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Caroline Clezar, MD1, Fabrizzio Souza, MD1, Nicolle Cassola, MD1, Carolina Benze, MD1, André Milani, MD1, Felipe Nasser, PhD2, Breno Affonso, PhD2, Jorge Amorim, PhD1, Fausto Miranda, Jr., PhD1

From 1Vascular Surgery Division, Department Of Surgery, Paulista School of Medicine, Federal Universivity of Sao Paulo, Brazil and 2Vascular and Endovascular Surgeon from Interventional Vascular Radiology Department, Israelite Albert Einstein Hospital, Sao Paulo, Brazil.

Endovascular Management of Drug-Eluting Balloons in the Lower Limbs

ABSTRACT: Lower-extremity PAD limits quality of life as it often results in severe limb ischemia, possible limb loss, and is accompanied by serious cardiovascular morbidity and high mortality. Interventional approaches have come a long way, with angioplasty and stenting remaining at the forefront. But arterial restenosis continues to limit the benefits of these treatments. New DEB technologies offer the hope of significant reductions of such problems, enhancing the results of angioplasty while, at the same time, providing the opportunity for avoidance of a permanent metal stent implant. Results so far are most encouraging, and are illustrated with several case examples. More and better trials and long-term outcomes in larger series of patients are eagerly awaited to deter-mine if the early promise becomes an established reality and a place of therapeutic prominence for DEB devices.

VASCULAR DISEASE MANAGEMENT 2013:10(12):E259-E263 Key words: angioplasty, critical limb ischemia, drug-eluting balloons, peripheral vascular disease, restenosis

Lower-extremity peripheral ar-terial disease (PAD) is a highly prevalent and morbid condition

carrying tremendous potential to cause severe leg ischemia, and is accompanied by notorious risks of premature cardio-vascular morbidity and mortality. Avoid-ance of limb loss and disability consti-tute the principal goals of treatment.

Complex and extensive PAD have steadily risen to become a serious chal-lenge for vascular specialists, mainly because of the frequent occurrence of long lesions, multiple stenoses, heavily calcified lesions, restenosis (arterial or intrastent), and chronic total occlusions1 often requiring the performance of dif-ficult and potentially risky leg bypass surgery.

Balloon angioplasty (PTA) alone has

proven disappointing when used to treat such complex atherosclerotic lesions. Bare-metal stents have fared better, at least in the short and mid term, but the long-term results have been compro-mised by the high rate of in-stent reste-nosis caused by neointimal hyperplasia.2,3 The problem is compounded further in the femoropopliteal segment because of its mobility and exposure to external forces that can lead to stent fractures and increased risk of restenosis.4,5 Athero-sclerotic lesions in the below-the-knee (BTK) arteries have similarly been ob-served to cause high rates of restenosis after angioplasty and stenting.4

One relatively new therapeutic option to prevent (and even treat) restenosis, and at the same time avoiding all poten-tial problems related to the implantation

of a permanent metal device, is through the use of drug-eluting balloons (DEB) that carry and release an antiprolifera-tive drug (such as Paclitaxel) directly in and around the target area of the vessel wall at the time of balloon inflation. The drug achieves a high concentration in the wall at the site of the lesion thereby inhibiting the above-referenced hyper-plastic response and leading to improved long-term patency.6,7

The purpose of this article is to pro-vide an overview of percutaneous DEB angioplasty of the lower limbs, and a brief technical description through the report of several clinical cases.

CASE 1A 51-year-old female former smoker

with diabetes, hypertension, and dys-

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lipidemia presented with intermittent claudication of the right calf and a non-healing right foot ulcer. Angiography showed several areas of long critical stenosis of the right superficial femoral artery (SFA) and total occlusion in its distal third – classified as a TASC II type C femoropopliteal lesion (Figure 1).

An initial attempt at antegrade crossing of the total occlusion with a Terumo hydrophilic guidewire (via retrograde puncture of the left com-mon femoral artery) proved unsuc-cessful. Then, retrograde puncture of the posterior tibial artery (using a 21g micropuncture needle) was performed with subsequent placement of a 5 Fr sheath (Figure 2).

The SFA was crossed with a 0.014˝ guidewire sheath reaching to the left common femoral artery.

