Available online 16 September 2022

Aortic valve stenosis is the most common valvular disease in Western countries, while atherosclerotic cardiovascular disease is the foremost cause of death and disability worldwide. Valve degeneration and atherosclerosis are mediated by inflammation and calcification and inevitably progress over time. Computed tomography can visualise the later stages of macroscopic calcification but fails to assess the early stages of microcalcification and cannot differentiate active from burnt out disease states. Molecular imaging has the ability to provide complementary information related to disease activity, which may allow us to detect disease early, to predict disease progression and to monitor preventive or therapeutic strategies for in both aortic stenosis and atherosclerosis. PET/CT is a non-invasive imaging technique that enables visualization of ongoing molecular processes within small structures, such as the coronary arteries or heart valves. 18F-sodium fluoride (18F-NaF) binds hydroxyapatite deposits in the extracellular matrix, with preferential binding to newly developing deposits of microcalcification, which provides an assessment of calcification activity. In recent years, 18F-NaF has attracted the attention of many research groups and has been evaluated in several pathological cardiovascular processes. Histologic validation of the 18F-NaF PET signal in valvular disease and atherosclerosis has been reported in multiple independent studies. The selective high-affinity binding of 18F-NaF to microscopic calcified deposits (beyond the resolution of μCT) has been demonstrated ex vivo, as well as its ability to distinguish between areas of macro- and active microcalcification. In addition, prospective clinical studies have shown that baseline 18F-NaF uptake in patients with aortic stenosis and mitral annular calcification is correlated with subsequent calcium deposition and valvular dysfunction after a follow-up period of 2 years. In patients with surgical bioprosthetic aortic valves but without morphological criteria for prosthetic degeneration, increased 18F-NaF uptake at baseline was associated with subsequent bioprosthetic degeneration over time. Similar data were obtained in a cohort of patients with transcatheter aortic valve implantation. Furthermore, several studies have confirmed the association of coronary 18F-NaF uptake with adverse atherosclerotic plaque features, active disease and future disease progression. 18F-NaF uptake is also associated with future fatal or nonfatal myocardial infarction in patients with established coronary artery disease. The link between 18F-NaF uptake and active atherosclerotic disease has not only been demonstrated in the coronary arteries, but also in peripheral arterial disease, abdominal aortic aneurysms and carotid atherosclerosis. It can be assumed that 18F-NaF PET/CT will strengthen the diagnostic toolbox of practitioners in the coming years. Indeed, there is a strong medical need to diagnose degenerative valvular disease and to detect active atherosclerotic disease states. Finally, the use of 18F-NaF as a biomarker to monitor the efficacy of drug therapies in preventing these pathological processes is attractive. In this review, we consider the role of 18F-NaF PET/CT imaging in cardiac valvular diseases and atherosclerosis.

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