Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS Coronary microevaginations (CME) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodeling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. METHODS AND RESULTS 557 patients from the translational OPTICO-ACS study program underwent optical coherence tomography (OCT) imaging of culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). 258 CLs had ruptured- (RFC) and 100 had intact fibrous cap (IFC) ACS as an underlying pathophysiology. CME were significantly more frequent in CL as compared to non-CL (25% vs. 4%, p < 0.001) and were more frequently observed in lesions with IFC-ACS as compared to RFC-ACS (55.0% vs. 12.7%, p < 0.001). CME were particularly prevalent in IFC-ACS causing CLs independent of a coronary bifurcation (IFC-ICB) as compared to IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4% vs. 43.7%, p = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (RR 3.36, 95%CI 1.67; 6.76, p = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both, culprit blood analysis (Culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, p = 0.048) and aspirated culprit thrombi (326 ± 162 cells/mm2 vs. 96 ± 87 cells/mm2; p = 0.017), whilst IFC-ACB confirmed the accumulation of CD4+-T-Cells as recently described. CONCLUSION This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system.