Polytetrafluoroethylene coating fragments during neuroendovascular therapy: An analysis of two damaged microguidewires

Abstract

Cerebral polymer coating embolism from intravascular devices represents a potentially serious complication to endovascular therapy (EVT). We report two cases of neuroendovascular treatment where filamentous polymer fragments were noted possibly due to damage of the surface coating during manipulation and backloading of microguidewires. As the exact origin of the debris was initially not known, microguidewires and fragments were examined with light microscopy, stereomicroscopy, scanning electron microscopy and attenuated-total-reflection Fourier transform infrared spectroscopy. Fragments consisted of polytetrafluoroethylene and silicone oil stemming from the proximal shaft of a standard microguidewire. To our knowledge, this is the first report of polytetrafluoroethylene coating fragments created during EVT. Future studies should assess the mechanism of polymer coating delamination and its potential consequences during EVT including inadvertent fragment migration into the cerebral circulation.

Introduction

Hydrophilic polymer coatings on intravascular devices facilitate endovascular maneuverability and reduce the risk of vessel injury by increasing the surface lubrication. ¹ On the other hand, polymer embolisms due to delamination or peeling off of the hydrophilic layers has been described. ² , ³ Cerebral embolism from polymer coating during endovascular therapy (EVT) was first reported in 1997 ¹ and has been demonstrated histopathologically after various diagnostic and therapeutic neurointerventional procedures. ¹ , ² ,^4–6 Although rarely described, serious morbidity and mortality due to ischemic infarction, intraparenchymal hemorrhage, granulomatous angiitis, chemical meningitis and brain abscesses may occur. ⁷ , ⁸ While the phenomenon per se is described in the literature, ⁷ the type and composition of polymers in delaminated coating fragments is largely unknown. Hitherto, only polyvinylpyrrolidone (PVP) has been identified in a delaminated coating fragment. ² We present two cases where fragments of polytetrafluoroethylene (PTFE; known as Teflon®) and silicone oil stemming from microguidewire coating were identified.

Case presentation

The first patient underwent preoperative embolization of a juvenile nasopharyngeal angiofibroma using a 6-French (Fr) Avanti®⁺ sheath (Cordis®, Miami, FL, USA), a 4-Fr Supertorque™ diagnostic catheter (Cordis®), and a 6-Fr Envoy guiding catheter (Codman Neuro, Raynham, MA, USA) together with two Headway 17 and 21 microcatheters (MicroVention®, Tustin, California, USA). Microcatheter navigation was performed over the 0.014″ Traxcess™ 14 (MicroVention®) and 0.014″ Asahi Chikai (Asahi Intecc, Aichi, Japan) microguidewires. During a reshaping maneuver of the Traxcess™ microguidewire, multiple blue colored fragments of 1–2 mm in diameter were noticed hanging from its tip as well as in the bowl with sterile saline used for wetting microguidewires and catheters (Figure 1(a) and (b)). The procedure was then halted and the guidewire was inspected with no obvious signs of surface damage. After changing microcatheter and microguidewire the procedure was continued. However, shortly after introducing a newly opened Traxcess™ microguidewire, another blue filamentous fragment was noted that appeared to be created near the tip of the introducer (Figure 1(c)). The procedure was now halted again and continued using the Asahi Chikai microguidewire with no other obvious fragments being observed.

Figure 1.

Photographs of fragments found during neuroendovascular therapy in patient 1 (scalebars 1 mm). (a) Small filaments stuck to the tip of the microguidewire. (b) Multiple fragments were found in the sterile saline bowl used for wetting the microguidewires. (c) Another fragment covered the microguidewire and appeared to be created near the tip of the introducer (arrow).

The second patient underwent embolization of a dural arteriovenous fistula using a Traxcess™ microguidewire. During the procedure a barely visible transparent filamentous fragment of approximately 5 cm length was noted. The Traxcess™ microguidewire was discarded and the procedure was completed with another microguidewire without technical difficulties.

In both patients, intravascular devices were handled in accordance with the manufacturers’ instructions by a senior neurointerventionalist who has been using this guidewire for >10 years. No angiographic evidence of distal vessel occlusion was observed during the endovascular procedures and neither patient developed post-procedural sequelae. The fragments encountered during EVT were used for more detailed analysis.

