Device Profile
The Pipeline embolization device for treatment of intracranial aneurysms Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Expert Rev. Med. Devices 11(2), 137–150 (2014)
Jorge L Eller1,5, Travis M Dumont1,5, Grant C Sorkin1,5, Maxim Mokin1,5, Elad I Levy1,2,4,5, Kenneth V Snyder1–5, L Nelson Hopkins1,2,4–6 and Adnan H Siddiqui*1,2,4–6 1 Department of Neurosurgery, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA 2 Department of Radiology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA 3 Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York Buffalo, NY, USA 4 Toshiba Stroke and Vascular Research Center, University at Buffalo, State University of New York, Buffalo, NY, USA 5 Department of Neurosurgery, Gates Vascular Institute, Kaleida Health, Buffalo, NY, USA 6 Jacobs Institute, Buffalo, NY, USA *Author for correspondence: Tel.: +1 716 218 1000 Fax: +1 716 859 7479 [email protected]
informahealthcare.com
Flow diversion is a new endovascular technique developed for treatment of intracranial aneurysms. It is based on stent-induced modification of blood flow within and around an aneurysm inflow zone, leading to gradual intra-aneurysmal thrombosis and subsequent atrophy, while preserving flow into the parent vessel and perforating branches. Flow-diversion technique is well-suited for the treatment of large, giant, wide-necked, and fusiform intracranial aneurysms because it does not rely on endosaccular packing with coils but rather on the strategy of placing a stent across the aneurysm “neck” or across the diseased segment of a vessel in case of a fusiform aneurysm. Over time, neointimal endothelium covers the flow diverter such that it becomes incorporated into the parent vessel wall and occludes the aneurysm from the circulation, effectively repairing the diseased parent vessel segment. This report describes in detail the Pipeline embolization device (ev3-Covidien, Irvine, California, USA), its mechanism of action and deployment technique, and reviews the pertinent literature regarding safety, efficacy and potential risks and complications associated with the use of this flow diverter. KEYWORDS: endovascular treatment . flow diversion . intracranial aneurysms . Pipeline embolization device
Intracranial aneurysms are acquired lesions with a prevalence of 5–10% estimated in the population [1]. Approximately 30,000 cases of subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms occur in the USA each year, leaving approximately 60% of victims dead or disabled [2]. The first surgical clipping of an intracranial aneurysm was performed by Walter Dandy in 1937 [3]. Developments in aneurysm surgery – including microsurgical techniques, new clip designs, development of brain protection, neuroanesthesia, neuromonitoring and bypass techniques – made surgical clipping the mainstay, time-tested treatment for intracranial aneurysms. In the early 1990s, the introduction of the Guglielmi detachable coil revolutionized the treatment of intracranial aneurysms by providing an endosaccular, endovascular alternative to surgical clipping [4], effectively paving the way for the new discipline of endovascular neurosurgery to emerge [5]. In the short timespan, since endovascular coiling has evolved to become the preferred treatment modality for most ruptured and unruptured intracranial aneurysms, with better survival and fewer poor outcomes in patients treated with
10.1586/17434440.2014.877188
this approach than with surgical clipping, as demonstrated by recent clinical trials [6,7]. The limitations of endovascular coiling, however, became apparent as time and experience accumulated. One of the main issues has been the long-term aneurysm occlusion rate, with significant numbers of aneurysms treated by coil embolization not angiographically cured at the time of mid-term follow-up assessment. For example, a single-center experience with 501 aneurysms treated endovascularly demonstrated a complete angiographic occlusion rate of only 38.3% at 1 year and, even after retreatment, approximately half the aneurysms required further intervention [8]. Additionally, the geometry of intracranial aneurysms determines the feasibility of effective treatment with endovascular coiling. Several adjunctive techniques and technologies have been advocated to improve angiographic and clinical outcomes associated with primary aneurysm coiling, including balloon-assisted coiling techniques, self-expanding intracranial stents for stent-assisted coiling and 3D, bioactive, and gel-coated coils. Despite these advancements, many aneurysms remain challenging to
2014 Informa UK Ltd
ISSN 1743-4440
137
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Device Profile
Eller, Dumont, Sorkin et al.