Angioplasty was performed using a 5 mm x 80 mm DEB catheter (Fig-ure 3). Post-angioplasty angiography showed a residual stenosis in the SFA, treated with a 6 mm x 40 mm self-expanding stent was deployed (Figure 4 A-C). The final control angiogram

Figure 1. Femoropopliteal long lesion.

Figure 2. Posterior tibial access.

Figure 3. Femoropopliteal long lesion drug-eluting balloon angioplasty.

Figure 4. Post angiography image (A); remaining stenosis (B); femoropopliteal self-expanding stent (C); Final angiogram of patent SFA (D).

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confirmed sat-isfactory paten-cy of the SFA t h r o u g h o u t (Figure 4D).

A follow-up diagnostic an-giogram at 3 months con-firmed the pa-tency of the right SFA and by physical exami-nation the pa-tient had com-plete healing of the ulcer and no claudication. However, at 6 months after the initial intervention, the patient complained of recur-rent claudication, and repeat angiography confirmed that the stent had become totally occluded and obvious fracture of the metal stent as well (Fig-ure 5). Reintervention was undertaken in the attempt to reopen the vessel; transluminal recanalization was followed by DEB angioplasty using a 6 x 120 and 4 x 80 mm DEB catheters. The procedure proved successful (Figure 6), and patient re-evaluation and testing 6 months later revealed continued patency without ev-idence of further restenosis in the right SFA.

CASE 2A 58-year-old man presented with a

history of endovascular revasculariza-tion of the right lower extremity who required treatment of a nonhealing right foot ulcer. The procedure had consisted of PTA of the right popliteal, posterior

tibial, and peroneal arteries. Addition-ally a left below-knee amputation had become necessary because of severe complications related to a diabetic foot. Reassessment and noninvasive Dop-pler and duplex ultrasound evaluation revealed evidence of significant post-PTA arterial restenosis at multiple lev-els. Reintervention via direct antegrade femoral puncture was performed, with repeat angioplasty involving the use of appropriately sized DEB balloon cath-eters for the various arterial segments with restenosis (Figures 7A-D). The pa-tient did well, and right leg circulation

remained intact and without evidence of restenosis 12 months later.

CASE 3A 60-year-old female with diabe-

tes, hypertension, and dyslipidemia complained of rapidly progressive left leg claudication of 10 months’ dura-tion. She could only walk very short distances and was incapacitated. Dop-pler ultrasound showed confirmed the presence of multilevel severe disease, and angiography revealed critical ste-nosis of the distal superficial femoral artery plus a long occlusion of the

Figure 5. Patent superficial femoral artery (A); femoropopliteal reocclusion (B and C); stent fracture (D and E).

Figure 6. Final drug-eluting balloon angioplasty.

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popliteal artery and tibioperoneal trunk. The lesions were classified as TASC II type D (Figure 8 A-B). Via direct antegrade femoral punc-ture, femoropopliteal, and tibiope-roneal trunk PTA with a 5 mm x 120 mm DEB balloon catheter was performed (Figure 8C). The pa-tient was asymptomatic and doing well 6 months later.

CASE 4A 66-year-old male heavy smoker

presented with chronic progressive claudication and a non-healing toe ulcer that had been present for 4 months. Angiography showed long-segment occlusion of the SFA with heavy calcifica-tion (Figure 9A). PTA was performed using a 5 mm x 120 mm DEB balloon catheter with a good result (Figure 9 B-C). Follow-up af-ter 6 months revealed a healed ulcer and no claudication.

DISCUSSIONThe development and commercial

availability of DEBs promise to enhance the long-term patency of lower-limb angioplasty. DEBs would appear to ef-fectively reduce or inhibit neointimal proliferation and, potentially, widen the horizons for endovascular treatment of femoropopliteal lesions TASC II types C and D. It is rapidly emerging as a good therapeutic option particularly for 2 subgroups of PAD patients: those who may not be good candidates for surgi-cal bypass operations, and in situation where placement of a stent is unappeal-ing or outright contraindicated – the so-called “no-stent zones” such as the femoral bifurcation, Hunter’s canal, the popliteal artery, and BTK arteries.