Initial considerations

Although microguidewire coating damage was suspected, the origin of the fragments was unclear, because the microguidewires appeared intact when inspected with the naked eye. The fragments in patient 1 were bluish and curled, while the fragment in patient 2 was transparent, uncurled, and fragile. The Traxcess™ microguidewire was used in both patients and it has a bluish proximal section. Therefore, Traxcess™ microguidewire test fragments were obtained by peeling off the surface of a new Traxcess™ microguidewire by backloading it through a metal introducer (Figure 2(a)).

Figure 2.

(a). Microguidewire coating fragment created by backloading a microguidewire through an introducer while exerting lateral stress on the microguidewire (scalebar 1 mm). When pulling back the introducer, the fragment was still attached to the microguidewire (arrow). The fragment curls up near the tip of the introducer (arrowhead). (b)-(c) Unstained light micrographs (scalebar 150  $\mathrm{\mu }\mathrm{m}$ ) show similar size and structure of a fragment created during treatment of patient 1 (b) and a Traxcess™ test fragment (c). The fragments have a central granular blue layer (arrow) and a transparent edge (arrowhead). (d) Stereomicrograph of a transparent fragment created during treatment of patient 2 consisting of the transparent layer (arrowhead) with a small stripe of the central blue layer (arrow). (e)-(f). Stereomicrographs show an intact surface (e) and a coating defect (f) in the proximal shaft of a Traxcess™ microguidewire used for EVT in patient 1. No damage was visible with the naked eye.

The Traxcess™ 14 is a steerable guidewire with a straight shapeable tip (catalog number GW1420040). The proximal portion (160 cm) consists of a stainless steel core wire covered with a silicone layer, which is coated with PTFE. The distal portion (40 cm) consists of a stainless steel coil and a distal radiopaque platinum-nickel coil that winds around a nickel-titanium alloy core wire. The distal segment is coated with a commercial hydrophilic coating (SLIP-COAT™, Argon Medical, Frisco, TX, USA) containing PVP, which is a commonly used hydrophilic polymer.

Material and methods

Microscopy

The fragments and both Traxcess™ microguidewires were initially examined by unstained light microscopy (BX53, Olympus, Tokyo, Japan) and stereomicroscopy (Stemi 508, Zeiss, Oberkochen, Germany). Three fragments obtained during EVT in patient 1 were subsequently examined by scanning electron microscopy (Quanta™ FEG 3D, FEI, Eindhoven, The Netherlands) for assessment of the microscopic structure. Samples were mounted on 12 mm aluminium stubs and sputter coated (ACE200, Leica Microsystems, Vienna, Austria) with 6 nm gold before microscopy.

Spectroscopy

The attenuated-total-reflectance (ATR) single-channel spectra of the samples were collected by a vacuum Fourier transform infrared (FTIR) spectrometer (VERTEX80v, Bruker Optics GmbH, Ettlingen, Germany) employing a single-reflection diamond ATR accessory. The FTIR apparatus was configured with a KBr on Ge beam splitter, a liquid nitrogen cooled HgCdTe detector and a globar thermal radiation source. Background single-channel spectra of the cleaned diamond crystal were collected in between sample measurements. The resulting absorption spectra of 2 cm⁻¹ resolution have been corrected for residual water vapor absorption and minor baseline drifts. Subsequently, extended ATR corrections were applied to account for the wavelength-dependent penetration depth of the infrared probe beam into the samples. The reference ATR-FTIR spectra were collected for commercially available PTFE powder (1 μm particle size, Merck) and liquid polydimethylsiloxane (PDMS; a type of silicone oil) (20 centistokes at 25 °C, Merck).

Results

Microscopy

Unstained light microscopy and stereomicroscopy showed that fragments were band-like and consisted of a blue granular layer and a uniform transparent layer (Figure 2(b) and (c)). If present, the blue material was noted in the central part of fragments, while the transparent material was visible at the rim. Thus, the transparent layer seemed to be a more superficial layer of the microguidewire compared to the blue granular layer. The Traxcess™ test fragment and the fragment in patient 1 had similar microscopic appearances with a width of 100 μm. In patient 2, the fragment had a width of 75 μm and consisted almost entirely of the outmost transparent layer (Figure 2(d)). All fragments were radiolucent and indissoluble in saline.

