This study aimed to evaluate the hemodynamic significance of in-stent restenosis (ISR) by using a combined anatomical-functional approach with photon-counting CT coronary angiography (APEX-CT CTA) and dynamic CT myocardial perfusion imaging (CT-MPI). We prospectively enrolled 239 symptomatic patients at least 9 months after PCI. All patients underwent APEX-CT CTA (assessing diameter stenosis [CTA%DS] and plaque composition) and CT-MPI (measuring myocardial blood flow [MBF] and relative myocardial blood volume [rMBV]). Invasive coronary angiography (CAG) and fractional flow reserve (FFR) served as the reference standard, with a composite ISR endpoint defined as CAG%DS ≥ 90% or CAG%DS ≥ 50% with FFR ≤ 0.80. Among 239 patients, 41 (17.2%) were ISR-positive. The ISR-positive group had significantly higher CTA%DS, lipid plaque proportion, diabetes prevalence, and smaller/longer stents, but lower MBF and rMBV. Multivariate analysis identified CTA%DS (OR = 6.801, 95% CI: 3.014-15.346) and rMBV > 0.7 (OR = 0.231, 95% CI: 0.079-0.673) as independent predictors, and their combination yielded an AUC of 0.949. In conclusion, APEX-CT CTA combined with CT-MPI enables dual anatomical-functional assessment of ISR, with CTA%DS and rMBV serving as key noninvasive indicators, though further validation of its long-term applicability and generalizability is warranted.
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