Longitudinal heterogeneity of arterial remodeling and endothelial shear stress in human coronary artery plaques and their effects on the natural history of atherosclerosis

Purpose: Expansive remodeling (ER) and low endothelial shear stress (ESS) critically determine the natural history of atherosclerosis, but they have only been investigated in a cross-sectional arterial axis. In this study, we assessed the longitudinal variation of remodeling and ESS along the length of individual plaques in human coronary arteries and their relation to subsequent plaque growth. Methods: We performed 3D coronary reconstruction by angiography/IVUS at baseline and at 6-10 months follow-up as part of the PREDICTION Study. In discrete baseline plaques (max thickness >0.5 mm, length 9 to 30 mm), we assessed arterial remodeling and ESS (using computational fluid dynamics) in 3mm-long segments. Plaque growth was evaluated in the same locations at follow-up. Results: In 313 arteries from 220 patients, 371 plaques (average length 16.6±0.4 mm) were identified. Of these plaques, 237 (63.9%) had evidence of remodeling while the remaining 134 (36.1%) showed no remodeling. The vast majority of remodeled plaques (93.2%) displayed heterogeneous remodeling patterns along their length: 52 plaques (23.5%) exhibited two remodeling patterns, 14 (6.3%) exhibited three remodeling patterns and 155 plaques (70.1%) showed a combination of one remodeling pattern in some areas of the plaque with absence of remodeling elsewhere (p<0.001). Of plaques with homogeneous remodeling, 18.8% had Excessive ER, 6.2% Compensatory ER, 12.5% Inadequate ER and 62.5% Constrictive remodeling (p<0.05). Similarly, 75.7% of all plaques demonstrated heterogeneous ESS profiles along their length: 20 plaques (7.1%) exhibited both low and high ESS, 79 (28.1%) both low and moderate ESS, 67 (23.8%) both moderate and high ESS; and 115 plaques (40.9%) showed all three ESS patterns (p<0.001). Of plaques with homogeneous ESS, 40% had low ESS, 20% moderate ESS and 40% high ESS. Segments with Excessive ER were associated with low ESS while constrictively remodeled segments with high ESS (p<0.001). Plaque growth at follow-up was primarily evident in segments with baseline low ESS (OR 1.4, 95% CI 1.1-1.7, p<0.05). Conclusions: Arterial remodeling and ESS patterns are not homogeneously distributed along the length of individual coronary plaques, but show significant longitudinal heterogeneity. Since Excessive ER is related to low ESS and subsequent plaque growth, the detailed characterization of remodeling and ESS profiles along the longitudinal aspect of lesions may enhance early identification of highest-risk plaques.