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Original Contribution

Single-Center Experience With Optical Coherence Tomography-Guided Directional Atherectomy System for Below-the-Knee Critical Limb Ischemia

Sehrish Memon, MD1;  Ramy Sedhom, MD2;  Sean Janzer, MD1;  Jon C. George, MD1

Issue: Vol. 1 - No. 1 - March 2021
Citation: 

J CRIT LIMB ISCHEM 2021;1(1):E3-E10.

Abstract

Background. Below-the-knee (BTK) peripheral arterial disease (PAD) more often presents as critical limb ischemia. Endovascular revascularization strategies continue to evolve to achieve long-term limb-salvage outcomes. A single-center experience with optical coherence tomography (OCT)-guided atherectomy using Pantheris SV (Avinger) is reported. Methods. All patients with PAD in femoropopliteal or infrapopliteal vessels (n = 27) who underwent plaque debulking by Pantheris SV were analyzed retrospectively. Baseline comorbidities, Rutherford classification, lesion length and characteristics, adjunctive treatment strategy, device-related failures/complications, and major adverse events were analyzed. Additionally, 6-month target-lesion revascularization (TLR) rate was available for 21 of 27 patients. Results. Mean patient age was 70.5 years, 16 patients (59%) were women, and 19 patients (70%) had Rutherford class 5 to 6 symptoms. A total of 58 vessels were treated, including 32 iliofemoropopliteal and 26 infrapopliteal vessels. Chronic occlusions were present in 19% of iliofemoropopliteal lesions and 17.2% of infrapopliteal lesions. The most commonly treated BTK lesion (12 of 26) was the anterior tibial artery (ATA). Following atherectomy, 21 were treated with angioplasty, 4 with angioplasty followed by coronary drug-eluting stent (DES), and 1 with cutting balloon and laser atherectomy. Four failures/complications occurred; 3 of these were device related (failure to pass through lesion due to proximal ATA angulation, coronary DES dislodgment while treating BTK in-stent restenosis, and 1 requiring laser atherectomy for no-flow post atherectomy and angioplasty). At 6 months, 2 of 21 patients (9.5%) required revascularization interventions. Conclusion. Treatment of BTK-PAD with imaging guided Pantheris SV atherectomy device appears to be safe, with low rate of TLR at 6 months. Future multicenter randomized trials are needed to confirm these findings.

J CRIT LIMB ISCHEM 2021;1(1):E3-E10.

Key words: atherectomy, below-the-knee, critical limb ischemia, optical coherence tomography

Introduction

Long, below-the-knee (BTK) lesions present a clinical challenge as the current body of evidence supports long-term limb salvage outcomes with drug-eluting-stent (DES) therapy, but for use in short and focal lesions only. Adequate plaque debulking prior to choice of adjunctive treatment may also allow superior delivery of drug therapy and may achieve improved clinical outcomes for adjunctive treatment with percutaneous transluminal angioplasty (PTA) or stents. 

To date, there are limited data available for the role of directional atherectomy (DA) in endovascular treatment of BTK peripheral artery disease (PAD). The Pantheris small vessel (SV) DA catheter (Avinger) is an optical coherence tomography (OCT)-guided atherectomy system for the treatment of small-vessel lower-extremity PAD. Direct visualization of plaque with the addition of an OCT imaging modality, as offered by the Pantheris SV catheter, avoids unintended adventitial injury, which has been linked to higher restenosis rates.1 A single-center experience with feasibility, safety, and durability of treatment of severe claudicants and critical limb ischemia (CLI) patients with the OCT-guided Pantheris SV atherectomy device is reviewed.

Methods

Study design. The Pantheris SV atherectomy system was introduced to our institution in July 2019 and all patients (n = 27) who underwent DA with the device were included in a single-center, observational, retrospective analysis of device use from July 2019 through July 2020. All patients provided informed consent for the procedure in accordance with the institution’s policy and following guidelines outlined by Good Clinical Practices, the Declaration of Helsinki, and the International Conference on Harmonization. 

