Debulking Atherectomy in the Peripheral Arteries: Is There a Role and What is the Evidence?

Endovascular atherectomy may be performed under local anesthesia using standard caliber arterial sheaths, ranging from 4 to 8Fr, and provides the theoretical advantage over balloon angioplasty that plaque is removed rather than pressed against the arterial wall, and subsequent balloon dilation is optional depending on the debulking effect. This contributes to substantial luminal gain with less barotrauma even if post-dilation is performed, decreasing the risk of dissection and/or neointimal hyperplasia, while avoiding stent placement. The latter omits the permanent inflammatory stimulus from the metallic stent mesh and facilitates future re-interventions including bypass surgery.

Currently, the only relative contraindications to endovascular atherectomy for infrainguinal lesions are subintimal lesion crossing and minimum vessel diameter smaller than that indicated for each device according to the instructions for use (IFU). Longer procedural time, larger sheath diameters, lesion (vessel diameter, long occlusions, stenosis, in-stent restenosis) and patient characteristics (comorbidities, clinical presentation, performance status, etc.) should be cautiously assessed and considered on a case-by-case basis.

Endovascular atherectomy devices can be divided into four categories according to the mechanism used for atheroma removal: directional, rotational or orbital and laser atherectomy devices. There are also chronic total occlusion (CTO) recanalization devices also approved for atherectomy. Until today, there are no data regarding the comparison of different atherectomy devices in PAD patients, while each device presents unique features with discrete advantages and disadvantages. All available devices and their technical characteristics are presented in Table 1, while possible advantages and disadvantages of each atherectomy category are outlined in Table 2. Purely thrombectomy devices without any plaque removal capacity (AngioJet, Penumbra, etc.) are not discussed in the present manuscript.

In directional atherectomy, plaque is removed by guiding the cutting device (cutter) of the catheter directly to the plaque, while by rotating the catheter to the preferred direction, the device accomplishes targeted atherosclerotic plaque removal. This is an advantage when treating eccentric lesions. Reasonable plaque volume is removed only by multiple passes. Removed plaque is packed into the nosecone, and after few passes, the catheter must be retrieved and the nosecone must be emptied in order to proceed with further debulking.

The SilverHawk™, TurboHawk™ and the newest HawkOne™ directional atherectomy, plaque excision systems (Medtronic, MN, USA) have received approval from the US Food and Drug Administration (FDA) for use in peripheral arterial lesion. The SilverHawk™ is a side-cutting cutting device. The catheter is equipped with a single rotating blade within a tubular cover which ends at a nosecone (collection area). The rotating blade is powered by a motor within the capital equipment. The TurboHawk™ is a similar system with four contoured blades, achieving more plaque removal with each pass and provides more aggressive atherectomy which is an advantage in the treatment of severely calcified lesions. The HawkOne™ is the most recent directional atherectomy catheter of this series and has been designed to provide more effective treatment for calcified lesions. It is a one blade, 7Fr platform with lower crossing profile, equipped with a preloaded distal flush tool simplifying the cleaning process necessitating less procedural steps (55% less time) and providing two times more cutting efficiency than the TurboHawk™. Although these devices do not have an aspirating mechanism, the majority of excised plaque is collected within the nosecone. Once the nosecone is full, the device must be retrieved and emptied before further use. Nevertheless, distal embolization remains an issue and their use without an appropriate protection arterial filter is not advisable. All three devices are available in various sizes for use in vessels with diameters ranging from 1.5 to 7 mm [9].

A novel directional atherectomy device which recently received FDA clearance is the Pantheris OCT-guided lumivascular atherectomy device (Avinger Inc., CA, USA). The Pantheris over-the-wire catheter is equipped with optical coherence tomography (OCT) technology to enhance directional atherectomy efficacy and safety, allowing targeted removal of eccentric plaque (characteristic of directional atherectomy), while minimizing the risk of non-diseased vessel wall trauma [10]. The catheter is using a side cutter with a conenose similar to the previously described directional atherectomy devices, without aspiration capability, but also utilizes an apposition balloon which enables OCT-guided depth modification of atherectomy. Moreover, direct visualization of the arterial lumen during atherectomy, without using ionizing radiation, reduces procedural X-ray exposure. The system is compatible with 7 or 8Fr sheaths (2 different catheters) and is indicated for the treatment of vessels ranging from 3 to 7 mm in diameter, but is not recommended for treating iliac, renal or carotid artery lesions [10].

