Morphological Predictors of Restenosis After Coronary Stenting in Humans

Abstract

Background — Experimental studies suggest that arterial injury and inflammation lead to increased neointimal growth after stenting. Despite the increased use of coronary stents in humans, there are only limited pathological data on the morphological features of in-stent restenosis. Methods and Results — Detailed histology was performed on 116 stents, implanted ≥90 days in 87 coronary arteries, from 56 patients (mean age, 59±13 years). The mean duration of stent implant was 10 months. In-stent restenosis was defined as a stent area stenosis of >75%. Lumen area increased as stent area increased ( r 2 =0.27, P =0.0001), but there was a much stronger correlation between stent area and neointimal area ( r 2 =0.70, P <0.0001). Arterial medial fracture was associated with a 29% increase ( P <0.01) in neointimal thickness compared with arteries with an intact media. Neointimal thickness ( P =0.0001), inflammatory cell density ( P <0.0001), and neointimal vascular channel density ( P <0.0001) were greater when struts were in contact with a ruptured arterial media compared with fibrous plaque or an intact fibrous cap. Stent strut penetration into a lipid core was associated with increased neointimal thickness ( P =0.04) and inflammatory cell density ( P =0.03). Neointimal inflammatory cell content was 2.4-fold greater in stents with restenosis versus no restenosis, and inflammation was associated with increased neoangiogenesis. Conclusions — Coronary stenting that is accompanied by medial damage or penetration of the stent into a lipid core induces increased arterial inflammation, which is associated with increased neointimal growth. These data suggest the use of stenting strategies that reduce inflammation and neoangiogenesis to reduce the incidence of restenosis.

Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

“…7,22,23,32,35,46,77,81,82,86 The mechanical impact of the investigated stents was evaluated in terms of the equivalent von Mises stress (ES) distribution predicted in the artery wall. The ES is calculated as follows:…”

“…Over the past two decades, several clinical studies have identified strong correlations between neointimal hyperplasia following coronary stent deployment and both stent-induced arterial injury 7,22,23,32,35,46,77,81,82,86 and altered vessel hemodynamics. 6,17,18,20,21,52,71,79,88 In light of these observations, a significant body of research has been carried out in this area.…”

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

“…Local production of cytokines (eg, interleukin [IL]-1, IL-6 and tumour necrosis factor-alpha [TNF-α]) by activated macrophages, VSMCs and endothelial cells also play a major role in inducing an inflammatory reaction at the site of injury (18)(19)(20). Increased neointimal macrophage infiltration correlates with the extent of neointima formation in humans (21). Vessel wall overstretching during PCI may also induce an inflammatory response by stimulating infiltration of inflammatory leukocytes into the adventitia (22).…”

Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury

“…To explore the role of AGGF1 in VSMCs functions, we studied neointimal formation, a process caused mostly by VSMCs proliferation and migration 19, 21, 24, 25, 26. Immunostaining showed that AGGF1 expression was dramatically reduced in carotid arteries with neointimal formation after vascular injury (Figure 1B and 1C).…”