Atherosclerosis: Practical Implications for Pathologists
Section 6 -
Percutaneous Coronary Intervention (PCI) - Angioplasty (PTCA) and Stenting
Case 5 - Percutaneous coronary intervention (PCI) - angioplasty (PTCA) and
This 63-year-old man had congestive heart failure with increasing dyspnea, orthopnea and paroxysmal
nocturnal dyspnea. Past history included prior CABG (LITA to LAD), angioplasty (PTCA) of his circumflex
artery 2 years ago, PTCA with stenting of his RCA one year ago, myocardial infarct, diabetes mellitus,
systemic arterial hypertension, peptic ulcer and heavy smoking.
He had worsening chest pain and developed pulmonary edema with respiratory failure requiring
intubation. He also developed atrial fibrillation, refractory to therapy.
Coronary catheterization showed a patent LITA graft, but with a severe distal LAD stenotic lesion
which was angioplastied (PTCA). Following this procedure he developed acute renal failure, probably from
the radiographic dye and systemic hypotension. Coagulopathy was noted with a high INR that was difficult
He continued to have episodes of pulmonary edema, atrial fibrillation and developed pulmonary
hemorrhage. Creatine kinase was noted to be elevated. Shortly thereafter he had a cardiac arrest and
Findings at complete autopsy: recent and prior angioplasty, CABG
- Old patchy subendocardial infarct of posterior left ventricle
- Recent myocardial infarct of anteroseptal and lateral left ventricle
- Coronary atherosclerosis - severe triple vessel coronary artery disease
- Prior angioplasty / PTCA effects of circumflex artery with restenosis - disrupted internal elastic lamina
with fibrointimal plaque
- Prior stent RCA - mild restenosis in the stent - fibrointimal plaque in the stent
- LITA graft patent; mild stenosis at anastomosis
- Recent angioplasty / PTCA effects in distal LAD - atherosclerotic plaque disruption with cracked plaque
- Severe pulmonary edema with moderate alveolar hemorrhage
Interventional Coronary Artery Pathology
The last decades have given rise to an explosion of interventional and surgical devices for the
management of atherosclerotic cardiovascular disease.  In many cases non-surgical procedures
(including vascular angioplasty) are replacing surgical procedures such as bypass grafting. Many
interventional cardiac procedures are done in North America each year. Every new technology creates new
pathological processes and challenges for pathological examination.
Techniques such as balloon angioplasty and stenting are now grouped by Cardiologists under the term
Percutanous coronary intervention - PCI.
Percutaneous Transluminal Coronary Angioplasty - PTCA - Balloon Angioplasty
Angioplasty represents a major advance in the treatment of coronary artery and vascular disease. The
procedure is used for individuals with stable and unstable angina (chest pain), congestive heart failure
secondary to ischemia, and with myocardial infarction (MI).
Balloon dilatation causes a radial expansion force to the artery wall with denudation of the
lining/endothelium of the artery, fracture of the atherosclerotic plaque, intramural dissection and
stretching of the vessel. The plaque is compressed and redistributed in the artery.
This procedure, by its very nature, generates vascular pathology with newly created complex
pro-thrombotic blood exposed surfaces. Complications include thrombosis, myocardial infarction, arterial
occlusion, thromboembolism, and vascular spasm - all of which may acutely close the vessel. Potent
anti-platelet agents are given to prevent this.
Acute pathological findings at angioplasty
|Plaque compression ||Intimal flaps|
|Plaque rupture ||Thrombus|
|Plaque cracking ||Dissection|
Chronically the artery narrows by a process termed "restenosis".
Restenosis occurs in approximately 30-40 % of patients after PTCA. Stents, especially drug eluting
types, have significantly decreased the rate of arterial restenosis.