In rotational atherectomy, plaque is excised by a concentrically rotating, specially designed tip (burr). As a result, luminal gain usually matches the size of the tip/burr used, and if a larger lumen is necessary, a larger catheter tip/burr should be utilized. The Pathway Jetstream PV Atherectomy System (Boston Scientific, MN, USA) is a cutting rotational atherectomy device with active debris aspiration, indicated for both acute thrombus removal and atherectomy of chronic lesions. It is a 7Fr sheath, over-the-wire system with two types of catheters: the SC catheter which is smaller, equipped with a single set of front cutting blades and the larger XC catheter equipped with a second set of larger blades proximal to the front cutting set that can be used in order to increase the diameter of the debulking effect of the atherectomy (Fig. 1). The aspiration port is situated proximal to these larger blades, and even more proximal infusion ports are enabling flushing during use. The Jetstream console (capital equipment) is designed to enable atherectomy, active aspiration, flushing and monitoring of the volume of blood products removed. Despite active aspiration, micro- and macro-embolization is possible, so filter protection is again advisable.

The Peripheral Rotablator™ system (Boston Scientific MN, USA) consists of an outside console that rotates concentrically a 5-micron diamond-coated catheter tip (burr). The unique feature of this device is that the luminal gain is predefined as it matches the size of the burr (ranges from 1.25 to 2.5 mm) creating a smooth lumen with specific diameter. However, as a 1.5-mm-diameter guide is integrated to the catheter, narrow lesions may be difficult to cross. The catheter requires 4 to 8Fr arterial sheaths and is compatible with a specific 0.009′′ guide wire. The maximum atherectomy time recommended for a single catheter is 15 min; after that, the burr is considered ineffective. Active aspiration is not available. The diamond-coated burr macerates the atheroma in debris smaller than red blood cells, which usually do not incite clinically significant embolization. Nevertheless, filter protection is recommended.

The Phoenix rotational atherectomy system (AtheroMed Inc., Menlo Park, CA, USA) consists of two main components: a single-use catheter without capital equipment and the Phoenix atherectomy handle. The long, flexible double-lumen catheter contains a torque shaft attached to a metallic front cutter at its distal tip. The rotating torque shaft enables rotational atherectomy by the cutter. The excised plaque is mechanically transported within the catheter using an Archimedes screw fixed on the outer surface of the shaft extended though the entire length of the catheter with a port on the handle connected with an external bag. The device received FDA clearance for peripheral use recently and is available in sizes ranging from 1.8 to 2.4 mm, compatible with 0.014 inch, 260 cm length guide wire and 5 to 7Fr sheaths. According to the IFU, there is no plaque volume limit that can be excised, and the minimum vessel diameter recommended for treatment is 3 mm. Again micro- and macro-embolization is possible and filter protection is recommended.

Finally, the Rotarex^® S (Straub Medical, Wangs, Switzerland) is a rotational thrombectomy device that that can be also used as an atherectomy device for chronic total occlusions. It has an active aspiration function enabling debris removal within an external bag. As the external metallic device rotates, the internal metallic helix rotates at a speed of 40.000–60.000 rounds per minute, creating a negative pressure and removing debris from circulation. It is compatible with sheaths from 6 to 10Fr and can be used to treat vessels from 3 to 8 mm in diameter. It may be advisable to combine use of thrombectomy devices like the Rotarex with peripheral filter protection to reduce the risk of distal thromboembolism [11].

Orbital atherectomy is a new endovascular atherectomy mechanism based on the high-speed rotational spin of the shaft and the orbital rotation of a specially designed debulking, diamond-coated crown. Plaque is removed by the orbital movement of the crown, while the debulking area increases with the increase of the rotational speed of the crown. This is the main difference compared to rotational atherectomy which uses a concentrically rotating burr, so luminal gain is as large as the burr size being utilized and is not modified by increased rotational speed.

It is currently performed only with the Diamondback 360° Peripheral Orbital Atherectomy System (Cardiovascular Systems Inc., St. Paul, MN, USA), which consisted of an orbiting eccentric diamond-coated crown mounted at the end of a shaft and a capital equipment (OAS pump). It is a 0.014-inch over-the-wire system using a proprietary guide wire (the ViperWire™), which provides more crossing support to that of a 0.009-inch guide wire used in rotational atherectomy, and it is the only atherectomy system compatible with 4Fr sheaths (up to 7Fr). Three types of crowns are available: A solid micro-crown is recommended for tortuous vessel anatomy, tight bends and distal below the ankle lesions, a solid crown is recommended for calcified lesions and maximum plaque removal in the short atherectomy time (additional diamond-coated surface area), and the classic crown is the most flexible and recommended for below the knee lesions. There is no aspiration function, and although small particulates created from crown rotation are not considered particularly hazardous, distal embolization cannot be excluded and the use of a peripheral protection filter is advised.

