Restenosis is the recurrence ofstenosis, a narrowing of ablood vessel, leading to restricted blood flow. Restenosis usually pertains to anartery or other largeblood vessel that has become narrowed, received treatment to clear the blockage, and subsequently become re-narrowed. This is usually restenosis of anartery, or other blood vessel, or possibly a vessel within anorgan.
Restenosis is a common adverse event of endovascular procedures. Procedures frequently used to treat vascular damage fromatherosclerosis and related narrowing and re-narrowing (restenosis) of blood vessels includevascular surgery,cardiac surgery, andangioplasty.[1]
When a stent is used and restenosis occurs, this is calledin-stent restenosis orISR.[2] If it occurs following balloon angioplasty, this is called post-angioplasty restenosis orPARS. The diagnostic threshold for restenosis in both ISR and PARS is ≥50% stenosis.[3]
If restenosis occurs after a procedure, follow-up imaging is not the only way to initially detect compromised blood flow. Symptoms may also suggest or signal restenosis, but this should be confirmed by imaging. For instance, a coronary stent patient who develops restenosis may experience recurrent chest pain (angina) or have a minor or major heart attack (myocardial infarction), though they may not report it. This is why it is important that a patient comply with follow-up screenings and the clinician follows through with a thorough clinical assessment. But it is also important to note that not all cases of restenosis lead to clinical symptoms, nor are they asymptomatic.[3]
Surgery to widen or unblock ablood vessel usually has a long-lasting beneficial effect on the patient. However, in some cases, the procedure itself can cause further narrowing of the vessel, or restenosis.Angioplasty, also calledpercutaneous transluminal coronary angioplasty (PTCA), is commonly used to treat blockages of thecoronary orperipheral arteries (such as in the limbs). The balloon inserted into the narrowing 'smashes' thecholesterol plaques (atherosclerosis) against theartery walls, thus widening the size of thelumen and increasing blood flow. However the action damages the artery walls, and they respond by usingphysiological mechanisms to repair the damage. (See physiology below.)[4]
Astent is a mesh, tube-like structure often used in conjunction withangioplasty to permanently hold open an artery, allowing for unrestricted blood flow, or to support a weakness in the artery wall called ananeurysm. The artery can react to the stent, perceive it as a foreign body, and respond by mounting animmune system response which leads to further narrowing near or inside the stent.[citation needed]
Damage to the blood vessel wall by angioplasty triggers a physiological response that can be divided into two stages. The first stage that occurs immediately after tissuetrauma, isthrombosis. Ablood clot forms at the site of damage and further hinders blood flow. This is accompanied by an inflammatoryimmune response.[citation needed]
The second stage tends to occur 3–6 months after surgery and is the result of theproliferation of cells in the media, a smooth muscle wall in the vessel. This is also known asNeointimal Hyperplasia (NIHA).[5]
Vessel restenosis is typically detected byangiography, but can also be detected by duplexultrasound and other imaging techniques.[6]
Late loss is synonymous withrestenosis and means loss of thelumenafter a procedure intended to open the vessel. It measures either the percent (relative) or absolute change in minimum luminal diameter (MLD) over the months following avascular procedure, such as the implantation of a stent graft. Late loss is one metric that is useful in determining the effectiveness of vascular interventions in clinical trials for either an individual patient or a group of patients.[citation needed]
Howeverlate loss is only part of the terminology in describing the outcomes of vascular interventions. For instance, the implantation of a stent graft will first provide anacute gain in lumen diameter. In other words, there is an immediate gain in lumen size because the implanted stent opens up the vessel. However, over time, the body's inflammatory immune response (described below in the "Causes" section) reacts to the stent graft via smooth muscle proliferation, etc., which pushes the stent graft back, narrowing the vessel andlosing at least a percentage of what was previouslygained, orlate loss.[citation needed]
Thenet gain of lumen diameter is the difference betweenacute gain andlate loss and is a measure of stent-graft effectiveness.[7]
Percent diameter restenosis (or just percent diameter stenosis) is a measure observed in individual patients and is typically calculated as the difference between the minimal (or minimum) luminal diameter (MLD) from the target reference vessel diameter (RVD), divided by the RVD, and multiplied by 100 to get the percentage of stenosis. It is an important measure needed to calculate binary restenosis (see Binary Restenosis section below). The RVD is typically calculated by averaging the MLD of the healthy part of the vessel both proximal and distal to the vessel lesion.[8]
There is some controversy over the accuracy of observing the lesion MLD itself, since many atherosclerotic lesions may create uneven "hills and valleys" within the lumen, making a true MLD difficult to obtain or estimate. Some research indicates calculating "area stenosis" is also a valid measure of actual vessel stenosis compared to diameter stenosis alone, but this requires additional analysis because a tracing of the lumen border must be performed. However, there are computer programs available to automatically perform this function. It may be helpful to obtain both percent diameter and area percent stenosis, especially since the two percentages may not always correlate with each other.[9]
Anocclusion, or the blocking of all blood flow through a vessel, is considered 100% percent diameter stenosis.
