- Email: [email protected]
Predictors of restenosis in the use of helical interwoven nitinol stents to treat femoropopliteal occlusive disease
Single-center experience and predictors of restenosis in the use of helical interwoven nitinol stents to treat femoropopliteal occlusive disease Yiu Che Chan, MBBS, MD, FRCS, Stephen W. Cheng, MBBS, MS, FRCS, and Grace C. Cheung, MMedSc, Hong Kong, China Background: The femoropopliteal arteries are subjected to considerable axial and bending deformity due to flexion at the hip and knee joints. The Supera helical interwoven nitinol stent system (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex) has good conformability and flexibility, with a very low incidence of mechanical fatigue. This study reviewed our experience with the use of Supera stents for femoropopliteal atherosclerotic lesions and identified risk factors for restenosis or occlusion. Methods: Patients with symptomatic femoropopliteal atherosclerotic diseases who underwent lower limb angioplasty and Supera stent insertion were studied. All patients had regular clinical follow-up and underwent a Doppler ultrasound examination at 3 months and then every 6 months, and radiography of the stents at 6, 12, 18, 24, 30, and 36 months. Patency rates were analyzed using Kaplan-Meier curves. We also evaluated the prospectively maintained cohort to identify predictors of restenosis. Results: From October 2011 to December 2014, 164 legs in 153 symptomatic patients (96 male, 57 female) with femoropopliteal occlusive disease, with mean age of 76.7 years (range 46-100 years), were included. Ninety-five patients (58%) had claudication, nine (5%) had rest pain, and 60 (37%) had tissue loss. Disease distribution was 64 proximal superficial femoral arteries (SFAs; 39%), 107 middle SFAs (65%), 127 distal SFAs (77%), 78 above-knee popliteal arteries (48%), and 19 below-knee popliteal arteries (12%). Lesion classification by TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) A, B, C, and D was 49 (30%), 79 (48%), 31 (19%), 3 (1%), respectively. The mean lesion length was 105.6 mm (range 3-400 mm), and more than one Supera stent was inserted in 26 patients. Procedure success (residual stenosis <30%) was achieved in 100% of procedures. The primary patency rates (>50% patency) at 6, 12, 24, and 30 months were (6standard error) 86.7% 6 3.1%, 81.4% 6 3.7%, 79.9% 6 4.0%, and 77 6 3.0%, respectively. The ankle-brachial pressure index increased from 0.57 6 0.15 preoperatively to 0.87 6 0.14 postoperatively. No stent fractures occurred. There were three 30-day deaths not related to the procedure or device, one major amputation 3 months after revascularization, and 29 late deaths (>30 days) of unrelated medical causes in followup. In-stent restenosis was associated with younger patient age and with dyslipidemia, long lesion, and stent length. Conclusions: Our midterm experience showed that the implantation of the helical interwoven nitinol stents in patients with femoropopliteal occlusive disease is safe and effective, with encouraging patency rates and clinical results. (J Vasc Surg 2015;-:1-9.)
Implantation of nitinol stents into the superficial femoral (SFA) and popliteal arteries is a widely used technique as a selective or routine adjunct to percutaneous transluminal angioplasty.1-3 Stents placed in the lower From the Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital. This project was supported by funding from the Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre. Author conflict of interest: none. Presented as an abstract at the Leipzig Interventional Course Asia-Pacific 2015, Lantau Island, Hong Kong, March 9-11, 2015. Reprint requests: Yiu Che Chan, MBBS, MD, FRCS, Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Flr K Block, Queen Mary Hospital, Pokfulam Rd, Hong Kong (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2015 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2015.05.030
limb arteries, especially those near the hip or knee joints, may fracture over time and can adversely affect the artery and cause restenosis or occlusion. In a study of 861 patients who underwent nitinol stenting of the femoropopliteal segments in 1017 limbs, Iida et al4 found that at least 104 limbs (10%) had stent fractures on follow-up. In another study by Scheinert et al5 of 121 legs in 93 patients treated by implantation of selfexpanding nitinol stents with a mean follow-up of 10.7 months, stent fractures were detected in 45 of 121 (37.2%) legs. The novel interwoven nitinol Supera stent (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex) has been shown to enhance strength, flexibility, and fracture and kink resistance,6 and it conforms well to the femoropopliteal arteries with joint movements. Our group has previously reported on the use of Supera stent in treating patients with symptomatic SFA and popliteal artery disease.7 In this study, we addressed the knowledge base gap with longer-term results with the Supera stent in a realworld setting, which is important given the deficiencies 1
2 Chan et al
noted with prior self-expanding stent series and the relative dearth of longer-term experiences with the Supera stent. METHODS All patients who participated in the study gave written consent. Institutional Review Board approval is not required in Hong Kong for this type of interventional study in which a Conformité Européene marked and locally approved interventional device is used that was commercially available. Study population. Methods of patient recruitment, procedure, and follow-up protocol were described in our previous publication.7 This current report is a continuation of the same study, but with additional patients and a longer follow-up period. All patients underwent preoperative arterial duplex imaging by dedicated and qualified vascular technologists or ultrasonographers in our vascular laboratory. The Duplex ultrasound scans identified the length, degree, and characteristics of target lesions. We routinely relied on accurate duplex ultrasound reporting of the peripheral arterial system before intervention, without the need to confirm the nature of our target lesion with another imaging modality. After the duplex results were available, patients were interviewed again, and if their symptoms persisted and they were keen for an endovascular revascularization, they were entered onto the waiting list for the procedure. Symptoms included intermittent claudication as reported by the patients or evidence of critical ischemia with rest pain or tissue loss, as defined as Rutherford categories 46 as critical ischaemia.8 Chronic critical limb ischemia can also be defined as persisting recurring rest pain requiring regular analgesia for more than 2 weeks, or ulcers, gangrene at the foot (tissue loss), with ankle systolic pressure of <50 mmHg.9 Clinical symptoms of intermittent claudication were further categorized in 15 patients (9%) who had mild claudication (could walk >300 m), 15 (9%) who had moderate claudication (could walk between 100 and 300 m), and 65 (40%) who had severe claudication (could walk <100 m). The study excluded patients with acute thrombus or aneurysm in the index limb/vessel, an unsalvageable limb, poor inflow or total absence of run-off vessels, very limited life-expectancy, or with doubts in their willingness or capability to allow follow-up examinations. The limb was deemed unsalvageable if there was extensive tissue loss, with or without sepsis, and would not benefit from revascularization. The decisions to exclude patients were left to the discretion of the individual operators. Patients with renal impairment (not on renal replacement therapy) who were deemed very high risk of developing contrast nephropathy and who could not tolerate the intervention or subsequent follow-up were excluded. Study procedure. All the patients in this study had a preoperative duplex ultrasound examination and diagnostic angiography of the lower limb with a standard contrast intra-arterial digital subtraction angiogram at the time of the endovascular intervention. All of the endovascular
JOURNAL OF VASCULAR SURGERY --- 2015
procedures were performed by experienced vascular specialists in our hybrid endovascular suite (Siemens Artis Zee Multipurpose System; Siemens, Munich, Germany) situated in the Minimally Invasive Surgical Centre. All patients were prescribed aspirin preoperatively. The procedures were performed under monitored anesthetic care, with antegrade or retrograde percutaneous access of the ipsilateral or contralateral common femoral artery with a 6F sheath for the diagnostic angiogram. All patients received intra-arterial heparin through the sheath. All patients were prescribed clopidogrel and aspirin for 3 months and remained on aspirin for life. From the computerized software (Siemens Artis Zee Multipurpose System) of the angiogram, it was possible to calculate and document the minimal luminal diameter, minimal luminal area, and the length of stensosis/ occlusion. Stenoses and occlusions were passed using 0.035-inch or 0.018-inch guidewires with the help of a 5F straight diagnostic catheter. The diameter of the target vessel was measured by computer, and the size of the angioplasty balloon catheters ranged in size from 4 to 7 mm in diameter by 20 to 200 mm in length and were inflated to nominal atmospheres for 1 minute. A completion angiogram was performed after balloon dilatation. In cases of severe recoil of very calcified plaque, repeat angioplasty was performed with adequate preparation of the target vessel. All of the Supera-stented target lesions were angioplastied with the balloon size 1 mm larger than the stent diameter according to the manufacturer’s instructions, with poststent dilatation. Stents were chosen to cover the length of the lesions. The Supera stents were premounted and delivered via a 6F or 7F catheter-based delivery system over a 0.014-inch or 0.018-inch wire. When more than one stent was needed, stents were overlapped for at least 10 mm. A completion angiogram was performed in all cases after stenting (Fig 1). Postprocedure assessment and follow-up. Clinical evaluation with ankle-brachial index (ABI), duplex ultrasonic follow-up examinations, and assessment of adverse events was performed before discharge from hospital. Clinical follow-up and duplex ultrasound imaging for evaluation of restenosis was performed routinely on all patients at 3, 6, 12, 18, 24, 30, and 36 months and every 6 months thereafter. Plain radiographs of the stent were taken at 6-month intervals to rule out stent fracture. All patients had electronic radiologic records on Clinical Management System-Electronic Patients Records. The plain radiographs of the stents were taken as anteroposterior and lateral views and viewed on the Centricity Enterprise Web Listener 1.0 (GE Healthcare Products, Waukesha, Wisc). The images can be magnified on the screen during viewing. The patency data were based on the actual date of the duplex examination. A patient missed a follow-up appointment was censored at the date of the last examination. The primary end point was postoperative restenosis (target lesion stenosis of >50% or occlusion) evaluated with
JOURNAL OF VASCULAR SURGERY Volume -, Number -
Chan et al 3
Fig 1. An angiogram shows (A) right popliteal artery stenosis with (B) angioplasty and (C) stenting. D, Anteroposterior and (E) lateral view plain radiographs show the Supera stent (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex).
