Two Blades-Up Runs Using the JetStream Navitus Atherectomy Device Achieve Optimal Tissue Debulking of Nonocclusive In-Stent Restenosis

Abstract

Purpose: To determine the number of runs with blades up (BU) using the JetStream Navitus to achieving optimal debulking in a porcine model of femoropopliteal artery in-stent restenosis (ISR). Methods: In this porcine model, 8 limbs were implanted with overlapping nitinol self-expanding stents. ISR was treated initially with 2 blades-down (BD) runs followed by 4 BU runs (BU1 to BU4). Quantitative vascular angiography (QVA) was performed at baseline, after 2 BD runs, and after each BU run. Plaque surface area and percent stenosis within the treated stented segment were measured. Intravascular ultrasound (IVUS) was used to measure minimum lumen area (MLA) and determine IVUS-derived plaque surface area. Results: QVA showed that plaque surface area was significantly reduced between baseline (83.9%±14.8%) and 2 BD (67.7%±17.0%, p=0.005) and BU1 (55.4%±9.0%, p=0.005) runs, and between BU1 and BU2 runs (50.7%±9.7%, p<0.05). Percent stenosis behaved similarly with no further reduction after BU2. There were no further reductions in plaque surface area or percent stenosis with BU 3 and 4 runs (p=0.10). Similarly, IVUS (24 lesions) confirmed optimal results with BU2 runs and no additional gain in MLA or reduction in plaque surface area with BU3 and 4. IVUS confirmed no orbital cutting with JetStream Navitus. There were no stent strut discontinuities on high-resolution radiographs following atherectomy. Conclusion: JetStream Navitus achieved optimal tissue debulking after 2 BD and 2 BU runs with no further statistical gain in debulking after the BU2 run. Operators treating ISR with JetStream Navitus may be advised to limit their debulking to 2 BD and 2 BU runs to achieve optimal debulking.

Keywords

in-stent restenosis optimal debulking atherectomy porcine model quantitative angiography intravascular ultrasound plaque surface area percent stenosis minimum lumen diameter

Introduction

The JetStream Navitus (Boston Scientific, Maple Grove, MN, USA) is a rotational atherectomy device that uses rotational cutting and aspiration to treat de novo or restenotic infrainguinal arterial obstructive disease. The device has 2 sets of blades: one set is at the tip of the catheter and the other (5 blades) is mounted proximal to the tip. Counterclockwise rotation expands the proximal blades and allows wider tissue cutting. The JetStream Navitus has been improved compared to its predecessor, the Pathway device, with the aspiration port placed proximal to the blades instead of distally, allowing a more robust aspiration capacity. The recommended use of this device with tips and tricks on how to operate it can be found in prior publications.^1,2

The use of this device in treating in-stent restenosis (ISR) is off label in the United States. Also, the optimal number of runs with the blades down (BD) or up (BU), defined as a single pass from proximal to distal within the restenotic stented segment, has not been defined. In this porcine stent/balloon injury overstretch model, the JetStream Navitus atherectomy system was tested on 4 animals (8 stented femoral arteries) to define the number of runs needed to maximize tissue debulking and determine whether stent strut discontinuity would occur.

Methods

Preprocedure Animal Care

A Yorkshire swine model was chosen as the experimental animal because of the similarity to humans in terms of the size and anatomy of the cardiovascular system. Furthermore, this model has been validated for the occurrence of restenosis within 1 month of stent/balloon overstretch injury, making it more practical for testing medical devices in treating ISR. All animals were held in quarantine and housed at CBSET (Lexington, MA, USA), a facility accredited by the American Association for Accreditation of Laboratory Animal Care, under conditions that met or exceeded requirements as set forth in the USDA guidelines.^3,4 Standard veterinary practices were performed during quarantine, including physical examinations and clinical pathology to determine health status before assignment to the study. A nutritionally balanced diet appropriate for the species was offered daily to all animals with water ad libitum. Animals were released from quarantine by the veterinary staff when deemed healthy.