The procedures were performed at a teaching hospital with 2 high-volume endovascular operators and 2 fellows in training under their close supervision. The data were extracted from the institution’s cardiac catheterization angiography and procedure documentation system. Patient-related baseline characteristics, including coexisting comorbidities, Rutherford classification, antiplatelet/anticoagulation regimen, type of vessel treated (femoropopliteal or infrapopliteal), and embolic protection device (EPD) use, were extracted. The lesion-related characteristics collected were length, amount of calcification, number of chronic total occlusion (CTO) lesions present, pre- and postatherectomy luminal stenosis, and final stenosis (post Pantheris and adjunctive treatments). The extent of luminal stenosis was adjudicated by fluoroscopy. Major adverse events related to device-associated failures or complications and procedure-related limb threat or amputation for all subjects, as well as target-lesion revascularization (TLR) or limb amputation 6 months after the procedure, were analyzed. 

Device description. The Pantheris SV catheter is a lumivascular, OCT-guided DA system for the treatment of BTK disease in peripheral vessels with a luminal diameter of 2-4 mm. It is advanced over an 0.014˝ guidewire and within a 6 Fr vascular sheath. Device components include an imaging fiber to allow visualization of arterial layers and a 3.5 cm nosecone to house the plaque excised by a stainless-steel cutter (Figure 1). Importantly, it excludes the opposition balloon used in other models of the Pantheris catheter line and thus has a lower crossing profile as well as a longer catheter length than the 7 Fr Pantheris catheter (0.086˝ vs 0.100˝ and 140 cm vs 110 cm, respectively).

Memon OCT Fig1

Results

A total of 27 patients presenting with peripheral lesions in both iliofemoropopliteal and infrapopliteal locations were treated with the Pantheris SV device over a 1-year period (Figure 2). The most commonly treated femoropopliteal vessel was the superficial femoral artery (SFA), of which 2 were in-stent restenosis (ISR) and 4 were CTOs. Of the 15 lesions treated in the SFA, 8 required stent implantation. As expected, these patients were of advanced age and had metabolic comorbidities (Table 1); most (59%) were women. The mean patient age was 70.5 years (range, 49-86 years) and the majority (85%) had PAD with prior stroke events (18.5%) or coronary artery disease (63%). Importantly, 19 of 27 patients (73%) had CLI, as indicated by reporting symptoms placing them in Rutherford classes 4-6. Medical management of these patients included statin therapy or a combination of antiplatelet/anticoagulation regimen, with the most common being aspirin 81 mg and clopidogrel 75 mg (Table 1). 

Memon OCT Fig2

Memon OCT Tab 1

Treatment of BTK lesions. The most commonly treated BTK vessel in this patient group was the anterior tibial artery (ATA), for a total of 12, of which 9 received adjunctive treatment with PTA alone and three had DES implantation after atherectomy (Table 2). The tibioperoneal trunk (TPT) was the second most commonly treated BTK vessel, all of which were treated with PTA alone following atherectomy with the Pantheris SV catheter. The posterior tibial (PT) artery was the least commonly treated vessel in the series; following atherectomy, 2 patients received adjunctive PTA, a coronary DES was placed in 1 patient, and 1 patient required combined treatment with a cutting balloon and adjunctive laser atherectomy (Table 2). Eleven lesions (19%) were iliofemoropopliteal CTOs while 10 (17.2%) were infrapopliteal CTOs. Thirteen of 27 had mild calcification and 7 of 27 had at least moderate calcification (Table 1). EPDs were used in conjunction with atherectomy in 22.2% of femoropopliteal lesions and 7.4% of infrapopliteal lesions without any complications. 

Memon OCT Tab 2

Fluoroscopy determined a mean preprocedural luminal stenosis of 85% and residual stenosis post atherectomy of 21.5%, a decrease in the extent of stenosis of 63.5%. The final mean residual luminal stenosis post Pantheris SV and adjunctive treatments was 8.3%, which was a further mean decrease in stenosis of 13% (Figure 3). 