Laser atherectomy uses excimer laser technology to ablate atheromatous peripheral arterial disease. Excimer laser atherectomy catheters (Turbo-Elite, Turbo-Power and Turbo-Tandem Spectranetics Corporation, Colorado Springs, CO, USA) are using ultraviolet radiation to remove atheroma from the arterial lumen with a thickness of 10 μm with each pulse of energy [9]. Excimer laser technology utilizes low penetration depth and pulsed delivery of high energy as to achieve the disruption of the atheroma that is in contact with the laser without damaging the surrounding arterial tissue. Laser atherectomy is indicated for both de novo and in-stent restenosis. The Turbo-Tandem is not designed to be used in total or subtotal occlusions, while the Turbo-Elite catheter is capable of crossing occlusions without the need of a guide wire. Catheter diameters range from 0.9 to 2.5 mm and are compatible with 4–8Fr sheaths. The device is powered by an external generator (CVX-300 excimer laser ablation system) and is most effective in a ratio of 2:3 with respect to catheter/vessel diameter. Catheter advancement is also important in delivering the appropriate amount of energy to the lesion and should be performed slowly with a rate of ≥0.5 ≤ 1 mm/s so as to remove plaque effectively and uniformly [12]. Importantly, laser should never be used in the presence of contrast media as this increases energy absorption leading to dissection or perforation. As blood also absorbs laser energy, saline flushing during laser atherectomy is essential in order to remove blood and contrast from the treated vessel. Micro- and macro-embolization has been described and the use of a protection filter is advisable.

The Crosser peripheral CTO recanalization system (Bard Peripheral Vascular Inc., Tempe, AZ, USA) has been developed as a CTO crossing system. However, during CTO, crossing operators noticed that after crossing the occlusion the device was creating a considerable patent tract corresponding to the catheter’s outer diameter or even larger and was therefore granted with FDA clearance for atherectomy. The system consists of capital equipment (generator and transducer) and a single-use disposable catheter. The capital equipment converts alternative current into high-frequency mechanical vibrations, transmitted through the catheter’s nitinol wire to its metallic tip. Saline flush is used to cool the tip of the catheter while in use. The system is compatible with sheaths and is available in over-the-wire and rapid exchange versions. The device is effective in crossing hard, calcified occlusions, but due to its specific CTO, crossing mechanism of action balloon angioplasty is required in the majority of the cases.

In the past few years, both femoropopliteal and infrapopliteal percutaneous atherectomy were investigated in several multicenter, randomized controlled trials (RCT), as well as in large-scale multicenter registries and retrospective analysis. In 2011, Shammas et al. published outcomes from a two-center, RCT comparing primary balloon angioplasty versus SilverHawk directional atherectomy with adjunctive balloon angioplasty in 58 patients suffering from intermittent claudication (IC; 46 patients) or critical limb ischemia (CLI; 12 patients). The majority of the cases (46/58 patients; 79%) involved femoropopliteal lesions, while in the remaining 21%, infrapopliteal lesions were also treated [13]. Procedural variables such as lesion length, stenosis severity, total occlusions and extent of vessel calcification were similar between the two study arms. The primary endpoint of the study was set at target lesion revascularization (TLR) at 1 year, while secondary endpoints included technical success, bailout stenting rate and target vessel revascularization (TVR). Technical success was 100% in the angioplasty arm versus 97.2% in the atherectomy arm. During follow-up, TLR (11.1 vs. 16.7%) and TVR (11.1 vs. 21.4%) were all similar in the atherectomy and angioplasty arms, respectively, but with a small numerical benefit in favor of directional atherectomy. However, atherectomy plus angioplasty resulted in significantly less bailout stenting due to suboptimal immediate technical result (27.6 vs. 62.1%; p = 0.017). On the other hand, distal macro-embolization was significantly higher in the atherectomy arm (64.7 vs. 0.0%; p < 0.001) [13].