duplex ultrasound imaging by an independent vascular ultrasonographers and vascular surgeons. The ultrasound criteria used for a restenosis >50% was prestenosis and a stenosis ratio of $2.0, or a peak systolic velocity of $200 cm/s.7 Secondary end points included technical interventional success rate, minimal lumen diameter, improvement of symptoms (change in Rutherford grade), change in ABI, major amputations, stent-related complications such as fractures, and all serious adverse events possibly related to the treatment. Statistical analysis. Counts and percentages are reported for categoric variables, and means and standard deviations are reported for qualitative variables. Comparisons between groups were made with the Student t-test and the c2 test. Patency rates were analyzed using Kaplan-Meier curves to compute time-to-event rates. The log-rank test assessed the potential effect of risk factors on outcome or complications in the univariate setting. Predictors for restenosis were also calculated. A P value of #.05 was taken to be statistically significant. All statistical analyses were performed using SPSS 20 software (IBM Corp, Armonk, NY). RESULTS Patient characteristics. The study period spanned from October 2011 to December 2014. A total of 153 consecutive patients (96 men, 57 women; age range, 46100 years) with 164 legs with symptomatic femoropopliteal lesions were treated with angioplasty and primary stenting using the Supera stent at our institution. Eighty-two were left-sided lesions, 82 were right-sided lesions, and 11 patients had bilateral interventions. Male patients were a mean age of 73.2 years (range, 46-92) and female patients were a mean age of 82.7 years (range,
63-100 years). Our cohort of 153 patients included some elderly patients, with a mean age of 76.7 years. Cardiovascular risk factors were prevalent: 127 patients (77%) were on regular antihypertensive medication, 68 (41%) were active smokers, 102 (62%) were diabetic, and 58 (35%) had proven hyperlipidemia (Table I). Indications for interventions were intermittent claudication in 95 limbs (58%), rest pain in (5%), and tissue loss in 60 (37%). The severity of intermittent claudication was ascertained by patient history only (Table I). In the same study period, our departmental database showed that we had 266 patients who had femoropopliteal/peripheral arterial disease but without revascularization. This number included eight patients who had primary amputations. In the same period, we performed 83 procedures in 74 patients with devices other than Supera stents, including 22 bypasses and 61 angioplasty procedures with or without stents. Supera stents were not used in these patients and they were not included in this current study. Lesions and procedural characteristics. All treatment were achieved with percutaneous endovascular procedures, with only one patient requiring open exploration of the common femoral artery performed under general anesthesia with patch angioplasty in conjunction with angioplasty and stenting of the SFA in view of a severely calcified common femoral artery (Table I). Lesion characteristics and number of runoff vessels are summarized in Table I. The arteries involved were the proximal SFA in 64 limbs (39%), the middle SFA in 107 (65%), the distal SFA in 127 (77%), the above-knee popliteal artery in 78 (48%), and the below-knee popliteal artery in 19 (12%). The length of the lesions varied from 5 to 400 mm, with a mean of 105.6 mm.
JOURNAL OF VASCULAR SURGERY --- 2015
4 Chan et al
Table I. Demographics, indications, lesion characteristics, and number of run-off vessels in the patients Variable
Patients (n ¼ 153), No. (%)
Prevalence of cardiovascular risk factors Smoking Hypertension Hyperlipidemia Diabetes
68 127 58 102
(44) (83) (38) (67)
Limbs (n ¼ 164), No. (%) Clinical category 1eMild claudication 2eModerate claudication 3eSevere claudication 4eIschemic rest pain 5eMinor tissue loss Diseased segment SFA Proximal Middle Distal Popliteal artery Above knee Below knee TASC II A B C D Occluded lesions Runoff vessels, No. 0 1 2 3
15 15 65 9 60
(9) (9) (40) (5) (37)
64 (39) 107 (65) 127 (77) 78 (48) 19 (12) 49 79 31 3 55
(30) (48) (19) (2) (34)
5 59 57 43
(3) (36) (35) (26)
SFA, Superficial femoral artery; TASC II, TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease.
A total of 191 stents, 4 to 6 mm in diameter and 40 to 200 mm in length (each stent) were implanted in these patients. The mean length of the stented artery was 122.1 mm (range 40-650 mm; standard error of the mean, 6.27) for a mean lesion length of 105.6 mm (range, 3-400 mm; standard error of the mean, 5.79). All of the lesions had poststent moulding. Technical success was 100%. Patient follow-up. The mean follow-up period was 15.17 months for the 153 patients. There were no perioperative or procedural-related or device-related deaths. One patient developed a 1.5-cm pseudoaneurysm in the groin, which was treated conservatively. One patient had emboli to peroneal artery treated successfully with intraoperative thrombolysis. There were three 30-day deaths not related to the procedure or the device. One was a 93-year-old woman with tissue loss who underwent a successful revascularization and was discharged on day 4 but was readmitted to hospital on day 10 with respiratory distress after suddenly collapsing at home. A 68-year-old woman with end-stage renal failure sustained a myocardial infarction that did not respond to
maximum medical therapy and died on day 26 after successful revascularization. The third patient was a 59-yearold man with carcinoma of the gall bladder who died of acute myocardial infarction on day 12 after the procedure. On follow-up, 29 patients (16 male, 13 female) had died (excluding the above 30-day deaths). The causes of death were pneumonia, cardiac, cardiac and renal causes, and gastrointestinal bleeding. ABI, stent patency, and stent fracture rates. The limb salvage rate was 99.3%, with only one patient receiving an above-knee amputation 3 months after revascularization due to septic nonhealing, painful, wet gangrene. Between baseline and discharge, the mean ABI increased significantly from 0.57 6 0.15 preoperatively to 0.87 6 0.14 postoperatively (P < .01 by paired t-test), with all patients reporting improvement in symptoms. All patients followed the set protocol, and the primary patency rates at 6, 12, 24, and 30 months were 86.7% 6 3.1%, 81.4% 6 3.7%, 79.9% 6 4.0%, and 77 6 3.0%, respectively (Fig 2). The 23 patients who had in-stent restenosis or instent occlusion included 9 with 50%, 6 with 70%, and 8 with reocclusion. Because the balloons and stents were self-financed by the patients, they preferred a conservative nonintervention if their symptoms improved. Predictors for restenosis (Table II) demonstrated that younger age, longer target lesions, and longer stented lengths were positive significant predictors for restenosis in this cohort (P ¼ .017, P ¼ .018, and P ¼ .003, respectively, by t-test). Patients with hyperlipidemia were more likely to have restenosis, but this did not quite reach statistical significance (P ¼ .052 by c2). The primary patency rate, as analyzed by the diseased segment of the SFA or popliteal artery and indication of treatment (claudication vs critical ischemia/tissue loss) is shown in Fig 3 and Fig 4, respectively. However, more restenosis occurred in patients who had 4-mm stents implanted (Fig 5). On follow-up of the patients with a mean follow-up period, none developed stent fracture on plain radiographs. DISCUSSION This study reflects a real-world experience with the use of Supera stents in femoropopliteal occlusive disease, with long challenging lesions: the mean length of the stented artery was 122.1 mm (range 40-650 mm; standard error of the mean, 6.27) for mean length of lesion of 105.6 mm (range, 3-400 mm; standard error of the mean, 5.79). In this cohort of patients, we identified that longer target lesions with more atherosclerotic burden and longer stented lengths were positive significant predictors for restenosis. Patients with hyperlipidemia were more likely to have restenosis, but this did not quite reach statistical significance. These risk factors were not obvious in our previous shorter-term results.7 Although hypercholesterolemia has not previously been directly correlated with worse outcomes for lower extremity vascular interventions, there is abundant evidence that hypercholesterolemia would contribute to widespread atherosclerosis and that
JOURNAL OF VASCULAR SURGERY Volume -, Number -
Chan et al 5
Fig 2. Kaplan-Meier curve shows overall primary patency rates, with error bars representing standard errors.
