Atherectomy for Calcified Femoropopliteal Disease: Are We Making Progress?

Femoropopliteal (FP) atherosclerotic disease is responsible for the majority of cases of symptomatic lower-extremity peripheral artery disease (PAD). FP disease has several unique and challenging features: it affects a mechanically dynamic vascular segment; patients present late with diffuse long lesions; large plaque burden; frequently superimposed calcification; and high incidence of presentation and progression to total occlusion. Endovascular technological advances have made minimally invasive percutaneous approach the treatment of choice in the initial management of the majority of symptomatic patients over the traditional surgical approach. However, endovascular treatment of the FP vascular bed remains challenging and is associated with poor long-term outcomes after percutaneous interventions, partly due to multiple biomechanical forces such as torsion, compression, stretching, flexion, and extension by muscular dynamics.¹ Although percutaneous transluminal angioplasty (PTA) may be an effective treatment for focal FP lesions, pooled primary patency rates for long lesions remain poor and 40%-50% of cases require bail-out stenting.² In that regard, the newer generations of nitinol self-expanding stents have become the predominant strategy for treatment of complex superficial femoral artery (SFA) lesions, either with primary or bail-out intent. Despite high acute procedural success rates with stenting, restenosis rates can be as high as 10%-40% at 6-24 months, stent fractures may occur at sites of excessive movement, and lack of effective therapy for restenosis has led many interventionalists to seek alternative treatment strategies.^2,3 Currently, the spectrum of endovascular options includes: PTA with plain balloons or drug-coated balloons; PTA with atherotomy or “specialty” balloons, ie, the Cutting balloon (Boston Scientific), AngioSculpt scoring balloon (AngioScore), and Chocolate balloon (TriReme Medical); primary or bail-out implantation of plain nitinol or drug-eluting stents; implantation of “special-design” stents (interwoven nitinol or polytetrafluoroethylene-covered stents); and plaque modification by means of debulking (atherectomy) devices.⁴

Atherectomy, commonly combined with low-pressure balloon angioplasty, has been used to modify and “debulk” heavily calcific plaque while minimizing vessel injury, with a goal of avoiding stent placement. In densely calcified vessels, atherectomy has been used to better “prepare” the vessel prior to stenting as a means of preventing incomplete and/or eccentric stent expansion. Another theoretical advantage of atherectomy is to minimize plaque shifting when treating ostial or bifurcation disease. Four different methods of atherectomy have been utilized for treatment of FP disease: plaque excision (directional) atherectomy; laser atheroablation; rotational atherectomy/aspiration; and orbital atherectomy. Directional or extractional atherectomy devices utilize resection and removal of atherosclerotic tissue with a cutting device that contains carbide rotating cutter discs. These devices vary in the number of inner blades and thus effectiveness of plaque removal. Examples include the SilverHawk, TurboHawk, and RockHawk device for calcified lesions (Covidien). Rotational atherectomy devices utilize a high-speed rotating cutting blade or a burr and employ a principle of differential cutting, debulking and modifying the surface of calcified atheromatous plaque while preserving the more elastic vessel wall. Current rotational atherectomy devices include: the Bayer Pathway PV system (currently Jetstream; Bayer Medical), which combines atherectomy and aspiration capability of potentially embolic material; rotational atherectomy (Rotoblator; Boston Scientific); as well as the investigational Phoenix atherectomy system (AtheroMed). Orbital atherectomy utilizes a diamond-coated tungsten crown that orbits 360° eccentrically within the vessel, while employing circumferential plaque removal by differential sanding. The CSI Diamondback Orbital atherectomy system (Cardiovascular Systems, Inc) includes two currently available versions: the Predator 360° and the Stealth 360° PAD system. Excimer laser atherectomy removes plaque by laser “photoablation” while minimizing damage to surrounding tissue. The Turbo-Booster/Turbo-Elite laser catheters (Spectranetics) have been studied in de novo and restenotic disease as well as to assist with crossing chronic occlusions.

Few randomized trials have been conducted to evaluate endovascular atherectomy devices in calcified FP vessels, with most of the data limited to single-arm studies and prospective registries.⁵ The United States Investigational Device Exemption protocols frequently exclude patients with moderate to severe calcification in order to avoid procedural or device-related adverse events (eg, perforations, dissections, embolization), which understandably occur more frequently in heavily calcified lesions. Prior studies of orbital atherectomy (OA) have included subsets of patients with calcification, ranging from 40%-50% of lesions with heavy calcification^6,7 to >90% with moderate to severe calcification in the CALCIUM 360° (Comparison of Orbital Atherectomy Plus Balloon Angioplasty vs Balloon Angioplasty Alone in Patients with Critical Limb Ischemia) trial.⁸

In the current issue of the Journal, Dattilo et al⁹ report the results of the COMPLIANCE 360° trial, a randomized, prospective, multicenter trial that compared acute and 12-month results in 50 patients (65 lesions) Rutherford class 2-4 between orbital atherectomy plus PTA versus PTA in calcified FP disease. Adequate debulking of FP disease occurred in 87% of lesions (defined as ≤30% residual diameter stenosis without stent placement). The authors have demonstrated that OA in conjunction with PTA achieved a greater luminal enlargement (luminal diameter, 4.6 mm vs 3.3 mm) and required lower balloon inflation pressures (4.0 atm vs 9.1 atm), which translated into a decreased need for bail-out stenting (5.3% vs 77.8%) in those undergoing OA plus PTA vs PTA only, respectively. Importantly, at 12 months, freedom from target lesion restenosis (TLR) or restenosis was achieved in ~80% of lesions in both groups, despite rare use of bail-out stenting after atherectomy. Periprocedural adverse events were seen infrequently with OA: perforations (0%); dissections (16%); and atheroembolization (2.6%). The results of this small trial are consistent with prior prospective registries in terms of relatively low rates of bail-out stenting (0.5%-8.5%), major and minor dissections (2.5%-15.8%), perforation (~1%), and embolization (0.5%-2.6%).^5-9 However, not surprisingly, the procedure duration was longer for OA versus PTA (96 minutes vs 70 minutes) for relatively short lesions (mean length, 56 mm vs 87 mm), with likely increases in contrast volume and radiation exposure.

