Case 1 -
Interventional Cardiovascular Pathology
Elena R. Ladich
CVPath Institute, Inc.
Virtual Slides as well as Still Images are displayed below.
For the fastest viewing of virtual slides, click:
under each thumbnail image below. You must have Aperio ImageScope installed on your PC.
Or, click on slide thumbnail images to view each slide
If you do not already have Aperio ImageScope, Windows users with administrator privileges may download and install a free version in order to view USCAP Virtual Slides. Click the icon on the right to get your free copy: ||
in a Web-based slide viewer, which is somewhat slower.
If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137.
Cypher Stent In Left Circumflex Artery With Late Stent Thrombosis (LST)
Since their commercial introduction in 2003, drug eluting stents (DES) have rapidly altered the
management of coronary artery disease. Prior to their development, the percutaneous management of
coronary artery disease was performed predominantly by implantation of bare metal stents (BMS). Although
BMS technology dramatically lowered the rate of restenosis compared with balloon angioplasty, in-stent
restenosis secondary to neointimal proliferation remained an important clinical problem.
The advent of 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. Two FDA approved
DES are currently in use-- Cypher (sirolimus-eluting) and Taxus (paclitaxel-eluting). Drug delivery from
the stent platform is controlled through polymer-based drug release. Clinical trials have shown that DES
have reduced the rate of angiographic restenosis by as much as 70% to 90% compared with BMS, however,
there is increasing concern over the risk of late stent thrombosis (> 30 days post
implantation) particularly following cessation of antiplatelet therapy. Although the rate of late
thrombosis appears to be similar in BMS and DES in clinical trials up to 12 months, in "real world"
clinical practice there is an increase in LST for patients with DES. The clinical implications of LST
are dire with a reported mortality of up to 45%.
Case 1 - Slide 1
Case 1 - Figure 1 - Platelet-rich thrombus around stent strut with persistent peri-strut fibrin (Movat x 10)
Case 1 - Figure 2 - Lumen with occlusive platelet-rich thrombus (Movat x 2)
Pathology of Coronary Artery Stenting
With the introduction of coronary artery stenting, a variety of pathologic responses related to
device implantation have been observed. Examination of postmortem human coronary arteries demonstrate
that after stenting, arteries follow a response to injury pattern of wound healing. Thrombus deposition
and acute inflammation are followed by a granulation tissue response with neovascularization, smooth
muscle proliferation and migration, and the replacement of acute by chronic inflammatory cells.
Restenosis after stenting occurs secondary to the accumulation of smooth muscle cells and extracellular
matrix (ECM). The ECM contains varying concentrations of proteoglycans, hyaluronan, and collagen (types
I and III). The ECM modulates important events within the developing neointima including cell
proliferation, migration, growth factor expression and remodeling. Proteoglycans and hyaluronan are
synthesized by smooth muscle cells and participate in regulation of vascular permeability, lipid
metabolism, and thrombosis.
The neointima remodels over time with changes in proteoglycans and replacement of type III collagen
with type I collagen. In summary, neointimal hyperplasia is a proliferative maladaptive healing response
to stent implantation and injury.
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. Delayed healing has been demonstrated in both Cypher and Taxus DES
at autopsy and 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, stent length, incomplete apposition caused by suboptimal stent deployment, in-stent
restenosis with superimposed thrombosis and struts penetrating the necrotic core. Breaching a necrotic
core may lead to the exposure of thrombogenic lipid content to flowing blood.
New stent technologies should aim to inhibit neointimal proliferation and promote endothelialization
without compromising healing in order to avoid late thrombotic complications.
- Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological mechanisms of fatal late coronary stent thrombosis in humans. Circulation, 2003; 108: 1701-1706
- Virmani R. Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie F. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation 2004; 109: 701-705
- Joner M, Finn A, Farb A, Mont E, Kolodgie F, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans. J Am Coll Cardiology, 2006; 48: 193-202.
- Farb A, Weber D, Koldogie F, Burke A, Virmani R. Morphological predictors of restenosis after coronary stenting in humans. Circulation 2002; 105: 2974-2980
- Moses, JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. NEJM 2003; 349: 1315-1323.