Abstract

Objectives: In-stent restenosis (ISR) is traditionally associated with neointimal hyperplasia. However, recent studies have suggested that an underlying progression of atherosclerotic process, different from intimal proliferation, could be present in these cases. We aimed to evaluate the patterns of plaque progression in ISR using a complex Multislice Angio Computed Tomography 64, Virtual Histology Intravascular ultrasound (VH-IVUS) and Optical Coherence Tomography (OCT) assessment. Methods: 23 subjects with symptomatic ISR documented by Angio CT mulslice assessment (6 months to 1 year after bare metal stent implantation) underwent coronarography followed by VH-IVUS and OCT. All ISR (n=23) and non-ISR plaques in the same native coronary artery (n=37) were screened and analyzed, including assessment of plaque density (by Angio CT), plaque composition - lipid content and necrotic core (by VH-IVUS) and assessment of the tissue structure and fibrous cap thickness by OCT. Results: ISR plaques tend to be larger in volume than non-ISR ones (plaque volume 92.5 mm3 vs 52.45 mm3 p<0.0001), as determined by Angio CT. They also present larger amounts of Low Density Plaque (LDP) <30 Hounsfield Units (HU) by Angio CT multislice (33.3 mm3 vs 17.5 mm3, p<0.0001) and higher contents of lipid reach atheroma by VH-IVUS (42% vs 24%, p=0.05). OCT analysis indicated the presence of an irregular lumen shape in 43.4% of ISR and 27% of non-ISR lesions (p=0.05). Also, by OCT restenotic tissue was heterogenous in 26.1% of cases, homogenous in 39.1% of cases and multilayered in 30.4% of cases. Presence of a cap thickness <100μm by OCT, identified in 14 of ISR lesions (60.8%) and in only 7 of non ISR lesions (18.9%), was associated with Angio CT markers of plaque vulnerability such as LDP <30 HU in 11 cases (47.8% of ISR and 28.5% of non ISR lesions, p<0.001) and VH-IVUS markers of instability (necrotic core in 21.7% of ISR lesions and 10.8% of non –ISR lesions, p=0.05 and >40% lipid reach atheroma burden in 39.1% of ISR lesions). Conclusions: Plaque characterization using a complex and combined Angio CT multislice, VH-IVUS and OCT assessment identified multiple stages of atherosclerosis development within the in-stent restenotic tissue, from very vulnerable stages to stable plaques. Markers of vulnerability identified by Multislice CT correlated well with OCT and VH-IVUS aspects indicative of an unstable pattern. However, the OCT assessment indicates a variety of plaque morphology within the ISR lesions, proving the presence of different stages of atherosclerosis in these lesions.

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