Memon OCT Fig 3

Adverse events. There were no periprocedural cardiovascular-related deaths and no unplanned major index-limb amputations at 6 months post procedure in available data from 21 of the 27 patients. There was 1 major bleeding event, a retroperitoneal hemorrhage, requiring the transfusion of 2 units of blood and placement of a covered stent (Table 3). Three device-related failures or complications occurred in this patient set: (1) the inability to advance the Pantheris SV catheter within a proximal ATA due to proximal vessel angulation for which only balloon angioplasty was performed of the mid and distal vessel; (2) no restoration of blood flow in a PT following DA and PTA requiring use of angioplasty with a cutting balloon followed by laser atherectomy; and (3) dislodgment of an indwelling coronary DES due to strut entanglement by the device, which was treated by snaring the stent and placement of another coronary DES (Table 4). Only 2 TLR events occurred after 6 months in data available for 21 of the patients (Table 3). The first included ISR of an SFA stent and CTO of a PT previously treated with DA and PTA, while the second was noted to have TPT restenosis and CTOs in both peroneal and PT arteries. All underwent wire-based recanalization and adjunctive PTA or intramedial temsirolimus infusion as part of the TAP-DANCE study in case of the SFA-ISR (Table 5). 

Memon OCT Tab 3Memon OCT Tab 4

Memon OCT Tab 5

Discussion

Current evidence of BTK therapy. Endovascular treatment of BTK disease is often in the setting of CLI, as symptoms are most likely manifested when more than 1 tibial vessel has severe atherosclerotic/calcific disease.2 BTK-CLI patients also predominantly have diabetes as a risk factor which, when present, is associated with a 5-year survival rate of only 25% and higher incidence of limb amputation and TLR.3 

Review of the literature shows that the treatment algorithm for BTK disease has evolved significantly in recent years. PTA is associated with elastic recoil and flow-limiting dissections in diseased peripheral vessels, which yield low long-term patency results from restenosis and the return of symptoms that affect patient quality of life.4 The BASIL trial comparing PTA with bypass surgery in CLI patients for infrainguinal disease showed similar amputation-free survival outcomes after 6 months between the 2 arms, with surgery associated with higher short-term cost, helping to pioneer BTK endovascular treatment.5 Comparison of placement of a bare-metal stent (BMS) with the use of PTA in BTK disease has noted poor mid-term outcomes with the BMS due to ISR from inflammation and neointimal hyperplasia initiated by stent placement, thus favoring a primary treatment strategy of PTA and use of BMS as bail-out option. Similarly, a propensity-matched analysis of 357 patients with BTK-CLI who were treated with a BMS vs PTA showed a higher target-extremity revascularization rate following stenting than with PTA (18.9% vs 11.1%, respectively; P<.01) over 1 year.6 In contrast with the use of BMS, DES therapy has shown promising results. Three multicenter randomized control trials, ACHILLES, YUKON-BTX, and DESTINY, have illustrated lower restenosis rates with DES than PTA (ACHILLES trial) and superior event-free survival and primary patency rates when comparing DES with BMS (YUKON-BTX and DESTINY trials).7-9 These findings were confirmed in the 5-year long-term follow-up PADI trial where paclitaxel-eluting stent compared with PTA-BMS had superior event-free survival and amputation rates (31.8% vs 20.4% [P=.04] and 26.2% vs 15.3% [P=.04], respectively) in addition to having higher long-term patency rates.10 

Drug-coated balloon (DCB) technology for treatment of longer infrapopliteal lesions was first investigated in the DEBATE-BTK trial, with a mean lesion length of 129 ± 83 mm. The study concluded that DCB in comparison with PTA had lower 1-year restenosis rates (27% vs 74.3%, respectively) and lower major adverse events (31% vs 51%, respectively, driven by TLR and ulcer healing), but no difference in amputation rate, limb salvage, or mortality.11 However, the prospective, multicenter, randomized IN.Pact Deep CLI trial of 358 CLI patients comparing DCB with PTA in a 2:1 fashion showed no difference in primary endpoint of late lumen loss or TLR, but a non-significantly higher amputation rate in the DCB group (8.8% DCB vs 3.6% PTA; P=.08) over a 12-month period.12 Currently, the best practice for BTK adjunctive treatment favors DES therapy; however, most lesions in the randomized trials are short and focal in nature and therefore a class IA or appropriate recommendation is given for <120-140 mm infrapopliteal lesions only.7-9,13