The same research group published later the results from another multicenter, RCT investigating infrapopliteal orbital atherectomy with adjunctive balloon angioplasty versus balloon angioplasty alone in a total of 50 patients presenting with CLI (Rutherford class 4 to 6) due to severe calcified infrapopliteal lesions [14]. Procedural success (atherectomy plus angioplasty 93.1% vs. angioplasty alone 82.4%; p = 0.27) and stent use (atherectomy plus angioplasty 6.9% vs. angioplasty alone 14.3%; p = 0.44) were similar between the two groups. At 1-year follow-up, no patient underwent major amputation, while freedom from target vessel revascularization and all-cause mortality rates were 93.3 and 100% in the atherectomy plus balloon angioplasty arm versus 80.0% (p = 0.14) and 68.4% (p = 0.01) in the balloon angioplasty alone arm, respectively. Post hoc analysis detected a 5.6 hazard ratio for major adverse events in cases of acute post-procedure residual stenosis >30% (p = 0.01). Based on these results, the authors concluded that orbital atherectomy could increase the probability of achieving an optimal angioplasty outcome and lead to fewer dissections, decreased bailout stenting rate and statistically significantly lower adjunctive balloon pressure compared to balloon angioplasty alone [14].

Another multicenter RCT, published in 2014, report immediate and midterm outcomes of orbital atherectomy plus balloon angioplasty compared to balloon angioplasty alone, in 50 patients with 65 calcified femoropopliteal lesions. Study’s primary endpoint was freedom from TLR (including adjunctive stenting), or Duplex ultrasound (DUS) defined restenosis at 6 months [15]. Stent was deemed necessary in 5.3% in the atherectomy arm and in 77.8% in the balloon angioplasty arm (p < 0.001). Freedom from TLR including adjunctive stenting or restenosis was noted in 77.1 versus 11.5% (p < 0.001) at 6 months and in 81.2 versus 78.3% at 1 year, excluding adjunctive stenting (p > 0.99), in the atherectomy and balloon angioplasty arm, respectively. Again, although less stent use was noted, atherectomy did not yield superior outcomes compared to standard balloon angioplasty [15].

The possible benefit from transcatheter debulking in the treatment of challenging femoropopliteal in-stent restenosis was investigated in a multicenter RCT by Dippel et al. In total, 250 patients presenting with IC or CLI (Rutherford Class 1 to 4) due to ISR were randomized (2:1 ratio) to undergo excimer laser atherectomy (ELA) with plain balloon angioplasty versus balloon angioplasty alone, in 40 US centers [16]. Primary efficacy endpoint was 6-month TLR and primary safety endpoint was 30-day major adverse event (death, amputation or TLR). Mean lesion length was similar around 19 cm, and in over 30% of the cases, total occlusions were treated, while the rate of vessels presenting calcifications was significantly higher in the ELA arm (27.1 vs. 9.1%; p = 0.002). ELA resulted in superior procedural success (93.5 vs. 82.7%; p = 0.01) and freedom from TLR (73.5 vs. 51.8%; p < 0.005), significantly fewer procedural complications and 30-day major adverse event rates (5.8 vs. 20.5%; p < 0.001), respectively. Moreover, ELA was associated with a 52% TLR reduction. The authors concluded that ELA plus balloon angioplasty significantly improves acute and midterm efficacy and safety outcomes of femoropopliteal ISR treatment compared with conventional PTA alone [16].

Finally, a 2014 meta-analysis summarized the outcomes of percutaneous transcatheter atherectomy in the femoropopliteal segment. The evidence synthesis included six RCTs comprising 287 patients (328 lesions) treated with atherectomy or balloon angioplasty for femoropopliteal artery disease alone [17]. Technical success, bailout stenting and distal arterial embolization were similar between the atherectomy and the angioplasty group. The 9-month primary patency was also similar between the two groups (Risk ratio: 0.90, 95% CI 0.56–1.46, p = 0.68, I ² = 69%). The authors concluded that these results did not show any procedural advantage or clinical improvement following debulking atherectomy of the femoropopliteal artery compared to plain balloon angioplasty alone. Nonetheless, this meta-analysis was based on limited, low-quality, heterogeneous evidence with high risk of bias [17].

