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18F-GP1正电子发射断层扫描与生物人工主动脉瓣血栓

18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus.

作者信息

Bing Rong, Deutsch Marcus-André, Sellers Stephanie L, Corral Carlos Alcaide, Andrews Jack P M, van Beek Edwin J R, Bleiziffer Sabine, Burchert Wolfgang, Clark Tim, Dey Damini, Friedrichs Kai, Gummert Jan F, Koglin Norman, Leipsic Jonathon A, Lindner Oliver, MacAskill Mark G, Milting Hendrik, Pessotto Renzo, Preuss Rainer, Raftis Jennifer B, Rudolph Tanja K, Rudolph Volker, Slomka Piotr, Stephens Andrew W, Tavares Adriana, Tzolos Evangelos, Weir Nick, White Audrey C, Williams Michelle C, Zabel Reinhard, Dweck Marc R, Hugenberg Verena, Newby David E

机构信息

BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.

Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany.

出版信息

JACC Cardiovasc Imaging. 2022 Jun;15(6):1107-1120. doi: 10.1016/j.jcmg.2021.11.015. Epub 2022 Jan 12.

Abstract

BACKGROUND

Bioprosthetic valve thrombosis may have implications for valve function and durability.

OBJECTIVES

Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves.

METHODS

Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT.

RESULTS

Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake.

CONCLUSIONS

Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875).

摘要

背景

生物人工瓣膜血栓形成可能影响瓣膜功能及耐久性。

目的

使用新型糖蛋白IIb/IIIa受体放射性示踪剂18F-GP1,我们研究了正电子发射断层扫描(PET)-计算机断层扫描(CT)能否检测生物人工主动脉瓣膜上的血栓形成。

方法

对人血小板及离体生物人工主动脉瓣膜进行体外实验。在一项前瞻性横断面研究中,生物人工主动脉瓣膜或正常天然主动脉瓣膜患者接受了超声心动图、CT血管造影及18F-GP1 PET-CT检查。

结果

流式细胞术分析、组织学、免疫组化及放射自显影显示18F-GP1选择性结合活化血小板糖蛋白IIb/IIIa受体及附着于人工瓣膜的血栓。共招募75名参与者:53名生物人工瓣膜患者(植入后中位时间37个月[四分位间距:12 - 80个月])及22名正常天然主动脉瓣膜患者。3名参与者有瓣膜阻塞性血栓形成,另外3名参与者在CT血管造影上有无症状的低密度瓣叶增厚。所有生物人工瓣膜在瓣叶上均显示局灶性18F-GP1摄取,但天然主动脉瓣膜均未显示:最大目标与本底比值中位数2.81(四分位间距:2.29 - 3.48)对比1.43(四分位间距:1.28 - 1.53)(P < 0.001)。较高的18F-GP1摄取与瓣膜植入持续时间及低密度瓣叶增厚独立相关。所有3名有瓣膜阻塞性血栓形成的参与者接受了3个月抗凝治疗,症状缓解,平均瓣膜压差改善,18F-GP1摄取降低。

结论

活化血小板附着是生物人工主动脉瓣膜上常见且持续存在的现象。血栓存在时18F-GP1摄取较高,抗凝治疗后降低,其有作为辅助临床工具的潜力。(18F-GP1 PET-CT检测生物人工主动脉瓣膜血栓形成;NCT04073875)

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