The fibrotic tissue volume of the plaque prior to PCI determines subsequent bare-metal in-stent restenosis

Purpose: We investigated whether plaque composition is related to subsequent bare-metal in-stent restenosis. Methods: IVUS with virtual histology was performed in 124 patients prior to the implantation of a single Vision stent in a de novo native coronary artery lesion. Exclusion criteria were diabetes, STEMI, CK-MB levels > twice the upper limit of normal within the past month and ostial or bifurcation lesions. In-stent restenosis was evaluated as Late Luminal Loss (LLL) on angiography (0.88 [0.37-1.23] mm), maximal percentage area stenosis (42 [33-59] %) and percentage volume intima hyperplasia (neointima volume divided by stent volume: 27 [20-36] %) on IVUS 6 months post-PCI. Right censoring caused by the IVUS probe dead space in cases with IVUS-neointima contact over >270°, was taken into account. Due to multi-collinearity of both absolute and relative virtual histology variables, a ridge trace based (λ = 0.6) multiple linear stepwise backward regression model was constructed. The model was corrected for implanted stent length (18 [15-23] mm), diameter (3.0 [2.75-3.5] mm) and total plaque volume pre-PCI (146 [80-201] mm3). Results: Fibrous tissue volume prior to PCI (49 [30-77] mm3) was significantly and independently (p=0.038) related to LLL. Moreover fibrous tissue percentage (56 [49-61] %) was also significantly related to LLL (p=0.011). Similarly, fibrous tissue volume pre-PCI proved independently related to maximal percentage area stenosis (p=0.041) and percentage volume intima hyperplasia (p=0.004). Neither absolute nor relative amount of fibrofatty, calcified or necrotic core tissue appeared related to any of the restenosis parameters. Remodeling index (0.95 [0.85-1.06]) and plaque burden (65 [59-71] %) were equally unrelated to restenosis in the presence of total fibrous plaque volume. Conclusions: The volume of fibrous tissue in the lesion prior to PCI is positively and independently related to late luminal loss, maximal percentage area stenosis and percentage volume intima hyperplasia 6 months after bare-metal stent implantation. This observation is in accordance with the prevailing hypothesis that smooth muscle cells, the predominant cell type populating neointima, arise from fibrotic intima or media layer. Plaques with more voluminous fibrotic tissue show more pronounced restenosis, even after correction for total plaque volume pre-PCI, implanted stent length and diameter.