Disease progression and plaque composition in patients with non-obstructive coronary artery disease (THRONE): A coronary computed tomography angiography follow-up study

BACKGROUND: Fractional flow reserve (FFR)-negative coronary lesions are usually managed medically. Lesion-specific plaque characterization and FFR changes over time remain elusive. AIMS: To assess disease progression in FFR-negative lesions over a two-year period using FFR derived from coronary CT angiography (CCTA) (FFRct) and to investigate whether FFR decline over a two-year period is associated with plaque characteristics. METHODS: This single-center prospective study included patients undergoing coronary angiography with one or more invasive intermediate lesions (FFR 0.81-0.90) in non-stented, non-culprit coronary arteries. Two years after the index procedure, patients underwent CCTA with FFRct and quantitative plaque analysis. RESULTS: We enrolled 131 patients (152 vessels). Two-year follow-up with FFRct and plaque analysis was available in 68 (52 ​%) patients (73 vessels). Compared to invasive FFR at baseline, FFRct at 2y follow-up was significantly lower (median difference -0.06) at vessel level analysis (p ​< ​0.001). FFR declined in 55 (75 ​%) lesions. The 35 study vessels with an FFRct≤0.80 ​at 2-year follow-up had higher total percent atheroma volume (PAV) (41 ​% vs. 23 ​%; p ​= ​0.002) and more high-risk plaque composition, including noncalcified PAV (30 ​% vs. 18 ​%; p ​= ​0.002), and low-attenuation PAV (1.1 ​% vs. 0.7 ​%; p ​= ​0.046) compared to vessels with an FFRct>0.80 (n ​= ​38). Rates of study vessel revascularization in the 131 patients were 6.9 ​% at 2 years and 15.1 ​% after 4.9 years of follow-up after index procedure. CONCLUSIONS: Rates of coronary revascularization are substantial in patients with medically managed intermediate lesions. In this selected cohort, an FFRct ≤0.80 ​at two-year follow-up was associated with higher plaque burden and presence of high-risk plaque composition.