treat surgically or endovascularly, such as large (>10 mm diameter) and/or giant (>25 mm diameter), wide-necked (aneurysms with a dome-to-neck ratio of 4 mm), had unfavorable dome-to-neck ratios (25 mm diameter) [33]. One patient enrolled in the study could not have the parent artery catheterized; therefore, PED placement was not attempted. Three patients died on postoperative Days 4, 11 and 14, respectively. Of the remaining 104 patients alive at 6 months, 97 patients had follow-up angiography demonstrating 73.6% complete occlusion at 6 months without major stenosis or use of adjunctive coils. Six patients (5.6%) experienced major ipsilateral stroke or neurological death at 6 months, five patients developed intraparenchymal hemorrhages distant from the aneurysm site and five patients presented with delayed parent vessel occlusions at the 1-year follow-up assessment. On the basis of the results of this trial, the FDA granted the aforementioned premarket approval for the PED for the endovascular treatment of adults (age 22 years or older) with large or giant wide-necked intracranial aneurysms in the ICA from the petrous to the superior hypophyseal segments. We have published the early results of a multicenter experience following the release of the PED in the US market [37]. A total of 62 procedures were performed to treat 58 aneurysms with PEDs. On average, two PEDs were used per aneurysm. Six postdeployment angioplasties were performed for maldeployment (kinking, stenosis or torsion). The major permanent procedural complication rate was 8.5%. Six postprocedural ischemic events were noted, five of which were in the posterior circulation and only one was permanent. There were four postprocedural hemorrhagic events (6.9%): three delayed ruptures and one distal parenchymal hemorrhage, all of which were fatal. Follow-up angiograms at 3 months were available for 19 patients; the rate of complete occlusion was 68% (13 patients). Although limited and early, this result compared favorably with alternate techniques given that only 17% of the aneurysms treated were small (50% of the perforator orifice is compromised by the PED, despite the presence of a flow gradient [44,45]. Nevertheless, long-term clinical follow-up data are lacking on this issue. Puffer et al. [46] reported that up to 25% of ophthalmic arteries would undergo thrombosis when covered with the PED. This may be due to competitive collateral flow from the external carotid artery that prevents a pressure gradient from developing, leading to occlusion of the proximal ophthalmic artery when covered by the PED. The need to place more than one PED in an overlapping fashion to provide enough metal coverage at the neck of an aneurysm and therefore enough flow diversion to initiate aneurysm thrombosis and occlusion has to be tempered by the need to allow enough flow across the stent pores to maintain perforating branch vessel patency. This delicate balance may be relatively straightforward in the ICA circulation – specifically within the ICA segments for which the device was granted FDA approval, namely, from the petrous to the superior hypophyseal artery; however, in the perforator-rich vertebrobasilar system, the situation is fairly different. Siddiqui et al. [47] recently published a case series of large or giant fusiform vertebrobasilar aneurysms treated with flow diversion. Four of seven patients treated with PEDs died. Two of those deaths were due to devastating brainstem strokes and two to postprocedural aneurysm rupture and SAH. In those patients who experienced ischemic events, the deployment of multiple, overlapping PEDs may have led to occlusion of perforating vessel branches. One must proceed with great care when using the PED in the posterior circulation and certainly attempt to place the least number of devices needed to disrupt aneurysm flow, preferably with only single PED coverage of perforator-rich territories. The risk of thromboembolism leading to Pipeline device occlusion or late in-stent stenosis is also important to consider. Although relatively uncommon, these are potentially devastating complications. The rate of PED thrombosis or stenosis was 1.9% in the PUFS trial [33] and approximately 5% in the Buenos Aires series [34]. Notably, one of the first two patients to undergo PED treatment in the USA under compassionate use (described above) later presented with occlusion of the treated vertebral artery just a few days after his antiplatelet medication was discontinued by another physician [32]. This fact underscores the likely need for at least single agent lifelong antiplatelet therapy to counteract the PED’s thrombogenic potential. Conversely, the risk of acute thrombosis must be weighed against the risk of immediate and/or delayed aneurysm rupture and SAH. Because aneurysm thrombosis and eventual occlusion after PED treatment are a gradual process, the risk of aneurysm rupture exists during the latency period following PED deployment. In a review of five prospective series of aneurysms treated with PED, the incidence of hemorrhage after flow diversion was 2% [26]. The underlying mechanism is unclear; among different hypotheses raised to explain these ruptures are redirection of flow within an ‘unstable’ aneurysm or inflammatory changes related to formation of an intra-aneurysmal clot 144
