Prognostic value and risk continuum of noninvasive fractional flow reserve derived from coronary CT angiography

Background: Coronary CT angiography with noninvasive fractional flow reserve (FFR) predicts lesion-specific ischemia when compared with invasive FFR. The longer term prognostic value of CT-derived FFR (FFR_CT) is unknown. Purpose: To determine the prognostic value of FFR_CT when compared with coronary CT angiography and describe the relationship of the numeric value of FFR_CT with outcomes. Materials and Methods: This prospective subanalysis of the NXT study (Clinicaltrials.gov: NCT01757678) evaluated participants suspected of having stable coronary artery disease who were referred for invasive angiography and who underwent FFR, coronary CT angiography, and FFR_CT. The incidence of the composite primary end point of death, myocardial infarction, and any revascularization and the composite secondary end point of major adverse cardiac events (MACE: cardiac death, myocardial infarction, unplanned revascularization) were compared for an FFR_CT of 0.8 or less versus stenosis of 50% or greater on coronary CT angiograms, with treating physicians blinded to the FFR_CT result. Results: Long-term outcomes were obtained in 206 individuals (age, 64 years 6 9.5), including 64% men. At median follow-up of 4.7 years, there were no cardiac deaths or myocardial infarctions in participants with normal FFR_CT. The incidence of the primary end point was more frequent in participants with positive FFR_CT compared with clinically significant stenosis at coronary CT angiography (73.4% [80 of 109] vs 48.7% [91 of 187], respectively; P , .001), with the majority of outcomes being planned revascularization. Corresponding hazard ratios (HRs) were 9.2 (95% confidence interval [CI]: 5.1, 17; P , .001) for FFR_CT and 5.9 (95% CI: 1.5, 24; P = .01) for coronary CT angiography. FFR_CT was a superior predictor compared with coronary CT angiography for primary end point (C-index FFR_CT, 0.76 vs coronary CT angiography, 0.54; P , .001) and MACE (FFR_CT, 0.71 vs coronary CT angiography, 0.52; P = .001). Frequency of MACE was higher in participants with positive FFR_CT compared with coronary CT angiography (15.6% [17 of 109] vs 10.2% [19 of 187], respectively; P = .02), driven by unplanned revascularization. MACE HR was 5.5 (95% CI: 1.6, 19; P = .006) for FFR_CT and 2.0 (95% CI: 0.3, 14; P = .46) for coronary CT angiography. Each 0.05-unit FFR_CT reduction was independently associated with greater incidence of primary end point (HR, 1.7; 95% CI: 1.4, 1.9; P , .001) and MACE (HR, 1.4; 95% CI: 1.1, 1.8; P , .001). Conclusion: In stable patients referred for invasive angiography, a CT-derived fractional flow reserve (FFR_CT) value of 0.8 or less was a predictor of long-term outcomes driven by planned and unplanned revascularization and was superior to clinically significant stenosis on coronary CT angiograms. Additionally, the numeric value of FFR_CT was an independent predictor of outcomes.