What is Restenosis of Stented Coronary Arteries?
Restenosis is the narrowing of a blood vessel after it has been widened through a medical procedure called angioplasty. Even with the improvements in stent technology, restenosis remains the most common reason for the failure of a specific procedure known as percutaneous coronary intervention (PCI). This procedure is used to treat blocked blood vessels in the heart.
In simpler terms, around mid-90s, doctors started using bare-metal stents to treat coronary artery disease, a condition where the blood vessels supplying the heart become narrowed. However, they noticed a new problem arising called in-stent restenosis (ISR). ISR happens when the blood vessel again gets narrowed within or near an area where a stent was placed before. This narrowing is more than half the normal width of the blood vessel.
Clinical restenosis refers to the return of the symptoms of decreased blood supply to the heart (ischemia) due to ISR that often needs another same procedure. In-segment restenosis is termed restenosis that happens anywhere within 5 millimeters from the ends of the stent.
Recurrent in-stent restenosis is when at least two of these repeated procedures at the stent have failed.
In traditional balloon angioplasty (where no stent is used), restenosis happens due to changes in the blood vessel shape and elastic recoil. But when restenosis happens after using a stent, it’s mainly due to an overgrowth of tissues, called neointimal proliferation, or a new narrowing process in the blood vessel, called neoatherosclerosis. ISR can either be diffuse (spread over more than 10 mm in length) or focal (spread less than 10 mm in length).
Clinically, when restenosis occurs, it often shows up as pain in the chest, or angina, or acute coronary syndrome. ISR can lead to serious health problems. A study involving 10,004 patients found that those showing restenosis during their 6-8 months check-up after a stent placement had a higher chance of dying within four years.
The medical community has made impressive strides in reducing the rate of restenosis and improving the treatment options for ISR in the past two decades. These improvements include better stent platforms, new medications, and better imaging techniques. As a result, doctors today can treat patients who earlier could only be managed by surgical procedures to improve blood supply to the heart. However, real-life data show a higher rate of ISR compared to clinical trials data. This difference is likely because the real-life data include more complicated cases.
What Causes Restenosis of Stented Coronary Arteries?
The factors that increase the risk of restenosis, a condition in which a blood vessel becomes narrow again after it has been unblocked, can be divided into three categories: patient characteristics, the type of blockage, and issues that come up during the procedure. Biological factors that can increase risk include diabetes and kidney problems. In fact, having diabetes can increase the risk of restenosis in a metal stent by 30% to 50%. Drug-eluting stents, another type of stent that releases medicine to prevent blockage, also have increased risk in people with diabetes.
Other factors involve biochemical conditions, like having high levels of serum matrix metalloproteinases (MMPs) – enzymes that break down proteins and support cell growth in blood vessels. These increse the risk of blood vessels getting narrow again. Certain blood characteristics are also a risk factor, such as the ratios of different types of white blood cells and the size of red blood cells and platelets. Some studies suggest that these factors can predict increased risk for restenosis in drug-eluting stents.
Genetics also play a role. The GENDER study identified mutations in several genes that are associated with higher risk of restenosis. From a mechanical perspective, more complex blood vessel blockages, long blockages, and small vessel sizes can predict a higher rate of restenosis. A stent more than 35 mm long, for example, almost doubles the risk of restenosis. If you have diabetes, a history of restenosis or a certain type of stent according to Mehran’s classification, you are also more likely to experience restenosis.
Procedural risks should be avoided, if at all possible. The most preventable cause of restenosis is not expanding the stent enough. This can happen if the stent is too small, not enough pressure is used during insertion, the blood vessel isn’t properly prepared, or the blood vessel is too hard due to calcium buildup. Besides the stent size, other causes of restenosis include not inserting the stent from one healthy part of the vessel to another or having a fracture in the stent. Lastly, drug resistance or local allergic reactions to drug-eluting stents can contribute to restenosis.
Risk Factors and Frequency for Restenosis of Stented Coronary Arteries
Identifying the precise rate of restenosis, or when a blood vessel becomes narrow again after treatment, can be challenging due to numerous factors and variables. Earlier, the rate of restenosis was somewhere between 32% and 55% of all angioplasties. This percentage dropped to between 17 to 41% during the Bare Metal Stent (BMS) era. However, with the introduction of the Drug-Eluting Stent (DES), the rate of restenosis has reduced further, usually staying below 10%.
The restenosis rate tends to be higher in cases of multivessel disease, that is when more than one vessel is affected, in comparison to just a single-vessel disease. Research has indicated a significantly higher likelihood of restenosis in patients with two or three-vessel diseases compared to those with a single-vessel disease.