Restenosis is a complex vascular healing process with thrombosis, chronic inflammation, myofibroblast
migration, proliferation and synthesis of extracellular matrix - processes similar to wound healing in
other sites. Early, the injured arterial wall may thrombose. The injured vessel and the adherent
thrombus release growth factors causing smooth muscle cell proliferation and migration. The smooth
muscle cells of the media layer proliferate and migrate to the neointima (the new intima). Myofibroblast
cells from the outside/adventitia of the vessel also contribute to this neointimal plaque. Recent
research has suggested that circulating stem cells and endothelial progenitor cells may be important
contributors to the neointimal formation process.
The restenotic plaque is not atherosclerosis. It contains little lipid and is smooth muscle and
extracellular matrix rich. It is the product of vascular wound healing.
Early (24 hours to 7 days) |
Intermediate (1 week to 1 month)
Late (weeks - months)
Neointima smooth muscle
Percutanous Angioplasty and Intervention in Non-coronary Vessels and Grafts
Angioplasty may also be used in peripheral vessels, including the carotids. It also may be utilized
to treat diseased vein grafts, but not without risk of complications, especially embolization. With the
bulky soft atheromatous plaques that vein grafts tend to get, many think this procedure should be avoided
and give preference to angioplasty of the native vessels, or re-do operation especially if arterial
conduits can be used.  If veins are treated then distal embolic protection devices are recommended
due to the near certain risk of emboli. Such distal protection devices are also being commonly used
after angioplasty of carotid arteries due to the risk of stroke.
These protection devices or filters are like windsocks or bags that are inflated or opened before the
procedure and then removed when the procedure is finished. When the pathologist examines the filter
material retrieved, the captured material is thrombus and plaque components including fibrous fragments,
calcium, cholesterol and atheroma with foam cells and plaque core material.  Distal embolization
post procedure may contribute to a "no reflow" state where despite a patent artery or graft, there is no
distal perfusion due to the microemboli, thrombus, endothelial swelling, interstitial myocardial edema,
and microvascular spasm and dysfunction. This state of poor perfusion is difficult to treat and is best
The other clinical situation where one can expect the risk of post - PCI distal embolization to be
high is primary PCI of a thrombosed artery in acute myocardial infarction. This type of primary
intervention is increasing, and is becoming the standard of practice, in centers where the infarct
patient can quickly reach the coronary cath lab.
Coronary Endarterectomy and Atherectomy
Angioplasty with balloon redistributes atherosclerotic plaque but does not remove plaque mass.
Processes such as endarterectomy and atherectomy (directional or rotational) actually remove plaque
material by excision or ablation. The acute and chronic vascular complications are similar to balloon
In coronary endarterectomy the surgeon opens the coronary artery and
physically removes the plaque. This is done at the time of bypass grafting so that the bypass graft may
be sewn into an adequate arterial lumen with good distal run off. A similar operation is done to open up
the carotid arteries in the neck (carotid endarterectomy), or the proximal leg arteries (often at the
time of peripheral bypass grafting). The endarterectomy sites may thrombose acutely and also chronically
undergo restenosis similar to angioplasty sites. 
Atherectomy procedures do not require opening the chest. Rather they are
closed interventional procedures where the heart is accessed via the peripheral arteries, usually the
groin vessels. With rotational atherectomy, a rotational drill breaks up the plaque. There is potential
extensive distal vessel embolization of plaque material. Embolic protection devices are utilized to
catch the released distal plaque material and prevent embolization. 
With directional atherectomy, a small cutting blade removes pieces of plaque and stores them in the
catheter, where they are later removed. Any layers of the arterial vessel may be removed including the
media and adventitia. It is disturbing to see adventitial tissues in the specimen and a phone call to
the clinician is warranted. Interestingly these individuals are usually fine clinically. One worries
about long term future arterial aneurysms, but these do not seem to be common probably due to fibrous
contraction and restenosis of the site. The resected arterial fragments represent a new opportunity to
obtain tissues from live patients and study atherosclerosis and vascular pathobiology.
