18F-GP1 positron emission tomography and bioprosthetic aortic valve thrombus

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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-computed tomography (PET-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. Seventy-five participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 [12-80] months), 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, while a further three participants had asymptomatic hypoattenuated leaflet thickening (HALT) 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 [interquartile range 2.29 to 3.48] versus 1.43 [1.28 to 1.53] (p<0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and HALT. All three participants with obstructive valve thrombosis were anticoagulated for three 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 utility as an adjunctive clinical tool.
Original languageEnglish
JournalJACC: Cardiovascular Imaging
DOIs
Publication statusPublished - 12 Jan 2022

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