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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

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

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 to 3.48) vs 1.43 (IQR: 1.28 to 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).

Original languageEnglish
JournalJACC: Cardiovascular Imaging
Early online date11 Jan 2022
DOIs
Publication statusPublished - 12 Jan 2022

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