Restenosis

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The phenomenon of vessel restenosis, an immune response to damaged tissue, is known to be a common adverse event and the Achilles heel of angioplasty and stenting. Reducing restenosis is one of the highest priorities in research and the development of new endovascular technologies. Restenosis rates of drug-eluting stents appear to be significantly lower than bare-metal stents, and research is underway to determine if drug-coated balloons also improve restenosis outcomes. PTCA stent NIH.gif
The phenomenon of vessel restenosis, an immune response to damaged tissue, is known to be a common adverse event and the Achilles heel of angioplasty and stenting. Reducing restenosis is one of the highest priorities in research and the development of new endovascular technologies. Restenosis rates of drug-eluting stents appear to be significantly lower than bare-metal stents, and research is underway to determine if drug-coated balloons also improve restenosis outcomes.

Restenosis is the recurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow. Restenosis usually pertains to an artery or other large blood vessel that has become narrowed, received treatment to clear the blockage and subsequently become renarrowed. This is usually restenosis of an artery, or other blood vessel, or possibly a vessel within an organ.

Contents

Restenosis is a common adverse event of endovascular procedures. Procedures frequently used to treat the vascular damage from atherosclerosis and related narrowing and renarrowing (restenosis) of blood vessels include vascular surgery, cardiac surgery, and angioplasty. [1]

When a stent is used and restenosis occurs, this is called in-stent restenosis or ISR. [2] 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. [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]

Causes

Surgery to widen or unblock a blood vessel 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 plaques (atherosclerosis) against the artery walls, thus widening the size of the lumen and increasing blood flow. However the action damages the artery walls, and they respond by using physiological mechanisms to repair the damage. (See physiology below.) [4]

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. The artery can react to the stent, perceive it as a foreign body, and respond by mounting an immune system response which leads to further narrowing near or inside the stent.[ citation needed ]

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. A blood clot forms at the site of damage and further hinders blood flow. This is accompanied by an inflammatory immune response.[ citation needed ]

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). [5]

Diagnosis

Imaging

Vessel restenosis is typically detected by angiography, but can also be detected by duplex ultrasound and other imaging techniques. [6]

As "late loss"

Conceptual schematic illustrating effectiveness of endovascular interventions on lumen diameter to improve blood flow as represented by acute gain, late loss (restenosis), and net gain. Late Loss Restenosis.png
Conceptual schematic illustrating effectiveness of endovascular interventions on lumen diameter to improve blood flow as represented by acute gain, late loss (restenosis), and net gain.

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.[ citation needed ]

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.[ citation needed ]

The net gain of lumen diameter is the difference between acute gain and late loss, and is a measure of stent-graft effectiveness. [7]

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. [8]

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. [9]

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". [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 group of patients to determine averages (descriptive measures of central tendency) or as a predictive variable.[ citation needed ]

Prevention

In the first stage of restenosis, administering anti-platelet drugs (called IIb/IIIa inhibitors) immediately after surgery greatly reduces the chance of a thrombosis occurring.[ citation needed ]

Drug-eluting stents, coated with pharmaceuticals that inhibit tissue growth and thus reduce the risk of restenosis from scar-tissue and cell proliferation, are now widely used. [11] These stents reduce the occurrence of restenosis, with clinical studies showing an incidence rate of 5% or lower. [3] [12] [13]

Treatment

If restenosis occurs without a stent, it is usually treated with more angioplasty.[ citation needed ] This treatment is also used if restenosis occurs at either the proximal or distal end of the stent.[ citation needed ]

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. [14]

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. [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 a faster drug delivery.

Alternative treatments include brachytherapy, or intracoronary radiation. The radiation kills cells and inhibits tissue growth (similar to a patient undergoing cancer therapy). [17]

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).[ citation needed ]

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. [18]

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. [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]

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. [20]

The 2006 SIROCCO trial compared the sirolimus drug-eluting stent with a bare nitinol stent for atherosclerotic lesions of the subsartorial 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) in subsartorial artery disease. At 1 year follow-up, restenosis was reported in 34.4% of stented patients versus 61.1% of PTA patients. [22]

See also

Related Research Articles

<span class="mw-page-title-main">Angioplasty</span> Procedure to widen narrow arteries or veins

Angioplasty, also known as balloon angioplasty and percutaneous transluminal angioplasty (PTA), is a minimally invasive endovascular procedure used to widen narrowed or obstructed arteries or veins, typically to treat arterial atherosclerosis. A deflated balloon attached to a catheter is passed over a guide-wire into the narrowed vessel and then inflated to a fixed size. The balloon forces expansion of the blood vessel and the surrounding muscular wall, allowing an improved blood flow. A stent may be inserted at the time of ballooning to ensure the vessel remains open, and the balloon is then deflated and withdrawn. Angioplasty has come to include all manner of vascular interventions that are typically performed percutaneously.

