Abstract Body (Do not enter title and authors here): Background: Anomalous aortic origin of a coronary artery (AAOCA) is associated with myocardial ischemia (MI) and sudden cardiac death. Symptoms, positive stress tests, and presence of “high-risk” morphologic features guide management. However, the optimal stress-testing strategy and the extent to which anatomic features cause MI remain unclear. We sought to assess the effect of coronary morphology on the presence of a positive result in different stress test modalities.

Methods: We retrospectively studied 548 adults with AAOCA at our institution (July 2015 - March 2023). Coronary morphology, defined from operative and imaging reports, included the affected coronary (right [RCA], left main [LMCA], left anterior descending, left circumflex) and course type (intramural, interarterial-only, transeptal, and other [prepulmonic and retroaortic]). Exercise and pharmacologic stress tests were available in 397 (72%) of patients, comprising 701 ECGs, 198 echocardiograms, 288 SPECTs, 135 PETs, and 102 dobutamine iFR catheterizations (positive if iFR <0.86). Since tests were repeated (n = 1,424), we used mixed-effect logistic regression to model the probability of a positive result based on coronary morphology, age, sex, comorbidities (e.g. coronary artery disease, myocardial bridge), and modality. For patients with iFR, random forest regression assessed associations between iFR as a continuous variable and the same predictors.

Results: Mean age at AAOCA diagnosis was 50.4 ± 16.9 years (SD), and 67% had chest pain. Compared to anomalous RCA, anomalous LMCA was more likely to have a positive stress test (OR 2.4, p = 0.02). Intramural course trended toward positive result (OR 1.9, p = 0.14), while the transeptal and interarterial had smaller effects. Compared to ECG, iFR was most likely to be positive (OR 27, p < 0.001), followed by PET (OR 8.4, p < 0.001). In iFR-only analysis, course type was most associated with a positive result: transeptal had the lowest mean stress iFR (0.77), followed by intramural (0.83), and interarterial (0.85).

Conclusions: In our large adult AAOCA cohort, coronary morphology correlated with a positive stress test, but this relationship was inconsistent across modalities. High-risk morphologic features alone were not reliably predictive of a positive result, and integrating functional testing is essential for risk stratification that guides management. Long-term follow-up is needed to determine the best ischemia testing strategy.