Degenerative histopathology in ascending aortic aneurysms: comparative analysis by aneurysm location

Aortic aneurysms have traditionally been studied as a single pathological entity, with emphasis on valve morphology. While histopathological differences between bicuspid (BAV) and tricuspid (TAV) aortopathy are well documented, less is known about how these mechanisms interact with aneurysm location within the ascending aorta. This gap complicates risk assessment and surgical planning beyond diameter-based criteria. We aimed to evaluate histopathological features of ascending aortic aneurysms across three topographical subgroups-root, tubular, and combined involvement-and assess modification by valve cuspidity. Using systematic criteria from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology consensus statement, the analysis focused on medial degeneration, adventitial alterations and atherosclerosis in patients undergoing ascending aortic surgery at a Finnish tertiary care center. The cohort comprised 296 patients with aneurysms located in the sinus of Valsalva (n = 122), tubular part (n = 130), and both regions (n = 44). Medial degeneration was present in all samples and predominantly moderate, with comparable median severity score of 2 (range 1-3, P = 0.829) across groups. In the overall cohort, no statistically significant differences were observed between topographical groups. Among TAV patients, tubular aneurysms demonstrated significantly higher histopathological scores for medial degeneration, elastic fiber fragmentation and loss, elastic fiber disorganisation, smooth muscle cell disorganization and nuclei loss, laminar medial collapse, medial fibrosis, adventitial fibrosis and atherosclerosis (all P < 0.05). In BAV patients, no statistical differences were found. Tubular aneurysms are characterized by more extensive wall remodeling and adventitial changes compared to root aneurysms, particularly in TAV patients. Notably, female sex emerged as a strong independent predictor of advanced medial and adventitial pathology. These findings underscore the importance of considering anatomical location, valve morphology, and sex in risk stratification and may inform surgical decision-making beyond diameter-based criteria.