INTRODUCTION

Since the introduction of the first transluminal balloon therapy in the late 1970s, the field of PCI has exploded. Technological advances have included the widespread application of metallic stents in the mid-1990s and the recent utilization of DES in the 21st century. Adjunctive pharmacological therapy has further allowed the interventional cardiologist to succeed in high-risk coronary intervention. The practice of evidence-based medicine has fuelled the need for randomized controlled trials to access the safety and efficacy of coronary intervention. Numerous devices and drugs have been subjected to intense scrutiny, which has further advanced the field of percutaneous endovascular intervention.

With the success of percutaneous treatment in the coronary tree over the last decade, there has been a growing interest in its application to the peripheral arterial circulation. Despite its all too frequent association with coronary arterial disease, peripheral arterial pathology historically has been under-diagnosed and treated. However, with advances in peripheral device technology and the experience gained in coronary intervention, treatment of peripheral arterial disease is increasingly becoming an integral part of an interventionalist’s practice.

Currently, a wide variety of balloons and stents are being utilized to treat aortic, iliac, femoral, renal, and carotid disease. The development of embolic protection devices has further allowed the advancement and application of these technologies. As a result, complication rates have decreased and have arguably allowed percutaneous therapy to become the preferred revascularization strategy. Randomized clinical trials continue to evolve and its results will ultimately dictate the superiority of a percutaneous rather than surgical approach. In this chapter, we will examine the current applications of percutaneous endovascular peripheral intervention and its potential to treat patients with severe disabling vascular disease.

CAROTID ANGIOPLASTY AND STENTING

Although it appears that the treatment of carotid disease has been a recent advance in peripheral intervention, elective carotid stenting first began over a decade ago. A multidisciplinary group, including Gary S. Roubin MD from the University of Alabama, began treating carotid lesions in 1994. This group was instrumental in introducing this technique to the field of interventional cardiology.

The rationale for a percutaneous vs. a surgical approach is multifactorial. From a technical standpoint, carotid stenting is less invasive and avoids the potential complications of a neck dissection that surgery involves. In addition, it does not require general anesthesia which can lead to various cardiovascular sequelae in high risk individuals. If complications do occur, symptoms are readily apparent because the patient is alert during the procedure. This allows the operator to identify the angiographic source of the patient’s symptoms and provide immediate therapy. Finally, clinical and anatomical features which would typically preclude a surgical intervention may be ideal or even low risk for a percutaneous approach. It is for these reasons that a percutaneous revascularization strategy has gained momentum over the past few years. In this section, the indications, basic technique, and clinical trial data of carotid intervention will be reviewed.

Carotid revascularization, whether it be percutaneous or surgical, is indicated for the prevention of stroke. Carotid disease may lead to a cerebrovascular accident (CVA) through a variety of mechanisms. A stenosis may be a source of thrombo-embolism or if severe can cause ischemic-related neurological sequelae. The term ‘TIA’ or transient ischemic attack is utilized frequently in clinical practice and can be a ‘wastebasket’ term to explain a variety of symptoms. This is because neurological symptoms can be subtle and attributable to other neuro-vascular phenomena. However, a ‘TIA’ is often the reason for a referral to a neurologist and ultimately for an extensive cerebrovascular evaluation. If carotid disease is identified, the decision to intervene can be a difficult one.

Currently, the decision to intervene with carotid disease is based primarily on two important clinical trials, NASCET and ACAS. NASCET (North American Symptomatic Carotid Endarterectomy Trial) was a prospective, multi-center randomized trial which compared carotid endarterectomy (CEA) to best medical therapy.³⁶ In this relatively low risk symptomatic cohort, the two-year outcome for CEA with respect to freedom from ipsilateral stroke or death was 92%. This is in contrast with the medical management arm, who fared much worse with a 72% freedom from the above clinical endpoints. Although there were some shortcomings of this trial, it did provide significant insight on the treatment of carotid disease. The second pivotal trial was ACAS, the Asymptomatic Carotid Atherosclerotic Study.³⁶ Unlike the patient population in NASCET, these individuals were asymptomatic and found to have carotid disease based on duplex imaging. At five years, there was a statistically significant reduction in the incidence of ipsilateral stroke with CEA vs. medical management, 4.7% vs. 9.4% respectively.