burden, with subsequent mural destabilization and rupture [26,43]. Kulcsar et al. [48] published a review of 13 cases from 12 centers worldwide of delayed aneurysm hemorrhage following flow diversion with the SILK device. All patients in their review had aneurysms with characteristics pertaining to a high risk of rupture, such as large size, symptomatic aneurysms and high aspect ratio (>1.6). However, treatment of these lesions with flow diversion may have led to changes in intraaneurysmal flow patterns that favored the formation of autolytic, aggressive thrombus associated with the presence of a persistent inflow jet into the aneurysm, ultimately leading to degradation of the aneurysm wall and rupture. This work underscores how much is still unknown about the effects of flow diversion in an individual patient and how parent vessel geometry and aneurysm flow configuration may influence its final outcome. A small cases series of complications related to giant distal intracranial aneurysms treated with the PED was reported by Siddiqui et al. [49]. In this report, these authors describe one case of aneurysm rupture within 24 h of PED implantation and another case of acute thrombosis of the PED–parent vessel within 6 h of PED implantation. They suggest loose packing of coils within large and/or giant aneurysms to reduce the likelihood of postprocedural aneurysmal rupture and, at the same time, avoid the possibility that a dense coil mass may result in thrombosis and/or acute occlusion of the PED. Another hemorrhagic complication of flow diversion is the occurrence of nonaneurysm-related intracerebral hemorrhages adjacent or within the dependent territories of the treated aneurysm, sometimes in the contralateral hemisphere within the anterior cerebral artery territory. In a systematic review of the PED literature, Leung et al. [43] estimated an incidence of 1.6% for this particular complication. The underlying etiology of these hemorrhages could be related to hemorrhagic transformation of embolic infarctions related to complex manipulations with more robust access support and distal access catheters (especially in the face of dual antiplatelet therapy). Additionally, suggestions have been made that materials used to coat the microcatheters may be physically stripping and embolizing in the distal territories. Another hypothesis is that there are postflow diversion hemodynamic changes in the dependent vascular territory such as hyperperfusion syndrome. For example, after flow through a giant aneurysm that effectively functioned as a giant capacitance reservoir with relative dependent territory ischemia and chronic vasodilation is streamlined, breakthrough hemorrhage results because of disrupted autoregulation. Another hypothesis reflects that markedly increased metal surface area exposed to the blood stream in the intracranial circulation and the shear forces to which platelets are exposed when crossing the surface of the PED or traversing in and out of the PED result in platelet activation despite dual antiplatelet therapy, leading to embolic strokes with secondary hemorrhagic conversion. Mass effect-related symptoms are expected to subside once large and/or giant aneurysms regress after flow diversion Expert Rev. Med. Devices 11(2), (2014)
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
The Pipeline embolization device for treatment of intracranial aneurysms
Device Profile
therapy. However, there are reports of A B temporary worsening of mass effect symptoms immediately after PED implantation, likely secondary to an inflammatory cascade following aneurysm thrombosis. In the Buenos Aires cases series, Lylyk et al. [34] reported three cases of giant aneurysms causing cranial nerve palsies that worsened postoperatively. Similarly, in the series of unruptured aneurysms treated with the PED by McAuliffe et al. [50], neurological deficits in 3 of the 16 patients who presented with mass effect worsened after C D treatment, despite receiving steroids. These mass effect symptoms eventually improved over time once the inflammatory response subsided. Berge et al. [51] reported MRI findings of perianeurysmal changes in five of the seven patients with worsening mass effect symptoms following flow diversion. These aneurysms were large and embedded in brain parenchyma without interposition of cerebrospinal fluid. Therefore, despite lack of significant evidence, we routinely recommend starting patients who have giant aneurysms or present with mass effect on steroids and taper them off Figure 6. A 62-year-old woman presented with left-hand weakness. Diagnostic steroid use slowly over 3 to 4 weeks. angiogram reveals a giant right internal carotid artery fusiform aneurysm: (A) right ICA Finally, another issue to be kept in injection, anteroposterior view; (B) 3D reconstruction demonstrates complex right ICA mind is that the PED’s mechanism of fusiform aneurysm; (C) three Pipeline devices were placed in overlapping fashion, action relies on its apposition against the covering the entire diseased segment of the right ICA; (D) Two-month follow-up angiogram shows complete involution of the aneurysm and normal right ICA anatomy. vessel wall to direct flow away from the aneurysm. Therefore, aneurysms previously treated by means of stent-assisted coiling will be less ame- rates approach 30% [52–57], despite the