Since the last century cardiovascular diseases (CVDs) is the leading cause of death worldwide. The prevalence of mortality due to heart attacks and strokes is significantly higher than any other cause. According to WHO (world health organization), cardiovascular diseases contributed to the death of approximately 18 million people in 2019. Coronary artery diseases are the most common CVD. Statistical studies showed that more than 40% of deaths caused by CVDs are attributed to the coronary artery. Although most cardiovascular diseases are preventable by simple lifestyle modifications, their treatment may be challenging.
Evolution of Vascular Stenting
In the 20th century, it was obvious to cardiologists that medications aren’t effective enough to cure all cardiovascular diseases which were a bit common back then, so they started to discover surgical solutions. Several milestones were made in the history of medicine, particularly interventional radiology. After the invention of angioplasty and performing the first coronary balloon angioplasty by the German radiologist Andreas Grüntzig. doctors collaborated and pushed forward for further innovations. Cardiologists observed the results of the performed balloon angioplasties and found that they have compromised long-term results as patients usually complain of recurrence of the attacks.
Balloon angioplasty which is now referred to as POBA (plain old balloon angioplasty) was an effective procedure, especially for patients with angina pectoris, yet the rate of restenosis of the unblocked artery was considerably high. Doctors worked on a more lasting solution for narrowing blood vessels. In 1986, a French cardiologist called Jacques Puel managed to implant a stent in a human coronary artery. Such a breakthrough was a remarkable event in the history of interventional cardiology. For Dr. Puel ‘s contributions, he is considered one of the pioneers of coronary angioplasty.
Origin of the Term “Stent”
The word “stent” was derived from an English dentist called Charles Thomas Stent. Dr. Charles was a famous dentist in the 19th century, he contributed greatly to the development of denture making. Dr. stent created a compound made of plastic resinous materials used to obtain the impression of the teeth and oral cavity that would help in making a perfectly fitting denture. Then, Stent’s compound was used in skin grafting and urology until the mid-80s when stents were gradually introduced in cardiology.
Stent Function, Material, and Types
So, what is a vascular stent? A stent is a short hollow expandable tube placed inside the lumen of an artery or vein to allow unobstructed flow of the blood. The procedure in which stents are implanted in the lumen of the blood vessel using a catheter will be discussed in detail later. Stents are made of metal mesh that helps it expand when placed inside the vessel. The idea of the stent is to restore the adequate blood supply of a certain organ by maintaining the patency of the supplying blood vessel (scaffolding) with fewer risks of restenosis. The procedure in which the stent is implanted is called stent angioplasty.
There are different materials from which stents are made. stents have metal mesh wire used to be made of stainless steel. However, Platinum-chromium, cobalt-chromium, nickel-titanium alloys, and tantalum have recently substituted stainless steel as they offer better structural durability and flexibility with thinner struts. Since the 80s, stents were adopted widely in clinical trials which eventually resulted in shaping their current form. Nowadays, stents have mainly two types which we will discuss separately:
1) Bare Metal Stents (BMS): are the traditional stents that were approved by the medical community in 1986 after proving their superiority over balloon angioplasty. The design and materials used in BMS are developed to overcome its poor flexibility and thick struts. Bare metal stents could be self-expanding or balloon expanding. Although BMS was an excellent solution for vascular occlusion and offered great results, acute and subacute restenosis of the unblocked portion was a little common complication. Doctors found that blood clots get stuck in the stents causing partial obstruction of the bloodstream and 25% of patients may need another procedure within six months after the procedure. Therefore, doctors had to give double anti-platelet therapy (DAPT) to their patients who underwent stenting to prevent the recurrence of stenosis.
2) Drug-Eluting Stent (DES): was introduced to the medical community in the late 90s when a Brazilian interventional cardiologist called Eduardo Sousa succeeded in performing the first-in-human sirolimus Drug-Eluting Stent implant in Sao Paolo, Brazil. Doubtlessly, Dr. Sousa had taken a step forward in revascularization and encouraged cardiologists to develop second and third generations of DES. Drug-eluting stents (DES) were created to particularly overcome the restenosis issues associated with BMS. They are made up of a BMS covered with a polymer that slowly releases medication to suppress the cell growth that may lead to restenosis. The potential risk of restenosis has been reduced significantly by the action the drug has been released by the polymer. DES releases the pharmacological agents for six to nine months.