Table II. Risk factor stratification for restenosisa Variable Male sex Age, years Risk factors Smoking Hypertension Hyperlipidemia Diabetes Symptoms Claudication Rest pain Tissue loss Clinical group Claudication Threatened limb loss Maximum stenosis Calcification Runoff vessels 0 1 2 3 Combined length of stents, mm Length of lesion
No restenosis (n ¼ 141) 88 (62) 77.6 6 10.1 58 109 54 84
(41) (77) (38) (60)
Restenosis (n ¼ 23)
Overall (N ¼ 164)
P
16 (70) 72.0 6 12.0
104 (63) 76.8 6 10.5
.509b .017c,d
10 18 4 18
(43) (78) (17) (78)
68 127 58 102
(41) (77) (35) (62)
87 (62) 15 (11) 51 (36)
14 (61) 2 (9) 9 (39)
101 (62) 17 (10) 60 (37)
81 (57) 59 (42) 87.8 6 11.3 66 (47)
13 (57) 10 (43) 90.8 6 11.1 10 (43)
94 (57) 69 (42) 88.2 6 11.3 76 (46)
5 (4) 50 (35) 49 (35) 37 (26) 116.2 6 66.9 98.9 6 68.4
0 (0) 9 (39) 8 (35) 6 (26) 158.7 6 132.5 147.1 6 93.7
5 (3) 59 (36) 57 (35) 43 (26) 122.1 6 80.2 105.6 6 74.1
.832b .919b .052b,d .087b .939b .777b .785b .904b .229c .766b .828b
.018c,d .003c,d
Categoric data are shown as mean 6 standard deviation and continuous data as number (%). Positive significant predictors by t-test for restenosis in this cohort were younger age (P ¼ .017), longer target lesions (P ¼ .018), and longer stented lengths (P ¼ .003). Patients with hyperlipidemia were more likely to have restenosis, but this did not quite reach statistical significance (P ¼ .052 by c2 test). b P value by c2 test. c P value by t-test. d Statistically significant. a
6 Chan et al
JOURNAL OF VASCULAR SURGERY --- 2015
Fig 3. The primary patency rate as analyzed by disease segment of the superficial femoral artery (SFA) or SFA with or without the popliteal artery.
lipid-lowering agents, such as statins, may help to control atherosclerotic disease in the lower extremities. We did not notice any stent fractures in our cohort. We also noticed that there was a statistically significant difference in primary patency rates between those patients who received 4-mm and 5-mm stents. We postulate that this was just due to small vessel diameter and not related to the stents themselves. Placement of stents at the femoropopliteal segment and popliteal artery has not been widely accepted by many vascular specialists because the biomechanical forces over the knee joint could predispose to stent fracture and restenosis.10-12 A review by Ansari et al13 on the biomechanics of the SFA and popliteal artery in patients with peripheral arterial disease showed that implanted stents undergo a variety of deformations as patients engage in their daily activities such as walking, sitting, or climbing. Musculoskeletal motions led to deformation of the proximal and middle SFA by shortening in the axial direction 4.0%, by twisting 2.1 /cm, and by bending 72.1 mm. Similarly, the distal SFA and proximal popliteal arteries were deformed even more, up to shortening in the axial direction 13.9%, by twisting 3.5 /cm, and by being pinched such that the aspect ratio of the lumen changed 4.6%. The distal popliteal artery also shortened in the axial direction
12.3%, by twisting 3.5 /cm, by bending 22.1 mm, and the luminal area changed by 12.5%.12 Because a stent is a permanent implant in the target vessels, that they would be subjected to a wide variety of torsion, compression, and stress is not surprising. A study by Scheinert et al,5 using systematic X-ray screening for stent fractures in 121 legs treated by implantation of selfexpanding nitinol stents after a mean follow-up time of 10.7 months, detected stent fractures in 37.2%. These were classified as minor (single-strut fracture) in 31 legs (48.4%), moderate (fracture of >1 strut) in 17 legs (26.6%), severe (complete separation of stent segments) in 16 legs (25.0%), and 34.4% of the stent fractures were associated with a total in-stent occlusion.5 The Supera stent is more flexible and resistant to compression so that it is more capable of withstanding the forces exerted upon it by the tortuosity and mobility of the femoral and popliteal vessels. The stent consists of six pairs of braided self-expanding closed end interwoven nitinol (nickel-titanium alloy) wires that is premounted on a 6F or 7F delivery system and delivered via a coaxial catheter-based delivery handle. The delivery system includes a reciprocating mechanism that incrementally moves the stent distally out of the outer sheath. This motion allows for the distal end of the stent to first come in contact
JOURNAL OF VASCULAR SURGERY Volume -, Number -
Chan et al 7
Fig 4. The primary patency rate as analyzed by indication of treatment for claudication vs critical ischemia/tissue loss.
with the targeted vessel, setting the distal reference point, and continues to feed the stent out of the sheath as the target wall is exposed by the proximal movement of the catheter. This stent deployment is achieved by the reciprocation of the thumb slide located on the handle. The Supera stent was formally launched in Leipzig, Germany, in 2010, with a full launch in Europe in the summer of 2010. We began using the stent it our institution in October 2011, being the first center to use this stent in Asia. In the United States, it received approved for peripheral use only by the Food and Drug Administration in March 2014.14 Only a handful of studies of the Supera stents have been published, and our results in this report of primary patency rates of 86.7%, 81.4%, 79.9%, 79.9%, 77% at 6, 12, 18, 24, and 30 months, respectively, in 164 legs are comparable to published series. Scheinert et al15 reported 2-years results of 137 Supera stents in 107 patients with a mean age of 68.9 years with symptomatic atherosclerotic femoropopliteal lesions, 31% of whom had total arterial occlusions. The mean lesion length was 9 cm, and the lesions were predominately in the SFA, with occasional involvement of the first segment of the popliteal artery. The stented segments were a mean length of 111.50 mm, and the mean primary and secondary stent patency rates at 6 months were 93.1% and 99.0%, respectively, and primary
and secondary stent patency rates at 12 months were 84.7% and 94.8%, respectively. No stent fractures were seen in the 91 patients examined.6 Goltz et al16 studied 40 patients who had angioplasty of their proximal and middle popliteal artery, followed by implantation of a Supera stent, and showed that the primary and secondary cumulative patency rates at 12 months in 34 patients were 68.4% and 79.8%, respectively. In the follow-up period, postprocedure radiographs were available for only seven of 40 patients (17.5%), and none developed any stent fractures.16 Rosenfield et al17 presented the 12-month outcomes from the SUPERB (Comparison of the Supera Peripheral System to a Performance Goal Derived from Balloon Angioplasty Clinical Trials in the Superficial Femoral Artery) study of the Supera Peripheral Stent System at the 10th Vascular InterVentional Advances (VIVA) Conference in October 2012. The SUPERB study was a Food and Drug Administration-approved investigational device exemption trial17 to evaluate the Supera stent in the treatment of patients with obstructive SFA disease. The study recruited 264 patients at 34 centers, treating 266 lesions with a mean length of 8 cm. The primary patency at 1 year was reported to be 86%, but formal results on this trial have not been published yet. In the SUPERB trial, elongation and compression of the stent during
8 Chan et al
JOURNAL OF VASCULAR SURGERY --- 2015
Fig 5. The primary patency rate as analyzed by patients who had 5-mm or 4-mm Supera stents (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex) implanted.
