Vascular responses to coronary calcification following implantation of newer-generation drug-eluting stents in humans: impact on healing

Abstract

Aims Vascular calcification is routinely encountered in percutaneous coronary intervention (PCI) and severe coronary calcification is a known predictor of in-stent restenosis and stent thrombosis. However, the histopathologic mechanisms behind such events have not been systematically described. Methods and results From our registry of 1211 stents, a total of 134 newer-generation drug-eluting stents (DES) (Xience, Resolute-Integrity, PROMUS-Element, and Synergy) with duration of implant ≥30 days were histologically analysed. The extent of calcification of the stented lesions was evaluated radiographically and divided into severe (SC, n = 46) and non-severely calcified lesions (NC, n = 88). The percent-uncovered struts per section {SC vs. NC; median 2.4 [interquartile range (IQR) 0.0–19.0] % vs. 0.0 (IQR 0.0–4.6) %, P = 0.02} and the presence of severe medial tears (MTs) (59% vs. 44%, respectively, P = 0.03) were greater in SC than NC. In addition, SC had a higher prevalence of ≥3 consecutive struts lying directly in contact with surface calcified area (3SC) (52% vs. 8%, respectively, P < 0.0001). Multivariate analysis demonstrated that sections with duration of implantation ≤6 months [odds ratio (OR): 7.7, P < 0.0001], 3SC (OR: 6.5, P < 0.0001), strut malapposition (OR: 5.0, P < 0.0001), and lack of MTs (OR: 2.5, P = 0.0005) were independent predictors of uncovered struts. Prevalence of neoatherosclerosis was significantly lower in SC than that of NC (24% vs. 44%, P = 0.02). Conclusion Severe calcification, especially surface calcified area is an independent predictor of uncovered struts and delayed healing after newer-generation DES implantation. These data expand of knowledge of the vascular responses of stenting of calcified arteries and suggests further understand of how best to deal with calcification in patients undergoing PCI.

Calcified nodule: A rare but important cause of acute coronary syndrome with worse clinical outcomes

“…CN has been described as a lesion frequently seen in older individuals with chronic kidney disease, and diabetes mellitus, who tends to have heavily calcified arteries where medial tear is often seen during PCI due to excessive balloon dilatation, which may lead to worse clinical outcomes in terms of TLR from neointimal proliferation [5,8]. In the current study, all patients received IVUS guided PCI, which may have reduced the risk of medial disruption and subsequent excessive neointimal hyperplasia.…”

“…In the current study, all patients received IVUS guided PCI, which may have reduced the risk of medial disruption and subsequent excessive neointimal hyperplasia. In addition, delayed in-stent strut neointimal coverage [5] and stent malapposition [9] were often identified in heavily calcified lesions where CN and stent struts are exposed to blood flow, subsequent thrombus formation and recurrence of ACS (e.g., majority are in-stent CN, minority are stent thrombosis [10]), or a silent thrombus with organization ( Fig. 1).…”

“…Nakamura et al reported histopathologic analysis of ISR lesions obtained by directional coronary atherectomy from hemodialysis patients and suggested that one of the potential mechanisms of in-stent CN is related to the protrusion of a CN (already present at the time of stenting) into the lumen through the stent struts [4]. In our institution, we have received over 1200 stents from 700 sudden death individuals for over 2 decades [5]. Although cases with in-stent CN are limited, most of the cases were caused by the protrusion of the CN into the stent strut, except a single case where CN occurred within the neointimal tissue 10 years after stent implantation (i.e., de novo) [6,7].…”

The biological responses and mechanisms of endothelial cells to magnesium alloy

“…Accordingly, the drug-eluting stent (DES) is applied for suppressing the excessive proliferation of VSMCs to alleviate ISR [ 9 , 10 ]. Despite that, the loading drugs, such as rapamycin (sirolimus) and paclitaxel, repress the excessive proliferation of VSMCs, but they also induce dysfunction of endothelial cells (ECs), which contributes to the delayed re-endothelialization and late stent thrombosis (LST) [ 11–16 ]. Biodegradable materials may disappear completely, thus avoid some lifelong problems caused by permanent implants, including permanent physical irritation and local chronic inflammatory reactions [ 17 ].…”

Pathology of severe coronary artery calcification treated with orbital atherectomy followed by balloon modification

“… 1 In this case, the crown rotated and ‘knocked’ the plate-like calcification discontinuously, thereby breaking the thick calcification without a medial tear, which avoided restenosis. 2 …”