development of skull nable to flow diversion therapy. In the series of Lylyk et al. [34], base approaches and surgical bypass strategies. Thus far, tradithe only aneurysm that remained patent at 12 months post- tional endovascular techniques have been unable to provide a PED implantation had been previously treated with stent- much better alternative for these lesions, with aneurysm occluassisted coiling. Therefore, the efficacy of the PED may be sion rates of only 57% and mortality rates varying between somewhat limited in cases of previously stented or stent-coiled 7.7 [58] and 11% [10–12]. Considering the poor natural history of giant aneurysms – 5-year cumulative rupture rates of 40% aneurysms. in the anterior circulation and 50% in the posterior circulation [9] – the search for alternative means of treatment Cost–effectiveness, alternative devices and/or becomes even more pressing. technology Despite the limitations and uncertainties described in the Alternatives to flow diversion treatment of large and/or giant, wide-necked and fusiform aneurysms include both surgical and preceding section, flow diversion appears to provide many endovascular options. From a surgical perspective, the options advantages in the management of large and/or giant intracranial are clipping, trapping, proximal (Hunterian) and/or distal par- aneurysms compared with surgical clipping and traditional ent vessel occlusion and wrapping, all of which are potentially endovascular options. Flow diversion aims at reconstructing the associated with the need for surgical bypass. From an endovas- diseased parent vessel segment and providing a scaffold for neocular perspective, one may find primary coiling, balloon- intimal growth and complete obliteration of the aneurysm, assisted coiling or stent-assisted coiling as viable options. How- regardless of the aneurysm fundus size or neck size, as opposed ever, all these alternative techniques fall short in providing an to traditional coiling strategies where these variables dictate the likelihood of success or failure and the risks and complications optimal solution to these challenging lesions. In the particular scenario of giant aneurysms, surgical mor- involved. As such, flow diversion seems particularly well suited tality rates remain as high as 10%, whereas surgical morbidity to treat these most complex aneurysms, with excellent occlusion informahealthcare.com
145
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Device Profile
Eller, Dumont, Sorkin et al.
rates and acceptable morbidity and mortality rates (FIGURE 6), as described above. Preliminary cost analyses of flow diversion so far have indicated that this treatment modality compares favorably with traditional endovascular stent-assisted coiling [59]; although in one study, it would become cost saving only in patients who would otherwise require treatment with 32 coils or more [60]. We expect that as other flow diversion strategies are introduced to the market place, such as the FRED and Surpass, the cost of each device will progressively decline. We similarly expect subsequent generations of these devices to perform in a safer and more effective fashion, bringing these previously poorly treated or untreated aneurysms into conformity with the current high standards of endovascular or microsurgical aneurysm treatment. Expert commentary
Our understanding of the pathogenesis of intracranial aneurysms continues to evolve. We have developed a hemodynamic model of aneurysmal genesis, which results from bilateral ligation of rabbit carotid arteries forcing rapid changes in the rabbit basilar artery including tortuosity, hypertrophy, fusiformal dilatation and a basilar terminus aneurysm [19,61]. These are not the first reports of a hemodynamic relationship, but clinically it has been well recognized, such as in the instance of previous carotid ligation and with flow-related aneurysms associated with arteriovenous malformations. This is not to discount intrinsic factors, such as family history, genetics and environmental exposures (such as cigarette smoking), all of which work to lower the threshold of hemodynamic insult [62]. Compared with all previous endovascular or microsurgical solutions, flow diversion attempts to address the affected vessel segment in its entirety. Buttressing the vessel walls with a microfilament-braided mesh allows for growth of endothelium across the aneurysmal ostium, regardless of its shape, size or configuration. We have recognized from previous angiographic endovascular cures that this endothelial separation of the parent vessel lumen and aneurysm is the ultimate cure that we seek. Flow diversion affords this most reliably for the more difficult to treat aneurysms. However, this paradigm shift comes with its own set of challenges and complications. We are encountering delayed aneurysmal rupture on a low but regular basis. We are encountering distal parenchymal hemorrhages at a low but steady rate. Although we have detailed some speculative hypotheses above, quite frankly, we do not have any clarity in terms of the pathogenesis for either of these devastating complications. It would be interesting to see if the newer flow diverters, such as Surpass or FRED, are also associated with these phenomena. If they are not, then these events may be more related to the nuances of the construct or delivery of the PED. Conversely (and more likely), if these devices are associated with similar complications, then they may reflect the underlying inherent conflict associated with superlative flow diversion cures, with a small but clear propensity for devastating hemorrhagic complications. Although both complications are hemorrhagic, they likely reflect differing mechanisms. We feel that the delayed ruptures 146
