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

BackgroundAnomalous 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. MethodsThis 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. ResultsStress 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). ConclusionsIn 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. Clinical PerspectivesO_ST_ABSWhat is new?C_ST_ABSO_LIIn this single-center registry of adults with anomalous aortic origin of a coronary artery (AAOCA), 75% of patients had stress testing, enabling the largest analysis of how anomalous coronary morphology impacts stress testing practices and the presence of ischemia. C_LIO_LIConsistent with published data in younger AAOCA cohorts, our adult population (mean age >50 years) trended toward increased risk of ischemia with an anomalous left coronary and intramural course. C_LIO_LIComparing various stress test modalities for AAOCA, instantaneous wave-free, followed by positron emission tomography and single-photon emission computed tomography, have higher odds of being positive for ischemia than electrocardiogram and echocardiograms. C_LI What are the clinical implications?O_LIAdults with AAOCA remain at risk for ischemia and require careful risk stratification, with coronary morphology and clinical symptoms informing stress test selection and result interpretation. C_LIO_LIFor higher risk morphologic variants of AAOCA, consider further risk stratification with invasive coronary provocative studies to detect inducible ischemia. C_LI