Management of carotid stenosis. History and today.

Internal carotid stenosis constitutes a significant clinical challenge, since it is the cause of 20-25% of ischemic brain strokes. The management of the internal carotid stenosis for many years has been raising controversies amongst neurologists, vascular surgeons and interventional radiologists mainly due to the introduction of endovascular stenting as an alternative to surgical treatment. Its application, however, requires knowledge of specific selection criteria for this kind of treatment as well as of the methods of monitoring patients after stent implantation into the internal carotid artery. Duplex Doppler ultrasound examination is currently a basis for the diagnosis of the arterial stenosis of precranial segments of the carotid arteries. It allows a reliable assessment of not only the course and morphology of the walls, but also of the hemodynamics of blood flow. Interventional treatment is applicable in patients with internal carotid stenosis of ≥70%, which is accompanied by an increase of the systolic flow velocity above 200 cm/s and the end-diastolic velocity above 50-60 cm/s in the stenotic lumen. In most cases, such a diagnosis in duplex Doppler ultrasound examination does not require any confirmation by additional diagnostic methods and if neurological symptoms are also present, it constitutes a single indication for interventional treatment. When deciding about choice of surgical or endovascular method of treatment, the following factors are of crucial importance: morphology of atherosclerotic plaque, its size, echogenicity, homogeneity of its structure, its surface and outlines. By means of ultrasound examinations, patients can be monitored after endovascular stent implantation. They enable evaluation of the degree of stent patency and allow for an early detection of symptoms indicating stenosis recurrence or presence of in-stent thrombosis. When interpreting the findings of the US checkup, it is essential to refer to the initial examination performed in the first days after the procedure and the next ones conducted during the monitoring period.

Introduction

For many years, the management of the internal carotid artery stenosis has been the subject of heated discussions amongst neurologists, vascular surgeons and interventional radiologists mainly due to the introduction of endovascular stenting as an alternative to surgical treatment(.

Internal carotid stenosis constitutes a significant clinical challenge, since it is the cause of 20–25% of ischemic brain strokes(. According to the latest data of the WHO (World Health Organization), stroke constitutes the second cause of death and the first cause of disability in the world. Each year 15 million people in the world experience ischemic stroke, 5 million of them die and 5 million remain disabled. In Europe, the number of deaths caused by ischemic brain stroke reaches 650,000 per year. Moreover, the costs of treatment are extremely high. In 2010 they constituted 74 million dollars. It is estimated that in 2050 they may reach 2 trillion dollars(.

The wide-ranging campaigns conducted for many years, which aimed at the reduction of stroke risk factors, primarily hypertension and nicotine addiction, have brought the expected outcomes and the incidence of ischemic brain stroke decreased. Nevertheless, the number of patients experiencing stroke continues to increase globally due to population ageing especially in highly developed countries.

The importance of the carotid artery was noticed as early as in the Antiquity. From the notes of Rufus of Ephesus, who lived in the first century AD, we know that the Greek name for this artery, karotide, meant ‘stupor’ or ‘deep dream.’ This name resulted from the observations that such symptoms may occur when this artery becomes compressed. Even Greek warriors were conscious of this. On the southern side of the Parthenon in Athens, the 31st metope presents a centaur, who compresses the internal carotid artery of the enemy in his combat with Lapith(.

Hippocrates was the first to describe ischemic brain stroke. He observed that patients suffering from stroke manifest it with the loss of consciousness and coma. For many years, it was believed that this condition and its course were in the hands of Gods and therefore, any attempts to treat it were futile. Only in 1905 did Chiari associate the occurrence of the disease symptoms with the presence of atherosclerotic plaques in the internal carotid artery. He put forward a hypothesis that neurological symptoms appeared in relation to arterial occlusion(. However, another half of the century passed before the first attempt to remove the obstruction from the arterial lumen, i.e. atherosclerotic plaques, took place. It happened in 1953. The surgery was performed by Dr. DeBakey who successfully removed atherosclerotic plaque and a freshly built-up clot from the internal carotid artery(.

In the subsequent years, the number of carotid endarterectomies rapidly increased (only in the United States, approximately 100,000 procedures were performed annually) despite arising doubts concerning appropriate patient selection and effectiveness of this surgery. In 1985, the Rand Corporation's analysis of 1,300 operations demonstrated that such surgery was indicated in merely 35% of patients and the postoperative complication rate reached 10%(.