Binary restenosis is traditionally defined as a reduction in the percent diameter stenosis of 50% or more (≥50%). It is also known as just "binary stenosis".[10] The term "binary" means that patients are placed in 2 groups, those who have ≥50% stenosis and those who have <50% stenosis. Binary restenosis is an epidemiological method of analyzing percent diameter stenosis for observing not only an individual patient, but also performing statistical techniques on a group of patients to determine averages (descriptive measures of central tendency) or as a predictive variable.[citation needed]
In the first stage of restenosis, administering anti-platelet drugs (called IIb/IIIa inhibitors) immediately after surgery greatly reduces the chance of athrombosis occurring.[citation needed]
Drug-eluting stents, coated withpharmaceuticals that inhibit tissue growth and thus reduce the risk of restenosis from scar tissue and cell proliferation, are now widely used.[11] Thesestents reduce the occurrence of restenosis, with clinical studies showing an incidence rate of 5% or lower.[3][12][13]
If restenosis occurs without astent, it is usually treated with moreangioplasty.[citation needed] This treatment is also used if restenosis occurs at either the proximal or distal end of thestent.[citation needed]
If restenosis occurs within astent (also known as in-stent stenosis), it may be treated with repeatedangioplasty and insertion of another stent inside the original, often with a drug-eluting stent.[14]
Over the past 5 years, ISR has been increasingly treated with adrug-coated balloon (DCB), which is a balloon coated with the same anti-cancer drugs that prevent restenosis, such asPaclitaxel.[15][16] The balloon avoids the need for a double layer of metal which is used when an in-stent restenosis is treated with another stent within the original stent. Additionally, DCB treatment does not leave an implant in the body and is designed for faster drug delivery.
Alternative treatments includebrachytherapy, or intracoronary radiation. The radiation kills cells and inhibits tissue growth (similar to a patient undergoing cancer therapy).[17]
Rates of restenosis differ between devices (e.g., stent-grafts, balloon angioplasty, etc.) and location of procedure (i.e., centrally located in the heart, such as the coronary artery, or in peripheral vessels such as the popliteal artery in the leg, the pudendal artery in the pelvis, or the carotid artery in the neck).[citation needed]
In cardiac procedures, balloon angioplasty without stent implantation has been associated with a high incidence of restenosis, with rates ranging from 25% to 50%, and the majority of these patients need further angioplasty within 6 months.[18]
A 2010 study in India comparing coronarydrug-eluting stents (DES) with coronarybare-metal stents (BMS) reported that restenosis developed in 23.1% of DES patients vs 48.8% in BMS patients, and female sex was found to be a statistically significant risk factor for developing restenosis.[19]
However, in newer-generation DES and BMS the restenosis rates are much lower. For example, the NORSTENT trial, presented in 2016, reports target-lesion revascularization rates of 5.3% and 10.3% for DES and BMS respectively.[13]
In peripheral procedures, rates are still high. A 2003 study of selective and systematic stenting for limb-threatening ischemia reported restenosis rates at 1year follow-up in 32.3% of selective stenting patients and 34.7% of systematic stenting patients.[20]
The 2006 SIROCCO trial compared the sirolimus drug-eluting stent with a bare nitinol stent for atherosclerotic lesions of thesubsartorial artery, reporting restenosis at 2 year follow-up was 22.9% and 21.1%, respectively.[21]
A 2009 study compared bare nitinol stents with percutaneous transluminal angioplasty (PTA) insubsartorial artery disease. At 1 year follow-up, restenosis was reported in 34.4% of stented patients versus 61.1% of PTA patients.[22]
