Long-term prognostic value of the serial changes of CT-derived fractional flow reserve and perivascular fat attenuation index

Objective: To investigate the serial changes of computed tomography (CT) fractional flow reserve (CT-FFR) and fat attenuation index (FAI), and explore their relationships with long-term clinical outcomes. Methods: Consecutive symptomatic patients with an intermediate pretest probability of coronary artery disease 1-4 were prospectively enrolled if coronary CT angiography (CCTA) revealed at least 1 lesion with 30-70% stenosis on major epicardial arteries. Follow-up CCTA was performed at 1 to 1.5-year intervals. All patients were further followed up after the second CCTA until September 2019. The Coronary Artery Disease-Reporting and Data System (CAD-RADS) grade, high-risk plaque features, lesion-specific CT-FFR, and FAI were measured for prognosis analysis. Results: A total of 263 patients were included in the analysis, and 38 major adverse cardiac events (MACEs) occurred. In the MACE group, the lesion-specific CT-FFR decreased significantly at the follow-up CCTA [0.80 (0.74-0.90) versus 0.85 (0.76-0.93); P=0.01], whereas the FAI did not notably increase (-70.4 +/- 8.9 versus -71.3 +/- 7.1 HU; P=0.436). In the non-MACE group, lesion-specific CT-FFR increased markedly [0.91 (0.84-0.95) versus 0.90 (0.82-0.94); P<0.001], while the FAI decreased substantially (-74.0 +/- 10.8 versus -72.4 +/- 11.5 HU; P=0.004). Decreased CT-FFR (adjusted overall hazard ratio =2.455; P=0.023) and increased FAI (adjusted hazard ratio =2.956; P=0.002) were the strongest independent predictors of MACEs. Serial changes of CT-FFR and FAI provided incremental prognostic value (Concordance statistic =0.716; P=0.003; over conventional clinical and imaging parameters (Concordance statistic =0.762; P=0.004). Conclusions: Decreased CT-FFR and increased FAI at follow-up CCTA were the 2 strongest predictors of MACEs. Serial changes of CT-FFR and FAI provided incremental prognostic value over conventional clinical and imaging parameters for risk stratification. In addition, decreased CT-FFR provided incremental predictive value for MACEs from 15 months after second CCTA, while increased FAI added prognostic value from the second CCTA onwards.