Endovascular Treatment of Peripheral Vascular Disease

Endovascular Treatment of Peripheral Vascular Disease Suhail Allaqaband, MD, FACC, FCCP, FSCAI, Romas Kirvaitis, MD, Fuad Jan, MD, and Tanvir Bajwa, MD, FACC, FSCAI Abstract: Peripheral arterial disease (PAD) affects about 27 million people in North America and Europe, accounting for up to 413,000 hospitalizations per year with 88,000 hospitalizations involving the lower extremities and 28,000 involving embolectomy or thrombectomy of lower limb arteries. Many patients are asymptomatic and, among symptomatic patients, atypical symptoms are more common than classic claudication. Peripheral arterial disease also correlates strongly with risk of major cardiovascular events, and patients with PAD have a high prevalence of coexistent coronary and cerebrovascular disease. Because the prevalence of PAD increases progressively with age, PAD is a growing clinical problem due to the increasingly aged population in the United States and other developed countries. Until recently, vascular surgical procedures were the only alternative to medical therapy in such patients. Today, endovascular practice, percutaneous transluminal angioplasty with or without stenting, is used far more frequently for all types of lower extremity occlusive lesions, reflecting the continuing advances in imaging techniques, angioplasty equipment, and endovascular expertise. The role of endovascular intervention in the treatment of limb-threatening ischemia is also expanding, and its promise of limb salvage and symptom relief with reduced morbidity and mortality makes percutaneous transluminal angioplasty/stenting an attractive alternative to surThe authors have no conflicts of interest to disclose. Curr Probl Cardiol 2009;34:359-476. 0146-2806/$ – see front matter doi:10.1016/j.cpcardiol.2009.05.001

Curr Probl Cardiol, September 2009

359

gery and, as most endovascular interventions are performed on an outpatient basis, hospital costs are cut considerably. In this monograph we discuss current endovascular intervention for treatment of occlusive PAD, aneurysmal arterial disease, and venous occlusive disease. (Curr Probl Cardiol 2009;34:359-476.) eripheral arterial disease (PAD) is most commonly a manifestation of atherosclerosis, although it can also result from thrombosis, embolism, fibromuscular dysplasia, or vasculitis and accounts for up to 20% of primary care visits, affecting some 8-10 million people in the United States.1 The term peripheral vascular disease (PVD), by contrast, encompasses a group of diseases that affect blood vessels, including not only PAD (lower and upper extremities) but also other atherosclerotic conditions (eg, renal artery disease, carotid disease, as well as venous thrombosis, venous insufficiency, aneurysmal disease, and lymphatic disorders). PAD correlates strongly with risk of major cardiovascular events, and patients with PAD have a high prevalence of coexistent coronary and cerebrovascular disease. In several large epidemiologic series, the prevalence of PAD, based on an abnormal ankle/brachial index (ABI), is reported to be anywhere from 3% in people aged 45-64 years2 to about 18%-27% in people over the age of 60,3,4 and generally higher in men than women and in blacks than non-Hispanic whites. In the same population-based studies, the prevalence of associated clinical cardiovascular disease may be as high as 47%-54%.3,4 Moreover, stroke and myocardial infarction are also seen to occur 3 times as frequently in patients with PAD compared with those without PAD, even among patients with no vascular symptoms.5 Angiographically significant coronary artery disease (CAD) occurs in approximately 60%-80% of patients with PAD.6 Also, patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as patients with a history of coronary or cerebrovascular disease.7,8 Two large international registries, REACH (REduction in Atherothrombosis for Continued Health) and AGATHA (A Global ATHerothrombosis Assessment),9,10 have detected a high coprevalence of CAD and cerebrovascular disease, with 62% of patients in REACH having both PAD and cerebrovascular disease, while 50% of patients with PAD in AGATHA had established CAD, prior stroke, transient ischemic attack, or carotid artery revascu-

P

360

Curr Probl Cardiol, September 2009

FIG 1. Risk of developing lower extremity PAD. The range for each risk factor is estimated from epidemiologic studies. The relative risks consider current smokers vs former smokers and nonsmokers, presence vs absence of diabetes and hypertension, and highest vs lowest quartile of homocysteine and C-reactive protein. The estimate for hypercholesterolemia is based on a 10% risk for each 10 mg/dL rise in total cholesterol. (Adapted from Dormandy JA, et al for the TransAtlantic Inter-Society Consensus (TASC) Working Group. Management of peripheral arterial disease (PAD). J Vasc Surg 2000;31:S1-S288.)

larization. Nevertheless, patients with PAD are often underdiagnosed and undertreated compared to patients with CAD. Thus, establishing a diagnosis of PAD is important, because of both the prognostic and the therapeutic implications. D.R. Holmes: The statistics of peripheral arterial disease are staggering—not only in terms of the frequency of the condition but also in the risk that patients have with this disease. Not only is there a strong relationship between peripheral arterial disease and coronary artery disease but also between peripheral arterial disease and cerebrovascular disease.

Risk Factors and Pathophysiology The major risk factors for PAD are the same as those for CAD and include older age (over 50 years), cigarette smoking, diabetes mellitus, hyperlipidemia, and hypertension. The risk of developing PAD increases progressively with the burden of contributing factors (Fig 1). Cigarette smoking is an exceptionally powerful risk factor for PAD11 and is 2-3 times more likely to cause lower extremity PAD than CAD.11,12 Lower extremity PAD may also be caused by thromboangiitis obliterans or Curr Probl Cardiol, September 2009

361

Buerger’s disease and systemic arteritis such as Takayasu’s arteritis. Current evidence supports the concept that the pathogenesis of PAD involves inflammation, and thus levels of leukocyte adhesion molecules, C-reactive protein, and fibrinogen independently correlate with the development of PAD.13 The American Diabetes Association currently recommends annual screening for PAD in people with diabetes. The screening should document any history of claudication and include palpation of pedal pulses. However, although routine screening for PAD in the general asymptomatic population is not currently supported by major organizations, including the U.S. Preventive Services Task Force, clinicians are expected to be alert to symptoms of PAD in persons at increased risk (over age 50, smokers, diabetics) and patients who have clinical evidence of vascular disease. Our experience suggests it is prudent to screen for CAD in the following groups of patients: a. Age ⬍ 50 years with diabetes, and 1 additional risk factor (eg, smoking, dyslipidemia, hypertension, or hyperhomocysteinemia) b. Age 50-69 years and history of smoking or diabetes c. Age 70 years and older d. Leg symptoms suggestive of claudication or ischemic rest pain e. Abnormal lower extremity pulse examination f. Known atherosclerotic coronary, carotid, or renal artery disease D.R. Holmes: The authors extend the indications for screening for peripheral arterial disease to include several groups of patients. An important group (e) includes patients with “abnormal lower extremity pulse examination.” This is a very important point. Training programs in primary care and cardiovascular medicine need to enhance the curricula devoted to peripheral vasculature.

Clinical Presentation and Classification PAD of the lower extremity is associated with a progressive decline in walking endurance and an increased rate of depression.14,15 Although classically associated with leg pain, features of intermittent claudication (Latin claudicare “to limp”) include pain in 1 or both legs on walking, primarily affecting the calves, that does not go away with continued walking and is relieved by rest. Most patients with PAD describe other leg pain symptoms or have no symptoms at all.16 Patients with upper extremity involvement usually present with pain in the distribution of the affected artery, with cold hands and fingers, numbness, and pallor. The natural history of PAD of the lower extremities is depicted in Fig 2. 362

Curr Probl Cardiol, September 2009

FIG 2. The natural history of atherosclerotic lower extremity peripheral arterial disease (PAD). Individuals with atherosclerotic lower extremity PAD may (a) be asymptomatic (without identified ischemic leg symptoms, albeit with a functional impairment); (b) present with leg symptoms (classic claudication or atypical leg symptoms); or (c) present with critical limb ischemia. All individuals with PAD face a risk of progressive limb ischemic symptoms, as well as a high short-term cardiovascular ischemic event rate and increased mortality. These event rates are most clearly defined for individuals with claudication or critical limb ischemia (CLI), and less well defined for individuals with asymptomatic PAD. CV, cardiovascular; MI, myocardial infarction. (Adapted with permission from Weitz JI, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: A critical review. Circulation 1996;94:3026-49.)

Among those with lower extremity intermittent claudication, 25% experience clinical deterioration, while less than 5%-10% of patients have critical leg ischemia (CLI) defined as ischemic pain in the distal foot, ischemic ulceration, or gangrene.17-21 Classification of PAD considers the severity of symptoms and abnormalities detected on physical examination. This provides a framework for the established guidelines for therapeutic intervention. Although various classifications have been suggested, the Fontaine and Rutherford classifications are widely accepted (Table 1). D.R. Holmes: It is important to remember that patients with peripheral arterial disease may not have symptoms of claudication either because the severity of disease is not as far advanced or for other reasons. Equally important factors may be that either the patients are limited in their exercise tolerance Curr Probl Cardiol, September 2009

363

TABLE 1. Classification of peripheral arterial disease: Fontaine’s stages and Rutherford’s categories Fontaine

Rutherford

Stage

Clinical

Grade

Category

Clinical

I Iia Iib

Asymptomatic Mild claudication Moderate-severe claudication Ischemic rest pain Ulceration or gangrene

0 I I I II III IV

0 1 2 3 4 5 6

Asymptomatic Mild claudication Moderate claudication Severe claudication Ischemic rest pain Minor tissue loss Ulceration or gangrene

III IV

Reproduced with permission from Dormandy JA, Rutherford RB, for the TransAtlantic InterSociety Consensus (TASC) Working Group, Management of peripheral arterial disease (PAD). J Vasc Surg 2000;31:S1-S296. Copyright Elsevier 2000.

by the presence of coronary artery disease or lung disease or the patient may be leading a sedentary lifestyle. This latter circumstance may be particularly true in very elderly patients.

Diagnosis Diagnosis of PAD requires screening that includes the following: obtaining thorough medical history, specifically eliciting leg symptoms, and identifying risk factors, targeting areas of the physical examination to findings specific to the disease, and potential supplemental diagnostic testing. Chronically, decreased blood flow contributes to signs of pallor, dependent rubor, and atrophic skin and nails, and to the development of ischemic ulcers from areas of minor trauma.22 Significant narrowing of the blood vessels at the various anatomic segments may also manifest as absent or reduced pulses or arterial bruits.23 Ancillary physical examination techniques for PAD include capillary refill time, Buerger’s test, and venous filling time. The ABI (ratio of the highest ankle systolic pressure divided by the highest brachial systolic pressure) is the accepted reference standard for the diagnosis of PAD. It is highly sensitive (95%) and specific (100%) when a threshold of ⬍ 0.9 is used to indicate an abnormal result.24,25 Other diagnostic tests include duplex ultrasound, contrast-enhanced magnetic resonance angiography, and contrast computed tomography (CT) angiography. However, the ABI is widely used because it is noninvasive, less expensive, and readily available. Not only does the ABI effectively identify patients with disease and accurately predict future vascular events,26 but the result also correlates with the severity of the 364

Curr Probl Cardiol, September 2009

disease. The risk of death related to CAD increases dramatically as the ABI decreases. The risk of 5-year mortality for a patient with an ABI ⬍ 0.85 is 10% and approaches 50% if the ABI drops to ⬍ 0.40. The bedside ABI serves as the pragmatic reference standard for PAD because it has been validated in clinical epidemiologic research.27 An ABI of 0.71-0.90 indicates the presence of mild PAD; an ABI of 0.41-0.70 indicates moderate PAD, and an ABI of 0.40 or less indicates severe PAD.28,29 Pain at rest or severe occlusive disease typically occurs with an ABI of less than 0.50, while ischemic or gangrenous extremities are associated with an ABI of less than 0.20.30 Heavily calcified arteries, as seen in diabetics and patients with end-stage renal disease, can lead to noncompressibility and ABI values well above normal (ⱖ 1.30). Very high ABI values are associated with increased mortality31 and should prompt further noninvasive testing (ie, duplex ultrasonography or toebrachial index measurement)30 to diagnose PAD. D.R. Holmes: As previously mentioned, in the past, training programs, primary care, internal medicine, and cardiovascular medicine have included scant portions on the curriculum devoted to peripheral arterial disease. In some institutions, this has been exacerbated by the fact that both vascular and general surgeons may provide the long-term care of patients with established peripheral arterial disease. It could be argued that bedside ABI should be a routine part of the physical examination of patients at risk for peripheral arterial disease.

Medical Treatment of Peripheral Artery Disease Treatment of patients with PAD is aimed at relief of exertional symptoms, improved walking capacity and quality-of-life, and, most importantly, prevention or slowing of the progression of systemic atherosclerosis and the related adverse cardiovascular outcomes. The 2005 Consensus Statement from the American College of Cardiology and the American Heart Association (ACC/AHA)6 on the management of patients with PAD recommends that all patients with PAD receive aggressive therapy to prevent subsequent atherosclerotic disease and clinical events. The guidelines for secondary prevention strategy include tobacco cessation, physical activity, dietary modification, weight maintenance, blood pressure control, cholesterol control, antiplatelet therapy, glycemic control, and angiotensin-converting enzyme inhibitor therapy.

Risk Factor Modification and Exercise Rehabilitation Smoking cessation is the most important modifiable risk factor in PAD, and smoking cessation favorably changes the natural history of the Curr Probl Cardiol, September 2009

365

disease. Antiplatelet therapy is recommended for all patients with PAD to prevent associated cardiovascular morbidity and mortality.6 Control of hypertension is an important component of all atherosclerosis risk reduction and thus an integral part of the treatment plan in patients with PAD. The goal hypertension level remains the same as for patients with CAD or diabetes. The recommended low-density lipoprotein cholesterol goal in patients with PAD is less than 100 mg/dL, but when the risk is very high, a low-density lipoprotein cholesterol goal of less than 70 mg/dL is a therapeutic option because of available clinical trial evidence. An HMG-CoA reductase inhibitor is the ideal first-line agent based on several studies showing beneficial effects of statin therapy in patients with PAD.32-35 Current guidelines recommend that patients with PAD and diabetes be treated to achieve a hemoglobin A1C of ⬍ 7%.6 A walking program is an essential component of treatment, with the recommendation that patients walk to the level of near-maximal pain for initial, supervised 30-minute walking sessions 3 times a week for 6 months. In 21 nonrandomized and randomized studies, exercise increased pain-free walking distance in patients with intermittent claudication by 180% and maximal walking distance by 120%.36

Pharmacotherapy Effective pharmacotherapy for symptomatic PAD has not evolved as rapidly as pharmacotherapy to treat CAD and most studies on the use of vasodilator drugs in patients with intermittent claudication have been disappointing. While additional agents (eg, naftidrofuryl) have been used in Europe, South America, and Asia, the only 2 drugs approved for use in the United States by the Food and Drug Administration (FDA) are pentoxifylline and cilostazol. Pentoxifylline has been shown to increase absolute claudication distance by 40-50 m, whereas the reported increase on cilostazol (the preferred agent) is 45-50 m.37,38 The former is usually associated with tachyphylaxis, while use of the latter sometimes results in diarrhea, headache, and palpitations and is contraindicated in patients with left ventricular dysfunction (ejection fraction ⬍ 40%).

D.R. Holmes: Given the overlap in risk factors for peripheral arterial disease, coronary artery disease, and carotid arterial disease, risk stratification and modification are of crucial importance. The role of exercise is of particular note as mentioned in the 21 nonrandomized and randomized studies. Careful follow-up care is essential for optimizing adherence to the therapeutic recommendations.

366

Curr Probl Cardiol, September 2009

Carotid Artery D.R. Holmes: Much literature divides patients into those patients with peripheral arterial disease and those with cerebrovascular disease. These two groups then are often discussed separately. The authors of this current article chose to include these two groups together, although that is not routine. The field of carotid revascularization continues to evolve. Several metaanalyses of carotid endarterectomy vs carotid arterial stenting have been published, some of which reached very different conclusions. As the authors point out, embolic protection devices are essential. The soon to be completed CREST trial should shed important light on the field. Issues remain in terms of patient selection (symptomatic vs asymptomatic), reimbursement, training program standards, and others. Longer term data from EVA-3S53,54 and SPACE55,56 are important. A good rule of thumb is that good stenting is better than bad surgery; good surgery is better than bad stenting, and good surgery and good stenting yield similar results.

Stroke is the third leading cause of death and the number 1 cause of disability in adults living in the United States. Most strokes are ischemic in nature, with carotid artery stenosis being a leading cause. Carotid endarterectomy (CEA) has been the standard of care for stroke prevention for a long time. NASCET (North American Symptomatic Carotid Endarterectomy Trial) randomized symptomatic patients (those with nondisabling stroke or transient ischemic attack within 180 days) with ⱖ 50% stenosis by angiography.39 The ACAS (Asymptomatic Carotid Atherosclerosis Study) Trial randomized asymptomatic patients with ⱖ 60% stenosis by angiography.40 Both NASCET and ACAS demonstrated that CEA plus aspirin (ASA) was superior to medical treatment alone. In 1995 and 1998, ad-hoc committees of the AHA published guidelines for CEA. Surgical risks, ranging from 3% to 6%, were considered acceptable.41 However, there is an important subset of patients with symptomatic or asymptomatic carotid disease: those who are at high risk for both stroke and CEA due to comorbidities or anatomic limitations. In such patients, there is considerable documentation in the literature of complication rates well above the ad-hoc committee’s recommended up to 6% acceptable limit. The following criteria indicate patients considered at high risk for CEA: 1. 2. 3. 4.

CAD requiring urgent coronary artery bypass surgery Stable or unstable angina Congestive heart failure (CHF) Evolving or recent myocardial infarction (⬍ 30 days)

Curr Probl Cardiol, September 2009

367

FIG 3. A 78-year-old woman with multiple comorbidities presenting with a transient ischemic attack. Angiogram shows severe stenosis in the left internal carotid artery (arrow) (A). Filter wire during stenting of left internal carotid artery (arrow) under BEACH study protocol (B). Angiogram after stent implantation (C). CCA, common carotid artery; ECA, external carotid artery; LICA, left internal carotid artery. (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

5. 6. 7. 8. 9. 10.

Previous ipsilateral CEA Contralateral occlusions of the carotid artery Chronic renal failure with creatinine ⱖ 1.5 mg/dL Age ⱖ 80 years Surgically inaccessible lesions Tracheotomy and contralateral laryngeal nerve paralysis

Current medical options offer little hope for these high-risk patients. In the NASCET Trial, medically treated patients with a stenosis ⱖ 70% had a 26% cumulative risk of an ipsilateral stroke within 2 years. In the same trial, medically treated patients with a stenosis of 50%-69% had a 22.2% risk for ipsilateral stroke within 5 years. In the ACAS Trial, asymptomatic patients with ⱖ 60% stenosis who were treated medically had a 5-year aggregate risk for any stroke or death of 11%. In contrast, outcomes for the same high-risk patient population who underwent carotid stenting (Fig 3) have been favorable. Results of the first carotid stenting study, which used independent neurologic assessment, were published by Yadav et al in 1997.42 In 107 patients, most whom met NASCET exclusion criteria for CEA, the success rate was 100%. Thirty-day risk for major stroke and death was only 2.4%. In 2000, Wholey et al published the second global review of carotid stenting. In 4757 patients, 5210 carotid artery stents were placed, with a success rate of 98.4%. The risk of major/minor stroke was again very low, 4.2%. Restenosis rate was 3.5% at 12 months.43 368

Curr Probl Cardiol, September 2009

FIG 4. ANGIOGUARD Rx Emboli Capture Guidewire System; Cordis Corporation, Miami Lakes, FL. (Reproduced with permission.)

Embolic Protection Devices Carotid artery stenting (CAS) without distal protection, compared to CAS with embolic protection devices (EPD), has demonstrated a 3-fold higher risk for stroke and death in a meta-analysis done on the use of EPDs.44 Improved outcomes in clinical trials have been attributed to the use of EPD in CAS.44-46 There are 2 mainlines of evolution in the development of EPDs: distal and proximal protection. In distal protection, the EPD must cross the lesion before being deployed. There are 2 types of distal EPDs: ● Balloon occlusion: PercuSurg (currently GuardWire plus Temporary Occlusion and Aspiration System; Medtronic, Minneapolis, MN) ● Filtration devices X ANGIOGUARD capture guidewire (Cordis Corporation, Miami, FL [Fig 4]) X ACCUNETEmbolic Protection System (Guidant Corp-Boston Scientific, Natick, MA) X Filter Wire EZEmbolic Protection System (Boston Scientific, Natick MA [Fig 5]) X Spider Distal Embolic Protection System (ev3 Inc, Plymouth, MN) X Emboshield Barewire Embolic Protection System (Abbott Vascular, Abbott Park, IL [Fig 6]) An alternative approach to distal EPD involves proximal occlusion (Fig 7) with flow-reversal in the common carotid artery (GORE Flow Reversal Curr Probl Cardiol, September 2009

369

FIG 5. Filter Wire EZ Embolic Protection System for saphenous vein grafts. (Image courtesy of Boston Scientific. ©2009 Boston Scientific Corporation or its affiliates. All rights reserved. Reproduced with permission.)

FIG 6. Emboshield (Image courtesy of Abbott Vascular ©2009 Abbott Laboratories. All rights reserved. Reproduced with permission.)

System; WL Gore & Associates, Flagstaff, AZ [Fig 8]; Parodi antiembolism system; Arteria Medical Science, Inc, San Francisco, CA). In using this EPD, it is not necessary to cross target lesions unprotected. This provides an option for patients with anatomy unsuitable for distal embolic protection (eg, 370

Curr Probl Cardiol, September 2009

tortuous internal carotid or limited landing zone). After proximal common carotid artery occlusion, a protective flow reversal in the stenosed internal carotid artery (ICA) is created. Flow reversal is created to avoid cerebral embolization during angioplasty and stent deployment.47 Current limitations of proximal EPDs include inability to cross the lesion for anatomic reasons, tortuosity of the ICA, inadequate landing-zone distal to the lesion, and failure of the filter to successfully trap all the emboli. Furthermore, during the initial crossing of the lesion, either by balloon or by filter, the brain is not protected from emboli.48 More recent EPDs, like the Emboshield, allow for the lesion to be crossed with a bare wire, after which the filter is loaded on the wire. This allows for better crossing of tight and tortuous lesions and more successful deployment of the EPD in most patients. Distal balloons have inherent problems. They do not afford complete occlusion of the ICA, and they fail to aspirate all the emboli, due to the phenomenon of suction shadow.48 Filter wires have an advantage in preserving flow during the procedure, but embolization may still occur, due to the pore size of the filter, due to failure to appose the vessel lumen completely, and during the retrieval phase.48 Problems associated with filter retrieval, passage of the aspiration catheter, and dissection/spasm of the distal ICA have also been reported.48,49 Use of proximal occlusion devices is contraindicated in patients with total occlusion of the target vessel, arterial anatomy with vessel tortuosity or disease involvement that does not allow correct and safe positioning of the components, severe intracranial stenosis distal to the target lesion, severe contralateral carotid artery disease preventing adequate cerebral blood circulation, or any intolerance to flow reversal. Furthermore, proximal EPDs, due to their large caliber, have the potential to cause dissection or spasm in the external carotid artery or the common carotid artery and require larger puncture sites. There is also the possibility of interrupting flow during protection.

Carotid Artery Stenting vs Carotid Endarterectomy Three recent large, multicenter, randomized trials comparing CAS to CEA attempted to clarify the efficacy of CAS in a broad range of carotid lesions in patients with varying degrees of symptoms, stenoses, and risk factors.50-56 A summary of key differences between the 3 studies, which likely impacted the overall results of these trials, is seen in Table 2. The SAPPHiRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) study was designed to test the hypothesis that CAS with an EPD is not inferior to CEA.50 Only patients who were suitable candidates for both CAS, as assessed by an intervenCurr Probl Cardiol, September 2009

371

372

Curr Probl Cardiol, September 2009

tionalist, and CEA, as evaluated by a surgeon, were randomized into the study. A total of 747 patients were originally enrolled in the study. Based on the eligibility criteria, 334 patients with either a symptomatic carotid artery stenosis of at least 50% or an asymptomatic stenosis of at least 80% (as assessed by Doppler ultrasound) were randomized to treatment with CAS or CEA. These patients had coexisting conditions that potentially increased the risk posed by CEA, and 29% of the randomized population had symptomatic stenoses. Patients were excluded if they were deemed to be at low risk for CEA. The primary endpoint (a cumulative incidence of major cardiovascular events at 1 year—a composite of death, stroke, or myocardial infarction within 30 days after the intervention or death or ipsilateral stroke between 31 days and 1 year) occurred in 20 (12.2%) patients undergoing CAS with EPD and 32 (20.1%) patients assigned to CEA (P ⫽ 0.004 for noninferiority, and P ⫽ 0.053 for superiority). At 1 year, repeat carotid revascularization was required in fewer patients who underwent CAS (0.6%) than CEA (4.3%; P ⫽ 0.04). In the long-term follow-up of the SAPPHiRE study, at 3 years, the prespecified major secondary endpoint occurred in 41 (24.6%) patients with CAS and 45 (26.9%) patients with CEA.51 There were 11 ipsilateral cerebrovascular accidents (CVAs) in the CAS group and 9 in the CEA group (P ⫽ NS). A total of 413 patients were ineligible for randomization: 406 patients from the nonrandomized group were entered into the stent registry and the remaining 7 patients were entered into the surgical registry. The fact that there were more patients turned down for CEA than for CAS during the study introduces a selection bias in the randomized population that would favor the CEA arm of the study.52 Despite this “selection bias,” no significant difference was reported in 3-year outcome between CAS and CEA. Requirements for inclusion of an interventionalist in the SAPPHiRE study were the completion of a median of 64 CAS procedures and a documented periprocedural stroke or death rate of ⬍ 6% before inclusion of the study. Only 2 types of stents could be used, along with a single mandatory EPD system. The EPD system was successfully deployed in 96% of the patients. Dual antiplatelet therapy was mandated for 24 hours

FIG 7. Sixty-year-old female with history of coronary artery disease was noted to have a carotid bruit (A). Shows a high-grade stenotic lesion in the LICA. Following this, the patient was enrolled in the EMPIRE study. (B) illustrates proximal GORE neuroprotection device in place. The upper arrowhead shows balloon in the ECA and the lower arrowhead indicates balloon in the LCCA. Successful endovascular stent placement and excellent flow is shown in (C). CCA, common carotid artery; LICA, left internal carotid artery; LECA, left external carotid artery. Curr Probl Cardiol, September 2009

373

FIG 8. GORE Flow Reversal System. CCA, common carotid artery; ECA, external carotid artery; ICA, internal carotid artery. (©2008 WL Gore and Associates, Inc. Reproduced with permission.)

before CAS and continued for 2-4 weeks after the procedure. Heparin was adjusted during the procedure to maintain a target activated partial thromboplastin time (aPTT) of 250-300 seconds. The EVA-3S (Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid stenosis) trial was a multicenter, randomized, noninferiority trial comparing CAS with CEA in patients with symptomatic carotid stenosis of at least 60%, as assessed by angiography according to NASCET criteria, or, if unavailable, by both Doppler ultrasound and magnetic resonance angiography.53 Exclusion criteria included unstable angina and restenosis after CEA, both of which would have likely benefited from CAS rather than CEA and which are present in a significant proportion of patients presenting in clinical practice with symptomatic or asymptomatic stenosis.52 The primary endpoint was incidence of any stroke or death within 30 days post treatment. The trial was stopped prematurely, after the inclusion of 527 patients, for reasons of both safety and 374

Curr Probl Cardiol, September 2009

futility.54 The 30-day incidence of any stroke or death was 3.9% after CEA and 9.6% after CAS, with a 2.5% relative risk of any stroke or death after CAS vs CEA. The 30-day incidence of disabling stroke or death was 1.5% with CEA and 3.4% after CAS, a 2.2% relative risk. At 6 months, the incidence of any stroke or death was 6.1% after CEA and 11.7% after CAS (P ⫽ 0.02). There was a trend toward more major local complications after CAS and more systemic complications (mainly pulmonary) after CEA (P ⫽ NS). Cranial nerve injury was more common after CEA than after CAS. In order for an interventionalist to participate in the EVA-3S study preenrollment requirements consisted of having performed ⱖ 12 CAS procedures without any specificity regarding periprocedural stroke or death rate associated with those cases. A second means of inclusion was possible if the interventionalist had performed ⱖ 35 supra-aortic trunk stents (no specific categories were specified except for including ⱖ 5 CAS). A third means of inclusion if the above 2 qualifications had failed to be met was for the interventionalist to enroll patients under the supervision of an experienced tutor. Under the EVA-3S trial, 39% of the CAS procedures performed were conducted by operators still in training. Investigators could choose between 5 different stents, and it was left to the discretion of the investigator as to which of the 7 different types of EPD systems would be used in the procedure. The EPD system was attempted in 92% of patients. Dual antiplatelet therapy was not mandated in the study. Eighty-three percent of patients were on dual antiplatelet therapy of varying duration before the procedure, and 85% received dual antiplatelet therapy of varying duration after the procedure. Heparin was used in 97.6% of cases, with requirements targeting specific activated clotting time or aPTT levels. The SPACE (Stent-Protected Angioplasty vs Carotid Endarterectomy) trial was a multinational, prospective, randomized study that enrolled 1200 patients with symptomatic carotid artery stenosis of at least 70% on duplex ultrasound (corresponding to ⱖ 50% NASCET stenosis level). Patients were randomized within 180 days to CAS or CEA. The primary endpoint was ipsilateral ischemic stroke or death from time of randomization to 30 days after the procedure. Exclusion criteria included patients with restenosis after CEA who would be more likely to benefit from CAS rather than CEA.55 Results on 1083 patients were included in the analysis. The rate of death or ipsilateral ischemic stroke was 6.84% for CAS and 6.34% for CEA (1-sided P ⫽ 0.09). SPACE failed to prove noninferiority of CAS compared with CEA for the periprocedural complication rate at 30 days. Under the study, the 2-year endpoints included several clinical endpoints and an incidence of recurrent carotid stenosis of at least 70%. Findings demonstrated no significant difference in incidence of ipsilateral Curr Probl Cardiol, September 2009

375

TABLE 2. Multicenter randomized trials of CAS vs CEA EVA-3S53,54 Number patients Symptomatic patients Exclusion criteria Operator experience for CAS

527 100% Unstable angina, restenosis after previous CEA 12 CAS or 35 supra-aortic stents with 5 CAS or supervision

Operator experience for CEA

ⱖ 25 CEAs in year before enrollment

Embolic protection devices

92% attempted, operator’s choice of 7 different EPDs

Antiplatelet

Not mandatory, no specified duration or preprocedure requirements 4y 11.1% CAS vs 6.2% CEA (P ⫽ 0.03)

Follow-up MAE

CAS, carotid artery stenting; CEA, carotid endarterectomy; MAE, major adverse events of death, stroke, or myocardial infarction.

ischemic stroke and no periprocedural stroke or death events up to 2 years post procedure between the CAS and CEA groups.56 Recurrent stenosis, as assessed by duplex ultrasound of 70% or more, was significantly more frequent in the CAS group compared with the CEA group. Despite the higher restenosis rate in the CAS group, only 2 instances of recurrent stenosis after CAS actually led to clinical neurological symptoms. There was a primary procedure failure rate of 3.2% in the CAS group. In order for an interventionalist to participate in the SPACE study preenrollment requirements consisted of having performed ⱖ 25 percutaneous transluminal coronary angioplasties (PTCAs) or stents without any requirement regarding carotid artery interventions or any maximum periprocedural stroke or death rate associated with those cases. Furthermore, prior experience with EPD was not specified. Three different types of stents could be used with the specific choice being left to the operator. In addition, it was also at the discretion of the operator as to which of the 5 different types of EPD systems could be used in the procedure. The EPD system was used in only 27% of the patients. Dual antiplatelet therapy was mandated for 3 days before CAS and continued for 30 days after the procedure. Heparin use was not defined by the study protocol and no requirements were made regarding target activated clotting time or aPTT levels when heparin was used. These 3 randomized studies reached different conclusions as to the efficacy of CAS compared to CEA in carotid lesions. Operator experience has been shown to significantly affect the outcome of carotid interventional procedures, especially when EPDs are used, and the evidence is 376

Curr Probl Cardiol, September 2009

TABLE 2. Continued SPACE55,56 1183 100% Restenosis after previous CEA 25 PTA or stent (location NOT specified) 25 consecutive CEAs with morbidity and mortality rates 27% attempted, operator’s choice of 5 different EPDs Mandatory 3 d preprocedure and 30 d after CAS 2y 9.5% CAS vs 8.8% CEA (P ⫽ 0.62)

SapphiRE50,51 334 29.9% Low risk for CEA Median 64 CAS with ⬍ 6% rate of periprocedural stroke or death Median 30 CEAs per year with stroke or death rate ⬍ 6% Mandatory, Angiogard (Cordis) Mandatory, 24 h before, 2-4 wks post procedure 3y 12.2% CAS vs 20.1% CEA (P ⫽ 0.004)

clear that a learning curve variable affects complication rates as well.44 SAPPHiRE had the most stringent enrollment criteria for study operators, requiring the most experience with CAS, along with EPDs. Enrollment criteria for the SPACE trial are somewhat ambiguous. The EVA-3S study allowed inexperienced interventionalists to contribute to the study outcome while being proctored for the procedure. There is evidence that embolization occurs with all CAS procedures. Thus, EPDs are considered by many an integral part of the standard of care in CAS.57 The addition of EPD to CAS requires more advanced technical skill and additional experience on the part of the interventionalist (ie, skillful manipulation of the EPD to ensure precise placement and maximum effectiveness with the least damage). In the hands of an inexperienced operator, lack of skill can negate any beneficial effect from the EPD and can affect outcome.52 This, in part, may explain the similar results found in patients treated with EPD vs those without, as seen in the EVA-3S study. Lower operator experience levels may also account for the higher failure-to-stent rates seen in EVA-3S and SPACE. In contrast to the lenient qualifying parameters for the interventionalist, surgeons involved in all 3 studies were required to meet stringent, uniform criteria. This may explain why the CEA complication rate in the EVA-3S study was lower than expected. This lower complication rate in the CEA group probably weighted the statistically significant difference found between the CAS and CEA groups. In contrast with the SAPPHiRE study, the SPACE and EVA-3S studies had no uniform criteria in regards to the number and types of stents and EPDs available to the operator. Case Curr Probl Cardiol, September 2009

377

TABLE 3. Nonrandomized trials of CAS in high-risk patients Study

No. of pts.

