Advanced Analyses of Coronary Computed Tomography Angiography to Predict Future Cardiac Events: A Meta-Analysis

BACKGROUND: Although coronary computed tomographic angiography (CTA) is widely used for anatomical evaluation, its advanced analyses, including plaque characterization, computed tomography-derived fractional flow reserve (CT-FFR), and radiomics signature extraction, hold promise for improved prediction of major adverse cardiovascular events (MACE).

OBJECTIVES: The aim of this meta-analysis was to assess the added prognostic value of advanced coronary CTA-based analyses in predicting MACE.

METHODS: A systematic search of PubMed, Embase, and CENTRAL identified studies reporting coronary CTA-based advanced analyses predicting MACE. The pooled HR of advanced coronary CTA-based analyses for the prediction of MACE was the primary outcome measure. The secondary endpoint included the mean difference in C index (ΔC index) between advanced coronary CTA-based predictive models and conventional models. MACE were defined according to study-level definitions. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42024606545).

RESULTS: Of 75 studies, 52 were included in the primary analysis of HRs (n = 58,123) and 32 in the secondary analysis of ΔC index. The median follow-up time was 36 months (Q1-Q3: 24-57 months). Most advanced coronary CTA-based analyses, including CT-FFR, high-risk plaque, fat attenuation index, total plaque volume or low-attenuation plaque volume, and radiomics-derived scores, demonstrated a significant and consistent association with MACE, observed across both pooled unadjusted and adjusted HRs. In particular, CT-FFR (HR: 6.14 [95% CI: 3.75-10.05]; P < 0.01) and high-risk plaque (HR: 4.05 [95% CI: 3.16-5.18]; P < 0.01) showed the strongest associations with MACE despite a moderate to severe between-studies heterogeneity for most of the pooled analyses.

CONCLUSIONS: Advanced coronary CTA-based analyses show consistent association to the occurrence of MACE, suggesting their potential for refining cardiovascular risk stratification on top of conventional clinical risk assessment. Given the heterogeneity of advanced imaging analyses by coronary CTA and their varying pathophysiological targets, future comparative studies are needed to evaluate their implementation in different clinical scenarios.