Assessing the prognostic value of artificial intelligence for opportunistic prediction of coronary artery calcium score on routine non-gated computed tomography in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitors (ICI) improve cancer outcomes but are associated with increased atherosclerotic cardiovascular risk. Opportunistic coronary artery calcium (CAC) assessment from routine non-gated computed tomography (CT) using artificial intelligence (AI) may enable rapid cardiovascular risk stratification in this population. We evaluated the association between AI-derived CAC (AI-CAC) scores and 1-year myocardial infarction (MI) and all-cause mortality in patients receiving ICI therapy. Methods: We conducted a retrospective multicenter study across three Mayo Clinic sites including patients who underwent chest CT within 3 months prior to ICI initiation between 2011 and 2022. Patients with prior coronary revascularization were excluded. AI-CAC scores derived from non-gated CT scans were categorized as 0, 1-99, 100-399, and ≥400. Cox regression analyses assessed associations with 1-year MI and all-cause mortality. Results: Among 1,873 patients (mean age 66 years; 43% women), lung cancer was most common (50.3%), and 91% had at least one cardiovascular risk factor. Higher CAC burden was associated with increased 1-year MI risk (overall p=0.0032). AI-CAC was not associated with all-cause mortality (p=0.79), likely reflecting high cancer-related mortality (50.7% at 1 year). Only 15% of patients were receiving statins despite one-third having CAC >100. Conclusions: Opportunistic AI-CAC assessment from routine CT scans provides modest prognostic value for MI risk among patients receiving ICI therapy and may identify opportunities to optimize preventive cardiovascular care. Elevated CAC should prompt risk factor modification rather than influence ICI treatment decisions. Prospective studies are warranted to evaluate clinical implementation and outcomes.