Treatment of femoropopliteal lesions with the AngioSculpt scoring balloon – results from the Heidelberg PANTHER registry
Abstract
Abstract.Background: Treatment of calcified femoropopliteal lesions remains challenging, even in the era of drug-eluting balloon angioplasty. Lesion recoil and dissections after standard balloon angioplasty in calcific lesions often require subsequent stent implantation. Additionally, poor patency rates in calcified lesions despite the use of drug-eluting balloons may be due to the limited penetration depth of the antiproliferative drug in the presence of vascular calcium deposits. Therefore, preparation of calcified lesions with the AngioSculpt™ scoring balloon might be a valuable option either as a stand-alone treatment, followed by drug-eluting balloon angioplasty or prior to subsequent stent deployment. Patients and methods: In this retrospective, single centre registry, 124 calcified femoropopliteal lesions were treated in 101 subsequent patients. All patients were treated with scoring balloon angioplasty, either alone, in combination with drug-eluting balloons, or prior to stent deployment. The primary outcome was safety and technical success during the index procedure as well as patency at six and 12 months, as evaluated by duplex sonography. Results: Successful scoring was safely performed in all 124 lesions with the AngioSculpt™ balloon. Overall primary patency after 12 months was 81.2 %. Patency rates did not differ significantly between the three treatment strategies. Degree of calcification did not predict patency. Improved clinical outcomes (Rutherford-Becker class and ankle-brachial index) were also observed in the study cohort. Conclusions: Preparation with the AngioSculpt™ scoring balloon offers a safe and valuable treatment option for calcified femoropopliteal lesions.
Introduction
Established predictors of restenosis following endovascular treatment of femoropopliteal lesions include presence of diabetes [1, 2], impaired renal function [2], lesion length [3, 4], chronic total occlusions [2], and degree of calcification [5]. Heavily calcified lesions remain challenging for a variety of reasons. First, intraluminal recanalization of calcified occlusions can be difficult or sometimes even impossible. Attempting to pass the occlusion via the subintimal space is a reasonable option; however, this often requires advanced techniques, such as additional retrograde access or the use of dedicated re-entry devices, adding complexity and costs to the endovascular procedure. Second, after successful passage with a wire, elastic recoil or flow-limiting dissections after primary balloon dilatations often require a bail-out stent placement. Although stent fractures are observed less frequently with new generation nitinol stents, recent data indicate that post-procedure stent areas may be a predictor of restenosis [6], and thus, lesion preparation prior to implantation may be important to ensure adequate stent expansion. Finally, the well-documented benefits of drug-eluting balloon (DEB) angioplasty [7–9] seem to be limited in heavily calcified lesions [5], potentially due to the reduced penetration depth of the antiproliferative agent. The latter could have potentially been overcome by advanced debulking techniques, such as directional atherectomy. However, this would add significant cost and complexity to the procedure.
Lesion preparation with scoring balloons might offer a valuable treatment approach for heavily calcified lesions due to controlled dilatation leading to less balloon slippage, fewer dissections, and reduced need for bail-out stenting [10]. Additionally, lesion scoring might lead to less elastic recoil, reducing the need for stents to maintain luminal gain [10]. Initial experience with the AngioSculpt™ scoring balloon were encouraging, proving safety and efficacy of the device in a rather small patient cohort with infrapopliteal lesions [10]. In the PANTHER registry (Evaluation of treatment of femoroPopliteal lesions with ANgioSculpT scoring balloon – HeidElberg Registry), we evaluated safety, technical success, and clinical outcomes in mild to severe calcified femoropopliteal lesions.
Patients and methods
Study population
This is a retrospective, single centre, non-randomized registry of patients with arterial occlusive disease that underwent peripheral intervention using a scoring balloon. Between January 2011 and December 2011, a total number of 124 calcified de novo and restenotic lesions were treated in 101 subsequent patients at our institution with the AngioSculpt™ scoring balloon (Figure 1), (Spectranetics, USA).
Study procedure
The criteria for interventional therapy were a reduced ankle-brachial index (ABI) at rest as well as clinical symptoms of claudication and/or insufficient wound healing. The use of the scoring balloon was prompted by the appearance of a calcified lesion on the angiogram. Degree of calcification was defined as follows: mild calcification – calcium deposits unilateral and < 3 cm longitudinal extension; moderate calcification – calcium deposits unilateral and > 3 cm longitudinal extension; severe calcification – dense bilateral calcium deposits independent of length. The scoring balloon used for therapy was the AngioSculpt™ balloon, which consists of a nitinol-coated scoring element mounted on a semi-compliant balloon with a low profile. The use of DEBs or stent implantation after scoring balloon angioplasty was performed at the discretion of the interventionist. Technical success was verified with angiographic imaging and was defined as absence of balloon rupture and ≤ 30 % residual stenosis after the final dilatation.
