Multimodal Stress Testing and Morphologic Predictors of Ischemia in Anomalous Aortic Origin of a Coronary Artery

Background: Anomalous aortic origin of a coronary artery (AAOCA) can cause myocardial ischemia and sudden cardiac death. The optimal stress-testing strategy and impact of coronary morphology on ischemia remain unclear. We assessed the effect of coronary morphology on stress-test completion and results across multiple test modalities. Methods: This retrospective cohort study included 531 adults with AAOCA at our institution (7/2015 – 3/2023). Coronary morphology was characterized by the anomalous coronary (right [RCA], left main [LMCA], left anterior descending [LAD], left circumflex) and the course type (intramural, interarterial-only, transseptal, and other [prepulmonic and retroaortic]). Exercise and pharmacologic stress tests were positive if ischemia included the territory of the anomalous coronary. A mixed-effect logistic regression modeled the odds of a positive test based on morphology, comorbidities, and modality. A random forest regression analyzed the stress iFR as a continuous outcome. Results: Stress test results were available for 396 (75%) of patients (age 50 +/- 17 years; 42% female). Stress testing included 699 ECGs, 198 echocardiograms, 288 SPECTs, 133 PETs, and 103 dobutamine iFR studies. Completion of invasive dobutamine iFR (versus noninvasive-only) stress testing was associated with high-risk coronary morphology, p<0.001. Coronary morphology that trended toward higher adjusted odds of ischemia included the anomalous LMCA (OR: 2.1, p=0.054) and intramural course (OR: 1.9, p=0.14). Compared to ECG, iFR had higher adjusted odds of a positive result (OR: 27, p<0.001), followed by PET (OR: 9.0, p<0.001). In the random forest regression, stress iFR value was lowest for LAD (0.75) compared to LMCA (0.83) and RCA (0.84). For course type, transseptal (strongly correlated with the anomalous LAD) had the lowest stress iFR (0.77), followed by intramural (0.83), and interarterial (0.88). Conclusions: In our adult AAOCA cohort, high-risk coronary morphology demonstrated a borderline association with ischemia on stress testing, whereas stress test modality was the strongest determinant of ischemia detection. Invasive stress testing was reserved for higher-risk coronary morphology. These findings underscore that effective risk stratification in AAOCA integrates clinical symptoms, coronary morphology, and stress test modality. Long-term follow-up is needed to determine the optimal strategy for ischemia evaluation.