Although no microguidewire damage was visible by the naked eye, stereomicroscopy showed multiple centimeter long scrapings in the proximal coating of the microguidewire in patient 1 (Figure 2(e) and (f)). The fragments imaged by scanning electron micrography had a smooth side corresponding to the outer surface of the microguidewire and a rough side created by peeling of the microguidewire coating (Figure 3(a) to (c)).

Figure 3.

Scanning electron micrographs with increasing magnification. (a) Fragment consisting of a single band measuring 90  $\mathrm{\mu }\mathrm{m}$ in width and 10  $\mathrm{\mu }\mathrm{m}$ in thickness. The band curls up to form a rounded structure with a diameter of 2 mm (scalebar 1 mm). (b) Folds created during delamination is clearly visible (scalebar 150  $\mathrm{\mu }\mathrm{m}$ ). (c) Appearance of the smooth outer surface (right) and the peeled of deeper layer (left) of the microguidewire fragment (scalebar 50  $\mathrm{\mu }\mathrm{m}$ ).

Spectroscopy

ATR-FTIR spectra of two fragments obtained during EVT showed similar absorption bands as a Traxcess™ test fragment from the proximal portion of the microguidewire (Figure 4(a) to (c)). All these fragments contained PTFE as seen by the characteristic absorption bands in the PTFE reference spectrum (Figure 4(e)). While the homogenous fragment obtained in patient 2 consisted only of PTFE (Figure 4(b)), the more heterogenous fragment in patient 1 had an additional absorption band at 1030 cm⁻¹ (Figure 4(a)). Analysis of a deeper Traxcess™ test fragment showed characteristic absorption bands in the fingerprint region of silicone oil (Figure 4(d)). Silicone oil has specific Si-O-Si stretching absorption bands at 1030 cm⁻¹ as illustrated in the collected reference spectrum of PDMS (Figure 4(f)). This finding indicates the presence of smaller amounts of silicone oil in the fragment from patient 1.

Figure 4.

ATR-FTIR fingerprint spectra between 450 cm⁻¹ and 1600 cm⁻¹ of fragments obtained during EVT in patient 1 (a) and patient 2 (b), and of test fragments from the Traxcess™ microguidewire’s superficial (c) and deep (d) layers together with collected reference ATR-FTIR spectra of polytetrafluoroethylene (e) and polydimethylsiloxane (f).

Discussion

Advances in development of surface coatings for endovascular guidewires and catheters have expanded the neurointerventionalist’s armamentarium. Increasing lubrication and maneuverability facilitates less traumatic catheterization of distal vessels with lower thrombogenicity and reduced risk of dissections and vasospasms. ¹ , ⁷ , ⁹ The routine use of polymer-coated devices in neurointerventional procedures has increased the risk of polymer coating embolism. Several reports have histopathologically identified polymer fragments in brain tissue after both diagnostic and therapeutic neurointerventional procedures such as thrombectomy and treatment of aneurysms with coil embolization or flow diversion. ² ,^4–7 A substantial risk of cerebral foreign body embolism is also found after cardiovascular and peripheral interventions. ³ Furthermore, intrathrombus deposition of polymers may occur in 33% of patients undergoing endovascular thrombectomy for acute large vessel stroke ⁸ and in 45% of patients undergoing percutaneous coronary intervention for acute myocardial infarctions. ¹⁰

The clinicopathological features of polymer embolism have been thoroughly reviewed and different histologic patterns of injuries described. ³ , ⁷ Polymer embolism can be associated with multifocal ischemic and hemorrhagic infarcts downstream from the site of neurointerventional procedures in a distribution depending on the particulate composition. ⁸ Arterial injury with intraarterial thrombus formation and narrowing or obliteration of vessel has been found. ⁷ Inflammatory changes include arteritis, chemical meningitis, sterile cerebral abscesses and granuloma formation. ² , ⁴ , ⁵ , ⁷ While infarction usually occurs within few hours post-procedure some secondary symptoms may present after days or even months. Delayed onset of symptoms can be caused by chronic neuroinflammation with vasogenic edema that may require corticosteroid and immunosuppressive therapy. ³ , ⁴ , ⁷ A cell-mediated allergic response to cerebral embolized polymers and their degradation products has been proposed as a possible mechanism for this rare phenomenon. ⁴

Cerebral polymer coating embolism represents a diagnostic challenge requiring microscopic identification of non-refractile, non-polarizable, granular, lamellated, and basophilic amorphous foreign bodies on hematoxylin and eosin stains in biopsied, resected or autopsied brain tissue. ³ , ⁴ , ⁷ Several reports have demonstrated that polymer fragments acquired ex vivo have similar histologic characteristics, ¹ , ² , ⁵ , ⁶ , ¹⁰ but only one study by Hu et al. ² identifies the type of polymer using FTIR-spectroscopy. In their paper, cerebral PVP emboli were found in two patients with delayed intraparenchymal hemorrhages.

