Abstract
Objective: To examine the efficacy and durability of an interwoven self-expanding nitinol stent for the treatment of superficial femoral and popliteal arteries.
Method: Consecutive patients with severely diseased superficial femoral and popliteal arteries who received SUPERA stents were retrospectively identified.
The patients were followed for 12 months by Doppler ultrasound examinations, stent roentgenograms, and estimation of Rutherford–Becker class and ankle-brachial index.
Results: From July 2012 to May 2014, 42 limbs in 36 patients (mean age, 61.5 7.5 years; 75% male) were treated with angioplasty and primary stenting. Total occlusions were present in 14 limbs, and 63.8% had either moderate or severe calcification. The mean ( SD) lesion length was 105 mm ( 28). Primary patency was 91.4% at 6 months and 85.7% at 12 months. The ankle brachial index increased from 0.57 0.19 preoperative to 0.91 0.12 postoperative. There was no procedural or device-related morbidity or mortality after revascularization and only one major amputation was observed on follow-up.
Conclusions: Our experience shows that, Supera stents are safe and effective in our cohort of patients, with acceptable patency rates. There were no stent fractures so far even with stenting of the femoropopliteal segments. Stent design provides a viable option for high-grade obstructive disease in the femoropopliteal artery.
Keywords
Superficial femoral artery, peripheral artery disease, occlusion, angioplasty, nitinol stent, stent fracture
Introduction
Percutaneous interventions for peripheral arterial dis-ease (PAD) in the superficial femoral artery (SFA) and the femoropopliteal artery have been associated with high restenosis rates and poor long-term patency with balloon angioplasty alone.1 Treatment strategies in the SFA and femoropopliteal artery are potentially com-promised by the high calcium content within the plaque and vessel wall, long length of lesions, and unique dynamic forces found within these arteries.2
Multiple clinical trials with laser-cut nitinol stents in primary stent placement have demonstrated improved patency rates compared with either percutaneous trans-luminal angioplasty with provisional stent placement or a predefined percutaneous transluminal angioplasty performance goal.3–5 However, with 12-month patency rates in these trials ranging from 53% to 83% after nitinol stent implantation, restenosis rates are still greater than desirable, especially in difficult lesion seg-ments. Another potential risk factor for reocclusion stems from stent fractures, which range from 0.4% to 8.1% at 12 months.6,7 Since then, significant improvements in the design of laser-cut nitinol stents have been made, which have increased the axial flexi-bility of the implants.6 While the rates of fractures reported with this second generation of nitinol stents tend to be lower, data on stented segments >15 cm are missing, and major stent fractures continue to occur after the treatment of shorter segments. In the recently reported DURABILITY study, a clear correlation was observed between major stent fractures and restenosis and target lesion revascularization.6
The objective of this analysis was to evaluate the performance and durability of a novel stent system designed to withstand the compression, torsion, bend-ing, lengthening, shortening, and pulsations found within the SFA. We report our single-center experience in patients with PAD who received interwoven nitinol stents in the femoropopliteal arteries.
Methods
Patients
All patients who received Supera interwoven nitinol stents (IDEV Technologies, Webster, TX, USA) in the femoropopliteal artery segment at our hospital were retrospectively identified. Patients underwent baseline physical examinations with a focus on lower limb ischemia, categorized according to the Rutherford–Becker classification (RBC). Ankle bra-chial index (ABI) measurements and duplex ultrasound studies were performed, followed by selective angiog-raphy of the femoropopliteal segment to outline the anatomy of the vessels and define the lesion characteristics.
Treatment and follow-up were according to the standard procedures implemented in our institution. All patients gave written informed consent before undergoing the procedure. To collect scientifically and clinically meaningful information, the study intention-ally included patients presenting with a wide variety of complex lesions in the femoropopliteal arteries, includ-ing heavy calcifications and total occlusions, without prespecified inclusion and exclusion criteria. The sys-tematic follow-up focused on the incidence of stent fractures and restenosis. Patients with lower limb femoropopliteal arterial stenosis or occlusions, as shown on preoperative duplex ultrasound assessment, were included in this study. Patients with acute throm-bus or aneurysm in the index vessel, unsalvageable limb, poor inflow or total absence of runoff vessels, lesions unsuitable for angioplasty, very limited life expectancy, or doubts in the willingness or capability to allow follow-up examination were excluded.
