Prognostic Value of Coronary Computed Tomography Angiography–Derived Fractional Flow Reserve From a Large Nationwide Cohort

BACKGROUND: The diagnostic value of coronary computed tomography angiography–derived fractional flow reserve (FFR-CT) in stable coronary artery disease is well established. The prognostic value of predicting future cardiovascular events is less clear, as studies are limited by small populations, variable measurement points, composite outcomes, and short follow-up. OBJECTIVES: A nationwide cohort of coronary computed tomography angiography with 3-year follow-up was used to examine the association between FFR-CT measurements and future cardiovascular events. METHODS: Patients receiving coronary computed tomography angiography and clinically indicated FFR-CT analysis (HeartFlow) for stable coronary artery disease between 2017 and 2020 at 27 sites across England were included. Lowest per-patient stenosis-specific and distal vessel FFR-CT measurements were related to individual outcomes of myocardial infarction (MI), cardiovascular mortality, all-cause mortality, and revascularization. FFR-CT measurements were divided into subgroups to investigate for a gradient of risk: normal FFR-CT (>0.8), borderline (0.71–0.8), reduced (0.51–0.7), and severely reduced (≤0.5). RESULTS: In total, 7836 patients aged 63 (56.0–71.0), 37.4% women, underwent FFR-CT analysis. Stenosis-specific FFR-CT was associated with future MI (hazard ratio [HR], 2.08–5.73; P <0.001), cardiovascular death (HR, 1.51–3.40; P <0.001), all-cause death (HR, 1.01–1.58; P =0.01), and revascularization (HR, 4.79–24.48; P <0.001), with lower FFR-CT values associated with incrementally greater risk. After adjusting for cardiovascular risk factors and coronary stenosis severity (Coronary Artery Disease Reporting and Data System), stenosis-specific FFR-CT≤0.7 was associated with MI (adjusted HR, 2.94–3.39; P <0.001), ≤0.5 with cardiovascular death (adjusted HR, 2.92; P =0.02), all-cause death (adjusted HR, 1.49; P =0.045), and ≤0.8 with revascularization (adjusted HR, 3.02–9.42; P <0.001). The addition of FFR-CT improved discrimination for MI or cardiovascular death compared with a risk factor and stenosis severity model (C index, 0.783; ∆C index, 0.012; P <0.001). An FFR-CT value of 0.67 defined the optimal cutoff for risk of future cardiovascular events. Distal-vessel FFR-CT was associated with outcomes similar to stenosis-specific FFR-CT. Stenosis-specific and distal-vessel FFR-CT discordance was common (36.4%), but when stenosis-specific FFR-CT was normal, event rates were low (1.5% at 3 years for MI or cardiovascular death). CONCLUSIONS: FFR-CT is associated with the individual outcomes of MI, cardiovascular death, and all-cause death independent of risk factors and stenosis severity, with lower FFR-CT values associated with worse outcomes. Reduced and severely reduced FFR-CT have the strongest association with future cardiovascular events, with a value of 0.67 defining the optimal risk threshold.