Aims
Artificial intelligence (AI) has enabled accurate and fast plaque quantification from coronary computed tomography angiography (CCTA). However, AI detects any coronary plaque in up to 97% of patients. To avoid overdiagnosis, a plaque burden safety cut-off for future coronary events is needed.

Methods and results
Percent atheroma volume (PAV) was quantified with AI-guided quantitative computed tomography in a blinded fashion. Safety cut-off derivation was performed in the Turku CCTA registry (Finland), and pre-defined as ≥90% sensitivity for acute coronary syndrome (ACS). External validation was performed in the Amsterdam CCTA registry (the Netherlands). In the derivation cohort, 100/2271 (4.4%) patients experienced ACS (median follow-up 6.9 years). A threshold of PAV ≥ 2.6% was derived with 90.0% sensitivity and negative predictive value (NPV) of 99.0%. In the validation cohort 27/568 (4.8%) experienced ACS (median follow-up 6.7 years) with PAV ≥ 2.6% showing 92.6% sensitivity and 99.0% NPV for ACS. In the derivation cohort, 45.2% of patients had PAV < 2.6 vs. 4.3% with PAV 0% (no plaque) (P < 0.001) (validation cohort: 34.3% PAV < 2.6 vs. 2.6% PAV 0%; P < 0.001). Patients with PAV ≥ 2.6% had higher adjusted ACS rates in the derivation [Hazard ratio (HR) 4.65, 95% confidence interval (CI) 2.33–9.28, P < 0.001] and validation cohort (HR 7.31, 95% CI 1.62–33.08, P = 0.010), respectively.

Conclusion
This study suggests that PAV up to 2.6% quantified by AI is associated with low-ACS risk in two independent patient cohorts. This cut-off may be helpful for clinical application of AI-guided CCTA analysis, which detects any plaque in up to 96–97% of patients.