This report was a stimulus to conduct well-planned randomized studies – NASCET (North American Symptomatic Carotid Endarterectomy Trial) in the United States and ECST (European Carotid Surgery Trial) in Europe, which would compare the outcomes of surgical and conservative treatment of patients with internal carotid stenosis(. Both studies unambiguously showed that the outcomes of surgical treatment were better than conservative treatment of symptomatic patients when the narrowing of the internal carotid artery exceeded 70% of the vessel's lumen. However, no differences between the outcomes of these two methods were noticed when the internal carotid stenosis was not greater than 70%. For many years, the results of these studies constituted the basis for the selection of patients with symptomatic internal carotid stenosis to surgery. The management of asymptomatic patients, on the other hand, was based on ACAS (Asymptomatic Carotid Atherosclerosis Study) and ACST (Asymptomatic Carotid Surgery Trial) studies, which stated that patients with stenosis exceeding 60% qualified for endarterectomy if the total rate of deaths and strokes in the centers providing such surgical treatment had not exceeded 3%(.

Controversies in the approach to the treatment of internal carotid stenosis were raised with the introduction of endovascular method of widening of the stenosed segment of carotid artery. The first internal carotid angioplasty was successfully performed by a German interventional radiologist Klaus Mathias in 1977. Only in the 1990s, however, did the procedure gain its due place among the methods for the treatment of the internal carotid stenosis(.

In 2011, numerous scientific associations of neurologists, vascular surgeons, interventional radiologists and cardiologists prepared common guidelines for treatment of patients with conditions affecting the extracranial segments of carotid and vertebral arteries. Chapter 9 of these guidelines contains information about the eligibility of patients for the treatment of internal carotid stenosis. The treatment should be applied to those patients who experienced TIA (transient ischemic attack) or “mini” ischemic stroke that does not cause permanent neurological deficits and who present internal carotid stenosis which is greater than 70% on ultrasound examination or 50% in angiography. Finally, stenting has been recognized as an alternative for surgical treatment(.

Moreover, there are some patients with increased surgical risk and they should be considered for endovascular stenting in the first instance. These patients include those with cardiac failure (AHA III/IV), after myocardial infarction (>24 h, <4 weeks), with unstable angina pectoris, advanced respiratory failure, contralateral internal carotid occlusion, multilevel stenosis, so called “short neck”, high bifurcation of the common carotid artery (C2–C3), restenosis after carotid endarterectomy or radiotherapy in the area of the neck.

Surgical procedures, in turn, are more effective in patients with: heparin intolerance, contraindications to antiplatelet medications, difficult anatomic vascular conditions (type III aortic arch, tortuous carotid arteries), circular atherosclerotic plaques or soft free-floating thrombus in the internal carotid artery.

Surgical treatment

The procedure is performed in local or, more rarely, general anesthesia. The incision runs along the anterior border of the sternocleidomastoid muscle, which enables exposure of the common, internal and external carotid arteries. If clamps placed on the artery prior to its incision cause symptoms of brain ischemia, it is necessary to use a temporary shunt. After an incision of the artery, atherosclerotic plaque is removed from its lumen. The arterial wall may be closed with a running suture, venous patch or synthetic graft.

Another way to conduct the procedure is to restore the patency by cutting of the internal carotid artery from the common carotid artery. When the atherosclerotic plaques have been removed, the patency of the vessel is surgically restored and the artery is reattached to the primary site.

Surgical procedures are highly effective and the total rate of completed strokes and deaths in the periprocedural period does not exceed 6%. The recurrence of stenosis is observed in 2–20% of cases(.