Symptoms

Follow-up

Primary endpoint

Results

BEACH CaRESS59,62

480 397

23.3% 32%

3y 1y

8.9% CAS No difference

PROCAR63 Capture64,65 Create66 CasesPMS67 EMPiREa

77 3500 419 1493

40% 14% 17.4% 21.8%

6 mo 30 d 30 d 30 d

MAE Composite death or stroke MANE MAE MACCE MAE

32%

30 d

MAE

60,61

245

6.5% MANE 6.3% 6.2% 5.0% 3.7%

CAS, carotid artery stenting; MAE, major adverse events (death, MI, or stroke); MACCE, major adverse cardiac and cerebrovascular events; MANE, major adverse neurological events. a Hopkins LN Empire Study results. presentation—20th Annual Transcatheter Cardiovascular Therapeutics (2008) Scientific Symposium.

reports detail technical problems that can occur when combining various stents with various EPDs which, depending on the carotid lesion involved, may result in an incompatibility between said devices.58 Finally, the combination of dual antiplatelet therapy with periprocedural anticoagulation has been shown to be crucial in maintaining patency and good outcome during endovascular procedures and has become the generally accepted standard of care for CAS.59 The lack of a strict antiplatelet and anticoagulation regimen in EVA-3S and SPACE likely favored the CEA groups, as patients who underwent CAS may not have been optimally treated during and after their procedures in these studies.

Nonrandomized Trials of Carotid Artery Stenting Seven recent registries on high-risk patients have demonstrated favorable outcomes for CAS with EPDs.59-67 These studies differed in the percentage of patients who were symptomatic, with the Prospective Multicenter Trial to Evaluate the Safety and Performance of the ev3 Protége™ Stent in the Treatment of Carotid Artery Stenosis (PROCAR), carotid revascularization using endarterectomy or stenting systems (CaRESS), and EMPiRE registries having the highest number of patients present with symptoms. Comparison to a CEA group was made in Boston Scientific EPI: A Carotid Stenting Trial for High-Risk Surgical Patients (BEACH), CaRESS, Escorts Multiple ProNova Implantation Registry (EMPiRE), and carotid artery stenting with emboli protection surveillance study (CASES-PMS), but only the CaRESS trial actively randomized patients to a surgical arm as opposed to comparing CAS patients to objective performance criteria (OPC) (Table 3). Consistent results with CAS were obtained in all of these registries, with acceptable event rates achieved. 378

Curr Probl Cardiol, September 2009

FIG 9. A 65-year-old man with history of severe dizziness spells. (A) Angiogram shows a severe ostial lesion in the right vertebral artery (arrow). (B) Vertebral and subclavian arteries after percutaneous intervention and stent implantation. Sub Cl, subclavian artery. (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

Vertebrobasilar Artery D.R. Holmes: The inclusion of a vascular neurologist on the team taking care of patients with cerebrovascular disease is of utmost importance. While vertebral stenoses can be identified, establishing the link between the stenosis and the symptoms is crucial. Unfortunately, the authors do not comment on the use of drug-eluting stents for vertebral disease or the need for embolic protection devices.

Patients who have vertebral artery occlusive disease usually present with vertigo, loss of balance, and gait problems. There is a high risk of stroke if this is untreated, and surgical options are risky with associated high morbidity. Berguer et al treated 290 patients surgically with no deaths but a high rate of complications [ie, development of either Horner’s syndrome (15%), recurrent laryngeal nerve palsy (2%), lymphocele (4%), or immediate thrombosis (1%)].68 In these patients, balloon angioplasty with stenting is an outpatient procedure that can be performed with a very high rate of success and low risk of complications. Jenkin et al reported a procedural success rate of 100% and no death or stroke.69 Malek et al reported a success rate ⬎ 95% and no major adverse cardiovascular event.70 In our practice, we recommend balloon angioplasty with stenting as the treatment of choice for patients who have symptomatic vertebrobasilar artery disease (Fig 9). Curr Probl Cardiol, September 2009

379

FIG 10. A 70-year-old woman with dizziness and left arm claudication had Doppler ultrasound that showed reversed flow in the vertebral artery. Angiogram shows severe left subclavian artery stenosis (white arrow) with no antegrade flow in vertebral artery (A). After stent implantation in the subclavian artery there is antegrade flow in the vertebral artery (black arrow) (B). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

Subclavian Artery Although occlusive disease of the subclavian artery is most often asymptomatic, when it is symptomatic, patients may present with subclavian-steal syndrome, with upper extremity claudication, or, in patients who have an internal mammary artery bypass graft, as subclavian-coronary-steal syndrome. Surgical treatment of subclavian artery stenosis is effective but, among other complications, carries a mortality rate of about 2% and a stroke rate of about 3%.71 Although initial reports on use of percutaneous transluminal angioplasty (PTA) alone showed mixed results with high restenosis rates, recent reports on subclavian artery stenting indicate high rates of procedural success (92%-100%) with good long-term patency rates (90%-100%).72-74 The largest databank to date is a multicenter registry evaluating the results of subclavian artery stenting in 258 patients.75 Overall, the rate of procedural success was 98.5% with a major complication rate of 1%. At a mean follow-up of 19 ⫾ 15 months, the primary patency rate was 89% and the secondary patency rate was 98.5%. These results suggest that subclavian artery stenting should be considered the primary treatment in patients who need revascularization for subclavian artery stenosis (Fig 10). D.R. Holmes: An important clinical scenario is the patient with an occluded left anterior descending, a patent left internal mammary artery graft to the LAD, but a significant proximal stenosis of the subclavian artery, which 380

Curr Probl Cardiol, September 2009

results in anterior ischemia. This can be treated by stenting the subclavian artery, although care must be taken to avoid the vertebral artery. One wishes that the authors would have discussed stent designs in this segment.

Renal Arteries Renal artery stenosis (RAS) is the most common cause of secondary hypertension. Atherosclerosis accounts for 90% of cases of RAS, whereas fibromuscular dysplasia (FMD) results in RAS in about 10% of cases. The incidence of atherosclerotic RAS increases with age and is more common in patients who have occlusive disease in other vascular territories. The incidence of RAS is about 0.1% in the general population but increases to 4.0% in patients with hypertension. In patients with combined CAD and hypertension, the rates can be as high as 10%-20%.76,77 At our institution, in 196 random patients who presented with diabetes and hypertension and underwent coronary angiography, renal angiography revealed 18% had RAS ⬎ 50%.76 Multivariate analysis shows RAS is predicted by female gender, systolic hypertension, reduced creatinine clearance, and atherosclerotic disease in the carotid or peripheral beds.78 Atherosclerotic RAS is progressive and, in a significant number of these patients, results in renal atrophy.79,80 Once RAS becomes ⬎ 60%, there is a progressive increase in stenosis at a rate of 5%-10% per year. Before percutaneous revascularization procedures became widely available, aortorenal bypass surgery was commonly performed to treat patients with RAS, but rates of perioperative mortality were 2%-6% with significant associated morbidity.81 Andreas Gruntzig first reported percutaneous revascularization of the renal arteries in 1978. Since then, the procedure has been refined and simplified until it has virtually replaced open surgical revascularization in patients with RAS (Fig 11).

D.R. Holmes: Although the authors have asserted that percutaneous revascularization has “virtually replaced open surgical revascularization,” there is indeed significant variability in opinion from center to center. The role of stenting vs medical therapy remains controversial. A major problem is inability to routinely use embolic protection devices and the fact that actual worsening renal function may result from renal stenting.

Predicting an individual patient’s blood pressure response to PTA/ stenting for RAS remains difficult.82 RAS should be suspected in hypertensive patients who have any of the following: Curr Probl Cardiol, September 2009

381

FIG 11. A 70-year-old Caucasian male with history of coronary heart disease and diabetes referred for severe uncontrolled hypertension. Renal angiogram demonstrates severe atherosclerotic disease in the left renal artery (A) with excellent technical success post stenting (B). Moderate reduction in blood pressure occurred, which has persisted 6 months post procedure.

● Onset of hypertension before age 30 or after age 55 (especially with no family history of hypertension) ● Blood pressure that is difficult to control despite multiple medications or is initially easy to control but becomes uncontrolled despite medications ● Sudden worsening of blood pressure control ● Recurrent pulmonary edema despite a normal left ventricular systolic function ● Sudden worsening of renal function with the introduction of angiotensin-converting enzyme inhibitors ● Renal failure of unknown etiology, especially in the absence of proteinuria or abnormal urinary sediment There is an association between renovascular disease and increased risk for future cardiovascular morbidity and coronary events, the combined risk significantly exceeding the risk for these conditions on their own as they occur in the general population. RAS is associated with female gender, systolic hypertension, reduced creatinine clearance, and peripheral arterial disease, especially disease of the carotids.78 Medical treatment with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) produces transient improvement in blood pressure control, which correlates with the underlying pathophysiological effect that RAS has on the kidney and the hypertension cascade. There is initial dependency on the renin-angiotensin system, which recruits and eventually shifts dependence toward the oxidative pathways. Renovascular hypertension in these patients corre382

Curr Probl Cardiol, September 2009

lates best with markers of oxidative stress.83 The oxidative stress pathway will normalize with successful revascularization.82,84 Early studies on revascularization in RAS failed to demonstrate a major benefit from angioplasty over the short term, but these studies had crossover rates from the medical therapy groups to revascularization as high as 44%, thereby underestimating the benefit of intervention on blood pressure levels in these patients.82,85 Intractable hypertension, despite aggressive medical management, has been viewed as a screening test for patients who may benefit from revascularization for RAS and warrants further diagnostic workup.82,85 The subset of patients with renovascular hypertension who would benefit from percutaneous intervention is difficult to identify. Multiple attempts at finding laboratory predictors of patients who are clinically responsive to PTA/stenting for RAS have been unsuccessful. Elevated brain natriuretic peptide was associated with clinical improvement of hypertension following PTA/stent for RAS, but the study population for this trial was nonrandomized and conducted in a small (27 patients), carefully selected patient population.86 Additional attempts have been made to better identify patients who are likely to have an improvement in blood pressure levels in response to PTA/stenting for RAS through the identification of an abnormal renal fractional flow reserve (FFR).87 One nonrandomized study prospectively enrolled 17 patients with unilateral RAS and medically refractory hypertension (BP ⬎ 140/90 mm Hg). Renal FFR was measured at maximal hyperemia induced by papaverine followed by renal stent placement. Blood pressure improvement was defined as BP ⬍ 140/90 mm Hg or an absolute decrease in diastolic blood pressure of 15 mm Hg on the same number of or on fewer medications. The average follow-up was 10 ⫾ 2 months. In patients with an abnormal renal FFR (⬍ 0.80) blood pressure improved at 90 days in 86% of patients compared with 30% in the normal renal FFR group (P ⫽ 0.04). Translesional pressure gradients alone (resting, peak, or hyperemic) failed to differentiate blood pressure responders from nonresponders. Although this study serves as a pilot study, caution is advised in applying these findings to clinical guidelines until larger, multicenter, prospectively randomized trials are conducted. When RAS is caused by FMD, results of PTA alone are excellent, with a success rate of 82%-100%, and a restenosis rate of about 10%, making PTA the treatment of choice in patients who have uncontrolled hypertension and fibromuscular dysplasia88 (Fig 12). By contrast, stand-alone PTA for atherosclerotic RAS has yielded poor results, due to high elastic recoil in the atherosclerotic ostial lesions. As is true when used in most other arteries, stents improve both immediate Curr Probl Cardiol, September 2009

383

FIG 12. A 40-year-old man with severe uncontrolled hypertension and abdominal bruits. Angiogram shows typical appearance of fibromuscular dysplasia (arrows) in right (A) and left (B) renal arteries. Angiogram after balloon angioplasty in both renal arteries (C, D). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

and long-term patency following PTA. Although not yet substantiated by reports from large randomized studies, many other reports89-95 show renal artery stenting to be highly effective, with rates for immediate technical success of 97%-100%, rates for procedure-related major complications of about 2%-3%, and rates for restenosis of 5%-21% (Table 4). Variations in reporting standards make it hard to judge the efficacy of renal artery stenting for patients who have hypertension and impaired renal function. Different parameters for ideal blood pressure level are used along with varying definitions of “cure” from renovascular hypertension, thereby making cross comparisons between studies not only difficult but also unreliable. The prospective differences between medically treated and PTA/stented patients in randomized control trials were 384

Curr Probl Cardiol, September 2009

far smaller than those witnessed in observational studies (⫺7/⫺3 mm Hg to ⫺22/⫺7 mm Hg, respectively).82 RAS appears to improve control of blood pressure in about 20%-57% of patients with a major adverse event (MAE) ranging from 8% to 11%, with associated restenosis rates of 14%-18%.82,86 However, the procedure “cures” hypertension in about 18% of the patients who have atherosclerotic RAS compared with ⬎ 60% of patients who have FMD. In approximately 26%-50% of patients with atherosclerotic RAS, renal artery stenting improves or stabilizes renal function only when EPDs are also used.82 The question arises as to whether blood pressure alone is an adequate marker of clinical events in patients with renovascular disease, even though it is considered a surrogate endpoint for essential hypertension.82 There is evidence that renal artery stenting is more effective if performed in the early stages of RAS [ie, before renal impairment becomes either severe (serum creatinine levels ⬎ 4.0 mg/dL) or permanent]. In addition, patients with renovascular disease can have multiple etiologies for their deterioration in renal function including the following: diabetes, hypertension, small vessel injury to the kidneys, atheroembolic disease, nephrosclerosis, and preexisting hypertension.82 Ignoring the possibility that the rate of progression of renal deterioration results from other coexistant etiologies is an inherent problem of all studies evaluating PTA/stenting in RAS; as a result, PTA/stenting in a large renal artery may resolve only a small component of the complex pathophysiological mechanism contributing to the decline in renal function. Dorros and coworkers published data from the multicenter PALMAZ stent renal artery stenosis revascularization registry96 on 1058 patients (1443 atherosclerotic renal arteries) in whom PALMAZ-SCHATZ Crown stent (Cordis Endovascular, Miami, FL) revascularization was successfully performed to improve poorly controlled hypertension, to preserve renal function, or to improve congestive heart failure. At 4-year follow-up, there were significant decreases in both systolic blood pressure (from 168 mm Hg to 147 mm Hg) and diastolic blood pressure (from 84 mm Hg to 78 mm Hg) as well as in serum creatinine levels (from 1.7 mg/dL to 1.3 mg/dL). In addition, renal function was improved or stabilized in 70% of patients who had unilateral RAS and in 92% of those who had bilateral RAS. The safety and effectiveness of the PALMAZ balloon expandable stent In the REnal artery after failed angioplasty (ASPIRE-2) study was a nonrandomized study that enrolled 208 patients with de novo or restenotic (ⱖ 70%) aorto-ostial RAS.97 Unsuccessful percutaneous transluminal renal angioplasty (PTRA) was defined as a ⱖ 50% residual stenosis, Curr Probl Cardiol, September 2009

385

TABLE 4. Renal artery stenting—Results in recent studies Study

No. of pts.

Arteries (N)

Follow-up (mo)

Technical success rate (%)

Lederman et al.89 Burket et al.90 Rodriguez-Lopez et al.91 Rocha-Singh et al.92 Dorros et al.93 White et al.94 Allaqaband et al.95 Pooled results

300 127 108 150 163 100 100 1048

363 171 125 180 202 133 119 1293

16 15 ⫾ 14 36 13.1 48 8.7 ⫾ 5 20 ⫾ 22 22.8

100 100 97.6 97.3 99 99 100 98.9

persistent translesional pressure gradient, or a flow-limiting dissection. The primary endpoint was the 9-month restenosis rate as quantified on angiography or duplex ultrasonography and adjudicated by core laboratory analysis. Secondary endpoints included renal function, blood pressure, and cumulative incidence of MAE and target lesion revascularization at 24 months. The stent procedure was immediately successful in 80.2% of the lesions treated. The 9-month restenosis rate was 17.4%. Systolic/diastolic blood pressure decreased from 168 ⫾ 25/82 ⫾ 13 mm Hg at baseline to 149 ⫾ 24/77 ⫾ 12 mm Hg at 9 months (P ⬍ 0.001 vs baseline), and 149 ⫾ 25/77 ⫾ 12 mm Hg at 24 months (P ⬍ 0.001 vs baseline). Mean serum creatinine concentration was unchanged from baseline values at 9 and 24 months. The 24-month cumulative rate of MAE was 19.7%. A greater final minimal luminal diameter was associated with reduced restenosis and confirmed the need for stent deployment other than PTA alone, in which minimal luminal diameter is limited due to elastic recoil. Only 47% of the ASPIRE-2 cohort experienced a significant decrease in blood pressure. One major criticism of the study was that an independent core laboratory evaluation of what was determined by the interventionalists to be ⱖ 70% stenosis was actually 61.5% and the post PTRA stenosis believed to be ⱖ 50% was actually only 35%. This implies that interventions were performed on potentially physiologically insignificant lesions rather than severe RAS lesions. Many patients actually had essential hypertension as the etiology of elevated blood pressure as opposed to renovascular hypertension, which explains the finding of inconsistent blood pressure response to PTA/stenting. This further highlights the importance of patient selection in PTA/stenting for RAS, especially in the context of a 20% MAE at 2-year follow-up. While there is evidence showing that revascularization improves renal arterial patency, there is much controversy as to whether there is enough substantial and reproducible evidence to suggest that this translates into a 386

Curr Probl Cardiol, September 2009

TABLE 4. Continued Hypertension cured or improved (%)

Renal function improved or stabilized (%)

Restenosis (%)

Major complications (%)

70 71 79 91 49 76 85 74.4

73 67 100 92 71 22 NR 70.8

21 7.8 5.5 12 NR 18.8 NR 13.2

2 3 3.2 1.3 1.8 2 4 2.47

benefit in renal function.98 The Angioplasty and STent for Renal Artery Lesions (ASTRAL) trial comparing renal function in atherosclerotic renovascular disease patients (serum creatinine, approximately 2 mg/dL) with significant stenosis (mean stenosis, 75%), randomized to either revascularization (PTA and/or stenting) with medical therapy (n ⫽ 403) or medical management alone (n ⫽ 403), was designed to provide this evidence.98 In the study, 4.4% of the medical group crossed over to the intervention group. The primary endpoint was an improvement in renal function. No distal EPDs were used in the study. Serum creatinine increased in both groups in the first 6 months, then remained relatively steady (0.2 mg/dL in both groups), and systolic blood pressure showed a decrease of 5 mm Hg. Patients on medical management showed a smaller decrease in diastolic blood pressure (⫺1 mm Hg) compared with revascularized patients (⫺3 mm Hg), but that difference was not significant. Furthermore, there was no significant difference in overall vascular events during follow-up or time to first renal event. At 1-year follow-up, there were no statistically significant differences in the rates of myocardial infarction, cerebrovascular events, or hospitalization (due to angina, heart failure, the need for percutaneous coronary intervention, or bypass surgery) between the intervention and medical therapy groups (66% vs 59%, P ⫽ 0.3). Risk-adjusted mortality was also the same in the 2 treatment arms (P ⫽ 0.6). Procedural complications occurred in 3% of the patients in the intervention group, including perforation or dissection of the renal artery along with incorrectly positioned stents. To date, ASTRAL is by far the largest randomized trial in atherosclerotic renovascular disease and the trial will continue until all 403 patients in each group have completed 4-year follow-up. The pRospective, multicENter, single-arm study evaluating the ExpreSS SD (RenAl Premounted Stent System; Boston Scientific Corporation) in the treatment of atherosClerotic lEsions in the aortorenal ostium Curr Probl Cardiol, September 2009

387

compared to PTRA (RENAISSANCE Trial) enrolled 100 patients with de novo or restenotic ostial atherosclerotic lesions ⱕ 15 mm long in vessels ⱖ 4.0 and ⱕ 7.0 mm diameter with a stenosis diameter ⱖ 70%.99 The primary endpoint, 9-month binary restenosis, was compared to OPC of 40% for PTRA. Follow-up was conducted over 3 years, with technical and procedural success achieved in 99% of the patients. There was a binary restenosis rate of 21.3% at 9 months, which was superior to OPC (P ⬍ 0.0001). There was an 87% concordance between angiography and ultrasonography in detection of binary restenosis at 9 months. There was significant improvement in peak systolic velocity and renal-to-aortic ratios at 9 months and 2 years, compared to baseline. MAE was 10.5% at 9 months and 20.9% at 3 years. The current consensus is to perform renal artery revascularization in patients who have RAS to preserve renal function or to improve control of hypertension. Available data support no clearcut recommendation as to the optimal timing of this intervention, and further study is needed. There is no doubt that PTA should be the procedure of choice in patients who have RAS due to FMD. However, in patients who have atherosclerotic RAS, a National Instututes of Health review panel concluded that the benefits of PTA/stenting are sufficiently ambiguous to warrant a prospective randomized trial designed to determine whether renal ischemia contributes to adverse cardiovascular and renal events, independent of the blood pressure level achieved. The cardiovascular Outcomes in Renal Atherosclerotic Lesions study is a long-term, randomized clinical trial comparing optimum medical therapy alone to stenting with optimum medical therapy using a composite cardiovascular and renal endpoint: cardiovascular or renal death, myocardial infarction, hospitalization for CHF, stroke, doubling of serum creatinine, and need for renal replacement therapy.100 The secondary endpoints include the following: all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. Randomization will occur in 1080 subjects and the results are expected in the year 2010. Initially, distal EPD use was mandatory but now is left to the discretion of the operator. Distal EPDs have been used extensively and effectively in percutaneous intervention on carotids, coronaries, and saphenous vein grafts. The overall benefit from PTA/stenting on renal function has been demonstrated to be either no improvement in renal function compared to medical management or minimal improvement in 20%-30% of patients, based on a meta-analysis of stent-case series reports.101 Although clinically infrequent, many patients may actually lose a fraction of their functional renal parenchyma during renal intervention due to atheroembolization, al388

Curr Probl Cardiol, September 2009

though the damage may remain undetected on routine laboratory examination.102 In the Renal Artery Stenting With or Without Distal Protection (RESIST) study, EPDs used in RAS have shown renal functional improvement/stabilization in 98% of cases and even further benefit is conveyed with the addition of platelet inhibition.101 One prospective analysis of renal artery stent revascularization with the Angioguard EPD in 63 high-risk patients with chronic renal insufficiency demonstrated 97% stabilization or improvement in renal function.103 Only 3% of patients had an inexorable decline in renal function, unchanged by the intervention. After a mean follow-up of 16.0 months, 94% of patients demonstrated stabilization or improvement in renal function. Sixty percent of the filter baskets contained embolic material. Another trial using the Guardwire balloon occlusion and aspiration EPD demonstrated similar findings in 32 patients, with a mean RAS of 79%.104 Immediate technical success was achieved in 100%. There was a statistically significant improvement between mean pre- and postintervention serum creatinine (1.9 vs 1.6 mg/dL, P ⬍ 0.001) and estimated glomerular filtration rate (eGFR) values (37 vs 43 mL/min/1.73 m2, P ⬍ 0.001) at 6-week follow-up. Renal function was defined as improved (20% increase) after 53% of the procedures and worsened in none (0%). These findings suggest that EPDs, in combination with PTA/stenting of appropriate RAS lesions, can prevent atheroembolic injury to the kidneys during the procedure. Currently, recommended ACC/AHA practice guidelines for endovascular treatment of renal artery stenosis are as follows.6

RAS in Patient With CHF or Unstable Angina Class I

(Class IIa)

Percutaneous revascularization is indicated for patients with hemodynamically significant RAS and recurrent unexplained CHF or pulmonary edema. Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and unstable angina.

RAS in Patients With Hypertension Class IIa

Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and accelerated hypertension, resistant hypertension, malignant hypertension, hypertension with an unexplained unilateral small kidney, and hypertension with intolerance to medication.

Curr Probl Cardiol, September 2009

389

RAS in Patients With Abnormal Renal Function Class IIa

Class IIb

Percutaneous revascularization is reasonable for patients with hemodynamically significant RAS and progressive chronic kidney disease with bilateral RAS or RAS in a solitary functioning kidney. Percutaneous revascularization may be considered in patients with RAS and chronic renal insufficiency with unilateral RAS.

RAS in an Asymptomatic Patient Class IIb

Percutaneous revascularization may be considered for treatment of bilateral or solitary viable kidney with a hemodynamically significant RAS.

D.R. Holmes: The authors’ identification of treatment of a significant renal artery stenosis in a patient with recurrent unexplained congestive heart failure or pulmonary edema is an important one. Even more important is the need for screening of the renal arteries in patients with recurrent unexplained congestive heart failure or pulmonary edema.

Mesenteric Ischemia D.R. Holmes: Chronic mesenteric ischemia is infrequent and may present with vague ill-defined symptoms. From a patient standpoint, identification and treatment of this condition can dramatically improve quality of life. Selecting the optimal treatment strategy is however very difficult because of the lack of evidence from well-designed clinical controlled trials.

Patients with chronic mesenteric ischemia (CMI) most often present in their sixth or seventh decade; 70% are female, and 30%-50% have had prior coronary or peripheral interventions.105,106 CMI accounts for less than 1 in every 1000 hospital admissions, with autopsy studies showing incidence of mesenteric ischemia ⬍ 0.01% in the general population.107 Atherosclerotic disease of the intestinal arteries has been demonstrated to be present in 14%-24% of patients undergoing abdominal or peripheral angiography.106 Splanchnic blood flow accounts for approximately 10% of cardiac output at rest and can increase to 35% following ingestion of a large meal.106 As a result, patients with CMI most often present with postprandial abdominal pain, weight loss, cachexia, nausea, and vomiting. Due to an extensive collateral splanchnic arterial network, most patients with atherosclerotic 390

Curr Probl Cardiol, September 2009

intestinal disease are asymptomatic until 2 or more major vessels are involved, but cases of intestinal ischemia have been reported because of single-vessel syndrome, virtually always involving the superior mesenteric artery (SMA). In addition, patients with previous abdominal surgery, in whom some of the normal collateral intestinal arterial connections have been interrupted, are especially vulnerable to SMA stenosis. Open surgical procedures typically involve either an antegrade supraceliac aortic bypass or a retrograde iliac bypass, accompanied by perioperative mortality rates up to 17% and morbidity rates of 15%-60%, with multi-organ system failure being a frequent complication.108 The endovascular approach for CMI has produced variable results, depending on the technique used: PTA only, PTA with selective stenting, or primary stenting (Fig 13). A cumulative review of the outcomes of recent studies reveals technical success is highest in studies using a primary stenting approach, followed by selective stenting, and, finally, PTA alone.105 The higher success rate of primary stenting is counterbalanced by a higher restenosis rate of approximately 35% over a 2-year period, but made up for, in part, by a significantly lower (3%) complication rate over the same follow-up interval.105 The remaining significant variables, including mortality, as well as both early and late symptomatic relief, were equal for all 3 approaches.105 Thirty-day mortality rates following endovascular treatment of CMI are approximately 2%-5% depending on the approach used; complication rates vary 3%-9%. Initial symptomatic relief for all 3 types of intervention is approximately 82%, which decreases to an unassisted symptomatic relief rate of 75% at 2 years.105 Due to the small number of patients with diagnosed CMI and the recent advent of stenting for CMI, long-term follow-up for all 3 interventional modalities is limited to a little over 3 years in the endovascular literature. Table 5 shows a comparison of recent endovascular registries for CMI.109-113 In contrast, a retrospective review comparing open surgical repair to endovascular procedures for CMI demonstrated equivalent survival at 3-year follow-up (62% ⫾ 9% open vs 63% ⫾ 14%), but a significantly lower morbidity rate and shorter hospital stay in the endovascular group (open vs endovascular; morbidity: 46% vs 19%; hospital stay: 23 days vs 1 day).114 Unlike the results seen in select registry studies, cumulative patencies at 6 months were not significantly different between the 2 groups. The cumulative freedom from symptoms was higher in the surgical group, probably due to the more complete revascularization accomplished with the surgical approach and to the presence of diseased collateral splanchnic circulation in symptomatic patients. No prospective, Curr Probl Cardiol, September 2009

391

FIG 13. An 80-year-old man with history of atherosclerotic cardiovascular disease and hypertension who presented with unremitting postprandial abdominal pain and weight loss. SMA, superior mesenteric artery.

randomized trials exist in the literature comparing surgery to endovascular treatment for CMI. Furthermore, drug-eluting stents (DES), recent advancements in stent technology, experienced-operator skill level, perioperative heparinization, and antiplatelet therapy were unavailable during these selective endovascular CMI studies; hence, the primary, primary-assisted, and secondary patency rates and symptomatic outcomes in these patients come from another era and are not suitable for comparison. 392

Curr Probl Cardiol, September 2009

Acute Mesenteric Ischemia The natural progression of atherosclerosis in 50% of CMI patients leads to acute mesenteric ischemia (AMI) with bowel infarction/necrosis and symptoms of an acute abdomen. Embolism is the most common cause of AMI, ranging from 30% to 50% of cases, with thrombosis accounting for 15%-30% of cases.106 Thrombotic etiologies carry the highest mortality, with rates reported at 90%, whereas embolic etiologies have 70% mortality rates.106 These high mortality rates occur due to the acute nature of the events, leaving insufficient time for adequate collaterals to form. Furthermore, mortality is directly proportional to the amount of intestine compromised by the occlusion. The greatest danger in AMI is necrotic bowel, requiring surgical resection. Endovascular treatment has been used in AMI only in the absence of peritoneal signs and in cases where intestinal viability can be assessed by clinical means or diagnostic imaging.105 It is also used in patients who have prohibitive comorbidities for surgical treatment, again without evidence of intestinal ischemia. Endovascular options, which include PTA or catheter-directed thrombolysis, have been used with good results in cases of acute mesenteric embolism and thrombosis.115 Currently, recommended ACC/AHA practice guidelines for endovascular treatment of mesenteric arterial disease are as follows.6

Chronic Intestinal Ischemia Class I

Percutaneous endovascular treatment of intestinal arterial stenosis is indicated in patients with chronic intestinal ischemia.