In 2003, johnson & johnson and cordis corp. had developed the first generation of DES approved by the FDA and called it CYPHER. The active agent released from the CYPHER stent was macrocyclic lactone, sirolimus which is a class of drugs that have a broad spectrum of action (antibiotic, antiproliferative and immunosuppressive). The first generation of DES was coated with a durable non-degradable polymer such as polyethylene-co-vinyl acetate (PEVA) and poly n-butyl methacrylate (PnBMA). This generation of DES was believed to have a controversial correlation with the incidence of MI (myocardial infarction)
The second generation of DES came out after a few years of the first generation. In this generation, doctors applied functional and structural modifications as Polymers were composed of newer, more biocompatible materials including zotarolimus, everolimus, and novolimus, resulting in a quicker onset of drug elution and better anti-proliferative action. Furthermore, pharmacological companies developed DES with biodegradable polymers which simply break down once it finishes releasing the drug leaving a bare-metal stent.
Since FDA approved the second generation of DES in 2008, it has become the option of choice, especially for patients with CAD (coronary artery disease). By 2017, eight companies were providing second-generation DES in the market. Currently, DES is used widely as it provides a non-invasive solution instead of the bypassing procedure. Cardiologists usually favor DES over BMS, they predict that DES will undergo more adjustments to fit almost every case scenario of arterial narrowing.
Statistical Review of Vascular Stenting
Stents are used to treat different medical conditions, but they are predominantly common in treating coronary artery diseases. the procedure in which the coronary artery is revascularized and supported with a stent is called Percutaneous Coronary Intervention (PCI). The percutaneous coronary intervention has become one of the most extensively performed procedures in modern cardiology, providing significant relief of anginal pain and preventing the occurrence of myocardial infarction. The number of the annually performed PCI is estimated to be more than 4.5 million procedures globally and about 900,000 in the US.
Frequent modifications and careful observation of the results of the stenting procedure had resulted in a high success rate. Many patients with cardiac problems have been effectively treated with drug-eluting stents (DES), avoiding more invasive interventions like coronary artery bypass surgery. In comparison to coronary bypassing, it seems that both have almost the same excellent outcomes. The success rate of PCI is variable and dependent on many factors such as the patient’s age, general health condition, and patient’s compliance. However, many cardiologists estimate that approximately 85% of patients resume their life normally after PCI.
Although some patients may claim that coronary stents reduce life expectancy, PCI improves the quality of life and restores the heart’s capacity. A study conducted in 2019 in Rotterdam, Netherlands showed that the survival rate at 10, 20, 30, and 35 years after PCI were 78%, 47%, 21%, and 12%, respectively. On the other hand, the mortality rate of stenting Is too low to be concerned about. Generally, 1.27 percent of PCI patients died in the hospital, ranging from 0.65 to 4.81 percent in elective PCI in patients with STEMI (prolonged complete obstruction of the coronary artery).
Indications and Candidates for Stent Implantation
Percutaneous coronary intervention is effective in treating heart attacks and other certain cardiac events but not all of them. It is just not considered a “cure-all” option for vascular stenosis or a non-questionably “better” alternative for CAD management. Stents are also used in other vascular narrowing conditions other than coronary artery diseases. We will discuss the most common indications for stent implantation.
1) STEMI (ST-Elevation Myocardial Infarction)
Is a serious medical condition caused by a severe shortage of the cardiac blood supply. Inadequacy of the blood supply for the exerted effort of the pumping heart muscle is usually expressed on ECG as elevated ST segment. Myocardial infarction (MI) which is also known as heart attack is the event in which cardiac tissues are beginning to die as a result of a lack of oxygen and nutrients. Myocardial infarction (MI) is usually developed gradually due to a sedentary lifestyle and unhealthy diet. The most typical presentation of MI is chest pain radiating to the left shoulder, neck, and jaw that exacerbates with physical effort and is relieved with rest.
it is believed that Primary percutaneous coronary intervention (PPCI) with stenting has become the gold standard revascularization approach for the treatment of ST-segment elevation myocardial infarction (STEMI) as it outperforms thrombolysis (breaking down blood clots) or balloon PCI alone. Cardiac tissues are sensitive to a lack of oxygen and can’t tolerate a lack of blood supply for a long period. Therefore, immediate medical intervention is always the key to avoiding irreversible damage to heart muscles. In case of complete coronary occlusion, the supplied muscular tissue will spontaneously start to infarct (die) after half 30 minutes.
