Abstract

Introduction: Low ESS, a pro-inflammatory stimulus, is an important predictor of coronary plaque development/progression. Whether low ESS adds incremental predictive value for future major adverse cardiac events (MACE) in untreated coronary lesions in high-risk patients with an acute coronary syndrome (ACS) is unknown. Methods: In the PROSPECT study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of non-culprit (nc) lesion MACE from untreated coronary lesions in 3 year followup (f/u) were large plaque burden (PB), small minimum lumen area (MLA), and thin cap fibroatheroma (TCFA) morphology. In the present analysis, all nc-lesions leading to a new MACE in f/u (nc-MACE lesions, n=50) and ~4-fold randomly selected control nc-lesions without f/u MACE (nc-non-MACE lesions) were analyzed. Baseline ESS for each lesion was calculated using computational fluid dynamics. A propensity score for low ESS was determined accounting for PB, MLA, TCFA, artery and location in the artery. Local ESS (lowest ESS in 90 o arc around the artery) was then examined for incremental association with MACE. Results: Imaging was sufficient for analysis in 32 nc-MACE lesions. Two nc-MACE lesions were excluded due to unreliable lesion morphology. Non-fibroatheromas were too few for analysis and excluded. Final dataset included 145 lesions: 13 nc-MACE TCFA, 10 nc-MACE thick cap fibroatheroma (ThCFA), and 122 non-nc-MACE lesions (63 TCFA, 59 ThCFA). Cumulative frequency distribution shows lesions responsible for future nc-MACE frequently exhibited low ESS (Figure). In a propensity-adjusted multivariable model, low ESS was strongly associated with nc-MACE in f/u (odds ratio 0.16 [95% CI 0.06-0.40], p<0.0001). Conclusions: After accounting for large PB, small MLA, TCFA, and lesion location, low local ESS adds significant and substantial incremental predictive value to identify high-risk untreated lesions likely to cause MACE during 3 year followup.

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