deployment, especially those with moderate to severe elongation, were found to be positive predictors of restenosis. We have not look at this issue in our current study. León et al18 showed in a cohort of 34 patients with 39 stents placed in the isolated popliteal artery that the primary, primary assisted, and secondary patency rates by duplex ultrasound imaging were 79.2%, 88.1%, and 93%, respectively. Six stent occlusions occurred, and six patients had hemodynamically significant in-stent restenosis. Three patients (8.8%) had limb loss, two related to uncontrolled infections, and one due to perioperative ischemic complications (both with patent stents at the time of limb loss). The overall mortality was 8.8% during the study period, and no stent fractures were identified. Werner et al19 recently reported the result of the Leipzig SUPERA 500 Registry with 527 limbs in 470 patients with femoropopliteal arterial disease treated with Supera stents. The mean lesion length was 126.4 mm, with total occlusions present in 277 limbs (52.6%). During a mean follow-up period of 21 months, the primary patency rates were 83.3% after 12 months and 72.8% at 2 years. The patency rates did not differ between SFA and popliteal lesions. Plain radiographs performed on 229 patients at a mean of 16.6 months did not show any evidence of stent fractures.
George et al20 reported the results of the SUPERA Interwoven Nitinol Stent Outcomes in Above-Knee IntErventions (SAKE) study on 98 limbs in 80 patients with an average of 14.3 months after intervention, and demonstrated satisfactory results with a primary patency of 96.9% and 85.8% at 6 and 12 months. No stent fractures were detected. The unique design of the Supera stent best conforms to the target vessel anatomy. Its combination of flexibility and radial strength may account for the ability of this stent to restore durable patency in a harsh environment for any endovascular device. The SFA and proximal popliteal artery are exposed to significant mechanical stress with bending and rotation of the knee. According to the manufacturers’ information, this Supera stent showed increased flexibility, duration, and radial force as a result of its new design. The radial force of the Supera stent at a diameter of 4 to 5 mm could be as much as 18 pounds.21 To date, no stent fractures with this type of stent has been reported in published literature. There are other case reports on the use of the Supera stents in hostile calcified vessels or as a bail-out option in an occluded popliteal segment with a fractured stent in situ.22,23 The stent could also be used in an occluded SFA complicated by a previously implanted, fractured
JOURNAL OF VASCULAR SURGERY Volume -, Number -
standard stent.24 We also reported the use of salvage angioplasty and Supera stenting of the distal anastomosis of femoropopliteal bypass graft with good midterm results.25 The findings of this report were inevitably limited by the nonrandomized single-center nature of the study, without a comparison study, and that the follow-up period is <5 years. We did not have a concurrent series of alternative therapies because there were fewer patients with other stents than in our Supera group. In addition, we did not want to use an historical group for comparison. Nonetheless, we present results up to 30 months involving Supera stents placed in a dynamic artery, and yet no fracture or mechanical fatigue was seen. We believe that this stent could be used safely and effectively even in the femoropopliteal artery. CONCLUSIONS Our experience showed that the implantation of the helical interwoven nitinol stents in patients with femoropopliteal occlusive disease is safe and effective, with encouraging patency rates and clinical results. AUTHOR CONTRIBUTIONS Conception and design: YC Analysis and interpretation: YC, GC Data collection: YC, GC Writing the article: YC Critical revision of the article: YC, SC, GC Final approval of the article: YC Statistical analysis: YC, GC Obtained funding: Not applicable Overall responsibility: YC REFERENCES 1. Twine CP, Coulston J, Shandall A, McLain AD. Angioplasty versus stenting for superficial femoral artery lesions. Cochrane Database Syst Rev 2009:CD006767. 2. Soga Y, Iida O, Hirano K, Yokoi H, Nanto S, Nobuyoshi M. Mid-term clinical outcome and predictors of vessel patency after femoropopliteal stenting with self-expandable nitinol stent. J Vasc Surg 2010;52: 608-15. 3. Laird JR, Katzen BT, Scheinert D, Lammer J, Carpenter J, Buchbinder M, et al; RESILIENT Investigators. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther 2012;19:1-9. 4. Iida O, Soga Y, Hirano K, Suzuki K, Yokoi H, Nobuyoshi M, et al. Long-term outcomes and risk stratification of patency following nitinol stenting in the femoropopliteal segment: retrospective multicenter analysis. J Endovasc Ther 2011;18:753-61. 5. Scheinert D, Scheinert S, Sax J, Piorkowski C, Bräunlich S, Ulrich M, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol 2005;45:312-5. 6. Goltz JP, Ritter CO, Kellersmann R, Klein D, Hahn D, Kickuth R. Endovascular treatment of popliteal artery segments P1 and P2 in patients with critical limb ischemia: initial experience using a helical nitinol stent with increased radial force. J Endovasc Ther 2012;19: 450-6.
Chan et al 9
7. Chan YC, Cheng SW, Ting AC, Cheung GC. Primary stenting of femoropopliteal atherosclerotic lesions using new helical interwoven nitinol stents. J Vasc Surg 2014;59:384-91. 8. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517-38. 9. European Working Group on Critical Limb Ischaemia. Second European consensus document on chronic critical limb ischaemia. Eur J Vasc Surg 1992;6(Suppl A):1-32. 10. Strecker EP, Boos IB, Göttmann D, Vetter S, Haase W. Popliteal artery stenting using flexible tantalum stents. Cardiovasc Intervent Radiol 2001;24:168-75. 11. Aghel A, Armstrong EJ. Recent advances in self-expanding stents for use in the superficial femoral and popliteal arteries. Expert Rev Cardiovasc Ther 2014;12:833-42. 12. Singh GD, Armstrong EJ, Laird JR. Femoropopliteal in-stent restenosis: current treatment strategies. J Cardiovasc Surg (Torino) 2014;55:325-33. 13. Ansari F, Pack LK, Brooks SS, Morrison TM. Design considerations for studies of the biomechanical environment of the femoropopliteal arteries. J Vasc Surg 2013;58:804-13. 14. U.S. Food and Drug Administration. Supera Peripheral Stent System e P120020. Available at: http://www.fda.gov/medicaldevices/products andmedicalprocedures/deviceapprovalsandclearances/recently-approved devices/ucm394171.htm. Accessed March 25, 2015. 15. Scheinert D, Grummt L, Piorkowski M, Sax J, Scheinert S, Ulrich M, et al. A novel self-expanding interwoven nitinol stent for complex femoropopliteal lesions: 24-month results of the SUPERA SFA registry. J Endovasc Ther 2011;18:745-52. 16. Abbott Vascular. Available at: http://www.idevmd.com/PR-101012VIVA_SUPERB_Data_Release.html. Accessed March 25, 2015. 17. ClinicalTrials.gov. Comparison of the SUperaÒ PERipheral System in the Superficial Femoral Artery (SUPERB). Available at: http://www. clinicaltrials.gov/ct2/show/NCT00933270?term¼superb&rank¼2. Accessed March 25, 2015. 18. León LR Jr, Dieter RS, Gadd CL, Ranellone E, Mills JL Sr, MonteroBaker MF, et al. Preliminary results of the initial United States experience with the Supera woven nitinol stent in the popliteal artery. J Vasc Surg 2013;57:1014-22. 19. Werner M, Paetzold A, Banning-Eichenseer U, Scheinert S, Piorkowski M, Ulrich M, et al. Treatment of complex atherosclerotic femoropopliteal artery disease with a self-expanding interwoven nitinol stent: midterm results from the Leipzig SUPERA 500 registry. EuroIntervention 2014;10:861-8. 20. George JC, Rosen ES, Nachtigall J, VanHise A, Kovach R. SUPERA Interwoven Nitinol Stent Outcomes in Above-Knee IntErventions (SAKE) study. J Vasc Interv Radiol 2014;25:954-61. 21. Isayama H, Nakai Y, Toyokawa Y, Togawa O, Gon C, Ito Y, et al. Measurement of radial and axial forces of biliary self-expandable metallic stents. Gastrointest Endosc 2009;70:37-44. 22. Goltz JP, Ritter CO, Petritsch B, Kellersmann R, Hahn D, Kickuth R. Endovascular treatment of acute limb ischemia secondary to fracture of a popliteal artery stent. J Vasc Interv Radiol 2010;21:1739-45. 23. Goltz JP, Ritter CO, Kenn W, Hahn D, Kickuth R. Immediate and complete stent collapse in the superficial femoral artery solved by implantation of a new helical nitinol stent. Cardiovasc Intervent Radiol 2011;34(Suppl 2):S307-11. 24. Vogel B, Strothmeyer A, Cebola R, Katus H, Blessing E. Crush implantation of a self-expanding interwoven stent over a subintimally recanalized standard stent in a TASC D lesion of the superficial femoral artery. Vasa 2012;41:458-62. 25. Chan YC, Cheng SW. Angioplasty and stenting of distal anastomotic stenosis of femoropopliteal bypass graft using helical interwoven nitinol stents. Int J Angiology 2014. http://dx.doi.org/10.1055/s-00341370888. Submitted Mar 25, 2015; accepted May 14, 2015.
