The inflammation-microvascular axis in prognosis: Integrated FAI and AMR assessment for risk stratification after PCI in NSTEMI patients.

BACKGROUND: Despite successful percutaneous coronary intervention (PCI), patients with non-ST-segment elevation myocardial infarction (NSTEMI) remain at risk of major adverse cardiovascular events (MACE). The combined prognostic value of pericoronary fat attenuation index (FAI), a marker of coronary inflammation from coronary computed tomography angiography (CCTA), and angiography-derived microcirculatory resistance (AMR), a marker of microvascular dysfunction, is underexplored. METHODS: This retrospective cohort included 508 NSTEMI patients who underwent successful PCI after pre-procedural CCTA. FAI and AMR were measured. The primary endpoint was MACE during follow-up. Sensitivity analyses using 1-year and 2-year time-restricted endpoints were performed to validate the robustness of the findings. Cox regression and machine learning models were used. Mediation analysis assessed the pathway from FAI to outcomes via AMR. RESULTS: Over a median follow-up of 620 days, MACE occurred in 146 patients (28.7%). High FAI (hazard ratio [HR] 1.03, P < 0.001) and high AMR (HR 1.75, P < 0.001) were independent predictors. The combined "High AMR/High FAI" phenotype had the highest risk. The FAI-AMR model improved prediction over a baseline clinical model (C-index increase Δ = 0.055, net reclassification improvement [NRI] = 0.809, integrated discrimination improvement [IDI] = 0.139, all P < 0.05). Exploratory mediation analysis suggested that approximately 29.4% of the statistical association between FAI and MACE was accounted for by AMR (P < 0.001). CONCLUSION: FAI and AMR are independent and complementary predictors of post-PCI MACE in NSTEMI. Their combined assessment identifies a high-risk phenotype and adds prognostic value. Microcirculatory dysfunction partially mediates the link between inflammation and outcomes, suggesting potential therapeutic targets.