Acute Intestinal Ischemia Class IIb

Percutaneous interventions (including transcatheter lytic therapy, balloon angioplasty, and stenting) are appropriate in selected patients with acute intestinal ischemia caused by arterial obstructions. Patients so treated may still require laparotomy.

Aortoiliac Bifurcation The TransAtlantic Inter-Society Consensus (TASC II) classification of aortoiliac lesions is shown in Fig 14. Aortoiliac occlusive disease (AIOD) can present with buttock, thigh, or hip claudication, CLI, or impotence. Erectile dysfunction may accompany buttock claudication in patients with absent femoral pulses, a condition termed Leriche’s syndrome, named after the surgeon who first described the condition in 1923. Historically, Curr Probl Cardiol, September 2009

393

TABLE 5. Endovascular intervention registries for chronic mesenteric ischemia

Sarac et al109 Silva et al110 Brown et al111 Landis et al112 Bajwa et al113

No. of pts.

Technical success

Follow-up

Mortality (30 d)

Morbidity

65 59 14 29 28

100% 96% 93% 97% 100%

1y 38 mo 13 mo 28.3 mo 22 mo

7.7% — 0% 6.9% 0%

30.8% — 0% 3.4% 0%

AIOD has been treated with surgical revascularization [ie, endarterectomy, aortobifemoral bypass (or occasionally axillobifemoral bypass, iliobifemoral bypass, and femorofemoral bypass)]. However, surgical intervention in AIOD is associated with a perioperative mortality of 3%-5% and a morbidity rate (infection, bleeding) of 8%-13%.116 Recent advances in endovascular technology and technique over the past decades have, however, allowed endovascular treatment to rapidly replace open surgery in mild to moderate lesions, defined as TASC class A and B lesions,17 although controversy remains over the best course of action in cases of severely calcified, long-segment, or extensive occlusion of the iliac arteries or the entire aortic bifurcation (TASC class C and D lesions). In general, however, catheter-based percutaneous therapies have become an established, safe (mortality 0%-2.3%), and effective method in the treatment of aorto-iliac occlusive disease. Endovascular treatment of AIOD with kissing stents is associated with low mortality and morbidity and good patency rates and has become the preferred option. The “kissing” balloon technique, with its deployment of a self-expanding or balloon-expandable stent, is the preferred method and involves positioning 2 balloons across the origins of both iliac arteries and inflating these balloons simultaneously, followed by stent placement. Procedural and clinical success is predictable, while mortality remains low. In a meta-analysis of data published on PTA and stent placement in AIOD in the 1990s, Bosch and Hunink117 demonstrated both immediate success (91% vs 96%) and good 4-year patency rates (65% vs 77%). Our results, and those of others118-128 using the kissing stent technique to reduce complications, have been excellent, in both the immediate postprocedure period and the long-term. Our rate of procedural success is 100% with a primary patency rate of 92% at ⬎ 18 months and a secondary patency rate of 100%.128 Although acute complications (distal embolization) are reported in 4% of patients undergoing stent placement using kissing technique, our patients had no vascular complications, myocardial infarctions, or perioperative deaths (Fig 15). 394

Curr Probl Cardiol, September 2009

TABLE 5. Continued Restenosis

Recurrent symptoms

Survival

Primary patency

Primary-assisted patency

— 29% 57% — 39%

25% 17% 9% — 50%

89% 81% — — 100%

65% 71% — 70.1% 61%

97% 83% — 87.9% 100%

Iliac Arteries Because they are easily accessible and relatively large vessels, the iliac arteries are ideally suited for endovascular intervention. Although aortofemoral bypass has traditionally been used for revascularization of occlusive iliac disease, this therapeutic approach carries a mortality rate of up to 5%, an early graft failure rate of 5.7%, and a patency rate after 2 years of 92.8%.129 With PTA, the initial technical success rate can be ⬎ 90%, with a 5-year primary patency rate of about 80%.130 However, in patients who have long calcified lesions, the success rate may be lower, in which case intravascular stents have been employed with excellent results. In fact, current guidelines recommend primary stent placement in the iliac arteries.6 Several studies have investigated the role of endovascular stents in treating iliac artery occlusive disease.117,131-135 Vorwerk et al132 used self-expanding WALLSTENT RX Biliary Endoprosthesis (Boston Scientific) to treat 109 patients with occlusive iliac disease after failed PTA and reported a primary patency rate of 82% and a secondary patency rate of 91% at 4 years. In a large multicenter study using PALMAZ-SCHATZ Crown balloon-expandable stents, technical success was achieved in 99% and clinical patency at 2 years was 84%.133 Scheinert and colleagues134 recently evaluated the role of primary stenting after excimer laser-assisted recanalization in 212 patients who had chronically occluded iliac arteries and reported technical success in 90% and a complication rate of 1.4% (arterial rupture or embolism) with rates of primary patency of 91% at 1 year, 84% at 2 years, and 76% at 4 years. Surgical and percutaneous treatment options for TASC class B and C lesions were compared in a nonrandomized observational fashion by Timaran and colleagues135 and there was no difference in limb salvage or survival at 5 years, although limited or compromised runoff seemed to predict higher failure rates. In 2 randomized controlled trials of surgery vs angioplasty for iliac occluCurr Probl Cardiol, September 2009

395

FIG 14. TASC II classification of aortoiliac lesions. AAA, abdominal aortic aneurysm; CFA, common femoral artery; CIA, common iliac artery; EIA, external iliac artery. (Reproduced with permission from Norgren et al. Inter-society consensus for the management of peripheral arterial disease [TASC II]. Eur J Vasc Endovasc Surg 2007;33:S1-S75.)

396

Curr Probl Cardiol, September 2009

FIG 15. A 71-year-old man with severe lifestyle-limiting claudication had bilateral iliac disease. Angiogram shows occluded right common iliac artery, moderate lesion in left common iliac artery, severe lesion in left external iliac artery (A). Self-expanding SMART Control stents (Cordis Corp, Minneapolis, MN) were deployed using a kissing technique followed by postdilatation using kissing balloons (B). Final angiogram after percutaneous intervention (C). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

sive disease and limb-threatening ischemia, there were no differences in 1- or 3-year cumulative rates for death, amputation, or revascularization failure.136,137 When long-term outcomes are combined from recent trials in patients with iliac stents, an acute procedural success rate of ⬎ 90% is seen, with 3 ⫾ 1 year primary patency rates of 74%-87% and secondary patency rates of 84%-95%, a serious complication rate of 1.4%, and a 30-day mortality risk of 0.5% (compared to 4% for aortofemoral bypass). Thus, patency rates of primary stenting compare favorably to surgical patency rates, while carrying a lower risk of mortality and morbidity.132,134,138-140 In summary, revascularization of aortoiliac occlusive disease has shifted from a predominantly surgical to an endovascular-based therapeutic approach, which has become the clinical standard of care in aortoiliac disease. The basis for this change in practice is the less invasive nature of PTA/stenting and its durable clinical success, in both immediate and long-term patency of the stented vessel. We believe stent placement offers higher procedural success and durability, similar to that of surgical reconstruction, with less risk and at reduced cost. In patients in whom vessel patency cannot be maintained, surgery remains a feasible option. Endovascular stent placement, in comparison with PTA alone, provides a larger acute gain in luminal diameter, scaffolding the lumen to prevent embolization of debris, and enhancing long-term patency. Both primary and “provisional” (following unsuccessful balloon angioplasty) stent placement compare favorably in acute hemodynamic results, effective target vessel revascularization, and low rate of repeat intervention. Based on current evidence, endovascular procedures are favored over surgical Curr Probl Cardiol, September 2009

397

revascularization in TASC class A and B lesions and in selected class C lesions, while patients with class TASC D lesions are generally considered surgical candidates. However, with technological advances in the form of re-entry devices and covered stent-grafts, many of the class D lesions are now amenable to an endovascular approach, the decision being made on a case-by-case basis. With regards to the type of the stent selected for therapy, the recently completed Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CrispStent) CRISP trial141 found no difference in patency of self-expanding nitinol stent (an alloy of nickel and titanium) vs balloon-expandable stainless steel stent. Current evidence suggests the type of stent used in iliac artery intervention does not affect immediate or long-term success. Therefore, choice of stent is usually individualized as determined by extent, nature of the lesion, ideal location of intervention, and operator’s experience level with a particular stent system. D.R. Holmes: The treatment of aorto-iliac disease has evolved from the surgical domain to an almost exclusively percutaneous approach. Depending on the specifics of the anatomy, specific approaches vary substantially, for example, stenotic vs aneurysmal disease. Several specialties are involved with the care of these patients—vascular surgeons, interventional radiologists, and interventional cardiologists. The long-term outcome of patients with this distribution of disease treated with percutaneous approaches is quite good.

Infrainguinal Disease D.R. Holmes: In distinction to patients with aorto-iliac disease, infrainguinal disease is much more difficult to treat and the more distal downstream the disease is, the worse the outcome. Critical limb ischemia is a very real threat. As the authors point out, randomized trial data are sparse. Issues include diffuseness of disease, presence of chronic occlusions, poor runoff, acute closure, and need for limb salvage in the setting of critical limb ischemia vs an orthopedic approach in terms of amputation. Of interest, the terms “primary” and “secondary” patency have come into use because of the rather ubiquitous need for subsequent procedures. In some centers, the long-term care of these patients is performed by vascular surgeons, although increasingly multidisciplinary vascular centers have been developed.

The TASC II classification of femoropopliteal lesions is shown below (Fig 16). Lower extremity atherosclerotic disease frequently leads to lifestylelimiting claudication and, sometimes, critical limb ischemia. Disease of 398

Curr Probl Cardiol, September 2009

FIG 16. TASC II classification of femoropopliteal lesions. CFA, common femoral artery; SFA, superficial femoral artery. (Reproduced with permission from Norgren et al. Inter-society consensus for the management of peripheral arterial disease [TASC II]. Eur J Vasc Endovasc Surg 2007;33:S1-S75.)

the infrainguinal vessels, which includes the common and superficial femoral and also the infrapopliteal arteries (below-the-knee), does not have the same long-term outcome as the aortoiliac segment, and more so in patients with poor distal runoff. Unlike the success achieved in the aortoiliac segment using PTA with or without stenting, results of endovascular therapy in the infrainguinal vessels have not been as durable (Figs 17 and 18).11 This may be, in part, because of the multiple levels of occlusive disease encountered in the infrainguinal vessels, and the unique biomechanical forces (Fig 19) that plague this segment of the arterial tree, leading to stent compression and fracture. Curr Probl Cardiol, September 2009

399

FIG 17. Durability of endovascular procedures in the lower extremity: primary patency rates with confidence intervals for iliac angioplasty, iliac stenting, femoropopliteal angioplasty and stenting, and below-the-knee angioplasty at 1 through 5 years. (Adapted with permission from Kandarpa K, et al. Transcatheter interventions for the treatment of peripheral atherosclerotic lesions: Part I. J Vasc Interv Radiol 2001;12:683-95.)

FIG 18. Durability of endovascular procedures in the lower extremity: complexity and clinical severity of lower extremity peripheral arterial disease. The figure also shows technical success achieved with endovascular procedures for lower extremity PAD and complication rate. (Adapted with permission from Kandarpa K, et al. Transcatheter interventions for the treatment of peripheral atherosclerotic lesions: Part I. J Vasc Interv Radiol 2001;12:683-95.)

Disease in this segment is also more aggressive, particularly in diabetics and smokers. The superficial femoral artery also has the ignominious distinction of being the most commonly diseased artery in the body, with total occlusions here being more common than in other vessels. Restenosis, secondary to neointimal hyperplasia, also continues to be a significant 400

Curr Probl Cardiol, September 2009

FIG 19. Biomechanical forces in the territory of the superficial femoral artery. (© Image courtesy of WL Gore and Associates, Inc. Reproduced with permission.)

limitation in endovascular treatment of the infrainguinal segment. Although adjunctive use of bare-metal stents, DES, and covered stent devices can improve patency rates, in-stent restenosis (ISR) continues to degrade initial technical success over time. Randomized trials comparing PTA and bypass surgery (BPS) in the infrainguinal segment are sparse. This could be explained by the fact that, traditionally, BPS has been commonly performed in extensive disease with long lesions and CLI, while PTA is more commonly performed in limited disease and short obstructions (following the original TASC I recommendations). However, Wolf and colleagues,142 in a multicenter, prospective randomized trial comparing PTA with BPS for treatment of iliac, femoral, or popliteal artery obstruction in 263 men, showed no significant difference in outcome over a median follow-up of 4 years (survival, patency, and limb salvage). The results of the Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) study,143 a recent randomized study of 452 patients undergoing either BPS or PTA, showed equivalent 2-year results between patients with CLI treated with first-line endovascular strategy vs those treated with surgery. In this study, survival to primary endpoint (amputation-free survival) was not statistically significant at 1 year; 68% for the surgical group and 71% for the PTA group; or at 3 years, 57% for the surgical group and 52% for the PTA group. Endovascular techniques and devices have developed at a rapid pace in the past few years. This less invasive method of revascularization is being increasingly used in several centers around the world and is associated with a significantly lower morbidity rate than traditional open-surgical reconstruction. Curr Probl Cardiol, September 2009

401

Common Femoral Artery Occlusive disease of the common femoral artery (CFA) is best treated with an open-surgical approach (iliofemoral bypass or endarterectomy with patch angioplasty) and is associated with a ⬎ 90% success rate (1-year patency rate of 80%) but with a heavy burden of postoperative morbidity (infection, hematomas, seromas) in ⬎ 15% of patients.144,145 Percutaneous revascularization for CFA disease is challenging because of the anatomical location of the vessel (ie, over the hip joint, where stent placement may be suboptimal and stent fracture becomes a concern). Here, it is potentially possible to use an open-architecture stent (ie, coil stent), which is resistant to fracture. In a small series of patients, Silva and colleagues146 recently reported their experience with provisional stent placement in CFA disease. They achieved a procedural success rate of 95% and event-free survival, including target vessel revascularization and amputation of 90%-95% at 1-year follow-up. Successful CFA stenting, in combination with debulking, rotational, or extraction atherectomy has also been reported.146,147 This technique is useful in patients who are poor surgical candidates and have CLI and severe lifestyle-limiting claudication. However, acute limb-threatening ischemia, with acute vessel closure leading to immediate limb loss, remains a concern. The profunda femoris artery has historically been revascularized by surgical treatment, although “percutaneous profundaplasty,” described by Silva and colleagues,148 achieved an immediate hemodynamic success rate of 97% with an in-hospital limb salvage rate of 94% and 88% at 3and 5-year follow-up, respectively, using provisional stenting with or without thrombolytic therapy. Thus, endovascular therapeutic approaches for treatment of infrainguinal vessels have, at best, limited success, but they offer an important alternative for the patient at high risk for an open surgical procedure.

Femoropopliteal Arteries D.R. Holmes: The frequent presence of a chronic (often very long) occlusion complicates the treatment of femoropopliteal disease. There are very limited data either short or long term on newer devices such as Pioneer, which may be used to optimize the outcome. The results of therapy appear to very lesion-specific—short focal lesions have much improved outcome compared with diffuse disease. The eventual role of drug-eluting stents in this setting requires further study and is the focus of the STRIDES and Zilver PTX study. The role of other stents, such as VIABAHN, offers significant advantages.

402

Curr Probl Cardiol, September 2009

Current procedural success for treatment of stenotic femoropopliteal occlusive disease and chronic total occlusion (CTO) is high and the advent of hydrophilic guidewires and catheters has enhanced ability to traverse occlusions in these segments, resulting in success in 80%-90% of cases. Use of devices like the Pioneer, Outback, and Frontrunner (re-entry catheters designed to facilitate controlled passage into the true arterial lumen after subintimal guidewire passage during recanalization procedures) has been associated with an 80%-100% technical success rate, crossing the desired occluded segment.149,150 These devices, as follows, have made it possible to traverse difficult occlusions and highly calcified lesions: a. Pioneer: an intravascular ultrasound-based tool that aids re-entry from a false lumen to a true lumen in recanalizing a CTO b. Outback: a fluoroscopy-based tool that aids re-entry from a false to a true lumen and facilitates recanalizing a CTO c. Frontrunner: a blunt microdissection tool that aids in recanalizing a CTO However, long-term patency still remains a concern and is about twice as common here as in the iliac segment, and optimal treatment of superficial femoral artery (SFA) disease in patients with intermittent claudication continues to be challenging. A variety of mechanical forces act on the SFA as it passes through the adductor canal and becomes the popliteal artery behind the knee (Fig 19). The femoropopliteal segment is subject to significant external forces, including torsion, elongation, and compression, related probably to the superficial course of the infrainguinal arteries and the impact of the surrounding muscles and tendons, and flexion/ extension associated with the hip and knee joints.151 Due to the nature of the axial compression and bending of the femoropopliteal segment that occurs with walking, sitting, standing, and climbing stairs, the extent to which a patient engages in these activities post intervention can significantly influence outcome following endovascular therapy in this region. The intrinsic stiffness of the vessel, which can often be calcified and thus less elastic, also contributes to deformation and affects outcome of endovascular procedures in the SFA. Percutaneous transluminal angioplasty in the SFA, as a means of revascularization, was initially undertaken for focal, short (⬍ 5 cm) lesions. Stenting was traditionally reserved for instances where there was a flow-limiting dissection or severe elastic recoil after PTA, because focal lesions in the SFA had been seen to respond equally well to PTA or stenting.152-157 Percutaneous treatment of SFA by balloon angioplasty or Curr Probl Cardiol, September 2009

403

stent placement was believed to have suboptimal long-term results based on the results of many small clinical trials.17 Primary patency rates for simple PTA have varied widely from 41% at 2-year follow-up158 to 70% at 5 years.159 The TASC II report calculated a weighted primary patency rate (PPR) for stenosis and occlusions, following femoropopliteal PTA, of 77% vs 65% at 1 year, 61% vs 48% at 3 years, and 5% vs 42% at 5 years. A meta-analysis by Kandarpa and colleagues160 demonstrated a 1-year patency rate for PTA of 26%-79%, declining to 12%-68% at 5 years. With the advent of selective stenting, patency rates improved for this segment and were found to vary from 48% to 80% at 1 year, declining to 22%-76% at 3 years. A meta-analysis by Muradin and coworkers a few years ago demonstrated better patency at 3-year follow-up for stents than for PTA in the most severely affected patients, those with occlusions and CLI.161 The TASC II report17 calculated a weighted PPR for PTA⫹ stenting for stenosis vs occlusion in the femoropopliteal segment of 75% vs 73% at 1 year and 66% vs 64% at 3 years. Although multiple small-series reports suggested nitinol stents improve durability of intervention in the infrainguinal area,162-166 it was not until 2006 that a single randomized trial167 demonstrated primary stent placement in femoropopliteal vessels, yielding superior patency rates and better functional outcome than provisional stent placement. Patients with long SFA lesions (mean length, 13 cm) were randomized between primary SFA stent placement (DYNALINK 0.018 Biliary Self-Expanding Stent System, Abbott Laboratories, Abbott Park, IL) and balloon angioplasty alone, and results revealed lower 6-month angiographic restenosis rates in the primary stent group (24% vs 43%; P ⫽ 0.05) with better functional improvement (ABI) and increased walking distance. The same authors,168 in a follow-up trial 2 years later (Balloon Angioplasty Versus Stenting With Nitinol Stents in the Superficial Femoral Artery [ABSOLUTE] trial), reported that stenting was superior to plain balloon angioplasty with respect to the occurrence of restenosis (49.2% vs 74.3%) by treatment-received analysis. Clinically, patients in the primary stent group showed a trend toward better treadmill walking capacity (average, 302 vs 196 m) and better ABI values (average, 0.88 vs 0.78) at 2 years. Reintervention rates also tended to be lower after primary stenting (37.0% vs 53.8%). The Femoral Artery Stenting Trial (FAST),169 a randomized, controlled multicenter trial, compared the impact of nitinol stenting (Bard LUMINEXX 6 F Biliary stent; CR Bard, Inc, Covington, GA) vs stand-alone balloon angioplasty (BA) in patients with short SFA lesions (mean lesion length 4.5 cm); although technical success was achieved in 95% of the 404

Curr Probl Cardiol, September 2009

stented group compared to 79% of the BA group, at 1 year, the PPR was 68.3% in the stented group compared to 61.4% in the BA group (P ⫽ 0.377). Target lesion revascularization (TLR) rates at 1 year were not significantly different (14.9% vs 18.3%) and no significant improvement was seen based on Rutherford category of peripheral arterial disease at 12-month follow-up. Hence nitinol stenting with Bard LUMINEXX, as opposed to PTA, did not improve angiographic and clinical outcome and the authors determined a larger trial was needed to demonstrate an advantage. To investigate the impact of nitinol stenting further, in light of the results of the FAST trial, Zeller and colleagues reported the results of the femoral artery CONFORMEXX trial (FACT),155 in which 110 patients with a single de novo ⬎ 70% SFA lesion ⬍ 10 cm long were treated with the CONFORMEXX self-expanding nitinol stent (Bard CONFORMEXX Biliary stent; CR Bard, Inc). Restenosis rate at 1 year was 23.3% (vs 38.6% for historical BA and 31.7% for FAST trial participants); target lesion revascularization rate was 7.4% (vs 18.3% for historical BA and 14.9% in the FAST trial), and 85.1% experienced improvement by at least 1 Rutherford category (P ⬍ 0.0001). Impressive success rates for SFA stenting were also reported in a 5-year follow-up study by Ferreira. SFA recanalization with nitinol self-expandable stents was reviewed (mean length, 19 cm; mean number of stents per patient, 2.8). The assisted primary patency rates were 96%, 90%, 90%, and 90% at 1, 2, 3, 4, and 5 years, respectively.170 Table 6 shows an overview of the recently completed trials in SFA revascularization. Additional evidence on SFA stenting is now emerging with the release of preliminary results from the Randomized Study Comparing the Edwards Self-Expanding LifeStent vs. Angioplasty alone In LEsions INvolving the Superficial femoral artery or proximal popliteal artery (RESILIENT) Trial. The 6-month patency rate in the RESILIENT trial (mean lesion length, 7 cm in the stent group and 6.4 cm in the BA group) has been reported to be 84% vs 53.8% and freedom from TLR 96.6% vs 56.1% at 6 months for the stent and BA groups, respectively. One-year patency in the stent group was reported as just under 80%. Covered stents or stent-grafts (self-expandable metal stents covered with a semipermeable or nonpermeable material) like the expanded polytetrafluoroethylene-covered nitinol stent-graft VIABAHN endoprosthesis (WL Gore & Associates, Inc, Flagstaff, AZ) are increasingly used to treat long-segment SFA lesions in the hope of reducing restenosis rates and improving long-term patency in occluded femoropopliteal vessels (Figs 20 and 21). Curr Probl Cardiol, September 2009

405

TABLE 6. Recent superficial femoral artery revascularization trials Schillinger 2006 (DYNALINK)167

Schillinger 2007 ABSOLUTE (DYNALINK)168

Trial: Characteristics

PTA

Stent

PTA

Stent

Number of patients Lesion type/length (mm) Occlusion (%) PPR at 1 y (%) Target lesion revascularization

53 92 ⫾ 64 17 67a NR

51 101 ⫾ 75 19 76a NR

52 93 16 31.8 NR

46 112 19 54 NR

NA, not applicable; NR, not reported; PPR, primary patency rate; PTA, percutaneous transluminal arterial angioplasty; TASC, TransAtlantic Inter-Society Consensus (TASC) Working Group; V, vessel. (Adapted from Dormandy JA, et al for the TransAtlantic Inter-Society Consensus (TASC) Working Group. management of peripheral arterial disease (PAD). J Vasc Surg 2000;31:S1S288. Reproduced with permission.) a Findings reported at 6 mo only.

It is believed that the stent covering prevents neointimal ingrowth through the interstices of the stent along the treated segment. In a recent review of the literature, Dorucci171 summarized the results of a study on 318 limbs treated with the VIABAHN stent-graft for SFA occlusive disease. The series followed 150 limbs for 3 years post insertion of VIABAHN stent (mean lesion length, 10.1 cm) and reported a primary and secondary patency rate of 64% and 80%, respectively. Kedora and colleagues172 documented similar patency rates at 12 months for 50 limbs treated with the VIABAHN endoprosthesis at 75.6% (primary) and 83.9% (secondary), respectively. At our institution,173 we followed 104 patients who underwent 115 endovascular repairs of de novo TASC Grade C or D SFA lesions using VIABAHN stent-graft. All patients were discharged on aspirin and clopidogrel and were followed clinically and with duplex scans at 1, 3, 6, and 12 months post procedure and longer, if clinically indicated. In-stent restenosis (ISR) was defined as a lumen loss of ⱖ 50% and patients with ISR on duplex scans underwent an angiogram for confirmation. The initial technical success was 100%. At a mean follow-up of 18 ⫾ 9 months, the PPR was 87.8% and secondary patency was 93.9%. There were 5 (4.3%) cases of total stent-graft occlusion, thus demonstrating that percutaneous revascularization of de novo, long, high-grade SFA lesions/occlusions with VIABAHN stent-graft is safe and feasible with excellent long-term patency. Similarly, the efficacy of VIABAHN/hemobahn in the treatment of severe SFA lesions was recently reported by Alimi and colleagues174 in 406

Curr Probl Cardiol, September 2009

TABLE 6. Continued

FAST (LUMINEXX)169

Fact (CONFORMEXX)155

Ferriera (Zilver)170

PTA

Stent

Stent

Stent

121 51.1 ⫾ 24 30 61.5 18.3% (1 y)

123 53.4 ⫾ 29.5 45 69.3 14.9% (2 y)

110 59.1 ⫾ 58.7 35 ⫾ 5 76.7 7.4% (2 y)

59 NR 90 NR

102 limbs treated for intermittent claudication, CLI, or acute limb ischemia (ALI). Lesions treated were TASC A, B, C, and D and associated with a good (2 or 3 leg arteries) or poor runoff (1 or none). Primary and secondary patency rates were 97 ⫾ 1.7% and 99 ⫾ 1% at 1 month, 74 ⫾ 4.8% and 84 ⫾ 4.1% at 1 year, and 71 ⫾ 9.5% and 79 ⫾ 8.5% at 3 years, after a mean follow-up of 30.2 months. They concluded that VIABAHN/ hemobahn endoprosthesis can achieve similar results to those of bypass surgery in TASC B and C SFA lesions and that severity of lesions, rather than preplacement symptoms or runoff, were the best predictors of success. In a study just released ahead of print, McQuade and colleagues175 prospectively randomized 100 limbs in 86 patients with SFA occlusive disease (all TASC A, B, C, and D lesions) to treatment with VIABAHN stent-graft vs femoral to above-knee popliteal artery bypass with synthetic graft material and followed them for 24 months. The stent-graft group demonstrated a PPR of 81%, 72%, and 63% with a secondary patency of 86%, 83%, and 74% at 6, 12, and 24 months, respectively. The surgical femoral-popliteal group demonstrated a PPR of 84%, 77%, and 64% with a secondary patency of 89%, 86%, and 76% at 6, 12, and 24 months, respectively (P ⫽ 0.716 and 0.695 for PPR and SPR, respectively). At our institution,176 we have used stent-grafts for ISR with measurable success. We recently followed 26 patients who underwent 32 endovascular repairs of ISR lesions of the SFA using VIABAHN stent-graft. All patients were followed closely with duplex scan at 1, 3, 6, and 12 months Curr Probl Cardiol, September 2009

407

FIG 20. A 68-year-old man with history of claudication. Angiogram shows a 20-cm occlusion of the right superficial femoral artery (arrows) (A). After percutaneous revascularization with VIABAHN (WL Gore and Associates, Inc) stent-graft (B). SFA, superficial femoral artery. (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

post procedure. The technical success rate was 100%, with no in-hospital mortality or morbidity. At a mean follow-up of 20 ⫾ 10.6 months, the PPR was 59.4% and the secondary patency was 65.6%. There were 6 (18.7%) cases of total stent-graft occlusion at mean follow-up. Although some results using covered stents are promising, other studies report less than favorable outcomes with these endoprostheses. Opponents of these devices argue that the covering blocks important collateral arteries arising from the stented artery, unlike bare metal stents where collaterals are preserved, and that this blocking of collaterals increases risk of stent-graft thrombosis, the treatment of which is cumbersome and costly. The Gore VIABAHN Endoprosthesis veRsus bAre Nitinol stenT (VIBRANT) study is a randomized, prospective multicenter clinical trial comparing the VIABAHN device to bare nitinol stents in 150 patients at 15 study sites over 3 years. Enrollment is complete in February 2008 and results are expected in 2009. Many other devices are available for endovascular treatment of infrainguinal disease, using the principles of debulking, cryoplasty, and brachytherapy. Most of these devices are used in SFA occlusive disease and, 408

Curr Probl Cardiol, September 2009

FIG 21. A 74-year-old man had a history of a nonhealing ulcer in his left foot. Angiogram shows a 15-cm occlusion of the left superficial femoral artery (arrows) (A). After percutaneous revascularization with VIABAHN (W.L. Gore and Associates, Inc) stent-graft (B). SFA, superficial femoral artery. (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

although none of them have been tested in randomized clinical trials, preliminary data are promising on these devices: a. Silver Hawk extraction atherectomy device: used for plaque extraction from infrainguinal vessels b. Excimer laser atherectomy: uses electromagnetic energy to ablate plaque and thrombus; this device also extracts plaque c. Cutting balloon atherotomy: facilitates angioplasty with controlled lesion dilation d. Polar cath cryotherapy: uses nitrous oxide to promote apoptosis and prevent neointimal hyperplasia; this device achieves angioplasty with transient cooling to ⫺5°C Ramaiah and colleagues177 demonstrated retrieval of large amounts of plaque using the Silver Hawk atherectomy device with an associated low repeat revascularization rate. However, this device is considerably more expensive than either a balloon catheter or a stent and, in the absence of controlled randomized data, interpretation of observed benefit is difficult. Curr Probl Cardiol, September 2009

409

Safety concerns with regards to perforation and distal embolization have also been raised in connection with debulking strategies.178-180 The PELA trial181 (Peripheral Excimer Laser Angioplasty), which randomized 251 patients with claudication and total SFA occlusion to PTA alone or excimer laser-assisted PTA, found no difference in patency rates or clinical events between the 2 at a 1-year follow-up. Scheinert and colleagues reported similar results182 in excimer laser-assisted recanalization of long chronic SFA occlusions, although the Belgian Laci study183 had shown good limb salvage rates (90.5%) at 6 months in a selected patient population. Thus, based on current evidence, debulking strategies do not convincingly add patency benefit to conventional percutaneous therapy with PTA/stenting. Endovascular cryotherapy or cryoplasty, which combines the dilation force of angioplasty with rapid freezing of the vessel wall, appears comparable to balloon angioplasty alone, with 9-month repeat revascularization rates of 18%.184 Despite its commercial availability, this device has not been tested for many years in any comparative trial. Similarly, the cutting balloon, originally developed and used to treat coronary stent restenosis, was approved for undilatable arteries, but has since been withdrawn, due to potential shaft separation of the catheter.185 Of these newer modalities, adjunctive endovascular brachytherapy has shown some promise, demonstrating a delaying effect on restenosis occurrence when compared to PTA alone.186,187 Restenotic lesions treated with brachytherapy seem to respond more favorably than de novo lesions.188 Iridium 192 was used in these studies, and recently, external beam irradiation of de novo SFA lesions after PTA has also been tried.189 At 1-year follow-up, the irradiated group registered significant benefit compared with the control group.