<span class="mw-page-title-main">Stent</span> Type of medical device

In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandable coronary, vascular and biliary stents, to simple plastic stents that allow urine to flow between kidney and bladder. "Stent" is also used as a verb to describe the placement of such a device, particularly when a disease such as atherosclerosis has pathologically narrowed a structure such as an artery.

<span class="mw-page-title-main">Coronary catheterization</span> Radiography of heart and blood vessels

A coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional (treatment) purposes.

<span class="mw-page-title-main">Stenosis</span> Abnormal narrowing of a blood vessel or other tubular organ or structure

A stenosis 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.

<span class="mw-page-title-main">Interventional cardiology</span>

Interventional cardiology is a branch of cardiology that deals specifically with the catheter based treatment of structural heart diseases. Andreas Gruentzig is considered the father of interventional cardiology after the development of angioplasty by interventional radiologist Charles Dotter.

Intravascular ultrasound (IVUS) or intravascular echocardiography is a medical imaging methodology using a specially designed catheter with a miniaturized ultrasound probe attached to the distal end of the catheter. The proximal end of the catheter is attached to computerized ultrasound equipment. It allows the application of ultrasound technology, such as piezoelectric transducer or CMUT, to see from inside blood vessels out through the surrounding blood column, visualizing the endothelium of blood vessels.

Andreas Roland Grüntzig was a German radiologist and cardiologist, with foundational interest, training and research in epidemiology and angiology. He is known for being the first to develop successful balloon angioplasty for expanding lumens of narrowed arteries. He was born in Dresden.

<span class="mw-page-title-main">Cardiac catheterization</span> Insertion of a catheter into a chamber or vessel of the heart

Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done both for diagnostic and interventional purposes.

<span class="mw-page-title-main">Percutaneous coronary intervention</span> Medical techniques used to manage coronary occlusion

Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the insertion of a permanent wire-meshed tube that is either drug eluting (DES) or composed of bare metal (BMS). The stent delivery balloon from the angioplasty catheter is inflated with media to force contact between the struts of the stent and the vessel wall, thus widening the blood vessel diameter. After accessing the blood stream through the femoral or radial artery, the procedure uses coronary catheterization to visualise the blood vessels on X-ray imaging. After this, an interventional cardiologist can perform a coronary angioplasty, using a balloon catheter in which a deflated balloon is advanced into the obstructed artery and inflated to relieve the narrowing; certain devices such as stents can be deployed to keep the blood vessel open. Various other procedures can also be performed.

<span class="mw-page-title-main">Drug-eluting stent</span> Peripheral or coronary stent

A drug-eluting stent (DES) is a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly release a drug to block cell proliferation. This prevents fibrosis that, together with clots (thrombi), could otherwise block the stented artery, a process called restenosis. The stent is usually placed within the peripheral or coronary artery by an interventional cardiologist or interventional radiologist during an angioplasty procedure.

<span class="mw-page-title-main">Carotid stenting</span>

Carotid artery stenting is an endovascular procedure where a stent is deployed within the lumen of the carotid artery to treat narrowing of the carotid artery and decrease the risk of stroke. It is used to treat narrowing of the carotid artery in high-risk patients, when carotid endarterectomy is considered too risky.

The history of invasive and interventional cardiology is complex, with multiple groups working independently on similar technologies. Invasive and interventional cardiology is currently closely associated with cardiologists, though the development and most of its early research and procedures were performed by diagnostic and interventional radiologists.

Fractional flow reserve (FFR) is a diagnostic technique used in coronary catheterization. FFR measures pressure differences across a coronary artery stenosis to determine the likelihood that the stenosis impedes oxygen delivery to the heart muscle.

<span class="mw-page-title-main">Coronary stent</span> Medical apparatus implanted into coronary arteries

A coronary stent is a tube-shaped device placed in the coronary arteries that supply blood to the heart, to keep the arteries open in the treatment of coronary heart disease. It is used in a procedure called percutaneous coronary intervention (PCI). Coronary stents are now used in more than 90% of PCI procedures. Stents reduce angina and have been shown to improve survival and decrease adverse events in an acute myocardial infarction.

<span class="mw-page-title-main">Zotarolimus</span> Chemical compound

Zotarolimus is an immunosuppressant. It is a semi-synthetic derivative of sirolimus (rapamycin). It was designed for use in stents with phosphorylcholine as a carrier. Zotarolimus, or ABT-578, was originally used on Abbott's coronary stent platforms to reduce early inflammation and restenosis; however, Zotarolimus failed Abbott's primary endpoint to bring their stent/drug delivery system to market. The drug was sold/distributed to Medtronic for use on their stent platforms, which is the same drug they use today. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology. The first human coronary stent implantation was first performed in 1986 by Puel et al. However, there are complications associated with stent use, development of thrombosis which impedes the efficiency of coronary stents, haemorrhagic and restenosis complications are problems associated with stents.