Patients with renal impairment who were deemed very high risk of developing contrast nephropathy would be optimized as much as possible and those who could not tolerate the intervention or subsequent follow-up were excluded.
Stent procedure and medical regimens
All patients had initial diagnostic angiography of the lower limb with standard contrast intra-arterial digital subtraction angiogram to outline the vascular anatomy and define the lesion characteristics and to confirm their candidacy for the study. The endovascular procedures were performed by experienced vascular specialists in a hybrid endovascular suite (Siemens Artis Zeego Multipurpose System; Siemens, Munich, Germany). The procedures were performed under monitored anes-thetic care or under local anesthesia, with ipsilateral or contralateral common femoral artery and retrograde popliteal artery accessed with a 6 F sheath for the diag-nostic angiogram. All the patients received intra-arter-ial heparin through the sheath. From the intraoperative angiogram, it was possible to calculate and document the diameter of the target vessel, the minimal luminal diameter, minimal luminal area, and the length of sten-osis–occlusion. Patients with chronic SFA occlusion underwent percutaneous recanalization from a retro-grade popliteal access. The popliteal artery was punc-tured using an 18-G needle under ultrasound guidance. After insertion of a 5–6 F introducer sheath, and per-formance of diagnostic angiogram, intravenous heparin (100 U/kg) was administered. For crossing the stenosis or occlusion, 0.035 road runner guidewire was used through the right judkins 5-6 guiding catheter. The ini-tial passage of the occlusion was carried out; the wire was exchanged for a 0.018-in. or 0.020-in. wire. The Rotarex device was introduced for chronic total occlu-sions and slowly moved forward with a to-and-fro motion at a speed of about 1–2 cm/s until the distal end of the occlusion was reached. A control angiogram was performed after the first passage and, if necessary, additional runs were performed until all thrombotic material was removed. After the first or second passage of the occlusion, the flow was checked by dye injection while the catheter was still in position distal to the occlusion. If flow was restored, the wire was pulled back into the catheter lumen, and the device was slowly retracted while rotating the slightly bent tip of the catheter. This allowed clearing thrombi from a larger area of the vessel. After recanalization of the SFA and proximal popliteal artery with balloon angio-plasty and Rotarex catheter system, Supera interwoven nitinol stents were deployed to cover the needed parts of the lesion (Figure 2). The interwoven nitinol Supera stent is constructed from six pairs of nitinol wires woven together to create a helical pattern. The wires form closed loops at both ends of the stent. The stent is premounted and delivered via a 6-F or 7-F catheter-based delivery system over a 0.014-in. or 0.018-in. wire. All lesions were routinely dilated before stent placement using a balloon 0.5–1.0 mm larger than the reference vessel diameter to allow adequate expansion of the stent. Stent length was selected so as to cover the lesion and at least 5 mm of lesion-free proximal and distal vessel. When more than one stent was needed, stents were over lapped for at least 10 mm. Dilation with a noncompliant balloon was performed after stent placement if the operator recognized that some segments of stent were underexpanded. A control angiogram was done to visualize the flow within the SFA and PA and to exclude the presence of thrombo-embolic material distally.
The antithrombotic regimen was administered per usual institutional practices, including periprocedural anticoagulation with weight-based heparin to maintain activated clotting time >250 s. Dual antiplatelet ther-apy with aspirin and clopidogrel was prescribed after the procedure for at least 30 days unless a contraindi-cation existed; this was followed by aspirin alone indefinitely.
Follow-up and study end points
All patients were evaluated before discharge from the hospital and were scheduled to return for ambulatory follow-up visits at 1, 6, 12, and 24 months after the procedure. At these visits, physical examinations, cat-egorization of the RBC, ABI measurements, and duplex ultrasound studies for the detection of restenosis were performed; the duplex ultrasound recordings were analyzed by an independent investigator. To confirm the integrity of the stent, and in compliance with the institution’s practices, plain roentgenograms of the stented segment were obtained between 12 and 24 months after the index procedure in two oblique views with the leg extended and with the knee bent.
The primary efficacy end point of this analysis was stent patency, defined as absence of binary restenosis (>50% decrease in vessel diameter) on duplex ultra-sound examination as represented by a peak systolic velocity ratio > 2.4.8 The secondary end points included (1) procedural success, defined as a, 30% residual vessel stenosis; (2) clinical status according to the RBC; (3) ABI measurements; (4) incidence of stent fractures on radiographic screening; and (5) the rate of target lesion revascularization.