The SFA is particularly difficult to treat because of exposure to powerful forces and stresses related to flexion, compression and torsion – as demon-strated in Case 1. Stent fracture, resteno-sis and occlusions can easily result from such influences. Beyond that, the overall restenosis rates after PTA alone range from 40% to 60% in the first year for short lesions and may reach up to 70% in long lesions.8

The BTK vasculature is another worthy and important therapeutic target for DEBs as these vessels are frequently involved – especially in the diabetic population – and PTA and stenting produce suboptimal results in arteries that tend to be small and calcified. The DEBATE-BTK trial showed that DEB angioplasty is more beneficial than conventional angio-plasty, both in terms of a lower reste-nosis (27% for DEB vs 65% for PTA) and reocclusion (16% for DEB vs 56% for PTA).9,10

Figure 7. Popliteal and tibioperoneal trunk lesion (A); popliteal drug-eluting balloon angioplasty (B); kissing tibioperoneal trunk drug-eluting balloon an-gioplasty (C); final angiogram (D).

Figure 8. Femoropopliteal long lesion (A); drug-eluting balloon angioplasty (B); final angiogram (C).

Figure 9. Superficial femoral artery occlusion (A); drug-eluting balloon angioplasty (B); final angiogram (C).

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Traditional bypass surgery remains first-line treatment for femoropopli-teal TASC II type D lesions, but this is changing rapidly at present, not only because of new and superior chronic total occlusion crossing devices but also because of better results from new en-doplasty technologies – DEB in partic-ular. Several trials have reported a good response in reducing late lumen loss and preventing neointimal hyperplasia, sig-nificantly lowering the restenosis rate at 6 months.6,7,8,10,11

CONCLUSIONDEB technology is an exciting new

tool for the management of many dif-ficult PAD patients, and results and studies so far would seem to confirm the concept works as hyperplastic reste-nosis can be prevented in the majority of instances. However, it is too soon to declare a total triumph. More and bet-ter studies as well a much larger pool of patients with long-term follow-up will eventually provide the final answers vascular specialists are awaiting. In the meantime, DEB angioplasty can be add-ed to the armamentarium with caution

and without fear as these devices do of-fer an exciting new option and renewed hope for avoidance of interventional complications and limb salvage.

Editor’s Note: Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript received April 26, 2013; fi-nal version accepted June 3, 2013.

Address for correspondence: Caroline Clezar, MD, R. Deputado Emilio Carlos, 1249, 3o andar, Campesina, Osasco/Sao Paolo, 06028-015, Brazil. Email: caroline.bessa@gmail.com n

REFERENCES1. Norgren L, Hiatt WR, Dormandy JA, et al.

Inter-society consensus for the manage-ment of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5-S67.

2. Duda SH, Bosiers M, Lammer J, et al. Sirolimus-eluting versus bare nitinol stent for obstructive superficial femoral artery disease: The SIROCCOII trial. J Vasc Interv Radiol. 2005;16(3):331-338.

3. 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(18):1879-1888.

4. Diehm NA, Hoppe H, and Do DD. Drug eluting balloons. Tech Vasc Interv Radiol. 2010;13(1):59-63.

5. Schillinger M, Minar E. Past, present and future of femoropopliteal stenting. J Endo-vasc Ther. 2009;16 Suppl 1:147-152.

6. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358(7):689-699.

7. Schmidt A, Piorkowski M, Werner M, et al. First experience with drug-eluting balloons in infrapopliteal arteries: restenosis rate and clinical outcome. J Am Coll Cardiol. 2011;58(11):1105–1109.

8. Schillinger M, Minar E. Percutaneous treatment of peripheral artery disease: novel techniques. Circulation. 2012;12(20):2433-2440.

9. Liistro F, Porto I, Angioli P, Grottil S, Ricci L, Kenneth D, Falsini G, Ventoruzzo G, Turini F, Bellandi G, Bolognese L. Drug eluting balloon n peripheral interven-tion for below the knee angioplasty evaluation (DEBATE BTK): A random-ized trial in diabetic patients with critical limb ischemia. http://circ.ahajournals.org/content/early/2013/06/24/CIRCULA-TIONAHA.113.00181

10. Bernstein, O, Chalmers, N. New treat-ments for infrapopliteal disease: devices, techniques, and outcomes so far. Cardiovasc Intervent Radiol. 2012;35(4):715–724.

11. Werk M, Albrecht T, Meyer DR, et al. Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty evidence from the randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;5(6):831-840.

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