Anatomical vs Physiological Lesion Characteristics in Prediction of Acute Coronary Syndrome

Background Acute coronary syndrome (ACS) arises from a complex interplay among luminal narrowing, plaque morphology, and hemodynamic environment. Objectives The authors aimed to compare the effectiveness of anatomy- and physiology-based ACS risk assessment. Methods In this international, multicenter, internal case-control study, 351 ACS patients who underwent coronary computed tomography angiography (CCTA) 1 month to 3 years before the event were analyzed. Lesions were classified as culprit or nonculprit based on invasive coronary angiography at the time of ACS. Core lab CCTA analyses assessed lesion-specific characteristics: stenosis severity, adverse plaque characteristics (APC) (low-attenuation plaque, positive remodeling, spotty calcification, napkin-ring sign), plaque burden at minimum lumen area, and changes in CCTA-derived fractional flow reserve (ΔFFR_CT). Diagnostic performance in identifying culprit lesions was compared. Results Among 2,451 lesions, 363 (14.8%) became ACS culprits, with a median interval of 375 [95.0-644.5] days. All anatomical and simulated physiological characteristics were independently associated with culprit lesions (all P < 0.001). In identifying ACS culprit lesions, plaque burden ≥70% showed the highest sensitivity of 90.6% (87.2%-93.2%) and ΔFFR_CT ≥0.10 had the highest specificity of 88.3% (86.9%-89.6%) %. Predictability was similar between ΔFFR_CT and the combined degree of stenosis, the number of APCs, and plaque burden (area under the curve 0.805 [0.782-0.829] vs 0.802 [0.777-0.826]; P = 0.748), with additive discrimination towards each other. Conclusions Luminal narrowing, plaque quality and quantity, and local hemodynamics were independent predictors of ACS, offering specificity in physiology and sensitivity in anatomy. A comprehensive assessment of them further refined the risk prediction for future ACS.