- Restenosis was significantly higher in those with two-vessel disease (odds ratio OR: 2.922)
- It was similarly higher in those with three-vessel disease (OR: 2.574)
Also, using first-generation DES rather than BMS, or using second-generation DES compared to the first-generation DES, have been found to predict lower rates of restenosis. Other predictors of worse restenosis outcome have been identified, such as a small vessel size, complex lesion, presence of diabetes mellitus, a history of bypass surgery, and longer total stent length.
Restenosis is a key factor that can predict future restenosis. The ICARUS Cooperation study specifically researched patients who had drug-eluting stent (DES) restenosis and were treated with drug-coated balloon (DCB) angioplasty. After a follow-up period of 6 to 9 months, recurrent restenosis was observed in about 20.8% of the patients. Key factors leading to recurrent restenosis were increased lesion length and reduced vessel size.
Signs and Symptoms of Restenosis of Stented Coronary Arteries
Restenosis is a condition where the coronary arteries become narrow again after a previous treatment. The symptoms of restenosis can differ greatly between patients, depending on individual factors and the location of the affected artery. Symptoms may include stable or unstable chest pain, or even a heart attack. The risk of having to have the affected vessel treated again depends on the severity of the condition, with risks ranging from 19% to 83%.
The time frame for restenosis to occur after a stent has been placed in a vessel can vary widely, and is classified as:
- Acute (within 24 hours after stent placement)
- Subacute (from 24 hours to 30 days)
- Late (30 days to 1 year)
- Very Late (more than 1 year)
In a study involving over 900 patients with restenosis, most presented with a condition called acute coronary syndrome. The type of stent initially placed did not significantly affect the presentation. Factors such as smoking and chronic kidney failure were associated with an increased risk of heart attack, while certain newer types of stents were associated with lower risks.
Testing for Restenosis of Stented Coronary Arteries
When a doctor suspects you might have a narrowing or blockage (restenosis) in your coronary arteries, they typically use a procedure called coronary angiography. This procedure helps your doctor visualise the inside of your arteries and possibly guide a treatment known as Percutaneous Coronary Intervention (PCI) – a non-surgical procedure that can be used to treat blocked heart arteries.
A particular study classified restenosis into four different types, based on how extensive they are and where they’re located. The study showed four types: very localized blockage (42% of cases), blockage extended a little within the stent (21% of cases), blockage extending outside the stent (30% of cases), and complete blockage (7% of cases).
There are also more advanced imaging techniques – Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) – which offer even more detailed views of your arteries and help doctors better understand the cause of the restenosis. This information can help tailor the most effective treatment plan.
Both IVUS and OCT can show if a stent (a small mesh tube that helps prop the artery open) isn’t fully expanded, whether there’s new tissue growth inside the stent or if the external elastic lamina (boundary of an artery) is visible for better balloon sizing during post-dilation. OCT, especially, is better at showing the specific differences between different types of artery blockages.
One imaging technology that some medical studies have shown to be quite accurate at detecting artery blockages is computed tomography angiography (CTA). This method uses a computer-linked X-ray machine to create a detailed picture of blood flow in the arteries. This could be an important tool for evaluating such conditions in the future.
New imaging technologies are also being developed to provide a very thorough image of artery plaque and its related conditions. This may eventually help doctors make more informed and accurate treatment decisions.
It’s also important to note that, in some cases, treatment might not be necessary right away. In fact, some studies have suggested that patients with moderate artery narrowing and no symptoms may not benefit from immediate treatment. Using a method known as fractional flow reserve (FFR) to measure blood pressure and flow through a specific part of an artery could help doctors identify which patients might actually benefit from revascularization – techniques to restore blood flow to the heart. These are decisions your doctor will make based on your individual condition.
Treatment Options for Restenosis of Stented Coronary Arteries
There are numerous treatment options available for treating ISR (In-stent restenosis), which is the re-narrowing of a previously unblocked blood vessel. The chosen therapy is based on the reasons for the ISR and patient characteristics. A medical imaging method called intravascular imaging helps in identifying the cause of ISR and tailoring the treatment accordingly.
In terms of medication, common prophylactics like Aspirin and Statins are recommended for those who have had PCI for coronary artery disease. However, no specific medication has been proven effective in preventing the progression of established ISR. Current treatments use antiplatelet agents as guideline-recommended but these are ineffective for treating ISR specifically. Promising initial results didn’t hold up in larger trials; thus, the use of medication such as abciximab and oral sirolimus is not a staple for ISR treatment.
Plain old balloon angioplasty (POBA) was traditionally a primary treatment to manage ISR. This is still considered a useful approach in certain conditions but can lead to injuries, procedural complications, and recurrence of ISR.
Vascular Brachytherapy (VBT) involves the use of a radioactive isotope to halt tissue growth in ISR, which can improve clinical outcomes better than other treatments. Nonetheless, its complexity and radiation dosage issues have limited its use.