Julio Palmaz is a doctor of vascular radiology at University of Texas Health Science Center at San Antonio. He studied at the National University of La Plata in Argentina, earning his medical degree in 1971. He then practiced vascular radiology at the San Martin University Hospital in La Plata before moving to the University of Texas Health and Science Center at San Antonio. He is known for inventing the balloon-expandable stent, for which he received a patent filed in 1985. It was recognized in Intellectual Property International Magazine as one of "Ten Patents that Changed the World" in the last century. His early stent research artifacts are now part of the medical collection of the Smithsonian Institution in Washington, DC. He continues to innovate on his initial designs, developing new endovascular devices.

<span class="mw-page-title-main">Bioresorbable stent</span>

In medicine, a stent is any device which is inserted into a blood vessel or other internal duct to expand it to prevent or alleviate a blockage. Traditionally, such devices are fabricated from metal mesh and remain in the body permanently or until removed through further surgical intervention. A bioresorbable stent serves the same purpose, but is manufactured from a material that may dissolve or be absorbed in the body.

<span class="mw-page-title-main">Reperfusion therapy</span>

Reperfusion therapy is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack. Reperfusion therapy includes drugs and surgery. The drugs are thrombolytics and fibrinolytics used in a process called thrombolysis. Surgeries performed may be minimally-invasive endovascular procedures such as a percutaneous coronary intervention (PCI), which involves coronary angioplasty. The angioplasty uses the insertion of a balloon and/or stents to open up the artery. Other surgeries performed are the more invasive bypass surgeries that graft arteries around blockages.

Neointimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in the thickening of arterial walls and decreased arterial lumen space. Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary interventions such as stenting or angioplasty. The term neointima is used because the cells in the hyperplastic regions of the vascular wall have histological characteristics of both intima and normal artery cells.

A dual therapy stent is a coronary artery stent that combines the technology of an antibody-coated stent and a drug-eluting stent. Currently, second-generation drug-eluting stents require long-term use of dual-antiplatelet therapy, which increases the risk of major bleeding occurrences in patients. Compared to drug-eluting stents, dual therapy stents have improved vessel regeneration and cell proliferation capabilities. As a result, dual therapy stents were developed to reduce the long-term need for dual-antiplatelet therapy.

