Aneurysmal Degeneration of Fluoropolymer-Coated Paclitaxel-Eluting Stent in the Superficial Femoral Artery. A Rising Concern

doi:10.21203/rs.3.rs-579108/v1

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Case Report

Aneurysmal Degeneration of Fluoropolymer-Coated Paclitaxel-Eluting Stent in the Superficial Femoral Artery. A Rising Concern

https://doi.org/10.21203/rs.3.rs-579108/v1

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Background: Although several clinical reports demonstrated a durable patency rate after a novel fluoropolymer-coated paclitaxel-eluting stent (Eluvia™; Boston Scientific, Marlborough, MA, USA) implantation, aneurysmal degeneration after implanting Eluvia™ has raised clinical concerns. Here, we report a case with exacerbated aneurysmal degeneration on serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation for a superficial femoral artery lesion.

Case presentation: A 79-year-old woman with claudication in the right lower extremity decreasing her quality of life was referred to our hospital. Pre-procedural angiography showed severe stenosis from the middle-to-distal part of the right superficial femoral artery, and Eluvia™ was implanted with optimal expansion. However, the patient had a recurrence of intermittent claudication in the right lower extremity 25 months thereafter. Angiography revealed de novo stenosis in the distal part of the popliteal artery and proximal stent edge restenosis at the Eluvia™ implantation site. Subsequently, the patient underwent endovascular therapy for these lesions. In addition, intravascular ultrasound at the time of endovascular therapy revealed vessel enlargement with a mean vessel diameter of 7.2-9.9 mm at the distal edge of the Eluvia™ implantation site. However, intermittent claudication on the right side recurred again 50 months after Eluvia™ implantation. Angiography demonstrated de novo severe stenosis from the distal part of the superficial femoral artery to the middle part of the popliteal artery. Furthermore, peri-stent contrast staining was found at the distal part of the Eluvia™ implantation site. Intravascular ultrasound showed a further enlargement of mean vessel diameter to 11.9 mm at the distal edge of the Eluvia™ stent. Moreover, enlargement of the lumen and stent malapposition were also found, suggesting exacerbated aneurysmal degeneration 50 months after Eluvia™ implantation.

Conclusions: We report a case with exacerbated aneurysmal degeneration on serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation for an SFA lesion. Long-term follow-up should be mandatory for patients receiving Eluvia™ implants.

Endocrinology & Metabolism

Endovascular therapy

fluoropolymer-coated paclitaxel-eluting stent

aneurysmal degeneration

With the development of anti-restenotic devices, endovascular therapy (EVT) has become the first-line treatment for femoropopliteal lesions. The IMPERIAL randomized trial compared a novel fluoropolymer-coated paclitaxel-eluting stent (Eluvia™; Boston Scientific, Marlborough, MA, USA) with a polymer-free paclitaxel-coated stent (Zilver PTX™; Cook Corporation, Bloomington, IN, USA), demonstrating a durable patency rate after Eluvia™ implantation [4, 5]. However, the problem of aneurysmal degeneration after Eluvia™ implantation has been raised as a clinical issue in several reports [4-6]. Here, we report a case with exacerbated aneurysmal degeneration on serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation for a superficial femoral artery (SFA) lesion.

