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 Raftis; Tanja 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

doi:10.1016/j.jcmg.2021.11.015

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 journal › Article › peer-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 (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).

Original language	English
Pages (from-to)	1107-1120
Journal	JACC: Cardiovascular Imaging
Volume	15
Issue number	6
Early online date	11 Jan 2022
DOIs	https://doi.org/10.1016/j.jcmg.2021.11.015
Publication status	Published - 12 Jan 2022

Keywords / Materials (for Non-textual outputs)

18F-GP1
bioprosthetic aortic valve replacement
positron emission tomography-computed tomography
thrombus

Access to Document

10.1016/j.jcmg.2021.11.015

Bing-JIMG070221-1057-TRAccepted author manuscript, 131 KB

Myocardial fibrosis activity in cardiovascular disease
Dweck, M. (Principal Investigator)
UK-based charities
1/12/21 → 30/11/24
Project: Research
Incidence, consequences and natural history of left ventricular thrombus after acute anterior myocardial infarction
Dweck, M. (Principal Investigator), Newby, D. (Co-investigator) & Tzolos, E. (Co-investigator)
UK-based charities
1/02/20 → 31/01/22
Project: Research
Bioprosthetic Valve Thrombosis
Newby, D. (Principal Investigator), Dweck, M. (Co-investigator), Tavares, A. (Co-investigator) & van Beek, E. (Co-investigator)
UK-based charities
1/06/19 → 31/05/21
Project: Research

Edinburgh Imaging Facility
Grant, A. (Manager), van Beek, E. (Manager) & Semple, S. (Manager)
Deanery of Clinical Sciences
Facility/equipment: Facility
Edinburgh Preclinical Imaging
Moran, C. (Manager), Thomson, A. (Manager), Lennen, R. J. (Manager), Tavares, A. (Manager), Alcaide-Corral, C. J. (Manager), Morgan, T. (Other), Cranston, I. (Other) & O'Rourke, K. (Other)
Deanery of Clinical Sciences
Facility/equipment: Facility

Cite this

Bing, R., Deutsch, M.-A., Sellers, S. L., Corral, C. A., Andrews, J. P. M., van Beek, E. J. R., Bleiziffer, S., Burchert, W., Clark, T., Dey, D., Friedrichs, K., Gummert, J. F., Koglin, N., Leipsic, J. A., Lindner, O., MacAskill, M. G., Milting, H., Pessotto, R., Preuss, R., ... Newby, D. E. (2022). 18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus. JACC: Cardiovascular Imaging, 15(6), 1107-1120. https://doi.org/10.1016/j.jcmg.2021.11.015

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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).",

keywords = "18F-GP1, bioprosthetic aortic valve replacement, positron emission tomography-computed tomography, thrombus",

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

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day = "12",

doi = "10.1016/j.jcmg.2021.11.015",

language = "English",

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journal = "JACC: Cardiovascular Imaging",

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Bing, R, Deutsch, M-A, Sellers, SL, Corral, CA, Andrews, JPM, van Beek, EJR, Bleiziffer, S, Burchert, W, Clark, T, Dey, D, Friedrichs, K, Gummert, JF, Koglin, N, Leipsic, JA, Lindner, O, MacAskill, MG, Milting, H, Pessotto, R, Preuss, R, Raftis, JB, Rudolph, TK, Rudolph, V, Slomka, P, Stephens, AW, Tavares, A, Tzolos, E, Weir, N, White, AC, Williams, MC, Zabel, R, Dweck, MR, Hugenberg, V & Newby, DE 2022, '18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus', JACC: Cardiovascular Imaging, vol. 15, no. 6, pp. 1107-1120. https://doi.org/10.1016/j.jcmg.2021.11.015

TY - JOUR

T1 - 18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus

AU - Bing, Rong

AU - Deutsch, Marcus-André

AU - Sellers, Stephanie L

AU - Corral, Carlos Alcaide

AU - Andrews, Jack P M

AU - van Beek, Edwin J R

AU - Bleiziffer, Sabine

AU - Burchert, Wolfgang

AU - Clark, Tim

AU - Dey, Damini

AU - Friedrichs, Kai

AU - Gummert, Jan F

AU - Koglin, Norman

AU - Leipsic, Jonathon A

AU - Lindner, Oliver

AU - MacAskill, Mark G

AU - Milting, Hendrik

AU - Pessotto, Renzo

AU - Preuss, Rainer

AU - Raftis, Jennifer B

AU - Rudolph, Tanja K

AU - Rudolph, Volker

AU - Slomka, Piotr

AU - Stephens, Andrew W

AU - Tavares, Adriana

AU - Tzolos, Evangelos

AU - Weir, Nick

AU - White, Audrey C

AU - Williams, Michelle C

AU - Zabel, Reinhard

AU - Dweck, Marc R

AU - Hugenberg, Verena

AU - Newby, David E

PY - 2022/1/12

Y1 - 2022/1/12

N2 - 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).

AB - 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).

KW - 18F-GP1

KW - bioprosthetic aortic valve replacement

KW - positron emission tomography-computed tomography

KW - thrombus

U2 - 10.1016/j.jcmg.2021.11.015

DO - 10.1016/j.jcmg.2021.11.015

M3 - Article

C2 - 35033495

SN - 1936-878X

VL - 15

SP - 1107

EP - 1120

JO - JACC: Cardiovascular Imaging

JF - JACC: Cardiovascular Imaging

IS - 6

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

Myocardial fibrosis activity in cardiovascular disease

Incidence, consequences and natural history of left ventricular thrombus after acute anterior myocardial infarction

Bioprosthetic Valve Thrombosis

Equipment

Edinburgh Imaging Facility

Edinburgh Preclinical Imaging

Cite this