Prognostic impact of coronary angiography-derived fractional flow reserve concordant versus discordant revascularization strategies in non-ST-elevation acute coronary syndrome

Background Computational pressure-flow dynamics-derived fractional flow reserve (caFFR) enables FFR determination from angiography alone, without invasive pressure wire or hyperaemic stimulus. While its diagnostic accuracy is well-established, the clinical impact of adhering to caFFR-guided revascularisation strategies in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) remains to be fully elucidated. Purpose To determine whether caFFR-concordant revascularisation improves cardiovascular outcomes compared with discordant strategies in NSTE-ACS patients. Methods This retrospective cohort study analysed 283 NSTE-ACS patients (mean age 67.4±12.7 years; 65.7% male) with interpretable three-vessel caFFR who underwent revascularisation between 2014 and 2017. Patients underwent revascularisation at the discretion of the proceduralist according to the angiographic and clinical data available at the time. Concordant strategy was defined as PCI of all ischaemic vessels (caFFR ≤0.80) with deferral of non-ischaemic vessels (caFFR >0.80); all other patterns constituted discordant strategies. To minimise indication bias, inverse probability of treatment weighting was used to balance baseline characteristics (standardised mean difference <0.10). The primary endpoint was Major Adverse Cardiovascular Events (MACE; composite of cardiovascular mortality, myocardial infarction, and ischaemia-driven revascularisation) over median 4.3-year follow-up (IQR 4.0–4.6). Weighted Cox regression and Kaplan-Meier analyses assessed time-to-event outcomes. Results After IPTW adjustment, 157 patients (55.5%) received concordant and 126 (44.5%) discordant revascularisation. Among discordant cases, 72 (57.1%) were overtreated and 54 (42.9%) undertreated. While composite MACE rates and risk were similar (concordant 14.6% vs. discordant 19.0%; weighted HR 1.30, 95%CI 0.69—2.44, p=0.413), discordant strategy significantly increased the incidence rate and risk of myocardial infarction (10.4% vs. 1.2%; weighted HR 8.13, 95%CI 1.73–38.30, p=0.008). Sub-analysis of the discordant group revealed that this risk was predominantly driven by a significantly higher risk of MI for undertreatment compared to overtreatment (weighted HR 5.64; 95% CI 1.12–28.34; p=0.036). There was also a trend towards increased MACE in the undertreated group (weighted HR 2.32; 95% CI 0.97–5.51; p=0.058). Conclusion In patients with NSTE-ACS, a revascularisation strategy discordant with caFFR—particularly the undertreatment of physiologically significant lesions—is associated with a significantly higher risk of myocardial infarction. These findings suggest that integrating caFFR into the clinical decision-making process for NSTE-ACS may improve prognostic outcomes by ensuring haemodynamically significant stenoses are appropriately addressed.