The current recommendations for any type of carotid revascularization are primarily based upon the results of these two important trials. Simply stated, patients can be divided into two groups: symptomatic and asymptomatic. In symptomatic patients, CEA is advised for 60% lesions in females and 50% lesions in males. However, this is only if the peri-procedural stroke or death rate is 6% or less. In asymptomatic patients, CEA is recommended for 70% lesions in females and 60% lesions in males. Again, this must be accomplished with a complication rate of 3% or less. Therefore, in order for a percutaneous approach to be widely adapted, its safety and efficacy must be comparable to the above surgical results.

Indications for carotid angioplasty and stenting continue to evolve as more clinical trial data becomes available. Various medical, neurological, and angiographic risk factors for carotid surgical revascularization have been identified based on previous CEA trials. These are listed in Table 28.1.³⁸ Identification of these risk factors is crucial before proceeding with revascularization. In addition, based on early experience with carotid stenting, a number of contraindications have been recognized. These are summarized in Table 28.2.³⁸ With improvements in catheter-based technique and equipment, the above mentioned criteria will continue to evolve. Operator experience should also influence the types of patients considered appropriate for a percutaneous approach.

TABLE 28.1

TABLE 28.2 CONTRAINDICATIONS TO STENTING

Although many of the above mentioned risk factors have been shown to increase both surgical and percutaneous complication rates, there are situations which overwhelmingly favor a percutaneous approach. These may include post-CEA restenosis, discrete stenosis in patients with prior neck radiation or radical dissection, discrete proximal or ostial common carotid lesions, and discrete lesions in the distal internal carotid or involving high bifurcations.⁴⁰ It is in these patients which percutaneous carotid intervention will hopefully find its niche and improve revascularization outcomes.

As with a majority of percutaneous cardiovascular procedures, a thorough non-invasive assessment is often performed. Aside from a detailed history and physical, adjunctive studies include carotid duplex, CT angiography, and magnetic resonance imaging/angiography (MRI/MRA). In patients with a previous history of TIA or CVA, collaboration with a neurologist is helpful for correlation of anatomical and clinical data. Once a decision has been made to pursue invasive testing, an extensive review of the risks and benefits of carotid angiography and/or stenting should be reviewed with the patient.

The technique of carotid angiography and/or stenting may vary somewhat among operators. Although details of various approaches are beyond the scope of this chapter, a basic review is warranted. The procedure can essentially be divided into six parts: (1) angiographic evaluation; (2) carotid sheath placement; (3) wire and embolic protection device (EPD) delivery; (4) pre-dilatation; (5) stent deployment; and (6) post-dilatation. The majority of diagnostic carotid procedures can be performed with one catheter, a 5 French Vitek. The catheter is shaped into a double curve with a tip, which allows for its upward orientation in the aortic arch. This allows for engagement of all brachiocephalic vessels and facilitates the advancement of a 0.038 glide wire for selective cannulation. The common carotid bifurcation is usually located at the level of C3 and C4, although there are numerous anatomical variations. Often a lateral and lateral oblique projection is ideal for separation of the internal and external carotid arteries.

Once the diagnostic study is completed and the location of the lesion has been identified, the Vitek catheter is advanced over the 0.038 glide wire into the ipslateral external carotid artery. A stiff 0.038 Amplatz wire is then exchanged for the glide wire and Vitek catheter is removed. Alternatively, a 0.014 Tad wire can also be utilized for this step. The stiffer wire provides adequate support for the insertion of a 7 French-90 cm sheath, which is placed in the common carotid artery. The dilator and wire are removed and anticoagulation is administered prior to inserting the 0.014 wire/EPD into the internal carotid artery. Similar to coronary intervention, an activated clotting time (ACT) of 200–250 seconds is recommended. At this time, a 0.014 coronary guide wire/filter device is advanced across the area of interest. Various wires and embolic protection are available for carotid intervention. The selection of the appropriate system will depend on the type of lesion as well as the operator’s familiarity with the equipment. The most commonly utilized filter wire at this time is the Accunet device (Cordis). The tip of the wire is usually placed at the base of the skull, and the filter is ideally deployed 2 cm distal to the stenosis.