A 79-year old woman with claudication in the right lower extremity which decreased her quality of life was referred to our hospital. Past medical history included hypertension, dyslipidemia and coronary artery disease. The ankle brachial index (ABI) on the right side was 0.71. Pre-procedural angiography showed severe stenosis from the middle-to-distal part of the right SFA and an Eluvia™ drug-eluting stent (DES) (7.0 × 150 mm) was implanted with optimal expansion (Figure 1A, 1B). After stent implantation, the ABI increased from 0.71 to 0.85 and the patient´s symptoms improved. Since then, she has been taking dual antiplatelet therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day). However, she had a recurrence of intermittent claudication in the right lower extremity 25 months after Eluvia™ implantation. Angiography revealed de novo stenosis in the distal part of the popliteal artery and proximal stent edge restenosis at the Eluvia™ implantation site (Figure 1C). Subsequently, the patient underwent endovascular therapy (EVT) with plain balloon angioplasty for severe stenosis in the distal part of the popliteal artery and a Zilver PTX™ (7.0 × 120 mm) was implanted for the proximal edge restenosis of the Eluvia™ stent. A completion angiogram showed an optimal angiographic result. In addition, intravascular ultrasound (IVUS, AltaView™; Terumo, Tokyo, Japan) at the time of EVT revealed vessel enlargement with a mean vessel diameter of 7.2-9.9 mm at the distal edge of the Eluvia™ implantation site (Figure 2a-2f). Thereafter, the patient was symptom-free until intermittent claudication on the right side recurred 50 months after Eluvia™ implantation. Angiography demonstrated de novo severe stenosis from the distal part of the SFA to the middle part of the popliteal artery. The popliteal artery lesion was dilated using a drug-coated balloon (INPACT Admiral™, 4.0 × 80 mm, Medtronic plc., Santa Rosa, CA, USA) and the distal SFA lesion was dilated using a drug-coated balloon (INPACT Admiral™, 6.0 × 120 mm), resulting in an adequate angiographic result. However, peri-stent contrast staining (PSS) was found by angiography at the distal part of the Eluvia™ implantation site (Figure 1D). IVUS showed a further enlargement of mean vessel diameter to 11.9 mm at the distal edge of the Eluvia™ stent (Figure 2g-2i). Moreover, an enlargement of the lumen and stent malapposition were also found, suggesting exacerbated aneurysmal degeneration 50 months after Eluvia™ implantation.

Here, we report a patient with exacerbated aneurysmal degeneration assessed by serial angiography and IVUS 50 months after Eluvia™ implantation for an SFA lesion. Although several clinical studies reported instances of aneurysmal degeneration 12 or 24 months after Eluvia™ implantation [4-6], there have been no reports of complications with exacerbated aneurysmal degeneration assessed by serial imaging device beyond 24 months after implantation. To the best of our knowledge, this is the first report showing worsening of aneurysmal degeneration assessed by serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation.

In coronary arteries, peri-stent contrast staining (PSS), that is defined as contrast staining outside the stent contour extending to ≥ 20% of the stent diameter after DES implantation, is rare and has a reported incidence ranging from 1.9% to 2.2% [7, 8]. PSS could be regarded as representing an abnormal response of the vessel wall caused by DES. Several mechanisms have been proposed to account for the development of PSS, including delayed re-endothelialization, inflammatory changes in the medial wall, and hypersensitivity reactions to drugs and polymers [9-11].

Although the 12-month duplex ultrasound examination in the IMPERIAL randomized trial reported aneurysmal degeneration in only 1.9% (6/309) of patients after Eluvia™ DES implantation [4], this rose to 8.1% (8/62) in the 12-month results of the Munster registry, thus inconsistent across studies [6]. In one of these cases, immunohistological analysis of the arterial wall revealed an infiltration of CD3⁺, CD56⁺ T cells [6]. Although the exact mechanisms responsible for aneurysmal degeneration after Eluvia™ implantation are not known, as with coronary arteries, vascular inflammation might be associated with this syndrome.

