Hybrid fluorine F 18-labelled-sodium fluoride ([18F]-sodium fluoride) positron emission tomography with computed tomography (PET-CT) imaging could help to identify patients with a bicuspid aortic valve at higher risk of progressive aortic enlargement, offering a potential novel approach to risk stratification beyond conventional diameter-based measurements.

Selecting patients with a bicuspid aortic valve for preventative aortic surgery is challenging as many individuals who later experience aortic dissection have diameters below current surgical thresholds.

A prospective cohort study conducted across tertiary care centres in Scotland between April 2019 and September 2023 and published in JAMA Network Open, examined whether hybrid [18F]-sodium fluoride PET-CT imaging could identify patients with a bicuspid aortic valve at greater risk of ascending aortic expansion.

The study enrolled 76 adults with a bicuspid aortic valve identified through cardiology clinics. Participants had a mean age of 52.6 years and 75% were male.

At baseline, all underwent hybrid [18F]-sodium fluoride PET-CT imaging followed immediately by cardiac magnetic resonance imaging (MRI) to assess aortic size and structure.

Follow-up MRI was performed after a median of 723 days (interquartile range (IQR) 515–787 days) in 56 patients to assess changes in ascending aortic diameter, which was the primary study outcome.

The median annual change in diameter was 0.6 mm per year (IQR 0.2–0.8), with observed changes ranging from –1.0 to 2.4 mm.

[18F]-sodium fluoride uptake and aortic expansion

Baseline uptake of [18F]-sodium fluoride in the ascending aorta, measured as a tissue-to-background ratio, showed a moderate inverse association with subsequent aortic growth. Lower baseline radiotracer uptake was associated with faster expansion of the ascending aorta (Pearson r = −0.37; P = 0.005).

This association remained significant after adjustment for potential confounders, including coarctation status (β = 0.70; 95% CI 0.55–0.88; P = 0.004). In contrast, factors such as age, sex, hypertension, diabetes, smoking status, aortic valve morphology and baseline aortic diameter were not associated with changes in aortic size during follow-up.

Higher [18F]-sodium fluoride uptake correlated with greater ascending aortic stiffness (Pearson r = 0.38; P < 0.001) – an association that persisted after adjustment for age, diabetes and baseline aortic diameter (β = 1.33; 95% CI 1.08–1.62; P = 0.007).

However, PET uptake was not associated with baseline aortic diameter (r = 0.08; P = 0.50), suggesting that microcalcification activity may represent a bicuspid aortic valve disease process independent of anatomical enlargement.

Implications for bicuspid aortic valve disease

Some caution is needed when interpreting the findings, however. As the study was conducted at a single centre with a relatively small cohort of patients with a bicuspid aortic valve, validation in larger populations and with patients having other types of aortopathy is necessary to determine whether this PET-CT imaging method could improve risk stratification and inform decisions on prophylactic aortic surgery.

Additionally, disease progression was evaluated using aortic expansion rather than clinical outcomes such as dissection or surgery, and follow-up was limited to two years, which may not capture longer-term complications.

The authors also emphasised that [18F]-sodium fluoride PET-CT imaging cannot distinguish between atherosclerotic and medial calcification, although the ascending aorta is usually less affected by atherosclerosis. Practical considerations such as cost, radiation exposure, and limited access to PET imaging may also influence clinical implementation.

The findings indicate two distinct bicuspid aortic valve disease subtypes. Higher [18F]-sodium fluoride uptake was associated with a microcalcified aortic wall phenotype that appeared independent of ascending aortic diameter.

In contrast, patients with low ascending aortic [18F]–sodium fluoride uptake had the most rapid aortic expansion, indicating reduced structural wall integrity and more progressive disease.

Taken together, the results suggest that [18F]-sodium fluoride PET imaging could represent a promising non-invasive approach for differentiating severe disease from less vulnerable forms in patients with a bicuspid aortic valve.

Reference
Nash J et al. Molecular Calcification Imaging and Ascending Aortic Disease in Patients With a Bicuspid Aortic Valve. JAMA Netw Open 2026;9(2):e2560385.