DA and BTK disease. Atherectomy devices (directional, orbital, rotational, or OCT guided) are infrequently utilized in BTK disease, which may in part be due to lack of dedicated device technology for BTK small-vessel disease and increased perceived risk of complications with their use. The TALON study, wherein infrapopliteal lesions were treated with SilverHawk DA, had a mean lesion length of 68.5 mm and required adjunctive treatment in 73.3% of lesions with stent deployment in 6.3% of lesions. The 6- and 12-month freedom from TLR rates were 90% and 80%, respectively.14 The DEFINITIVE LE cohort of 189 infrapopliteal vessels treated with SilverHawk DA had a mean lesion length of 58 ± 44 mm with 20% occlusions and a primary patency rate of 84% at 1-year follow-up and freedom from major amputation rate of 97.1%, with significant clinical and quality of life improvements.15 A recent retrospective study of 97 patients with BTK-CLI comparing different treatment strategies in a single-center, retrospective observational manner over a period of 5 years showed reocclusion rates at 30 months post intervention to be higher with PTA alone (58.1%) than with adjunctive atherectomy and PTA (33.3%) or atherectomy with stenting (50%).16 The atherectomy devices used at the center included HawkOne, SilverHawk, TurboHawk (Medtronic), or orbital atherectomy. It has been demonstrated that drug absorption can be greatly reduced when deposited onto plaque vs directly onto the intra-arterial layers. Therefore, achieving greater plaque debulking with direct visual guidance can greatly impact the efficacy and resorption of drug-eluting therapies, ie, DCB or DES.17

Pantheris SV and benefits of OCT-guided DA. The Pantheris SV atherectomy catheter received Food and Drug Administration marketing clearance for the treatment of PAD in vessels with diameters of 2-4 mm in April 2019. The lumivascular technology allows for visualization of intra-arterial wall structures with identification of media, internal and external elastic lamina, and adventitia, along with stent struts and dissections. Plaque morphology (calcium, fibroatheromas, thrombus, necrotic core) can also be readily identified.18 Adventitial disruption has been associated with a 97% 1-year incidence of restenosis in comparison with 11% when its not disrupted.1 OCT-guided plaque debulking can avoid this disruption and may provide improved outcomes. The seminal single-arm, multicenter VISION trial, which evaluated first-generation outcomes with femoropopliteal Pantheris DA device, showed a high rate of plaque-only debulking with <1% adventitia measured on histologic plaque specimens and no dissections or perforations.19 In contrast, fluoroscopy-guided DA with the TurboHawk DA catheter found a mean volume of 16% adventitia noted in tissue collected during atherectomy in 1 study.20 The 6- and 12-month TLR rates reported in the VISION trial were 6.4% and 14%, respectively,16 as compared with a 6-month TLR rate of 10% reported in the TALON registry, where 601 patients were treated with fluoroscopy-guided SilverHawk DA.19 The more recently completed DEFINITIVE LE study evaluated 799 patients treated with SilverHawk and TurboHawk DA systems and reported a primary patency rate of 78% for all lesions and 65% in CTO lesions at 12 months post procedure.15 OCT-guided DA is also helpful in planning adjunctive therapy, as it can identify short segments of plaque burden or flow-limiting dissections avoiding unnecessarily longer stents. Lesion length measurements performed with OCT imaging in the VISION trial were significantly longer than the lengths measured by fluoroscopy (72.4 mm vs 53.1 mm, respectively; P<.001).19 Fluoroscopy times can also be greatly reduced with OCT-guided DA, as most plaque debulking can be accomplished without radiation with improved adherence to the “as low as reasonably allowable” radiation principle. 

Implications of Pantheris SV on BTK treatment. Image-guided BTK atherectomy with the Pantheris SV catheter appears to be safe, with a low incidence of device failure or complications and appreciably low freedom from TLR at 6 months post procedure. While this study demonstrated that the catheter can be successfully utilized for all types of BTK lesions, including CTOs and ISRs, ATA angulation appears to present a challenge for device advancement. Further prospective analysis on the angles that deem the device difficult to advance should be undertaken. There was 1 stent dislodgment in treating a PT lesion, which was adequately treated with snaring the stent and restenting that portion of the vessel. It is important to note that this complication occurred early, within 2 months of introduction of the device at a teaching institution. Thus, a larger sample is needed to formally evaluate outcomes of Pantheris SV DA for treatment of BTK-ISR. The 1 case with no flow post DA and PTA may be related to a multitude of factors, including distal embolus, arterial spasm, or thrombus. This particular lesion was also noted to contain severe calcification and required use of a coronary cutting balloon and laser atherectomy in order to reduce luminal stenosis sufficiently to restore blood flow. The device’s performance in severely calcified lesions also necessitates further investigation. There were also only 2 TLRs over a 6-month follow-up available for 21 of the patients, signaling durable mid-term clinical outcomes. 