Other atherectomy devices have been examined for treatment of calcified FP disease as well. The TALON (Treating Peripherals with SilverHawk: Outcomes Collection) registry included 601 patients treated with a directional atherectomy device (SilverHawk) in addition to provisional PTA or stent.¹⁰ The majority of lesions were superficial femoral artery (SFA)/popliteal lesions (63%), ~65% of all lesions had moderate to severe calcification, and 27% were total occlusions; the primary patency rate at 12 months of follow-up was 80%. More recently, the DEFINITIVE Ca⁺⁺ registry evaluated 133 patients (168 lesions) with moderate to severe calcified FP disease treated with the SilverHawk or TurboHawk plaque excision devices, used in conjunction with the SpiderFX embolic protection filter (Covidien) in those with Rutherford 2-4 category and a mean lesion length of 3.9 cm.¹¹ The investigators reported that adequate debulking of calcified SFA/popliteal disease occurred in 92% of lesions (defined as ≤50% residual diameter stenosis), assessed per angiographic core laboratory. Adjunctive stenting was required in 4.1% with few major adverse events at 30 days: dissection 0.8%; perforation 2.3%; and embolization 2.3%. Safety of rotational atherectomy in calcified lesions was seen in the multicenter Pathway PVD trial, a proof-of concept study that demonstrated the safety of the Jetstream device in 172 patients, ~50% with moderate to high calcification.¹² The periprocedural complication rate in this study was low (1%), with primary patency of 62% at 12 months in short lesions with a mean length of 2.7 cm. The Jetstream G3 device is currently being tested in the Jetstream G3 Calcium study to detect calcium removal and luminal gain by intravascular ultrasound imaging. Excimer laser atherectomy was examined in the CELLO (CliRpath Excimer Laser System to Enlarge Lumen Openings) single-arm, prospective, multicenter registry.¹³ The study recruited 65 patients (62% had moderate to severe calcification) with a mean lesion length of 5.6 cm and showed a primary patency of 54% with a freedom from TLR of 77% at 12 months of follow-up. 

The interest in atherectomy devices has recently been renewed given encouraging data for drug-coated balloons (DCBs), which can locally deliver antirestenotic therapy to the vessel wall during PTA. Calcified atheromatous plaque represents a barrier to biological effects of antiproliferative drug due to suboptimal drug delivery and absorption.¹⁴ The rationale for combining atherectomy and DCB is logical: to initially debulk severe calcific plaque and then apply DCB once the drug delivery is optimized. Cioppa et al¹⁵ have demonstrated in a small study (n = 30) that a combination of directional atherectomy (with a distal protection device) and DCB can result in a low rate of bail-out stenting (6.5%) and 90% 12-month primary patency rate. Several ongoing randomized trials are currently evaluating a strategy of combining atherectomy and DCB versus paclitaxel-DCB only strategy.⁵ Another strategy that deserves future investigations would be combining atherectomy with temporary scaffolding provided through bioabsorbable stents, which would eliminate future risks of stent fracture and long-term inflammation.

Calcified FP disease continues to present a challenge due to limited options of current gold-standard therapies, poor acute and long-term outcomes with PTA, compressive forces resulting in underexpansion, and inferior long-term patency with nitinol stents. Atherectomy devices can reduce the burden of calcific atheromatous plaque, change vessel compliance, and reduce vessel wall trauma, leading to a decrease in need for bail-out stenting. The advantages of avoiding stenting is the ability to reintervene without a foreign body in place and avoiding potential deleterious effects of stent fractures. Unfortunately, most of the atherectomy data are derived from single-arm observational studies or case series, rather than randomized clinical trials. In this respect, the trial by Dattilo et al adds to the limited body of data examining the effectiveness of atherectomy in FP bed. However, there have been no comparative efficacy or safety studies evaluating the four United States Food and Drug Administration approved atherectomy devices to guide practitioners regarding optimal device selection. Given evolving financial pressures and the emphasis on cost-effectiveness, it should be recognized that atherectomy devices carry higher capital equipment-related costs, particularly when used in conjunction with distal protection filters. Further robust, randomized, prospective, protocol-driven trials are needed with independent core laboratory adjudication of device-related acute and/or 30-day adverse events, 12-month target lesion patency, as well as clinically relevant endpoints, such as amputation-free survival in limb ischemia population. Additional studies are warranted to identify subsets of patients benefiting from atherectomy and to establish an effective, safe, and cost-sensitive strategy, which may include a combination of atherectomy and emerging technologies, such as drug-eluting stents, DCBs, and possibly bioabsorbable stent platforms to ensure a more durable patency in this complex, calcified FP vascular bed.

References

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From the Greenberg Division of Cardiology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports no conflicts of interest regarding the content herein.

Address for correspondence: Dmitriy N. Feldman, MD, Director of Endovascular Services, Assistant Professor of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, Greenberg Division of Cardiology, 520 East 70th Street, Starr-434 Pavilion, New York, NY 10021. Email: dnf9001@med.cornell.edu