The plaque hypothesis: understanding mechanisms of plaque progression and destabilization, and implications for clinical management.

PURPOSE OF REVIEW: Major adverse cardiac events (MACE) typically arise from nonflow-limiting coronary artery disease and not from flow-limiting obstructions that cause ischemia. This review elaborates the current understanding of the mechanism(s) for plaque development, progression, and destabilization and how identification of these high-risk features can optimally inform clinical management. RECENT FINDINGS: Advanced invasive and noninvasive coronary imaging and computational postprocessing enhance an understanding of pathobiologic/pathophysiologic features of coronary artery plaques prone to destabilization and MACE. Early investigations of high-risk plaques focused on anatomic and biochemical characteristics (large plaque burden, severe luminal obstruction, thin cap fibroatheroma morphology, and large lipid pool), but more recent studies underscore that additional factors, particularly biomechanical factors [low endothelial shear stress (ESS), high ESS gradient, plaque structural stress, and axial plaque stress], provide the critical incremental stimulus acting on the anatomic substrate to provoke plaque destabilization. These destabilizing features are often located in areas distant from the flow-limiting obstruction or may exist in plaques without any flow limitation. Identification of these high-risk, synergistic plaque features enable identification of plaques prone to destabilize regardless of the presence or absence of a severe obstruction (Plaque Hypothesis). SUMMARY: Local plaque topography, hemodynamic patterns, and internal plaque constituents constitute high-risk features that may be located along the entire course of the coronary plaque, including both flow-limiting and nonflow-limiting regions. For coronary interventions to have optimal clinical impact, it will be critical to direct their application to the plaque area(s) at highest risk.

Comprehensive biomechanical and anatomical atherosclerotic plaque metrics predict major adverse cardiovascular events: A new tool for clinical decision making.

BACKGROUND AND AIMS: Anatomical imaging alone of coronary atherosclerotic plaques is insufficient to identify risk of future adverse events and guide management of non-culprit lesions. Low endothelial shear stress (ESS) and high plaque structural stress (PSS) are associated with events, but individually their predictive value is insufficient for risk prediction. We determined whether combining multiple complementary, biomechanical and anatomical plaque characteristics improves outcome prediction sufficiently to inform clinical decision-making. METHODS: We examined baseline ESS, ESS gradient (ESSG), PSS, and PSS heterogeneity index (HI), and plaque burden in 22 lesions that developed subsequent events and 64 control lesions that remained quiescent from the PROSPECT study. RESULTS: 86 fibroatheromas were analysed from 67 patients. Lesions with events showed higher PSS HI (0.32 vs. 0.24, p<0.001), lower local ESS (0.56Pa vs. 0.91Pa, p = 0.007), and higher ESSG (3.82 Pa/mm vs. 1.96 Pa/mm, p = 0.007), while high PSS HI (hazard ratio [HR] 3.9, p = 0.006), high ESSG (HR 3.4, p = 0.007) and plaque burden>70 % (HR 2.6, p = 0.02) were independent outcome predictors in multivariate analysis. Combining low ESS, high ESSG, and high PSS HI gave both high positive predictive value (80 %), which increased further combined with plaque burden>70 %, and negative predictive value (81.6 %). Low ESS, high ESSG, and high PSS HI co-localised spatially within 1 mm in lesions with events, and importantly, this cluster was distant from the minimum lumen area site. CONCLUSIONS: Combining complementary biomechanical and anatomical metrics significantly improves risk-stratification of individual coronary lesions. If confirmed from larger prospective studies, our results may inform targeted revascularisation vs. conservative management strategies.