2) NSTEMI
Which stands for non-ST elevated myocardial infarction is almost the same clinically as STEMI. As referred by its abbreviation, NSTEMI is characterized by the absence of the specific electrical pattern presented in the ECG of most heart attacks. Patients with NSTEMI could be more challenging to get diagnosed but fortunately, NSTEMI is believed to be presented with the same symptoms as STEMI which will guide the attention of the doctor toward cardiac issues. It is believed that both STEMI and NSTEMI are as severe and require rapid assessment and intervention. The earlier PCI is performed on patients with CAD (coronary artery disease), the better the outcome and the fewer complications.
3) Renal Artery Stenosis (Narrowing)
Is a less common indication of stent placement than CAD. Kidneys are vital organs that regulate blood pressure by filtering blood, producing urine, and maintaining the quantity of salt and moisture in the body. Kidneys are created to monitor blood pressure according to their input. In the case of renal artery stenosis, renal input is reduced making the kidney excrete a hormone called renin which will elevate blood pressure. This cycle will eventually lead to renovascular hypertension, a kind of elevated blood pressure. Renovascular hypertension strains the heart and can potentially progress to renal failure, requiring dialysis or a kidney transplant.
4) Severe Upper/Lower Limb Claudication
Result from a shortage of blood flow that doesn’t meet the needs of muscles. Peripheral Vasodilators and Blood thinners such as anti-platelets could treat this condition by enhancing peripheral blood circulation. In 2012 FDA approved the usage of vascular DES in treating PAD (peripheral artery disease) after many clinical trials.
5) Prinzmetal (Variant Angina)
Is a quite uncommon coronary artery disease in which the coronary arteries constrict and its muscles spasm spontaneously in the form of attacks even at rest. This condition is usually controlled by medications. However, in resistant cases, stent implantation could help reduce the severity of the attacks. PCI may provide some considerable benefits to those experiencing variant angina, however, when the procedure is required is still disputable.
Contraindications
Stent placement is a life-saving procedure, therefore it has no absolute contraindication. Some relative contraindications may compromise the outcome of the procedure or put the patient at potential risk of complications. General guidelines for any angiographic procedure are outlined including some limitations such as renal impairment, which may restrict the capacity of the kidney to metabolize iodinated contrast (injected dye) for the operation, or pregnancy, which would make the radiation exposure contraindicated. Recommendations for peripheral stenting include not to implant stents in the flexing regions such as the popliteal fossa (back of the knee) or easily compressible areas, which may result in stent crushing.
Since PCI is the most common form of stenting procedure, we will enumerate its contraindications into 1. Coagulopathy is a broad medical disorder in which the blood tends to bleed or clot excessively. Patients with uncontrolled coagulopathy will be at a life-threatening risk of internal hemorrhage or another vascular occlusion if they undergo a stenting procedure. Patients with stable angina are usually asked to perform a blood clotting profile to assess their eligibility for PCI.
- Critical left main coronary stenosis without collateral blood flow to the left anterior descending artery from a native artery or a patent bypass graft. Although CABG (coronary artery bypass grafting) is usually preferred in this condition, PCI is increasingly performed for selected patients after careful investigations.
- Stenosis of less than 50% of the artery is considered mild vascular blockage. Cardiologists usually prefer conservative management in treating this case because the risk of stenting or bypassing the occluded artery may outweigh their benefits. In such conditions, doctors prescribe blood thinners such as aspirin and ask their patients to modify their lifestyle by stopping smoking and following a healthier diet.
- An artery with a diameter of less than 1.5 mm is contraindicated to be implanted with a stent because its lumen would be too small and may rupture.