Animal Preparation

All animals were pretreated 1 day before stent implantation with aspirin 650 orally and clopidogrel 300 mg orally. They were maintained on aspirin (81 mg daily orally) and clopidogrel (75 mg daily orally) thereafter until euthanized. Animals received Telazol (4–6 mg/kg) intramuscularly as a preanesthetic. Isoflurane anesthesia was then administered to effect via mask/nosecone, and endotracheal intubation was then performed. Following intubation, the animals were maintained on continuous inhalant isoflurane anesthesia delivered for the remainder of the procedure. Perioperative nifedipine (10 mg/animal placed sublingually) was also administered. The animals were prepared for surgery using accepted veterinary care standards. Electrocardiogram leads, a pulse oximetry sensor, and a temperature probe were placed for continuous monitoring of vital signs. Preemptive analgesia (buprenorphine; 0.01–0.03 mg/kg), was administered intramuscularly at anesthesia (prior to surgical incision). The incision site was prepared and appropriately draped for aseptic procedures.

Stent Implantation Procedure

The right carotid artery was accessed using a cutdown approach. An introducer sheath was advanced into the artery and heparin (50–200 U/kg) was administered intravenously to prolong the activated coagulation time to a target of >275 seconds. A guide catheter was then advanced to the iliac arteries under fluoroscopic guidance. The femoral arteries were crossed with a 0.035-inch J-tipped guidewire, and the target segment was dilated 3 times (30 seconds each) with an oversized angioplasty balloon at various pressures and to achieve a 1.2 to 1.5 balloon:artery ratio. Two overlapping 40-mm-long nitinol S.M.A.R.T. self-expanding stents (5.0 and 6.0 mm in diameter; Cordis Corporation, Bridgewater, NJ, USA) were then deployed to the dilated target lesion (sized 1.2:1 stent:artery). The amount of overlap was either 100% (n=2) or 25% to 50% (n=6). The same process was repeated for the contralateral leg. A total of 8 stents were deployed in 4 limbs. Following stent implantation in both left and right femoral arteries, the animal was weaned off the anesthetic and extubated. Buprenorphine 0.01 to 0.03 mg/kg was administered intramuscularly every ~4 to 12 hours to provide analgesic coverage through at least the first 24 postoperative hours

Atherectomy Procedure

Animals were brought back to the fluoroscopy suite approximately 1 month after stent implantation. The anesthesia procedure was repeated as described above. Carotid artery access was obtained using the cutdown method. Angiographic images of the target vessel were obtained with contrast media to characterize the degree of ISR. Quantitative vessel angiography (QVA; Centricity Cardiology CA1000 Cardiac Review 2.0 software) was used to measure minimum lumen diameter (MLD), plaque surface area (PSA), and percent stenosis. An optimal residual stenosis after atherectomy alone was defined as a residual percent stenosis <50%.

Atherectomy was then carried on by advancing the cutter at a slow speed of 1 to 2 mm per seconds from the proximal to distal end of the stented segment (one run) over a Spartacore wire (Abbott Vascular, Redwood City, CA, USA). Two atherectomy runs with BD followed by QVA at the lesion site was performed. Atherectomy was then repeated with BU for 4 runs and with QVA of the lesion after each run (Figure 1).

Intravascular ultrasound (IVUS) quantitative measurements were also performed at baseline, after 2 BD runs, and after each BU run (BU1, BU2, BU3, BU4) on a total of 24 locations in the proximal, mid, and distal parts of the stented segments (Figure 2). Minimum lumen area (MLA) within each of the 24 locations was determined. PSA was calculated from the total stented area at each location minus the MLA. Finally, MLA and PSA at baseline were plotted against net MLA gain and PSA reduction (BU MLA or PSA − baseline MLA or PSA), respectively. The minimum MLA and PSA ranges at baseline needed for an increase in MLA by 1 to 2 mm and reduction in PSA by 5% to 10% from baseline were determined.

Device interaction with the implanted stent and subsequent damage of the stent was carefully evaluated under fluoroscopy. The process was repeated for the contralateral limb. After the last treatment, the animal was euthanized. Stents were evaluated postmortem with high resolution radiographs to determine strut damage.

Statistical Analysis

Descriptive analysis was performed on all angiographic variables. Single-sample Wilcoxon signed-rank test was performed between MLA obtained after BU runs and theoretical maximal MLA of the XC 2.4-3.4 cutter with BU model. Line graphs were performed to illustrate the change in MLD, MLA, PSA (with IVUS) and percent stenosis with each treatment. Wilcoxon signed-rank test and paired t test (1-tail) were performed to compare baseline, BD, and BU 1 to 4 runs using the statistical package in Minitab 17 (State College, PA, USA).

