Rong Bing1, Marcus-André Deutsch2, Stephanie L Sellers3, Carlos Alcaide Corral4, Jack P M Andrews4, Edwin J R van Beek5, Sabine Bleiziffer6, Wolfgang Burchert7, Tim Clark8, Damini Dey9, Kai Friedrichs10, Jan F Gummert6, Norman Koglin11, Jonathon A Leipsic3, Oliver Lindner7, Mark G MacAskill4, Hendrik Milting12, Renzo Pessotto13, Rainer Preuss7, Jennifer B Raftis4, Tanja K Rudolph10, Volker Rudolph10, Piotr Slomka9, Andrew W Stephens11, Adriana Tavares4, Evangelos Tzolos4, Nick Weir8, Audrey C White4, Michelle C Williams5, Reinhard Zabel7, Marc R Dweck4, Verena Hugenberg7, David E Newby4. 1. BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: rong.bing@ed.ac.uk. 2. Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany. Electronic address: mdeutsch@hdz-nrw.de. 3. Department of Radiology and Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, British Columbia, Canada. 4. BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. 5. BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Edinburgh Imaging, Queen's Medical Research Institute, Edinburgh, United Kingdom. 6. Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany. 7. Institute of Radiology, Nuclear Medicine and Molecular Imaging, Heart and Diabetes Center North Rhine-Westphalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany. 8. Edinburgh Imaging, Queen's Medical Research Institute, Edinburgh, United Kingdom. 9. Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA. 10. Department of General and Interventional Cardiology/Angiology, Heart and Diabetes Center North Rhine-Westphalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany. 11. Life Molecular Imaging GmbH, Berlin, Germany. 12. Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Heart and Diabetes Center North Rhine-Westphalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany. 13. Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
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).
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).