- patients with diffusely diseased arteries without focal stenotic areas wouldn’t get much better after stenting because the procedure depends on restoring the patency of a certain portion of an artery.
The Technique of the Procedure
Percutaneous coronary intervention which is also called PTCA (percutaneous transluminal coronary angioplasty) is a catheter-based procedure. The procedure involving cardiac catheterization is performed during an angiogram in the angiography suite (operating room equipped with radiological and screening equipment). PCI is performed by an interventional cardiologist and takes 30 minutes to 3 hours according to the doctor’s experience and complications he may encounter. Patients undergoing PCI are usually awake but don’t feel pain during the procedure because of the sedative and the local anesthesia applied at the site of access.
Percutaneous coronary intervention (PCI) is typically performed through the femoral or radial arteries and less commonly through the brachial or ulnar arteries. Overall, the radial artery has become the most frequent route of access for cardiac catheterization procedures because it could be more easily compressed against the radial bone when compared to the femoral artery. However, due to its small size, access to the radial artery requires greater experience and competency. After making a tiny incision, a catheter (long hollow tube) will be inserted into the blood vessel.
When the catheter reaches the aorta, a contrast dye will be injected into the coronaries. With x-ray fluoroscopy, the contrast dye helps visualize the site of stenosis in the coronaries and assess its severity. After locating the stenotic area, an expandable balloon at the tip of the catheter will be introduced there. Then the balloon will be inflated which will restore the arterial patency and stretch the stent over it. Finally, the balloon is deflated, and the catheter will be withdrawn leaving a stent at the site of stenosis to prevent recurrence. After removing the catheter, bandages will be applied at the site of the incision and the patient will have to stay in a recovery room for a few hours to be observed.
Complications
Although procedural complications of PCI have declined in recent years, substantial concerns remain. The risk of developing a complication whether during the procedure or post-operative is variable, yet in modern medical practice, the probable risks of PCI may be reliably anticipated. Although PCI is a minimally invasive procedure, patients should be aware of its risks and complications. Complications of PCI include:
- Bleeding whether external at the site of incision or internal due to rupture of a blood vessel. Arterial fragility may predispose its injury during the procedure that will lead to pseudoaneurysm or a hematoma (pooling of the blood outside the blood vessel).
- Nephropathy (kidney injury) caused by contrast dye is a considerable complication, particularly for patients with compromised renal function. Kidneys are responsible for the excretion of contrast dyes, so it would be an overload for diseased kidneys to perform this task. Tests evaluating how healthy the kidney is are usually conducted before the procedure, yet urgent cases may not have the time for proper pre-operative assessment.
- An infection has become a less commonly reported complication of the catheter-based procedure due to advanced sanitization measures applied at most catheterization suites.
- Thrombosis is found to be more common in old patients and patients with a coagulopathic disorder. Patients are asked to take blood thinners after the procedure to reduce the risk of thrombosis and distal embolism. Embolism is a circulating thrombus that will eventually get stuck in a peripheral blood vessel and occlude its blood flow.
- Restenosis at the site of stent implantation is considered a failure or a complication of the procedure. In the case of peripheral stenting, it may be caused by an external compression on the blood vessel.
- Arrhythmia and stroke are probable life-threatening complications for almost all cardiac procedures.
Recovery
After the procedure, the patient’s vital signs will be monitored for a few hours while he is laying in bed. Most patients could leave the hospital on the same day of the procedure, but they can’t drive home by themselves. Also, patients will be given some instructions to follow as avoiding strenuous activities and practicing sports for at least one week. Doctors also prescribe prophylactic anti-platelets such as low-dose aspirin for about one year.
Alternatives
If the patient is eligible to undergo vascular stenting, his doctor will discuss the available alternative options. These options include:
- CABG (coronary artery bypass graft) surgery is believed to provide better long-term results. However, CABG is an invasive surgery that involves scarring and more risks.
- Atherectomy is a procedure of drilling and removing the deposits and plaques which had built up in the lumen of the blood vessel.
- Percutaneous laser coronary angioplasty
- Blood thinners and anticoagulant medications