Results

The mean vessel diameter was 4.7±0.6 mm and mean lesion length was 61.5±12.6 mm. The mean baseline (n=8) MLD was 1.73±0.84 mm. Following 2BD and 1 BU runs, the mean MLDs were 2.6±0.7 mm (p=0.025) and 3.12±0.39 mm (p=0.005), respectively, vs baseline MLD. There was also a significant increase in MLD between 2BD runs and BU1 run (p=0.005). No statistical difference in MLD was seen between BU runs (p>0.05; Figure 3A).

PSA was significantly reduced between baseline (83.9%±14.8%) and 2 BD (67.7%±17.0%, p=0.005) and BU1 (55.4%±9.0%, p=0.005) runs and between BU1 and BU2 runs (50.7%±9.7%, p<0.05). No differences in PSA were seen between the BU2, BU3, and BU4 runs (p>0.05). Percent stenosis was reduced from a mean of 63.13%±16.91% to 44.97%±15.0% (p=0.005) with BD runs and to 33.51%±6.73% (p=0.005) with BU1 run. There was also a significant reduction in percent stenosis between 2 BD runs and BU1 run (p=0.01) and between BU1 and BU2 runs (30.1%±7.0%, p=0.05). No difference between percent stenosis was seen between BU 2 to 4 runs (p=0.10; Figure 3B).

The mean baseline MLA by IVUS was 7.8±2.7 mm². Following 2BD and 1 BU runs, the mean MLAs were 8.1±2.5 mm² (p<0.044) and 8.7±2.0 mm² (p=0.007), respectively, when compared to baseline MLA. There was also a significant increase in MLA between 2BD runs and BU1 run (p=0.033) and between BU1 and BU2 runs (9.4±2.4 mm², p=0.007). No statistical difference in MLA was seen between BU 2 to 3 runs (p>0.05; Figure 4A).

PSA was significantly reduced between baseline (65.2%±11.7%) and 2 BD (63.0%±10.5%, p=0.015) and BU1 (60.7%±9.2%, p=0.011) runs and between BU1 and BU2 runs (57.5%±7.5%, p=0.025). No differences in PSA were seen between the BU2, BU3, and BU4 runs (p=0.12; Figure 4B)

Vessel area measured by IVUS at the site of the treated stenosis remained unchanged between baseline and BU4 run (23.3±5.8 vs 22.5±4.9 mm², respectively; p=0.73). Further-more, a significant correlation was seen between MLA at baseline and change in MLA after BU runs (p=0.006; Figure 5A) and between PSA at baseline and change in PSA after BU runs (p<0.0001; Figure 5B). An approximate baseline MLA of 8.0 to 9.0 mm² led to an MLA gain of 1 to 2 mm² and an approximate baseline PSA of 60% to 70% led to a reduction in PSA by 5% to 10% using the large cutter BU mode. Finally, theoretical MLA achievable from the XC BU 2.4-3.4 device is 9.08 mm² (A = πr2 using r=3.4/2=1.7 mm). No difference was seen between this calculated MLA and the IVUS measured MLAs after BU runs, indicating no orbital effect of the device on tissue cutting.

There were no observed angiographic stent disruptions or stent strut discontinuity with IVUS or high-resolution radiography (Figure 6) with JetStream Navitus atherectomy.

Discussion

JetStream Navitus atherectomy is a rotational cutter with active aspiration capacity. Although JetStream Navitus is approved in the United States for treating de novo and nonstent restenotic lesions of the infrainguinal vessels, it is off label in treating ISR. The degree of its effectiveness in debulking restenotic tissue and the number of runs needed to achieve optimal plaque cutting has not yet been defined or quantified. In this porcine model of ISR, JetStream Navitus atherectomy appears to be effective in significantly reducing percent stenosis and PSA and increasing MLD and MLA within the stented segment, with no complications or adverse interaction with the stent. These findings need to be validated in adequately powered clinical trials.