Pre-dilatation is subsequently performed with a 4.0 mm balloon unless the stenosis is pre-occlusive or the artery is occluded. In these cases, a step-wise pre-dilatation strategy is advised with the initial placement of a 2 mm balloon. Short, repeat inflations are performed with careful monitoring of the heart rate, blood pressure, and patient symptomatology. Once adequate pre-dilation has been accomplished, the balloon is removed and a self-expanding stent is loaded onto the wire. Self-expanding stents are utilized much more frequently than balloon-expandable stents for a number of reasons. One, with balloon-expandable stents, the stent has to be differentially expanded to accommodate to the size of the common carotid artery, bifurcation, and internal carotid artery. Therefore, more than one balloon has to be delivered for optimal dilatation and stent expansion. Secondly, the balloon can rupture while deploying the stent and there may be difficulty in advancing the balloon-stent assembly through the guiding sheath. Finally, balloon-expandable stents tend to occlude the external carotid artery. There have been a few reports of external compression with the balloon expandable stents. For these reasons, self-expanding stents are recommended for carotid intervention in a majority of cases. The final step to successful carotid stenting is post-dilatation. A 5–6 mm balloon is utilized depending upon the size of the internal carotid artery. Once this has been performed, the retrieval sheath of the EPD is advanced over the filter, and the wire and filter are removed as one unit together. Final angiographic images are obtained through the common carotid sheath and the procedure is complete. A carotid angiogram both pre-intervention and post-intervention is demonstrated in Fig. 28.1.

Figure 28.1 A, A discrete internal carotid stenosis. B, Post carotid angioplasty and stenting.

Careful post-procedural monitoring of these patients is vital since they are prone to a number of possible complications. These include puncture-site bleeding issues, transient brady-arrhythmias, hypotension, and neurologic sequelae from thrombotic and athero-embolic material. Early recognition of these potential adverse outcomes of carotid revascularization is crucial. Vasopressor and vagolytic agents are often utilized for post-procedural hemodynamic alterations. These hemodynamic changes are often secondary to the mechanical pressure on the carotid baro-receptors. This effect can result in hypotension up to 24–48 hours after the procedure depending upon the sensitivity of the baro-receptors. Usually there are no long-term clinical ramifications if this is treated in a prudent manner. Rarer complications such as carotid dissection, carotid perforation, and cerebral hemorrhage can obviously be fatal. The technical aspects of neurovascular rescue to treat these scenarios are beyond the scope of this chapter. However, as procedure-dedicated equipment continues to evolve and operator experience improves, it is anticipated that these complications will be infrequently encountered.

As alluded to above, the indications and technical aspects of a percutaneous approach to carotid revascularization have been evolving over the past decade. Just as NASCET and ACAS sought to establish the superiority of surgery over medical therapy for the treatment of carotid disease, percutaneous carotid intervention had to prove its safety and efficacy as well. Initially, the CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study) trial was conducted in Great Britain.⁴¹ This was a prospective, randomized, controlled trial comparing CEA vs. carotid angioplasty in higher risk, symptomatic patients with high-grade carotid stenoses. Approximately two-thirds of the patients in the percutaneous arm were treated with carotid angioplasty without stenting. Despite sub-optimal equipment and operator experience in the percutaneous arm, both early and late outcomes were similar in the two groups. The 30-day incidence of major stroke and death was approximately 5% and the incidence for all strokes (disabling and non-disabling) was 11% in both arms.

The advent of EPD and improved stent design lead to the first randomized, prospective, multi-center trial for comparison of carotid stenting with protection vs. CEA. The SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial was conducted in 2002 and randomized a total of 307 patients.⁴² Eligible patients could be either asymptomatic with >80% stenoses by ultrasound or symptomatic with >50% stenosis and one high-risk factor (see Table 28.3). The primary endpoint was the incidence of MACE, including death, stroke, or MI within 30 days of the procedure. At 30 days, SAPPHIRE reported a composite endpoint of 5.8% and 12.6% for carotid stenting with embolic protection and CEA, respectively. In addition, complication rates were similar among the two groups of patients with respect to TIA and major bleeding. There was a statistically significant difference in cranial nerve injury, 0% in the stenting arm and 5.3% in the CEA arm. One-year results presented in 2003 demonstrated a MACE rate of 11.9% and 19.9% for carotid stenting and CEA respectively. SAPPHIRE was a landmark trial because it was the first randomized study to compare carotid stenting with distal embolic protection with carotid surgery in high-risk patients. Its results prove the hypothesis that among patients with severe carotid artery stenosis and coexisting conditions, carotid stenting is not inferior to carotid endarterectomy.

TABLE 28.3 FDA-APPROVED AND INVESTIGATIONAL ENDOGRAFTS