ABSTRACT: Endovascular treatment options for peripheral arterial disease of the lower extremity include percutaneous transluminal angioplasty, stent implantation, and atherectomy. Drug-eluting balloons (DEB) show promise in reducing long-term restenosis and target lesion revascularization rates by limiting postprocedural neointimal hyperplasia. However, dense calcification is thought to act as a barrier to successful deposition of antiproliferative drug. Atherectomy prior to DEB angioplasty is one approach to reduce mural calcification and improve the efficacy of drug delivery.
VASCULAR DISEASE MANAGEMENT 2017;14(1):E6-E10
Key words: drug-eluting balloon angioplasty, atherectomy
Endovascular treatment options for peripheral arterial disease (PAD) of the lower extremity include percutaneous transluminal angioplasty (PTA), stent placement, and atherectomy. However, PTA alone with or without stenting is associated with a significant risk of restenosis. Conventional PTA of femoropopliteal lesions is associated with a restenosis rate of 40% to 60% at 1 year.1 This is thought to be a result of vessel trauma, as PTA relies of vessel wall stretching and eccentric plaque fracture.2 Atherectomy may debulk atherosclerotic lesions but still results in late neointimal hyperplasia, possibly related to additional mechanisms of vessel injury during intervention.3 Drug-eluting technologies, such as drug-eluting balloons (DEB) and drug-eluting stents (DES) reduce neointimal hyperplasia via the deposition of antiproliferative drug into the medial layer of the treated artery.2 However, dense atherosclerotic calcification limits mural drug deposition and probably reduces the resulting antiproliferative effect.4 Vessel preparation with atherectomy prior to DEB angioplasty may have a role in debulking calcific plaque and hence improving effective drug deposition. Herein, we describe our preferred method for vessel preparation with rotational atherectomy prior to DEB angioplasty in heavily calcified vessels.
A 55-year-old male with coronary artery disease, peripheral vascular disease, and history of left lower extremity revascularization presented with disabling right lower-extremity claudication (one-half block). Antegrade access was obtained in the right common femoral artery and a long 7 Fr sheath was placed. Right lower-extremity angiography revealed occlusion of the mid right superficial femoral artery (SFA) with distal reconstitution via collaterals at the right popliteal artery and patent 3-vessel runoff to the foot (Figure 1A and 1B). Parallel linear opacities were noted along the expected course of the distal SFA that were compatible with eccentric calcified plaque.
Intra-arterial heparin was administered. A 0.014" wire was used to cross the long segment occlusion, over which a crossing catheter was advanced, and the crossing wire was replaced with a stiff support microwire (Figure 1C). A rotational atherectomy catheter with active aspiration (Jetstream Atherectomy System, Boston Scientific) was advanced to the level of the occlusion. One-pass atherectomy was performed in the blades-down position, followed by an additional pass in the blades-up position (Figure 1D).
Angiography was repeated through the sheath and revealed improved flow through the previously occluded segment. A 4 mm balloon was used to predilate along the length of the SFA and popliteal artery (Figure 1E). A 6 mm x 120 mm IN.PACT Admiral DEB (Medtronic) was advanced over the wire to the popliteal artery, and distal SFA and inflation was maintained for approximately 3 minutes. The process was repeated with 2 additional DEBs more proximally to the level of the mid SFA (Figure 1F). Final digital subtraction angiography revealed a patent treated vessel and the procedure was terminated.
Given the perceived advantages of drug-eluting technologies in maintaining long-term vessel patency, our preference is to utilize DEB and DES when feasible. Long-segment steno-occlusive disease of the femoropopliteal axis poses challenges to both approaches. Stents are avoided in long segments and at stress points unless persistent significant stenosis or flow-limiting dissection is seen post angioplasty. Our approach with heavily calcified vessels that would otherwise benefit from DEB angioplasty is to pretreat the vessel with a rotational or orbital atherectomy system to debulk eccentric calcium and improve drug delivery. Following atherectomy, the native lesion is treated as with standard DEB angioplasty: predilatation is performed 1 mm to 2 mm undersized to the reference vessel diameter, and the DEB is sized equivalent to the reference vessel diameter and kept inflated for 1-3 minutes. When the treated lesion length exceeds the length of the DEB, 1 cm to 2 cm of overlap is obtained with subsequent balloons.
Paclitaxel selectively inhibits arterial smooth muscle cell proliferation and the ensuing deposition of extracellular matrix, which otherwise contribute to neointimal hyperplasia following endovascular intervention.5 DEB delivery of paclitaxel is dependent on successful penetration and deposition of antiproliferative drug into the medial layer of the target artery. New technologies aim to minimize loss of drug into the vasculature and enhance deliverability to the vessel wall.6 At present, 2 DEBs containing paclitaxel have received US Food and Drug Administration approval due to promising long-term restenosis and target lesions revascularization rates in clinical trials (Table 1).