Previous experience in Europe with the Pathway device⁶ and early experience with the JetStream Navitus⁷ indicated safety and good success in ISR. Findings from this animal model demonstrate the effectiveness of the JetStream Navitus in treating ISR with a clear stepwise debulking using BD and BU runs. Using more than 2 BU runs exerts minimal additional debulking effect, which is statistically not significant. Therefore we conclude that the majority of the debulking process occurs with the second BU run, an important finding to guide the operators to limit their debulking with the larger BU cutter to only 2 runs, potentially reducing complications, including distal embolization that is typically associated with atherectomy^8–11 and adverse device-stent interaction. The latter, however, was not observed using high resolution radiography of implanted stents following 4 BU runs, supporting the safety of this device in ISR treatment.

Using IVUS, JetStream Navitus is a true debulking device with no Dottering effect. In one study of post–JetStream Navitus atherectomy, total vessel volume remained unchanged, but tissue volume was reduced and MLD was increased significantly.⁵ Our IVUS data confirm the same findings by showing that MLA is increased and PSA is reduced, indicating true tissue excision within a nitinol self-expanding stent. Furthermore, the median MLA change seen after BU runs was statistically similar to the theoretical MLA calculated using a BU large cutter, which indicates that effective cutting is limited to the perimeter of the device, with no “wobbling” or “orbital” effect. This is a limitation of the device in treating femoropopliteal ISR, as suboptimal tissue excision is therefore expected in larger vessel diameter (possibly 7 mm or higher).

In this model, stents were positioned at different overlapping lengths to test the safety of the device in treating short or long overlapping stent segments, particularly when the blades are up. No adverse events or stent-device interaction were seen. Also, there was no angiographic evidence of dissection or distal embolization following JetStream Navitus atherectomy, but it should be noted that these lesions are relatively short and not totally occluded; thus, they have a low potential for embolization.

Finally, adjunctive balloon angioplasty was not performed after the JetStream Navitus as the intention of the study was to test the effectiveness and safety of the device itself rather than the final outcome after adjunctive balloon angioplasty. The residual narrowing post atherectomy was a mean of 30.1%, which is consistent with effective tissue debulking (<50% residual) with the JetStream Navitus alone and without balloon angioplasty. This residual narrowing was accomplished in a mean vessel diameter of 4.7 mm. The acute effectiveness of the JetStream Navitus in cutting and removing restenotic tissue within a femoropopliteal stent does not necessarily reflect better long-term effectiveness in reducing target lesion revascularization (TLR) or improving patency compared with angioplasty alone. Randomized studies comparing the JetStream Navitus to balloon angioplasty, drug-eluting stents (DES), covered stents, or drug-coated balloons (DCB) are not available at this time. However, data from observational studies¹² and the recent randomized Excimer Laser Atherectomy for Treatment of Femoropopliteal In-Stent Restenosis (EXCITE) trial¹³ showed that tissue excision using excimer laser and adjunctive balloon angioplasty had a higher acute procedure success and better intermediate-term results compared to balloon angioplasty alone in treating femoropopliteal ISR, indicating that tissue excision prior to angioplasty is a superior strategy to balloon angioplasty alone. Although prospective comparative data in treating femoropopliteal ISR between various atherectomy devices is not available, a retrospective analysis suggested no difference in 1-year outcome between excimer laser and SilverHawk atherectomy.¹⁴

The value of JetStream atherectomy alone or as an adjunctive therapy to DCB or DES in treating femoropopliteal ISR when compared to these devices alone is still unknown. A recent study showed that laser with DCB is superior to DCB alone in patients with limb ischemia and femoropopliteal ISR, with better TLR and fewer amputations.¹⁵ Cost-effectiveness comparative data are needed before any one strategy can be recommended.

This study’s findings apply to nonoccluded ISR. In this animal model, there were no total occlusions, so the extent of debulking is unclear in these lesions. Furthermore, animal model restenotic tissue of 1-month duration may be softer and possibly more likely to respond to cutting than several months old restenotic tissue in humans. Further data are needed to clarify this concept. Finally, this study is of limited clinical significance. Clinical trials using the 2 BD/2BU runs method are needed to determine if this translates into better clinical outcome

Conclusion

Operators may limit their debulking technique in nonoccluded ISR using JetStream Navitus atherectomy to 2 BD runs and 2 BU runs to accomplish acute optimal cutting and potentially reduce complications from excessive debulking.

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Nicolas W. Shammas receives educational and research grants from Boston Scientific and is a trainer for the JetStream atherectomy device. Full disclosure at

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study has been supported by a grant from Boston Scientific, Maple Grove, MN, USA.

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