Endovascular treatment

The procedure is performed in local anesthesia. The first stage consists of a transcutaneous placement of a catheter in the common femoral artery, which, in order to perform angiography, is then passed into the common carotid arteries using X-ray guidance. This examination confirms stenosis diagnosed in the previous imaging examinations and allows for the selection of the most suitable projection for the selective catheterization of the internal carotid artery. Most of the procedures are performed with the use of cerebral protection devices which ensure that the embolic material released from the atherosclerotic plaques does not reach the cerebral arteries. The most commonly used devices are filters which in the closed form are passed through the narrowing and opened above it in the internal carotid artery(. The narrowing frequently requires an initial dilatation which is performed with a balloon catheter. Next, the stent is introduced so that it covers the stenotic lumen and its proximal and distal ends positioned in unchanged segments of the artery. In most of the cases the stent covers the opening of the external carotid artery, which, however, rarely causes its occlusion. Nitinol stents of various diameters are most frequently used. The distal end of the stent, with a lower diameter, is placed in the internal carotid artery and the proximal end, with greater diameter, in the common carotid artery (figs. 1 and 2). Stents have various designs of the nitinol net. There are open-cell stents, which are more flexible and better adapt to the arterial walls, and closed-cell stents, which are stiffer and often do not perfectly adapt to the walls. Stent designs affect the flow parameters which can be assessed in Doppler examination within the first days after stent implantation. In closed-cell stents, the blood flow velocity is initially 20% higher than in the case of open-cell stents(. Stents usually require remodeling by means of a balloon catheter. The procedure is concluded with angiography examination which confirms its effectiveness. In the case of highly calcified atherosclerotic plaques, residual stenosis may be present, but should not exceed 30% of the lumen (fig. 3).

Fig. 1 A

Color Doppler sonography. Large plaque causing highgrade stenosis of internal carotid artery

Fig. 2 A

Color Doppler sonography. Ulcerated atherosclerotic plaque causing high-grade stenosis of the internal carotid artery

Fig. 3 A

Color Doppler sonography. Large plaque causing stenosis of internal carotid artery

Spectral display shows high systolic velocity (PSV, 273 cm/s) in the center of the stenotic lumen

Arteriography of the left common carotid artery. High-grade stenosis in the proximal part of internal carotid artery

Control arteriography after stent implantation

Self-expanding stent for the carotid artery

Power Doppler sonography confirms the patency and adequate position of the stent

Spectral display shows the normalization of systolic velocity (PSV, 49 cm/s) in the internal carotid artery

Spectral display shows high systolic velocity (PSV, 360 cm/s) in the center of the stenotic lumen

Arteriography of the left common carotid artery. Irregular surface of the stenosed internal carotid artery

Control arteriography after stent implantation

Color Doppler sonography confirms the patency and adequate position of the stent

Spectral display shows the normalization of systolic velocity (PSV, 45 cm/s) in the internal carotid artery

Spectral display shows high systolic velocity (PSV, 400 cm/s) in the stenotic lumen

Arteriography of the right common carotid artery. High-grade stenosis in the proximal part of the internal carotid artery

Control arteriography after stent implantation

Sonography confirms residual stenosis

Systolic velocity (PSV, 153 cm/s) in the stenotic segment of the carotid artery

The internal carotid stenting technique is characterized by a high rate of technical success reaching 95–99%. The total rate of completed strokes and deaths in the periprocedural period does not exceed 0.5–5%. Delayed complications are a consequence of in-stent thrombosis which is observed very rarely in up to 0.3% of cases or restenosis in 0.7–25% of cases(.

Ultrasound examination

Carotid stenosis is usually a consequence of atherosclerotic lesions. Early detection and proper assessment of both the morphology of atherosclerotic plaque and the degree of stenosis as well as associated hemodynamic disorders greatly influence the selection of the treatment method – surgical or endovascular.

Duplex Doppler ultrasound examination is currently the basis for the diagnosis of arterial stenosis of precranial fragments of the carotid arteries. It allows for a reliable assessment of not only the course and morphology of the walls but also of the hemodynamics of blood flow. When diagnosed and assessed in the duplex Doppler ultrasound examination, hemodynamically significant internal carotid stenosis >70% in most cases does not require any confirmation by additional diagnostic methods. If it occurs in patients manifesting neurological symptoms, in many centers it constitutes a single indication for interventional treatment. There are, however, certain limitations that may affect the diagnostic effectiveness of duplex Doppler examination. The most common constraints encompass: calcified atherosclerotic plaques, difficulties to adjust appropriate Doppler angle of insonation and low values of blood flow velocity in the subtotal/subocclusive stenoses. Furthermore, high bifurcation of the carotid arteries and abundant adipose tissue constitute additional factors hindering accurate diagnosis.