Cutting and scoring balloons and debulking technologies like rotational atherectomy and laser techniques have also been put to use for ISR treatment. These methods facilitate better balloon anchoring during angioplasty and remove excessive stenotic tissue respectively. But so far, studies haven’t confirmed their superiority over other methods in clinical outcomes or safety.
Repeat stenting with BMS (Bare-Metal Stents) can improve the short-term appearance of ISR but may lead to subsequent lumen loss. Despite this, repeat BMS placement has been shown to bring better results in patients with large vessel ISR and stent edge disease as compared to POBA.
Using DES (Drug-Eluting Stents) is another promising treatment option. Studies suggest that they decrease restenosis rates and improve clinical outcomes in comparison to balloon angioplasty. DES is commonly used to manage DES-ISR, but data suggests there is a risk of ISR recurrence in these patients.
Furthermore, Drug-coated balloons (DCB) and Bioresorbable Vascular scaffolds (BVS) are being explored as the development continues to treat ISR by avoiding the drawback of multiple layers of stent struts, which could lead to excessive layering of stent materials inside the vessel, referred to as “onion skinning effect.”
Finally, in comparing all treatment modalities, the use of everolimus-eluting stents—a type of DES—and DCB have shown promising results in reducing ISR. So far, stents and balloons coated with this drug have led to superior clinical outcomes and are being considered as efficient treatment options for ISR, among the ones available. Nevertheless, the optimal treatment would depend on the patient’s specific needs and the nature of their ISR.
What else can Restenosis of Stented Coronary Arteries be?
If a patient with a history of heart disease and previous stent placement experiences recurring symptoms of reduced blood flow to the heart, various causes could be responsible. These include:
- Insufficient restoration of blood flow during the initial stent placement
- A clot forming within the stent
- The progression of disease in other arteries
- Re-narrowing of the arteries after surgery (restenosis)
Patients who didn’t get enough blood flow restored at the time of stent placement would likely continue to experience heart-related symptoms afterwards. On repeat x-ray imaging of the arteries, it can appear like the stent was positioned incorrectly. A clot within the stent would cause a sudden episode of symptoms, due to abrupt blockage. The development of plaque buildup within the stent – seen more frequently with drug-coated stents – is linked to an increased risk of clot formation within the stent. Lastly, most patients requiring stent placement for heart disease often have disease in multiple arteries, of varying severity.
What to expect with Restenosis of Stented Coronary Arteries
The introduction of the second-generation drug-eluting stents has greatly improved the results of PCI, a procedure to clear blocked arteries. Because of these advancements, the rate of arteries getting blockages again after treatment is now around 5 to 10%. Regular exercise and healthy diet routines, alongside double medication to prevent blood clots, can further help patients to minimize unwanted complications.
Events like these unwanted complications are closely linked to the final area covered by the stent. Therefore, trying to cover as much area as possible with these stents can help to lessen these complications.
Possible Complications When Diagnosed with Restenosis of Stented Coronary Arteries
Complications from restenosis, or the re-narrowing of the arteries, can cause conditions like steady angina, unstable angina, and acute heart problems. It can even lead to severe conditions such as an acute heart attack or mortality. Procedures that aim to improve blood flow, like In-Stent Restenosis (ISR), can also face complications. These include issues like bleeding from the site of procedure, incomplete expansion of the stent (a small mesh tube that’s used to treat narrow or weak arteries), incomplete revascularization, tearing of the coronary artery, and clot formation within the stent.
Possible Complications are:
- Steady angina
- Unstable angina
- Acute heart problems
- Acute myocardial infarction (heart attack)
- Death
- Bleeding from the site of the procedure
- Incomplete expansion of the stent
- Incomplete revascularization
- Tearing of the coronary artery
- Clot formation within the stent
Preventing Restenosis of Stented Coronary Arteries
Even though newer versions of stent devices, which are tiny tube-shaped devices, for treating narrow or blocked coronary arteries, have shown better results, the problem of the blockage returning – known as In-Stent restenosis (ISR) – still happens in about 10% of cases.
Certain conditions can increase your chance of such a blockage happening again after the stent is put in place. These conditions include:
1. Poorly managed diabetes
2. Ongoing cigarette smoking
3. High levels of LDL cholesterol, what you might know as “bad cholesterol”
4. Poorly managed high blood pressure
5. Kidney problems
It’s important to have these conditions under control and to keep a close eye on them. Quitting smoking, getting moderate amounts of exercise, and losing weight are all recommended lifestyle changes to consider.
There’s also a risk that the metal of the stent can make blood clots form inside the stent, which can lead to serious issues. To counter this, doctors usually prescribe a dual antiplatelet therapy (DAPT), which includes aspirin and another medication to prevent blood clots. This treatment should be taken exactly as the doctor instructed and for as long as they advised. It’s important not to stop or change this treatment without getting the approval of your heart doctor first.