fall into two categories based on timing, early or late. Early ruptures likely reflect hemodynamic alterations, such as a repositioned flow-vector ‘jet’ following PED placement or an endoleak-type phenomenon with a ball valve effect in which the rate of incoming and outgoing flow is slightly mismatched and overwhelms aneurysm wall elasticity. Delayed ruptures likely reflect a balance between complete aneurysm thrombosis (preventing any further flow within the aneurysm and sealed by endothelial overgrowth across the aneurysm ostium) versus thrombosis-mediated inflammatory disruption of the aneurysmal wall (in the presence of persistent – even limited – aneurysmal flow), leading to rupture. Distal parenchymal hemorrhages appear to be either hemorrhagic transformations of embolic events or hyperperfusiontype breakdown of circulatory autoregulation post-PED placement. There is some empiric association with either under- or over-responsiveness to clopidogrel response testing. This remains entirely unproven but has caused us to be extremely responsive to results on the P2Y12 assays by titrating underresponse with additional or alternate medications and overresponse with dose reduction. The other new element introduced by PEDs is the need for more complex access supportive devices. We are routinely using larger guides and more complex intermediate catheters to deliver these devices reliably. The effect of these additional developments on complications from these procedures remains unclear. Although the pertinent literature documents several limitations associated with flow diversion at present – such as reduced efficacy in previously treated aneurysms, need for dual antiplatelet therapy (which poses a problem for treatment of ruptured aneurysms or in patients who are noncompliant) and inability to treat distal and/or bifurcation aneurysms (such as MCA bifurcation or anterior communicating artery aneurysms) – as well as clear risks (such as delayed aneurysm rupture, thromboembolic complications, nonaneurysm-related intracranial hemorrhage and worsening of mass effect symptoms), flow diversion represents a paradigm shift in the treatment of intracranial aneurysms. Recently, Szikora presented the preliminary results from the IntrePED registry at the Leipzig Interventional Course Conference, Paris France (11–13 June 2013), which included consecutive patients enrolled at 17 sites in 6 countries. A total of 906 aneurysms of all types and locations were treated in 793 patients with 88% of patients having a follow-up of >12 months. In this highly heterogeneous group, these results included delayed rupture in nine patients (1%), intracerebral hemorrhage in 1.6%, ischemic stroke in 6.5%, in-stent stenosis in 1.5%, permanent cranial neuropathy in 0.3% and all-cause mortality in 4.1%. All-cause morbidity–mortality was 8.2%. Delayed ruptures and intraparenchymal hemorrhages were much more common in large and giant aneurysms. Although this data set needs to undergo peer review, it reflects the growing volume of experience, which as with any new technology, improves with operator experience and understanding of pitfalls, strategies and indications with time. Expert Rev. Med. Devices 11(2), (2014)
The Pipeline embolization device for treatment of intracranial aneurysms
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Five-year view
The PED is a first-generation flow diverter intended for treatment of the most challenging intracranial aneurysms. Many of the problems and limitations encountered with this device will certainly be solved by further refinements and developments of this technology. For instance, deployment of the PED can sometimes be challenging, given the difficulty in navigating a relatively stiff device (especially the longer PEDs) through tortuous anatomy and the significant foreshortening of the device once deployed. It is expected that the next iterations of this device will have a much easier and predictable deployment system, minimizing the likelihood of maldeployment and the need for multiple devices. New iterations of the PED are being developed to counter some of the deployment issues noted above. In addition, newer devices such as the FRED are made of nitinol and therefore behave much more like laser cut stents with markedly less foreshortening. The next question will be whether the preciseness of delivery will take away from the success of the braided design. Additional strategies may be using coated stents to reduce or eliminate the need for dual antiplatelet therapy, thereby opening options for ruptured aneurysms. The question remains whether that will alter the rate of distal parenchymal hemorrhages. Moreover, it is likely that the science of flow diversion will evolve, with computational flow dynamic simulations and in vivo laboratory experiments shining light into the mechanisms of delayed aneurysm rupture, nonaneurysm-related intracerebral