Implantation of nitinol stents into the superficial femoral (SFA) and popliteal arteries is a widely used technique as a selective or routine adjunct to percutaneous transluminal angioplasty.1-3 Stents placed in the lower From the Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital. This project was supported by funding from the Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre. Author conflict of interest: none. Presented as an abstract at the Leipzig Interventional Course Asia-Pacific 2015, Lantau Island, Hong Kong, March 9-11, 2015. Reprint requests: Yiu Che Chan, MBBS, MD, FRCS, Division of Vascular & Endovascular Surgery, Department of Surgery, University of Hong Kong Medical Centre, South Wing, 14th Flr K Block, Queen Mary Hospital, Pokfulam Rd, Hong Kong (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2015 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2015.05.030
limb arteries, especially those near the hip or knee joints, may fracture over time and can adversely affect the artery and cause restenosis or occlusion. In a study of 861 patients who underwent nitinol stenting of the femoropopliteal segments in 1017 limbs, Iida et al4 found that at least 104 limbs (10%) had stent fractures on follow-up. In another study by Scheinert et al5 of 121 legs in 93 patients treated by implantation of selfexpanding nitinol stents with a mean follow-up of 10.7 months, stent fractures were detected in 45 of 121 (37.2%) legs. The novel interwoven nitinol Supera stent (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex) has been shown to enhance strength, flexibility, and fracture and kink resistance,6 and it conforms well to the femoropopliteal arteries with joint movements. Our group has previously reported on the use of Supera stent in treating patients with symptomatic SFA and popliteal artery disease.7 In this study, we addressed the knowledge base gap with longer-term results with the Supera stent in a realworld setting, which is important given the deficiencies 1
2 Chan et al
noted with prior self-expanding stent series and the relative dearth of longer-term experiences with the Supera stent. METHODS All patients who participated in the study gave written consent. Institutional Review Board approval is not required in Hong Kong for this type of interventional study in which a Conformité Européene marked and locally approved interventional device is used that was commercially available. Study population. Methods of patient recruitment, procedure, and follow-up protocol were described in our previous publication.7 This current report is a continuation of the same study, but with additional patients and a longer follow-up period. All patients underwent preoperative arterial duplex imaging by dedicated and qualified vascular technologists or ultrasonographers in our vascular laboratory. The Duplex ultrasound scans identified the length, degree, and characteristics of target lesions. We routinely relied on accurate duplex ultrasound reporting of the peripheral arterial system before intervention, without the need to confirm the nature of our target lesion with another imaging modality. After the duplex results were available, patients were interviewed again, and if their symptoms persisted and they were keen for an endovascular revascularization, they were entered onto the waiting list for the procedure. Symptoms included intermittent claudication as reported by the patients or evidence of critical ischemia with rest pain or tissue loss, as defined as Rutherford categories 46 as critical ischaemia.8 Chronic critical limb ischemia can also be defined as persisting recurring rest pain requiring regular analgesia for more than 2 weeks, or ulcers, gangrene at the foot (tissue loss), with ankle systolic pressure of <50 mmHg.9 Clinical symptoms of intermittent claudication were further categorized in 15 patients (9%) who had mild claudication (could walk >300 m), 15 (9%) who had moderate claudication (could walk between 100 and 300 m), and 65 (40%) who had severe claudication (could walk <100 m). The study excluded patients with acute thrombus or aneurysm in the index limb/vessel, an unsalvageable limb, poor inflow or total absence of run-off vessels, very limited life-expectancy, or with doubts in their willingness or capability to allow follow-up examinations. The limb was deemed unsalvageable if there was extensive tissue loss, with or without sepsis, and would not benefit from revascularization. The decisions to exclude patients were left to the discretion of the individual operators. Patients with renal impairment (not on renal replacement therapy) who were deemed very high risk of developing contrast nephropathy and who could not tolerate the intervention or subsequent follow-up were excluded. Study procedure. All the patients in this study had a preoperative duplex ultrasound examination and diagnostic angiography of the lower limb with a standard contrast intra-arterial digital subtraction angiogram at the time of the endovascular intervention. All of the endovascular
JOURNAL OF VASCULAR SURGERY --- 2015
procedures were performed by experienced vascular specialists in our hybrid endovascular suite (Siemens Artis Zee Multipurpose System; Siemens, Munich, Germany) situated in the Minimally Invasive Surgical Centre. All patients were prescribed aspirin preoperatively. The procedures were performed under monitored anesthetic care, with antegrade or retrograde percutaneous access of the ipsilateral or contralateral common femoral artery with a 6F sheath for the diagnostic angiogram. All patients received intra-arterial heparin through the sheath. All patients were prescribed clopidogrel and aspirin for 3 months and remained on aspirin for life. From the computerized software (Siemens Artis Zee Multipurpose System) of the angiogram, it was possible to calculate and document the minimal luminal diameter, minimal luminal area, and the length of stensosis/ occlusion. Stenoses and occlusions were passed using 0.035-inch or 0.018-inch guidewires with the help of a 5F straight diagnostic catheter. The diameter of the target vessel was measured by computer, and the size of the angioplasty balloon catheters ranged in size from 4 to 7 mm in diameter by 20 to 200 mm in length and were inflated to nominal atmospheres for 1 minute. A completion angiogram was performed after balloon dilatation. In cases of severe recoil of very calcified plaque, repeat angioplasty was performed with adequate preparation of the target vessel. All of the Supera-stented target lesions were angioplastied with the balloon size 1 mm larger than the stent diameter according to the manufacturer’s instructions, with poststent dilatation. Stents were chosen to cover the length of the lesions. The Supera stents were premounted and delivered via a 6F or 7F catheter-based delivery system over a 0.014-inch or 0.018-inch wire. When more than one stent was needed, stents were overlapped for at least 10 mm. A completion angiogram was performed in all cases after stenting (Fig 1). Postprocedure assessment and follow-up. Clinical evaluation with ankle-brachial index (ABI), duplex ultrasonic follow-up examinations, and assessment of adverse events was performed before discharge from hospital. Clinical follow-up and duplex ultrasound imaging for evaluation of restenosis was performed routinely on all patients at 3, 6, 12, 18, 24, 30, and 36 months and every 6 months thereafter. Plain radiographs of the stent were taken at 6-month intervals to rule out stent fracture. All patients had electronic radiologic records on Clinical Management System-Electronic Patients Records. The plain radiographs of the stents were taken as anteroposterior and lateral views and viewed on the Centricity Enterprise Web Listener 1.0 (GE Healthcare Products, Waukesha, Wisc). The images can be magnified on the screen during viewing. The patency data were based on the actual date of the duplex examination. A patient missed a follow-up appointment was censored at the date of the last examination. The primary end point was postoperative restenosis (target lesion stenosis of >50% or occlusion) evaluated with
JOURNAL OF VASCULAR SURGERY Volume -, Number -
Chan et al 3
Fig 1. An angiogram shows (A) right popliteal artery stenosis with (B) angioplasty and (C) stenting. D, Anteroposterior and (E) lateral view plain radiographs show the Supera stent (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex).
