Correlation of Intravascular Ultrasound Findings With Histopathological Analysis of Thrombus Aspirates in Patients With Very Late Drug-Eluting Stent Thrombosis

Abstract

Background-Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. Methods and Results-The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls).Of 28 patients with very late DES ST, 10 patients (1020Ϯ283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2Ϯ2.4 mm 2 and evidence of vessel remodeling (index, 1.6Ϯ0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263Ϯ149 white blood cells per high-power field) and eosinophils (DES, 20Ϯ24 eosinophils per high-power field; sirolimus-eluting stents, 34Ϯ28; paclitaxel-eluting stents, 6Ϯ6; P for sirolimus-eluting stents versus paclitaxel-eluting stentsϭ0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20Ϯ24) than in those from spontaneous acute myocardial infarction (7Ϯ10), early bare-metal stent ST (1Ϯ1), early DES ST (1Ϯ2), and late bare-metal stent ST (2Ϯ3; P from ANOVAϭ0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm 2 increase in ISA cross-sectional area. Conclusions-Very

Long-term outcomes of biodegradable versus durable polymer drug-eluting stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of individual patient data from three randomised trials

“…This is thought to be due to a combination of factors including adverse lesion morphology and high thrombus burden, persistent inflammation and increased platelet reactivity, as well as chronic processes associated with delayed healing and vessel remodelling 21 . Additionally, intravascular imaging following DES implantation in STEMI has shown that at follow-up a higher proportion of struts remains uncovered compared to BMS [22][23][24] and that incomplete DES apposition 25,26 is observed more frequently, a finding that appears to indicate adverse vessel remodelling and confer a higher risk of subsequent stent thrombosis. Given this background, BP-DES may represent an attractive solution for patients with STEMI, as complete polymer biodegradation after drug elution is expected to result in a vessel wallstent interaction resembling that seen after bare metal stenting.…”

Guidelines on myocardial revascularization

“…Possibly, under some circumstances or with some DES, DAPT for 3 months could be sufficient but the evidence is not robust [219]. Recent evidence shows that (very) late stent thrombosis results from delayed hypersensitivity to components of the drug polymer device combination that causes necrotizing vasculitis and late malapposition [238]. Diabetics may require a longer duration of DAPT.…”

Triple, simultaneous, very late coronary stent thrombosis

“…3---8 Delayed neointimal coverage and a hypersensitivity reaction to components of the drug-polymer-stent combination, together with ongoing vessel inflammation, impaired healing and abnormal remodeling leading to late and very late acquired stent malapposition, have been associated with VLST, but the precise mechanism is still unknown. 9---13 Patient-related factors (including compliance with antiplatelet therapy), procedural and post-procedural factors (including type and duration of antiplatelet therapy) probably interact and predispose the patient to ST. 2,3,10 Endothelial dysfunction has also been described as an adverse consequence following coronary DES implantation, although its clinical significance is still unknown. 14 In fact, although DES target vascular smooth muscle cell proliferation and migration (neointimal hyperplasia), the key factors in the development of restenosis, they impair re-endothelialization and promote late in-stent neoatherosclerosis, a new concept whose precise mechanism is also unknown, that acts as another substrate for VLST.…”

“…15,16 This also involves both proximal and distal nonstented reference segments and leads to delayed arterial healing, impairment of endothelial nitric oxide synthesis and imbalance between endothelium-derived relaxing and contracting factors, resulting in a thrombogenic environment and paradoxical vasoconstriction of the adjacent segments. 10,16 Moreover, stent-induced mechanical changes in vessel geometry modify its response to endothelial injury and have been linked to the pathobiology of ST. 17 To the best of our knowledge, this is the first report of a VLST, 81 months post-PCI, simultaneously occurring in the three coronary artery territories following discontinuation of antiplatelet therapy.…”

“…Unfortunately there was no histopathological analysis of thrombus aspirates to search for eosinophilic infiltrates, which are common in thrombi from very late DES thrombosis associated with hypersensitivity reactions to the drug---polymer---stent combination, and related to the extent of stent malapposition. 10 Several mechanisms have been implicated in this positive vascular remodeling, such as procedure-related acute vessel injury, hypersensitivity reactions to the stent polymer coatings, toxic effects of antiproliferative drugs on the vessel, and even focal infections. 14--- 21 We hypothesize that a complex interplay of several thrombogenic factors probably acted together to create this ''perfect storm'' scenario that ended in a dramatic triple stent thrombosis: significant underlying endothelial dysfunction provoking an abnormal response to endothelial shear stress, abnormal rheological conditions and possible very late acquired stent malapposition; recent discontinuation of antiplatelet therapy (probably playing a pivotal role); and an inflammatory state ---a recent gout attack, which has also been linked to acute MI.…”