High-Risk Morphological and Physiological Coronary Disease Attributes as Outcome Markers After Medical Treatment and Revascularization

Objectives: This study sought to evaluate the prognostic impact of plaque morphology and coronary physiology on outcomes after medical treatment or percutaneous coronary intervention (PCI).

Background: Although fractional flow reserve (FFR) is currently best practice, morphological characteristics of coronary artery disease also contribute to outcomes.

Methods: A total of 872 vessels in 538 patients were evaluated by invasive FFR and coronary computed tomography angiography. High-risk attributes (HRA) were defined as high-risk physiological attribute (invasive FFR ≤0.8) and high-risk morphological attributes including: 1) local plaque burden (minimum lumen area <4 mm² and plaque burden ≥70%); 2) adverse plaque characteristics ≥2; and 3) global plaque burden (total plaque volume ≥306.5 mm³ and percent atheroma volume ≥32.2%). The primary outcome was the composite of revascularization, myocardial infarction, or cardiac death at 5 years.

Results: The mean FFR was 0.88 ± 0.08, and PCI was performed in 239 vessels. The primary outcome occurred in 54 vessels (6.2%). All high-risk morphological attributes were associated with the increased risk of adverse outcomes after adjustment for FFR ≤0.8 and demonstrated direct prognostic effect not mediated by FFR ≤0.8. The 5-year event risk proportionally increased as the number of HRA increased (p for trend <0.001) with lower risk in the PCI group than the medical treatment group in vessels with 1 or 2 HRA (9.7% vs. 14.7%), but not in vessels with either 0 or ≥3 HRA. Of the vessels with pre-procedural FFR ≤0.8, ischemia relief by PCI (pre-PCI FFR ≤0.8 and post-PCI FFR >0.8) significantly reduced vessel-oriented composite outcome risk compared with medical treatment alone in vessels with 0 or 1 high-risk morphological attributes (hazard ratio: 0.33; 95% confidence interval: 0.12 to 0.93; p = 0.035), but the risk reduction was attenuated in vessels with ≥2 high-risk morphological attributes.

Conclusions: High-risk morphological attributes offered additive prognostic value to coronary physiology and may optimize selection of treatment strategies by adding to FFR-based risk predictions (CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model; NCT04037163).