duplex ultrasound imaging by an independent vascular ultrasonographers and vascular surgeons. The ultrasound criteria used for a restenosis >50% was prestenosis and a stenosis ratio of $2.0, or a peak systolic velocity of $200 cm/s.7 Secondary end points included technical interventional success rate, minimal lumen diameter, improvement of symptoms (change in Rutherford grade), change in ABI, major amputations, stent-related complications such as fractures, and all serious adverse events possibly related to the treatment. Statistical analysis. Counts and percentages are reported for categoric variables, and means and standard deviations are reported for qualitative variables. Comparisons between groups were made with the Student t-test and the c2 test. Patency rates were analyzed using Kaplan-Meier curves to compute time-to-event rates. The log-rank test assessed the potential effect of risk factors on outcome or complications in the univariate setting. Predictors for restenosis were also calculated. A P value of #.05 was taken to be statistically significant. All statistical analyses were performed using SPSS 20 software (IBM Corp, Armonk, NY). RESULTS Patient characteristics. The study period spanned from October 2011 to December 2014. A total of 153 consecutive patients (96 men, 57 women; age range, 46100 years) with 164 legs with symptomatic femoropopliteal lesions were treated with angioplasty and primary stenting using the Supera stent at our institution. Eighty-two were left-sided lesions, 82 were right-sided lesions, and 11 patients had bilateral interventions. Male patients were a mean age of 73.2 years (range, 46-92) and female patients were a mean age of 82.7 years (range,
63-100 years). Our cohort of 153 patients included some elderly patients, with a mean age of 76.7 years. Cardiovascular risk factors were prevalent: 127 patients (77%) were on regular antihypertensive medication, 68 (41%) were active smokers, 102 (62%) were diabetic, and 58 (35%) had proven hyperlipidemia (Table I). Indications for interventions were intermittent claudication in 95 limbs (58%), rest pain in (5%), and tissue loss in 60 (37%). The severity of intermittent claudication was ascertained by patient history only (Table I). In the same study period, our departmental database showed that we had 266 patients who had femoropopliteal/peripheral arterial disease but without revascularization. This number included eight patients who had primary amputations. In the same period, we performed 83 procedures in 74 patients with devices other than Supera stents, including 22 bypasses and 61 angioplasty procedures with or without stents. Supera stents were not used in these patients and they were not included in this current study. Lesions and procedural characteristics. All treatment were achieved with percutaneous endovascular procedures, with only one patient requiring open exploration of the common femoral artery performed under general anesthesia with patch angioplasty in conjunction with angioplasty and stenting of the SFA in view of a severely calcified common femoral artery (Table I). Lesion characteristics and number of runoff vessels are summarized in Table I. The arteries involved were the proximal SFA in 64 limbs (39%), the middle SFA in 107 (65%), the distal SFA in 127 (77%), the above-knee popliteal artery in 78 (48%), and the below-knee popliteal artery in 19 (12%). The length of the lesions varied from 5 to 400 mm, with a mean of 105.6 mm.
JOURNAL OF VASCULAR SURGERY --- 2015
4 Chan et al
Table I. Demographics, indications, lesion characteristics, and number of run-off vessels in the patients Variable
Patients (n ¼ 153), No. (%)
Prevalence of cardiovascular risk factors Smoking Hypertension Hyperlipidemia Diabetes
68 127 58 102
(44) (83) (38) (67)
Limbs (n ¼ 164), No. (%) Clinical category 1eMild claudication 2eModerate claudication 3eSevere claudication 4eIschemic rest pain 5eMinor tissue loss Diseased segment SFA Proximal Middle Distal Popliteal artery Above knee Below knee TASC II A B C D Occluded lesions Runoff vessels, No. 0 1 2 3
15 15 65 9 60
(9) (9) (40) (5) (37)
64 (39) 107 (65) 127 (77) 78 (48) 19 (12) 49 79 31 3 55
(30) (48) (19) (2) (34)
5 59 57 43
(3) (36) (35) (26)
SFA, Superficial femoral artery; TASC II, TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease.
A total of 191 stents, 4 to 6 mm in diameter and 40 to 200 mm in length (each stent) were implanted in these patients. The mean length of the stented artery was 122.1 mm (range 40-650 mm; standard error of the mean, 6.27) for a mean lesion length of 105.6 mm (range, 3-400 mm; standard error of the mean, 5.79). All of the lesions had poststent moulding. Technical success was 100%. Patient follow-up. The mean follow-up period was 15.17 months for the 153 patients. There were no perioperative or procedural-related or device-related deaths. One patient developed a 1.5-cm pseudoaneurysm in the groin, which was treated conservatively. One patient had emboli to peroneal artery treated successfully with intraoperative thrombolysis. There were three 30-day deaths not related to the procedure or the device. One was a 93-year-old woman with tissue loss who underwent a successful revascularization and was discharged on day 4 but was readmitted to hospital on day 10 with respiratory distress after suddenly collapsing at home. A 68-year-old woman with end-stage renal failure sustained a myocardial infarction that did not respond to
maximum medical therapy and died on day 26 after successful revascularization. The third patient was a 59-yearold man with carcinoma of the gall bladder who died of acute myocardial infarction on day 12 after the procedure. On follow-up, 29 patients (16 male, 13 female) had died (excluding the above 30-day deaths). The causes of death were pneumonia, cardiac, cardiac and renal causes, and gastrointestinal bleeding. ABI, stent patency, and stent fracture rates. The limb salvage rate was 99.3%, with only one patient receiving an above-knee amputation 3 months after revascularization due to septic nonhealing, painful, wet gangrene. Between baseline and discharge, the mean ABI increased significantly from 0.57 6 0.15 preoperatively to 0.87 6 0.14 postoperatively (P < .01 by paired t-test), with all patients reporting improvement in symptoms. All patients followed the set protocol, and the primary patency rates at 6, 12, 24, and 30 months were 86.7% 6 3.1%, 81.4% 6 3.7%, 79.9% 6 4.0%, and 77 6 3.0%, respectively (Fig 2). The 23 patients who had in-stent restenosis or instent occlusion included 9 with 50%, 6 with 70%, and 8 with reocclusion. Because the balloons and stents were self-financed by the patients, they preferred a conservative nonintervention if their symptoms improved. Predictors for restenosis (Table II) demonstrated that younger age, longer target lesions, and longer stented lengths were positive significant predictors for restenosis in this cohort (P ¼ .017, P ¼ .018, and P ¼ .003, respectively, by t-test). Patients with hyperlipidemia were more likely to have restenosis, but this did not quite reach statistical significance (P ¼ .052 by c2). The primary patency rate, as analyzed by the diseased segment of the SFA or popliteal artery and indication of treatment (claudication vs critical ischemia/tissue loss) is shown in Fig 3 and Fig 4, respectively. However, more restenosis occurred in patients who had 4-mm stents implanted (Fig 5). On follow-up of the patients with a mean follow-up period, none developed stent fracture on plain radiographs. DISCUSSION This study reflects a real-world experience with the use of Supera stents in femoropopliteal occlusive disease, with long challenging lesions: the mean length of the stented artery was 122.1 mm (range 40-650 mm; standard error of the mean, 6.27) for mean length of lesion of 105.6 mm (range, 3-400 mm; standard error of the mean, 5.79). In this cohort of patients, we identified that longer target lesions with more atherosclerotic burden and longer stented lengths were positive significant predictors for restenosis. Patients with hyperlipidemia were more likely to have restenosis, but this did not quite reach statistical significance. These risk factors were not obvious in our previous shorter-term results.7 Although hypercholesterolemia has not previously been directly correlated with worse outcomes for lower extremity vascular interventions, there is abundant evidence that hypercholesterolemia would contribute to widespread atherosclerosis and that
JOURNAL OF VASCULAR SURGERY Volume -, Number -
Chan et al 5
Fig 2. Kaplan-Meier curve shows overall primary patency rates, with error bars representing standard errors.
