Validation and application of OCT tissue attenuation index for the detection of neointimal foam cells.

Neointimal infiltration with foamy macrophages is recognized as an early and important sign of de-novo atherosclerosis after stent implantation (neoatherosclerosis). Recent histopathological studies have proven that automated quantification of signal attenuation using intravascular optical coherence tomography (OCT) imaging allows for sensitive identification of macrophages in native atherosclerotic disease. Whether this is true for neointimal foam cells in the setting of neoatherosclerosis remains unknown. Autopsy samples of stented coronary arteries (n = 13 cases) were evaluated by histology and OCT. After co-registration with histology, the attenuation rate of emitted laser light was measured in regions with and without neointimal foamy macrophages relative to its peak intensity at the blood-tissue interface. Attenuation index was subsequently determined as slope of a regression curve fitted to individual data points. Receiver operating curve (ROC) analysis was used to establish an optimal cut-off for detecting foamy macrophages in homogenous and non-homogenous neointima, respectively. Finally, the tissue attenuation index was applied to confirm or exclude the presence of neointimal foamy macrophages in symptomatic patients presenting with in-stent restenosis and undergoing intravascular OCT imaging (n = 29 cases). Tissue attenuation index derived from post-mortem samples differed significantly between histologically confirmed regions with and without neointimal foamy macrophages (- 1.23 ± 1.42 vs. - 0.52 ± 1.79, p < 0.05). ROC analysis was able to distinguish neointima with foamy macrophage infiltration from neointima without (93% sensitivity, 73% specificity, cut-off - 0.79, AUC 0.87 for homogenous neointima and 40% sensitivity, 95% specificity, cut-off - 1.93, AUC 0.69 for non-homogenous neointima). In symptomatic patients presenting with in-stent restenosis after stent implantation and undergoing intravascular imaging with OCT, neointimal foamy macrophages were detected in 34.2% of homogenous and 43.6% of non-homogenous neointimal ROI's evaluated. OCT-derived and histopathologically validated tissue attenuation index enables identification of neointimal foamy macrophages in stented coronary arteries. Such image-based post-processing software algorithm may help discern and triage subjects at increased risk for device-related events.

Assessment of a pro-healing stent in an animal model of early neoatherosclerosis.

BACKGROUND: Neoatherosclerosis represents an accelerated manifestation of atherosclerosis in nascent neointima after stenting, associated with adverse events. We investigated whether improved reendothelialization using RGD-coated stents results in diminished vascular permeability and reduced foam cell formation compared to standard DES in atherosclerotic rabbits. METHODS AND RESULTS: Neointimal foam cell formation was induced in rabbits (n = 7). Enhanced endothelial integrity in RGD-coated stents resulted in decreased vascular permeability relative to DES, which was further confirmed by SEM and TEM. Cell culture experiments examined the effect of everolimus on endothelial integrity. Increasing concentrations of everolimus resulted in a dose-dependent decrease of endothelial cell junctions and foam cell transformation of monocytes, confirming the relevance of endothelial integrity in preventing permeability of LDL. CONCLUSION: Incomplete endothelial integrity was confirmed as a key factor of neointimal foam cell formation following stent implantation. Pro-healing stent coatings may facilitate reendothelialization and reduce the risk of neoatherosclerosis.

Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent Relative to Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex Vivo in a Swine Shunt Model.

OBJECTIVES: This study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model. BACKGROUND: Previous pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers. METHODS: An ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy. RESULTS: Xience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p < 0.001; Synergy: 8.64, 95% CI: 4.43 to 12.84, p < 0.001; Nobori: 4.22, 95% CI: -0.06 to 8.49, p = 0.055; Orsiro: 2.95, 95% CI: -1.26 to 7.15, p = 0.286). The number of cell nuclei on strut surfaces was also the least in Xience-EES, with a significant difference relative to BioMatrix Flex, Nobori, and Orsiro (mean ratios: BioMatrix Flex: 4.73, 95% CI: 2.46 to 9.08, p < 0.001; Synergy: 1.44, 95% CI: 0.75 to 2.76, p = 0.51; Nobori: 5.97, 95% CI: 3.11 to 11.44, p < 0.001; Orsiro: 5.16, 95% CI: 2.69 to 9.91, p < 0.001). CONCLUSIONS: Xience-EES's overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis.