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Journal of the American College of Cardiology Vol. 50, No. 6, 2007© 2007 by the American College of Cardiology Foundation ISSN 0735-1097/07/$32.00P

STATE-OF-THE-ART PAPER

Current Treatment of Peripheral Arterial DiseaseRole of Percutaneous Interventional Therapies

Ehtisham Mahmud, MD,* Jeffrey J. Cavendish, MD,† Ali Salami, MD*

San Diego, California

Despite advances in medical therapies to help prevent the development of atherosclerosis and improve themanagement of patients with established peripheral arterial disease (PAD), the prevalence of PAD and associ-ated morbidity remains high. Over the past decade, percutaneous revascularization therapies for the treatmentof patients with PAD have evolved tremendously, and a great number of patients can now be offered treatmentoptions that are less invasive than traditional surgical options. With the surgical approach, there is significantsymptomatic improvement, but the associated morbidity and mortality preclude its routine use. Although newerpercutaneous treatment options are associated with lower procedural complications, the technical advanceshave outpaced the evaluation of these treatments in adequately designed clinical studies, and therapeutic op-tions are available that may not have been rigorously investigated. Therefore, for physicians treating patientswith PAD, an understanding of the various therapies available, along with the inherent benefits and limitationsof each treatment option is imperative as a greater number of patients with PAD are being encountered.(J Am Coll Cardiol 2007;50:473–90) © 2007 by the American College of Cardiology Foundation

ublished by Elsevier Inc. doi:10.1016/j.jacc.2007.03.056

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therosclerosis is a systemic disease that affects all majorascular territories. The risk factors associated with theevelopment of atherosclerosis in the coronary arteries areell known and are remarkably consistent for other vascular

erritories (1,2). In the lower extremities, active smoking,yslipidemia, and inflammation are associated with progres-ion of large-vessel atherosclerotic disease, whereas onlyiabetes is associated with progression of small-vessel dis-ase (3). Despite advances in medical therapies to preventtherosclerosis and better manage patients with establishederipheral arterial disease (PAD), the incidence of PADontinues to increase, and associated morbidity remainsigh, especially as the population ages (4). Over the pastecade, percutaneous revascularization therapies for thereatment of patients with PAD have evolved tremendously,nd a great number of patients can be offered treatmentptions that are less invasive than traditional surgical op-ions. Some of these technical advances have outpaced thevaluation of these treatments in adequately designed clin-cal studies, and therapeutic options are available that mayot have been rigorously investigated. Therefore, for phy-icians treating patients with PAD, an understanding of thearious therapies available, along with the inherent benefits

rom the *Division of Cardiovascular Medicine, University of California, San Diegochool of Medicine, San Diego, California; and the †Naval Medical Center, Saniego, California. The views, opinions, and assertions contained in this work are

hose of the authors and are not to be construed as official or as reflecting the viewsf the U.S. Navy, Department of Defense, or the U.S. Government.

bManuscript received October 17, 2006; revised manuscript received March 12,

007, accepted March 14, 2007.

nd limitations of each treatment option is imperative as areater number of patients with PAD are being encountered.

rachiocephalic and Subclavian Artery Disease

he primary disease affecting the extracranial aortic archessels is progressive atherosclerosis. An endovascular ap-roach to revascularization is preferred for the treatment oftherosclerotic extracranial (noninternal carotid) aortic archessel disease (Table 1), although there are no randomizedlinical trials directly comparing this approach with contem-orary surgery. However, the endovascular approach is lessnvasive, and a comprehensive review of the publishediterature demonstrates comparable procedural success (97%s. 96% surgery), lower procedural complications (6% vs.6% surgery), lower mortality (0% vs. 2% surgery), andower major morbidity (stroke: 0% vs. 3% surgery), alongith excellent long-term patency (97% at 20 months vs.4% at 51 months with surgery) (5). Radiation-inducedasculitis and Takayasu’s arteritis affecting these vessels havelso been described (1,6,7). Radiation-induced vasculitis isssociated with poor wound healing after surgery. There-ore, obstructive disease associated with it is preferentiallyreated by endovascular techniques (8). In contrast, owing toanvascular inflammation and, often, concomitant aneurys-al disease, treatment for Takayasu’s arteritis is generally

urgical, using Dacron grafts as bypass conduits (7).The proximal left subclavian artery is the most commonly

iseased arch vessel with significant stenosis (as determinedy a systolic blood pressure difference of �15 mm Hg
etween the right and left arm), noted in 7.1% of patients

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474 Mahmud et al. JACC Vol. 50, No. 6, 2007Current Treatment of PAD August 7, 2007:473–90

referred to a noninvasive vascularlaboratory for any indication (9).In patients undergoing coronaryangiography and requiring coro-nary artery bypass graft (CABG)surgery, 5.3% have angiographi-cally significant left subclavianstenosis, whereas 11.5% of pa-tients with known PAD referredfor coronary angiography alsohave angiographically significantleft subclavian stenosis (10). Inthe presence of clinically signifi-cant subclavian stenosis, patientscan develop upper extremityclaudication and subclavian stealsyndrome, a reversal of flow inthe vertebral artery causing diz-ziness, vertigo, and, rarely, syn-cope with upper extremity exer-tion. In the presence of diseasedistal to the vertebral artery, pa-tients present with arm claudica-tion only. In contrast, when theinnominate artery is affected, pa-tients present with subclaviansteal syndrome, often with pro-found dizziness and/or syncopein the presence of flow reversal in

he right vertebral and carotid arteries. The use of the leftnternal mammary artery (LIMA) during CABG surgery inatients with severe left subclavian stenosis is associatedith coronary-subclavian steal syndrome, leading to reversalf flow in the LIMA graft to the left anterior descendingoronary artery (LAD) with left arm exertion. These pa-ients often present with angina, particularly with the use ofheir left arm. If high-grade stenosis of the left subclavianrtery is present at the time of CABG surgery, maturationf the LIMA graft to the LAD is also hindered, potentiallyeading to early graft failure. Therefore, as an increasinglyomplex group of patients are being referred for surgicalevascularization, preoperative subclavian angiography at

Abbreviationsand Acronyms

AAA � abdominal aorticaneurysm

BE � balloon expandable

BMS � bare-metal stent(s)

CABG � coronary arterybypass graft

CAD � coronary arterydisease

CEA � carotidendarterectomy

CTO � chronic totalocclusion

DES � drug-eluting stent(s)

LAD � left anteriordescending coronary artery

LIMA � left internalmammary artery

MI � myocardial infarction

PAD � peripheral arterialdisease

RAS � renal arterystenosis

SE � self-expanding

SFA � superficial femoralartery

ndications for Endovascularreatment of Aortic Arch Vessel Stenoses

Table 1 Indications for EndovascularTreatment of Aortic Arch Vessel Stenoses

1. Upper extremity claudication

2. Bilateral subclavian stenosis

● Need to accurately assess blood pressure noninvasively

3. Subclavian steal syndrome

4. Coronary-subclavian steal syndrome

5. Left subclavian stenosis �50% before CABG with LIMA to the LAD

6. Symptomatic common carotid stenosis

7. Symptomatic vertebral artery stenosis

8. Before-dialysis shunt placement

wABG � coronary artery bypass graft surgery; LAD � left anterior descending artery; LIMA � left

nternal mammary artery.

he time of diagnostic cardiac catheterization to allow ade-uate treatment of this vessel before CABG surgery isecommended.ndovascular treatment. Thoracic aortic arch angiogra-hy helps determine the extent of disease affecting the archnd ostia of the great vessels and is always recommendedefore proceeding with an intervention. Patients with ath-rosclerotic disease affecting the subclavian artery are bestreated with balloon-expandable (BE) stents, as the ostiumf this vessel is often calcified and there is significant elasticecoil after balloon angioplasty alone (Fig. 1). The vertebralrtery takes off in close proximity to the origin of the leftubclavian artery, and the placement of a stent across theertebral artery is not appropriate in the presence of aontralateral vertebral artery occlusion because posteriorerebral circulation can then be compromised. In such cases,urgery is generally indicated. In a large series of patientsith symptomatic subclavian disease treated with stenting,rimary success was achieved in 100% of patients withtenotic lesions and 53.8% of patients with a chronic totalcclusion (CTO), with the lowest complication rate inatients treated with direct stenting without predilation11). The subclavian artery is a large-diameter vessel with aigh flow rate, and both stent thrombosis and restenosisates (secondary patency 97.7% at 3 years) are low unlessecanalization is attempted for a complete occlusion (11).here are no drug-eluting stents (DES) available for vesselsf this diameter, and it is highly unlikely that they will bepecifically investigated for this vascular territory, as excel-ent clinical outcomes are achieved with the current gener-tion of bare-metal stents (BMS). Surgery is reservedrimarily for symptomatic subclavian occlusion and involvesn extrathoracic carotid-subclavian artery bypass with poly-etrafluroethylene or a carotid-subclavian transposition,hich as isolated operations have a mortality of 0% to 1%

nd an excellent long-term patency (12).The incidence of hemodynamically significant atheroscle-

otic disease is lower in the innominate, right subclavian,nd common carotid arteries. Endovascular stenting is alsohe procedure of choice for disease affecting the ostial/roximal stenoses of all these vessels. In the largest series onhe subject (13), published almost a decade ago, excellentrocedural success (94.3%) with percutaneous treatment ofhese vessels was reported, albeit with high proceduralomplications (17.8%) and only 84% patency at 35-monthollow-up. A number of investigators (5,14–18) have re-orted their experiences with contemporary endovascularreatment of the brachiocephalic vessels, with a unifyingheme of high initial procedural success (90% to 100%), lowajor complication rates (0% to 4%), and excellent long-

erm patency (90% to 100%). The presence of calcifiedtherosclerotic plaque increases the potential for recoil andestenosis, which is mitigated by the use of BE stents ratherhan balloon angioplasty alone. Long-term surgical out-omes remain excellent, though this approach is associated
ith higher periprocedural complications (5). Treatment of

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475JACC Vol. 50, No. 6, 2007 Mahmud et al.August 7, 2007:473–90 Current Treatment of PAD

ymptomatic obstruction involving brachiocephalic vesselypass grafts (Dacron) has also been described, using BEtents with 100% procedural success and 13.6% restenosis at9-month follow-up (19).

arotid and Intracranial Disease

troke is the third leading cause of mortality and the leadingause of disability in the U.S. (20). Carotid atherosclerosisommonly affects the carotid bulb and extends into thenternal carotid artery. It may be associated with 20% ofschemic cerebrovascular events and is one of the treatableauses of initial and recurrent strokes. The NASCETNorth American Symptomatic Endarterectomy Trial)21,22) and ECST (European Carotid Surgery Trial)23,24) demonstrated that patients with symptomatic ca-otid stenosis (carotid distribution transient ischemic attackr stroke in the preceding 6 months) and an internal carotidtenosis of 70% to 99% benefit from carotid endarterectomyCEA) versus medical therapy, with a 2- to 3-year reductionn ipsilateral stroke from 22% to 27% (medical therapy) to% to 15% (CEA). Though this benefit was greatest foresions with �70% stenosis, a subsequent meta-analysisemonstrated that at 5-year follow-up, benefit also existedor lesions with 50% to 69% stenosis (25). In asymptomaticatients, the ACAS (Asymptomatic Carotid Atheroscle-otic Study) (26) and ACST (Asymptomatic Carotid Sur-ery Trial) (27) demonstrated a reduction in ipsilateraltroke and any perioperative death or stroke, from 11% to2% (optimal medical therapy) to 5% to 6% (CEA) at-year follow-up in the presence of a �60% internal carotidrtery stenosis. The American Heart Association (AHA)troke Council supports these findings and recommendsEA for symptomatic patients with �50% internal carotid

tenosis and asymptomatic patients with a �60% stenosis,

Figure 1 Subclavian Stenting for Subclavian Steal Syndrome

An 83-year-old woman presented with left arm claudication and dizziness with exerupper extremities with systolic blood pressure being 30 mm Hg lower in her left arreversal of flow in the left vertebral artery. (B) There is severe elastic recoil of the28 mm Omnilink (Guidant, Temecula, California) stent is placed. (C) No residual sClinical follow-up demonstrated no recurrence of symptoms at 6 months.

rovided that surgeons can perform CEA with a complica- a

ion rate �6% in symptomatic patients and �3% in asymp-omatic patients (28).

arotid stenting. At the time of the initial reporting ofesults from NASCET and ECST, the first large multi-enter randomized clinical trial comparing an endovascularpproach to CEA for symptomatic patients with carotidtenosis was also initiated. In the CAVATAS (Carotid andertebral Artery Transluminal Angioplasty Study), 504atients were randomized to carotid balloon angioplastywith 26% stent use) versus CEA. The risk of death andpsilateral stroke at 30 days and 3 years was comparableetween the 2 strategies, with a higher risk of cranial nervealsy (8.7% CEA vs. 0% angioplasty, p � 0.0001) but

ower risk of restenosis at 1 year (4% CEA vs. 14%ngioplasty, p � 0.001) with CEA (29). Despite the lackf randomized controlled trial data demonstrating theuperiority of carotid stenting over balloon angioplasty ineducing restenosis, carotid stenting was increasinglyndertaken, as it enabled the treatment of arterial dissec-ions and addressed immediate elastic recoil after balloonngioplasty. Three-year restenosis rates with carotidtenting were reported to be �3%, but distal emboli tohe brain appeared to result in a prohibitively high risk oftroke (30). With the advent of distal embolic protectionevices, it became apparent that microemboli to the brainuring carotid stenting could be reduced, as early reports30 –33) indicated a 30-day stroke/death rate with carotidtenting to be 5% to 6% without distal embolic protectionut 2% to 3% with the use of these devices. Althoughhese were not randomized comparisons, these data haveed to a routine use of distal embolic protection duringarotid stenting. Distal embolic protection can bechieved with either filter devices or distal and proximalcclusion devices. Distal occlusion devices are not toler-

f her left arm. Asymmetric blood pressure measurements were noted in her) Angiography reveals a high grade ostial left subclavian stenosis (arrow) andbclavian artery after balloon angioplasty alone and a balloon expandable 9.0 �

s remains and antegrade flow in the left vertebral artery is immediately restored.

tion om. (Aleft sutenosi

ted by �5% of patients, and with the easier use of filter

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evices, along with comparable clinical outcomes, filterevices are predominantly used (34).Most patients enrolled in clinical trials comparing CEA

ith medical therapy were deemed to be optimal candidatesor CEA and had a low risk of surgical complications21–27). In patients considered high risk for complicationsith CEA (Table 2), the optimal treatment strategy hadeen unclear. In the multicenter SAPPHIRE (Stenting andngioplasty in Patients at High Risk for Endarterectomy)

rial, the investigators randomized 334 high-risk patients toEA versus carotid stenting with distal embolic protection

35). Patients enrolled in this trial were symptomatic with a50% stenosis (29%) or asymptomatic with a �80% ste-

osis in the internal carotid artery, elderly (mean age 73ears), and had a high percentage of coronary artery diseaseCAD) (81%). The trial demonstrated noninferiority ofarotid stenting with distal embolic protection when com-ared with CEA in the primary outcomes of death, ipsilat-ral stroke, or myocardial infarction (MI) at 30 days andpsilateral stroke and death between 31 days and 1 year20.1% CEA vs. 12.2% stenting, p � 0.004 for noninferi-rity) (Fig. 2). A higher risk of cranial nerve palsy (4.9%EA vs. 0% stenting, p � 0.004) and repeat revasculariza-

ion (4.3% CEA vs. 0.6% stenting, p � 0.04) was also seenn the surgical group. Multiple registries with variouself-expanding stents and distal embolic protection devicesave demonstrated similar results for carotid stenting inatients at high risk for CEA (30-day risk of stroke, death,nd MI 3.8% to 8.6%) (36–38). Using distal embolicrotection and self-expanding (SE) stents, good angio-raphic results (Fig. 3) and excellent clinical outcomes cane expected. However, it is important to note that these datare applicable to patients at high risk for CEA, the majority

igh-Risk Features for Carotid Endarterectomy

Table 2 High-Risk Features for Carotid Endarterectomy

SAPPHIRE trial (35)

1. Clinically significant cardiac disease (congestive heart failure, abnormalstress test, or need for open-heart surgery)

2. Severe pulmonary disease

3. Contralateral carotid occlusion

4. Contralateral laryngeal-nerve palsy

5. Previous radical neck surgery or radiation therapy to the neck

6. Recurrent stenosis after endarterectomy

7. Age �80 yrs

Main CMS criteria

1. Congestive heart failure NYHA functional class III/IV

2. Left ventricular ejection fraction �30%

3. Unstable angina

4. Contralateral carotid occlusion

5. Recent myocardial infarction

6. Previous endarterectomy with recurrent stenosis

7. Earlier radiation treatment to the neck

8. Surgically inaccessible lesion

MS � Centers for Medicare and Medicaid Services; NYHA � New York Heart Association;APPHIRE � Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy.

f whom were also asymptomatic in the studies.

The results of 2 recent randomized clinical trials (enrolledymptomatic patients not at high risk for CEA) comparingarotid stenting with CEA appear discordant with the re-ults of the SAPPHIRE trial and have called into questionhe benefits of carotid stenting for some patients (39,40). Inhe multicenter SPACE (Stent-Supported Percutaneousngioplasty of the Carotid Artery versus Endarterectomy)

rial, the investigators randomized 1,200 patients with aransient ischemic attack (TIA) or moderate stroke in thereceding 6 months to carotid stenting versus CEA. Therimary end point of death or ipsilateral ischemic stroke at0 days did not meet the prespecified criteria for noninfe-iority of stenting to CEA (6.34% CEA vs. 6.84% stenting,� 0.09 for noninferiority) (39). In the EVA-3S (Endar-

erectomy versus Angioplasty in Patients with Symptomaticevere Carotid Stenosis) trial, 527 patients with a TIA orondisabling stroke in the preceding 4 months were ran-omized to carotid stenting versus CEA. The trial was

Figure 2 1-Year Results of the SAPPHIRE Trial

Major adverse events were defined as a composite of death, stroke, or myocar-dial infarction within 30 days, or death or ipsilateral stroke between 31 daysand 1 year. In the intention-to-treat analysis (A), the rate of event-free survivalat 1 year was 87.8% among patients randomly assigned to carotid stenting,compared with 79.9% among those randomly assigned to endarterectomy (p �

0.053). In the actual-treatment analysis (B), the rate of event-free survival at1 year was 88.0% among patients who received a stent, compared with 79.9%among those who underwent endarterectomy (p � 0.048). I bars represent 1.5times the standard error. Reproduced with permission from Yadav et al. (35).

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rematurely stopped because of safety concerns; the primarynd point of death or any stroke at 30 days was higher in thetenting group (3.9% CEA vs. 9.6% stenting, p � 0.01 foruperiority) (40). The limitations in interpreting the resultsf these trials include the variability in the training of theperators performing carotid stenting, limited use of distalmbolic protection devices (27% SPACE; 92% EVA-3S),nd the surprisingly low event rate in the surgical arm ofVA-3S. Furthermore, MI rates with either strategy inoth trials were not systematically collected and reported.evertheless, these data suggest that in symptomatic pa-

ients who are not at high risk for cardiovascular complica-ions from CEA and have surgically accessible lesions, theole of carotid stenting remains limited at the present time.n multiple ongoing clinical trials, including the Nationalnstitutes of Health-sponsored CREST (Carotid Revascu-arization versus Endarterectomy Trial), low-risk patientsith carotid stenosis are being randomized to carotid

Figure 3 Carotid Stenting in a Symptomatic Patient

An 82-year-old man with a recent transient ischemic attack affecting the righthemisphere of his body, and accelerating angina, was noted to have a high-grade stenosis in the left internal carotid artery by duplex ultrasonography.(A) Angiography reveals a 90% stenosis of the left internal carotid artery.(B) Owing to proximal vessel tortousity, after the sheath is placed in the com-mon carotid artery, tortousity is displaced distally to the internal carotid artery.(C) After placement of a distal embolic protection device Accunet (Guidant,Temecula, California) and treating the lesion with a self expanding 6 to 8 � 40mm Acculink (Guidant) nitinol stent, �60% residual stenosis remains. (D) Afterballoon dilation with a 5.0 � 20 mm ViaTrac balloon (Guidant), �30% residualstenosis remains. CC � common carotid artery; EC � external carotid artery;IC � internal carotid artery.

tenting with distal embolic protection versus CEA. Until d

he results of these trials are reported, low-risk patientshould likely be treated with CEA, although patient pref-rence may occasionally dictate otherwise. On a precaution-ry note, results from the lead-in phase of CREST revealedhat the 30-day risk of stroke and death was significantlyigher for octogenarians treated with carotid stenting12.1%, age �80 years vs. 3.2%, age �80 years; p � 0.0001)41). However, as most octogenarians have also been ex-luded from CEA trials, the optimal treatment strategy forhis population remains unclear.laque characterization. Though the significance of ca-

otid stenosis is based on either angiographic or Dopplerltrasound data, little attention has been paid to plaqueharacteristics that may be better predictors of the likeli-ood of a stroke. For example, a high-grade (�70%tenosis) fibrotic lesion may be less likely to lead to anmbolic/ischemic cerebral event compared with a moderate50% stenosis) lesion that is lipid-rich, friable, ulcerated,nd therefore more vulnerable. Surface ultrasound effec-ively quantifies carotid arterial wall thickening, which is atrong indicator for the presence of CAD (42,43). Further-ore, there is significant correlation between carotid and

oronary plaque vulnerability (44,45), with plaque echoge-ecity assessed by ultrasound with integrated backscatterIBS) predicting lipid content of plaques (46,47). Echolu-ent plaques with low IBS values are macrophage-rich (48)nd associated with lipid-rich vulnerable lesions (49).cholucent carotid plaques detected by IBS analysis alsoredict cardiovascular events in patients with CAD (44),hereas treatment with pravastatin in nonhypercholste-

olemic patients with CAD results in a reduction in carotidlaque echogenecity without a change in plaque volume,ndicating plaque stabilization (50) (Fig. 4). Using B-modeltrasound, symptomatic carotid plaques were found to beore echolucent and less calcified than asymptomatic

laques and were also associated with a greater degree ofistopathologic plaque necrosis, indicative of plaque insta-ility (51). A reduction in plaque echogenecity and the usef statins are both associated with a lower likelihood of aerebrovascular event after CEA (52,53), whereas at pathol-gy, unstable plaques are seen more often with CEA inatients who have had a TIA or stroke (54). Assessment ofarotid plaque by magnetic resonance imaging in lesions0% to 79% by ultrasound reveal that vulnerable plaqueharacteristics, including the presence of thin or rupturedbrous caps, intraplaque hemorrhage, larger lipid rich/ecrotic cores, and larger maximum wall thickness, aressociated with the occurrence of future cerebrovascularvents (55). Carotid plaque echolucency also predicts anncreased likelihood of a stroke during carotid stenting (56),ut the role of statins in reducing this before carotidtenting is currently unknown.ntracranial revascularization. Intracranial atheroscleroticisease affects both the anterior and posterior cerebralirculation with symptoms of a TIA or stroke in the vascular
istribution of the affected artery; it accounts for approxi-

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ately 10% of all strokes. The treatment of intracranialtherosclerosis is predominantly medical, using antiplateletherapy and aggressive risk factor modification. However,espite optimal medical therapy, recurrent cerebrovascularvents (symptomatic patients with a 50% to 99% intracranialtenosis) are reported to be as high as 38.2% over a 2-yeareriod, with the highest recurrence in patients with hemo-ynamically significant lesions (57). The indications andptimal revascularization techniques for patients with intra-ranial atherosclerosis remain controversial. There haveeen a number of case series (57–60) showing the successfulse of both BMS and DES in treating patients with middleerebral, intracranial internal carotid, basilar, and vertebraltenotic disease (Fig. 5). However, the procedural compli-ation rates in some of these series are high (�14%eurologic complications) (57,58). No study has yetemonstrated the superiority of the endovascular ap-roach over medical therapy. A consensus document byhe American Society of Interventional and Therapeuticeuroradiology, Society of Interventional Radiology, and

he American Society of Neuroradiology recommends

Figure 4 Carotid Ultrasound for Plaque Morphology

(A,B) Representative ultrasound images of atherosclerotic carotid plaques withultrasound analysis. (A) Regular B-mode image of carotid atheroma as shownby arrowheads. Plaque-intima-media thickness (IMT)max was measured in thismode as shown by an arrow. (B) Integrated backscatter (IBS)-mode image. Thered dotted line indicates the region of interest (ROI) in the plaque (intima-media complex), and the blue dotted line indicates the ROI in the adventitiausing the manual outline definition mode. Values of cIBS and plaque-IMTmax ofthis plaque are �19.6 dB and 2.44 mm, respectively. (C,D) RepresentativeIBS images of carotid atheroma from baseline to follow-up. (C) Carotid ather-oma at pretreatment. Values of cIBS and plaque-IMTmax of this plaque are�17.8 dB and 2.05 mm, respectively. (D) The same carotid atheroma post-pravastatin therapy (6 months). Values of cIBS and plaque-IMTmax of this plaqueare �14.2 dB and 2.10 mm, respectively. CCA � common carotid artery; ICA� internal carotid artery. Adapted with permission from Watanabe et al. (50).

hat intracranial angioplasty/stenting be reserved for pa-

ients with a 50% to 99% intracranial stenosis in whomedical therapy has failed (61). The treatment of acute

troke in thrombolytic ineligible or thrombolytic failureatients with percutaneous revascularization using mechan-cal thrombectomy, adjunctive stenting, and local delivery ofbrinolytic therapy has been described with relatively goodesults (62–64) (Fig. 6). We support this approach, butcknowledge that the data supporting it are largely descrip-ive and have not been subjected to adequately controlledlinical trials. In contrast, the treatment of intracranialneurysms and arteriovenous malformations with endovas-ular coiling and local injection of glue, respectively, are wellefined and routinely performed (65,66).

enal Artery Stenosis

ypertension affects more than 25% of the worldwide adultopulation (67). Although the vast majority have essential

Figure 5 Basilar Artery Stenting for Lightheadedness

A 78-year-old woman presented with episodic lightheadedness, and a completework-up including magnetic resonance angiography (MRA) of the brain sug-gested a high-grade stenosis of the basilar artery (BA). (A) Intracerebral angio-graphy confirms a high-grade proximal BA stenosis (arrow) of 95%. (B) Afterballoon dilation, �30% residual stenosis remains. She had difficulty with herbalance and vision for 1 month after the procedure, but then her symptomscompletely resolved. (C) Six months later with symptom recurrence, an MRAdemonstrated restenosis of the BA, which is confirmed by intracerebral angio-graphy. Note the hypoplastic left vertebral artery (LVA). (D) After placement ofa 2.5 � 12 mm Taxus (Boston Scientific, Natick, Massachusetts) drug-elutingcoronary stent (thick arrow), �20% residual stenosis remains, and the patienthas had no further neurological events at 24-month follow-up. The hypoplasticLVA and the left inferior cerebellar artery (LICA) (thin arrows) both remainpatent after stent placement across these vessels. LPCA � left posterior cere-bral artery; RPCA � right posterior cerebral artery; RVA � right vertebral artery.

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ypertension, it is important to identify patients withecondary treatable causes of hypertension, especially ath-rosclerotic renal artery stenosis (RAS), the most commonause of renovascular hypertension (68). Clinical clues to theresence of RAS include onset of hypertension before age0 years or severe hypertension after age 55 years, exacer-ation of well-controlled hypertension, malignant hyperten-ion, progressive renal insufficiency, azotemia with initiationf angiotensin-converting enzyme inhibitor therapy, renaltrophy, or cardiac dysfunction (Tables 3 and 4) (69).oninvasive tools for detecting RAS have sensitivities

anging from 80% to 100%, whereas their specificity variesrom 75% to 100% (Table 5) (70). An overview of variousoninvasive studies (70) demonstrates that both computedomographic angiography and magnetic resonance angio-raphy are more accurate than ultrasound or the captoprilenal scan in diagnosing RAS, but ultrasound does have thedded benefit of providing information regarding renalunctional reserve. Furthermore, ultrasound evaluation isften the first screening test as it is inexpensive, does not

Figure 6 Intracranial Local Thrombolysis After Iatrogenic Strok

A 52-year-old man who had undergone a previous renal transplant and coronary arrior descending artery (LAD) was occluded, a proximal LAD lesion was stented. He45 min after the procedure, the patient had right hemianopsia, and emergent intrahead excluded an intracranial hemorrhage. (A) Anterior circulation angiography: lefand middle cerebral (MC) arteries without significant disease of the intracranial intwith intracranial imaging demonstrates left posterior cerebral artery (PCA) occlusiobeyond the occlusion in the left PCA via the vertebral artery approach, and contrasAfter local delivery of intra-arterial thrombolytic therapy, flow is restored in the left� basilar artery; VA � vertebral artery.

equire contrast, is both sensitive and specific, and provides I

nformation regarding kidney size and renal resistive index.high renal artery end-diastolic velocity (�90 cm/s) and

ow renal resistive index (�75 to 80) identify patientsithout microvascular disease or increased resistance in the

egmental arteries and who are therefore more likely toerive a clinical benefit from renal artery revascularization71,72).

In the context of high clinical suspicion, a renal arteryngiogram in multiple views is desirable and remains thegold standard” for the diagnosis of RAS. Among patientsndergoing cardiac catheterization and not previously sus-ected of having atherosclerotic RAS with any of: 1) severeypertension; 2) unexplained renal dysfunction; 3) acuteulmonary edema with hypertension; or 4) severe athero-clerosis, 39% had renal atherosclerosis, with 14.3%aving �50% RAS (73). Traditionally, an angiographictenosis �70%, a resting pressure gradient of �20 mmg across the stenosis, or unmasking of resistive renal

rtery lesions with intrarenal injection of papaverine orcetylcholine has been required for revascularization (74).

pass graft surgery presented with unstable angina. As the graft to the left ante-nd eptifibatide were used as the antithrombotic and antiplatelet regimen. About

ral angiography was performed after a computerized tomography scan of theon carotid angiography with intracranial imaging reveals patent anterior (AC)

carotid artery (IC). (B) Posterior circulation angiography: left vertebral angiographyw). (C) A Tracker catheter (Boston Scientific, Natick, Massachusetts) is placedtion through the catheter confirms the patency of the distal vasculature. (D)ith the patient leaving the hospital with only a mild residual visual field cut. BA

e

tery byparin acerebt commernaln (arrot injecPCA w

n an interesting study, De Bruyne et al. (75) demonstrated

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ncreased renin production associated with renal stenoseshat had a distal to proximal renal artery pressure drop of

10%, suggesting that this might also identify hemody-amically significant RAS. Medical therapy is, however,referred over renal revascularization for patients with RASnd advanced renal disease as manifested by chronic renalailure (creatinine �2.5 mg/dl with unilateral RAS), pro-einuria (�1 g/day), diffuse intrarenal vascular disease, renaltrophy (kidney length �7.0 cm), or a resistive index �8076).

enal artery balloon angioplasty. Fibromuscular dysplasias a nonatherosclerotic, noninflammatory disease that mostommonly affects the renal and internal carotid arteries (77).he etiology of this condition remains unknown, but it

ccounts for �10% of renovascular hypertension and isredominantly diagnosed in young women (77). Percutane-us transluminal renal artery balloon angioplasty (PTRA) ishe preferred treatment strategy for renovascular hyperten-ion resulting from fibromuscular dysplasia, but the dataupporting this approach are largely descriptive and fromhe prestent era (78). Although this approach works well foratients with fibromuscular dysplasia, the diagnosis ofemodynamically significant disease by angiography in thisondition can be difficult. We have described the use of aressure measurement wire to obtain pressure gradients

linical Clues to theiagnosis of Renal Artery Stenosis

Table 3 Clinical Clues to theDiagnosis of Renal Artery Stenosis

1. Onset of hypertension at �30 yrs of age or severe hypertension at�55 yrs of age (Class I; Level of Evidence: B)

2. Accelerated, resistant, or malignant hypertension (Class I; Level ofEvidence: C)

3. Unexplained atrophic kidney or size discrepancy �1.5 cm between kidneys(Class I; Level of Evidence: B)

4. Sudden, unexplained pulmonary edema (Class I; Level of Evidence: B)

5. Unexplained renal dysfunction, including individuals starting renalreplacement therapy (Class IIa; Level of Evidence: B)

6. Development of new azotemia or worsening renal function afteradministration of an ACE inhibitor or ARB agent (Class I; Level of Evidence: B)

7. Multivessel coronary artery disease or peripheral arterial disease (Class IIb;Level of Evidence: B)

8. Unexplained congestive heart failure or refractory angina (Class IIb; Level ofEvidence: C)

ee Table 4 for definition of classification and level of evidence.ACE � angiotensin-converting enzyme; ARB � angiotensin receptor blocker.

lassifications and Levels of Evidence

Table 4 Classifications and Levels of Evidence

Classification

Class I: Intervention is useful and effective

Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy

Class IIb: Usefulness/efficacy less well-established by evidence/opinion

Class III: Intervention is not useful/effective and may be harmful

Levels of Evidence

A: Sufficient evidence from multiple randomized trials

B: Limited evidence from single, randomized trial or other nonrandomizedstudies

mC: Based on expert opinion, case studies, or standard of care

hroughout the diseased segment in patients with fibromus-ular dysplasia, which can be helpful in determining theignificance of a specific stenosis and appropriate treatmentFig. 7) (79).

The results of PTRA alone have been disappointing inhe treatment of atherosclerotic RAS, which accounts forhe vast majority of patients with renovascular hypertension.n the DRASTIC (Dutch Renal Artery Stenosis Interven-ion Cooperative) trial, 106 patients with atheroscleroticAS, hypertension despite treatment with �2 antihyper-

ensive medications, and a serum creatinine �2.3 mg/dlere randomized to PTRA versus medical therapy. This

tudy demonstrated that PTRA offered little benefit overedical therapy for the treatment of hypertension (80).owever, major limitations of this study included the enroll-ent of patients with insignificant RAS, a 44% crossover fromedical therapy to PTRA, and low use of stents (20%).evertheless, because of the scant data that previously existed

n the subject, this study had a broad impact on clinicalractice, and enthusiasm for percutaneous revascularization ofatients with atherosclerotic RAS diminished.enal artery stenting. The frequent involvement of thestial renal artery in atherosclerotic RAS leads to highlastic recoil with PTRA and subsequently high restenosisates of 42% to 47% (81,82). The problem of elastic recoil islleviated by using BE stents, which provide mechanicalcaffolding (Fig. 8). Results from observational studies haveemonstrated that renal stenting is safe and effective ineducing blood pressure (83,84). A randomized trial provedhe superiority of renal stenting over PTRA for immediaterocedural success (88% stent vs. 57% PTRA) and loweringestenosis rates (14% stent vs. 48% PTRA) (85). However,linical, angiographic, and biomarker criteria that identifyndividual patients who may respond to renal stenting areimited, although serum brain naturetic peptide �80 pg/ml

ay be one such marker (86). Concerns have existedegarding the deleterious effects of renal stenting on renalunction in patients with chronic renal insufficiency (83).hese concerns were largely allayed by recent studies (87,88)emonstrating improvement or stabilization of renal functionfter unilateral or bilateral renal stenting in patients withtherosclerotic RAS and progressive renal insufficiency.

In patients with RAS and hypertension (BP �140/90m Hg) despite treatment with at least 2 antihypertensiveedications, renal stenting results in systolic blood pressure

eduction of 20 mm Hg and the use of 1 less antihyperten-ive medication (89). This improvement in blood pressure is

oninvasive Tests tovaluate Renal Artery Stenosis

Table 5 Noninvasive Tests toEvaluate Renal Artery Stenosis

Test Sensitivity (%) Specificity (%)

Duplex ultrasonography 80–90 80–90

Magnetic resonance angiography 88–100 75–100

Computed tomographic angiography 94–100 92–99

aintained at the 2-year interval, but these results were

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btained at the expense of a 17.4% restenosis rate. Althoughrachytherapy and cutting balloon atherotomy have beensed successfully for renal artery in-stent restenosis (90,91),ong-term outcomes are unknown. The use of coronary

ES has also been described for small renal arteries (92),ut no well-designed studies to determine adequate doses ofhe eluting drug for this vessel have been performed. Theargest DES is only 3.5 mm in diameter, a size that isnadequate for renal stenting (normal diameter 4 to 7 mm).

istal embolic protection devices have also been used toapture atherosclerotic debris and prevent it from distalmbolization during renal stenting (93). Theoretically, thisay help preserve renal function. Although surgical revas-

ularization is effective for the treatment of RAS, its role isimited and will likely not be subjected to a randomizedlinical trial against renal stenting owing to the higherorbidity and mortality of the surgical approach.Long-term outcome data after renal stenting using end

oints such as stroke, MI, heart failure, renal failure, andeath need to be obtained. These data are being gathered inhe ongoing CORAL (Cardiovascular Outcomes in Renaltherosclerotic Lesions) study (94). This National Heart,

Figure 7 Renal Artery Angioplasty for Fibromuscular Dysplasia

A 39-year-old woman presented with poorly controlled hypertension despite being tgram suggested right renal artery stenosis. (A) Selective right renal artery angiogr(B) Selective right renal artery angiography after percutaneous transluminal balloowith a minor angiographic change (arrow) just before the renal artery bifurcation. (renal artery pressure (Pa), phasic and mean distal renal artery pressure (Pd), andrenal artery peak-to-peak systolic gradient of 42 mm Hg, mean pressure gradient osuccessful PTA, PressureWire measurement reveals a 0 mm Hg residual gradienttension resolved at follow-up examination, and she did not require any antihyperte

ung, and Blood Institute-sponsored study is to test the a

ypothesis that renal ischemia, with its consequent neu-oendocrine activation, contributes to adverse cardiovascularnd renal events, independently of the blood pressurechieved. The results of this trial are years away, but on theasis of the currently available data, patients with athero-clerotic RAS who are hypertensive (blood pressure140/90 mm Hg) despite treatment with �2 antihyper-

ensive medications, a serum creatinine �3.0 mg/dl, and aidney �8 cm in length should be considered for renalrtery stenting. In such patients, good procedural outcomesnd the long-term benefits of improved blood pressureontrol and renal function preservation can be expected.

ortoiliac and Iliac Disease

therosclerosis affecting iliac or aortoiliac vessels manifestss hip, thigh, or leg claudication and can certainly contributeo critical limb ischemia. Isolated stenosis or occlusion ofhe terminal aorta is fairly uncommon but can result in theeriche syndrome with claudication of the upper thighs anduttocks, erectile dysfunction, and diminished femoralulses. Obstructive atherosclerotic disease of the terminal

ypertension

with 2 antihypertensive medications. A renal artery magnetic resonance angio-emonstrating the classic “beaded” appearance of fibromuscular dysplasia.oplasty (PTA) continues to demonstrate the classic “beaded” appearance of FMDsults of PressureWire measurement depicting the phasic and mean proximalnal flow reserve (FFR). This figure demonstrates a distal renal artery to proximalm Hg, and a mean distal to proximal artery pressure ratio of 0.71. (D) After

mean distal to proximal renal artery pressure ratio of 1.0. The patient’s hyper-herapy. Adapted with permission from Mahmud et al. (79).

and H

reatedaphy dn angiC) Refractiof 30 m

and ansive t

orta and the iliac arteries is preferentially treated with

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ndovascular techniques rather than surgery. In 1999, therans-Atlantic Inter-Society Consensus (TASC) groupeveloped treatment guidelines for symptomatic lesions inhe iliac arteries based on lesion location and characteristicsTable 6) (95). The recommendations were for treatingASC type A to B lesions with an endovascular approach andASC type C to D lesions surgically. However, with rapid

volution of endovascular techniques, TASC type C and Dliac lesions can be treated percutaneously as well, withong-term patency rates comparable to aortofemoral bypassurgery without the associated morbidity and mortality (96).ndovascular stenting. Atherosclerosis affecting the ter-inal aorta commonly also involves the bifurcation of the

ommon iliac arteries. These bifurcation lesions can bereated using a bilateral retrograde femoral arterial ap-roach. The choice of BE versus SE stents to treat these

esions is determined by a number of factors, includingperator preference. Isolated ostial and nonostial commonliac lesions are better treated with BE stents, which areasier to place accurately and have superior radial strengthnd better radiovisibility. The “kissing stent” technique withE stents is recommended when there is minimal diseaseffecting the terminal aorta and the ostia of both commonliac arteries are being treated. Excellent procedural out-omes (100% success without any major adverse events) andong-term patency (primary patency 92% and secondaryatency 100% at 20 months) have been reported with thispproach, even in a cohort of high-risk patients with diseaseffecting the terminal aorta and aortoiliac bifurcation (97).n the presence of atherosclerosis affecting the terminalorta, to minimize the risk of aortic dissection, the “huggingtent” (Fig. 9) technique using 2 SE stents deployedimultaneously from the terminal aorta into each respectiveommon iliac artery may be preferred.

The iliac arteries, particularly the external iliac artery,

Figure 8 Renal Artery Stenting for Renovascular Hypertension

A 69-year-old man with a serum creatinine of 1.7 mg/dl and hypertension (blood pwent magnetic resonance angiogram, which revealed a left renal artery stenosis. (90% (arrow) in the presence of an accessory left renal artery. (B) After balloon an(arrow) without complete resolution of the pressure gradient across the stenosis.in the main renal artery (arrow) and a 3.5 � 13 mm Cypher drug-eluting stent (Co6-month follow-up, the patient had a blood pressure of 130/85 mm Hg and requir

ave a high rate of dissection and elastic recoil. Therefore,CT

rimary stenting is performed in the vast majority of theseases, with few operators still using a provisional stentingtrategy. A small randomized trial comparing balloon an-ioplasty (with provisional stenting) against primary stent-ng for iliac stenoses demonstrated no difference in proce-ural success or 2-year clinical outcomes (98). However, aeta-analysis of 14 studies performed since 1990 involving

ither balloon angioplasty or stenting to treat iliac stenosesevealed higher procedural success with stenting and a 39%ower risk of long-term failure with stenting compared withalloon angioplasty (99). The 3-year assisted patency rateor stenting of occluded iliac arteries is 80% to 90%96,100), which compares favorably to surgical revascular-zation (5-year patency of aortobifemoral grafts: 91% for

e 158/97 mm Hg) despite treatment with 4 antihypertensive medications under-selective left renal artery angiography, a high-grade left renal artery stenosis ofsty, there is evidence of elastic recoil at the ostium and a residual stenosister placement of a 6.0 � 18 mm Herculink stent (Guidant, Temecula, California)iami, Florida) in the accessory renal artery, no residual stenosis remains. Attment with 2 antihypertensive medications.

ASC Classification of Iliac Lesions

Table 6 TASC Classification of Iliac Lesions

Type A

1. Single stenosis �3 cm of the CIA or EIA (unilateral/bilateral)

Type B

2. Single stenosis 3–10 cm in length, not extending into the CFA

3. Total of 2 stenoses �5 cm long in the CIA and/or EIA; not extendingto CFA

4. Unilateral CIA occlusion

Type C

5. Bilateral stenoses 5–10 cm length of CIA and/or EIA; not extending to CFA

6. Unilateral EIA occlusion not extending to CFA

7. Unilateral EIA stenosis extending to CFA

8. Bilateral CIA occlusion

Type D

9. Diffuse, multiple unilateral stenoses of CIA, EIA, and CFA (usually �10 cm)

10. Unilateral occlusion involving both the CIA and EIA

11. Bilateral EIA occlusions

12. Diffuse disease involving the aorta and both iliac arteries

13. Iliac stenoses in a patient with an abdominal aortic aneurysm or otherlesion requiring aortic or iliac surgery

ressurA) Ongiopla(C) Afrdis, Med trea

FA � common femoral artery; CIA � common iliac artery; EIA � external iliac artery; TASC �

ransAtlantic Inter-Society Consensus.

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laudication and 88% for critical limb ischemia) without thessociated 8.3% surgical morbidity and 3.3% surgical mor-ality (101). Lower primary patency with endovascularevascularization of iliac arteries has been noted in theresence of diabetes, critical limb ischemia, poor distalunoff, renal insufficiency, and female gender (96,102).

TOs. Hydrophilic wires and catheters can be used toraverse CTOs in the peripheral vasculature, but this tech-ique is somewhat limited if the wire becomes subintimal,nd entrance to the true lumen beyond the occlusion is notchieved. Recently, true lumen re-entry catheters haveecome available for treating CTOs in the iliac and super-cial femoral arteries, which enable much higher proceduraluccess. In a series of 87 CTOs in the iliac and superficialemoral arteries, the investigators reported failure to re-analize 28% of CTOs with standard techniques, all ofhich they successfully traversed and treated with the

ssistance of either the intravascular ultrasound-based Pio-eer (Medtronic, Minneapolis, Minnesota) or fluoroscopy-ased Outback (Cordis, Miami, Florida) re-entry catheter103). In another series of 44 patients, controlled blunticrodissection with a novel device developed for this

urpose is reported to be successful in recanalizing 91% ofcreening Guidelines for Populations atigh Risk for Abdominal Aortic Aneurysms

Table 7 Screening Guidelines for Populations atHigh Risk for Abdominal Aortic Aneurysms

Class I

1. Men 60 yrs of age or older who are either the siblings or offspring ofpatients with AAAs should undergo physical examination and ultrasoundscreening for detection of aortic aneurysms. (Level of Evidence: B)

Class IIa

2. Men who are 65 to 75 yrs of age who have ever smoked should undergoa physical examination and 1-time ultrasound screening for detectionof AAAs. (Level of Evidence: B)

Figure 9 Iliac Stenting for Claudication

A 68-year-old man presented with severe lifestyle-limiting claudication despite maxand an aggressive control of all modifiable risk factors including smoking cessatiomagnetic resonance angiogram, suggested severe bilateral aortoiliac and externalgrade disease in the left and right common and external iliac arteries. (B) Kissing(Guidant, Temecula, California) stents in the left and right common iliac arteries inplaced in an overlapping manner in the left external iliac artery. (C) Final abdominents followed by dramatic symptomatic improvement.

ee Table 4 for classification and level of evidence.AAA � abdominal aortic aneurysms.

S

TOs in the iliac and femoral arteries (104). Patients withnoncrossable lesion in the iliac artery or a concomitant

arge infra-abdominal aneurysm are best treated surgically.

bdominal Aortic Aneurysms (AAA)

bdominal aortic aneurysm remains a significant cause oforbidity and mortality owing to rupture, thromboembolic

schemic complications, and compression of adjacent struc-ures. Risk factors for the development of an AAA includege, smoking, hypertension, higher body mass index, andlcohol consumption (105). Men with a family history of anAA in a primary relative or who have smoked are at higher

isk for developing an AAA (69). The most recent screening

ndications for Abdominalortic Aneurysm Repair

Table 8 Indications for AbdominalAortic Aneurysm Repair

Class I

1. Patients with infrarenal or juxtarenal AAAs measuring 5.5 cm or largershould undergo repair to eliminate the risk of rupture. (Level of Evidence: B)

2. Patients with infrarenal or juxtarenal AAAs measuring 4.0 to 5.4 cm indiameter should be monitored by ultrasound or CT scans every 6 to 12months to detect expansion. (Level of Evidence: A)

Class IIa

1. Repair can be beneficial in patients with infrarenal or juxtarenal AAAs 5.0 to5.4 cm in diameter. (Level of Evidence: B)

2. Repair is probably indicated in patients with suprarenal or type IVthoracoabdominal aortic aneurysms larger than 5.5 to 6.0 cm. (Level ofEvidence: B)

3. In patients with AAAs smaller than 4.0 cm in diameter, monitoring byultrasound examination every 2 to 3 yrs is reasonable. (Level ofEvidence: B)

Class III

1. Intervention is not recommended for asymptomatic infrarenal or juxtarenalAAAs if they measure �5.0 cm in diameter in men or �4.5 cm in diameterin women. (Level of Evidence: A)

medical therapy including aspirin, cilostazol, atorvastatin, an exercise program,ninvasive work-up, including ankle-brachial indices (�0.60 bilaterally) and aisease. (A) Abdominal angiography demonstrates bilateral long-segment high-n angioplasty after placement of 2 self-expanding 9.0 � 100 mm Absolutehugging stent” manner. An additional 8.0 � 56 mm Absolute stent is alsoogram reveals no significant residual stenosis and resolution of all resting gradi-

imumn. A noiliac dballoothe “

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uidelines (Table 7) endorsed by the American College ofardiology (ACC) and AHA advocate the frequent use of

bdominal ultrasound to detect the presence of an AAA inigh-risk patients and at least once in low-risk patients overhe age of 60 years (69).

Aneurysm size is the single most accurate predictor of theisk of complications. In asymptomatic patients, repair isndicated once the size exceeds 5.5 cm (106). However, inatients with the clinical triad of abdominal and/or backain, a pulsatile abdominal mass, and hypotension, imme-iate evaluation is required. The ACC/AHA guidelines alsoddress the indications for the ongoing monitoring andreatment of an AAA (Tables 8 and 9) (69). Although openurgical repair of AAA remains the standard technique, thisperation has substantial morbidity and a perioperative

anagement of AAA: Openurgical Repair Versus Endovascular Repair

Table 9 Management of AAA: OpenSurgical Repair Versus Endovascular Repair

Class I

1. Open repair of infrarenal AAAs and/or common iliac aneurysms is indicatedin patients who are good or average surgical candidates. (Level ofEvidence: B)

2. Periodic long-term surveillance imaging should be performed to monitor foran endoleak, to document shrinkage or stability of the excluded aneurysmsac, and to determine the need for further intervention in patients whohave undergone endovascular repair of infrarenal aortic and/or iliacaneurysms. (Level of Evidence: B)

Class IIa

1. Endovascular repair of infrarenal aortic and/or common iliac aneurysms isreasonable in patients at high risk of complications from open operationsbecause of cardiopulmonary or other associated diseases. (Level ofEvidence: B)

Class IIb

1. Endovascular repair of infrarenal aortic and/or common iliac aneurysmsmay be considered in patients at low or average surgical risk. (Level ofEvidence: B)


Medical Therapy for Claudication

Table 10 Medical Therapy for Claudication

Therapy

Supervised exercise program (116) 30–45 m

Cilostazol (phosphodiesteraseinhibitor); mechanism ofbenefit unknown (117)

100 mg

Pentoxifylline (lowers blood viscosityby modifying red blood cellconformability); mechanism ofbenefit unclear (116,118)

400 mg

Antiplatelet agents (118,119):

Aspirin 75–325

Clopidogrel (aspirin-intolerant) 75 mg Q

Risk factor modification(116,118,120): Goals:

Blood pressure BP �13

Diabetes HbA1C �

Lipids LDL cho

Smoking Cessatio

BID � twice a day; BP � blood pressure; HbA1C � glycosylated hemoglobin; Ldaily; TID � three times a day.

ortality of 4% to 7% (107,108). Endovascular repair resultsn fewer periprocedural complications, including less bloodoss, fewer cardiac and pulmonary complications, and ahorter hospitalization stay, but it is associated with a higherate of reintervention predominantly to treat endoleaks andaintain graft patency (109–113). With further advances in

echnology, these complications will likely diminish, and thendications for endovascular repair may further expand.

nfrainguinal Disease

therosclerosis affecting the lower extremities frequentlyeads to lifestyle-limiting claudication and can lead toritical limb ischemia. Disease affecting the lower extremityeripheral vessels is most progressive in smokers and dia-etics and has the worst outcomes, regardless of therapies,n patients with poor distal arterial runoff (114,115). Inatients with claudication, exercise programs increase walk-ng distance (compared with medical therapy), but mosttudies were performed before contemporary percutaneousevascularization techniques (116). It is quite possible thatggressive medical therapy, smoking cessation, an exerciserogram, and secondary risk factor modification (Table 10)117–120) with adjunctive percutaneous revascularization ofhe infrainguinal vessels would result in an incrementalmprovement in exercise ability and improved long-termlinical outcomes. In fact, a recent longitudinal study of 300atients undergoing lower extremity percutaneous revascu-

arization with contemporary medical therapy demonstratesmprovement in symptoms, functional status, and quality ofife at 3-year follow-up (121). Infrainguinal disease isivided and treated on the basis of 3 anatomic segments.ommon femoral artery. Atherosclerotic disease affecting

he common femoral artery is best treated surgically with anliofemoral bypass operation or endarterectomy with patch

ency Benefit

/week Comparable to cilostazol

Improves walking distance:40%–60%

Improves walking distance:20%–25%

Decreases risk of MI, strokeand vascular death

Decreases risk of MI, stroke,vascular death, andmicrovascular ischemicevents

m Hg

l �100 mg/dl

Frequ

in 3 �

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DL � low-density lipoprotein; MI � myocardial infarction; QD � once

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CTO � chronic total occlusion; SFA � superficial femoral artery.


ngioplasty (122). As this vessel lies over the hip joint,lacement of stents is suboptimal, and restenosis or stenthrombosis can be associated with acute limb-threateningschemia as circulation to both the superficial femoral arterySFA) and the profunda femoris can be compromisedimultaneously. Common femoral artery stenting, and de-ulking with rotational atherectomy or extraction atherec-omy for patients who are poor candidates for surgery andresent with critical limb ischemia or severe lifestyle-

imiting claudication, have all been described (123,124).owever, acute vessel closure or late restenosis are both

ssociated with the risk of limb loss.uperficial femoral artery. Percutaneous treatment of theFA by balloon angioplasty or stenting is associated withuboptimal long-term clinical outcomes. Short, focal (�5m) lesions in the SFA respond well to balloon angioplastylone, with primary and secondary patency rates comparableo stenting (125). Therefore, endovascular stenting in theFA is generally indicated only in the presence of aow-limiting dissection or severe elastic recoil after balloonngioplasty. A recent randomized controlled clinical trial inhich patients with long SFA lesions (mean length 13 cm)ere enrolled revealed that stenting with SE nitinol stents

eads to lower 6-month angiographic restenosis rates com-ared with balloon angioplasty alone (24% stent vs. 43%alloon angioplasty, p � 0.05) and may be the preferredpproach (126). However, in the majority of patients withtherosclerosis of the SFA, the disease is often diffuse,ssociated with chronically occluded segments, and cannvolve the region of the adductor canal. This leads to issuesf vessel and stent flexion, elongation, and torsion duringoutine daily activities, which in turn are associated with theevelopment of stent fractures (Fig. 10) (127). Self-xpanding drug-eluting nitinol stents have also been inves-igated for use in the SFA in a randomized clinical trial, but

scularization

Utility

CA) Plaque extraction from the SFA andinfrapopliteal vessels.

prings, CO) Electromagnetic energy is used to ablateplaque and thrombus in the SFA andinfrapopliteal vessels.

MA) Facilitates balloon angioplasty withcontrolled lesion dilation.

Balloon angioplasty with transient coolingto –5° C using nitrous oxide topromote apoptosis and preventneointimal proliferation.

Blunt microdissection tool to help in therecanalization of a CTO.

Facilitates re-entry from a false to a truelumen in recanalizing a CTO(fluoroscopy-based).

N) Facilitates re-entry from a false to a truelumen in recanalizing a CTO(intravascular ultrasound-based).

Figure 10 Stent Fracture in the Superficial Femoral Artery

Self-expanding nitinol stent 9 months after implantation showing a severestent fracture in the distal and a moderate stent fracture (arrows; left panel)in the proximal part of the stent. Angiographically, both lesions were associ-ated with a restenosis �50% diameter reduction (arrows; right panel). Repro-duced with permission from Scheinert et al. (127).

New Devices for Lower Extremity Revascularization

Table 11 New Devices for Lower Extremity Reva

Device Manufacturer

SilverHawk Extraction Atherectomy Foxhollow (Redwood City,

Excimer Laser Atherectomy Spectranetics (Colorado S

Cutting Balloon Atherotomy Boston Scientific (Natick,

Polar Cath Cryotherapy Boston Scientific

Frontrunner Cordis (Miami, FL)

Outback Cordis

Pioneer Medtronic (Minneapolis, M

do

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id not reveal a difference in angiographic or clinicalutcomes compared with a SE nitinol stent (128).A number of devices have recently become available for

se in the peripheral vasculature (Table 11); most are usedor the treatment of lesions affecting the SFA. Thesenclude extraction atherectomy with the SilverHawk (Fox-ollow, Redwood City, California), laser atherectomySpectranetics, Colorado Springs, Colorado), cutting bal-oon atherotomy (Boston Scientific, Natick, Massachusetts),nd cryotherapy (Boston Scientific). Devices that aid in theecanalization of CTOs include the Pioneer (Medtronic),utback (Cordis), and Frontrunner (Cordis) catheters.one of these devices has been tested in randomized clinical

rials; even the registry outcome data with these devices haveot been rigorously controlled or monitored. This has led tonumber of these devices being used with unclear long-

erm benefits. Recently, enthusiasm for the SilverHawktherectomy device has been noted, and when it is used inhe SFA, large amounts of plaque can be retrieved (Fig. 11).his appears to result in low repeat revascularization rates in

ymptomatic patients who undergo plaque excision (129).imilarly, laser atherectomy may increase limb salvage rates

n patients with limb ischemia but is rarely used (130).ryotherapy appears comparable to balloon angioplasty

lone in the treatment of focal SFA lesions, with 9-monthepeat revascularization rates of 18% (131).

It appears, therefore, that for lesions in the SFA up to 10m in length, endovascular stenting with nitinol SE stentsr extraction atherectomy both seem reasonable options andre superior to balloon angioplasty alone. However, the rolesf stenting, atherectomy, and cryotherapy need to be better

Figure 11 Extraction Atherectomy of the Superficial Femoral A

A 64-year-old woman with right leg claudication (ankle-brachial index 0.68) despitephy with lower extremity runoff. (A) An occluded right superficial femoral artery (SF(B) The occlusion in the right SFA (arrow) is just beyond the ostium of the vessel.wire is exchanged over an end-hole catheter to a 0.014-inch BMW wire (Guidant, Tter is performed. (D) Final angiographic result after significant plaque extraction. Dsite of atherectomy and the patient remained clinically asymptomatic. CFA � comm

efined because the options for the treatment of restenosis c

n this vessel remain limited. Brachytherapy has been triednd shown to be successful (132) but is not widely available,nd long-term benefits are unclear. For long-term success ofercutaneous revascularization of the SFA, good in-flownd, at a minimum, single-vessel runoff to the foot areesirable. Surgical femoral-popliteal bypass operation re-ains an option for patients with chronic limb ischemia.elow-the-knee. Obstructive atherosclerotic disease af-

ecting the popliteal and infrapopliteal vessels is treatedercutaneously or with medical therapy. For patients witheverely symptomatic claudication unresponsive to medicalherapy and an aggressive exercise program, infrapoplitealngioplasty, atherectomy, and stenting should be consid-red. The use of DES has been described for below-the-nee revascularization with a low restenosis rate (133,134).his has also led to the approval in Europe of the BE

irolimus-eluting stent Cypher (Cordis) for this indication.owever, there is a paucity of long-term data regarding the

enefit of this strategy. In cases of limb salvage where inlineow is required to help heal an ulcer, ischemic area, or

nfection, aggressive percutaneous revascularization is indi-ated and has been shown to increase tissue healing andeduce the incidence of amputation resulting in limb salvage133,135).

onclusions

remendous advances were made over the past decade inew techniques and devices for the treatment of atheroscle-otic disease affecting the peripheral arterial vessels. Histor-cally, patients with symptomatic PAD were treated medi-

ssive medical therapy and an exercise program underwent abdominal angiogra-beyond the ostium is noted with three vessel runoff to the foot via collaterals.

fter traversing the stenosis with a 0.035-inch guidewire (Terumo, Japan), thela, California), and atherectomy with a SilverHawk (Foxhollow, California) cathe-ultrasound follow-up at 12 months revealed no evidence of restenosis at themoral artery.

rtery

aggreA) just(C) A

emecuuplexon fe

ally, with surgical revascularization reserved as an option

fihnmorfmwt

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R


or advanced disease. There is significant symptomaticmprovement with the surgical approach, but the associatedigh morbidity and mortality preclude its routine use. Theewer percutaneous treatment options are associated withuch lower procedural complications and good long-term

utcomes. Although more randomized clinical trials andegistries with independent monitoring need to be per-ormed, the threshold for percutaneous revascularizationay also need to be lowered, as a greater number of patientsith symptomatic peripheral vascular disease can now be

reated with lower procedural risks.

eprint requests and correspondence: Dr. Ehtisham Mahmud,irector, Cardiovascular Catheterization Laboratories, University

f California, San Diego Medical Center, 200 West Arbor Drive,an Diego, California 92103-8784. E-mail: [email protected].

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current treatment of peripheral arterial disease · panvascular inﬂammation and, often,...

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