Restenosis is the recurrence of
stenosis
A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture).
''Stricture' ...
, a narrowing of a
blood vessel
Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from ...
, leading to restricted blood flow. Restenosis usually pertains to an
artery
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
or other large
blood vessel
Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from ...
that has become narrowed, received treatment to clear the blockage and subsequently become renarrowed. This is usually restenosis of an
artery
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
, or other blood vessel, or possibly a vessel within an
organ.
Restenosis is a common adverse event of endovascular procedures. Procedures frequently used to treat the vascular damage from
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...
and related narrowing and renarrowing (restenosis) of blood vessels include
vascular surgery
Vascular surgery is a surgical subspecialty in which diseases of the vascular system, or arteries, veins and lymphatic circulation, are managed by medical therapy, minimally-invasive catheter procedures and surgical reconstruction. The specialt ...
,
cardiac surgery
Cardiac surgery, or cardiovascular surgery, is surgery on the heart or great vessels performed by cardiac surgeons. It is often used to treat complications of ischemic heart disease (for example, with coronary artery bypass grafting); to ...
, and
angioplasty.
When a stent is used and restenosis occurs, this is called in-stent restenosis or ISR. If it occurs following balloon angioplasty, this is called post-angioplasty restenosis or PARS. The diagnostic threshold for restenosis in both ISR or PARS is ≥50% stenosis.
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
Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.
Angina is typically the result of obstruc ...
) or have a minor or major heart attack (
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ...
), 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.
Causes
Surgery to widen or unblock a
blood vessel
Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from ...
usually has a long-lasting beneficial effect for the patient. However, in some cases, the procedure itself can cause further narrowing of the vessel, or restenosis.
Angioplasty, also called
percutaneous transluminal coronary angioplasty (PTCA), is commonly used to treat blockages of the
coronary or
peripheral arteries (such as in the limbs). The balloon inserted into the narrowing 'smashes' the
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membr ...
plaques (
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...
) against the
artery walls
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
, thus widening the size of the
lumen and increasing blood flow. However the action damages the artery walls, and they respond by using
physiological
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemica ...
mechanisms to repair the damage. (See physiology below.)
A
stent is a mesh, tube-like structure often used in conjunction with
angioplasty to permanently hold open an artery, allowing for unrestricted blood flow, or to support a weakness in the artery wall called an
aneurysm
An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus ...
. The artery can react to the stent, perceive it as a foreign body, and respond by mounting an
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
response which leads to further narrowing near or inside the stent.
Physiology
Damage to the blood vessel wall by angioplasty triggers physiological response that can be divided into two stages. The first stage that occurs immediately after tissue
trauma, is
thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...
. A
blood clot forms at the site of damage and further hinders blood flow. This is accompanied by an inflammatory
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
.
The second stage tends to occur 3–6 months after surgery and is the result of
proliferation of cells in the media, a smooth muscle wall in the vessel. This is also known as
Neointimal Hyperplasia (NIHA).
Diagnosis
Imaging
Vessel restenosis is typically detected by
angiography
Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...
, but can also be detected by duplex
ultrasound
Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...
and other imaging techniques.
As "late loss"
Late loss is synonymous with restenosis, and literally means loss of the
lumen ''after'' 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 a
vascular 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.
But late 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 an acute 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 literally pushes the stent-graft back, narrowing the vessel and ''losing'' at least a percentage of what was previously ''gained'', or late loss.
The net gain of lumen diameter is the difference between acute gain and late loss, and is a measure of stent-graft effectiveness.
Percent diameter restenosis
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.
There is some controversy of 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.
An
occlusion, or the blocking of all blood flow through a vessel, is considered 100% percent diameter stenosis.
Binary restenosis
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". 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 group of patients to determine averages (descriptive measures of central tendency) or as a predictive variable.
Prevention
In the first stage of restenosis, administering anti-
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
drugs (called IIb/IIIa inhibitors) immediately after surgery greatly reduces the chance of a
thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...
occurring.
Drug-eluting stents, coated with
pharmaceuticals
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and ...
that inhibit tissue growth and thus reduce the risk of restenosis from scar-tissue and cell proliferation, are now widely used. These
stents reduce the occurrence of restenosis, with clinical studies showing an incidence rate of 5% or lower.
Treatment
If restenosis occurs without a
stent, it is usually treated with more
angioplasty. This treatment is also used if restenosis occurs at either the proximal or distal end of the
stent.
If restenosis occurs within a
stent (also known as in-stent stenosis), it may be treated with repeated
angioplasty and insertion of another stent inside the original, often with a drug-eluting stent.
Over the past 5 years, ISR is increasingly treated with a
drug-coated balloon (DCB), which is a balloon coated with the same anticancer drugs that prevent restenosis, such as
Paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical can ...
. 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 a faster drug delivery.
Alternative treatments include
brachytherapy
Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prost ...
, or intracoronary radiation. The radiation kills cells and inhibits tissue growth (similar to a patient undergoing cancer therapy).
Incidence
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).
Rates in cardiac procedures
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.
A 2010 study in India comparing coronary
drug-eluting stents (DES) with coronary
bare-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.
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.
Rates in peripheral procedures
In peripheral procedures, rates are still high. A 2003 study of selective and systematic stenting for limb-threatening ischemia reported restenosis rates at 1 year follow-up in 32.3% of selective stenting patients and 34.7% of systematic stenting patients.
The 2006 SIROCCO trial compared the sirolimus drug-eluting stent with a bare nitinol stent for atherosclerotic lesions of the
subsartorial artery
The femoral artery is a large artery in the thigh and the main arterial supply to the thigh and leg. The femoral artery gives off the deep femoral artery or profunda femoris artery and descends along the anteromedial part of the thigh in the fem ...
, reporting restenosis at 2 year follow-up was 22.9% and 21.1%, respectively.
A 2009 study compared bare nitinol stents with percutaneous transluminal angioplasty (PTA) in
subsartorial artery
The femoral artery is a large artery in the thigh and the main arterial supply to the thigh and leg. The femoral artery gives off the deep femoral artery or profunda femoris artery and descends along the anteromedial part of the thigh in the fem ...
disease. At 1 year follow-up, restenosis was reported in 34.4% of stented patients versus 61.1% of PTA patients.
See also
*
Angioplasty
*
Drug-eluting stent
*
Neointimal hyperplasia
*
Stent
* Images of restenosis with
bare-metal stents and
drug-eluting stents ar
here
References
{{reflist
Cardiology
Surgery