Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS: Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. METHODS AND RESULTS: The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P < 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P < 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS. CONCLUSIONS: The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov (NCT03129503).

Impact of real-time angiographic co-registered optical coherence tomography on percutaneous coronary intervention: the OPTICO-integration II trial.

AIMS: Longitudinal geographic mismatch (LGM) as well as edge dissections are associated with an increased risk of adverse events after percutaneous coronary intervention (PCI). Recently, a novel system of real-time optical coherence tomography (OCT) with angiographic co-registration (ACR) became available and allows matched integration of cross-sectional OCT images to angiography. The OPTICO-integration II trial sought to assess the impact of ACR for PCI planning on the risk of LGM and edge dissections. METHODS: A total of 84 patients were prospectively randomized to ACR-guided PCI, OCT-guided PCI (without co-registration), and angiography-guided PCI. Primary endpoint was a composite of major edge dissection and/or LGM as assessed by post-PCI OCT. RESULTS: The primary endpoint was significantly reduced in ACR-guided PCI (4.2%) as compared to OCT-guided PCI (19.1%; p = 0.03) and angiography-guided PCI (25.5%; p < 0.01). Rates of LGM were 4.2%, 17.0%, and 22.9% in the ACR-guided PCI, in the OCT-guided PCI, and the angiography-guided PCI groups, respectively (ACR vs. OCT p = 0.04; ACR vs. angiography p = 0.04). The number of major edge dissections was low and without significant differences among the study groups (0% vs. 2.1% vs. 4.3%). CONCLUSION: This study for the first time demonstrates superiority of ACR-guided PCI over OCT- and angiography-guided PCI in reducing the composite endpoint of major edge dissection and LGM, which was meanly driven by a reduction of LGM.