Statistical analysis
Statistical analysis was performed with Graphpad Instat software (version 3 for Mac; version 11.5, GraphPad Software Inc.). Descriptive statistics were used to present the mean standard deviation or median (range) for continuous variables and the counts (percentages) for categorical variables. Cumulative patency rates with their standard errors were estimated using Kaplan–Meier analysis. Comparisons of mean ABI and RBCs at various time points were made using the Student’s t-test for depend-ent samples. Statistical significance was defined as p < 0.05.
Results
Patient characteristics
From July 2012 to May, 36 consecutive patients (26 males) with symptomatic femoropopliteal lesions were treated with angioplasty and primary stenting using the Supera stent at our institution. Twenty-two were left-sided lesions, 14 were right-sided lesions, and 4 patients have bilateral interventions. Mean ( SD) age was 61.5 ( 7.3) years. (Range, 56–82 years); 26 (72%) patients were male. Demographic data, risk factors, and comor-bidities are summarized in Table 1.
Of the 42 interventions performed, most (64.2%) involved the SFA only, and 14.2% involved the poplit-eal artery only (Table 1). Before the interventions, total occlusions were present in 14 limbs (38.8%), 22% had tissue loss, and 63.8 % of lesions showed moderate or severe calcification on fluoroscopy. Cardiovascular risk factors were prevalent; 80.5% (29 patients) were on antihypertensive medication, 72% (26 patients) were active smokers, 52.7% (19 patients) were diabetic, and 30.5% (11 patients) had proven hyperlipidemia (Table 1). The majority (29, 80.5%) of patients pre-sented with severe claudication (Rutherford–Becker category 3); 7 (19.4%) had critical limb ischemia (Rutherford–Becker category 4–5).
Lesions and procedural characteristics
Lesion characteristics and number of runoff vessels are summarized in Table 2, with 14 (38.8%) cases involving the proximal SFA, 20 (55.5%) cases involving the mid-SFA, 23 (63.8%) cases involving the distal-SFA, 17 (47.2%) cases involving the above-knee popliteal artery, and 10 (27.7%) cases involving the below-knee popliteal artery. The mean lesion length was 105 mm ( 28), and over half (20, 55.5%) of the lesions were moderately to severely calcified.
Technical success (puncture of the popliteal artery or femoral artery with Doppler Ultrasound (DUS) guid-ance and SFA recanalization) was achieved in all patients. Endoluminal recanalization was possible from the popliteal access in most of the patients with chronic total occlusions (n ¼ 13). SFA recanalization in one case was obtained through the subintimal space. We did not use reentry device for crossing chronic total occlusions. Procedure success (visually estimated residual arterial stenosis <30%) was achieved in 35 (97.2%) patients (Figure 1). The average number of stents implanted per limb was 1.6 (range, 1–4). Total stent mean ( SD) length was 124 mm ( 45); stent diameter ranged from 4 to 7 mm, with 6 mm being the most frequently used diameter (Table 2). Between base-line and discharge, the mean RBC decreased from 3.18 0.5 to 2.36 1.2 (p < 0.0001); the mean ABI increased from 0.57 0.19 preoperative to 0.91 0.12 postoperative (p < 0.0001).
Follow-up
The mean follow-up period was 13.8 months for 36 patients. There were no perioperative or procedural/ device-related mortality. Clinical evaluation with ABI assessment of adverse events was planned predischarge from hospital. Clinical follow-up and duplex ultra-sound for evaluation of restenosis will be performed routinely on all the patients at 1, 3, 6, and 12 months. Based on the need for revascularization according to clinical indications, the patency rate was 94.2% at 6 months and 85.7% at 12 months (Figure 2, Table 3), and the assisted patency rate was 96.8%.
Reintervention was required in three patients who had in-stent restenosis with 50%, 70%, 80% stenosis, and two patients who had at or before 12 months; throughout the follow-up period (Table 3). Procedures selected for reinterventions were at the dis-cretion of the operator. Most reinterventions included percutaneous mechanic thrombectomy (PMT) with Aspirex catheter (Straub Medical, Switzerland) com-bined with balloon angioplasty. Unfortunately, one patient was diagnosed with a second instance of in-stent thrombosis, which was again treated with PMT. He remains asymptomatic and with no evidence of hemodynamically significant recurrence. No stent frac-tures were observed by fluoroscopy (Figure 3).