References

  1. ↑ Forgos, Richard N. (August 2004). "Restenosis After Angioplasty and Stenting".
  2. ↑ Bennett, M. R (2003). "In-Stent Stenosis: Pathology and Implications for the Development of Drug Eluting Stents". Heart. 89 (2): 218–24. doi:10.1136/heart.89.2.218. PMC   1767562 . PMID   12527687.
  3. 1 2 3 Hamid, H; Coltart, J (2007). "'Miracle stents' - a future without restenosis". McGill Journal of Medicine. 10 (2): 105–11. PMC   2323487 . PMID   18523610.
  4. ↑ Kirchengast, M; Münter, K (1998). "Endothelin and restenosis". Cardiovascular Research. 39 (3): 550–5. doi: 10.1016/S0008-6363(98)00143-6 . PMID   9861296.
  5. ↑ Clowes, Alexander M.D. VascularWeb, Society for Vascular Surgery https://dev.vascularweb.org/research/Pages/prevention-of-neointimal-hyperplasia-taxol-,-rapamycin-,-and-radiation.aspx%5B%5D
  6. ↑ "Index".
  7. ↑ Kuntz, R. E.; Safian, R. D.; Carrozza, J. P.; Fishman, R. F.; Mansour, M.; Baim, D. S. (1992). "The importance of acute luminal diameter in determining restenosis after coronary atherectomy or stenting". Circulation. 86 (6): 1827–35. doi: 10.1161/01.CIR.86.6.1827 . PMID   1451255.
  8. ↑ Meijboom, W. Bob; Van Mieghem, Carlos A.G.; Van Pelt, Niels; Weustink, Annick; Pugliese, Francesca; Mollet, Nico R.; Boersma, Eric; Regar, Eveline; et al. (2008). "Comprehensive Assessment of Coronary Artery Stenoses". Journal of the American College of Cardiology. 52 (8): 636–43. doi: 10.1016/j.jacc.2008.05.024 . PMID   18702967.
  9. ↑ Ota, H.; Takase, K.; Rikimaru, H.; Tsuboi, M.; Yamada, T.; Sato, A.; Higano, S.; Ishibashi, T.; Takahashi, S. (2005). "Quantitative Vascular Measurements in Arterial Occlusive Disease". Radiographics. 25 (5): 1141–58. doi:10.1148/rg.255055014. PMID   16160101.
  10. ↑ Serruys, P. W.; Foley, D. P.; De Feyter, Pim J. (31 December 1993). Quantitative Coronary Angiography in Clinical Practice. pp. 613–614. ISBN   9780792323686.
  11. ↑ Raffoul, Jad; Nasir, Ammar; Klein, Andrew J. P. (2018). "Technological Advances in Stent Therapies: a Year in Review". Current Treatment Options in Cardiovascular Medicine. 20 (5): 36. doi:10.1007/s11936-018-0630-2. ISSN   1092-8464. PMID   29627909. S2CID   4789492.
  12. ↑ Waksman, Ron; Pakala, Rajbabu (2009). "Drug-Eluting Balloon". Circulation: Cardiovascular Interventions. 2 (4): 352–358. doi: 10.1161/CIRCINTERVENTIONS.109.873703 . PMID   20031739.
  13. 1 2 Fernández-Ruiz, Irene (2016). "Drug-eluting or bare-metal stents?". Nature Reviews Cardiology. 13 (11): 631. doi:10.1038/nrcardio.2016.160. ISSN   1759-5002. PMID   27629515. S2CID   39324460.
  14. ↑ Jukema, J. Wouter; Ahmed, Tarek A. N.; Verschuren, Jeffrey J. W.; Quax, Paul H. A. (2012). "Restenosis after PCI. Part 2: prevention and therapy". Nature Reviews Cardiology. 9 (2): 79–90. doi:10.1038/nrcardio.2011.148. ISSN   1759-5002. PMID   21989052. S2CID   9794637.
  15. ↑ Wu, Ridong; Li, Zilun; Wang, Mian; Chang, Guangqi; Yao, Chen; Wang, Shenming (June 2017). "Paclitaxel-coated versus uncoated balloon angioplasty for femoropopliteal artery in-stent restenosis". International Journal of Surgery. 42: 72–82. doi: 10.1016/j.ijsu.2017.04.057 . PMID   28461145.
  16. ↑ Kolachalama, Vijaya B.; Shazly, Tarek; Vipul C. Chitalia; Lyle, Chimera; Azar, Dara A.; Chang, Gary H. (2019-05-02). "Intrinsic coating morphology modulates acute drug transfer in drug-coated balloon therapy". Scientific Reports. 9 (1): 6839. Bibcode:2019NatSR...9.6839C. doi: 10.1038/s41598-019-43095-9 . ISSN   2045-2322. PMC   6497887 . PMID   31048704.
  17. ↑ Andras, Alina; Hansrani, Monica; Stewart, Marlene; Stansby, Gerard (2014-01-08). "Intravascular brachytherapy for peripheral vascular disease". Cochrane Database of Systematic Reviews. 2014 (1): CD003504. doi:10.1002/14651858.cd003504.pub2. ISSN   1465-1858. PMC   6863108 . PMID   24399686.
  18. ↑ Grech, E. D (2003). "Percutaneous coronary intervention. I: History and development". BMJ. 326 (7398): 1080–2. doi:10.1136/bmj.326.7398.1080. PMC   1125993 . PMID   12750213.
  19. ↑ Mohan, S; Dhall, A (2010). "A comparative study of restenosis rates in bare metal and drug-eluting stents". The International Journal of Angiology. 19 (2): e66–72. doi:10.1055/s-0031-1278368. PMC   3005409 . PMID   22477592.
  20. ↑ Becquemin, Jean-Pierre; Favre, Jean-Pierre; Marzelle, Jean; Nemoz, Chantal; Corsin, Caroline; Leizorovicz, Alain (2003). "Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: A multicenter prospective randomized study". Journal of Vascular Surgery. 37 (3): 487–94. doi: 10.1067/mva.2003.155 . PMID   12618680.
  21. ↑ Duda, Stephan H.; Bosiers, Marc; Lammer, Johannes; Scheinert, Dierk; Zeller, Thomas; Oliva, Vincent; Tielbeek, Alexander; Anderson, John; et al. (2006). "Drug-Eluting and Bare Nitinol Stents for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery:Long-term Results from the SIROCCO Trial". Journal of Endovascular Therapy. 13 (6): 701–10. doi:10.1583/05-1704.1. PMID   17154704. S2CID   34610436.
  22. ↑ Dick, Petra; Wallner, Hubert; Sabeti, Schila; Loewe, Christian; Mlekusch, Wolfgang; Lammer, Johannes; Koppensteiner, Renate; Minar, Erich; Schillinger, Martin (2009). "Balloon angioplasty versus stenting with nitinol stents in intermediate length superficial femoral artery lesions". Catheterization and Cardiovascular Interventions. 74 (7): 1090–5. doi:10.1002/ccd.22128. PMID   19859954. S2CID   33540816.
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