Enrollment for a IMAGE-BTK clinical study evaluating the safety and efficacy of the Pantheris SV for the treatment of BTK disease began in January 2020, with 30-day, 6-month, and 1-year freedom from TLR and primary patency outcomes to be determined for a total of 60 patients.21 The present study is the first to provide observational procedural safety, efficacy, and 6-month TLR outcomes with use of the Pantheris SV. 

Study limitations. This study is an observational, retrospective, small-sample size analysis of all patients undergoing treatment with Pantheris SV atherectomy in the past year at a teaching institution with a high volume of endovascular procedures; as such, biases like the expertise of the operator cannot be determined. A randomized trial comparing OCT-guided atherectomy with adjunctive treatment vs non-imaging guided atherectomy would yield stronger evidence in favor of one treatment over the other. The adjunctive treatment also needs randomization to ascertain which interventional treatment is best suited in BTK lesions with added DA. The antiplatelet/anticoagulant regimen also varied among study subjects. Given the benefits of low-dose rivaroxaban in the COMPASS and VOYAGER-PAD trials, especially in CLI patients, the outcomes may differ with uniform treatment cohorts.22,23 Finally, due to relatively high loss to follow-up (n = 6; 22%), these outcomes including TLR rates may be underestimated.

Conclusion

OCT-guided DA with the Pantheris SV catheter appears to be safe and effective, with a low number of complications and low TLR rates at 6 months. Larger, multicenter, randomized trials are needed to further validate these results.

Disclosures

From the 1Division of Cardiovascular Disease, Einstein Medical Center, Philadelphia, Pennsylvania; and 2Division of Internal Medicine, Einstein Medical Center, Philadelphia, Pennsylvania.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Janzer and Dr George report consultant income from Avinger. The remaining authors report no conflicts of interest regarding the content herein. 

Manuscript accepted January 11, 2021.

Address for correspondence: Jon C. George, MD, 5501 Old York Road, Philadelphia, PA 19141. Email: jcgeorgemd@gmail.com

Abstract
Introduction
Methods
Results
Discussion
Conclusion

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3. Spiliopoulos S, Theodosiadou V, Katsanos K, et al. Long-term clinical outcomes of infrapopliteal drug-eluting stent placement for critical limb ischemia in diabetic patients. J Vasc Interv Radiol. 2015;26:1423-1430. 

4. Katsanos K, Spiliopoulos S, Krokidis M, et al. Does below-the-knee placement of drug-eluting stents improve clinical outcomes? J Cardiovasc Surg (Torino). 2012;53:195-203. 

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6. Ahn J, Rha S. One-year follow-up of stenting versus standard balloon angioplasty for the below-knee arteries in Korean patients: a propensity score-matched analysis [TCTAP abstract A-0880]. J Am Coll Cardiol. 2018;71:S51.

7. Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial. J Am Coll Cardiol. 2012;60:2290-2295.

8. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs bare-metal stents for treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-center, randomized clinical trial. Eur Heart J. 2011;32:2274-2281.

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15. McKinsey JF, Zeller T, Rocha-Singh KJ. Lower extremity revascularization using directional atherectomy: 12-month prospective results of the DEFINITIVE LE study. JACC Cardiovasc Interv. 2014;7:923-933. 

16. Thunuguntla S, Echeruo O, Mild C, et al. Superior short-term patency of stents over balloons in infrapopliteal artery disease. School of Medicine Publications and Presentations. 2020:81. 

17. Virmani R. The relevance of paclitaxel dose and coating for efficacy and safety. Paper presented at: LINC 2015; January 25, 2015; Leipzig, Germany. 

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22. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319-1330. 

23. Capell WH, Bonaca MP, Nehler MR, et al. Rationale and design for the vascular outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD). Am Heart J. 2018;199:83-91.