hemorrhage and the relationship of a particular aneurysm inflow zone and the application of flow diversion to its respective parent vessel. Once these relationships are well understood, it will be possible to predict aneurysm behavior as related to particular changes in flow brought about by a specific flow diverter device and therefore minimize or avoid altogether the occurrence of the aforementioned complications. There is the possibility that if we can design asymmetric stents with a particular surface acting as a flow diverter, then we could avoid perforator-related complications. However, we currently do not have fluoroscopic abilities to fully harness design modifications that would allow us to reliably deploy directional stents. Microangiographic fluoroscopy may hold the key to such strategies [63]. Following the same line of reasoning, the need for adjunctive aneurysm coiling together with PED implantation will also be better understood and its effects predicted in flow dynamic simulations, making the utilization of devices such as the PED safer and associated outcomes more predictable. The inflammatory reaction associated with intra-aneurysmal thrombosis will also be better understood, leading to proper management strategies to avoid degradation of the aneurysm wall and rupture as well as minimization of mass effect symptoms. Also, further refinements in the device will likely minimize the risk of perforating vessel occlusion and the incidence of thromboembolic complications, making this device safer and effective in treating posterior circulation aneurysms as well. As further experience is gained worldwide with the utilization of the PED in the treatment of various types of aneurysms informahealthcare.com
Device Profile
and the device itself is further refined and developed by industry, it is likely that flow diverters will have an ever-widening range of applications including the treatment of ruptured aneurysms, blister aneurysms, dissecting aneurysms, perforatorrich territory aneurysms and bifurcation aneurysms. Acknowledgements
The authors thank N Aronoff, MLS, at the Kaleida Health Libraries for providing literature search and reference retrieval assistances and PH Dressel, BFA, for assistance with preparation of the illustrations and DJ Zimmer for editorial assistance (both at University at Buffalo Neurosurgery). Financial & competing interests disclosure
TM Dumont, JL Eller and GC Sorkin report no financial relationships. LN Hopkins receives grant/research support from Toshiba; serves as a consultant to Abbott, Boston Scientific, Cordis, Micrus and Silk Road; holds financial interests in AccessClosure, Augmenix, Boston Scientific, Claret Medical, Endomation, Micrus and Valor Medical; holds a board/trustee/ officer position with Access Closure and Claret Medical; serves on Abbott Vascular’s speakers’ bureau; and has received honoraria from Bard, Boston Scientific, Cleveland Clinic, Complete Conference Management, Cordis, Memorial Health Care System and the Society for Cardiovascular Angiography and Interventions (SCAI). EI Levy receives research grant support, other research support (devices) and honoraria from Boston Scientific and research support from Codman & Shurtleff, Inc. and ev3/Covidien Vascular Therapies; has ownership interests in Intratech Medical Ltd. and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman & Shurtleff, Inc.; serves as a consultant per project and/or per hour for Codman & Shurtleff, Inc., ev3/Covidien Vascular Therapies and TheraSyn Sensors, Inc.; and receives fees for carotid stent training from Abbott Vascular and ev3/Covidien Vascular Therapies. EI Levy receives no consulting salary arrangements. All consulting is per project and/or per hour. M Mokin has received an educational grant from Toshiba. AH Siddiqui has received research grants from the National Institutes of Health (co-investigator: NINDS 1R01NS064592-01A1; not related to present device review) and the University at Buffalo (Research Development Award); holds financial interests in Hotspur, Intratech Medical, StimSox, Valor Medical and Blockade Medical; serves as a consultant to Codman & Shurtleff, Inc., Concentric Medical, Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Inc., Stryker Neurovascular and Pulsar Vascular; belongs to the speakers’ bureaus of Codman & Shurtleff, Inc. and Genentech; serves on National Steering Committees for Penumbra, Inc. 3D Separator Trial and Covidien SWIFT PRIME Trial; serves on an advisory board for Codman & Shurtleff and Covidien Vascular Therapies; and has received honoraria from American Association of Neurological Surgeons’ courses, Annual Peripheral Angioplasty and All That Jazz Course, Penumbra, Inc. and from Abbott Vascular and Codman & Shurtleff, Inc. for training other neurointerventionists in carotid stenting and for training physicians in endovascular stenting for aneurysms. AH Siddiqui receives no consulting salary arrangements. All consulting is per project and/or per hour. KV Snyder serves as a consultant and a member of the speakers’ bureau for Toshiba and has received honoraria from Toshiba. He serves as a member of the speakers’ bureau for and has received honoraria from ev3 and The Stroke Group. 147
Device Profile
Eller, Dumont, Sorkin et al.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Key issues .
