Prognostic significance of non-ischemic computational pressure-flow dynamics derived fractional flow reserve in stable coronary artery disease patients in LAD versus non-LAD artery lesions

Computational pressure-flow dynamics derived fractional flow reserve (caFFR) is an angiographic-derived index to determine the fractional flow reserve (FFR) without the need of invasive pressure wire and hyperaemic stimulus. Although the safety of FFR-guided deferral of revascularization in non-ischemic lesions is well-established, physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because the LAD often supplies a large territory of myocardium. It has been suggested that because of the relatively large area of myocardium at risk, only hyperaemia-based indexes can be trusted for decision-making in the LAD. However, whether caFFR guided deferral of LAD lesions is safe compared to non-LAD lesions is unclear. The aim of the study is to investigate the prognostic implications of caFFR for non-ischemic deferred LAD compared to non-LAD lesions in stable coronary artery disease (CAD) patients. Among the 1552 stable CAD patients who were recruited from 2014-2017, 650 of the stable CAD patients (mean age=63.3±12.2, 65.2% male) had non-ischemic lesions defined by caFFR≥0.80 and did not undergo PCI for said lesions. The primary endpoint was the vessel-oriented composite endpoint (VOCE), defined as vessel-related cardiovascular mortality, vessel-related myocardial infarction (MI) and any unplanned revascularisation at median follow-up time of 4.4 years. Survival curves were constructed using Kaplan-Meier estimates and differences between groups were tested using the log-rank test. Cox proportional hazards model was also used to evaluate the association between an LAD artery and the risk of VOCE, with parameters with P<0.1 upon univariate analysis entered into multivariable Cox model. A total of 430 (23.1%) LAD and 1434 non-LAD (76.9%) non-ischemic lesions that had not undergone PCI were studied. Mean caFFR was 0.90±0.04 amongst LAD lesions and 0.92±0.04 for non-LAD lesions (P<0.001). LAD lesions had significantly higher incidence rates than non-LAD lesions in terms of VOCE (6.0% vs 3.0%; P=0.003), MI (2.1% vs 0.6%; P=0.007), and unplanned revascularisation (4.9% vs 2.4%; P=0.009). After multivariate adjustment, LAD lesions had a significantly higher risk than non-LAD lesions in terms of VOCE (HR 1.80; 95%CI 1.10-2.95; P=0.019), vessel-related MI (HR 3.54; 95%CI 1.36-9.20; P=0.010), and unplanned revascularisation (HR 1.82; 95%CI 1.06-3.14; P=0.031). In stable CAD patients, caFFR-based deferral has superior prognostic durability in non-LAD lesions compared to LAD lesions during long-term follow up. This novel index could enhance risk stratification of non-ischemic vessels in stable CAD patients for LAD and non-LAD lesions. Kaplan-Meier curves for VOCE