Complications
The in-hospital adverse events were limited to one peri-procedural pseudoaneurysm, which was managed by manual compression and two minor access site bleed-ing. There were no periprocedural major bleeding epi-sodes requiring transfusion. With all patients under the care of their primary physician, complications that did not require therapy or required only minor therapy with minor sequelae (class A or B according to Society of Interventional Radiology Reporting Standards)9 were not captured. There were two major complications occurred (grades C–E) during the follow-up period (one amputation, one limb-threatening ische-mia requiring PMT) and three patients died of unre-lated cardiopulmonary–renal causes on follow-up. The patient who had undergone amputation of the ischemic limb was treated successfully eight months ago with Rotarex catheter and two Supera stents. He was living in another city and came back to our hospital with necrosis and irreversible phase for revasculariza-tion. Before arriving to our center, he stayed in different hospitals with critical limb ischemia for five days. Therefore, we have no chance to do for limb salvage.
Discussion
Long-term high patency of femoropopliteal artery revascularization remains a challenge. Factors affecting outcomes include increasing lesion length, presence of multiple lesions, chronic total occlusion, tissue loss, diabetes, and the coexistence of inflow and outflow dis-ease.3,6,10 Endovascular stents have significantly increased the patency rate beyond that of balloon angioplasty alone. However, the femoropopliteal artery is subjected to numerous extrinsic forces requir-ing self-expandable stents in this region to have optimal strength, flexibility, durability, and conformability.11 In addition, the high compressive forces applied against nitinol stents by rigid calcified plaques result in incom-plete and eccentric stent expansion, linked to inferior patency outcomes compared with fully expanded stents.12 The stents exert a variable degree of chronic outward force on the artery wall and increase artery patency by decreasing failure from restenosis compared with balloon.
This article describes our initial experience on the primary stenting using Supera stents for treating symp-tomatic patients with femoropopliteal atherosclerotic lesions. Our cohort of consecutive patients included an elderly proportion, with 22% having tissue loss. The majority of our patients had atherosclerotic disease involving the severely calcified SFA and the popliteal artery. Our primary patency rate of 85.7% at 12 months is comparable to the few published series in the literature. In all of the patients who followed the protocol and had biplane radiographs of the stents, none developed stent fractures on follow-up.
The novel Supera interwoven self-expanding nitinol stent, which has been studied in this analysis, consists of woven nitinol wires braided in a tubular mesh con-figuration. The design configuration results in a stent that is flexible, compliant, and self-expanding and has a very high radial resistive strength. These features make the stent more suitable to withstand dynamic forces such as compression, torsion, bending, shortening, and pulsation. In a previous analysis of its use in the SFA, the device has been shown to have very good patency rates up to two years, as well as a complete absence of stent fractures.13
The Supera stent design resulted in superior vessel lumen preservation, specifically in severely calcified lesions, compared with traditional nitinol stent designs. In this retrospective evaluation of 36 patients receiving treatment in 42 limbs, the mean follow-up period was 13.8 months with a mean lesion length of 13.5 ( 38) cm. Using a definition of patency based on free-dom from clinically driven target lesion revasculariza-tion, Kaplan–Meier estimates of primary patency and assisted primary patency were 85.8% and 96.8% at 12 months, respectively.
Rosenfield presented the 12-month outcomes of the Supera Peripheral Stent System.14 This SUPERB study evaluate the Supera stent in treating patients with obstructive SFA in 264 patients in 34 centers, treating 266 lesions with a mean length of 8 cm. Primary patency at one year was 86% with no reported stent fractures at one year. The two-year clinical outcomes of the Supera Peripheral Stent System from Supera 500, a long-term registry, which was also presented at the Tenth Vascular InterVentional Advances Conference by Scheinert et al.13 This registry included 495 patients with 528 lesions, with 53% of the patients with occlu-sive disease, and a mean stented segment length of 12.6 cm. The primary end points at one and two years were 84.1% and 73.0%, respectively.
