Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre-PCI focal or diffuse disease patterns combined with post-PCI quantitative flow ratio (QFR). Methods and Results Pre-PCI QFR derived pullback pressure gradient (PPG) (QFR-PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre-PCI QFR-PPG and post-PCI QFR. Vessel-oriented composite outcome, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre-PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08-3.44; P=0.02) or low post-PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61-8.87; P=0.001) demonstrated higher vessel-oriented composite outcome risk after stent implantation. Of note, despite high post-PCI QFR achieved, vessels with low pre-PCI QFR-PPG presented higher risk of vessel-oriented composite outcome than those with high pre-PCI QFR-PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09-3.76; P=0.03) and pre-PCI QFR-PPG demonstrated direct prognostic effect not mediated by post-PCI QFR. Integration of groups classified by pre-PCI QFR-PPG and post-PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C-index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre-PCI focal or diffuse disease patterns assessed by QFR-PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post-PCI QFR. Integration of both pre-PCI and post-PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.

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