Prevalence, anatomy and impact of abnormal aortic origin of a coronary artery (AOOCA) in non-genetic, non-atherosclerotic aneurysmal arteriopathies

Abstract Background Abnormal aortic origin of a coronary artery (AAOCA) is a congenital anomaly where a coronary artery arises from a wrong aortic location. The current complex classifications can be simplified into an abnormal origin from the wrong aortic coronary sinus (CS), with either a malignant (inter-arterial) or non-malignant course, also considering the angulated (slit-like) origin. The prevalence of isolated AAOCA in the general population is estimated to be 1% and up to 2-3% in coronary imaging seris. AAOCA can remain asymptomatic throughout life or cause myocardial ischemia, particularly during exertion in athletes, where it has been linked to an increased risk of sudden cardiac death. Coronary imaging ensures precise diagnosis. Its prevalence in genetic arteriopathies is unknown. Purpose The study aimed to assess the prevalence and types of AAOCA in suspected genetic arteriopathies with root and/or ascending dilation and high probability of aortic repair in the life course. Methods This is a retrospective observational study that included consecutive (2011-2024) patients who underwent validated institutional diagnostic work-up for suspected syndromic or isolated genetic arteriopathies. The work-up included clinical and genetic evaluation, multidisciplinary assessment, genetic counseling, NGS testing (multi gene panels, clinical exome in familial cases with negative gene panels), ECG-gated CCTA, whole-body CTA, and systematic follow-up. AAOCA was classified by origin (site/type) and course. Myocardial bridges were excluded. Scintigraphy was performed in symptomatic patients or those with mild kinesis abnormalities. Results The cohort consists of 1649 patients (981 males, 668 females, age: 42.28 ± 15.55 years) who were referred for clinical and genetic evaluation of syndromic and isolated arteriopathies: 1007 patients were genetic-positive and 642 genetic-negative (Table 1). We identified 50 AAOCA (3%), including 7 cases of a right coronary artery originating from the left coronary sinus with a malignant inter-arterial course; 6 left circumflex from the right coronary sinus with retroaortic course; 6 from the correct sinus but angulated, slit-like origin; 29 with less relevant abnormalities (Table 2). The prevalence did not differ in genetic-positive (34/1007, 3.3%) and genetic-negative cases (16/642, 2.5%) (p=0.31). No patients underwent surgery for AAOCA. Two patients experienced SCAD at rest. Conclusions In genetic and non-genetic arteriopathies, AAOCA prevalence aligns with imaging series, representing a comorbidity unrelated to genetic defects. ESC guidelines (IIbC) suggest considering surgery for asymptomatic patients with L-AAOCA under 35 without both myocardial ischemia and high-risk anatomy, yet decision-making remains complex for those likely to require TAA repair. While major complications are rare, the uncertainty surrounding long-term outcomes and management highlights the need for further research to refine clinical strategies.Table 1:CCTA cohort Table 2:AAOCA distribution