Case 4 -
Hypersensitivity in Cypher Sirolimus-eluting Stent / Accelerated Neoatherosclerosis in Taxus Paclitaxel-eluting Stent
Renu Virmani, CV Path, Gaithersburg, MD
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Case #4a: 67 year old woman with a history of acute MI and left circumflex (LCA) balloon angioplasty in 1999, BMS placement in LCA in 2000, DES (Cypher sirolimus-eluting stents) placement in LAD and LD1 in 2006, BMS placement in LD1 in 2007, and DES (Taxus Liberte Paclitaxel-eluting stents and Endeavor Resolute Zotarolimus-eluting stents) in RCA in 2007; presented with AMI and cardiogenic shock in April 2010.
Case #4b: 61 year old black male, with history of ischemic cardiomyopathy, ventricular and supraventricular arrhythmias, hypertension, hyperlipidemia, diabetes, acute and chronic renal failure, coronary artery stents in LAD and RCA 10 years ago (BMS), in LCX 9 years ago (BMS), and in RI 4 years ago (DES). The subject received AICD placement 8 years ago and replacement 2 years ago, and recent ablation; found deceased on floor at home.
Case 4a - Figure 5
extensive inflammation with eosinophil infiltration (Luna, 1000x).
Case 4b - Figure 1
low-power image of BMS implanted in RCA (Movat, 20x).
Case 4b - Figure 2
newly formed necrotic core within the in- stent area. A number of cholesterol crystals (needle- shaped) were identified in the core. (Movat, 100x)
Case 4b - Figure 3
low-power image of Taxus stent implanted in RI (Movat, 20x).
The advent of Drug-eluting stent (DES) has substantially reduced the incidence of restenosis after
stent implantation. The stents act as a vector for local drug delivery altering in-stent pathophysiology
by delivering high concentrations of antiproliferative compounds directly to the site of arterial injury.
On the other hand, there is increasing concern over the risk of late stent thrombosis particularly
following cessation of antiplatelet therapy. The clinical implications of LST are dire with a reported
mortality of up to 45%.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Case #4a: In the Cypher sirolimus-eluting stent implanted for 3.5 years in left anterior descending
artery (LAD), there is extensive peri-strut chronic inflammation with lymphocytes, macrophages,
eosinophils and focal granulomatous inflammation with multinucleated giant cells; multiple foci of
malapposition of stent struts with extensive fibrin-rich thrombus interposed between stents and vessel
wall. In the area of bare metal stent (BMS) implanted for 2.5 years in diagonal branch, there is up to
40% luminal narrowing by fibrous neointimal thickening with minimal inflammation.
Case #4b: BMS implanted for 10 years in proximal right coronary artery (RCA) showed peri-strut
angiogenesis and newly formed necrotic core within the in-stent area. Taxus paclitaxel-eluting stent
placed for 4 years in proximal and distal ramus intermedius (RI) demonstrated necrotic core formation
around struts. The fibrous cap was thinned and infiltrated by macrophages and lymphocytes. There was
adherent fibrin and platelet rich thrombus in the lumen area.
Late DES thrombosis due to ;
i) Delayed arterial healing (Poor endothelialization, residual necrotic core prolapse, fibrin
Case #4a - Hypersensitivity in Cypher sirolimus-eluting stent
Case #4b - Accelerated neoatherosclerosis in Taxus paclitaxel-eluting stent
Review of the Literature/Treatment Options:
Late stent thrombosis (LST) The major pathologic finding distinguishing DES from BMS is demonstration
of significant delay in arterial healing characterized by persistent peristrut fibrin deposition, a
decrease in smooth muscle cells, and poor endothelialization, which is a major risk factor for LST . In
addition, local arterial hypersensitivity with extensive eosinophilic infiltrate of the intima and media
has been observed in cases of LST
It has been postulated that a combination of factors including
delayed endothelialization due to antiproliferative drugs and/or persistence of the nonerodable polymer
contribute to the hypersensitivity reactions. Other factors associated with LST include stent
malapposition (arterial wall expansion), stenting over major branch points, incomplete apposition, stent
fracture, in-stent restenosis with superimposed thrombosis, and struts penetrating the necrotic core
Furthermore, emerging evidences suggest in-stent neoatherosclerosis as an important substrate for late
stent failure for both BMS and DES especially in the extended phase. A recent histopathological study
revealed that neoatherosclerosis in DES is more frequent and occurs earlier than in BMS likely from poor
endothelialization or dysfunction .
New stent technologies should aim both to inhibit neointimal proliferation and to promote
endothelialization without compromising healing. Further modifications of stent design may overcome the
problem of LST associated with current devices, which should improve early clinical outcomes of patients
treated by interventional means.
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- Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, Kolodgie FD, Finn AV, Virmani R. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol. 2011;57:1314-1322