To our knowledge, the formation of PTFE coating fragments during EVT has not yet been reported. Fragments were heterogenous in size and morphology, and some contained silicone oil from a deeper layer of the Traxcess™ microguidewire. Cerebral PTFE and polyethylene terephthalate (PETE; known as Dacron) emboli have been observed in the 70-ies in patients with the polymer-coated Beall mitral valve prosthesis and may cause widespread microinfarcts with associated granulomatous inflammation. ¹¹ However, animal studies with carotid artery injections of microscopic PTFE particles showed only a mild inflammatory foreign body reaction to particles in the brain parenchyma, but no evidence of demyelination or cerebral infarction after 6 months. ¹² , ¹³ The long-term consequences of cerebral PTFE deposits in EVT patients are currently unknown.

In 2015, the U.S. Food and Drug Administration issued a safety communication describing delamination of coatings on medical devices mainly involving guidewires. ¹⁴ No specific manufacturers were associated with higher risks than others. ¹⁴ As the benefit of lubricious coatings still outweigh the risk of polymer emboli, care must be taken to reduce this risk. ¹⁴ Firstly, preparation of microguidewires in accordance with the manufacturer’s instruction is important for activation of polymer coatings. Polymer emboli are thought to be created due to excess friction between intravascular devices and/or vessel walls. ³ Especially tight coupling of sheaths, catheters, and guidewires during co- and triaxial catheterizations may potentially form polymer emboli. In addition, we believe that frequent backloading of microguidewires may create small coating fragments at the tip of metal introducers ¹⁵ that could adhere to the microguidewire. Although FDA cautioned against the use of coated devices through needles, metal cannulas, and other sharp-edged devices, ¹⁴ many coated microguidewires still come in a package with a dedicated metal introducer. These insertion tools often have relative sharp edges at their tips, that may damage the coating if the microguidewire bend during manipulation. Thus, a risk of polymer embolism may exist whenever a guidewire is changed or shaped and reintroduced while using those insertion tools. ¹⁵ Therefore, the use of metal introducers for front- and particularly backloading should be minimized, and performed with great care. Frontloading of microguidewires should be preferred whenever possible, because it reduces the length of the guidewire being exposed to the edge of the introducer.

Polymer delamination has previously been reported for various intravascular devices and is likely not unique for the Traxcess™ microguidewire. ¹⁴ It is also important to keep in mind that some fragments may be so small that they can escape the naked eye of the operator, and thus can occur more frequently than has been observed so far. ³ , ⁸ Finally, the source of foreign body embolism may also relate to manufacturing, packing, and storage of devices or to contamination in the angiosuite with gaze and dust fibers.⁸

Conclusion

In conclusion, polymer coating fragments that may be scraped off the guidewire surface during manipulation in neuroendovascular procedures may contain PTFE (Teflon®) and silicone oil. Thus, both substances can potentially migrate into the cerebral circulation. Cerebral PTFE embolism may induce a chronic inflammatory foreign body reaction with unknown long-term effects, in addition to the immediate risk of ischemic and hemorrhagic infarcts.

Although polymer coating embolism has been described and discussed, more specific material analyses are needed to better characterize the composition of polymer coating fragments. While the measurement of ATR-FTIR spectra of embolized polymers in tissue samples can be limited by the small amount of available polymer, ¹ , ² this study suggests that spectroscopic assessment of device fragments ex vivo with similar histopathological appearance may help to identify the polymer. Identification of endovascular tools with non-durable polymer coatings is desirable in order to improve safety and efficacy of neurointerventional procedures.

Abbreviation list

ATR-FTIR: Attenuated-total-reflection Fourier transform infrared spectroscopy; EVT: Endovascular therapy; Fr: French; PDMS: polydimethylsiloxane; PETE: polyethylene terephthalate; PTFE: polytetrafluoroethylene; PVP: polyvinylpyrrolidone.