Eluvia™ is coated with the primer polymer poly (n-butyl methacrylate) and an active layer composed of the matrix polymer poly (vinylidene fluoride-co-hexafluoropropylene). These coatings permit the elution of paclitaxel over approximately 12 months at a dose density of 0.167 μg paclitaxel per mm² stent surface area [4]. Farb et al. showed a dose-dependent increase in fibrin deposition and medial necrosis after deployment of paclitaxel-eluting stents in rabbit iliac arteries [12]. Another previous pathological report mentioned that the features of paclitaxel-eluting stent implantation included excessive para-strut fibrin deposition and incomplete stent apposition in patients with late stent thrombosis, suggesting that paclitaxel itself was responsible [13]. In fact, although Zilver PTX™ is a paclitaxel-coated stent without polymer, some clinical reports also recorded cases with PSS on angiography or extra stent lumen enlargement on serial optical coherence tomography after Zilver PTX™ implantation at later times [14, 15]. Therefore, it is possible that paclitaxel itself similarly induces vascular inflammation after Eluvia™ implantation and may contribute to aneurysmal degeneration. It has been reported that the polymer coatings could also cause increased vessel inflammation, which is sometimes severe, even leading to medial disruption and aneurysm [16-18]. Pathological studies regarding vascular responses to Zilver PTX™ versus Eluvia™ showed higher inflammatory reactions around struts in the latter 1-, 3-, 6- and 12-months after implantation, possibly caused by continuous exposure to paclitaxel, or the presence of the durable polymer coating [19]. Furthermore, 24-month results of the IMPERIAL randomized trial showed hypoechogenic halo suggestive of aneurysmal degeneration in 33.7% of patients after Eluvia™ implantation and 21.4% after Zilver PTX™ implantation, but this difference was not statistically significant [5]. The frequency of aneurysmal degeneration 24 months after Eluvia™ implantation increased compared to what was seen at 12 months [4, 5]. Thus, although there was no significant difference, the frequency of occurrence of aneurysmal degeneration tended to be greater for Eluvia™ than Zilver PTX™ [5]. Judging from these results, the durable polymer employed by Eluvia™ might be associated with more vessel inflammation, resulting in aneurysmal degeneration at later times. According to the manufacturers of the stent platforms, the constant outward self-expanding force is greater in Eluvia™ than Zilver PTX™, which itself might contribute to vessel inflammation,

Although data on the clinical parameters of patients with aneurysmal degeneration in PAD are scarce, a previous report on coronary artery disease showed that PSS found within 12 months after DES implantation was potentially associated with subsequent target lesion revascularization and very late stent thrombosis [7]. Bisdas et al. reported that 5 of 62 patients treated by Eluvia™ implantation had aneurysmal degeneration and one of these presented with clinical worsening caused by the occlusion of the stent [6]. Given these data, long-term follow-up should be mandatory for patients receiving Eluvia™ implantation. Further investigation is warranted to evaluate the impact of aneurysmal degeneration after Eluvia™ implantation on clinical outcomes. Although dual antiplatelet therapy is recommended for at least 60 days after Eluvia™ implantation, its prolongation might be worth considering in patients with aneurysmal degeneration.

We report a case with exacerbated aneurysmal degeneration on serial angiography and intravascular ultrasound 50 months after Eluvia™ implantation for an SFA lesion. Long-term follow-up should be mandatory for patients receiving Eluvia™ implants.

ABI: Ankle brachial index

DES: Drug-eluting stent

EVT: Endovascular therapy

IVUS: Intravascular ultrasound

PSS: Peri-stent contrast staining

SFA: Superficial femoral artery

Ethics approval and consent to participate

All procedures performer in studies involving human participant were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendment or comparable ethical standards. Patient’s specific consent was obtained for this report, and consent by the Institutional Review Board was not required.

Consent for publication

Consent for publication was obtained from the patients for publication of this case report and any accompanying images.

Availability of data and materials

Not applicable.

Competing interests

O.I. has a remuneration from Medtronic Japan and Boston scientific Japan, and T.M. has a research grant from Abbott vascular Japan. T.T. have no disclosures to report.

Funding

Not applicable.

Authors' contributions

All authors have made substantial contributions to all of the following: 1) conception and design and interpretation of data, or both; 2) drafting of the manuscript or revising it critically for important intellectual content; and 3) final approval of the manuscript submitted.

Acknowledgements

Not applicable.

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Aneurysmal Degeneration of Fluoropolymer-Coated Paclitaxel-Eluting Stent in the Superficial Femoral Artery. A Rising Concern

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Case presentation

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