Findings demonstrate risk of future acute coronary syndrome (ACS)-causing culprit lesions in relation to coronary computed tomographic angiography (CCTA)-derived adverse geometric characteristics (AGCs) capturing lesion location and vessel geometry. Adverse geometric features could offer additive prognostic information beyond plaque evaluation in CCTA.

• In this substudy of a multicenter nested case-control cohort study, patients with ACS and a culprit lesion precursor detected on baseline CCTA (n = 116) and propensity score–matched non-ACS controls (n = 116) were included.

• Of 548 coronary lesions in 116 patients with incident ACS after CCTA, more chances of developing into culprit lesions were observed for lesions with a short distance from the ostium or located within vessel bifurcations or tortuous segments.

• A greater number of these adverse geometric features were demonstrated by culprit lesion precursors vs the highest-grade stenosis lesions in 116 matched controls.

• Multivariable Cox regression analysis showed a greater risk of future culprit lesions in relation to an increasing number of AGCs (hazard ratio [HR] for 1 AGC, 2.90; HR for ≥2 AGCs, 6.84).

• Incremental discriminatory value for culprit lesion precursors was offered by adverse geometric features when incorporated to a model consisting of stenosis severity, adverse morphological plaque features, and quantitative plaque features(area under the curve, 0.766 vs 0.733).

• A higher frequency of lesions with adverse plaque characteristics, AGCs, or both was found in ACS patients vs control patients.