Fluid dynamics-informed CCTA-derived geometric parameters in right coronary artery anomalies predict abnormal invasive Adenosine-FFR and Dobutamine-FFR

Background Traditional anatomical assessment of stenosis in right anomalous aortic origin of coronary arteries (R-AAOCA) may not capture the complex, eccentrically shaped lumen and its perimeter-dependent resistance, and may therefore underestimate flow limitation. R-AAOCA involves both fixed stenosis, similar to atherosclerotic plaques (assessable with invasive adenosine-derived fractional flow reserve, FFR Adenosine ), and additional stress-induced dynamic stenosis; both components can be captured with dobutamine-derived FFR (FFR Dobutamine ). We hypothesized that fluid dynamics-informed geometric parameters provide a physiologically grounded description with enhanced discriminative value compared with conventional geometric parameters for predicting FFR Adenosine and FFR Dobutamine . Methods We performed a retrospective analysis of prospectively enrolled participants from the National Registry of Coronary Anomalies (NARCO) who underwent invasive FFR Adenosine and FFR Dobutamine assessment. We calculated multiple CCTA-derived geometric parameters organized into two categories: (1) conventional geometric parameters including cross-sectional area (A), perimeter (P), minor and major axes at the ostium and intramural lumen area (ILA; i.e., the point of maximal stenosis), and effective diameter (D eff = ( 4 A / π ) ); and conventional stenosis ratios including the area stenosis ratio (ASR) and effective diameter stenosis ratio (EDSR); (2) fluid dynamics-informed parameters comprising shape descriptors: including hydraulic diameter (D h = 4A/P), elliptic ratio (ER = major/minor axis), circularity (C = 4πA/P 2 ), and hydraulic diameter stenosis ratio (HDSR); and resistance-based indices including resistance index (RI = L × P 4 /A 4 ), ostial angulation penalty (OAP = A ostial /A ref × [1 + tan(θ)]), and comprehensive stenosis score (CSS = RI × ER × [1 + sin(θ)]) integrating resistance, shape-dependent losses, and take-off angle (θ) effects. The invasive reference was hemodynamic relevance (i.e. FFR≤0.80) in FFR Adenosine and FFR Dobutamine . We assessed Pearson correlation with FFR, univariable linear regression (R 2 ), logistic regression with odds ratios (OR), and ROC AUC for classification (FFR≤0.80). Results A total of 81 R-AAOCA patients were included with a mean age of 52.3 ± 12.0 years and a mean body mass index of 27.0 ± 5.1 kg/m 2 ; 27 patients (33.3%) were female. FFR Adenosine ≤0.80 was observed in 5 (6.2%) patients and FFR Dobutamine ≤0.80 in 16 (19.8%) patients. The highest discriminatory power to predict abnormal FFR Adenosine was observed for the RI (AUC = 0.97, 95% CI 0.92-1.00), followed by the OAP (AUC = 0.97, 95% CI 0.92-1.00), ostial area (AUC = 0.96, 95% CI 0.90-1.00), CSS (AUC = 0.95, 95% CI 0.89-0.99), and ostial minor diameter (AUC = 0.95, 95% CI 0.90-0.99). The highest discriminatory power to predict abnormal FFR Dobutamine was observed for ostial minor diameter (AUC = 0.85, 95% CI 0.74-0.94), followed by RI (AUC = 0.83, 95% CI 0.68-0.95) and ILA minor diameter (AUC = 0.81, 95% CI 0.69-0.92). RI explained 45% of the variance in FFR Adenosine and 43% of the variance in FFR Dobutamine . At optimal thresholds, RI achieved 100% sensitivity and 95% specificity for predicting abnormal FFR Adenosine , whereas ostial minor diameter achieved 100% sensitivity and 57% specificity for predicting abnormal FFR Dobutamine . Conclusions In patients with R-AAOCA, CCTA-derived fluid dynamics-informed metrics showed high diagnostic performance for identifying hemodynamically relevant fixed stenosis (i.e., defined by abnormal FFR Adenosine ), with discriminatory ability comparable to conventional geometric parameters. For combined fixed and stress-induced dynamic stenosis (i.e., defined by abnormal FFRDobutamine), both approaches performed similarly but with lower accuracy, underscoring the need for more advanced noninvasive modeling approaches that explicitly capture the stress-induced dynamic component.