Abstract 10038: Combined Low Endothelial Shear Stress and High Plaque Structural Stress Heterogeneity Predicts Non-Culprit Major Adverse Cardiovascular Events; Insights From the PROSPECT Study

Abstract

Introduction: Low endothelial shear stress (ESS) is a pro-atherogenic stimulus associated with coronary plaque development, while high plaque structural stress (PSS) and its heterogeneity is associated with plaque destabilization. Previous studies showed that combining ESS and PSS additively predicts plaque progression, but no studies have determined their ability to predict major adverse cardiovascular events (MACE). We examined whether combining ESS and PSS improves MACE prediction in patients with acute coronary syndrome. Methods: We examined baseline ESS, ESS gradient, PSS, and PSS heterogeneity index (HI) in 22 non-culprit lesions (NCL) leading to future MACE, and 64 randomly selected control NCLs without MACE from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. ESS was calculated by computational fluid dynamics and PSS by finite element analysis on co-registered lesions. Results: 86 lesions (55 thin-cap and 31 thick-cap fibroatheromas) were analyzed from 67 patients. Lesions that caused future MACE showed baseline higher PSS HI (0.32 vs. 0.24, p<0.001), lower ESS (0.56 vs. 0.91 Pa, p=0.007), higher ESS gradient (3.82 vs. 1.96 Pa/mm, p=0.007), smaller minimum lumen area (MLA, 3.83 vs. 5.05 mm 2 , p=0.002), and larger plaque burden (PB, 70% vs. 59.4%, p<0.001). Independent predictors of MACE in multivariate analysis included high PSS HI (hazard ratio [HR] 3.9, 95% confidence interval [CI] 1.5-10.4, p=0.006), high ESS gradient (HR 3.4, 95% CI 1.4-8.1, p=0.007), and high PB at the MLA (HR 2.6, 95% CI 1.1-6.3, p=0.035). Combining low ESS and high PSS HI improved test specificity to 0.83 and positive predictive value (PPV) to 59.3%, while maintaining high sensitivity at 0.73 and high negative predictive value (NPV) at 89.8%. Combining low ESS, high ESS gradient, and high PSS HI further improved prognostication, predicting 80% of MACE over 3-year follow-up (p<0.001). Conclusions: Combining baseline low ESS, high ESS gradient and high PSS heterogeneity significantly improves risk stratification of NCLs over each parameter alone. Combining parameters exceeds PPV and NPV achieved by imaging alone, and may identify lesions suitable for preemptive intervention strategies to avert future MACE.