Multi-tracer positron emission tomography and bioprosthetic aortic valve function

Abstract Background Structural valve degeneration limits the lifespan of bioprosthetic aortic valves, yet its pathogenesis remains incompletely understood. Positron emitting radiotracers, fluorine-18 GP1 (18FGP1), gallium-68 fibroblast activation protein inhibitor (68GaFAPI-46) and fluorine-18 sodium fluoride (18FNaF), provide a readout of thrombosis, fibrosis and microcalcification activity, respectively. Understanding the interplay between these processes may inform novel valve designs or medical treatments to extend bioprosthetic valve durability. Purpose To assess the relationship between thrombosis, fibrosis and microcalcification, and their impact on structural bioprosthetic valve degeneration. Methods In a prospective single-centre study, patients with prior surgical or transcatheter aortic valve replacement underwent transthoracic echocardiography and hybrid computed tomography angiography and positron emission tomography with 18FGP1, 18FNaF and 68GaFAPI-46 radiotracers at three distinct timepoints. Radiotracer uptake was quantified using the maximum (SUVmax) and mean (SUVmean) standardised uptake values within a standardised volume of interest including the leaflets, but not the struts of the bioprosthetic aortic valves. Results A total of 31 participants were recruited between October 2019 and March 2021. Most (87%) were male with a median age of 72 years (IQR 66 – 76). The majority (84%) had undergone surgical valve replacement at a median of 45 months (IQR 13 – 80) prior to their baseline visit. Of the 28 participants who attended all study visits, 12 (42.9%) had at least 1 haemodynamic marker of valve dysfunction on echocardiography, although only 1 patient had clinically significant structural valve degeneration. 18FGP1 and 68Ga-FAPI-46 uptake were visualised in the leaflets of all bioprosthetic aortic valves, whilst 18FNaF uptake was seen in 77.4% (figure 1). 18FGP1 activity (measured using both SUVmax, and SUVmean for the whole valve) was positively associated with both 18FNaF and 68GaFAPI-46 activity. (figure 2). In this modest sample size, there were no differences in uptake of 18FGP1, 18FNaF or 68GaFAPI-46 between participants with and without haemodynamic markers of bioprosthetic valve degeneration. Conclusion Active thrombosis, fibrosis and microcalcification commonly occur on bioprosthetic aortic valves. Greater thrombosis activity is associated with both increased fibroblast activation and calcification activity, suggesting it may play an important role alongside these other processes in the pathophysiology of bioprosthetic valve degeneration. Adequately sized, longitudinal cohort studies are required to further delineate these pathways.Figure 1. Figure 2.