Table II. Risk factor stratification for restenosisa Variable Male sex Age, years Risk factors Smoking Hypertension Hyperlipidemia Diabetes Symptoms Claudication Rest pain Tissue loss Clinical group Claudication Threatened limb loss Maximum stenosis Calcification Runoff vessels 0 1 2 3 Combined length of stents, mm Length of lesion
No restenosis (n ¼ 141) 88 (62) 77.6 6 10.1 58 109 54 84
(41) (77) (38) (60)
Restenosis (n ¼ 23)
Overall (N ¼ 164)
P
16 (70) 72.0 6 12.0
104 (63) 76.8 6 10.5
.509b .017c,d
10 18 4 18
(43) (78) (17) (78)
68 127 58 102
(41) (77) (35) (62)
87 (62) 15 (11) 51 (36)
14 (61) 2 (9) 9 (39)
101 (62) 17 (10) 60 (37)
81 (57) 59 (42) 87.8 6 11.3 66 (47)
13 (57) 10 (43) 90.8 6 11.1 10 (43)
94 (57) 69 (42) 88.2 6 11.3 76 (46)
5 (4) 50 (35) 49 (35) 37 (26) 116.2 6 66.9 98.9 6 68.4
0 (0) 9 (39) 8 (35) 6 (26) 158.7 6 132.5 147.1 6 93.7
5 (3) 59 (36) 57 (35) 43 (26) 122.1 6 80.2 105.6 6 74.1
.832b .919b .052b,d .087b .939b .777b .785b .904b .229c .766b .828b
.018c,d .003c,d
Categoric data are shown as mean 6 standard deviation and continuous data as number (%). Positive significant predictors by t-test for restenosis in this cohort were younger age (P ¼ .017), longer target lesions (P ¼ .018), and longer stented lengths (P ¼ .003). Patients with hyperlipidemia were more likely to have restenosis, but this did not quite reach statistical significance (P ¼ .052 by c2 test). b P value by c2 test. c P value by t-test. d Statistically significant. a
6 Chan et al
JOURNAL OF VASCULAR SURGERY --- 2015
Fig 3. The primary patency rate as analyzed by disease segment of the superficial femoral artery (SFA) or SFA with or without the popliteal artery.
lipid-lowering agents, such as statins, may help to control atherosclerotic disease in the lower extremities. We did not notice any stent fractures in our cohort. We also noticed that there was a statistically significant difference in primary patency rates between those patients who received 4-mm and 5-mm stents. We postulate that this was just due to small vessel diameter and not related to the stents themselves. Placement of stents at the femoropopliteal segment and popliteal artery has not been widely accepted by many vascular specialists because the biomechanical forces over the knee joint could predispose to stent fracture and restenosis.10-12 A review by Ansari et al13 on the biomechanics of the SFA and popliteal artery in patients with peripheral arterial disease showed that implanted stents undergo a variety of deformations as patients engage in their daily activities such as walking, sitting, or climbing. Musculoskeletal motions led to deformation of the proximal and middle SFA by shortening in the axial direction 4.0%, by twisting 2.1 /cm, and by bending 72.1 mm. Similarly, the distal SFA and proximal popliteal arteries were deformed even more, up to shortening in the axial direction 13.9%, by twisting 3.5 /cm, and by being pinched such that the aspect ratio of the lumen changed 4.6%. The distal popliteal artery also shortened in the axial direction
12.3%, by twisting 3.5 /cm, by bending 22.1 mm, and the luminal area changed by 12.5%.12 Because a stent is a permanent implant in the target vessels, that they would be subjected to a wide variety of torsion, compression, and stress is not surprising. A study by Scheinert et al,5 using systematic X-ray screening for stent fractures in 121 legs treated by implantation of selfexpanding nitinol stents after a mean follow-up time of 10.7 months, detected stent fractures in 37.2%. These were classified as minor (single-strut fracture) in 31 legs (48.4%), moderate (fracture of >1 strut) in 17 legs (26.6%), severe (complete separation of stent segments) in 16 legs (25.0%), and 34.4% of the stent fractures were associated with a total in-stent occlusion.5 The Supera stent is more flexible and resistant to compression so that it is more capable of withstanding the forces exerted upon it by the tortuosity and mobility of the femoral and popliteal vessels. The stent consists of six pairs of braided self-expanding closed end interwoven nitinol (nickel-titanium alloy) wires that is premounted on a 6F or 7F delivery system and delivered via a coaxial catheter-based delivery handle. The delivery system includes a reciprocating mechanism that incrementally moves the stent distally out of the outer sheath. This motion allows for the distal end of the stent to first come in contact
JOURNAL OF VASCULAR SURGERY Volume -, Number -
Chan et al 7
Fig 4. The primary patency rate as analyzed by indication of treatment for claudication vs critical ischemia/tissue loss.
with the targeted vessel, setting the distal reference point, and continues to feed the stent out of the sheath as the target wall is exposed by the proximal movement of the catheter. This stent deployment is achieved by the reciprocation of the thumb slide located on the handle. The Supera stent was formally launched in Leipzig, Germany, in 2010, with a full launch in Europe in the summer of 2010. We began using the stent it our institution in October 2011, being the first center to use this stent in Asia. In the United States, it received approved for peripheral use only by the Food and Drug Administration in March 2014.14 Only a handful of studies of the Supera stents have been published, and our results in this report of primary patency rates of 86.7%, 81.4%, 79.9%, 79.9%, 77% at 6, 12, 18, 24, and 30 months, respectively, in 164 legs are comparable to published series. Scheinert et al15 reported 2-years results of 137 Supera stents in 107 patients with a mean age of 68.9 years with symptomatic atherosclerotic femoropopliteal lesions, 31% of whom had total arterial occlusions. The mean lesion length was 9 cm, and the lesions were predominately in the SFA, with occasional involvement of the first segment of the popliteal artery. The stented segments were a mean length of 111.50 mm, and the mean primary and secondary stent patency rates at 6 months were 93.1% and 99.0%, respectively, and primary
and secondary stent patency rates at 12 months were 84.7% and 94.8%, respectively. No stent fractures were seen in the 91 patients examined.6 Goltz et al16 studied 40 patients who had angioplasty of their proximal and middle popliteal artery, followed by implantation of a Supera stent, and showed that the primary and secondary cumulative patency rates at 12 months in 34 patients were 68.4% and 79.8%, respectively. In the follow-up period, postprocedure radiographs were available for only seven of 40 patients (17.5%), and none developed any stent fractures.16 Rosenfield et al17 presented the 12-month outcomes from the SUPERB (Comparison of the Supera Peripheral System to a Performance Goal Derived from Balloon Angioplasty Clinical Trials in the Superficial Femoral Artery) study of the Supera Peripheral Stent System at the 10th Vascular InterVentional Advances (VIVA) Conference in October 2012. The SUPERB study was a Food and Drug Administration-approved investigational device exemption trial17 to evaluate the Supera stent in the treatment of patients with obstructive SFA disease. The study recruited 264 patients at 34 centers, treating 266 lesions with a mean length of 8 cm. The primary patency at 1 year was reported to be 86%, but formal results on this trial have not been published yet. In the SUPERB trial, elongation and compression of the stent during
8 Chan et al
JOURNAL OF VASCULAR SURGERY --- 2015
Fig 5. The primary patency rate as analyzed by patients who had 5-mm or 4-mm Supera stents (IDEV Technologies, Inc/Abbott Laboratories, Inc, Webster, Tex) implanted.
deployment, especially those with moderate to severe elongation, were found to be positive predictors of restenosis. We have not look at this issue in our current study. León et al18 showed in a cohort of 34 patients with 39 stents placed in the isolated popliteal artery that the primary, primary assisted, and secondary patency rates by duplex ultrasound imaging were 79.2%, 88.1%, and 93%, respectively. Six stent occlusions occurred, and six patients had hemodynamically significant in-stent restenosis. Three patients (8.8%) had limb loss, two related to uncontrolled infections, and one due to perioperative ischemic complications (both with patent stents at the time of limb loss). The overall mortality was 8.8% during the study period, and no stent fractures were identified. Werner et al19 recently reported the result of the Leipzig SUPERA 500 Registry with 527 limbs in 470 patients with femoropopliteal arterial disease treated with Supera stents. The mean lesion length was 126.4 mm, with total occlusions present in 277 limbs (52.6%). During a mean follow-up period of 21 months, the primary patency rates were 83.3% after 12 months and 72.8% at 2 years. The patency rates did not differ between SFA and popliteal lesions. Plain radiographs performed on 229 patients at a mean of 16.6 months did not show any evidence of stent fractures.
