Molecular Calcification Imaging and Ascending Aortic Disease in Patients With a Bicuspid Aortic Valve.

Importance: Selection of patients with a bicuspid aortic valve and aortopathy for prophylactic aortic surgery remains challenging. In thoracic aortopathy, aortic medial elastin fiber fragmentation initially leads to microcalcification but later declines with progressive loss of elastin content and reduced structural integrity. Objective: To determine whether aortic microcalcification detected using fluorine F 18-labeled [18F]-sodium fluoride positron emission tomography (PET) is associated with future aortic diameter expansion. Design, Setting, and Participants: This prospective longitudinal cohort study was conducted in tertiary care centers across Scotland from April 4, 2019, to September 15, 2023. Participants included patients with a bicuspid aortic valve. Data analysis was performed from May 21, 2024, to March 4, 2025. Exposures: Hybrid [18F]-sodium fluoride PET and computed tomography. Main Outcomes and Measures: Baseline ascending aortic [18F]-sodium fluoride uptake was measured as mean tissue to background ratio. The primary outcome was ascending aortic diameter expansion during 24 months on cardiac magnetic resonance imaging (MRI). Results: Seventy-six patients with a bicuspid aortic valve (mean [SD] age, 52.6 [7.5] years; 57 [75.0%] male) underwent baseline [18F]-sodium fluoride PET and MRI. Fifty-six patients underwent follow-up MRI after a median of 723 (IQR, 515-787) days. There was an inverse correlation between baseline ascending aortic [18F]-sodium fluoride uptake and annual change in diameter (Pearson r = -0.37; P = .005), which remained after adjustment for confounders in multivariable regression analysis. Ascending aortic [18F]-sodium fluoride was not correlated with baseline diameter (Pearson r = 0.08; P = .50) but was moderately correlated with baseline ascending aortic stiffness index (Pearson r = 0.38; P < .001). Conclusion and Relevance: In this cohort study of patients with a bicuspid aortic valve, the most rapid aortic growth was seen in those with low [18F]-sodium fluoride ascending aortic uptake, indicating reduced aortic wall integrity. High ascending aortic [18F]-sodium fluoride uptake was associated with a stiffer and slow-growing ascending aortic phenotype. These findings suggest that [18F]-sodium fluoride PET imaging represents a promising new noninvasive approach to identify a microcalcified disease phenotype in thoracic aortopathy among patients with a bicuspid aortic valve.