Histopathological zonal patterns in ascending aortic aneurysm with bicuspid and tricuspid aortic valves

While medial degeneration is the recognized substrate of ascending thoracic aortic aneurysm (TAA), data on its regional heterogeneity are lacking, particularly regarding bicuspid (BAV) and tricuspid (TAV) aortic valves. This study performed level-by-level histological analysis of the ascending aorta in TAA. Surgical specimens from sinotubular junction (STJ), mid-ascending aorta (AscA), and proximal aortic arch (PrAA) were obtained from 66 TAA patients (25 BAV, 41 TAV). Histological assessment followed SCVP/AECVP criteria. Medial degeneration was universal (100%), with elastic fiber fragmentation most prevalent across all levels. TAV patients exhibited a more severe phenotype, with significantly higher prevalence of translamellar mucoid accumulation (T-MEMA) in STJ (54% vs. 24%, p = 0.019) and AscA (45% vs. 13%, p = 0.010), diffuse elastic fiber loss in STJ (29% vs. 8%, p = 0.041), and smooth muscle cell nuclei loss in STJ (41% vs. 16%, p = 0.032) and AscA (50% vs. 22%, p = 0.028). Atherosclerosis was significantly more prevalent in TAV patients overall (65.9% vs. 28.0%, p = 0.003) and specifically in PrAA (43% vs. 14%, p = 0.021), with severe lesions exclusive to this group. This first systematic multi-level analysis reveals that TAA is characterized by regional and valve-dependent heterogeneity: in TAV patients, degenerative markers predominated proximally, whereas atherosclerotic involvement was more pronounced distally.