Although numerous studies emphasize the importance of morphological assessment of the arteries and plaques, the primary criterion of patient selection for an interventional procedure is hemodynamics of the blood flow in the internal carotid artery. The color-coded images presenting blood flow and Doppler frequency spectrum are subject to analysis. With the advancement of atherosclerosis and gradual lumen narrowing, increased blood flow velocity is observed in the stenotic segments of the artery. Color Doppler presents a mosaic of colors in both flow directions in the region of stenosis (aliasing). Additionally, the Doppler spectral display presents an increase of peak systolic and end-diastolic velocities.

In practice, when the arterial lumen narrows to 50 or even 60% in its cross-section, no blood flow disorders are detected or only a slight acceleration of systolic velocity up to 150 cm/s is noted. Stenoses in the range of 60–69% are defined as hemodynamically borderline stenoses if the peak systolic velocity is not greater than 200 cm/s and the end-diastolic velocity is lower than 40 cm/s. Greater values indicate hemodynamically significant stenoses: the narrowing in the range or 70–84% is described as intermediate and those ranging from 85% to 95% – as high-grade. In these cases, the systolic velocity always exceeds 200 cm/s and the end-diastolic velocity is greater than 40–50 cm/s. Initially, it was believed that there was a directly proportional correlation between the degree of stenosis and the velocity, i.e. the greater stenosis, the greater velocity. It was quickly observed, however, that accurate indication of the level of hemodynamically significant stenosis also depends on other factors. The condition of the remaining arteries supplying the brain is of vital importance, in particular the patency of the contralateral internal carotid artery (possible compensation). Besides, heart beat and arterial blood pressure naturally influence the blood flow velocity in the stenotic lumen. Hence, the accurate evaluation of the degree of stenosis of >70% results from various factors which may be correctly interpreted only by experienced sonographers. Subtotal stenoses of >95% occur when on morphological assessment, significant stenosis is found and the peak systolic velocity exceeds 400–500 cm/s with a subsequent evident signal reduction above the site of stenosis. If, however the peak systolic velocity decreases in the stenotic lumen with a visible reduction of the internal carotid arterial lumen above the site of stenosis, it is justified to diagnose borderline occlusion, so called subocclusion.

Interventional treatment, stenting or surgery, is applied in patients with internal carotid stenosis of ≥70%, which is accompanied by an increase of the peak systolic velocity above 200 cm/s and the end-diastolic velocity above 50–60 cm/s. As has been mentioned above, accurate evaluation of the stenosis degree within the range of 70–95% is not crucial while making treatment-related decisions. Numerous experiences show the lack of measurable benefits of restoring the patency in most cases of subtotal stenoses and in all cases of subocclusions(.

When selecting a surgical or endovascular treatment of internal carotid stenosis, the following factors are of crucial importance: morphology of atherosclerotic plaque, its size, echogenicity, homogeneity of its structure, its surface and outlines. These parameters are assessed on the basis of grey-scale imaging (B-mode) and with the color-coded blood flow option (color/power Doppler). The size of the plaque is evaluated as its maximal thickness, length in the internal carotid artery and maximal cross-sectional area or its volume measured by a 3D option. As for their echogenicity, plaques may be divided into two basic groups: regular, i.e. homogeneous (hypo-, iso- and hyperechoic) and irregular, i.e. heterogeneous. Plaque echogenicity is compared with the echogenicity of the sternocleidomastoid muscle. Hypoechoic plaques contain large amounts of lipids and consist of lipid core and thin fibrous cap. Hyperechoic plaques, in turn, have a thick fibrous cap and frequently include calcifications accompanied by acoustic shadows. Irregular plaques consist of lipids in more than 40% and are called vulnerable/unstable. They are more likely to rupture. Finally, heterogeneous plaques include more calcifications and undergo hemorrhagic conversion more often than homogeneous ones. The surface of a plaque is also analyzed. When the plaque's border facing the lumen is not smooth, it is described as irregular. The surface defects which fill in with “color” in Doppler examination and with the depth and width of at least 1 mm are called ulcerations(.

The patients with plaques of low echogenicity or heterogeneous plaques with irregular surface and ulcerations do not constitute the best candidates for endovascular stenting since the risk of releasing embolic material during stent implantation is high. In such cases, surgical treatment is always considered in the first instance. On the other hand, the experiences gathered within the last several years demonstrated that the presence of so-called vulnerable plaques do not constitute a contraindication to stenting since appropriately chosen technique and equipment allow for an effective and safe stenting procedure.