In contrast, several clinical trials evaluating various standard nitinol stents enrolled patients with shorter lesions. The Edwards Life sciences Self-Expanding Stent Peripheral Vascular Disease Study (RESILIENT) trial evaluated the Life Stent (Bard Peripheral Vascular, Tempe, Arizona) in 134 patients with mean lesion length of 7.1 cm and found a one-year primary patency of 81%.15 Other trials evaluating standard nitinol stents have had lower one-year patency results. The Safety and Effectiveness Study of Ever Flex Stent to Treat Symptomatic Femoral-popliteal Atherosclerosis (DURABILITYII) trial (Covidien, Mansfield, MA) in 287 patients with mean lesion length of 8.9 cm reported a one-year primary patency of 77%.16 The evaluation of the Zilver PTX Drug-Eluting Stent in the Above-the-Knee Femoro-popliteal Artery trial evaluated the Zilver PTX (Cook, Inc, Bloomington, IN) drug-eluting stent in 241 patients with mean lesion length of 5.4 cm and found a primary patency at one year of 83%.17
Stents placement at the femoropopliteal junction and proximal/midpopliteal artery is not widely accepted by many vascular specialists because the biomechanical forces over the knee joint can predispose to stent fracture and restenosis.18,19 The femoropopliteal arterial seg-ment, especially the part behind the knee joint (known to be exposed to many mechanical influences such as crossing of flexion points as well as interaction with the surrounding musculature and the artery) is con-stantly exposed to relevant external forces, including compression, torsion, and elongation during locomo-tion. In a large prospective series with 121 cases in which different types of uncovered nitinol stents were used, Scheinert et al. reported stent fractures in 37% (45 out of 121 legs had 64 fractures) after a mean follow-up of 11 months.20 The stent fractures in this series ranged from fracture of single struts to complete separation of stent segments, and about one third of the cases resulted in occlusion of the artery. Despite this, in our series on follow-up of the patients with a mean follow-up period, none of them developed stent fracture on plain radiographs. Stent fractures can also cause restenosis with significantly lower primary patency rate, although fractures without causing hemodynamic significance may run a more benign course and may not need reintervention. Stent fractures may damage the arterial wall and result in development of a pseudoa-neurysm.21 Chang et al. retrospectively reviewed 18 patients who underwent stent placement in popliteal arteries and found that one limb had stent fracture at one month and seven limbs developed fractures at the three-month follow-up.22 At two-years follow-up, there were just four limbs, which did not have stent fracture. The primary patency was much lower in fractured stents.
Despite the challenging study population (27.7% total occlusions, lesion length > 10 cm, and primarily severe to critical limb ischemia), a 97.2% technical suc-cess rate was achieved, which resulted in significant clinical improvement. To achieve these excellent implantation results, we had to be more precise during the stent implantation process than would be required with standard laser-cut nitinol stents. First, careful attention was paid to properly match the stent diameter (1:1) to the reference vessel diameter to ensure that the stent could be deployed close to its nominal diameter, where it reaches its highest radial strength. Moreover, to ensure optimal compliance of the vessel during stent deployment, the artery was systematically predilated using a balloon catheter with a diameter that was at least equal to the reference vessel diameter. In selected cases with very rigid, calcified lesions, the artery was dilated with oversized or high-pressure bal-loons before stenting.
Most importantly, in our analysis, the Supera stent was very durable and remained free from fractures at a mean of 13.8 months despite the relatively long length of the stented segment (mean 124 45 mm) and the fact that nearly half of the stents were implanted into the distal SFA partially extending into the proximal popliteal segment. Similarly, the primary patency rates of 94.2% and 85.7% at 6 and 12 months, respect-ively, are very encouraging and compared favorably with the reported literature.
One of the limitations to our study is that it was a single vascular center experience. Our study has a high proportion of patients with critical limb ischemia, and many of the patients are elderly. We regard our initial results as being as accurate as possible, and the primary Supera stenting was encouraging with no clinical limb loss, no device related morbidity–mortality, and no stent fractures. Since there is as yet little long-term experience with this new helical stent worldwide, we recommended continuous surveillance of the treated segment with color-coded Doppler sonography. However, the number of patients studied is relatively small and lacks random-ization. There will inevitably be patient selection bias, which may have influenced the results.
Conclusion
Implantation of a novel self-expanding Supera stent achieved very encouraging acute and follow-up results in a cohort of patients with a wide range of femoropo-pliteal lesions. The interwoven nitinol stent design provides flexibility, and strength translate into high long-term patency and fracture resistance. Although the data are promising, additional multicenter studies are needed.
