Background: Acute coronary syndrome (ACS) arises from a complex interplay among luminal narrowing, plaque morphology, and hemodynamic environment.
Objectives: We 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 CT angiography
(CCTA) 1 month to 3 years before the event were analyzed. Lesions were classified as culprit or non-culprit 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 (ΔFFRCT). 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 ΔFFRCT >=0.10 had the highest specificity of 88.3 (86.9 - 89.6) %. Predictability was similar between ΔFFRCT and the combined degree of stenosis, the number of APCs, and plaque burden (AUC 0.805 [0.782-0.829] vs. 0.802 [0.777-0.826], P =0.748), with additive discrimination towards each other.
Conclusion: 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.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Seokhun Yang, MD
Important Dates
Date of Release: December 8, 2025
Term of Approval/Date of CME/MOC Expiration: December 7, 2026