A total of 5000 IU heparin was administered after insertion of either a crossover or an antegrade introducer sheath according to our standard protocol. In the majority of cases, wire passage was achieved within the lumen. No predilatations were performed prior to use of the scoring balloon. The stenosis was dilated by manometrically controlled inflation of the scoring balloon with a contrast agent and saline mixture for 30 to 60 seconds.
In cases with heavily calcified lesions with dense circumferential deposits of calcium, scoring balloons were specifically used to prepare the lesion for subsequent implantation of a Supera™ stent (Abbott), a stent with a unique interwoven design, characteristic for a fourfold increased radial strength as compared to standard nitinol stents. The AngioSculpt™ balloon, with its potential to reduce recoil in fibrotic or calcified lesions, might be of value in those challenging situations since adequate lesion preparation prior to stent deployment is crucial for appropriate expansion of the Supera™ stent. Provisional stenting was performed in cases where flow-limiting dissections persisted despite prolonged dilatations. The scoring balloon was also used to prepare the lesion for DEB use in calcified lesions. DEBs (In.PACT Admiral™, Medtronic, USA) were inflated for at least 60 seconds. In cases where the entire lesion could not be covered with one DEB, an overlap of at least 1 cm was provided with an additional DEB.
After the sheath was withdrawn, a closure system (Starclose™, Abbott) was used, or, in rare cases, manual compression was performed and a pressure bandage was applied for four to six hours. Dual antiplatelet therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day) was recommended for a minimum of four weeks following the procedure and aspirin (100 mg/day) alone thereafter.
Study endpoints
Patient follow-up was scheduled six and 12 months after the index procedure. As part of our clinical routine, patients were asked to report their symptom-free walking distance, presence of rest pain or appearance or changes of wounds in the index limb, if applicable. Rutherford-Becker Classification (RBC) was obtained and compared with the pre-procedural score. Finally, ABI and pulse wave velocity were obtained by duplex ultrasound. A peak systolic velocity ratio of ≥ 2.4 was defined as a significant stenosis and considered a loss of patency. In cases in which a clinically-driven angiography was performed, the index lesion was imaged and a binary stenosis of ≥ 50 % was defined as loss of patency. Secondary patency was defined as absence of significant stenosis after target lesion or target vessel revascularization at each defined time point.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee as well as with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Statistical analysis
Continuous patient data are provided as mean ± standard deviation (SD) and categorical variables are given in frequency and percentage. Statistical differences of continuous variables were determined using paired and unpaired Student’s t-tests (two-sided tests), where appropriate. The change of Rutherford classification from baseline to six-month and 12-month follow-up was calculated for each patient individually using non-parametric Wilcoxon signed-rank test. P < 0.05 was considered statistically significant. Kaplan-Meier analyses were performed to estimate patency and target lesion revascularization. Statistical analyses were performed with GraphPad Prism 6.0 software (GraphPad Software, La Jolla, CA, USA).
Results
Baseline characteristics of patients and lesions are listed in Tables 1 and 2. Successful scoring (defined as crossing of the lesion and inflation to at least nominal pressure without balloon rupture) was performed in all 124 lesions with the AngioSculpt™ balloon; lesions were treated with either scoring balloon angioplasty alone (37.1 %; n = 46), scoring balloon followed by DEB inflation (32.3 %; n = 40) or scoring balloon followed by stent deployment (30.6 %; n = 38). Twenty occlusions (16.1 %) and 104 stenoses (83.9 %) were treated. The average degree of stenosis was 85 %. Lesions in a vessel with a vascular distance of more than 3 cm were counted as two separate lesions.
According to the Trans-Atlantic Inter-Society Consensus (TASC) classifications, short stenoses and occlusions that are less than 5 cm long are currently seen as an indication for percutaneous transluminal angioplasty (PTA) of the thigh arteries. In our study, the average length of treated lesions was 7.4 cm (1.5–30 cm). Out of a total of 124 lesions, 52 short lesions (41.9 %) under 5 cm length and 48 lesions (38.7 %) with a length of five to 10 cm were treated. Twenty-four lesions (19.4 %) measured over 10 cm. Compared to the scoring balloon only treatment, lesions treated with the combination of scoring balloon and stent were longer (average length: 10.1 cm vs. 6.1 cm) and were more often occluded (31.6 % vs. 2.2 %).
