
血管内NIRF纤维蛋白分子成像利用可临床转化的技术改进了对未愈合支架的检测,该技术可补充OCT。相当比例的被OCT判定为已覆盖的支柱实际上被纤维蛋白覆盖,尤其是在DES中,因此这类支架可能仍具有血栓形成倾向。这些发现对支架愈合的独立临床OCT评估的特异性具有重要意义。