Drug-eluting Stents Despite the broad acceptance and use of DES in endovascular coronary procedures, experience with DES in peripheral vascular disease is limited to 2 small, randomized multicenter studies with mixed results. The first published randomized trial evaluating DES in PVD was the 2-phase SIROCCO trial (SIROlimus Coated Cordis smart stents for the treatment of Obstructive SFA disease).162-164 In the initial phase (SIROCCO I), the use of DES in the femoropopliteal arteries looked promising. Duda and colleagues164 reported on the effectiveness of placement of bare stents vs self-expanding nitinol stents coated with a polymer impregnated with sirolimus (Rapamycin) in patients with SFA obstructions. At 6 months, 410

Curr Probl Cardiol, September 2009

17.6% of 17 patients in the uncoated group demonstrated ISR compared with 0 of 13 in the sirolimus group. The second phase, SIROCCO II,157 was a multicenter, double-blind, prospectively randomized trial in which 57 patients who had CLI and either SFA occlusion (66.7%) or stenosis were randomly assigned to undergo either sirolimus-eluting stent implantation or bare-metal nitinol stent implantation. Although at 6 months the results were encouraging (0% ISR in the coated group compared to 11.6% in the uncoated group), the reduction of restenosis was lost at 18 months; 20.9% in the DES group and 17.3% in the uncoated group had developed restenosis. Thus, SIROCCO II failed to reveal any angiographic or clinical endpoint improvement using bare-metal nitinol stent over sirolimus-eluting (SE) nitinol stent. Currently, results are awaited on 2 major DES trials in the treatment of infrainguinal disease: the STRIDES trial (SFA Treatment with Drug Eluting Stents Study) and the Zilver PTX study. The former is a prospective, European nonrandomized controlled trial evaluating the safety and performance of the DYNALINK™ DYNALINK-E everolimus-eluting peripheral stent system in above-the-knee de novo or restenotic lesions, while the latter is a multicenter, prospectively randomized trial comparing uncoated nitinol SE stents (Zilver stent) to stents coated with paclitaxel applied without a polymer in patients with atherosclerotic stenosis or occlusion of SFA. Drug delivery from a coated conventional angioplasty balloon was tested in the recently published THUNDER trial190 (local Taxan with sHort time exposure for reduction of restenosis in Distal artERies), where use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease was found to be associated with significant reduction in late lumen loss and target-lesion revascularization. One hundred fifty-four patients with femoropopliteal occlusive disease (mean lesion length, 7.4 ⫾ 6.5 cm) were randomized to treatment with standard balloon catheters coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, or uncoated balloons without paclitaxel (control). At 6 months, mean late lumen loss was 1.7 ⫾ 1.8 mm in the control group, as compared with 0.4 ⫾ 1.2 mm (P ⬍ 0.001) in the group treated with paclitaxel-coated balloons and 2.2 ⫾ 1.6 mm (P ⫽ 0.11) in the group treated with paclitaxel in the contrast medium.

Pitfalls The use of stents (PALMAZ-SCHATZ Crown stent, WALLSTENT, SMART Nitinol Stent System [Cordis Endovascular], SelfX self-expandCurr Probl Cardiol, September 2009

411

ing stent system [Abbott Vascular], Bard LUMINEXX, etc) placed in the SFA and popliteal arteries has been associated with fractures151,162,163 that can result in thrombosis, early restenosis, and pseudoaneurysm formation. Stent fractures in the SFA can also impact the drug-eluting systems by: a. Disrupting uniform drug delivery b. Causing vessel injury c. Requiring prolonged drug delivery, a variable not found in the coronary circulation.143 Although BE stents are particularly susceptible to compression in this region and restenosis is not uncommon,191 the more flexible SE nitinol stents are not immune. In fact, a relatively high rate of stent fracture was identified in the SIRROCO I trial (18.2%). Scheinert and colleagues151 detected stent fractures in 37.2% of patients treated with SE nitinol stents after a mean follow-up of 10.7 months (mean length of stented segment, 15.7 cm) and found PPR significantly lower for patients with stent fractures (41.1% vs 84.3%, P ⬍ 0.0001). Although in the newer studies of SFA stenting, stent fractures have not been systematically studied (most studies reporting only restenosis rates). The FAST trial reported a stent fracture rate of 12% and, interestingly, the restenosis rate in patients with stent fractures was not statistically different from that in patients without stent fractures (20% vs 28%, P ⫽ 0.7). Different stent designs or materials may be more prone to fracture, although this has not yet been systematically studied,151,192 and risk of stent fracture increases with the length of the stented segment.151 Stent fracture may be associated with reduction in overall patency rate, although the latter remains a controversial issue, because a consistent relationship between stent fractures and restenosis has not been established. In summary, treatment of femoropopliteal occlusive disease remains a challenge, perhaps because in most patients, the atherosclerotic process in the SFA is diffuse, associated with chronically occluded segments, and may involve the region of the adductor canal with its issues of stent torsion, elongation, and stent flexion during normal daily activities, leading to the development of stent fractures.151 PTA and stenting can achieve good intermediate-term primary patency rates while relieving symptoms; however, long-term results with these interventions remain disappointing, especially when the disease burden within the SFA becomes more diffuse and complex. Newer stent designs, stent-grafts, or 412

Curr Probl Cardiol, September 2009

DES may improve upon these results, while alternative modalities (brachytherapy, cryoplasty, laser, etc) will continue to be used, albeit judiciously, in complex femoropopliteal disease. The role of stenting and DES in the treatment of SFA occlusive disease will be more clear when the final results are released from the RESILIENT study, the Zilver PTX trial, and the STRIDES trial.

Infrapopliteal Arteries D.R. Holmes: Treatment of infrapopliteal disease is among the most difficult situations encountered given the diffuse nature of the disease and the presence of inflow disease. As the authors point out, the metrics of success are not long-term patency but relief of rest pain, improved healing of skin ulcers, and limb salvage. The continued application of drug-eluting stents offers significant promise.

The anterior tibial, peroneal, and posterior tibial arteries are often involved in multilevel PAD in the distal extremity, more in combination than as isolated vessels. Revascularization attempts below the knee must, therefore, take into account the severity and distribution of disease in the more proximal vessels. It is rare to find infrapopliteal disease without coexistent proximal disease. Also, isolated tibioperoneal disease rarely causes disabling or lifestyle-limiting claudication or rest pain unless disease is present in the proximal part of the tibioperoneal trunk, affecting the common inflow into all 3 vessels. Thus, sometimes, symptomatic relief for multilevel disease-associated claudication is achieved simply by correcting inflow into the more proximal obstructing vessels and revascularization of tibioperoneal vessels is reserved for patients with CLI, in which restoration of uninterrupted patency to at least 1 of the vessels to the foot is required to heal the lesion (for example, in the presence of ischemic ulcer). Based on studies carried out by Veith and colleagues, which reported decrease in procedure-related amputation from 49% to 14%,193-195 tibial artery bypass surgery became the standard of care in the 1990s. However, over the past decade or so, the introduction of new smaller diameter balloons and guidewires and the use of coronary equipment allowing uncomplicated access to the infrapopliteal tree have made an endovascular approach with infrapopliteal angioplasty a viable alternative to surgical bypass, largely replacing the traditional surgical bypass procedure.196-198 Success of endovascular therapy in this area is usually measured by relief of rest pain, improved ulcer healing rate, and Curr Probl Cardiol, September 2009

413

FIG 22. A 67-year-old man had a history of nonhealing ulcer in the left foot. Angiogram shows severe disease below the knee with occluded anterior tibialis artery, severely diseased tibioperoneal trunk (white arrow), and occluded posterior tibial artery (black arrow) (A). After percutaneous balloon angioplasty of tibioperoneal trunk and posterior tibial artery (B). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

avoidance of amputation. Success is not measured by achieving long-term patency, because post angioplasty restenosis has historically plagued the infrainguinal and infrapopliteal arteries, with reobstruction rates below the knee ranging from 32% to 50% at 6-month angiographic follow-up after successful percutaneous recanalization.199-202 The primary goal of infrapopliteal arterial intervention for CLI is to restore at least 1 unobstructed line of blood flow to the distal foot. Augmentation of collateral inflow usually yields limited limb salvage benefits, whereas at least 1 patent tibial artery with adequate pedal runoff will promote tissue healing.199,201,203 Although no large studies have been completed, several reports199-201,204-214 have demonstrated the feasibility, safety, and efficacy of tibioperoneal PTA (Fig 22), combined with atherectomy and stenting as adjuvant procedures. Primary procedural success rates are high for ideal lesions, and cumulative 2- to 5-year limb salvage and patency rates of 80%-90% can be achieved with modern endovascular techniques rivaling those of surgical reconstruction.215,216 The technical success rates for infrapopliteal angioplasty range between 78% and 100%,211,213,217-219 while a random-effects meta-analysis demonstrated a technical success rate of 93% and a 1- and 2-year limb salvage rate of 79% and 74%, respectively.159,211 In comparison, the limb salvage rates for distal bypass at 1 and 2 years are 79% and 74%, and up to 414

Curr Probl Cardiol, September 2009

one-third of surgical patients require repeat intervention to maintain graft patency.211 Dorros and colleagues,209 in one of the largest studies on PTA in tibioperoneal trunk limb salvage, reported successful procedural outcome in 92% of treated lesions, while rest pain was relieved or blood flow to a lower extremity was improved in 95% of the endangered limbs. Clinical 5-year follow-up of the successfully revascularized CLI patients documented a limb salvage rate of 91%. Raouf and associates220 recently reviewed their experience with 54 consecutive popliteal arteries treated with angioplasty for single or multiple stenosis (mean lesion length, 1.2 cm). Stents were used in 6 patients for salvage of a suboptimal result and were placed in the above-knee popliteal artery only. The technical success was 100%. At 2 years, the primary patency for claudicants was 87.0% ⫾ 7.0%. Our experience in patients with lifestyle-limiting claudication with or without CLI has been the same, with 95% procedural success and 86% limb salvage rates.221 Although there are little long-term data regarding the benefit of stent use in below-knee disease, use of stenting in the tibioperoneal trunk, in an effort to increase patency rates and limb salvage, has been undertaken, and, currently, there are a few reports199,222-224 that describe the application of stents in the arteries below the knee. Feiring and colleagues223 reported that below-knee stent-supported PTA for critical limb ischemia not only improved ABI more than tibial bypass, it also healed ulcerations, relieved rest pain, and improved ambulation. Siablis and colleagues,199 in a recent, small, prospective randomized trial of angioplasty vs stenting, using a carbon-coated stent (carbos tent), showed better 6-month angiographic patency rates for stenting (84% vs 61% using a 70% diameter threshold on CT angiography measurements). DES have been used in the tibioperoneal trunk, with reports of low restenosis rate. Sirolimus-eluting stents have already demonstrated marked short-term angiographic and clinical efficacy in the infrapopliteal arteries.199,202,224,225 Recently, Siablis and colleagues,199 in a nonrandomized comparison of tibioperoneal stenting in 58 patients (28 BMS and 29 SES), demonstrated a marked reduction in restenosis at 6 months from 55% in BMS to 4% in the DES category. This led to the approval of the BE sirolimus-eluting stent CYPHER (Cordis Corporation, Warren, NJ) in Europe for this indication. The same authors, in a more recent study of stenting226 performed as a bailout procedure for suboptimal angioplasty (flow-limiting dissection, elastic recoil, or postangioplasty residual stenosis ⬎ 30%), reported that, after 1 year, sirolimus-eluting stents were steadily associated with increased primary patency (P ⫽ 0.001) and significantly less in-stent (P ⫽ 0.001) and in-segment (P ⬍ 0.001) binary Curr Probl Cardiol, September 2009

415

restenosis. Sirolimus-eluting stents were also associated with significantly fewer cumulative target lesion reinterventions at 6 months and 1 year. No significant differences between the DES and bare-metal stent groups were noted at 1 year with respect to mortality (10% vs 13.8%, respectively), minor amputation (17.2% vs 10.3%), or limb salvage (100% vs 96%). In Germany, patients were recently enrolled in a study on the Cypher stent with abciximab, and preliminary reports of 6-month patency are reported to be high (⬎ 90%-95%).227 Thus, in cases of limb salvage, where the inflow is required to help heal an ischemic ulcer or infection, aggressive percutaneous revascularization is indicated and has been shown to increase tissue healing and reduce the incidence of amputation, resulting in limb salvage.199,228 In summary, there has been a paradigm shift in the management of tibioperoneal occlusive disease, with safe and effective revascularization being achieved with current endovascular techniques in this high-risk cohort of patients. When anatomically feasible, PTA is now considered a reasonable and appropriate first option for revascularization of all patients, even those with low surgical risk for infrapopliteal bypass. In addition, the availability of effective and less invasive options currently permits a lower threshold for intervention in such cases, and more so in that subset of patients who claudicate solely based on the infrapopliteal nature of their disease. Infrapopliteal PTA also helps those patients with claudication and severely impaired runoff that are undergoing proximal vessel revascularization (surgery or PTA).

Endovascular Therapy for Acute Limb Ischemia D.R. Holmes: Acute limb ischemia is a true medical and often surgical emergency. Centers involved in the specialized care of patients with peripheral artery disease must be very familiar with the strategies of care available to optimize outcome. Centers not involved with such specialized care must evolve strategies and protocols for rapid referral and transfer of patients.

Acute limb ischemia, a medical emergency, is defined as sudden onset (⬍ 14 days) of symptomatic, diminished, or worsening limb perfusion that endangers both limb and life.229 To prevent irreversible nerve and muscle damage, treatment is focused on rapid restoration of arterial blood flow to the ischemic limb. The traditional 5 p’s of ALI include the following: 1. Pain 2. Pulselessness 416

Curr Probl Cardiol, September 2009

3. Pallor 4. Paresthesia 5. Paralysis Due to inaccuracy of pulse palpation and physical examination, all patients with ALI should have a Doppler assessment of the pulses at the time of presentation and an immediate evaluation by a vascular specialist. An important clinical endpoint for all patients who present with ALI is tissue viability (threatened vs viable limb), and presence of rest pain, sensory loss, and muscle weakness help differentiate between the 2. By contrast, muscle rigor, tenderness, and findings of pain with passive movement are late signs of advanced ischemia and probable tissue loss and about 10% of patients with ALI present as unsalvageable. Acute limb ischemia is associated with a high morbidity and mortality and elderly patients are at particularly high risk for severe local and systemic complications.229 The initial goal of treatment for ALI is prevention of thrombus propagation and, therefore, immediate anticoagulation with heparin is initiated. Immediate surgical revascularization (thromboembolectomy/ endarterectomy/bypass/graft revision) is usually indicated for the profoundly ischemic limb (sensory/motor deficits of very short duration), although recent advances in endovascular management have changed practice patterns. Traditional open-surgical revascularization has a high amputation and mortality rate,230,231 while catheter-directed thrombolysis (CDT) is a minimally invasive approach that is better tolerated by patients with multiple comorbidities.232 Catheter-directed thrombolysis (Fig 23) offers the following advantages when compared with surgical revascularization: 1. 2. 3. 4. 5.

Lower mortality Less complex procedure Reperfusion achieved at a lower pressure Lower risk of reperfusion injury Further definition of the underlying lesions by angiography with appropriate adjunctive management 6. Reduced risk of endothelial trauma and clot lysis in branch vessels too small for embolectomy balloons CDT is based on the principle that activation of fibrin-bound plasminogen to the active enzyme plasmin is the most effective means of lysing thrombi, and direct delivery of a thrombolytic agent produces increased activity at the desired location, protects intrathrombus plasmin from circulating antiplasmins, and permits effective thrombolysis at a reduced dose. Three randomized trials compared intrathrombotic thrombolysis of Curr Probl Cardiol, September 2009

417

FIG 23. A 54-year-old woman with a history of aortobifemoral bypass presents with acute onset of severe rest pain in right lower extremity. Aortogram shows occlusion in the right limb of the graft (arrow) (A). Angiogram after 16 hours of catheter directed thrombolysis (B). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

urokinase or recombinant tissue plasminogen activator with initial surgical intervention (Rochester, STILES, and Topas) and confirmed the role of CDT as a first-line treatment strategy for ALI.233-235 Although the limb salvage rate for CDT at 1 year in all of these trials was the same as the limb salvage rate for surgical revascularization (82%-88%), the mortality rate at 1 year was significantly lower: 16% at 1 year in the Rochester study vs 42% for surgery; 6.5% vs 8.5% in the STILES trial; and 13.3% vs 15.7% in Topas. Acute limb ischemia, associated with acutely occluded bypass grafts, was seen to have a better outcome than acute occlusion in native vessels in both Topas and STILES. Thus, the studies demonstrated a reduction in the magnitude of interventions required and a better early survival with thrombolysis. However, use of thrombolytics is associated with hemorrhagic complications and stroke and there are also reports of recurrent ischemia.159,236-239 Therefore, CDT is mainly recommended for graft thromboses or in situ thromboses of native vessels of short duration. In an attempt to reduce infusion time and dose of thrombolytic agent needed to achieve reperfusion, various techniques have been developed to accelerate lysis of the thrombus. These aim for initial high-dose delivery of a thrombolytic agent over a shorter period and include such techniques as forced periodic (eg, pulse-spray) infusion with a special infusion pump.240-243 Two prospective, randomized studies that compared con418

Curr Probl Cardiol, September 2009

ventional low-dose infusion with different techniques using high-dose thrombolysis demonstrated contradictory results.244,245 A more recent study by Plate and colleagues,246 however, did not demonstrate any disadvantage with high-dose, short-duration lytic therapy (120 minutes) compared to low-dose long-duration (25 hours) therapy, with major bleeding events occurring in 7% patients with high-dose vs 13% with the low-dose regimen and mortality at 1 month being 10% and 11%, respectively. In addition to CDT, other minimally invasive techniques, such as percutaneous aspiration thrombectomy or percutaneous mechanical thrombectomy (PMT), have been employed in treatment of the acutely ischemic limb.247,248 PMT allows rapid debulking of thrombus burden, as a stand-alone thrombectomy therapy or as an adjunct to thrombolytic therapy to decrease symptomatic ischemia time.249 A combination of these techniques with pharmacologic thrombolysis may speed up clot lysis and decrease time to revascularization. Percutaneous aspiration thrombectomy uses a thin-walled, large-lumen catheter and suction with a 50-mL syringe to remove embolus or thrombus from native arteries, bypass grafts, and runoff vessels. It is used together with fibrinolysis to reduce time and dose of the fibrinolytic agent or as a stand-alone procedure. PMT devices use the principle of hydrodynamic recirculation. Dissolution of the thrombus occurs within an area of continuous mixing referred to as the “hydrodynamic vortex,” where the thrombus is trapped, dissolves, and is finally evacuated. By contrast, nonrecirculation devices, which function primarily by direct mechanical thrombus fragmentation, have been used less frequently for peripheral arterial disease because of the higher risk of peripheral embolization and the higher potential for vascular injury. The efficiency of PMT depends mainly on the age of the thrombus; fresh thrombus responds better than older organized clot. Small clinical series have demonstrated short-term (30-day) limb salvage of 80%-90%. Small series have shown that rheolytic thrombectomy (RT), with or without chemical lysis,250,251 leads to effective thrombus removal in a short time and reduces major adverse events in ALI patients. In a series reported by Allie et al,251 the 30-day limb salvage rate was 91% in 49 ALI patients using the power-pulse spray technique (P-PS) and RT. Shammas and colleagues252 recently studied the presence of thrombus, using intravascular ultrasound to evaluate the feasibility of combined thrombolysis (P-PS) and RT in patients with ALI and recent-onset (6 months) limb ischemia, and observed that the application of the P-PS/RT led to partial or complete thrombus resolution in about two-thirds of the patients treated and the overall safety outcome was favorable. Curr Probl Cardiol, September 2009

419

After limb reperfusion is achieved, there is increased capillary permeability that may result in local edema and compartment syndrome, leading to regional venule obstruction, nerve dysfunction, and, eventually, capillary and arteriolar obstruction and muscle and nerve infarction. Clinical presentation includes pain out of proportion to physical signs, paresthesia, and edema. Compartment pressures ⱖ 20 mm Hg are an indication for fasciotomy. The anterior compartment is most commonly involved, but the deep posterior compartment can also be affected. Another complication following reperfusion is rhabdomyolysis, leading to renal failure if not recognized early. Following successful revascularization, prolonged warfarin therapy (3-6 months) is initiated, despite the cumulative bleeding risk, because recurrent limb ischemia is a frequent problem.

Angiogenesis in Critical Limb Ischemia Targeting patients with CLI and very few or no revascularization options, many studies have attempted to use angiogenic gene therapy (ie, the strategy of administering growth factors to stimulate angiogenesis and bypass obstructions). Currently, preclinical studies are underway to identify the potential for complementary or synergistic effects of certain combinations of angiogenic gene therapy in hopes of identifying the most efficient and safe biological combination. In more than 1000 patients treated with gene therapy for therapeutic angiogenesis, evidence has accumulated regarding the safety of these approaches in humans.253-268 Disparity remains between the results of randomized trials conducted to date but can probably be explained by differences in the patients studied, the angiogenic growth factors targeted, the vehicles used, or the modes of delivery. There were several large, randomized placebo-controlled trials on patients with PAD studying the impact of angiogenic factors on stimulation of vascular growth (angiogenesis/arteriogenesis): the therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC) trial (intra-arterial infusion of fibroblast growth factor-29 in 190 patients)259; the Regional Angiogenesis with Vascular Endothelial growth factor in peripheral arterial disease (RAVE) trial (intramuscular injection of adenoviral VEGF 121 gene in 105 patients)266; and the STimulation of ARTeriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease (START) trial (subcutaneously injection of granulocyte-macrophage colonystimulating factor in 40 patients).269 None of the high expectations accompanying the start of these trials were met. None of the methods tested resulted in improvement in walking capacity. In summary, although evidence is not consistent, results of several pilot 420

Curr Probl Cardiol, September 2009

studies and a few clinical studies have shown that angiogenic growth factors promote development of collateral arteries (therapeutic angiogenesis) and that angiogenesis can be achieved either by use of growth factors or by genes encoding these proteins. D.R. Holmes: The field of vascular gene therapy for patients with peripheral arterial disease has indeed been disappointing. Whether this is the result of using the wrong agents or the wrong delivery approaches, or whether these have been applied in the wrong patients, is unclear.

We end the discussion by summarizing the current ACC/AHA recommendations for endovascular treatment of PAD.

Recommendations Endovascular Treatment for Claudication Class I 1. Endovascular procedures are indicated for individuals with a vocational or lifestyle-limiting disability due to intermittent claudication when clinical features suggest a reasonable likelihood of symptomatic improvement with endovascular intervention and (a) there has been an inadequate response to exercise or pharmacologic therapy and/or (b) there is a very favorable risk-benefit ratio (eg, focal aortoiliac occlusive disease). (Level of evidence: A) 2. Endovascular intervention is recommended as the preferred revascularization technique for TASC type A iliac and femoropopliteal arterial lesions. (Level of evidence: B) 3. Stenting is effective as primary therapy for common iliac artery stenosis and occlusions. (Level of evidence: B) Class IIa 1. Stents (and other adjunctive techniques such as lasers, cutting balloons, atherectomy devices, and thermal devices) can be useful in the femoral, popliteal, and tibial arteries as salvage therapy for a suboptimal or failed result from balloon dilation (eg, residual diameter stenosis greater than 50%, or flow-limiting dissection). (Level of evidence: C) Class IIb 1. The effectiveness of stents, atherectomy, cutting balloons, thermal devices, and lasers for the treatment of femoral-popliteal arterial Curr Probl Cardiol, September 2009

421

lesions (except to salvage a suboptimal result from balloon dilation) is not well established. (Level of evidence: A) 2. The effectiveness of uncoated/uncovered stents, atherectomy, cutting balloons, thermal devices, and lasers for the treatment of infrapopliteal lesions (except to salvage a suboptimal result from balloon dilation) is not well established. (Level of evidence: C) Class III 1. Endovascular intervention is not indicated if there is no significant pressure gradient across a stenosis despite flow augmentation with vasodilators. (Level of evidence: C) 2. Primary stent placement is not recommended in the femoral, popliteal, or tibial arteries. (Level of evidence: C) 3. Endovascular intervention is not indicated as prophylactic therapy in an asymptomatic patient with lower extremity PAD. (Level of evidence: C)

Recommendations Thrombolysis for Acute and Chronic Limb Ischemia Class I

Class IIa

Class IIb

Catheter-based thrombolysis is an effective and beneficial therapy and is indicated for patients with acute limb ischemia (Rutherford Categories I and IIa) of less than 14 days duration. (Level of evidence: A) Mechanical thrombectomy devices can be used as adjunctive therapy for acute limb ischemia due to peripheral arterial occlusion. (Level of evidence: B) Catheter-based thrombolysis or thrombectomy may be considered for patients with acute limb ischemia (Rutherford Category IIb) of more than 14 days duration. (Level of evidence: B)

Classification of Recommendations Class I. Conditions for which there is evidence for and/or general agreement that a given procedure or treatment is beneficial, useful, and effective. Class II. Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. 422

Curr Probl Cardiol, September 2009

Class IIa. Weight of evidence/opinion is in favor of usefulness/efficacy. Class IIb. Usefulness/efficacy is less well established by evidence/ opinion. Class III. Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful.

Level of Evidence ● Level of evidence (A): data derived from multiple randomized clinical trials or meta-analyses. ● Level of evidence (B): data derived from a single randomized trial or nonrandomized studies. ● Level of evidence (C): only consensus opinion of experts, case studies, or standard-of-care.

Endovascular Therapy for Aneurysmal Arterial Disease D.R. Holmes: The treatment of aneurysmal arterial disease has undergone revolutionary changes with the increasingly widespread use of percutaneous strategies. In some patients and centers, endovascular therapy has replaced standard surgery. Given the wide range of pathology encountered, a wide range of technology has developed. Optimizing the outcome in these patients requires tailoring creative patient-specific therapy, knowledge of sophisticated imaging techniques with 3-dimensional reconstruction, and a team approach of vascular specialists. Continued technological advances will allow for more successful long-lasting treatment strategies for an increasing number of patient and lesion subsets.

Descending Thoracic Aorta The prevalence of thoracic aortic aneurysm (TAA) is estimated to be 10 of every 100,000 elderly adults.270 The incidence of TAA has been increasing, in part, due to improved detection with CT as well as an increase in the percentage of elderly patients in the population. Thirty percent to 40% of these aneurysms occur exclusively in the descending thoracic aorta (DTA). Thoracic aortic aneurysms most often result from cystic medial degeneration that leads to weakening of the aortic wall. Cystic medial degeneration occurs normally with aging and is increased with hypertension. When it occurs in young patients, it is most often due to Marfan syndrome or other, less common, connective tissue disorders, such as Ehlers-Danlos syndrome. Curr Probl Cardiol, September 2009

423

The natural history of TAA is less defined than for abdominal aortic aneurysms. A significant risk of rupture and death is associated with descending thoracic aneurysm. The 5-year survival rate of unoperated DTA is approximately 13%, whereas the 5-year survival rate of patients treated with surgery is 70%-79%.271 Mortality for DTA surgical repair ranges from 5% to 20% in elective cases and increases to 50% in emergent cases, with paraplegic complications occurring in 5%-25% of cases.271 Spinal cord ischemia is considered the most grave prognostic indicator in predicting effectiveness of repair of DTA. As a result, a significant proportion of patients with DTA is considered nonoperative and is limited to medical therapy alone. The risk of rupture is directly related to the size of the aneurysm. Coady et al found that, in an ascending aorta, diameter of an aneurysm ⬎ 6 cm increased risk of rupture or dissection by 25% and, in a descending aorta, diameter of an aneurysm ⬎ 7 cm increased the risk by 37%.272 Davies et al reported an annual rate of rupture and dissection of 2% for aneurysms ⬍ 5 cm, 3% for aneurysms 5-5.9 cm, and 7% for aneurysms ⬎ 6 cm in diameter.273 Therefore, the risk appears to rise abruptly as thoracic aneurysms reach a size of 6 cm. Indications for intervention in patients with thoracic aneurysm include the following271: ● Symptoms, regardless of size ● Diameter of 50 mm for ascending aneurysm and 60 mm for descending aneurysm (early in some subgroups, ie, Marfan syndrome patients) ● Diameter of DTA ⬎ 2 ⫻ transverse diameter of adjacent normal aortic segment ● Growth rate ⬎ 10 mm/y ● Complications associated with aneurysm that increase risk of rupture, such as dissection, leak, or ulceration. Thoracic endovascular aortic repair (TEVAR) has been shown to be a less invasive alternative to open surgical repair (Figs 24 and 25). A study comparing TEVAR and open surgery for DTA in low-risk patients enrolled 140 patients at 17 sites to evaluate the Gore TAG® endoprosthesis.274 These patients were compared to a surgical control cohort of 94 patients, which included both historical and concurrent subjects. Technical success was achieved in 137 patients, with a perioperative mortality of 2.1% vs 11.7% in the surgical group (P ⬍ 0.001). Thirty-days analysis revealed a statistically significant lower incidence of respiratory failure (4% vs 20%) and renal insufficiency (1% vs 13%) in the TEVAR group. Spinal cord ischemia occurred in 3% of the TEVAR 424

Curr Probl Cardiol, September 2009

FIG 24. A 70-year-old male with a large descending thoracic aneurysm treated with TEVAR with a Gore TAG device.

group vs 14% of the surgical group, which was statistically significant. At 2 years, 50% of those with spinal cord ischemia in the TEVAR group had complete neurological recovery, whereas 75% of paraplegics in the surgical group died. There was a higher incidence of peripheral vascular complications in the TEVAR group (14%). Benefits of the endovascular approach included shorter mean lengths of intensive care unit (ICU) stay (2.6 vs 5.2 days) along with shorter total hospital stay (7.4 vs 14.4 days). The Achilles heel of TEVAR is the endoleak and, at 1- and 2-year follow-up, the incidence of endoleaks was 6% and 9%, respectively. Through 2 years of follow-up, there were 3 reinterventions in the TEVAR cohort and none in the open-surgical control cohort. Kaplan-Meier analysis revealed no difference in overall mortality at 2 years. Additionally, the overall stroke rate was similar in both groups. An additional 51 patients were enrolled after revision of the endograft in 2003, and the data were pooled with the previous patients. At 5 years, aneurysm-related mortality was lower for TAG patients compared with open controls (2.8% vs 11.7%, respectively, P ⱕ 0.008). No differences in all-cause mortality were noted, with 68% of TAG patients and 67% of open controls surviving to 5 years (P ⱕ 0.43). Major adverse events at 5 years were significantly reduced in the TAG group: 57.9% vs 78.7% (P ⱕ 0.001). Endoleaks in the TAG group decreased from 8.1% at 1 month to Curr Probl Cardiol, September 2009

425

FIG 25. A 35-year-old female is admitted with intractable back pain and fever (A). Angiogram reveals a ruptured mycotic aneurysm of the descending thoracic aorta (arrowhead pointing to a contained rupture) (B). After endovascular intervention was deemed inadvisable, the patient underwent an endovascular repair of the ruptured mycotic DTA aneurysm. Three years post EVR, the patient is doing well on lifelong antibiotics.

4.3% at 5 years. Major aneurysm-related reinterventions were required in 5 patients (3.6%) in the TEVAR group, most of which addressed endoleaks. At 5 years, there have been no ruptures, 1 migration, no collapse, and 20 instances of fracture in 19 patients, all before the revision of the TAG graft. Hence, at 5 years, TEVAR was found to be superior to surgical repair for the treatment of DTA. The aneurysmal sac enlargements seen in the early part of the study were attributed to the endograft design and, when later modified, the DTA post TEVAR enlargement phenomenon was resolved with the new design. Despite a low-risk surgical patient population, when randomized to treatment of DTA by surgery vs TEVAR, there was a significantly lower incidence of perioperative mortality, spinal cord ischemia, respiratory and renal failure, and ICU and hospital stay in the TEVAR group, but there was a higher incidence of peripheral vascular complications. This implies that, even when patients are optimal candidates for surgical intervention, the outcomes with surgery still yield unacceptably high rates of mortality 426

Curr Probl Cardiol, September 2009

and post procedure paralysis. The patients who survive the surgical procedure for DTA repair have the same survival rate at 2 years as the TEVAR group.

Abdominal Aorta The definition of an abdominal aortic aneurysm (AAA) is focal enlargement of the abdominal aorta (usually involving the infrarenal portion) to a diameter ⬎ 50% larger than normal or to ⬎ 3 cm in its largest true transverse dimension.275 Infrarenal aortic aneurysms are more common than thoracic aneurysms. Untreated, the major complication is rupture, leading to death. Aneurysmal rupture is directly related to aneurysm size, according to Laplace’s Law (ie, tension on the aortic wall is the product of the artery’s radius ⫻ blood pressure).276 In the Mayo Clinic’s recent population-based study, if the last ultrasound study revealed an AAA diameter of ⬎ 4 cm, the estimated risk of rupture was 0% per year, with increases to 1% per year for diameters of 4.0-4.9 cm, 11% per year for diameters of 5.0-5.9 cm, and 25% per year for diameters ⬎ 6 cm.277 At least 1 million Americans have a clinically recognized AAA, but only 70,000-80,000 surgical repairs are performed annually. Many of the patients are over age 70 and have other serious comorbidities.278 Consequently, their operative risk is increased, prohibiting open surgical repair. The risk of mortality from a ruptured aneurysm is extremely high. Twenty-five percent of patients die before reaching a hospital; another 51% die at the hospital without undergoing surgery and, in those who have surgery, the operative mortality is 46%, with an overall 30-day survival of just 11%.279 Indications for repair in patients with AAA include the following: ● Diameter of 5.5 cm or larger278 (5.0-5.5 cm for women) ● Growth rate of 1 cm/y ● Symptoms related to the aneurysm regardless of size Open surgery has remained the gold standard for repair of AAAs. First reported by Dubost et al in 1951, the technique has evolved and significant improvement in mortality and morbidity rates has been achieved. However, even in low-risk patients, open repair of AAA is associated with a mortality rate of 0%-5%.279 In a Mayo Clinic 36-year population-based study in Olmstead County, Minnesota, 30-day mortality was 5% in 307 patients who underwent elective open surgical repair for an AAA.280 The Canadian multicenter study reported similar results of 5.4%.281 In 1991, Parodi and coworkers described the first successful implantation of an endoluminal stent-graft in a patient with an infrarenal AAA.282 Curr Probl Cardiol, September 2009

427

FIG 26. A 73-year-old man with history of coronary artery disease, congestive heart failure (ejection fraction of 30%), and hypertension was diagnosed with a large (8.5 cm) infrarenal AAA. Angiogram showing infrarenal AAA (A). No evidence of endoleak after successful EVAR repair with a AneuRx stent-graft (Medtronic, Inc, Minneapolis, MN) (B). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

FIG 27. A 72-year-old man had a 5.4 cm sacular AAA and history of coronary bypass and hypertension. Angiograms before GoreExcluder (W.L. Gore and Associates, Inc) stent-graft implantation (A) and after implantation (B). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

At least 10 different devices have been used for endovascular aneurysm repair (EVAR) of AAA, 4 of which have FDA approval and are commercially available in the US (Figs 26 and 27). Most asymptomatic AAAs are discovered incidentally, on CT scan for some unrelated diagnostic workup. Currently, the ACC/AHA have not 428

Curr Probl Cardiol, September 2009

released clinical guidelines relating to screening patients for AAAs. The advent of EVAR has added a significant treatment option for patients with AAAs, even for those once considered inoperable. The benefits of EVAR in an elective setting include reduced perioperative mortality, decreased ICU and overall hospital stay, decreased blood loss, and improved physical recovery as early as 1 week after the procedure, with earlier return to baseline function.283 Early mortality associated with EVAR has been generally less than 3%. Several studies have shown mortality levels to be less than those associated with open surgical repair (ie, 1.9% in the AneuRx Phase I, II, and III studies284 and 1.7% in the Eurostar study285). There are limited data regarding long-term reintervention and rupture after surgical repair or EVAR.286-293 Similarly, data are scarce on long-term laparotomy-related reintervention for bowel obstructions and ventral hernias, following surgical repair.290 Most of the information we have is from studies with follow-up of 3 years or less, with survival rates between 96% at 3 years294 and 62% at 4 years.295 From the Eurostar registry, the largest database for EVAR of AAA, Harris and Buth showed a survival of 80% at 5 years.296 The Gore Excluder US Multi-Center Trial confirmed decreased rates of major adverse cardiovascular events (MACE) with marked differences in 30-day events of hemorrhage, and pulmonary, cardiac, and bowel complication rates when compared with traditional open surgical procedure.283,297 Freedom from MACE was sustained at 2 years and favored the EVAR group. CT scan evaluation of the aneurysm sac in patients with the Ancure and Zenith endoprostheses showed the highest rate of sac shrinkage in the absence of endoleak, with other grafts such as the Excluder achieving lower rates.283,297-303 Furthermore, if necessary, EVAR can be performed under local or regional anesthesia, thereby eliminating the added morbidity associated using general anesthesia.283 The EVAR-1 Trial recruited patients at 41 British hospitals whose operators were proficient in the EVAR technique.287 A total of 1082 elective (nonemergency) patients were randomized to receive either EVAR (n ⫽ 543) or open surgical AAA repair (n ⫽ 539). Inclusion criteria were as follows: age of at least 60 years, aneurysm diameter of 5.5 cm or more, and a reasonable candidate for open surgical repair. The primary measure of outcome was all-cause mortality. In the study, 1047 (97%) patients underwent AAA repair and 1008 (93%) received their allocated treatment. There was a statistically significant difference in 30-day mortality between the groups, with the EVAR group having a 1.7% operative mortality vs 4.7% in the surgical group (P ⫽ 0.009). Secondary interventions were more common in patients allocated to the Curr Probl Cardiol, September 2009

429

EVAR wing (9.8%) as compared to the surgical group (5.8%, P ⫽ 0.02), with the majority of interventions secondary to surgery performed for reasons other than the aneurysm repair, endoleaks being the next most common secondary intervention. The number of patients who continued in the EVAR-1 trial to the full 4 years of follow-up was less than 25% of the total. The Dutch Randomized Endovascular Aneurysmal Management Trial was a multicenter, randomized trial comparing open surgical with EVAR repair in 345 patients with AAA of at least 5 cm in diameter who were considered suitable candidates for both techniques.289 Patients in this study were considered at low surgical risk. Operative mortality rate was 4.6% in the open-repair group and 1.2% in the EVAR group, resulting in a risk ratio of 3.9%. EVAR was associated with shorter duration of procedure, less blood loss, as well as less blood transfusion, shorter ICU stay, decreased need for postoperative mechanical ventilation, shorter duration of mechanical ventilation for those in whom it was required, and a shorter total hospital stay. Most of the increased complications in the surgical group were due primarily to a higher rate of pulmonary complications. A review of all the perioperative rates of death and complications, long-term survival, rupture, and reinterventions was analyzed in Medicare patients who underwent either open surgical repair or EVAR of AAA from 2001 to 2004, with follow-up data until 2005.290 Propensity score-matched cohorts were created for the surgical and EVAR groups, with 22,830 matched patients in each cohort. Perioperative mortality was lower after EVAR than after open surgical repair (1.2% vs 4.8%, P ⬍ 0.001), and the reduction in mortality increased with age (2.1% difference for those 67-69 years old vs 8.5% for those 85 years or older, P ⬍ 0.001). A summary of randomized, multicenter EVAR trials is found in Table 7.

ACC/AHA Practice Guidelines for Endovascular Treatment of Abdominal and/or Iliac Aneurysms6 Class I 1. Infrarenal or juxtarenal AAAs measuring 5.5 cm or larger should undergo repair to eliminate the risk of rupture. 2. Patients with infrarenal or juxtarenal AAAs measuring 4.0-5.4 cm should be monitored by ultrasound or CT scans every 6-12 months to detect expansion. 3. Periodic long-term surveillance imaging should be performed to monitor for endoleak, to document shrinkage or stability of the 430

Curr Probl Cardiol, September 2009

TABLE 7. Randomized trials of EVAR for AAA repair

No. of patients Gore excluder297 EVAR-1287

Dream289

Medicare Database290

Total: 334 EVAR ⫽ 235 Surgery ⫽ 99 Total: 1082 EVAR ⫽ 543 Surgery ⫽ 539 Total: 345 EVAR ⫽ 174 Surgery ⫽ 171 Total: 45,660 EVAR ⫽ 22,830 Surgery ⫽ 22,830

Major inclusion criteria

Primary outcome

Results (EVAR vs Surgery)

AAA ⬎ 4.5 cm

Major adverse events

14% vs 57% (P ⬍ 0.0001)

Age ⬎ 60 AAA ⬎ 5.5 cm

All cause mortality

1.7% vs 4.7% (P ⫽ 0.009)

AAA ⬎ 5 cm

Operative mortality

1.2% vs 4.6% (P ⫽ 0.1)

Age ⬎ 67

Perioperative 1.2% vs 4.8% death and (P ⬍ 0.001) complications

AAA, abdominal aortic aneurysm; EVAR, endovascular repair.

excluded aneurysm sac, and to determine the need for further intervention in patients who have undergone endovascular repair of infrarenal aortic and/or iliac aneurysms. Class IIa 1. Repair can be beneficial in patients with infrarenal or juxtarenal AAAs measuring 5.0-5.4 cm in diameter. 2. Repair is probably indicated in patients with suprarenal or type IV thoracoabdominal aortic aneurysms larger than 5.5-6.0 cm. 3. In patients with AAAs smaller than 4.0 cm in diameter, monitoring by ultrasound every 2-3 years is reasonable. 4. Endovascular repair of infrarenal aortic and/or iliac aneurysms is reasonable in patients at high risk of complications from open operations. Class IIb 1. Endovascular repair of infrarenal aortic and/or iliac aneurysms may be considered in patients at low or average surgical risk.

Mesenteric/Visceral Arteries Due to an increase in the use of diagnostic imaging, incidental findings of celiac and superior mesenteric artery aneurysms are becoming more common. Various treatment options exist for repair of these aneurysms depending on their size, the artery involved, the nature of related symptoms, and the risk for rupture.304 Hepatic artery pseudoaneurysms Curr Probl Cardiol, September 2009

431

FIG 28. (A) Celiac angiogram showing large left hepatic artery aneurysm with evidence of free contrast extravasation (arrowhead). LHA, left hepatic artery, RHA, right hepatic artery, PHA, proper hepatic artery, GDA, gastroduodenal artery (B). Post procedure angiogram showing complete exclusion of the aneurysm with JOSTENT (Abbott Vascular, Abbott Park, IL) (C). Magnetic resonance angiography of abdomen showing 2.1-cm hepatic artery aneurysm. ([Reproduced with permission from Hashim et al. Leaking hepatic artery aneurysm successfully treated with covered stent: case report with review of the literature. Catheter Cardiovasc Interv 2009 [Jan 29; Epub ahead of print]).

and true aneurysms are associated with a high rate of rupture (Fig 28), and there is agreement that these should be repaired.305,306 Symptomatic splenic artery aneurysms ⱖ 2 cm, found in liver transplant recipients or in women of childbearing age, are associated with a high risk of rupture and should also be repaired.306 Aneurysms involving the celiac trunk, SMA, gastroduodenal artery, and pancreaticoduodenal artery have an unpredictable rate of rupture and should be repaired. Treatment options include embolization, PTA/stenting, or surgical repair. Endovascular 432

Curr Probl Cardiol, September 2009

treatment is an option in patients who are considered inoperable due to comorbidities. A recent study examined 35 patients with mesenteric aneurysm treated with endovascular coil embolization or stenting and compared them to 24 patients treated by open surgical repair.304 The endovascular technical success rate was 89%, with failures successfully treated by repeat coil embolization. These patients had a shorter inhospital length of stay as compared to the surgical group. There were no significant differences in reintervention, complication, or mortality rates at 30 days. Persistent perfusion of the aneurysm was the most common complication. The endovascular group had a higher percentage of patients with comorbidities, including cancer, than the surgical group.

Iliac Arteries Iliac artery aneurysms (IAA) are most commonly associated with AAA, accounting for up to 50% of all cases. It is rare to find an isolated aneurysm of the iliac artery (incidence, 0.03%-0.1%).307 Although most aneurysms in this region are asymptomatic, symptoms may be present secondary to local compression, thrombosis, or distal embolization of atheromatous debris. Expansive growth and subsequent rupture of iliac artery aneurysms are also well documented.308 Elective endovascular repair of isolated IAAs is indicated in patients with the following criteria: ● Asymptomatic if ⬎ 3.5 cm in diameter ● Rapid increase in diameter (⬎ 0.5 cm/y) ● Symptomatic regardless of size As with surgical repair of AAA, open surgical repair of IAA is a major procedure that is associated with high rates of procedure-related morbidity and mortality. Placement of an endovascular stent-graft, if technically feasible (good neck and adequate iliac artery size), provides a less invasive way to exclude an IAA. In a report on 48 patients who underwent implantation of an endoprotheses in the iliac artery, Scheinert et al309 achieved a rate of technical success of 97.9% for complete exclusion of an aneurysm. Primary patency rates were 100% after 1 year, 97.9% after 2 years, 94.9% after 3 years, and 87.6% after 4 years. Sahgal et al recently reported that 30 of their 31 patients had a decrease in the size of their iliac aneurysm (35 true isolated IAAs) after treatment with endovascular graft (EVG) repair and coil embolization of the hypogastric artery or its branches.310 It is thus both feasible and safe to attempt percutaneous exclusion of IAA by endovascular stent-graft implantation. As a minimally invasive procedure Curr Probl Cardiol, September 2009

433

associated with very low rates of procedure-related morbidity and mortality, we recommend it as the primary alternative to open surgical repair. One study compared open surgical repair to endovascular repair of common iliac artery aneurysms (CIAAs).311 This retrospective study examined 715 CIAAs (65% bilateral) in 438 patients. To determine guidelines for elective CIAA repair, it was necessary to assess the expansion rates of CIAAs. Patients were divided into 3 groups based on associated pathology: group 1 (377 patients), current or previously repaired AAA; group 2 (15 patients), associated internal iliac artery aneurysms (IIAA); and group 3 (46 patients), isolated CIAAs. They determined that the median expansion rate was 0.29 cm/y with hypertension predicting faster expansion. CIAAs ruptured in 5% and AAAs ruptured in 4%. Ninety percent of the repairs were elective, and the endovascular and surgical groups registered no difference in 30-day mortality. There were more frequent complications with longer hospitalizations in the open repair group. Five-year primary (95%) and secondary (99.6%) patency rates, freedom from reintervention, and survival rates were similar between the groups. As no rupture occurred when the CIAA was ⬍ 3.8 cm, it is reasonable to initiate elective repair in asymptomatic patients with CIAA ⱖ 3.5 cm and the study’s findings support endovascular repair as the first-line treatment for anatomically suitable CIAA repair. Endovascular repair was compared to surgical repair in 55 patients with 58 solitary iliac artery aneurysms (SIAAs) at two European University hospitals.312 The endovascular group (33 SIAAs) had a higher proportion of patients with hypertension. Three-year primary patency rates were similar between the 2 groups (endovascular 97%, surgery 100%). There was no evidence of endoleaks, kinking, or graft migration. CT scans demonstrated stable aneurysms in 26 patients, whereas 7 aneurysms demonstrated regression. Operative time, blood loss, and postoperative hospital stay were significantly less in the endovascular group. Secondary interventions were not required in either group. Better intraoperative and early postoperative outcomes, as well as durable mid- and long-term results in patients treated with endovascular repair, indicate that endovascular techniques should be offered as first-line therapy in the treatment of SIAAs.

Popliteal Artery Popliteal artery aneurysms, defined as localized dilatations of the popliteal artery ⬎ 2 cm in diameter, are the most common aneurysms of the peripheral arteries, with a prevalence of 1% in men age 65-80 years.313 434

Curr Probl Cardiol, September 2009

Popliteal aneurysms have a well-documented natural history and can lead to significant morbidity. Complication rates of untreated popliteal aneurysms range from 15% to 25% at 1 year and increase to 60%-75% at 5 years.314 Even when asymptomatic, with good distal runoff, they should be repaired electively. Popliteal aneurysms frequently are found in association with aneurysms occurring at other sites, being bilateral in 50% of cases, and associated with AAAs in one-third of cases. The aneurysm is confined solely to the popliteal artery in 50% of cases. Further complicating treatment options is the fact that the aneurysm is typically not confined to the popliteal artery but extends distally in 40% of patients to involve the anterior tibial artery and tibioperoneal trunk and, in 10%, it extends proximally to involve the distal SFA. Most patients are symptomatic, with 30% of these patients presenting with acute limb ischemia caused, not by rupture, but by either thrombosis or distal embolization. The amputation rate in patients who present with acute limb ischemia due to popliteal artery aneurysm may be as high as 15%.315 Open surgical ligation and bypass with saphenous vein graft has been the procedure of choice for preventing complications. No randomized trials have been conducted to compare results of treatment of popliteal artery aneurysm by medical management with surgery. Dawson et al, reporting on results following elective surgery for popliteal artery aneurysms, found a 90% rate for limb salvage and an 80% rate for graft patency.316 Mortality and limb loss have been reported; up to 1% of patients will have residual symptoms after surgery.317 Endovascular popliteal aneurysm repair (EVPAR) using covered stents has been found to be safe and feasible, with several studies reporting patency rates of 60%-70% at 18 months (Fig 29). Tielliu et al reported on their prospective study of 28 patients with 23 popliteal artery aneurysms, all of whom underwent endovascular repair with a self-expanding stent-graft.318 Technical success in placing the stent-graft and excluding the aneurysm was 100%. During a median follow-up of 15 months, 5 of 23 stent-grafts became occluded, resulting in a cumulative patency rate of 74%. All reocclusions occurred within 6 months of intervention; 2 occlusions were successfully recannulated, and none of the 3 patients with persisting occlusion required an amputation. At 2 years, the primary and secondary patency rates were 77% and 87%, respectively. Only one-third of the patients received postprocedural antiplatelet or anticoagulation therapy. The only variable associated with success was treatment with clopidogrel. EVPAR, using the VIABAHN endoprosthesis, was compared with open-surgical approach in 56 popliteal artery aneurysms, with 15 popliCurr Probl Cardiol, September 2009

435

FIG 29. A 54-year-old man was found to have a 4-cm unilateral popliteal aneurysm (arrow). Before VIABAHN (W.L. Gore and Associates, Inc) stent-graft implantation (A) and after implantation (B). (Reproduced with permission from Allaqaband et al. Endovascular treatment of peripheral vascular disease. Curr Probl Cardiol 2006;31:711-60.)

teal aneurysms being repaired endovascularly.314 Primary and secondary patency, along with survival, was similar between the 2 groups at 24-month follow-up. Major complications occurred in 7% of both groups. Endoleaks were discovered in 15% of the EVPAR group (mostly type 1 and 3), which were subsequently treated with stenting. Mean length of stay was significantly less in the EVPAR group (0.9 vs 4.9 days). A prospective randomized study of 30 patients compared patients who were candidates for both EVPAR and open surgical repair. Primary and secondary patency rates were 87% and 100%, respectively, at 24-month follow-up.319 One common reason for graft failure in EVPAR is angulation and movement at the knee joint level. The development of a stent made of nitinol rings supported by thin polyester (anaconda limbs) was intended to overcome these common complications. The stent was evaluated in 14 patients, 6 of whom were symptomatic. In 6 patients, the stent crossed the knee joint. Primary patency was 93% at 6 months with 1 stent occlusion. There were no deaths in the study.320 436

Curr Probl Cardiol, September 2009

Guidelines for popliteal aneurysm treatment with EVPAR include the following321: ● ● ● ● ●

Symptomatic aneurysms Presence of thrombus Size ⱖ 2 cm in size Presence of proximal and distal landing zones ⱖ 3 cm At least a 2-vessel runoff below the knee.

Endovascular Therapy for Deep Vein Thrombosis D.R. Holmes: Evaluation and treatment of venous disease covers a large data set and many clinical scenarios ranging from patients following bedrest or surgical procedures on orthopedic hospital wards to patients with pacemakers or malignancy. Presentation varies greatly as does the number of approaches. All physicians need to be comfortable with basic issues of deep vein thrombosis and pulmonary emboli because they are so commonly seen. One large issue is that of treatment of venous insufficiency, a problem that causes significant symptoms in many patients following the index acute event. These problems may be difficult to treat. Newer surgical approaches are used in select patients; in addition, there is interest in development of endovascular approaches. This field is as yet quite young.

Although anticoagulation is the mainstay of therapy in deep venous thrombosis (DVT), pharmacothrombolytic therapy and endovascular approaches are frequently used in the presence of severely symptomatic acute thrombosis. CDT, in which the pharmacologic agent is infused directly into the vicinity of the clot, can accomplish effective rapid thrombus dissolution at a lower total dose of the thrombolytic agent. Several reports have demonstrated successful results for CDT in upper and lower extremity DVT, regardless of etiology, with near-complete thrombus clearance ranging from 72% to 88%,322-330 the completeness of the response mainly being dependent upon the chronicity of the thrombus. In addition to CDT, as is true with ALI, percutaneous mechanical thrombectomy is used as an adjunct therapy to facilitate thrombolysis and reduce infusion time. It is generally believed that thrombotic occlusions of ⬎ 2-weeks duration are less likely to respond to pharmacothrombolysis.322 As a result, because of the risk of hemorrhagic complications, CDT is usually not recommended for chronic occlusions.

Lower Extremity Venous thromboembolism (VTE), including DVT and pulmonary embolism, is a common condition affecting about 7 per 10,000 personCurr Probl Cardiol, September 2009

437

years among community residents331,332 and recurs in about 20% of patients after 5 years.333,334 A community-wide study by Anderson and colleagues in the 1980s reported an incidence rate of pulmonary embolism, with or without DVT, of 2.3 per 10,000.335 Conventional treatment for acute DVT is directed toward prevention of clot propagation, relief of local symptoms, and prevention of pulmonary embolism. Significant risk reduction is achieved by anticoagulating with unfractionated heparin, low-molecular-weight heparin, and warfarin.336-343 Although pulmonary embolism (PE) remains the most feared complication of DVT (PE occurs in about 10% of cases), the most common and costly complication is chronic venous insufficiency (postphlebitic syndrome), which develops in many patients after DVT and is accompanied by serious symptoms affecting quality-of-life in 33%87%.344-347 This is probably because anticoagulation does not physically remove the thrombus nor does it preserve valve function or prevent postthrombotic syndrome, but only prevents propagation and embolization.348-351 Surgical removal of the clot by thrombectomy is associated with high recurrence rates and is rarely performed nowadays. However, with the advent of catheter-based therapy, results are much better and, in cases where the benefit is expected to exceed the risk, aggressive endoluminal removal of thrombus is usually considered. Thus, young patients at risk for postphlebitic chronic venous problems (lower short-term risk and a greater lifespan to accrue long-term benefit), those with significant iliofemoral clot burden, patients with possible May-Thurner syndrome (see later), patients with severe local symptoms, and patients with overwhelming symptomatic outflow obstruction and acutely threatened limb (acute phlegmasia; onset, 10 days) are the usual candidates. Patients with DVT related to diffuse malignancy or malignant obstruction are not ideal candidates. Catheter-directed thrombolysis involves administration of thrombolytics directly through the side ports of a catheter traversing the thrombus. Only 1 randomized trial has evaluated catheter-directed thrombolysis in lower extremity DVT. It compared catheter-directed thrombolysis followed by 6 months of warfarin using intravenous heparin followed by warfarin.352 This study enrolled 35 of 207 screened patients with acute iliofemoral DVT; most exclusions were due to recent surgery. Some patients had already received heparin at the time of enrollment. Six months after treatment, the patency rate was significantly higher in the group that received CDT (13 of 18 [72%] vs 2 of 17 [12%]), and the prevalence of venous reflux was significantly lower (2 of 18 [11%] vs 7 438

Curr Probl Cardiol, September 2009

of 17 [41%]). Fourteen studies of CDT have been observational (Table 8). The largest series, from the National Deep Venous Thrombosis Registry, involved 287 patients enrolled from 63 centers for treatment of symptomatic iliofemoral and femoropopliteal DVT with catheter-directed thrombolysis.353 Greater than 50% lysis was achieved in 83% of cases. The degree of lysis correlated with long-term outcomes: 100%, 50%99%, and under 50% lysis resulted in 1-year patency rates of 79%, 52%, and 32%, respectively. Acute occlusions were more thoroughly lysed than chronic occlusions (34% vs 19% for complete lysis; 86% vs 68% for significant lysis). Patients with iliofemoral DVT had significantly greater 1-year patency rates than patients with femoral-popliteal DVT (64% vs 47%). The other published studies on catheter-directed thrombolysis of DVT have been single-institution case series, with combined data on 802 patients.354-367 The enrolled patients were heterogeneous, with upper or lower extremity DVT, and most series had minimal long-term follow-up. The rates of complete thrombolysis (95% lysis) ranged from 40% to 92% across series, and rates of complete or partial thrombolysis (defined as 50%-100% lysis) ranged from 50% to 100%. Besides the Venous Registry, only 4 studies report on the long-term results of catheterdirected thrombolysis, with generally favorable results for vein patency, postthrombotic syndrome, and venous competence.355,364-366 Rates of major bleeding in these case series ranged from 0% to 13%, and rates of minor bleeding ranged from 0% to 25%. There was no uniformity in assessment methods. In the Venous Registry, 1 fatal intracranial hemorrhage and 1 subdural hematoma occurred. There were no other reports of intracranial hemorrhage. The literature thus suggests that catheter-directed thrombolysis may be efficacious in well-chosen patients. Additional randomized trials are needed to confirm that the outcomes of patients treated with catheter-directed thrombolysis are superior to those of patients receiving standard anticoagulation, to better define which patients may benefit most from this therapy, and to more thoroughly evaluate the risks of this procedure. Currently, evidence on how the magnitude of clot burden influences response to catheter-directed thrombolysis is limited. Mechanical thrombolysis refers to the technique of physical, usually “real-time,” removal of thrombus (as opposed to allowing lytic drugs to break up clot). These techniques can be used before beginning chemical thrombolysis or during treatment, as experience and individual findings suggest. The 2 most common devices/techniques are the Angiojet (Possis Medical, Minneapolis, MN) and the Arrow-Trerotola PTD (Arrow Curr Probl Cardiol, September 2009

439

TABLE 8. Catheter-directed thrombolysis for deep venous thrombosis Study

Lytic agent

Number pts.

Significant lysis, %

Randomized trials Elsharawy and Elzayat 2002

SK

35

SK: 100 AC: 0

Cohort studies Grunwald and Hofmann 2004 Sugimoto et al 2003

t-PA t-PA or UK

82 54

Castaneda et al 2002 Razavi et al 2002 Horne et al 2000

r-PA TNK t-PA

25 36 28

Ouriel et al 2000 Mewissen et al 1999 Raju et al 1998 Bjarnason et al 1997 Semba and Dake 1994 Ogawa et al 2005 Laiho et al 2004 Sillesen et al 2005 Acharya et al 2005

r-PA UK UK UK UK UK r-PA r-PA r-PA

97-100 t-PA: 87 UK: 83 (P ⫽ 0.69) 92 83 UE: 59 LE: 90 NR NR 71 NR 92 54 81 93 100

11 303 24 87 27 24 16 45 5 (postpartum)

AC, anticoagulant; LE, lower extremity; NR, not reported; r-PA, reteplase; SK, streptokinase; t-PA, tissue plasminogen activator; TNK, tenecteplase; UE, upper extremity, UK, urokinase. (From Segal JB, et al. Management of venous thromboembolism: a systematic review for a practice guideline. Ann Internal Med 2007;146:211-22. Reproduced with permission.) a Combined complication rates from treatment of arterial and venous occlusions. b Significant lysis is the sum of partial lysis and complete lysis.

International, Inc, Reading, PA). The Arrow-Trerotola PTD device acts as an “eggbeater” to physically macerate the clot; the macerated clot, ideally of very small particulate size, will pass centrally and be taken care of by the lungs. In contrast, the Angiojet physically removes clot by the Venturi effect, produced by a jet of high-velocity crystalloid solution. Treatment area for the Angiojet is obviously less than the Trerotola device, but this technique carries with it the advantage of physically removing the thrombus rather than sending it proximally within the body. Although experience is less with this device, the Trellis Peripheral Infusion System (Bacchus Vascular, Santa Clara, CA) potentially combines the benefits of both with very rapid treatment of the entire lesion in 1 sitting; if residual thrombus is present, tissue plasminogen activator can be infused, per protocol above, for a short period, but usually thrombus removal is complete. Factors limiting widespread use of percutaneous therapy are lack of prospective, randomized data, safety concerns of thrombolytic agents vs anticoagulation, cost of inpatient catheter-directed therapy vs outpatient 440

Curr Probl Cardiol, September 2009

TABLE 8. Continued Partial lysis, %

Complete lysis, %

SK: 39 AC: 0

SK: 61 AC: 0

26-50 t-PA: 29 UK: 47 (P ⫽ 0.59) 0 33 UE: NR LE: 50 NR 52 17 NR 20 33 NR NR 20

50-71 t-PA: 58 UK: 47 (P ⫽ 0.39) 92 50 UE: 59 LE: 40 73 31 NR 79 72 21 NR NR 80

Major bleeding, %

Minor bleeding, %

0

0

3-8 t-PA: 2b UK: 2b (P ⫽ 0.96) 4 2b 0

10-16 t-PA: 9b UK: 10a (P ⫽ 0.80) 0 7b 21

9 11 8 6 0 0 13 2

18 16 8 13

NR

NR 0 25 9 NR

anticoagulation, lack of awareness by primary care physicians that these techniques exist, and lack of an accepted reporting system and clinical benefit endpoint.367 Because postphlebitic syndrome is such a late complication, randomized clinical trials are difficult to perform, although the long-term financial impact and quality-of-life in patients with established postphlebitic syndrome are poor. May-Thurner Syndrome. Compression of the left common iliac vein by an overriding common iliac artery, as described by May and Thurner for the first time in 1956, may cause ipsilateral leg edema, pain, or deep-vein thrombosis368,369 and may be suspected when iliofemoral thrombosis occurs on the left side (Fig 30). Recently, Kim and colleagues370 described results of CDT and angioplasty with or without stenting of the compressed common iliac vein and found that angioplasty and stenting of the iliac vein resulted in reocclusion of the stent in 5% of patients, whereas angioplasty alone resulted in reocclusion in all patients. In another recent series of 11 patients, Husmann and colleagues371 reported a technical success rate of 100%, a Curr Probl Cardiol, September 2009

441

FIG 30. A 60-year-old male is admitted for severe left lower extremity pain and swelling after a transatlantic flight (A). Large clot in the left common iliac vein (LCIV) and the inferior vena cava (IVC) (B). Iliac vein stenosis (arrowhead) unmasked after thrombolysis and thrombectomy (C). Deployment of a self-expanding stent in the LCIV (arrowhead) which, however, remains underexpanded at the site of the stenosis (D). Post PTA showing fully expanded stent with good antegrade flow.

primary patency rate of 82%, and an assisted patency rate of 91% at 6 months, which remained unchanged over a mean follow-up of 22 months. Although long-term follow-up data remain sparse in this group of patients, current evidence suggests that stenting of the iliac vein following surgical CDT or surgical thrombectomy is feasible, reduces the risk of recurrent thrombosis, and is associated with a good patency rate and a favorable clinical outcome, reducing postthrombotic complications. Inferior Vena Cava Filters. Although, in most circumstances, VTE is effectively managed with conventional anticoagulation, with a low incidence of recurrent thrombotic events (0.6-1.5 events per 100 patient442

Curr Probl Cardiol, September 2009

years) and major bleeding during therapy (⬃0.9-4.6 events per 100 patient-years),372-374 vena-caval interruption has been in use for the treatment of DVT to prevent pulmonary embolism since the early 1970s (Mobin-Uddin umbrella filter). Since 1865, when Armand Trousseau first introduced the concept, vena-caval interruption evolved from surgical ligation of the inferior vena cava (IVC) to percutaneous intervention, with the recent introduction of retrievable filters. With these advances in technology, there has been a dramatic increase in the use of IVC filters (about 49,000 placed annually in the United States).375 Despite the vast number of reports on the use of IVC filters (over 500 English language clinical studies including 107 case series since 1973), only 1 randomized controlled trial measured their clinical efficacy.376,377 The case series data (outcomes of 9533 patients who received 1 of 9 different vena-caval filters) are severely limited by the absence of a control group, significant differences between studies in population characteristics, and the varying durations and completeness of follow-up. In these case series, most of the available filters have been seen to be roughly equivalent to one another but somewhat less effective than anticoagulation in the prevention of PE. Several recently released and/or less extensively studied filter models like Günther Tulip (Cook Medical, Inc, Bloomington, IN), vena Tech LP (B. Braun Medical, Inc, Bethlehem, PA), and TrapEase (Cordis, Corp, Warren, NJ) appear to have lower PE event rates.376 However, the small study populations, short follow-up durations, and wide 95% confidence intervals suggest that these estimates are fairly imprecise. Decousus and colleagues377 randomly assigned 400 patients with proximal DVT with or without PE (but judged to be at high risk for PE) to 2 treatment groups (vena cava filter group or no filter group) along with unfractionated heparin or enoxaparin, followed by a vitamin K antagonist. Four different types of permanent vena-caval filters were used: the VenaTech filter (56% of patients randomized to the filter group), the titanium Greenfield filter (Boston Scientific) (26.5%), the cardial filter (Bard, Saint Étienne, France—not available in this country), or the Gianturco-Roehm Bird’s Nest filter (Cook Medical, Inc) (15.5%). Pulmonary ventilation-perfusion scanning was performed within 48 hours of enrollment and again after 8 or 12 days if no symptomatic PE had occurred. After 12 days, filter recipients had significantly fewer total (symptomatic and asymptomatic) PEs than the group without filters (1.1% vs 4.8% P ⫽ 0.03). Filter placement, however, was not associated with a reduction in symptomatic PE. Eight years later, significantly fewer filter recipients had a symptomatic PE than patients without filters. However, Curr Probl Cardiol, September 2009

443

DVT was significantly more common among the patients in the filter group compared to the nonfilter group (20.8% vs 11.8% P ⫽ 0.02) and mortality was similar in both (21.6% vs no filter 20.1% P ⫽ 0.65). Only 35% of patients received vitamin K antagonists over the study period378 because, at the time this study was initiated, extended-duration anticoagulation was not used for patients at high risk for recurrence as often as it is today. These data indicate that filters, when used in conjunction with anticoagulation, offer a short-term reduction in the total number of symptomatic and asymptomatic PE, at the cost of a long-term increase in recurrent DVT without any reduction in mortality. In addition, this study provides no information about the effectiveness of filters for patients who do not receive early anticoagulation, the typical patient for whom filter placement is considered. White and colleagues,379 in a population-based observational study, identified patients with VTE who did and did not receive vena-caval filters between January 1991 and December 1995. After adjustment for risk factors associated with recurrent VTE, recipients of vena-caval filters were as likely as nonrecipients to be admitted for pulmonary embolism. Filter placement was associated with 2-fold increase in the risk of subsequent venous thrombosis, although interestingly, only among patients with an initial episode of PE. The time to recurrent PE was similar in filter recipients and nonrecipients. Among patients without a previous hospitalization for VTE treatment, mortality was higher for filter recipients than control patients (relative hazard ratio, 1.71 [CI, 1.55-1.88]). Because it is unlikely that filter placement alone is responsible for this mortality difference, it underscores the potential limitations of this type of analysis, that unidentified comorbidities may have been partially responsible for the inferior outcome of filter recipients. Despite this limitation, the White study provides valuable information that should be considered by any physician contemplating the use of a vena-caval filter for the treatment of VTE.376 In our opinion, vena-caval filters are a valuable treatment option for patients who cannot receive anticoagulation (eg, for patients in whom anticoagulation is contraindicated). In addition potential benefit may be accrued in patients with failure of adequate anticoagulation, thrombolysis of ileo-caval thrombus, pulmonary thromboembolectomy in patients with chronic thromboembolic pulmonary hypertension, and as prophylaxis in high-risk trauma patients where occurrence of DVT is high. Several other unsubstantiated indications exist (eg, cancer and COPD patients): those with poor cardiopulmonary reserve, pregnancy, organ transplant, and as a prophylactic measure in bariatric surgery patients and burn patients. Data 444

Curr Probl Cardiol, September 2009

on such indications are limited and, therefore, no firm recommendations are available. In some of these conditions, retrievable vena-caval filters (eg, Günther Tulip filter, the only 1 available in this country) would seem to be ideally suited to providing temporary protection until effective pharmacologic therapy could be initiated safely.

Upper Extremity Deep vein thrombosis of the upper extremity is an increasingly recognized condition and can progress to both venous gangrene and pulmonary embolism (7%-20%),380-384 with long-term sequelae of postphlebetic syndrome and functional disability. The common etiologies include the following: 1. Primary subclavian-axillary vein thrombosis (Paget-Schroetter syndrome) 2. Chronic intravenous indwelling central venous catheters 3. Pacemaker or defibrillator devices 4. Hypercoagulable states 5. Vasculitides 6. Fibrosing mediastinitis 7. Trauma (first rib and clavicular fractures) and recent chest/neck surgery 8. Mediastinal and thoracic malignancy and/or adenopathy Duplex ultrasound, venography, and contrast-enhanced computed tomography are the common modalities used for diagnosing the condition, while magnetic resonance venography is a new modality that can accurately determine the patency of central veins. Primary Subclavian Axillary Vein Thrombosis. This well-characterized clinical entity with over 14 variants, described by Roos,385 usually affects young individuals (10/100,000/y) and occurs most often (70%) in the dominant upper extremity after a period of unusual exercise or shoulder abduction. Also called thoracic outlet syndrome, thoracic inlet syndrome, effort thrombosis, Paget-Schroetter syndrome, and scalene anticus syndrome, its presenting symptoms include arm edema, venous congestion, pain, coldness, and cyanosis. In the absence of contraindications, patients presenting with acute or subacute vascular symptoms, with venographically documented axillary subclavian vein thrombosis, usually undergo early CDT with or without adjunctive percutaneous mechanical thrombectomy.323,325,386,387 Balloon angioplasty is best avoided because it is believed to have no role in relieving the extrinsic pinch of the subclavian vein in thoracic outlet syndrome, although occasionally it may Curr Probl Cardiol, September 2009

445

be useful when intraluminal venous scarring or residual organized thrombus, in addition to extrinsic compression, persists after thrombolytic therapy. Stent placement is not employed because persistent positional pinching can lead to compression, kinking, or fracture of the stent, with a high risk for recurrent thrombosis. Secondary Venous Thrombosis in the Upper Extremity and Central Veins. With an increasing number of patients requiring long-term intravenous instrumentation, secondary causes of upper extremity and central vein thrombosis are on the rise. These include long-term indwelling central venous catheters (hemodialysis, cancer patient, total parenteral nutrition, transfusions) and transvenous permanent pacemaker and defibrillator insertions. Virtually all types of secondary benign or malignant central venous obstructions (excluding primary extrinsic compression at the thoracic outlet) can be treated with the endovascular approach. When thrombosis is present, CDT and percutaneous mechanical thrombectomy techniques are used initially, and the underlying occlusive disease or organized thrombus is addressed with the placement of endovascular stents, preferably of the self-expanding variety. Despite the lack of large-scale prospective studies, several of the published series on endovascular treatment of central venous obstruction, particularly superior vena cava (SVC) obstruction, report dramatic improvement in patient symptoms in addition to a low rate of complications and a good long-term patency rate.388,389 In the setting of central venous thrombosis complicating a chronic indwelling catheter, it is a common practice to have the catheter removed, a practice that can lead to the loss of a valuable vascular access route. In most patients, catheters in place to treat an underlying occlusive lesion do not have to be removed; CDT and subsequent stent placement can be accomplished by repositioning the catheter using a variety of in situ maneuvers.390 Even in cases of pacemaker-associated central venous stenosis, stent placement over the pacemaker leads can be safely undertaken.391

Superior Vena Cava Syndrome SVC syndrome is usually a clinical diagnosis, with the patient presenting with classic signs and symptoms of engorged conjunctivae, cyanosis, severe headache, visual disturbance, and dilated neck, arm, and chest-wall veins. Contrast-enhanced CT, with multiplanar reformatting, allows accurate diagnosis and can show the extent, level, and cause of SVC obstruction. The presence of dilated collateral vessels is highly suggestive of SVC obstruction, with a sensitivity of 96% and a specificity of 92%.392-394 Magnetic resonance venography is an alternative investiga446

Curr Probl Cardiol, September 2009

tive tool that is useful in assessing the large central veins, with a 100% sensitivity, specificity, and accuracy level.395,396 Malignancy is the most common etiology for SVC syndrome, although a recent report suggests that benign etiologies may now comprise up to 40% of cases.397 Besides malignancy, intravascular devices (long-term indwelling central venous catheters, pacing wires, etc), fibrosing mediastinitis, infection, sarcoidosis, radiation therapy,398 and, occasionally, hypercoagulable states, also are known to cause SVC syndrome. Endovascular placement of a percutaneous stent (Fig 31) is currently a premier option to relieve symptoms in most patients with SVC syndrome of both the benign and the malignant varieties, given its proven efficacy, low complication and good patency rate,388 and the fact that it does not affect delivery of radiotherapy or chemotherapy in cases when SVC syndrome is due to a malignant etiology. The complication rate is low and the patency rate is high for this procedure. Since the first description by Charnsangavej et al of the use of an endoprosthesis to treat obstruction of the vena cava in dogs,399 numerous reports have supported the role of catheter-related thrombolysis, balloon angioplasty, and stenting for treatment of this syndrome.400-406 Mathias et al reported a series of 176 patients who had malignant obstruction of the SVC and were treated primarily with balloon dilation and stent placement.400 Twenty-seven of these patients needed adjunctive catheterdirected thrombolysis. Technical success was achieved in 97% of procedures with no major complications; resolution of symptoms was almost immediate in nearly all treated patients. In a more recent series407 of 70 consecutive patients undergoing treatment for benign SVC syndrome, endovascular repair (EVR) was attempted in 32 patients and was successful in 28 (88%); 19 had stenting, 14 had PTA, and 2 had thrombolytic therapy with PTA. Periprocedural morbidity was 19% after open surgical reconstruction (OSR) and 4% in the EVR group. A recent systematic review402 of different treatment options for SVC obstruction in patients with lung cancer found that endovascular stenting improved symptoms in 95% of cases; 11% of patients relapsed, usually because of thrombosis or tumor in-growth in the stent. This is superior to chemotherapy and radiotherapy, which have response rates of 84% and 78% and relapse rates of 17% and 19% for small-cell lung cancer and nonsmall-cell lung cancer, respectively. Endovascular stenting usually relieves symptoms within 0-72 hours, whereas chemotherapy or radiotherapy can take up to 2 weeks; therefore, early stenting is advised for rapid relief of symptoms.403-405 Although tumor in-growth or thrombosis can occur, most patients with Curr Probl Cardiol, September 2009

447

FIG 31. A 60-year-old female with lung cancer and SVC syndrome (A and B). Superior vena cava (SVC) syndrome secondary to external compression of bilateral innominate veins and the SVC (C and D) after percutaneous intervention using 2 self-expanding SMART Control stents deployed in a kissing manner extending into the innominate veins.

SVC obstruction from malignancy have a short life expectancy and the stent remains patent until death. Stent thrombosis rates are low324,406 and can be treated with thromboaspiration, thrombolysis, or further stent insertion; secondary patency rates are good.402,407 Endovascular treatment with stent placement has also been shown to be a highly effective and safe approach in cases of SVC syndrome resulting from benign causes.324,408-412 448

Curr Probl Cardiol, September 2009

In cases of superimposed thrombosis with SVC syndrome, pharmacothrombolytic therapy and/or percutaneous mechanical thrombectomy are initially performed and are usually followed by balloon angioplasty and stent placement of the underlying occlusive pathology. Endovascular treatment is the preferred therapy for SVC syndrome of a benign etiology, given the efficacy and safety of this approach, the lack of effective medical therapeutic alternatives, and the high morbidity rate of surgical alternatives.

ACCP Guidelines Relating to DVT and IVC Filters 1. Catheter-directed thrombolysis for acute DVT a. Selected patients with extensive acute proximal DVT (eg, iliofemoral DVT, symptoms for ⬍ 14 days, good functional status, and life expectancy of ⬎ 1 year) who have a low risk of bleeding, to reduce acute symptoms and postthrombotic morbidity if appropriate expertise and resources are available (grade 2B). b. After successful catheter-directed thrombolysis in patients with acute DVT, correction of underlying venous lesions using balloon angioplasty and stents is suggested (grade 2C). c. Pharmacomechanical thrombolysis (eg, with inclusion of thrombus fragmentation and/or aspiration), in preference to catheter-directed thrombolysis alone, is suggested to shorten treatment time if appropriate expertise and resources are available (grade 2C). d. After successful catheter-directed thrombolysis in patients with acute DVT, the same intensity and duration of anticoagulant therapy as for comparable patients who do not undergo catheterdirected thrombolysis is recommended (grade 1C). 2. Vena-caval filters for the initial treatment of DVT a. For patients with DVT, the college recommends against the routine use of a vena cava filter in addition to anticoagulants (grade 1A). b. For patients with acute proximal DVT, if anticoagulant therapy is not possible because of the risk of bleeding, an inferior vena cava filter is recommended (grade 1C). c. For patients with acute DVT who have an inferior vena cava filter inserted as an alternative to anticoagulation, it is recommended that they should subsequently receive a conventional course of anticoagulant therapy if their risk of bleeding resolves (grade 1C).

Grading Grade 1. If benefits do or do not outweigh risks, burden, and costs, a strong recommendation is designated as grade 1. Curr Probl Cardiol, September 2009

449

Grade 2. If there is less certainty about the magnitude of the benefits and risks, burden, and costs, a weaker grade 2 recommendation is made. Support for these recommendations may come from high-quality, moderate-quality, or low-quality evidence labeled, respectively, A, B, and C. The phrase “recommend” is used for strong recommendations (grade 1A, 1B, 1C) and “suggest” for weaker recommendations (2A, 2B, 2C).

Conclusions Endovascular therapy for both occlusive and aneurysmal disease has revolutionized the treatment of peripheral artery disease. Stents have become the default strategy in most endovascular interventions because of the excellent immediate results and durable long-term patency. In the recent past, vascular surgery (the only available treatment for severe peripheral vascular disease) was frequently postponed until rest pain or gangrene forced the issue. The risks of morbidity and death from vascular surgery were simply too high to justify intervening earlier to help patients who had claudication. The consequences of this benign neglect ranged from lifestyle-limiting infirmity to severe ischemia that left no choice but amputation if the patient’s life was to be saved. When considering our treatment options (percutaneous revascularization, conservative medical treatment, or surgical revascularization), we need to judiciously evaluate the scope of the problem in light of the standard question: “Does the benefit of this procedure outweigh the risk?” In answering this question, it is encouraging that the risk related to endovascular intervention is much lower and our expectation of benefits higher for so many patients who a decade ago would have been considered ineligible. At our institution, we triage patients who present with PVD into (1) those who have claudication and (2) those who have rest pain and ischemic ulceration. (Regardless of how they are categorized, all patients are thoroughly evaluated to rule out CAD by cardiac angiography or pharmacologic stress testing.) In all the above patients, an aggressive risk-factor modification, an exercise program, and foot care, with referral to a podiatrist if needed, is absolutely essential. As PAD is a progressive disease, with significant risk of limb loss, high-risk patients, especially diabetics, smokers, those with pain at rest, and ischemic ulceration, are treated immediately, beginning with angiography, so that pulsatile flow is re-established either by endovascular treatment or by surgical bypass. For the low-risk group of patients presenting only with symptoms of claudication, the key consideration is the extent to which their symptoms limit their lifestyle and/or impair their 450

Curr Probl Cardiol, September 2009

ability to earn a living. If there are no significant limitations in either regard, patients are treated with an exercise program, coronary artery disease risk factor modification, and medications for relief of symptoms. By contrast, a limitation in either sphere of activity makes endovascular treatment an attractive choice. In patients suspected of having renal artery stenosis (difficult to control blood pressure, worsening of renal function or recurrent congestive heart failure with no other obvious reason), we recommend proceeding to renal angiography followed by angioplasty and stenting. Recently, the FDA approved covered stents (VIABAHN) for treatment of severe occlusive disease of the superficial femoral artery. This has improved the long-term patency of SFA intervention. Lower profile covered stents, coated with heparin, may improve short-term and longterm results significantly. For high-risk patients with carotid disease, carotid artery stenting with embolic protection device is the treatment of choice. For low-risk patients with carotid disease, carotid endarterectomy is still the treatment of choice, pending results of ongoing trials. For patients with aneurysmal disease involving the infrarenal or descending thoracic aorta, or the popliteal, iliac, and/or visceral arteries, endovascular repair has become the treatment of choice. It offers patients a minimally invasive alternative to major surgical procedures at a much lower risk and a shorter hospital stay. Soon, with the availability of fenestrated stent-grafts, we may be able to treat aneurysms of the ascending aorta, aortic arch, and suprarenal aorta. Endovascular treatment has now established itself as the first choice for treatment of peripheral arterial disease. We hope this monograph helps you to understand the natural history of peripheral arterial disease and give you up-to-date treatment options for your patients.

D.R. Holmes: The authors present a very up-to-date review of a very large field, which includes peripheral arterial as well as carotid arterial disease, and includes stenotic disease as well as aneurysmal disease. It is exhaustively referenced and can serve as an excellent compendium on extremely important groups of patients and diseases.

Acknowledgments The authors gratefully acknowledge Barbara Danek for the editorial preparation of the manuscript, Chris Martin and Joe Grundle for proofreading, and Brian Miller and Brian Schurrer for help in preparing illustrations. Curr Probl Cardiol, September 2009

451

REFERENCES 1. Diehm C, Schuster A, Allenberg JR, et al. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: Cross-sectional study. Atherosclerosis 2004;172:95-105. 2. Zheng ZJ, Sharrett AR, Chambless LE, et al. Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: The atherosclerosis risk in communities (ARIC) study. Atherosclerosis 1997;131:115-25. 3. Fowkes FGR, Housley E, Cawood EHH, et al. for the Edinburgh Artery Study. Prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol 1991;20:384-92. 4. Newman AB, Sutton-Tyrrell K, Rutan GH, et al. Lower extremity arterial disease in elderly subjects with systolic hypertension. J Clin Epidemiol 1991;44:15-20. 5. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381-6. 6. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology, Society for Vascular Medicine and Biology and The American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients with Peripheral Arterial Disease). J Am Coll Cardiol 2006;47:1239-312. 7. Newman AB, Shemanski L, Manolio TA, et al. Ankle-arm index as a predictor of cardiovascular disease and mortality in the cardiovascular health study. Arterioscler Thromb Vasc Biol 1999;19:538-45. 8. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (Caprie). Lancet 1996;348:1329-39. 9. Baumgartner I, Hirsch AT, Abola TB, et al. Cardiovascular risk profile and outcome of patients with abdominal aortic aneurysm in out-patients with atherothrombosis: Data from the Reduction Of Atherothrombosis For Continued Health (REACH) Registry. J Vasc Surg 2008;48:808-13. 10. Fowkes FG, Low LP, Tuta S, et al. for the AGATHA Investigators. Ankle brachial index and the extent of atherothrombosis in 8891 patients with or at risk of vascular disease: Results of the international AGATHA study. Eur Heart J 2006;27:1861-7. 11. Criqui MH, Denenberg JO, Langer RD, et al. The epidemiology of peripheral arterial disease: Importance of identifying the population at risk. Vasc Med 1997; 2:221-6. 12. Price JF, Mowbray PI, Lee AJ, et al. Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh artery study. Eur Heart J 1999;20:344-53. 13. Barani J, Nilsson JA, Matiasson I, et al. Inflammatory mediators are associated with 1-year mortality in critical limb ischemia. J Vasc Surg 2005;42:75-80. 14. McDermott MM, Greenland P, Guralnik JM, et al. Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease. J Gen Intern Med 2003;18:461-7. 452

Curr Probl Cardiol, September 2009

15. McDermott MM, Liu K, Greenland P, et al. Functional decline in peripheral arterial disease: Associations with the ankle brachial index and leg symptoms. J Am Med Assoc 2004;292:453-61. 16. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. J Am Med Assoc 2001; 286:1317-24. 17. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45(suppl):S5-67. 18. Dormandy JA, Murray GD. The fate of the claudicant: A prospective study of 1969 claudicants. Eur J Vasc Surg 1991;5:131-3. 19. Jelnes R, Gaardsting O, Hougaard Jensen K, et al. Fate in intermittent claudication: Outcome and risk factors. Br Med J 1986;293:1137-40. 20. Belch JJ, Topol EJ, Agnelli G, et al. Prevention of Atherothrombotic Disease Network. Critical issues in peripheral arterial disease detection and management: A call to action. Arch Intern Med 2003;163:884-92. 21. Dormandy JA, Heeck L, Vig S. The fate of patients with critical leg ischemia. Semin Vasc Surg 1999;12:142-7. 22. DeGowin R, DeGowin E. The blood vessels/circulation of limbs. In: DeGowin, EL, DeGowin, RL, editors. DeGowin And DeGowin’S Bedside Diagnostic Examination, 5th edition. New York, NY: Macmillan, 1987. p. 415-66. 23. Woods BO. Clinical evaluation of the peripheral vasculature. Cardiol Clin 1991;9:413-27. 24. Ouriel K, McDonnell AE, Metz CE, et al. Critical evaluation of stress testing in the diagnosis of peripheral vascular disease. Surgery 1982;91:686-93. 25. Baxter GM, Polak JF. Lower limb colour flow imaging: A comparison with ankle: Brachial measurements and angiography. Clin Radiol 1993;47:91-5. 26. Doobay AV, Anand SS. Sensitivity and specificity of the ankle-brachial index to predict future cardiovascular outcomes: A systematic review. Arterioscler Thromb Vasc Biol 2005;25:1463-9. 27. Newman AB, Siscovick DS, Manolio TA, et al; Cardiovascular Health Study (CHS) Collaborative Research Group. Ankle-arm index as a marker of atherosclerosis in the cardiovascular health study. Circulation 1993;88:837-45. 28. Sumner DS, Strandness DE, Jr.The relationship between calf blood flow and ankle blood pressure in patients with intermittent claudication. Surgery 1969;65:763-71. 29. Olin JW. Clinical evaluation and office-based detection of peripheral arterial disease. Society for Vascular Medicine and Biology and Society for Vascular Nursing. Peripheral Arterial Disease: Marker of Cardiovascular Risk. Manchester, Mass: SVMB/SVM; 1999. http://www.svmb.org/medpro/cme/pl/cme_partl.html (accessed November 2, 2000). 30. Sacks D, Bakal CW, Beatty PT, et al. Position statement on the use of the ankle-brachial index in the evaluation of patients with peripheral vascular disease: A consensus statement developed by the standards division of the Society of Cardiovascular and Interventional Radiology. J Vasc Interv Radiol 2002;13:353. 31. Resnick HE, Lindsay RS, McDermott MM, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: The strong heart study. Circulation 2004;109:733-9. 32. Collins R, Armitage J, Parish S, et al. for the Heart Protection Study Collaborative Curr Probl Cardiol, September 2009

453

33.

34.

35. 36. 37.

38.

39.

40.

41. 42. 43. 44. 45. 46.

47.

48. 49. 50.

454

Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 2002;360:7-22. Feringa HH, Karagiannis SE, van Waning VH, et al. The effect of intensified lipid-lowering therapy on long-term prognosis in patients with peripheral arterial disease. J Vasc Surg 2007;45:936-43. Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 2003;107:1848-51. Schillinger M, Exner M, Mlekusch W, et al. Statin therapy improves cardiovascular outcome of patients with peripheral artery disease. Eur Heart J 2004;25:742-8. Gardner AW, Poehlman ET. Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. J Am Med Assoc 1995;274:975-80. Hood SC, Moher D, Barber GG. Management of intermittent claudication with pentoxifylline: Meta-analysis of randomized controlled trials. CMAJ 1996;155: 1053. Regensteiner JG, Ware JE Jr, McCarthy WJ, et al. Effect of cilostazol on treadmill walking, community based walking ability and health related quality of life in patients with intermittent claudication due to peripheral arterial disease: Metaanalysis of six randomized controlled trials. J Am Geriatr Soc 2002;50:1939-46. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-53. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study (ACAS). Endarterectomy for asymptomatic carotid artery stenosis. J Am Med Assoc 1995;273:1421-8. Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy. AHA scientific statement. Circulation 1998;97:501-9. Yadav JS, Roubin GS, Iyer S, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997;95:376-81. Wholey MH, Wholey M, Mathias K, et al. Global experience in cervical carotid artery stent placement. Catheter Cardiovasc Interv 2000;50:160-7. Lin PH, Bush RL, Peden EK, et al. Carotid artery stenting with neuroprotection: Assessing the learning curve and treatment outcome. Am J Surg 2005;190:850-7. Mathias KD. Angioplasty and stenting for carotid lesions. Adv Surg 2002; 32:225-43. Cremonesi A, Manetti R, Setacci F, et al. Protected carotid stenting: Clinical advantages and complications of embolic protection devices in 442 consecutive patients. Stroke 2003;34:1936-41. Ribo M, Molina CA, Alvarez B, et al. Transcranial Doppler monitoring of transcervical carotid stenting with flow reversal protection: A novel carotid revascularization technique. Stroke 2006;37:2846-9. Ohki T. The dark side of embolic protection devices. Endovasc Today 2003;9: 111-9. Reimers B, Corvaja N, Moshiri S, et al. Cerebral protection with filter devices during carotid artery stenting. Circulation 2001;104:12-5. Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004;351:1493-501. Curr Probl Cardiol, September 2009

51. Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008;358:1572-9. 52. Harjai KJ, Mehta RH. Trials and tribulations of carotid artery stenting: The interventionalists’ perspective on sapphire, EVA-3S, and SPACE trials. J Interv Cardiol 2007;20:389-94. 53. Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006;355:1660-71. 54. Mas JL, Trinquart L, Leys D, et al. Endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis (EVA-3S) trial: Results up to 4 years from a randomized, multicenter trial. Lancet Neurol 2008;7:885-92. 55. Ringleb PA, Allenberg J, Berger J, et al. for the SPACE Collaborative Group. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: A randomised non-inferiority trial. Lancet 2006;368: 1239-47. 56. Eckstein HH, Ringleb P, Allenberg JR, et al. Results of the stent-protected angioplasty versus carotid endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: A multinational, prospective, randomised trial. Lancet Neurol 2008;7:893-902. 57. Roubin GS, Iyer S, Halkin A, et al. Realizing the potential of carotid artery stenting: Proposed paradigms for patient selection and procedural technique. Circulation 2006;113:2021-30. 58. Peel G, Wholey MH, Hagino RT, et al. Percutaneous carotid artery intervention: A word of caution about mixing stent/filter systems. J Endovasc Ther 2007; 14:110-2. 59. Markus HS, Droste DW, Kaps M, et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: The clopidogrel and aspirin for reduction of emboli in symptomatic carotid stenosis (caress) trial. Circulation 2005;111:2233-40. 60. White CJ, Iyer SS, Hopkins LN, et al; BEACH Trial Investigators. Carotid stenting with distal protection in high surgical risk patients: The BEACH trial 30 day results. Catheter Cardiovasc Interv 2006;67:503-12. 61. Iyer SS, White CJ, Hopkins LN, et al. Carotid artery revascularization in high-surgical-risk patients using the carotid WALLSTENT and FilterWire ex/EZ: 1-year outcomes in the BEACH pivotal group. J Am Coll Cardiol 2008;51:427-34. 62. White RA, Diethrich E, Fogarty TJ, et al. for the CaRESS Steering Committee. Carotid revascularization using endarterectomy or stenting systems (CaRESS) Phase I clinical trial: 1-year results. J Vasc Surg 2005;42:213-9. 63. Sugita J, Cremonesi A, Van Elst F, et al. European carotid PROCAR trial: Prospective multicenter trial to evaluate the safety and performance of the ev3 protégé stent in the treatment of carotid artery stenosis—1- and 6-month follow-up. J Interv Cardiol 2006;19:215-21. 64. Gray WA, Yadav JS, Verta P, et al. The CAPTURE registry: Results of carotid stenting with embolic protection in the post approval setting. J Vasc Surg 2005; 42:213-9. 65. Gray WA, Yadav JS, Verta P, et al. The CAPTURE registry: Results of carotid stenting with embolic protection in the post approval setting. Catheter Cardiovasc Interv 2007;69:341-8. Curr Probl Cardiol, September 2009

455

66. Safian RD, Bresnahan JF, Jaff MR, et al. Protected carotid stenting in high-risk patients with severe carotid artery stenosis. J Am Coll Cardiol 2006;47:2384-9. 67. Katzen BT, Criado FJ, Ramee SR, et al. Carotid artery stenting with emboli protection surveillance study: Thirty-day results of the CASES-PMS study. Catheter Cardiovasc Interv 2007;70:316-23. 68. Berguer R, Flynn LM, Kline RA, et al. Surgical reconstruction of the extracranial vertebral artery: Management and outcome. J Vasc Surg 2000;31:9-18. 69. Jenkins JS, White CJ, Ramee SR, et al. Vertebral artery stenting. Catheter Cardiovasc Interv 2001;54:1-5. 70. Malek AM, Higashida RT, Phatouros CC, et al. Treatment of posterior circulation ischemia with extracranial percutaneous balloon angioplasty and stent placement. Stroke 1999;30:2073-85. 71. Beebe HG, Stark R, Johnson ML, et al. Choices of operation for subclavian vertebral arterial disease. Am J Surg 1980;139:616-23. 72. Hadjipetrou P, Cox S, Piemonte T, et al. Percutaneous revascularization of atherosclerotic obstruction of aortic arch vessels. J Am Coll Cardiol 1999; 33:1238-45. 73. Rodriguez-Lopez JA, Werner A, Martinez R, et al. Stenting for atherosclerotic occlusive disease of the subclavian artery. Ann Vasc Surg 1999;13:254-60. 74. Al-Mubarak N, Liu MW, Dean LS, et al. Immediate and late outcomes of subclavian artery stenting. Catheter Cardiovasc Interv 1999;46:169-72. 75. Jain SP, Zhang SY, Khosla S, et al. Subclavian and innominate arteries stenting: Acute and long term results. J Am Coll Cardiol 1998;31:63A. 76. Jean WJ, Al-bitar I, Zwicke DL, et al. High incidence of renal artery stenosis in patients with coronary artery disease. Catheter Cardiovasc Interv 1994;32:8-10. 77. Weber-Mzell D, Kotanko P, Schumacher M, et al. Coronary anatomy predicts presence or absence of renal artery stenosis. A prospective study in patients undergoing cardiac catheterization for suspected coronary artery disease. Eur Heart J 2002;23:1684-91. 78. Buller CE, Nogareda JG, Ramanathan K, et al. The profile of cardiac patients with renal artery stenosis. J Am Coll Cardiol 2004;43:1606-13. 79. Caps MT, Perissinotto C, Zierler RE, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation 1998;98:2866-72. 80. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int 1998;53:735-42. 81. Hansen KJ, Starr SM, Sands RE, et al. Contemporary surgical management of renovascular disease. J Vasc Surg 1991;16:319-31. 82. Textor SC. Renovascular hypertension in 2007: Where are we now? Curr Cardiol Rep 2007;9:453-61. 83. Welch WJ, Mendonca M, Aslam S, et al. Roles of oxidative stress and AT1 receptors in renal hemodynamics and oxygenation in the postclipped 2K,1C kidney. Hypertension 2003;41:692-6. 84. Parildar M, Parildar Z, Oran I, et al. Nitric oxide and oxidative stress in atherosclerotic renovascular hypertension: Effects of endovascular treatment. J Vasc Interv Radiol 2003;14:887-92. 85. Balk E, Raman G, Chung M, et al. Effectiveness of management strategies for renal artery stenosis: A systematic review. Ann Intern Med 2006;145:901-12. 456

Curr Probl Cardiol, September 2009

86. Silva JA, Chan AW, White CJ, et al. Elevated brain natriuretic peptide predicts blood pressure response after stent revascularization in patients with renal artery stenosis. Circulation 2005;111:328-33. 87. Mitchell JA, Subramanian R, White CJ, et al. Predicting blood pressure improvement in hypertensive patients after renal artery stent placement: Renal fractional flow reserve. Catheter Cardiovasc Interv 2007;69:685-9. 88. Kidney D, Deutsch LS. The indications and results of percutaneous transluminal angioplasty and stenting in renal artery stenosis. Semin Vasc Surg 1996;9:188-97. 89. Lederman RJ, Mendelsohn FO, Santos R, et al. Primary renal artery stenting: Characteristics and outcomes after 363 procedures. Am Heart J 2001;142:314-23. 90. Burket MW, Cooper CJ, Kennedy DJ, et al. Renal artery angioplasty and stent placement: Predictors of a favorable outcome. Am Heart J 2000;139:64-71. 91. Rodriguez-Lopez JA, Werner A, Ray LI, et al. Renal artery stenosis treated with stent deployment: Indications, technique, and outcome for 108 patients. J Vasc Surg 1999;29:617-24. 92. Rocha-Singh KJ, Mishkel G, Katholi RE, et al. Clinical predictors of improved long-term blood pressure control after successful stenting of hypertensive patients with obstructive renal artery atherosclerosis. Catheter Cardiovasc Interv 1999; 47:167-72. 93. Dorros G, Jaff M, Mathiak L, et al. Four-year follow-up of Palmaz-Schatz Stent revascularization as treatment for atherosclerotic renal artery stenosis. Circulation 1998;98:642-47. 94. White CJ, Ramee SR, Collins TJ, et al. Renal artery stent placement: Utility in lesions difficult to treat with balloon angioplasty. J Am Coll Cardiol 1997; 30:1445-50. 95. Allaqaband S, Shaikh F, Zaidi S, et al. Blood pressure control after renal artery stenting in 100 consecutive hypertensive patients with atherosclerotic renal artery stenosis. Am J Cardiol 2003;92:53L. 96. Dorros G, Jaff M, Mathiak L, et al. Multicenter PALMAZ stent renal artery stenosis revascularization registry report: Four-year follow-up of 1058 successful patients. Catheter Cardiovasc Interv 2002;55:182-8. 97. Rocha-Singh K, Jaff MR, Rosenfield K. Aspire-2 Trial Investigators. evaluation of the safety and effectiveness of renal artery stenting after unsuccessful balloon angioplasty: The aspire-2 study. J Am Coll Cardiol 2005;46:776-83. 98. Mistry S, Ives N, Harding J, et al. Angioplasty and stent for renal artery lesions (ASTRAL trial): Rationale, methods, and results so far. J Hum Hypertens 2007; 21:511-5. 99. Rocha-Singh K, Jaff MR, Kelley EL, et al. Renal artery stenting with noninvasive duplex ultrasound follow-up: 3-year results from the RENAISSANCE renal stent trial. Catheter Cardiovasc Interv 2008;72:853-62. 100. Cooper CJ, Murphy TP, Matsumoto A, et al. Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: Rationale and design of the CORAL trial. Am Heart J 2006;152:59-66. 101. Dubel GJ, Murphy TP. Distal embolic protection for renal arterial interventions. Cardiovasc Interv Radiol 2008;31:14-22. 102. Cooper CJ, Haller ST, Coyler W, et al. Embolic protection and platelet inhibition during renal artery stenting. Circulation 2008;117:2752-60. Curr Probl Cardiol, September 2009

457

103. Holden A, Hill A, Jaff MR, et al. renal artery stent revascularization with embolic protection in patients with ischemic nephropathy. Kidney Int 2006;70:948-55. 104. Edwards MS, Craven BL, Stafford J, et al. Distal embolic protection during renal artery angioplasty and stenting. J Vasc Surg 2006;44:128-35. 105. Kougias P, El Sayed HF, Zhow W, et al. Management of chronic mesenteric ischemia. The role of endovascular therapy. J Endovasc Ther 2007;14:395-405. 106. Herbert GS, Steele SR. Acute and chronic mesenteric ischemia. Surg Clin North Am 2007;87:1115-34. 107. Acosta S, Ogren M, Sternby NH, et al. Fatal nonocclusive mesenteric ischaemia: Population-based incidence and risk factors. J Intern Med 2006;259(3):305-13. 108. Park WM, Cherry KJ, Chua HK, et al. Current results of open revascularization for chronic mesenteric ischemia: A standard for comparison. J Vasc Surg 2002;35: 853-9. 109. Sarac TP, Altinel O, Kashyap V, et al. Endovascular treatment of stenotic and occluded visceral arteries for chronic mesenteric ischemia. J Vasc Surg 2008; 47:485-91. 110. Silva JA, White CJ, Collins TJ, et al. Endovascular therapy for chronic mesenteric ischemia. J Am Coll Cardiol 2006;47:944-50. 111. Brown DJ, Schermerhorn ML, Powell RJ, et al. Mesenteric stenting for chronic mesenteric ischemia. J Vasc Surg 2005;42:268-74. 112. Landis MS, Rajan DK, Simons ME, et al. Percutaneous management of chronic mesenteric ischemia: Outcomes after intervention. J Vasc Interv Radiol 2005; 16:1319-25. 113. Saeed A, Saeed A, Solis J, et al. Longevity of superior mesenteric artery stents[abstract]. JACC Cardiovascular Interventions 2009 (in press). 114. Sivamurthy N, Rhodes JM, Lee D, et al. Endovascular versus open mesenteric revascularization: Immediate benefits do not equate with short-term functional outcomes. J Am Coll Surg 2006;202:859-67. 115. Lim RP, Dowling RJ, Thomson KR. Angioplasty and stenting of the superior mesenteric in acute mesenteric ischemia. Australas Radiol 2004;48:426-9. 116. de Vries SO, Hunink MG. Results of aortic bifurcation grafts for aortoiliac occlusive disease: A meta-analysis. J Vasc Surg 1997;26:558-69. 117. Bosch JL, Hunink MG. Meta-analysis of the results of percutaneous transluminal angioplasty and stent placement for aortoiliac occlusive disease. Radiology 1997; 204:87-96. 118. d’Othee BJ, Haulon S, Mounier-Vehier C, et al. Percutaneous endovascular treatment for stenoses and occlusions of infrarenal aorta and aortoiliac bifurcation: Midterm results. Eur J Vasc Endovasc Surg 2002;24:516-23. 119. Greiner A, Dessl A, Klein-Weigel P, et al. Kissing stents for treatment of complex aortoiliac disease. Eur J Vasc Endovasc Surg 2003;26:161-5. 120. Greiner A, Muhlthaler H, Neuhauser B, et al. Does stent overlap influence the patency rate of aortoiliac kissing stents? J Endovasc Ther 2005;12:696-703. 121. Houston JG, Bhat R, Ross R, et al. Long-term results after placement of aortic bifurcation self-expanding stents: 10 year mortality, stent restenosis, and distal disease progression. Cardiovasc Interv Radiol 2007;30:42-7. 122. Maynar M, Zander T, Qian Z, et al. Bifurcated endoprosthesis for treatment of aortoiliac occlusive lesions. J Endovasc Ther 2005;12:22-7. 458

Curr Probl Cardiol, September 2009

123. Mendelsohn FO, Santos RM, Crowley JJ, et al. Kissing stents in the aortic bifurcation. Am Heart J 1998;136:600-5. 124. Mohamed F, Sarkar B, Timmons G, et al. Outcome of “Kissing stents” for aortoiliac atherosclerotic disease, including the effect on the non-diseased contralateral iliac limb. Cardiovasc Interv Radiol 2002;25:472-5. 125. Piffaretti G, Tozzi M, Lomazzi C, et al. Mid-term results of endovascular reconstruction for aorto-iliac obstructive disease. Int Angiol 2007;26(1):18-25. 126. Scheinert D, Schroder M, Balzer JO, et al. Stent-supported reconstruction of the aortoiliac bifurcation with the kissing balloon technique. Circulation 1999;100(19) (suppl):II295-300. 127. Yilmaz S, Sindel T, Golbasi I, et al. Aortoiliac kissing stents: Long-term results and analysis of risk factors affecting patency. J Endovasc Ther 2006;13: 291-301. 128. Mouanoutoua M, Maddikunta R, Allaqaband S, et al. Endovascular intervention of aortoiliac occlusive disease in high-risk patients using the kissing stents technique: Long-term results. Catheter Cardiovasc Interv 2003;60:320-6. 129. Ameli FM, Stein M, Provan JL, et al. Predictors of surgical outcome in patients undergoing aortobifemoral bypass reconstruction. J Cardiovasc Surg 1990;30: 333-9. 130. Johnston KW, Rae M, Hogg-Johnston SA, et al. 5-Year results of a prospective study of percutaneous transluminal angioplasty. Ann Surg 1987;206:403-13. 131. Vorwerk D, Günther RW, Schürmann K, et al. Primary stent placement for chronic iliac artery occlusions: Follow-up results in 103 patients. Radiology 1995;194: 745-9. 132. Vorwerk D, Günther RW, Schürmann K, et al. Aortic and iliac stenoses: Follow-up results of stent placement after insufficient balloon angioplasty in 118 cases. Radiology 1996;198:45-8. 133. Palmaz JC, Laborde JC, Rivera FJ, et al. Stenting of the iliac arteries with the Palmaz stent: Experience from a multicenter trial. Cardiovasc Interv Radiol 1992;15:291-7. 134. Scheinert D, Schröder M, Ludwig J, et al. Stent-supported recanalization of chronic iliac artery occlusions. Am J Med 2001;110:708-15. 135. Timaran CH, Ohki T, Gargiulo NJ, et al. Iliac artery stenting in patients with poor distal runoff: Influences of concomitant infrainguinal arterial reconstruction. J Vasc Surg 2003;38:479-84. 136. Wilson SE, Wolf GL, Cross AP. Percutaneous transluminal angioplasty versus operation for peripheral arteriosclerosis: Report of a prospective randomized trial in a selected group of patients. J Vasc Surg 1989;9:1-9. 137. Holm J, Arfvidsson B, Jivegard L, et al. Chronic lower limb ischaemia: A prospective randomised controlled study comparing the 1-year results of vascular surgery and percutaneous transluminal angioplasty (PTA). Eur J Vasc Surg 1991; 5:517-22. 138. Murphy TP, Ariaratnam NS, Carney WI Jr, et al. Aortoiliac insufficiency: Long-term experience with stent placement for treatment. Radiology 2004;231: 243-9. 139. Park KB, Do YS, Kim JH, et al. Stent placement for chronic iliac arterial occlusive disease: The results of 10 years experience in a single institution. Korean J Radiol 2005;6:256-66. Curr Probl Cardiol, September 2009

459

140. Henry M, Amor M, Ethevenot G, et al. Palmaz stent placement in iliac and femoropopliteal arteries: Primary and secondary patency in 310 patients with 2-4-year follow-up. Radiology 1995;197:167-74. 141. Ponec D, Jaff MR, Swischuk J, et al; CRISP Study Investigators. The nitinol SMART stent vs Wallstent for suboptimal iliac artery angioplasty: CRISP-US trial results. J Vasc Interv Radiol 2004;15:911-8. 142. Wolf GL, Wilson SE, Cross AP, et al. Surgery or balloon angioplasty for peripheral vascular disease: A randomized clinical trial. Principal investigators and their Associates of Veterans Administration cooperative Study Number 199. J Vasc Interv Radiol 1993;4:639-48. 143. Adam DJ, Beard JD, Cleveland T, et al. BASIL trial participants. bypass versus angioplasty in severe ischaemia of the leg (BASIL): Multicenter, randomszed controlled trial. Lancet 2005;366:1925-34. 144. Springhorn ME, Kinney M, Littooy FN, et al. Inflow atherosclerotic disease localized to the common femoral artery: Treatment and outcome. Ann Vasc Surg 1991;5:234-40. 145. Mukherjee D, Inahara T. Endarterectomy as the procedure of choice for atherosclerotic occlusive lesions of the common femoral artery. Am J Surg 1989;157: 498-500. 146. Silva JA, White CJ, Quintana H, et al. Percutaneous revascularization of the common femoral artery for limb ischemia. Catheter Cardiovasc Interv 2004;62: 230-3. 147. Mahmud E, Keramati S, Salami A, et al. Expanded applications of rotational atherectomy in contemporary coronary and peripheral interventional practice. J Invasive Cardiol 2005;17:207-10. 148. Silva JA, White CJ, Ranee SR, et al. Percutaneous profundoplasty in the treatment of lower extremity ischemia: Results of long-term surveillance. J Endovasc Ther 2001;8:75-82. 149. Jacobs DL, Montaganahalli RL, Cox DE, et al. True lumen re-entry to facilitate subintimal angioplasty and stenting of total chronic occlusion. J Vasc Surg 2006;43:1291-6. 150. Lin S, Mckinsey JF. Plaque excision for the treatment of infrainguinal arterial occlusive disease. Tech Vasc Interv Radiol 2005;8:165-8. 151. Scheinert D, Scheinert S, Sax J, et al. Prevalence of clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol 2005;45:312-5. 152. Cejna M, Thurnher S, Illiasch H, et al. PTA v Palmaz Stent placement in femoropopliteal artery obstructions: A multicenter prospective randomized study. J Vasc Interv Radiol 2001;12:23-31. 153. Zdanowski Z, Albrechtsson U, Lundin A, et al. Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study. Int Angiol 1999;18:251-5. 154. Vroegindeweij D, Vos LD, Tielbeek AV, et al. Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: A comparative randomized study. Cardiovasc Interv Radiol 1997;20:420-25. 155. Zeller T, Tiefenbacher C, Steinkamp HJ, et al. Nitinol stent implantation in TASC A and B superficial femoral artery lesions: The femoral artery Conformexx trial (FACT). J Endovasc Ther 2008;15:390-8. 460

Curr Probl Cardiol, September 2009

156. Grimm J, Müller-Hulsbeck S, Jahnke T, et al. Randomized study to compare PTA alone versus PTA with Palmaz stent placement for femoropopliteal lesions. J Vasc Interv Radiol 2001;12:935-41. 157. Becquemin J-P, Favre J-P, Marzelle J. Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: A multicenter prospective randomized study. J Vasc Surg 2003;37:487-94. 158. Henriksen LO, Jorgensen B, Holstein PE, et al. Percutaneous transluminal angioplasty of infrarenal arteries in intermittent claudication. Acta Chir Scand 1988;154:573-6. 159. Krepel VM, van Andel GJ, van Erp WF, et al. Percutaneous transluminal angioplasty of the femoropopliteal artery: Initial and long-term results. Radiology 1985;156:325-8. 160. Kandarpa K, Becker GJ, Hunink MG, et al. Transcatheter interventions for the treatment of peripheral atherosclerotic lesions. Part 1. J Vasc Interv Radiol 2001;12:683-95. 161. Muradin GS, Bosch JL, Stijnen T, et al. Balloon dilation and stent implantation for treatment of femoropopliteal arterial disease: Meta-analysis. Radiology 2001;221: 137-45. 162. Duda SH, Pusich B, Richter G, et al. Sirolimus-eluting stents for the treatment of obstructive superficial femoral artery disease: Six-month results. Circulation 2002;106:1505-9. 163. Sabeti S, Mlekusch W, Amighi J, et al. Primary patency of long-segment self-expanding nitinol stents in the femoropopliteal arteries. J Endovasc Ther 2005;12:6-12. 164. Duda SH, Bosiers M, Lammer J, et al. Sirolimus-eluting versus bare nitinol stent for obstructive superficial femoral artery disease: The sirocco II trial. J Vasc Interv Radiol 2005;16:331-8. 165. Sabeti S, Schillinger M, Amighi J, et al. Primary patency of femoropopliteal arteries treated with nitinol versus stainless steel self-expanding stents: Propensity score-adjusted analysis. Radiology 2004;232:516-21. 166. Lugmayr HF, Holzer H, Kastner M, et al. Treatment of complex arteriosclerotic lesions with nitinol stents in the superficial femoral and popliteal arteries: A midterm follow-up. Radiology 2002;222:37-43. 167. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med 2006;354:1879-88. 168. Schillinger M, Sabeti S, Dick P, et al. Sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting. Circulation 2007;115:2745-9. 169. Krankenberg H, Schlüter M, Steinkamp HJ, et al. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: The femoral artery stenting trial (FAST). Circulation 2007;116: 285-92. 170. Ferreira M. Lanziotti L, Monteiro M, et al. superficial femoral artery recanalization with self-expanding nitinol stents: Long-term follow up results. Eur J Vasc Endovasc Surg 2007;34:702-8. 171. Dorrucci V. Treatment of superficial femoral artery occlusive disease. J Cardiovasc Surg 2004;45:193-201. 172. Kedora J, Hohmann S, Garrett W, et al. Randomized comparison of percutaCurr Probl Cardiol, September 2009

461

188.

neous Viabahn stent grafts vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral arterial occlusive disease. J Vasc Surg 2007;45:10-6. Kazemi S, Tumuluri R, Allaqaband S, et al. Percutaneous revascularization of femoropopliteal arteries with self-expanding nitinol stents—Immediate success and one-year results. J Am Coll Cardiol 2005;3(suppl 1):68A. Alimi Ys, Hakam Z, Hartung O, et al. Efficacy of Viabahn in the treatment of severe superficial femoral artery lesions: Which factors influence long term patency? Eur J Vasc Endovasc Surg 2008;35:346-52. McQuade K, Gable D, Hohman S, et al. Randomized comparison of ePTFE/nitinol self-expanding stent-graft vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral artery occlusive disease. J Vasc Surg 2009;49:109-16. Djelmani-Hani M, Nazir A, Taha M, et al. VIABAHN stent-graft for symptomatic recurrent in-stent restenosis of superficial femoral artery: Immediate success and long term patency [Abstracts]. MJ Cardiol 2007;100(8):199L. Ramaiah V, Gammon R, Kiesz S, et al. Midterm outcomes from the TALON Registry: Treating peripherals with SilverHawk: Outcomes collection. J Endovasc Ther 2006;13:592-602. Zeller T, Rastan A, Schwärzwalder U, et al. Percutaneous peripheral atherectomy of femoropopliteal stenoses using a new-generation device: Six-month results from a single-center experience. J Endovasc Ther 2004;11:676-85. Suri R, Wholey MH, Postoak D, et al. Distal embolic protection during femoropopliteal atherectomy. Catheter Cardiovasc Interv 2006;67:417-22. Zeller T, Rastan A, Sixt S, et al. Long-term results after directional atherectomy of femoropopliteal lesions. J Am Coll Cardiol 2006;48:1573-8. Steinkamp HJ, Rademaker J, Wissgott C, et al. Percutaneous transluminal laser angioplasty versus balloon dilation for treatment of popliteal artery occlusions. J Endovasc Ther 2002;9:882-8. Scheinert D, Laird JR Jr, Schöroder M, et al. Excimer laser-assisted recanalization of long, chronic superficial femoral artery occlusions. J Endovasc Ther 2001;8: 156-66. Bosiers M, Peeters P, Elist FV, et al. excimer laser assisted angioplasty for critical limb ischemia. results of the LACI Belgium study. Eur J Vasc Endovasc Surg 2005;29:613-9. Laird J, Jaff MR, Biamino G, et al. Cryoplasty for the treatment of femoropopliteal arterial disease: Results of a prospective, multicenter registry. J Vasc Interv Radiol 2005;16:1067-73. United States Food and Drug Administration. Center for Devices and Radiological Health. Class 1 Recall: Boston Scientific Flextome Cutting Balloon Systems. Available at: http://www.fda.gov/cdrh/recalls/recall-120705.html. Accessed January 29, 2009. Diehm N, Silvestro A, Do DD, et al. Endovascular brachytherapy after femoropopliteal balloon angioplasty fails to show robust clinical benefit over time. J Endovasc Ther 2005;12:723-30. Wolfram RM, Budinsky AC, Pokrajac B, et al. Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty: Five-year follow-up: Prospective randomized study. Radiology 2006;240:878-84. Wolfram RM, Budinsky AC, Pokrajac B, et al. Endovascular brachytherapy:

462

Curr Probl Cardiol, September 2009

173.

174.

175.

176.

177.

178.

179. 180. 181.

182.

183.

184.

185.

186.

187.

189.

190. 191. 192.

193. 194.

195.

196. 197.

198.

199.

200.

201. 202.

203.

204. 205.

Restenosis in de novo versus recurrent lesions of femoropopliteal artery: The Vienna experience. Radiology 2005;236:338-42. Therasse E, Donath D, Lesperance J, et al. External beam radiation to prevent restenosis after superficial femoral artery balloon angioplasty. Circulation 2005; 111:3310-5. Tepe G, Zeller T, Albretch T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med 2008;358:689-99. Rosenfield K, Schainfield R, Pieczek A, et al. Restenosis of endovascular stents from stent compression. J Am Coll Cardiol 1997;29:328-38. Schlager O, Dick P, Sabeti S, et al. Long-segment-SFA stenting-the dark sides: In-stent restenosis, clinical deterioration and stent fractures. J Endovasc Ther 2005;12:676-84. Veith FJ, Gupta SK, Ascer E, et al. Improved strategies for secondary operations on infrainguinal arteries. Ann Vasc Surg 1990;4:85-93. Ascer E, Collier P, Gupta SK, et al. Reoperation for polytetrafluoroethylene bypass failure: The importance of distal outflow site and operative technique in determining outcome. J Vasc Surg 1987;5:298-310. Veith FJ, Gupta SK, Wengerter KR, et al. Changing arteriosclerotic disease patterns and management strategies in lower-limb threatening ischemia. Ann Surg 1990;212:412-14. Bakal CW, Cynamon J, Sprayregan S. Infrapopliteal percutaneous transluminal angioplasty: What we know. Radiology 1996;200:33-43. Schwarten DE, Cutcliff WB. Arterial occlusive disease below the knee: Treatment with percutaneous transluminal angioplasty with low profile catheters and steerable guide wires. Radiology 1988;169:71-4. Hayes PD, Chokkalingam A, Jones R, et al. Arterial perforation during infrainguinal lower limb angioplasty does not worsen outcome: Results from 1409 patients. J Endovasc Ther 2002;9:422-7. Siablis D, Kraniotis P, Karnabatidis D, et al. Sirolimus-eluting versus bare stents for bailout after suboptimal infrapopliteal angioplasty for critical limb ischemia: 6-month angiographic results from a nonrandomized prospective single-center study. J Endovasc Ther 2005;12:685-95. Söder HK, Manninen HI, Jaakkola P, et al. Prospective trial of infrapopliteal artery balloon angioplasty for critical limb ischemia: Angiographic and clinical results. J Vasc Interv Radiol 2000;11:1021-31. Tsetis D, Belli AM. The role of infrapopliteal angioplasty. Br J Radiol 2004; 77:1007-15. Scheinert D, Ulrich M, Scheinert S, et al. Comparison of sirolimus-eluting vs baremetal stents for the treatment of infrapopliteal obstructions. Eurointervention 2006;2:169-74. Bakal CW, Sprayregen S, Scheinbaum K, et al. Percutaneous transluminal angioplasty of the infrapopliteal arteries: Results in 53 patients. AJR Am J Roentgenol 1990;154:171-4. Sivananthan UM, Browne TF, Thorley PJ, et al. Percutaneous transluminal angioplasty of the tibial arteries. Br J Surg 1994;81:1282-5. Varty K, Bolia A, Naylor AR, et al. Infrapopliteal percutaneous transluminal angioplasty: A safe and successful procedure. Eur J Vasc Endovasc Surg 1995; 9:341-5.

Curr Probl Cardiol, September 2009

463

206. Dorros G, Jaff MR, Murphy KJ, et al. The acute outcome of tibioperoneal vessel angioplasty in 417 cases with claudication and critical limb ischemia. Catheter Cardiovasc Diagn 1998;45:251-6. 207. Desgranges P, Kobeiter K, d’Audiffret A, et al. Acute occlusion of popliteal and/or tibial arteries: The value of percutaneous treatment. Eur J Vasc Endovasc Surg 2000;20:138-45. 208. Hagino RT, Fujitani RM, Dawson DL, et al. Does infrapopliteal arterial runoff predict success for popliteal artery aneurysmorrhaphy? Am J Surg 1994;168(6): 652-6. 209. Dorros G, Jaff MR, Dorros AM, et al. Tibioperoneal (outflow lesion) angioplasty can be used as primary treatment in 235 patients with critical limb ischemia: Five-year follow-up. Circulation 2001;104:2057-62. 210. Tsetis DK, Michalis LK, Rees MR, et al. Vibrational angioplasty in the treatment of chronic infrapopliteal arterial occlusions: Preliminary experience. J Endovasc Ther 2002;9:889-95. 211. Rastogi S, Stavropoulos SW. Infrapopliteal angioplasty. Tech Vasc Interv Radiol 2004;7:33-9. 212. Spinosa DJ, Leung DA, Matsumoto AH, et al. Percutaneous intentional extraluminal recanalization in patients with chronic critical limb ischemia. Radiology 2004;232:499-507. 213. Nasr MK, McCarthy J, Hardman J, et al. The increasing role of percutaneous transluminal angioplasty in the primary management of critical limb ischaemia. Eur J Vasc Endovasc Surg 2002;23:398-403. 214. Rand T, Basile A, Cejna M, et al. PTA versus carbofilm-coated stents in infrapopliteal arteries: Pilot study. Cardiovasc Interv Radiol 2006;29:29-38. 215. Faglia E, Mantero M, Caminiti M, et al. Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers: Clinical results of a multicentric study of 221 consecutive diabetic subjects. J Intern Med 2002;252:225-32. 216. Faglia E, Dalla PL, Clerici G, et al. Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischemia: Prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003. Eur J Vasc Endovasc Surg 2005;29:620-7. 217. Bull PG, Mendel H, Hold M, et al. Distal popliteal and tibioperoneal transluminal angioplasty: Long-term follow up. J Vasc Interv Radiol 1992;3:45-53. 218. Brown KT, Moore Ed, Getrajdman GI, et al. Infrapopliteal angioplasty; long-term follow up. J Vasc Interv Radiol 1993;4:139-44. 219. Tamura S, Sniderman KW, Beinart C, et al. Percutaneous transluminal angioplasty of the popliteal artery and its branches. Radiology 1982;143:645-8. 220. Abdul Raouf A, Rouleau Y, Clement A, et al. Endoluminal angioplasty of the popliteal artery. review of 54 consecutive patients. Eur J Vasc Endovasc Surg 2005;30:610-3. 221. Shalev Y, Fortsas MJ, Schmidt DH, et al. A modification of the peripheral angioplasty procedure to treat below-the-knee vascular disease: Initial success and late outcome in 97 patients. J Am Coll Cardiol 1996;27:191A. 222. Grant AG, White CJ, Collins TJ, et al. Infrapopliteal drug-eluting stents for chronic limb ischemia. Circulation 2006;114(Suppl II):II-820. 223. Feiring AJ, Wesolowski AA, Lade S. Primary stent supported angioplasty for 464

Curr Probl Cardiol, September 2009

224. 225.

226.

227. 228.

229. 230. 231. 232.

233.

234.

235.

236.

237. 238.

239. 240.

treatment of below-knee critical limb ischemia and severe claudication: Early and one year outcomes. J Am Coll Cardiol 2004;44:2307-14. Commeau P, Barragan P, Roguebert PO. Sirolimus for below the knee lesions: mid-term results of SiroBTK study. Catheter Cardiovasc Interv 2006;68:793-8. Bosiers M, Deloose K, Verbist J, et al. Percutaneous transluminal angioplasty for treatment of ‘“below-the-knee”’ critical limb ischemia: Early outcomes following the use of sirolimus-eluting stents. J Cardiovasc Surg 2006;47:171-6. Siablis D, Karnabatidis D, Katsanos K, et al. Sirolimus-eluting versus bare stents for bailout after suboptimal infrapopliteal angioplasty for critical limb ischemia: Enduring 1 year angiographic and clinical benefit. J Endovasc Ther 2007;14(2): 241-50. Tepe G. Drug-eluting stents for infrainguinal occlusive disease: Progress and challenges. Semin Vasc Surg 2006;19:102-8. Bosiers M, Hart JP, Deloose K, et al. Endovascular therapy as the primary approach for limb salvage in patients with critical limb ischemia: Experience with 443 infrapopliteal procedures. Vascular 2006;14:63-9. Braithwaite BD, Davies B, Birch PA, et al. Management of acute leg ischemia in the elderly. Br J Surg 1998;85:217e:220. Blaisdell FW, Steele M, Allen RE. Management of acute lower extremity arterial ischemia due to embolism and thrombosis. Surgery 1978;84:822-34. Clason AE, Stonebridge PA, Duncan AJ, et al. Morbidity and mortality in acute lower limb ischaemia: A 5-year review. Eur J Vasc Surg 1989;3:339-43. Ouriel K. Endovascular techniques in the treatment of acute limb ischemia: Thrombolytic agents, trials, and percutaneous mechanical thrombectomy techniques. Semin Vasc Surg 2003;16:270-9. STILE Investigators. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. The STILE trial. Ann Surg 1994;220:251-66. Ouriel K, Shortell C, Deweese J, et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994;19:1021-30. Ouriel K, Veith FJ, Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. N Engl J Med 1998;338:1105-11. Palfreyman SJ, Booth A, Michaels JA. A systematic review of intra-arterial thrombolytic therapy for lower-limb ischaemia. Eur J Vasc Endovasc Surg 2000; 19(2):143-57. Berridge DC, Kessel D, Robertson I. Surgery versus thrombolysis for acute limb ischaemia: Initial management. Cochrane Database Syst Rev 2002;3:CD002784. Swischuk JL, Fox PF, Young K, et al. Transcatheter intraarterial infusion of rt-PA for acute lower limb ischemia: Results and complications. J Vasc Interv Radiol 2001;12:423-30. Nehler MR, Mueller RJ, McLafferty RB, et al. Outcome of catheter-directed thrombolysis for lower extremity arterial bypass occlusion. J Vasc Surg 2003;37:72-8. McNamara TO, Fischer JR. Thrombolysis of peripheral arterial and graft occlusions: Improved results using high-dose urokinase. AJR Am J Roentgenol 1985;144:769-75.

Curr Probl Cardiol, September 2009

465

241. Sullivan KL, Gardiner GA Jr, Shapiro MJ, et al. Acceleration of thrombolysis with a high-dose transthrombus bolus technique. Radiology 1989;173:805-8. 242. Valji K, Bookstein JJ, Roberts AC, et al. Pulse-spray pharmacomechanical thrombolysis of thrombosed hemodialysis access grafts: Long-term experience and comparison of original and current techniques. AJR Am J Roentgenol 1995; 164:1495-500. 243. Armon MP, Yusuf SW, Whitaker SC, et al. Results of 100 cases of Puls-espray thrombolysis for acute and subacute leg ischaemia. Br J Surg 1997;84:47-50. 244. Kandarpa K, Chopra PS, Aruny JE, et al. Intraarterial thrombolysis of lower extremity occlusions: Prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion. Radiology 1993;188: 861-7. 245. Braithwaite BD, Buckenham TM, Galland RB, et al. Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group. Br J Surg 1997;84:646-50. 246. Plate G, Jansson I, Forssell C, et al. Thrombolysis for acute lower limb ischaemia—A prospective, randomised, multicenter study comparing two strategies. Eur J Vasc Endovasc Surg 2006;31:651-60. 247. Silva JA, Ramee SR, Collins TJ, et al. Rheolytic thrombectomy in the treatment of acute limb-threatening ischemia: Immediate results and six-month follow-up of the multicenter AngioJet registry. Possis Peripheral AngioJet Study AngioJet Investigators. Catheter Cardiovasc Diagn 1998;45:386-93. 248. Wagner HJ, Müller-Hülsbeck S, Pitton MB, et al. Rapid thrombectomy with a hydrodynamic catheter: Results from a prospective, multicenter trial. Radiology 1997;205:675-81. 249. Ansel GM, Botti CF, Silver MJ. Treatment of acute limb ischemia with a percutaneous mechanical thrombectomy-based endovascular approach: 5-year limb salvage and survival results from a single center series. Catheter Cardiovasc Interv 2008;72:325-30. 250. Ansel GM, George BS, Botti CF, et al. Rheolytic thrombectomy in the management of limb ischemia: 30-Day results from a multicenter registry. J Endovasc Ther 2002;9:395-402. 251. Allie DE, Hebert CJ, Lirtzman MD, et al. Novel simultaneous combination chemical thrombolysis/rheolytic thrombectomy therapy for acute critical limb ischemia: The power-pulse spray technique. Catheter Cardiovasc Interv 2004; 63:512-22. 252. Shammas NW, Dippel EJ, Shammas G, et al. Dethrombosis of the lower extremity arteries using the power-pulse spray technique in patients with recent onset thrombotic occlusions: Results of the DETHROMBOSIS Registry. J Endovasc Ther 2008;15:570-9. 253. Grossman PM, Mendelsohn F, Henry TD, et al. Results from a Phase II multicenter, double-blind placebo-controlled study of del-1 (VLTS-589) for intermittent claudication in subjects with peripheral arterial disease. Am Heart J 2007;153:874-80. 254. Mann MJ, Whittemore AD, Donaldson MC, et al. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: The PREVENT single-centre, randomised, controlled trial. Lancet 1999;354:1493-8. 255. Comerota AJ, Throm RC, Miller KA, et al. Naked plasmid DNA encoding 466

Curr Probl Cardiol, September 2009

256.

257.

258.

259.

260.

261.

262.

263.

264.

265.

266.

267.

268.

fibroblast growth factor Type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: Preliminary results of a Phase I trial. J Vasc Surg 2002;35:930-6. Henry TD, Mendelsohn F, Comerota A, et al. Dose and regimen effects of intramuscular NV1FGF in patients with critical limb ischemia: A randomized, double-blind, placebo-controlled study. Eur Heart J 2006;27(suppl 1):235. Nikol S, Baumgartner I, Van Belle E, et al for the TALISMAN 201 Investigators. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther 2008;16:972-8. Cooper LT Jr, Hiatt WR, Creager MA, et al. Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication. Vasc Med 2001;6:235-9. Lazarous DF, Unger EF, Epstein SE, et al. Basic fibroblast growth factor in patients with intermittent claudication: Results of a Phase I trial. J Am Coll Cardiol 2000;36:1239-44. Lederman RJ, Mendelsohn FO, Anderson RD, et al; TRAFFIC Investigators. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): A randomised trial. Lancet 2002;359: 2053-8. Marui A, Tabata Y, Kojima S, et al. A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel: An initial report of the Phase I-IIa study. Circul J 2007;71:1181-6. Matyas L, Schulte KL, Dormandy JA, et al. Arteriogenic gene therapy in patients with unreconstructable critical limb ischemia: A randomized, placebo-controlled clinical trial of adenovirus 5-delivered fibroblast growth factor-4. Hum Gene Ther 2005;16:1202-11. Morishita R, Aoki M, Hashiya N, et al. Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease erratum. Hypertension 2006;48:e7; 2004;44:203-9. Powell RJ, Simons M, Mendelsohn FO, et al. Results of a double-blind, placebocontrolled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation 2008;118:58-65. Rajagopalan S, Olin J, Deitcher S, et al. Use of a constitutively active hypoxiainducible factor-1alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients: Phase I dose-escalation experience. Circulation 2007;115: 1234-43. Rajagopalan S, Mohler ER III, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: A Phase II randomized, double-blind, con-trolled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 2003;108:1933-8. Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 1996;348:370-4. Isner JM, Baumgartner I, Rauh G, et al. Treatment of thromboangiitis obliterans

Curr Probl Cardiol, September 2009

467

285.

(Buerger’s disease) by intramuscular gene transfer of vascular endothelial growth factor: Preliminary clinical results. J Vasc Surg 1998;28:964-73. van Royen N, Schirmer SH, Atasever B, et al. START Trial. A pilot study on stimulation of ARTteriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease. Circulation 2005;112:1040-6. Clouse WD, Hallett JW Jr, Schaff HV, et al. Improved prognosis of thoracic aortic aneurysms: A population based study. J Am Med Assoc 1998;280:1926-9. Katzen BY, Dake MD, MacLean AA, et al. Endovascular repair of abdominal and thoracic aortic aneurysms. Circulation 2005;112:1663-75. Coady MA, Rizzo JA, Hammond GL, et al. Surgical intervention criteria for thoracic aortic aneurysms: A study of growth rates and complications. Ann Thorac Surg 1999;67:1922-6. Davies RR, Goldstein LJ, Coady MA, et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: Simple prediction based on size. Ann Thorac Surg 2002;73:17-27. Bavaria JE, Appoo JJ, Makaroun MS, et al. Endovascular stent grafting versus open surgical repair of descending thoracic aortic aneurysms in low-risk patients: A multicenter comparative trial. J Thorac Cardiovasc Surg 2007;133:369-77. Hodges TC, Cronenwett J. Abdominal aortic and iliac artery aneurysms: Clinical presentation, natural history, and indications for intervention. In: Perler BA, Becker GJ, editors. Vascular Intervention: A Clinical Approach. New York, NY: Thieme, 1998. p. 339-50. Kaufman JA, Geller SC, Brewster DC, et al. Endovascular repair of abdominal aortic aneurysms: Current status and future directions. AJR Am J Roentgenol 2000;175:289-302. Nevitt MP, Ballard DJ, Hallett JW. Prognosis of abdominal aortic aneurysms. A population-based study. N Engl J Med 1989;321:1009-14. Hallett JW Jr. Management of abdominal aortic aneurysms. Mayo Clin Proc 2000; 75:395-9. Hollier LH, Taylor LM Jr, Ochsner J. Recommended indications for operative treatment of abdominal aortic aneurysms: Report of a subcommittee of the Joint Council of the Society for Vascular Surgery and the International Society for Cardiovascular Surgery. J Vasc Surg 1992;15:1046-56. Hallett JW, Marshall DM, Petterson TM, et al. Graft-related complications after abdominal aortic aneurysm repair: Reassurance from a 36-year population-based experience. J Vasc Surg 1997;25:277-86. Johnston KW. Nonruptured abdominal aortic aneurysm: Six-year follow-up results from the multicenter prospective Canadian aneurysm study. Canadian Society for Vascular Surgery Aneurysm Study Group. J Vasc Surg 1994;20:163-70. Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms. Ann Vasc Surg 1991;5:491-9. Longo GM, Eskandari MK. Overview of success of EVAR: Progress to date. Semin Vasc Surg 2004;17:307-13. Zarins CK, White RA, Moll FL, et al. The AneuRx stent-graft: Four-year results and worldwide experience 2000. J Vasc Surg 2001;33:S135-45. Buth J, van Marrewijk CJ, Harris PL, et al. Outcome of endovascular abdominal

468

Curr Probl Cardiol, September 2009

269.

270. 271. 272.

273.

274.

275.

276.

277. 278. 279.

280.

281.

282. 283. 284.

286.

287.

288.

289.

290.

291.

292.

293.

294.

295. 296. 297.

298.

299. 300.

301.

aortic aneurysm repair in patients with conditions considered unfit for an open procedure: A report on the Eurostar experience. J Vasc Surg 2002;35:211-21. Leurs LJ, Bell R, Degrieck Y, et al. Endovascular treatment of thoracic aortic diseases: Combined experience from the Eurostar and UK thoracic endograft registries. J Vasc Surg 2004;40:670-80. Greenhalgh RM, Allison DJ, Bell PR, et al. Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: Randomized controlled trial. Lancet 2004; 364:843-48. Greenhalgh RM, Allison DJ, Bell PR, et al. Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic aneurysm (EVAR trial 2): Randomized controlled trial. Lancet 2005;365:2187-92. Prinssen M, Verhoeven EL, Buth J, et al. A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. N Engl J Med 2004;351:1607-18. Schermerhorn ML, O’Malley AJ, Jhaveri R, et al. Endovascular vs. open repair of abdominal aortic aneurysms in the Medicare population. N Engl J Med 2008; 358:464-74. Hallett JW Jr, Marshall DM, Petterson TM, et al. Graft-related complications after abdominal aortic aneurysm repair: Reassurance from a 36-year population-based experience. J Vasc Surg 1997;25:277-84. Biancari F, Ylonen K, Anttila V, et al. Durability of open repair of infrarenal abdominal aortic aneurysm: A 15-year follow-up study. J Vasc Surg 2002;35: 87-93. Siami FS, for the Lifeline Registry of EVAR Publications Committee. Lifeline registry of endovascular aneurysm repair: Long-term primary outcome measures. J Vasc Surg 2005;42:1-10. May J, White GH, Waugh R, et al. Improved survival after endoluminal repair with second-generation prostheses compared with open repair in the treatment of abdominal aortic aneurysms: A 5-year concurrent comparison using life table method. J Vasc Surg 2001;33(2)(suppl):S21-6. Zarins CK; AneuRx Clinical Investigators. The US AneuRx Clinical Trial: 6-year clinical update 2002. J Vasc Surg 2003;37:904-8. Harris PL, Buth J. An update on the important findings from the Eurostar EVAR registry. Vascular 2004;12:33-8. Kibbe MR, Matsumura JS. The Excluder Investigators: The Gore Excluder US Multi-Center Trial: Analysis of adverse events at 2 years. Semin Vasc Surg 2003;16:144-50. Matsumura JS, Brewster DC, Makaroun MS, et al. A multicenter controlled clinical trial of open versus endovascular treatment of abdominal aortic aneurysm. J Vasc Surg 2003;37:262-71. Moore WS. The Guidant Ancure bifurcation endograft: Five-year follow-up. Semin Vasc Surg 2003;16:139-43. Moore WS, Matsumura JS, Makaroun MS, et al. Five-year interim comparison of the Guidant bifurcated endograft with open repair of abdominal aortic aneurysm. J Vasc Surg 2003;38:46-55. Greenberg R. The Zenith Investigators: The zenith AAA endovascular graft for abdominal aortic aneurysms: Clinical update. Semin Vasc Surg 2003;16:151-7.

Curr Probl Cardiol, September 2009

469

302. Sternbergh WC III, Money SR, Greenberg RK, et al. Influence of endograft oversizing on device migration, endoleak, aneurysm shrinkage, and aortic neck dilation: Results from the Zenith Multicenter Trial. J Vasc Surg 2004;39:20-6. 303. Bertges DJ, Chow K, Wyers MC, et al. Abdominal aortic aneurysm size regression after endovascular repair is endograft dependent. J Vasc Surg 2003;37:716-23. 304. Sachdev U, Baril DT, Ellozy SH, et al. Management of aneurysms involving branches of the celiac and superior mesenteric arteries: A comparison of surgical and endovascular therapy. J Vasc Surg 2006;44:718-24. 305. Abbas MA, Fowl RJ, Stone WN, et al. Hepatic artery aneurysm: Factors that predict complications. J Vasc Surg 2003;38:41-5. 306. Berceli SA. Hepatic and splenic artery aneurysms. Semin Vasc Surg 2005;18: 196-201. 307. Nachbur BH, Inderbitzi RG, Bar W. Isolated iliac aneurysms. Eur J Vasc Surg 1991;5:375-81. Richardson JW, Greenfield LJ. 308. Richardson JW, Greenfield LJ. Natural history and management of iliac aneurysms. J Vasc Surg 1988;8:165-71. 309. Scheinert D, Schroder M, Steinkamp H, et al. Treatment of iliac artery aneurysms by percutaneous implantation of stent grafts. Circulation 2000;102:III-253-8. 310. Sahgal A, Veith F, Lipsitz E, et al. Diameter changes in isolated iliac artery aneurysms 1 to 6 years after endovascular graft repair. J Vasc Surg 2001;33:289-95. 311. Huand Y, Gloviczki P, Duncan AA, et al. Common iliac artery aneurysm: Expansion rate and results of open surgical and endovascular repair. J Vasc Surg 2008;47:1203-11. 312. Pitoulias GA, Donas KP, Schulte S, et al. Isolated iliac artery aneurysms: Endovascular versus open elective repair. J Vasc Surg 2007;46:648-54. 313. Trickett JP, Scott RAP, Tilney HS. Screening and management of asymptomatic popliteal aneurysms. J Med Screen 2002;9:92-3. 314. Curi MA, Geraghty PJ, Merion OA, et al. Mid-term outcomes of endovascular popliteal artery aneurysm repair. J Vasc Surg 2007;45:505-10. 315. Thompson MM, Sayers RD. Arterial aneurysms. In: Companion to Specialist Surgical Practice, Vol VII. Arterial Surgery. London: WB Saunders, 1998. 316. Dawson I, Sie RB, van Bockel JH. Atherosclerotic popliteal aneurysm. Br J Surg 1997;84:293-9. 317. Michaels JA, Galland RB. Management of asymptomatic popliteal aneurysms: The use of a markov decision tree to determine the criteria for a conservative approach. Eur J Vasc Surg 1993;7:136-43. 318. Tielliu IFJ, Verhoeven ELG, Prins TR, et al. Treatment of popliteal artery aneurysms with the Hemobahn stent-graft. J Endovasc Ther 2003;10:111-6. 319. Antonello M, Frigatti P, Battocchio P, et al. Open repair versus endovascular treatment for asymptomatic popliteal artery aneurysm: Results of a prospective randomized study. J Vasc Surg 2005;42:185-93. 320. Cina CS, Moor R, Maggisano R, et al. Endovascular repair of popliteal artery aneurysms with anaconda limbs: Technique and early results. Catheter Cardiovasc Int 2008;72:716-24. 321. Siauw R, Koh EH, Walker SR. Endovascular repair of polyteal artery aneurysms: Techniques, current evidence and recent experience. Aust NZ J Surg 2006; 76:505-11. 470

Curr Probl Cardiol, September 2009

322. Chang R, Horne MK, Mayo DJ, et al. Pulse-spray treatment of subclavian and jugular venous thrombi with recombinant tissue plasminogen activator. J Vasc Interv Radiol 1996;7:845-51. 323. Adelman MA, Stone DH, Riles TS, et al. A multidisciplinary approach to the treatment of Paget-Schroetter syndrome. Ann Vasc Surg 1997;11:149-54. 324. Kee ST, Kinoshita L, Razavi MK, et al. Superior vena cava syndrome: Treatment with catheter-directed thrombolysis and endovascular stent placement. Radiology 1998;206:187-93. 325. Angle N, Gelabert HA, Farooq MM, et al. Safety and efficacy of early surgical decompression of the thoracic outlet outlet for Paget-Schroetter syndrome. Ann Vasc Surg 2001;15:37-42. 326. Machleder HI. Evaluation of a new treatment strategy for Paget-Schroetter syndrome: Spontaneous thrombosis of the axillary-subclavian vein. J Vasc Surg 1993;17:305-15. 327. Molina JE. Need for emergency treatment in subclavian vein effort thrombosis. J Am Coll Surg 1995;181:414-20. 328. Urschel HC Jr, Razzuk MA, Paget-Schroetter. Syndrome: What is the best management? Ann Thorac Surg 2000;69:1663-8. 329. Kreienberg PB, Chang BB, Darling RC III, et al. Long-term results in patients treated with thrombolysis, thoracic inlet decompression, and subclavian vein stenting for Paget-Schroetter syndrome. J Vasc Surg 2001;33(suppl):S100-5. 330. Lokanathan R, Salvian AJ, Chen JC, et al. Outcome after thrombolysis and selective thoracic outlet decompression for primary axillary vein thrombosis. J Vasc Surg 2001;33:783-8. 331. Heit JA, Melton LJ III, Lohse CM, et al. Incidence of venous thromboembolism in hospitalized patients vs community residents. Mayo Clin Proc 2001;76: 1102-10. 332. Fowkes FJ, Price JF, Fowkes FG. Incidence of diagnosed deep vein thrombosis in the general population: Systematic review. Eur J Vasc Endovasc Surg 2003;25:1-5. 333. Hansson PO, Sörbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: Incidence and risk factors. Arch Intern Med 2000;160:769-74. 334. Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: A population-based cohort study. Arch Intern Med 2000;160:761-8. 335. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism the Worcester DVT study. Arch Intern Med 1991;151:933-8. 336. Gould MK, Dembitzer AD, Doyle RL, et al. Low molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999;130: 800-9. 337. Hirsh J, Siragusa S, Cosmi B, et al. Low molecular weight heparins (LMWH) in the treatment of patients with acute venous thromboembolism. Thromb Haemost 1995;74:360-3. 338. van Den Belt AG, Prins MH, Lensing AW, et al. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev 2000:CD001100. 339. Chong BH, Brighton TA, Baker RI, et al; ASTH DVT Study Group. Once-daily Curr Probl Cardiol, September 2009

471

354.

enoxaparin in the outpatient setting versus unfractionated heparin in hospital for the treatment of symptomatic deep-vein thrombosis. J Thromb Thrombolysis 2005; 19:173-81. Schulman S, Rhedin AS, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med 1995;332: 1661-5. Pinede L, Ninet J, Duhaut P et al. Investigators of the Dure’e Optimale du Traitement AntiVitamines K” (DOTA VK) Study. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation 2001;103:2453-60. Ridker PM, Goldhaber SZ, Danielson E, et al; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003;348:1425-34. Agnelli G, Prandoni P, Becattini C et al; Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003;139:19-25. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7. Akesson H, Brudin L, Dahlström JA, et al. Venous function assessed during a 5-year period after acute Ilio-femoral venous thrombosis treated with anticoagulation. Eur J Vasc Surg 1990;4:43-8. Saarinen J, Sisto T, Laurikka J, et al. Late sequelae of acute deep venous thrombosis: Evaluation five to ten years later. Phlebology 1995;10:106-9. Janssen MC, Haenen JH, van Asten WM, et al. Clinical and hemodynamic sequelae of deep venous thrombosis: Retrospective evaluation after 7-13 years. Clin Sci 1997;93:7-12. Brandjes DPM, Büller HR, Heijboer H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997;349:759-62. Elliot MS, Immelman EJ, Jeffery P, et al. A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal venous thrombosis: An interim report of a prospective trial. Br J Surg 1979;66:838-43. Arnesen H, Høiseth A, Ly B. Streptokinase or heparin in the treatment of deep vein thrombosis: Follow-up results of a prospective study. Acta Med Scand 1982; 211:65-8. Meissner MH, Manzo RA, Bergelin RO, et al. Deep venous insufficiency: The relationship between lysis and subsequent reflux. J Vasc Surg 1993;18:596-605, discussion, 606-8. Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg 2002;24:209-14. Mewissen MW, Seabrook GR, Meissner MH, et al. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: Report of a national multicenter registry. Radiology 1999;211:39-49. Bjarnason H, Kruse JR, Asinger DA, et al. Iliofemoral deep venous thrombosis:

472

Curr Probl Cardiol, September 2009

340.

341.

342.

343.

344. 345.

346. 347.

348.

349.

350.

351.

352.

353.

355. 356. 357. 358.

359.

360. 361.

362.

363.

364.

365.

366.

367. 368.

369. 370. 371.

Safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol 1997;8:405-18. Semba CP, Dake MD. Iliofemoral deep venous thrombosis: Aggressive therapy with catheter-directed thrombolysis. Radiology 1994;191:487-94. Razavi MK, Wong H, Kee ST, et al. Initial clinical results of tenecteplase (TNK) in catheter-directed thrombolytic therapy. J Endovasc Ther 2002;9:593-8. Raju S, Fountain T, McPherson SH. Catheter-directed thrombolysis for deep venous thrombosis. J Miss State Med Assoc 1998;39:81-4. Castaneda F, Li R, Young K, et al. Catheter directed thrombolysis in deep venous thrombosis with use of reteplase: Immediate results and complications from a pilot study. J Vasc Interv Radiol 2002;13:577-80. Horne MK III, Mayo DJ, Cannon RO III, et al. Intraclot recombinant tissue plasminogen activator in the treatment of deep venous thrombosis of the lower and upper extremities. Am J Med 2000;108:251-5. Ouriel K, Katzen B, Mewissen M, et al. Reteplase in the treatment of peripheral arterial and venous occlusions: A pilot study. J Vasc Interv Radiol 2000;11:849-54. Sugimoto K, Hofmann LV, Razavi MK, et al. The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions. J Vasc Surg 2003;37:512-7. Acharya G, Singh K, Hansen JB, et al. Catheter-directed thrombolysis for the management of postpartum deep venous thrombosis. Acta Obstet Gynecol Scand 2005;84:155-8. Ogawa T, Hoshino S, Midorikawa H, et al. Intermittent pneumatic compression of the foot and calf improves the outcome of catheter-directed thrombolysis using low-dose urokinase in patients with acute proximal venous thrombosis of the leg. J Vasc Surg 2005;42:940-4. Laiho MK, Oinonen A, Sugano N, et al. Preservation of venous valve function after catheter-directed and systemic thrombolysis for deep venous thrombosis. Eur J Vasc Endovasc Surg 2004;28:391-6. Sillesen H, Just S, Jørgensen M, et al. Catheter directed thrombolysis for treatment of Ilio-femoral deep venous thrombosis is durable, preserves venous valve function and may prevent chronic venous insufficiency. Eur J Vasc Endovasc Surg 2005; 30:556-62. Grunwald MR, Hofmann LV. Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis. J Vasc Interv Radiol 2004;15:347-52. Semba CP, Razavi MK, Kee ST, et al. Thrombolysis for lower extremity deep venous thrombosis. Tech Vasc Interv Radiol 2004;7:68-78. May R, Thurner J. A vascular spur in the vena iliaca communis sinistral as a cause of predominantly left-sided thrombosis of the pelvic veins. Z Kreislaufforsch 1956;45:912-22. May R, Thurner J. The cause of the predominantly sinistral occurrence of thrombosis of the pelvic veins. Angiology 1957;8:419-27. Kim JY, Choi D, Guk Ko Y, et al. Percutaneous treatment of deep vein thrombosis in May–Thurner syndrome. Cardiovasc Interv Radiol 2006;29:571-5. Husmann MJ, Heller G, Kalka C, et al. Stenting of common iliac vein obstructions combined with regional thrombolysis and thrombectomy in acute deep vein thrombosis. Eur J Vasc Endovasc Surg 2007;34:87-91.

Curr Probl Cardiol, September 2009

473

372. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901-7. 373. Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003;349:631-9. 374. Schulman S, Granqvist S, Holmström M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group. N Engl J Med 1997;336:393-8. 375. Stein PD, Kayali F, Olson RE. Twenty-one year trends in the use of inferior vena cava filters. Arch Intern Med 2004;164:1541-5. 376. Hann CL, Streiff MB. The role of vena caval filters in the management of venous thromboembolism. Blood Rev 2005;19:179-202. 377. Decousus H, Leizorovicz A, Parent F, et al; The PREPIC Study Group. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. the prévention du risque d’embolie pulmonaire par interruption randomized study. N Engl J Med 1998;338:409-15. 378. PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: The PREPIC (prevention du risque d’embolie pulmonaire par interruption cave) randomized study. Circulation 2005;112:416-22. 379. White RH, Zhou H, Kim J, et al. A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. Arch Intern Med 2000;160:2033-41. 380. Horattas MC, Wright DJ, Fenton AH, et al. Changing concepts of deep venous thrombosis of the upper extremity—Report of a series and review of the literature. Surgery 1988;104:561-7. 381. Kammen BF, Soulen MC. Phlegmasia cerulea dolens of the upper extremity. J Vasc Interv Radiol 1995;6:283-6. 382. Bolitho DG, Elwood ET, Roberts F. Phlegmasia cerulea dolens of the upper extremity. Ann Plast Surg 2000;45:644-6. 383. Hingorani A, Ascher E, Lorenson E, et al. Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population. J Vasc Surg 1997;26:853-60. 384. Monreal M, Raventos A, Lerma R, et al. Pulmonary embolism in patients with upper extremity DVT associated to venous central lines—A prospective study. Thromb Haemost 1994;72:548-50. 385. Roos DB. Congenital anomalies associated with thoracic outlet syndrome: Anatomy, symptoms, diagnosis, and treatment. Am J Surg 1976;132:771-8. 386. AbuRahma AF, Robinson PA. Effort subclavian vein thrombosis: Evolution of management. J Endovasc Ther 2000;7:302-8. 387. Rutherford RB, Hurlbert SN. Primary subclavian-axillary vein thrombosis: Consensus and commentary. Cardiovasc Surg 1996;4:420-3. 388. Yim CD, Sane SS, Bjarnason H. Superior vena cava stenting. Radiol Clin North Am 2000;38:409-24. 389. Schindler N, Vogelzang RL. Superior vena cava syndrome: Experience with endovascular stents and surgical therapy. Surg Clin North Am 1999;79:683-94. 390. Stockx L, Raat H, Donck J, et al. Repositioning and leaving in situ the central 474

Curr Probl Cardiol, September 2009

391. 392. 393. 394.

395. 396.

397. 398. 399.

400.

401.

402.

403. 404.

405.

406. 407. 408.

venous catheter during percutaneous treatment of associated superior vena cava syndrome: A report of eight cases. Cardiovasc Interv Radiol 1999;22:224-6. Slonim SM, Semba CP, Sze DY, et al. Placement of SVC stents over pacemaker wires for the treatment of SVC syndrome. J Vasc Interv Radiol 2000;11:215-9. Bechtold RE, Wolfman NT, Karstaedt N, et al. Superior vena caval obstruction: Detection using CT. Radiology 1985;157:485-7. Kim HJ, Kim HS, Chung SH. Diagnosis of superior vena cava syndrome: Importance of collateral vessels. AJR Am J Roentgenol 1993;161:539-42. Eren S, Karaman A, Okur A. The superior vena cava syndrome caused by malignant disease. Imaging with multi-detector row CT. Eur J Radiol 2006;59: 93-103. Lin J, Zhou KR, Chen ZW, et al. Vena cava 3D contrast-enhanced MR venography: A pictorial review. Cardiovasc Interv Radiol 2005;28:795-805. Thornton MJ, Ryan R, Varghese JC, et al. A threedimensional gadoliniumenhanced MR venography technique for imaging central veins. AJR Am J Roentgenol 1999;173:999-1003. Rice TW, Rodriguez RM, Light RW. The superior vena cava syndrome: Clinical characteristics and evolving etiology. Medicine 2006;85:37-42. Markman M. Diagnosis and management of superior vena cava syndrome. Cleve Clin J Med 1999;66:59-61. Charnsangavej C, Carrasco C, Wallace S, et al. Stenosis of the vena cava: Preliminary assessment of treatment with expandable metallic stent. Radiology 1986;161:295-8. Mathias K, Jäger H, Willaschek J, et al. Interventional radiology in central venous obstructions. Dilatation–stent implantation–thrombolysis. Radiologe 1998;38: 606-13. Sunder SK, Ekong EA, Sivalingam K, et al. Superior vena cava thrombosis due to pacing electrodes: Successful treatment with combined thrombolysis and angioplasty. Am Heart J 1992;123:790-2. Rowell NP, Gleeson FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: A systematic review. Clin Oncol 2002;14:338-51. Ostler PJ, Clarke DP, Watkinson AF, et al. Superior vena cava obstruction: A modern management strategy. Clin Oncol 1997;9:83-9. Smayra T, Otal P, Chabbert V, et al. Long-term results of endovascular stent placement in the superior caval venous system. Cardiovasc Interv Radiol 2001; 24:388-94. Nicholson AA, Ettles DF, Arnold A, et al. Treatment of malignant superior vena cava obstruction: Metal stents or radiation therapy. J Vasc Interv Radiol 1997; 8:781-8. Crowe MT, Davies CH, Gaines PA. Percutaneous management of superior vena cava occlusions. Cardiovasc Interv Radiol 1995;18:367-72. Rizvi AZ, Kalra M, Bjarnason H, et al. Benign superior vena cava syndrome: Stenting is now the first line of treatment. J Vasc Surg 2008;47:372-80. Lanciego C, Chacón JL, Julián A, et al. Stenting as first option for endovascular treatment of malignant superior vena cava syndrome. AJR Am J Roentgenol 2001;177:585-93.

Curr Probl Cardiol, September 2009

475

409. Bissett D, Kaye SB, Baxter G, et al. Successful thrombolysis of SVC thrombosis associated with Hickman lines and continuous infusion chemotherapy. Clin Oncol 1996;8:247-9. 410. Barakat K, Robinson NM, Spurrell RA. Transvenous pacing lead-induced thrombosis: A series of cases with a review of the literature. Cardiology 2000; 93:142-8. 411. Qanadli SD, El Hajjam M, Mignon F, et al. Subacute and chronic benign superior vena cava obstructions: Endovascular treatment with self-expanding metallic stents. AJR Am J Roentgenol 1999;173:159-64. 412. Edwards RD, Jackson JE. Case report: Superior vena caval obstruction treated by thrombolysis, mechanical thrombectomy and metallic stents. Clin Radiol 1993; 48:215-7.

476

Curr Probl Cardiol, September 2009