Various diameters of the AngioSculpt™ balloons were used in the treated patient collective. Seventy-two lesions (58.1 %) were treated with a balloon diameter of 5.0 mm, and 37 lesions (29.8 %) with a balloon diameter of 6.0 mm. The degree of calcification was determined by the examiner before the intervention. Out of 124 lesions, 54 lesions (43.5 %) showed a particularly severe degree of calcifications, 43 lesions (34.7 %) a moderate degree, and 27 lesions (21.8 %) a mild degree of calcification. The initial angiography only detected 3-vessel and 2-vessel outflows in the lower leg in 77 lesions (62.1 %). Forty lesions (32.3 %) initially showed 1-vessel outflow. In seven treated lesions (5.6 %), no vascular outflow could be imaged in the patient’s lower leg.
At six-month follow-up, 60 lesions in 48 patients (out of an initially treated 124 lesions in 101 patients) were checked with duplex sonography. The primary patency rate in this group was 91.7 %; out of 60 lesions, 55 lesions were patent, i. e. < 50 % stenosed without an interim intervention. Two lesions had been successfully re-treated, i. e. a total of 57 lesions were patent at six months, with a secondary patency rate equalling 95 %.
At 12-month follow-up, 69 patients (85 lesions) out of 101 patients (124 lesions) at baseline were assessed with duplex sonography. Overall, the primary patency rate was 81.2 %; meaning out of 85 lesions, 69 lesions were patent, i. e. < 50 % stenosed without an interim intervention. Nine lesions had been successfully re-treated during follow-up and were patent at the 12 month time-point, while seven lesions were occluded, accumulating in a secondary patency rate of 91.8 %.
Patency rates did not differ significantly between the three treatment strategies (scoring only: 81.5 % [22 out of 27]; scoring plus DEB: 83.9 % [26 out of 31]; scoring plus stent: 77.8 % [21 out of 27] [Figure 2]). Degree of lesion calcification did not predict patency after six and 12 months (Figure 3). The strongest predictor of primary patency was lesion length (< 5 cm: 85.7 %, 5–10 cm: 86.5 %, > 10 cm: 53.8 %). In patients who were treated due to claudication (66 lesions in 53 patients), the overall primary patency rate was 83.3 %, and the secondary patency rate equalled 93.9 %. Patients with critical limb ischaemia (CLI) at baseline showed an overall primary patency rate of 73.7 % and a secondary patency rate of 84.2 %. Figure 4 shows angiographic images of a severe stenosis before and after intervention and at the 12-month follow-up.
In addition, 16 patients with 18 lesions had to be excluded from the analyses due to failure to attend the 12-month follow-up examinations. In seven patients, this was due to a subjective state of well-being. These were classified as lost to follow-up. For nine initially treated patients, a lack of contact data made scheduling a visit or enquiring about the current state of health and complaints impossible. These nine patients were classified as dropouts and taken into account in all analyses.
RBC and ABI improved significantly after six and 12 months. The baseline showed an initial ABI of 0.63 ± 0.22 (n = 70) and > 1.3 in 20 patients, considered not evaluable due to medial sclerosis. In the six-month follow-up, the ABI was 0.79 ± 0.29 (n = 34 >; p < 0.01) and at the 12-month follow-up, the ABI improved to 0.85 ± 0.17 (n = 54; p < 0.0001). The average Rutherford class at baseline was 3.35 ± 1.12 and improved to 1.71 ± 1.80 at six months (n = 53; p < 0.0001) and 1.22 ± 1.36 at 12 months (n = 69; p < 0.0001).
Discussion
In the current study, a scoring balloon was used to treat mild to severely calcified lesions, either alone or in combination with a stent or DEB, and resulted in high paten-cy rates and improved clinical outcomes at 12-month follow-up.
