Dongming Hou

Drug-Eluting Stent Thrombosis: The Kounis Hypersensitivity-Associated Acute Coronary Syndrome Revisited

The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administrations Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.

Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent.

OBJECTIVESnThe current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model.nnnBACKGROUNDnNobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available.nnnMETHODSnA total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured.nnnRESULTSnHistological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents.nnnCONCLUSIONSnOur data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.

NEOINTIMAL TISSUE CLASSIFICATION USING OPTIMAL COHERENCE TOMOGRAPHY AFTER PACLITAXEL-COATING BALLOON TREATMENT IN PIG IN-STENT STENOSIS MODEL

Background: Paclitaxel-coating balloon (PCB) is a promising devise for treatment of in-stent restenosis (ISR). Recently, paclitaxel-eluting stent (PES) implantation has been reported to induce heterogeneous arterial healing as compared to sirolimus-eluting stent in optical coherence tomography (OCT) and angioscopy studies. The aim of this study is to evaluate histopathological indings with OCT and histology after PCB treatment in pig ISR model.

Vascular function of bioabsorbable stented site after complete absorption of the stent

Background: Drug-eluting bioabsorbable stents (DEBSs) represent a new device-based therapy for coronary artery disease. It has been reported that the stented segment becomes re-endothelialized after 1 month and the segments proximal and distal to the stented site are functional at 2 years. In order to examine whether after complete degradation the DEBS site function was similar to the unstented segments, we performed ex vivo vasomotor function studies using pig coronary arteries. Methods: Eighteen months after implantation in the pig coronary arteries, 10 DEBS sites [four left anterior descending (LAD), four right coronary, and two left circumflex arteries] were assessed for vasomotor function using an organ chamber apparatus. They were stimulated with potassium chloride (KCl), prostaglandin2α (PGF), and three concentrations of endothelin-1 (ET). Endothelium-dependant relaxation (EDR) to substance P (SbP; 0.01–100 pM) and endothelium-independent relaxation (EIDR) to sodium nitroprusside (SNP; 0.001–10 μM) were assessed following constriction with PGF. Remaining stent segments were fixed for histologic examination. Results: DEBS sites showed rapid response to low and high concentrations of KCl, PGF, and ET. EIDR showed concentration-dependent relaxation to SNP (13.3±4.3%, 21.3±5.6%, 52.7±7.1%, 85.5±5.4%, and 100±0%). However, there was no EDR to SbP concentration-dependent stimulation. Hematoxylin/eosin and Verhoeff–Masson staining showed evidence of smooth muscle cell (SMC) migration across polymer struts, and formation of a new abluminal layer was observed. There was complete polymer strut degradation, infiltration of inflammatory cells, and minor fibrosis around some DEBS sites. Myocardial degeneration (∼1×1.5 cm) was found in the septum adjacent to the stented LAD sites (n=4). Vessel wall within the stented segment was thicker and the lumen was narrower than in the proximal and distal segments. Conclusion: During DEBS degradation period, medial SMCs migrate to the neointima developing new layers. We have demonstrated for the first time the ex vivo contraction and relaxation responses at DEBS sites to vasoactive agents after complete degradation of the stent. SMCs recovered contractile and relaxing capabilities in this segment but endothelial function was still impaired.

Resolution of adjacent stent-induced saphenous vein graft compression: sequel to the nutcracker.

We had previously presented the first reported case of dynamic distal saphenous vein graft (SVG) anastomotic compression by adjacent stents. We hereby report follow-up angiography 5 months later, which revealed near resolution of this finding. A 56-year-old man, with postcoronary bypass surgery 6 years ago and multiple-stent placements, presented with an acute anterolateral ST-elevation myocardial infarction 5 months ago. Emergent cardiac catheterization revealed recurrent in-stent restenosis of the proximal segment of the SVG to the first diagonal branch. This SVG contained a “full metal jacket” of overlapping drug-eluting stents (DES) extending from the ostium to virtually the distal anastomosis. In particular, the culprit proximal stenotic segment contained a double layer of DES. An additional incidental finding of cyclic systolic luminal collapse or kinking was demonstrated in the short segment of distal anastomosis, just beyond stent termination. Curiously, this site demonstrated no such compression during another angiogram 4 months prior. A midnative, left anterior descending stent could be seen just below this segment (Figure 1). These 2 structures collectively resembled the 2 limbs of a nutcracker, with the anastomosis at the crux or fulcrum (Figure 2). In light of the preexistent DES double layer, as well as nonideal SVG outflow, decision was made against deployment of a third stent; and serial balloon dilatations yielded an angiographically acceptable result in the proximal SVG segment. Additionally, stent deployment was not performed at the distal anastomotic site of dynamic compression due to concerns of stent distortion. The patient presented again with possible acute coronary syndrome 5 months later. Repeat catheterization demonstrated adequate patency at the previous proximal angioplasty site. However, the dynamic anastomotic compression had essentially resolved distally (Figure 3). He was subsequently discharged Angiology Volume 59 Number 5 October/November 2008 647-648