Densely calcified atherosclerosis reduces the efficacy of PTA1 and increases the risk for flow-limiting dissections.7 Furthermore, calcium is not reliably detected by standard angiography. Eccentric calcification poses additional problems when DEB angioplasty is planned. Dense calcification is thought to act as a physical barrier to penetration, mitigating the perceived long-term benefits of paclitaxel deposition. This concept was recognized in the planning phases of several clinical trials. The BIOLUX-PI and LEVANT-I trials, which examined the use of DEBs in femoropopliteal lesions, both excluded heavily calcified lesions.8,9 The BIOLUX-PII trial examining DEBs in below-the-knee interventions established noninferiority and safety relative to PTA. However, in explaining the lack of a statistically significant benefit of DEB angioplasty, the authors suggested that more baseline calcified lesions in the DCB arm may have played a role in reduced drug delivery, affecting outcomes.10
Fanelli et al in 2014 correlated DEB performance with degree of vessel calcification. In this study, the authors classified vessel calcification according to circumferential involvement and length of calcification as seen on preprocedure computed tomography angiography.4 Sixty patients were treated with DEB angioplasty and followed to 12 months. Restenosis was significantly higher in patients with more complete circumferential calcium (>270 degrees) relative to less calcification (<90 degrees), as indicated by ankle-brachial index, late lumen loss, and primary patency outcomes. Complications associated with large calcium burden included flow-limiting dissections and residual stenosis, both occurring only in patients with >50% circumferential calcifications.4
Cioppa et al in 2012 reported the use of DEB with directional atherectomy to overcome problems faced with heavily calcified femoropopliteal lesions.11 Thirty patients underwent directional atherectomy with TurboHawk (Covidien) followed by DEB with IN.PACT Admiral paclitaxel-coated balloon. Target lesions revascularization rate was 10% at 1 year, with secondary patency of 100%, comparing favorably to DEB, PTA, or atherectomy alone.12
DEB in the femoropopliteal axis is safe, effective, and demonstrates improved long-term outcomes relative to PTA alone. Early evidence regarding the use DEB in densely calcified lesions suggest that efficacy is decreased with increased circumferential vessel calcification. Debulking with atherectomy is one method of overcoming this limitation. Early experiences with this approach have been favorable, but studies examining its long-term efficacy are lacking.
Editor’s note: Disclosures: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Lookstein reports consultancy to Boston Scientific and research support from Boston Scientific, Bard, and Veniti Medical.
Manuscript received September 27, 2016; manuscript accepted October 31, 2016.
Address for correspondence: Marcin K. Kolber, MD, Mount Sinai Beth Israel Department of Radiology, 1st Avenue at 16 St., New York, NY 10003 United States. Email: firstname.lastname@example.org
- Schillinger M, Minar E. Percutaneous treatment of peripheral artery disease: novel techniques. Circulation. 2012;126(20):2433-2440.
- Kashyap VS, Pavkov ML, Bishop PD, et al. Angiography underestimates peripheral atherosclerosis: lumenography revisited. J Endovasc Ther. 2008;15(1):117-125.
- Mintz GS, Kimura T, Nobuyoshi M, Leon MB. Intravascular ultrasound assessment of the relation between early and late changes in arterial area and neointimal hyperplasia after percutaneous transluminal coronary angioplasty and directional coronary atherectomy. Am J Cardiol. 1999;83(11):1518-1523.
- Fanelli F, Cannavale A, Gazzetti M, et al. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease. Cardiovasc Intervent Radiol. 2014;37(4):898-907.
- Axel DI, Kunert W, Goggelmann C, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96(2):636-645.
- Herten M, Torsello GB, Schonefeld E, Stahlhoff S. Critical appraisal of paclitaxel balloon angioplasty for femoral-popliteal arterial disease. Vasc Health Risk Manag. 2016;12:341-356.
- Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty. An observational study using intravascular ultrasound. Circulation. 1992;86(1):64-70.
- Scheinert D, Schulte KL, Zeller T, Lammer J, Tepe G. Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial. J Endovasc Ther. 2015;22(1):14-21.
- Scheinert D, Duda S, Zeller T, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon angioplasty. JACC Cardiovasc Intervent. 2014;7(1):10-19.
- Zeller T, Beschorner U, Pilger E, et al. Paclitaxel-coated balloon in infrapopliteal arteries: 12-month results from the BIOLUX P-II randomized trial (BIOTRONIK’S-first in man study of the Passeo-18 LUX drug releasing PTA balloon catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries). JACC Cardiovasc Intervent. 2015;8(12):1614-1622.
- Cioppa A, Stabile E, Popusoi G, et al. Combined treatment of heavy calcified femoro-popliteal lesions using directional atherectomy and a paclitaxel coated balloon: One-year single centre clinical results. Cardiovasc Revasc Med. 2012;13(4):219-223.
- Razavi MK, Mustapha JA, Miller LE. Contemporary systematic review and meta-analysis of early outcomes with percutaneous treatment for infrapopliteal atherosclerotic disease. J Vasc Intervent Radiol. 2014;25(10):1489-1496, 96 e1-3.
- Tepe G, Schnorr B, Albrecht T, et al. Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year follow-up of the THUNDER trial. JACC Cardiovasc Intervent. 2015;8(1 Pt A):102-108.
- Werk M, Langner S, Reinkensmeier B, et al. Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Circulation. 2008;118(13):1358-1365.
- Liistro F, Grotti S, Porto I, et al. Drug-eluting balloon in peripheral intervention for the superficial femoral artery: the DEBATE-SFA randomized trial (drug eluting balloon in peripheral intervention for the superficial femoral artery). JACC Cardiovasc Intervent. 2013;6(12):1295-1302.
- 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.
- Laird JR, Schneider PA, Tepe G, et al. Durability of treatment effect using a drug-coated balloon for femoropopliteal lesions: 24-month results of IN.PACT SFA. J Am Coll Cardiol. 2015;66(21):2329-2338.
- Rosenfield K, Jaff MR, White CJ, et al. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. New Engl J Med. 2015;373(2):145-153.