Power Doppler sonography. In-stent restenosis

Spectral display shows high systolic velocity (PSV, 209 cm/s) in the internal carotid artery

Arteriography of the right common carotid artery. In-stent restenosis

Control arteriography after balloon angioplasty

Power Doppler confirms successful angioplasty

Spectral display shows the normalization of systolic velocity (PSV, 76 cm/s)

Color Doppler sonography. Irregular atherosclerotic plaque causing high-grade stenosis of the internal carotid artery

Arteriography of the right common carotid artery. Irregular lumen of the stenosed internal carotid artery

Control arteriography after stent implantation

Color Doppler sonography reveals in-stent thrombosis

The evaluation of the outcomes of carotid endovascular stenting requires regular checkups. Ultrasound examination using Doppler options is performed within several days after the procedure (initial examination) and subsequently, after 6 and 12 months. During each scanning, the examiner should assess artery patency in the region of the stent since there is a risk of in-stent restenosis or thrombosis. Restenosis may be a consequence of further development of atherosclerotic lesion or proliferation of the vascular endothelium as a response to a foreign body, i.e. the stent. The examiner should also assess the position of the stent, measure its smallest diameter, register the Doppler spectral displays of blood flow and note the values of the systolic and end-diastolic velocities in the area of the stent, above it – in the internal carotid artery, and below it – in the common carotid artery. It is extremely important to be able to refer to the ultrasound image obtained directly after stent implantation and in the subsequent US checkups. The flow values assessed in the first days after stent implantation may slightly change in response to stent “adjustment” to the vessel wall in the first week following the procedure. One should also remember about residual stenosis (up to 30% of the lumen) which may remain after endovascular stenting. The diagnosis of the narrowing in the stent is based on the increased values of systolic and end-diastolic velocities(. According to the most commonly assumed criteria, the recurrence of stenosis of 30% is diagnosed when the systolic velocity exceeds 150 cm/s, 50% stenosis – with the velocity of 200 cm/s and 70% stenosis – with the velocity of 350 cm/s. However, monitoring the values of systolic velocity in subsequent examinations seem to be more beneficial than a very strict adherence to the criteria mentioned above. It is estimated that recurrent stenosis resulting from an excessive growth of endothelium occurs within 6–12 months after stent implantation. Therefore, in this period, control examinations are vital. If the patency of the stented carotid artery is maintained after 12 months, it is recommended to perform US checkups once a year(.

During the examination, the entire stent should be visualized, which may be difficult especially in patients with so-called “high” carotid artery bifurcation. In such cases, the peripheral fragment of the stent is hard to assess due to the Doppler signal which is too weak. Nevertheless, it needs to be remembered that the evaluation of this fragment is of crucial importance since that is where the stenosis resulting from excessive endothelium proliferation reappears in most cases. If in duplex Doppler examination the distal end of the stent can not be adequately visualized and restenosis is suspected, further imaging examinations should be performed. Out of the non-invasive techniques, CT angiography gives the best results. MRA examinations, however, are not used due to the deformation of the magnetic field induced by stents, which despite being made of non-paramagnetic nitinol, cause artefacts hinder accurate assessment. In most of those cases arteriography is considered. Not only does it ensure the best assessment of the stent lumen but also, if needed, allows for simultaneous balloon angioplasty in order to restore the correct blood flow in the artery.

Conclusion

Currently, more and more patients classify for endovascular stenting of internal carotid artery stenosis. The primary and in most cases adequate diagnosis of the narrowing is based on ultrasound examination. It allows for an estimation of stenosis degree as well as for thorough assessment of the morphology of the atherosclerotic plaques, which is significant for the selection of the treatment method, either surgical or endovascular o. The latter is primarily used in patients manifesting neurological symptoms and stenosis of ≥70% of the internal carotid artery. Moreover, atherosclerotic lesions in these patients should not show signs of unstable plaques. Patients, who underwent endovascular stenting are monitored by means of ultrasound examinations. The aim is an evaluation of the stent patency taking into account the possibility of in-stent restenosis or thrombosis. When interpreting the findings of the US control examinations, it is essential to refer to the initial scan performed in the first days after the procedure and the subsequent ones conducted during the monitoring period.