Restenosis Causes

There are many reasons for ongoing inflammation in the coronary artery, and prolonged healing, after angioplasty, with or without stent insertion. This chronic state of inflammation predisposes to neointimal hyperplasia.

The primary causes of inflammation and restenosis in stents include:

1. Characteristics of the original stenosis:

• The presence of a bypass graft
• A chronic complete block of the vessels
• Calcification of the lesions
• Blockage involving the ostia, the openings of the arteries and the main branches
• Blockage of the left anterior descending coronary artery
• Multiple or complex arterial blocks
• Following an acute heart attack or an in-stent restenosis (ISR)

2. Medical factors such as:

• Diabetes mellitus
• Hypersensitivity to the stent polymer
• Chronic biological reactions to the stent and/or balloon injury
• Delayed healing responses
• Drug resistanc e to the cytotoxic drugs or cytostatic drugs used in the stent if it is a drug-eluting stent (DES)

Hypersensitive reactions may arise due to the nickel or molybdenum released from the stainless steel of which most stents were formerly made. Newer stents are made of cobalt-chromium which does not release these ions. However, they can still cause hypersensitivity due to other components, such as the formulation ingredients of the drug, the polymer which carries the drugs, or the stent platform. The type of drug used is also important.

In drug-eluting stents, the drug inhibits the proliferation of inflammatory cells and smooth muscle cells. However, it also prevents the normal growth of the endothelium to cover the metal stent platform. Thus, once the antiplatelet drug is no longer released, the exposed bare metal or polymer of the stent invites thrombosis.  In some patients, the cells of the vessel wall lying directly behind the stent die off faster, leaving pockets of blood where scar tissue forms.

3. Mechanical causes:

• Under-expansion of the stents, which typically occurs during the process of implantation. Here, even though the stent is well applied to the vessel wall, its lumen is much smaller than it should be.
• Malapposition, when the stent is not properly applied to the wall of the artery, so that a space filled with blood can be detected between the stent and the vessel wall. This is more common with
  • too small stents
  • tortuous and coiled arteries
• Difficulty in implantation of DES may strip off part of the special drug coating, leading to a non-uniform distribution of the antiplatelet drug.

4. Technical factors relating to the stent:

• Stents which do not cover the whole area of the arterial wall that was injured by the angioplasty
• Longer stents
• Use of overlapping or end-to-end stents
• Stent fractures
• Short gaps between overlapping stents, where the drug level is low
• Small arteries
• Longer or multi-artery lesions
• Poor run-off

The interaction of these factors may predispose the recurrence of stenosis at or near the site of the original blockage.

References

• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323487/
• http://cardiovascres.oxfordjournals.org/content/31/6/835?ijkey=ef49165ebec392d0e3a9f45b5f67e25aa2ec9bd2&keytype2=tf_ipsecsha
• http://content.onlinejacc.org/article.aspx?articleid=1143964
• http://www.aafp.org/afp/2009/1201/p1245.html