Endovascular coiling, with or without balloon or stent assistance, has become the preferred treatment modality for most intracranial aneurysms.
.
Large, giant, wide-necked and fusiform intracranial aneurysms remain particularly challenging, with low aneurysm occlusion rates and significant morbidity and mortality associated with surgical or endovascular treatment.
.
Flow diversion represents a paradigm change in endovascular aneurysm treatment, whereby the diseased segment of the parent vessel is reconstituted with a high metal, low-porosity stent that diverts flow away from the aneurysm, leading to aneurysm thrombosis, shrink-
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
age and neointimal parent vessel remodeling. .
Because flow diversion does not rely on endosaccular filling of the aneurysm with coils, the size of the aneurysm sac or neck is less relevant to its effectiveness; therefore, it seems a well-suited technique for the treatment of large, giant or fusiform aneurysms for which no optimal treatment alternative exists.
.
Notwithstanding the limitations and potential complications associated with flow diversion, it offers a promising new technique in the field of endovascular neurosurgery.
(ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 2005;366(9488):809-17
References Papers of special note have been highlighted as: . of interest .. of considerable interest 1.
Caranci F, Briganti F, Cirillo L, et al. Epidemiology and genetics of intracranial aneurysms. Eur J Radiol 2013;82(10): 1598-605
intracranial aneurysms. Neurosurgery 2008; 63(4):662-75 13.
Li MH, Li YD, Fang C, et al. Endovascular treatment of giant or very large intracranial aneurysms with different modalities: an analysis of 20 cases. Neuroradiology 2007;49(10):819-28
14.
Nakase H, Shin Y, Kanemoto Y, et al. Long-term outcome of unruptured giant cerebral aneurysms. Neurol Med Chir (Tokyo) 2006;46(8):379-86
15.
Nanda A, Sonig A, Banerjee AD, Javalkar VK. Microsurgical management of giant intracranial aneurysm: a single surgeon experience from Louisiana State University. Shreveport. World Neurosurg 2012;[Epub ahead of print]
.
Recent clinical trials demonstrating better survival and fewer poor outcomes of endovascular coiling when compared to surgical clipping in the treatment of intracranial aneurysms.
8.
Dandy WE. Intracranial aneurysm of the internal carotid artery: cured by operation. Ann Surg 1938;107(5):654-9
Raymond J, Guilbert F, Weill A, et al. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 2003;34(6):1398-403
9.
16.
Guglielmi G, Vinuela F, Dion J, Duckwiler G. Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: preliminary clinical experience. J Neurosurg 1991;75(1):8-14
International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms – risk of rupture and risks of surgical intervention. N Engl J Med 1998;339(24):1725-33
Colby GP, Paul AR, Radvany MG, et al. A single center comparison of coiling versus stent assisted coiling in 90 consecutive paraophthalmic region aneurysms. J Neurointerv Surg 2012;4(2):116-20
.
17.
5.
Guglielmi G. History of the genesis of detachable coils. A review. J Neurosurg 2009;111(1):1-8
First landmark trial describing risk of aneurysm rupture as it relates to aneurysm size and location.
10.
6.
McDougall CG, Spetzler RF, Zabramski JM, et al. The Barrow ruptured aneurysm trial. J Neurosurg 2012;116(1): 135-44
Biondi A, Jean B, Vivas E, et al. Giant and large peripheral cerebral aneurysms: etiopathologic considerations, endovascular treatment, and long-term follow-up. AJNR Am J Neuroradiol 2006;27(8):1685-92
Piotin M, Blanc R, Spelle L, et al. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 2010; 41(1):110-15
18.
