Mysteries behind stent struts

Intracoronary stents were introduced over a decade ago to reduce restenosis rates by eliminating early recoil and late remodeling of the vessel after percutaneous coronary intervention. Although stent implantation provides vessel support and optimal angiographic outcome, it is associated with various degrees of intimal hyperplasia (IH) consisting of matrix proteoglycan content and smooth muscle and inflammatory cells that fill the intrastent area and manifest in different patterns (focal diffuse and proliferative) of in-stent restenosis [1]. The mechanisms for the development of IH have been identified in part. Among them are the traditional contributors associated with the restenosis process, such as cytokines derived from platelet deposition on the stent, inflammatory [2] and foreign body reactions, metal allergies, and smooth muscle cell proliferation, which is related to degree of injury. Stent design and strut thickness were also identified as contributors to IH [3]. Over the years, lesion subsets and anatomical considerations such as vessel size, lesion and stent length, and bifurcation disease have also been identified as predictors for neointima formation [4]. Despite multiple approaches and efforts to minimize the neointimal formation following stenting, the amount of IH seen at 6 months could not be abolished. Also, patient subsets with metabolic abnormalities such as diabetes, patients with chronic renal failure, and those with high C reactive protein were considered to be at higher risk for developing in-stent restenosis [5]. The clinical impact of neointima formation was seen only on patients who developed > 50% narrowing of the intrastent lumen, who presented with anginal symptoms, and who required repeat revascularization. The dynamic behind the IH was not consistent and was difficult to predict; while some patients experienced aggressive progression of IH, others tended to regress spontaneously. Many attempts were targeted to reduce the process on neointima formation poststenting, yet only the use of drug-eluting stents (DES) successfully resulted in a significant reduction of IH at 6–8 months when compared to bare metal stents (BMS). The dynamics beyond this time point are still under investigation, however. Hong et al. [6] attempted to address the question of status of IH behind bare metal stent struts by conducting an intravascular ultrasound (IVUS) study with 6and 24-month follow-up on 120 patients. The authors report dynamic processes of regression or progression between 6and 24 months in nearly all the patients in their analysis. It is a comfort to find that there was no further recoil in the stents between 6 and 24 months and that the stent lumen depends only on the status of the degree of inrastent intima. While regression of intima was observed in 76% of the lesions, progression was demonstrated in 24% of the lesions. While the progression of IH can be explained by an ongoing inflammation process, regression of IH can be explained by absorption of the edematous component of the protegycan content. What is not clear is the time point at which this process is stabilized: is it 12, 18, or 36 months? The 6-month angiographic time point was chosen based on angiographic findings of restenosis, and recently this time point was shifted to 8–9 months, which reflects more complete healing after bare metal stenting. The IVUS studies performed by Hong et al. [6] and others suggest that there is an ongoing dynamic behind the stent struts. Yet, these are small changes that may have no clinical impact. In the Hong et al. [6] analysis, for the majority of patients, these changes were minimal and within the error of the study. In 77/120 (64%) of the lesions, an increase or decrease in IH was < 0.3 mm, while in only 14/ 120 (11.6%) of the lesions, the change was > 1.0 mm. The clinical relevance of these findings in the Hong et al. [6] study are limited since only a handful of patients who had progression required delayed revascularization and none of the patients canceled planned intervention due to potential regression of restenosis. It is hard to imagine that we will be able to convince a symptomatic patient with in-stent restenosis to wait until regression occurs, meanwhile keeping the patient on medical therapy, especially when there is no clue as to which of these processes will regress or progress.