In order to improve patency, the combination of lesion debulking using percutaneous atherectomy and subsequent DCB application has been implemented. Drug-coated balloons are proved to be an effective treatment option that does not require a permanent stent [34‐36]. Rates of bailout stenting in of DCB studies range from 4% in the THUNDER (Local Taxane with Short Exposure for Reduction of Restenosis in Distal Arteries) study to 12.3% in the Italian Registry and 21% in the PACIFIER study [34]. One small Italian registry trial was recently published with results from a series of 30 patients with severely calcified SFA lesions. Mean lesion length treated was 115 ± 35 cm and 13% were occlusions. The authors performed intravascular ultrasound-guided directional atherectomy under filter protection using the TurboHawk system, followed by application of a drug-eluting balloon (In.PACT ADMIRAL, Medtronic, USA). The authors reported a very promising 1-year primary patency of 90%, which needs further validation in larger trials. No procedure-related adverse events were noted, and bailout stenting was necessary in 6.5% [37]. Primary angiographic patency was 94.1% when more plaque was removed with directional atherectomy (<30% residual stenosis was achieved) compared to 68.8% patency when less plaque was removed (>30% residual stenosis) before treatment with the DCB [37].

A confirmatory comparative study called the DEFINITIVE AR trial (Atherectomy Followed by a Drug Coated Balloon to Treat Peripheral Arterial Disease; ClinicalTrials.gov Identifier: NCT01366482) has been recently completed and results were presented. This was a multicenter, randomized, controlled trial sponsored by Medtronic, comparing upfront atherectomy with the TurboHawk™ or SilverHawk^® plaque excision systems followed by drug-eluting balloon angioplasty versus a drug-eluting balloon (Cotavance™ Drug-Eluting Balloon), as a single approach, in patients with Rutherford 2 to 4 disease due to 7- to 15-cm superficial femoral and/or popliteal lesions. Patients were randomized 1:1 to either directional atherectomy plus DCB group under filter protection (DAART; n = 48) or to the paclitaxel-coated balloon alone (n = 54). Results were recently presented at the 2015 Charing Cross Symposium by Zeller T. Significantly lower flow-limiting dissection rate was noted in the DAART arm (2 vs. 19%, p = 0.01), and the need for bailout stent was only 4.1%. One-year restenosis rate by DUS (PSVR ≤ 2.4, without TLR) and evaluated by an independent core laboratory was 93.4% for the DAART arm and 89.6% for the DCB arm (nonsignificant p > 0.05). Angiographic patency (≤50% stenosis and without TLR) again assessed by independent core laboratory was 82.4% in the DAART arm and 71.8% in the DCB arm. DEFINITIVE AR provided higher level of evidence regarding the possible additional benefit of performing debulking atherectomy prior to the use of a drug-eluting balloon. The investigators concluded that the DEFINITIVE AR resulted by trend in potentially better outcomes in challenging lesion subsets such as severely calcified ones, ≥10 cm lesions and CTOs. However, a sufficiently powered study to confirm or refute this potential benefit is still missing. Following this initial experience, Medtronic has launched the REALITY study, a multicenter, prospective, single-arm observational angiographic and duplex ultrasound core laboratory-adjudicated study that will enroll 250 patients at up to 20 US centers to evaluate adjunctive use of directional atherectomy and DCB treatment in patients with symptomatic PAD in long, calcified SFA and/or popliteal artery lesions.

An even more interesting treatment combination would be atheroma debulking using percutaneous atherectomy followed by bioabsorbable drug-eluting stent deployment. In this way, all possible advantages of endovascular technologies, such as transcatheter plaque excision, optimal lesion preparation to allow placement of a bioresorbable scaffold, maximal luminal gain without elastic recoil, long-lasting drug delivery for inhibition of neointimal hyperplasia, as well as no permanent metal implant, will be combined in order to provide the optimal treatment effect for PAD patients. Further technological developments that will minimize the risk of distal embolization, reduce device profile and accelerate procedural time could also be key elements in order to establish percutaneous atherectomy as the first-line endovascular PAD treatment option with superior patency outcomes and no permanent metal stents.

In conclusion, percutaneous transcatheter atherectomy can achieve significant plaque removal and downstage the anatomical complexity of PAD. Current evidence indicates that femoropopliteal and infrapopliteal percutaneous atherectomy may achieve a high technical success with significantly lower bailout stenting rates. On the other hand, there is absence of robust evidence that long-term patency results are improved by the application of transcatheter atherectomy alone. Therefore, high-quality data from studies investigating novel hybrid treatment strategies, for example combination of atherectomy and drug-eluting technologies, are necessary.