Histological assessment of the intramural segment in adults with an anomalous aortic origin of a coronary artery with an interarterial course

BACKGROUND: An intramural course in an anomalous aortic origin of a coronary artery (AAOCA) is a high-risk feature for sudden cardiac death (SCD). One of the proposed mechanisms for this association involves a "flap valve" effect in the intramural segment. The (patho-)histological characteristics of this segment may contribute to risk stratification, however, current data are scarce. The aim of this study was to identify the histological features of the intramural segment and their potential relevance to vascular wall properties and the aortic valve commissure, thereby providing insights into possible functional implications of AAOCA. METHODS: This prospective multicenter study included consecutive pediatric and adult AAOCA patients who underwent surgical unroofing between 2021 and 2024. The excised arterial vascular wall tissue (i.e. the intramural segment), was immunohistochemically examined for vascular wall components. Two independent observers reviewed the data, correlating findings with preoperative CTA to assess spatial relationships with surrounding aortic and AAOCA tissues. Results were also compared with a post-mortem AAOCA specimen and control tissues. RESULTS: Fifteen patients (mean age 42.9 ± 14.0 years, age range 11-66 years, 60% female) undergoing surgery for AAOCA were included. Fourteen patients (93%) had an anomalous aortic origin of a right coronary artery (AAORCA) and one patient (7%) had an anomalous aortic origin of a left coronary artery (AAOLCA). The mean intramural segment length was 7.8 ± 3.6 mm in AAORCA and 16.0 mm in the AAOLCA. Histologically, a two-layered tunica media without interposing tunica adventitia was identified in all intramural segments. Pre-operative CTA showed a close spatial relationship of the aortic side of the intramural segment with the aortic valve commissure. In line with this, extensive fibrous tissue was observed histologically on the aortic side of the intramural segment, consistent with commissure. In contrast, the vascular wall on the coronary arterial side of the intramural segment showed overall medial degeneration, characterized by mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, elastic fiber thinning, loss of smooth muscle cell nuclei, and collagen alterations. These abnormalities were more prevalent with increasing age. CONCLUSION: Histology of the intramural segment revealed structural alterations which may be consistent with reduced vascular compliance. Further studies, including post-SCD specimens, are needed to refine risk stratification.