Restenosis
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Restenosis Microchapters |
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Diagnosis |
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Treatment |
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Restenosis On the Web |
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American Roentgen Ray Society Images of Restenosis |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-In-Chief:: Bhaskar Purushottam, M.D. [2]
Overview
Restenosis literally means the reoccurrence of stenosis. This is usually restenosis of an artery, or other blood vessel, but possibly any hollow organ that has been "unblocked". This term is common in vascular surgery, cardiac surgery, interventional radiology, or interventional cardiology following angioplasty, all branches of medicine that frequently treat stenotic lesions. In simple words, coronary re-stenosis can be considered as the reduction in the lumen diameter after a percutaneous coronary intervention (PCI), which induces iatrogenic arterial injury and results in neointimal tissue proliferation.[1] It can be defined based on angiography or as clinical restenosis. By angiography, the term 'Binary Angiographic Re-stenosis' is defined as > 50% luminal narrowing at follow-up angiography.[2] However, the most widely accepted and relevant definition would be a 'Clinical Re-stenosis', which is defined as need for a repeat target lesion revascularization (TLR) due to symptomatic coronary ischemia from the previously intervened vessel (proposed by the Academic Research Consortium). Therefore, this definition needs angiographic narrowing as well as clinical correlation. If the lesion does not meet angiographic criteria, but meets the criteria for a physiologically significant lesion by fractional flow reserve (FFR) or anatomically by intravascular ultrasound (IVUS) with the appropriate clinical context, it is still considered 'Clinical Re-stenosis'. PCI has evolved significantly from plain balloon angioplasty to the development of biodegradable stents in the last few decades. Currently, almost all coronary interventions use a bare metal stent (BMS) or more so a drug eluting stent (DES). Hence, the discussion in the following paragraphs will focus on in-stent re-stenosis of drug eluting and bare metal stents.
Coronary Restenosis
There are probably several mechanisms that lead to restenosis. An important one is the inflammatory response, which induces tissue proliferation around an angioplasty site.
Cardiologists have tried a number of approaches to decrease the risk of restenosis. Stenting is becoming more commonplace; replacing balloon angioplasty. During the stenting procedure, a metal mesh (stent) is deployed against the wall of the artery revascularizing the artery. Other approaches include local radiotherapy and the use of immunosuppressive drugs, coated onto the stenting mesh. Analogues of rapamycin, such as tacrolimus (FK-506), sirolimus and more so everolimus, normally used as immunosuppressants but recently discovered to also inhibit the proliferation of vascular smooth muscle cells, have appeared to be quite effective in preventing restenosis in clinical trials. Antisense knockdown of c-myc, a protein critical for progression of cell replication, is another approach to inhibit cell proliferation in the artery wall and has been through preliminary clinical trials using Morpholino oligos.
Clinical Presentation
In-stent restenosis (ISR) can be clinically silent, but majority of them present with recurrent symptoms of angina. The incidence of recurrent angina pectoris after a percutaneous coronary intervention (PCI) was reported in the past to be around 50% with a wide range. This number may have reduced as most the PCIs end up in a DES as opposed to a BMS. The positive predictive value of symptoms indicating a significant stenosis is as low as 60%. ISR is often thought to be a benign phenomenon since the process of neointimal formation and proliferation is of gradual onset and progressive in nature. Given the pathophysiology of coronary re-stenosis, it is thought that re-stenosis is a rare cause of acute myocardial infarction or death. However, there are several reports which have shown that ISR can present as an acute coronary syndrome. 26% to 53% and 3.5% to 20% of BMS ISR can present as unstable angina and myocardial infarction, respectively. Similarly, 16% to 66% and 1% to 20% of DES ISR can present as unstable angina and myocardial infarction, respectively. A highly stenotic ISR lesion can lead to an non-occlusive thrombus, which can result in an acute coronary syndrome. Also, patients with clinically silent re-stenosis can be identified on coronary cineangiograms when neighbouring plaques undergo rupture or intimal tear and present as an acute coronary syndrome. Sometimes, local plaque rupture or intimal tear can initiate an inflammatory process which can promote thrombosis of neighbouring stenotic lesions. Thus, it is important to thoroughly evaluate the patient as coronary re-stenosis can present as an acute coronary syndrome.
BMS ISR has been reported to occur usually after five and half months after stent implantation. The time frame for DES ISR presentation is not well-known with one study reporting a mean time duration of 12 months. Delayed restenosis is known to occur especially with DES. There have been reports, using intravascular ultrasound that have shown neointimal proliferation to occur even at 4 years after stent implantation. The exact reasons as to why this delayed neointimal proliferation occurs is not well known. Some of the suspected pathophysiological mechanisms are delayed healing response, persistent biological reaction caused by the drug present in the polymer, or a hypersensitivity reaction to the polymer and a possible a genetic predisposition. This eludes to the fact that the clinician should entertain the possibility of coronary re-stenosis in patients who present with recurrent angina about 2 years after the stent implantation.
Among the clinical predictors of coronary re-stenosis, diabetes mellitus continues to be a strong clinical predictor. In a study conducted by Singh et al., they found that patients with treated diabetes mellitus had a 45% higher risk of restenosis compared with nondiabetics. Interestingly, in their study they found that current smokers have less restenosis. This smoker's paradox has been described in the past. Some of the other predictors are increasing age, female sex and chronic renal disease and patients on hemodialysis. Angiographic and other predictors are listed under the other sections.
Related Chapters
References
- ↑ Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R (2010). "In-stent restenosis in the drug-eluting stent era". J Am Coll Cardiol. 56 (23): 1897–907. doi:10.1016/j.jacc.2010.07.028. PMID 21109112.
- ↑ Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF; et al. (1999). "Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome". Circulation. 100 (18): 1872–8. PMID 10545431.