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ObjectivesThe aim of this study was to describe the potential of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression.BackgroundAs well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis.MethodsPatients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery.ResultsAmong 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting.ConclusionsNative coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.

Background: The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction., Objectives: The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18 F-GP1., Methods: In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary 18 F-GP1 PET/CT angiography. Coronary artery 18 F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios., Results: 18 F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary 18 F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher 18 F-GP1 uptake. Extracoronary cardiac 18 F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus., Conclusions: Coronary 18 F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With 18 F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966)., Competing Interests: Funding Support and Author Disclosures The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board. This work was supported by several grant funding organizations. Drs Tzolos (FS/CRTF/20/24086), Williams (FS/ICRF/20/26002, FS/11/014, and CH/09/002), Newby (CH/09/002, RG/16/10/32375, and RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr van Beek is supported by the Scottish Imaging Network: A Platform of Scientific Excellence. Dr Mills is supported by the British Heart Foundation through the award of Personal Chair and a Programme Grant (CH/F/21/90010 and RG/20/10/34966). Dr Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). Dr Slomka and FusionQuant analysis tools are supported by National Heart, Lung, and Blood Institute grant 5R01HL135557. Dr Dey and Autoplaque analysis tools are supported by National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. Drs Koglin and Stephens are employees of Life Molecular Imaging, which provided reagents for radiotracer production. Dr Williams is a member of the Speakers Bureau for Canon Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Acute aortic syndrome is associated with aortic medial degeneration. 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) detects microscopic tissue calcification as a marker of disease activity., Objectives: In a proof-of-concept study, this investigation aimed to establish whether 18 F-NaF PET combined with computed tomography (CT) angiography could identify aortic medial disease activity in patients with acute aortic syndrome., Methods: Patients with aortic dissection or intramural hematomas and control subjects underwent 18 F-NaF PET/CT angiography of the aorta. Aortic 18 F-NaF uptake was measured at the most diseased segment, and the maximum value was corrected for background blood pool activity (maximum tissue-to-background ratio [TBR max ]). Radiotracer uptake was compared with change in aortic size and major adverse aortic events (aortic rupture, aorta-related death, or aortic repair) over 45 ± 13 months., Results: Aortic 18 F-NaF uptake co-localized with histologically defined regions of microcalcification and elastin disruption. Compared with control subjects, patients with acute aortic syndrome had increased 18 F-NaF uptake (TBR max : 1.36 ± 0.39 [n = 20] vs 2.02 ± 0.42 [n = 47] respectively; P < 0.001) with enhanced uptake at the site of intimal disruption (+27.5%; P < 0.001). 18 F-NaF uptake in the false lumen was associated with aortic growth (+7.1 mm/year; P = 0.011), and uptake in the outer aortic wall was associated with major adverse aortic events (HR: 8.5 [95% CI: 1.4-50.4]; P = 0.019)., Conclusions: In patients with acute aortic syndrome, 18 F-NaF uptake was enhanced at sites of disease activity and was associated with aortic growth and clinical events. 18 F-NaF PET/CT holds promise as a noninvasive marker of disease severity and future risk in patients with acute aortic syndrome. ( 18 F Sodium Fluoride PET/CT in Acute Aortic Syndrome [FAASt]; NCT03647566)., Competing Interests: Funding Support and Author Disclosure All funding support is from the United Kingdom. Mr Syed and Drs Fletcher, Dweck, Shah, and Tavares, Mr Kaczynki, and Dr Newby were supported by the British Heart Foundation (FS/18/31/33676, FS/19/15/34155, FS/11/014, FS/14/78/31020, CH/09/002, RG/16/10/32375, RE/18/5/34216). Dr Dweck has received the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). Dr Newby has received a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr van Beek has been supported by the Scottish Imaging Network—a Platform of Scientific Excellence (SINAPSE). Edinburgh Clinical Research Facility and Edinburgh Imaging Facility are supported by NHS Research Scotland. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

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)., Competing Interests: Funding Support and Author Disclosures This work was funded by the British Heart Foundation, London, United Kingdom (RG/16/10/32375 and PG/19/40/34422). The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland (NRS) through National Health Service Lothian Health Board. This work and Drs Bing, Tzolos, Williams, Dweck, and Newby are supported by the British Heart Foundation (PG/19/40/34422, FS/ICRF/20/26002, FS/CRTF/20/24086, FS/14/78/31020, CH/09/002, RG/16/10/32375, RE/18/5/34216, FS/SCRF/21/32010). Dr van Beek is supported by the Scottish Imaging Network. Dr Sellers is supported by fellowships from the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research. Drs Koglin and Stephens are employees of Life Molecular Imaging GmbH, who provided reagents for radiotracer production. Dr Leipsic is supported by a Canadian Research Chair in Advanced CardioPulmonary Imaging and the Jon DeHaan Award for Innovation in Cardiology; is a consultant for Edward Lifesciences; and provides computed tomography core laboratory services to Edwards Lifesciences, Medtronic, Neovasc, Aegis, and Tendyne, for which no direct compensation is received. Dr Williams is supported by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (PCL/17/04). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)