Left anterior descending artery lesions retain excess risk despite coronary angiography derived-fractional flow reserve concordant revascularisation

Background Current guidelines advocate physiology-guided revascularisation in stable ischaemic heart disease (SIHD), with the expectation that functional optimisation may standardise outcomes across coronary territories. Computational pressure-flow dynamics-derived fractional flow reserve (caFFR) is an angiography-derived index that determines FFR without invasive pressure wire or hyperaemic stimulus. However, whether physiological guidance fully accounts for the inherent risk associated with left anterior descending (LAD) artery lesions remains incompletely understood. Purpose To determine whether caFFR-concordant treatment mitigates the established prognostic disadvantage of LAD lesions in SIHD. Methods In this retrospective cohort study of 1679 SIHD patients, caFFR was analysed in 5037 vessels. Patients underwent revascularization at the discretion of the proceduralist according to the angiographic and clinical data available at the time. Treatment decisions were classified by concordance with caFFR (revascularisation for caFFR ≤0.80; deferral for >0.80). The primary endpoint was the vessel-oriented composite endpoint, defined as vessel-related cardiovascular mortality, myocardial infarction (MI) and unplanned revascularisation at median 4.4-year follow-up. Results Among 3500 analysable vessels, 2720 (77.7%) were treated concordantly with caFFR, with 827 (30.4%) LAD and 1893 (69.6%) non-LAD vessels. Despite physiology-concordant management, LAD lesions demonstrated significantly higher event rates than non-LAD lesions (VOCE: 7.1% vs 4.8%, P=0.014; MI: 1.9% vs 0.8%, P=0.010). In multivariable analysis, concordantly managed LAD lesions remained independently associated with increased risk of VOCE (HR 1.49; 95% CI 1.08-2.07; P=0.016) and MI (HR 2.46; 95% CI 1.21-4.97; P=0.012). Notably, significant interaction was observed between LAD territory and ischaemic status (P-interaction=0.040): ischaemic LAD lesions (caFFR ≤0.80) exhibited heightened risk (HR 1.79; 95% CI 1.13–2.83), whereas non-ischaemic LAD lesions showed no excess risk (HR 0.90; 95% CI 0.56–1.46). Conclusion Even when revascularisation decisions are concordant with caFFR, LAD lesions continue to confer higher long-term risk of vessel-oriented events and myocardial infarction compared with non-LAD lesions. These findings suggest that physiological guidance, while essential, may benefit from integration with anatomical and vessel-specific considerations. Comprehensive risk stratification incorporating both functional assessment and coronary territory may further optimize decision-making in LAD disease.