Standard balloon angioplasty has clear limitations, particularly in heavily calcified lesions. Additionally, traditional cutting balloon angioplasty has failed to prove superiority over standard balloon angioplasty in the treatment of primary [11] and in-stent restenotic peripheral lesions [11]. Therefore, the use of scoring balloon angioplasty might be more suitable in the presence of significant vascular calcification. Indeed, 12-month patency rates were encouraging after AngioSculpt™ scoring balloon angioplasty in a small cohort of patients with calcified infrapopliteal lesions [12]. Primary and secondary patency was exceptionally high after 12 months in our present registry (81.2 % and 91.8 %, respectively) and correlated also with favourable clinical outcomes, such as improvement in RBC and ABI. Conflicting data between standard cutting balloons and the AngioSculpt™ scoring balloon might also be explained by a somewhat different mode of action between the two approaches: in a cutting balloon, longitudinal oriented razor blades provide a rather “static” cutting of the plaque, whereas the nitinol wires, wrapped around the semi-compliant AngioSculpt™ balloon, might offer a more dynamic, and potentially more effective, lesion incision during inflation.
The strongest predictor for primary patency in our registry after 12 months was lesion length. Primary patency after one year was outstanding in short lesions, but somewhat disappointing in lesions that extended a total length of 10 cm (53.8 %). Use of the AngioSculpt™ balloon might therefore be a valuable treatment option for rather short, heavily calcified femoropopliteal lesions.
Calcification per se was not an exclusion criterion in the landmark DEB trials that convincingly proved the concept of local release of paclitaxel to inhibit restenosis in femoropopliteal lesions [7–9]. However, there is no well-established classification to assess severity and extension of vascular calcium deposits. Fanelli et al. used CT scans to assess longitudinal as well as circumferential extensions of vascular calcium deposits [5]. Circumferential calcium distribution was a better predictor for loss of patency than longitudinal extension of vascular calcification. Since there was no control group treated with standard angioplasty, it remains speculation, whether calcification really limits the benefits of antiproliferative therapy or if it generally results in poorer long-term patency.
There are different concepts of lesion preparation prior to the use of DEBs. One option is to remove the plaque and thereby reduce the perfusion barrier to improve penetration of the antiproliferative agent into the vessel wall. Scoring of severely calcified lesions obviously does not remove plaque, but might help to enhance penetration depth of paclitaxel by breaking up the relevant perfusion barrier, in particular, in cases of full circumferential coverage of the vessel by calcium deposits. In our retrospective registry, primary patency was 83.9 % after 12 months in the patient cohort that underwent combination therapy of scoring balloon angioplasty followed by DEB treatment and is therefore comparable with the outcome in patients that underwent AngioSculpt™ PTA only. Of note, lesion characteristics differed substantially between those two cohorts. Rate of occlusions were significantly higher in the combination group (17.5 % vs. 2.2 %) and more likely prompted the interventionist to use an antiproliferative treatment strategy. Whether lesion preparation prior to treatment with a DEB improves outcome clearly needs to be evaluated in a randomized controlled trial.
The rate of bail-out stenting was relatively high in our registry. Flow limiting dissections or significant residual stenosis due to recoil prompted the interventionist to use stents in the present cohort. Reported 12-month primary patency rates of several Supera™ registries vary widely between 68.4 and 87.7 % [13–15], with a substantial heterogeneity of lesion and patient characteristics. In our study, patency rates were 77.8 % after 12 months in the patient cohort that underwent stent placement after the use of the AngioSculpt™ balloon angioplasty. Lesion characteristics in the stent group differed significantly from those of the other cohorts with the highest rate of occlusions (31.6 %) and lesion length (10.1 cm). Therefore, lesions that underwent subsequent stent placement were the most challenging of the present registry.
Limitations
The main limitation of this retrospective registry is that the use of adjunctive therapies post scoring balloon angioplasty (drug eluting-balloons, stenting etc.) was based on the judgement of the interventionist and did not occur in a prospective randomized fashion. Another limitation is the lack of generally accepted calcification scores, which makes it difficult to compare our results with other published data. Finally, relevant variables were unevenly distributed and interdependent and can therefore only be determined by multivariable regression models in adequately powered prospective studies.
Conclusions
In summary, AngioSculpt™ treatment in severely calcified lesions was able to produce an acceptable high patency rate after six and 12 months. The therapy of calcified lesions using AngioSculpt™ represents a safe and effective method, which also offers a promising treatment option, potentially in combination with DEB or stents. The present registry generates the hypothesis that calcification might no longer translate into poorer patency as long as proper lesion preparation is performed with scoring balloon angioplasty. This idea warrants further evaluation in the setting of a prospective randomized clinical trial.
Conflicts of interest: Erwin Blessing received research funding support and speakers honoraria from Spectranetics. All of the other authors have nothing to disclose.
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