Vascular stents have revolutionized interventional vascular medicine. Programs of "minimally
invasive" medicine include surgery procedures and interventional vascular devices. Stents may be used
to treat stenotic native arterial plaques or treat post-procedural complications such as PTCA related
abrupt closure due to thrombosis, or intimal flaps. Vein grafts may also be stented. 
These metal stents are placed on the outside of a balloon. Inflation of the balloon opposes and
embeds the stents into the vascular wall. The stent provides metal scaffolding and thus creates a large
regular lumen supporting the intimal flaps and dissections. Since most stents are stiff metals, they
limit vascular recoil, prevent spasm and increase blood flow. This decreases thrombosis and potentially
decreases chronic restenosis.
Early stent vascular pathology shows damage to the inner endothelial lining, stretching of the blood
vessel wall and accumulation of fibrin and white blood cells. These eventually cover with neointimal
cells and the wires of the stents become embedded. The neointima cells are myofibroblast - like smooth
muscle cells with collagenous and glycosaminoglycan extracellular matrix. Some of the neointimal cells
derive from the arterial wall while others probably originate from circulating stem or endothelial
The endothelium eventually grows back and covers the stents, although this takes time. The body
recognizes stents as foreign bodies and there is foreign body giant cell type reaction.  The
inflammation related to the stent struts is now being recognized as an important component of the healing
process after this intervention.
Coronary stents range in size from 2.5 mm to 6 mm diameter and from 8 to 15 mm in length. Many
different stent types and materials have been designed and each has its own distinctive pathology and
complications. Recently there is much promise of drug eluting coated stents with pharmaceutical agents
designed to prevent smooth muscle migration or proliferation. Anti-growth factor and anti-proliferative
agents, such as rapamycin (Sirolimus) and Taxol, have also been tried with variable
These drug eluting stents have concerns of delayed healing, delayed endothelialization and the potential
for late thrombotic events. Future stents may include bioabsorbable and different metals, organic
materials, innovative drugs and polymers or antibody coated stents.
The use of radiation delivered via an intraluminal catheter in the stent has also been found to be
promising in some studies, although others have found extensive scar adjacent to the stent limiting the
effectiveness of the procedure. Delayed thrombosis due to delayed endothelialization is a concern.
"Blind spots" of poor radiation treatment may also be found to be responsible for post-procedure
restenosis. Currently, radiation may have a role in treating "in stent" restenosis. It may be falling
out of favor and its role in the era of drug eluting stents remains to be seen. 
Metal stents require special histological processing to cut them. One may remove the stent struts
manually using a dissecting microscope, but this destroys the overall architecture of the vessel.
Alternatively, and with more effort, the stents are plastic embedded and ground or cut using a blade;
techniques similar to those developed for study of bone disease.
With these special
histological procedures, stent pathology may be evaluated. This may be important in the evaluation of
stented arterial segments that may have occluded shortly after the procedure and caused death. One can
determine if the stent is thrombosed or if there is another cause for the bad outcome. It also may be
important to know the status of a stent when a patient with a stent is found with apparent sudden death.
Other stents (different sizes and types) are used in the esophagus, bile ducts, urethra,
ureters, aorta and large veins. Stents with prosthetic graft material are utilized in large vessel
pathology including aortic dissections and aneurysms, including abdominal aortic aneurysms. Composite
stent grafts with bio-engineered materials are being developed and studied. Stents loaded with cells and
polymers containing growth factors will prove to be interesting in the near future. Bio-stents with
absorbable components are under investigation. Different polymers for drug elution with variable time
and means of delivery are also interesting.
Stenting of a Vessel with Plaque
Top - The catheter with the stent is advanced into the diseased
Middle - The inflated balloon deploys
the stent into the vascular wall, compressing the original plaque
Bottom - The successfully deployed stent
has displaced the plaque and opened the lumen
Right - intravascular Ultrasound (IVUS) images
Modified from http://www.heartbc.ca/books/ptca/ptca5types.htm
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