George et al20 reported the results of the SUPERA Interwoven Nitinol Stent Outcomes in Above-Knee IntErventions (SAKE) study on 98 limbs in 80 patients with an average of 14.3 months after intervention, and demonstrated satisfactory results with a primary patency of 96.9% and 85.8% at 6 and 12 months. No stent fractures were detected. The unique design of the Supera stent best conforms to the target vessel anatomy. Its combination of flexibility and radial strength may account for the ability of this stent to restore durable patency in a harsh environment for any endovascular device. The SFA and proximal popliteal artery are exposed to significant mechanical stress with bending and rotation of the knee. According to the manufacturers’ information, this Supera stent showed increased flexibility, duration, and radial force as a result of its new design. The radial force of the Supera stent at a diameter of 4 to 5 mm could be as much as 18 pounds.21 To date, no stent fractures with this type of stent has been reported in published literature. There are other case reports on the use of the Supera stents in hostile calcified vessels or as a bail-out option in an occluded popliteal segment with a fractured stent in situ.22,23 The stent could also be used in an occluded SFA complicated by a previously implanted, fractured
JOURNAL OF VASCULAR SURGERY Volume -, Number -
standard stent.24 We also reported the use of salvage angioplasty and Supera stenting of the distal anastomosis of femoropopliteal bypass graft with good midterm results.25 The findings of this report were inevitably limited by the nonrandomized single-center nature of the study, without a comparison study, and that the follow-up period is <5 years. We did not have a concurrent series of alternative therapies because there were fewer patients with other stents than in our Supera group. In addition, we did not want to use an historical group for comparison. Nonetheless, we present results up to 30 months involving Supera stents placed in a dynamic artery, and yet no fracture or mechanical fatigue was seen. We believe that this stent could be used safely and effectively even in the femoropopliteal artery. CONCLUSIONS Our experience showed that the implantation of the helical interwoven nitinol stents in patients with femoropopliteal occlusive disease is safe and effective, with encouraging patency rates and clinical results. AUTHOR CONTRIBUTIONS Conception and design: YC Analysis and interpretation: YC, GC Data collection: YC, GC Writing the article: YC Critical revision of the article: YC, SC, GC Final approval of the article: YC Statistical analysis: YC, GC Obtained funding: Not applicable Overall responsibility: YC REFERENCES 1. Twine CP, Coulston J, Shandall A, McLain AD. Angioplasty versus stenting for superficial femoral artery lesions. Cochrane Database Syst Rev 2009:CD006767. 2. Soga Y, Iida O, Hirano K, Yokoi H, Nanto S, Nobuyoshi M. Mid-term clinical outcome and predictors of vessel patency after femoropopliteal stenting with self-expandable nitinol stent. J Vasc Surg 2010;52: 608-15. 3. Laird JR, Katzen BT, Scheinert D, Lammer J, Carpenter J, Buchbinder M, et al; RESILIENT Investigators. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther 2012;19:1-9. 4. Iida O, Soga Y, Hirano K, Suzuki K, Yokoi H, Nobuyoshi M, et al. Long-term outcomes and risk stratification of patency following nitinol stenting in the femoropopliteal segment: retrospective multicenter analysis. J Endovasc Ther 2011;18:753-61. 5. Scheinert D, Scheinert S, Sax J, Piorkowski C, Bräunlich S, Ulrich M, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol 2005;45:312-5. 6. Goltz JP, Ritter CO, Kellersmann R, Klein D, Hahn D, Kickuth R. Endovascular treatment of popliteal artery segments P1 and P2 in patients with critical limb ischemia: initial experience using a helical nitinol stent with increased radial force. J Endovasc Ther 2012;19: 450-6.
Chan et al 9
7. Chan YC, Cheng SW, Ting AC, Cheung GC. Primary stenting of femoropopliteal atherosclerotic lesions using new helical interwoven nitinol stents. J Vasc Surg 2014;59:384-91. 8. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517-38. 9. European Working Group on Critical Limb Ischaemia. Second European consensus document on chronic critical limb ischaemia. Eur J Vasc Surg 1992;6(Suppl A):1-32. 10. Strecker EP, Boos IB, Göttmann D, Vetter S, Haase W. Popliteal artery stenting using flexible tantalum stents. Cardiovasc Intervent Radiol 2001;24:168-75. 11. Aghel A, Armstrong EJ. Recent advances in self-expanding stents for use in the superficial femoral and popliteal arteries. Expert Rev Cardiovasc Ther 2014;12:833-42. 12. Singh GD, Armstrong EJ, Laird JR. Femoropopliteal in-stent restenosis: current treatment strategies. J Cardiovasc Surg (Torino) 2014;55:325-33. 13. Ansari F, Pack LK, Brooks SS, Morrison TM. Design considerations for studies of the biomechanical environment of the femoropopliteal arteries. J Vasc Surg 2013;58:804-13. 14. U.S. Food and Drug Administration. Supera Peripheral Stent System e P120020. Available at: http://www.fda.gov/medicaldevices/products andmedicalprocedures/deviceapprovalsandclearances/recently-approved devices/ucm394171.htm. Accessed March 25, 2015. 15. Scheinert D, Grummt L, Piorkowski M, Sax J, Scheinert S, Ulrich M, et al. A novel self-expanding interwoven nitinol stent for complex femoropopliteal lesions: 24-month results of the SUPERA SFA registry. J Endovasc Ther 2011;18:745-52. 16. Abbott Vascular. Available at: http://www.idevmd.com/PR-101012VIVA_SUPERB_Data_Release.html. Accessed March 25, 2015. 17. ClinicalTrials.gov. Comparison of the SUperaÒ PERipheral System in the Superficial Femoral Artery (SUPERB). Available at: http://www. clinicaltrials.gov/ct2/show/NCT00933270?term¼superb&rank¼2. Accessed March 25, 2015. 18. León LR Jr, Dieter RS, Gadd CL, Ranellone E, Mills JL Sr, MonteroBaker MF, et al. Preliminary results of the initial United States experience with the Supera woven nitinol stent in the popliteal artery. J Vasc Surg 2013;57:1014-22. 19. Werner M, Paetzold A, Banning-Eichenseer U, Scheinert S, Piorkowski M, Ulrich M, et al. Treatment of complex atherosclerotic femoropopliteal artery disease with a self-expanding interwoven nitinol stent: midterm results from the Leipzig SUPERA 500 registry. EuroIntervention 2014;10:861-8. 20. George JC, Rosen ES, Nachtigall J, VanHise A, Kovach R. SUPERA Interwoven Nitinol Stent Outcomes in Above-Knee IntErventions (SAKE) study. J Vasc Interv Radiol 2014;25:954-61. 21. Isayama H, Nakai Y, Toyokawa Y, Togawa O, Gon C, Ito Y, et al. Measurement of radial and axial forces of biliary self-expandable metallic stents. Gastrointest Endosc 2009;70:37-44. 22. Goltz JP, Ritter CO, Petritsch B, Kellersmann R, Hahn D, Kickuth R. Endovascular treatment of acute limb ischemia secondary to fracture of a popliteal artery stent. J Vasc Interv Radiol 2010;21:1739-45. 23. Goltz JP, Ritter CO, Kenn W, Hahn D, Kickuth R. Immediate and complete stent collapse in the superficial femoral artery solved by implantation of a new helical nitinol stent. Cardiovasc Intervent Radiol 2011;34(Suppl 2):S307-11. 24. Vogel B, Strothmeyer A, Cebola R, Katus H, Blessing E. Crush implantation of a self-expanding interwoven stent over a subintimally recanalized standard stent in a TASC D lesion of the superficial femoral artery. Vasa 2012;41:458-62. 25. Chan YC, Cheng SW. Angioplasty and stenting of distal anastomotic stenosis of femoropopliteal bypass graft using helical interwoven nitinol stents. Int J Angiology 2014. http://dx.doi.org/10.1055/s-00341370888. Submitted Mar 25, 2015; accepted May 14, 2015.