.
Recent clinical trials demonstrating better survival and fewer poor outcomes of endovascular coiling when compared to surgical clipping in the treatment of intracranial aneurysms.
Aenis M, Stancampiano AP, Wakhloo AK, Lieber BB. Modeling of flow in a straight stented and nonstented side wall aneurysm model. J Biomech Eng 1997;119(2):206-12
19.
Hoi Y, Ionita CN, Tranquebar RV, et al. Flow modification in canine intracranial aneurysm model by an asymmetric stent: studies using digital subtraction angiography (DSA) and image-based computational fluid dynamics (CFD) analyses. Proc Soc Photo Opt Instrum Eng 2006;6143:61430J
2.
3.
4.
7.
Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 2012;43(6):1711-37
Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial
148
11.
12.
Hauck EF, Welch BG, White JA, et al. Stent/coil treatment of very large and giant unruptured ophthalmic and cavernous aneurysms. Surg Neurol 2009;71(1):19-24 Jahromi BS, Mocco J, Bang JA, et al. Clinical and angiographic outcome after endovascular management of giant
Expert Rev. Med. Devices 11(2), (2014)
The Pipeline embolization device for treatment of intracranial aneurysms
20.
Wakhloo AK, Schellhammer F, de Vries J, et al. Self-expanding and balloon-expandable stents in the treatment of carotid aneurysms: an experimental study in a canine model. AJNR Am J Neuroradiol 1994;15(3): 493-502
21.
Lawson MF, Newman WC, Chi YY, et al. Stent-associated flow remodeling causes further occlusion of incompletely coiled aneurysms. Neurosurgery 2011;69(3): 598-604
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
22.
23.
24.
25.
26.
Benndorf G, Herbon U, Sollmann WP, Campi A. Treatment of a ruptured dissecting vertebral artery aneurysm with double stent placement: case report. AJNR Am J Neuroradiol 2001;22(10):1844-8 Vanninen R, Manninen H, Ronkainen A. Broad-based intracranial aneurysms: thrombosis induced by stent placement. AJNR Am J Neuroradiol 2003;24(2):263-6 Wanke I, Forsting M. Stents for intracranial wide-necked aneurysms: more than mechanical protection. Neuroradiology 2008;50(12):991-8 Kim M, Levy EI, Meng H, Hopkins LN. Quantification of hemodynamic changes induced by virtual placement of multiple stents across a wide-necked basilar trunk aneurysm. Neurosurgery 2007;61(6): 1305-13 D’Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial aneurysms: a review. Stroke 2011;42(8): 2363-8
..
Excellent review of hemodynamic and structures properties of flow diverters.
27.
Liou TM, Li YC. Effects of stent porosity on hemodynamics in a sidewall aneurysm model. J Biomech 2008;41(6):1174-83
28.
29.
30.
31.
Kallmes DF, Ding YH, Dai D, et al. A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke 2007;38(8):2346-52 Kallmes DF, Ding YH, Dai D, et al. A second-generation, endoluminal, flow-disrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 2009;30(6):1153-8 Wong GK, Kwan MC, Ng RY, et al. Flow diverters for treatment of intracranial aneurysms: current status and ongoing clinical trials. J Clin Neurosci 2011;18(6): 737-40 Fiorella D, Lylyk P, Szikora I, et al. Curative cerebrovascular reconstruction with the Pipeline embolization device: the emergence of definitive endovascular therapy for intracranial aneurysms. J Neurointerv Surg 2009;1(1):56-65
informahealthcare.com
32.
Fiorella D, Woo HH, Albuquerque FC, Nelson PK. Definitive reconstruction of circumferential, fusiform intracranial aneurysms with the Pipeline embolization device. Neurosurgery 2008;62(5):1115-21
.
First clinical studies describing treatment outcomes with the Pipeline embolization device.
33.
Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013;267:858-68
..
First clinical studies describing treatment outcomes with the Pipeline embolization device.
34.
Lylyk P, Miranda C, Ceratto R, et al. Curative endovascular reconstruction of cerebral aneurysms with the Pipeline embolization device: the Buenos Aires experience. Neurosurgery 2009;64(4):632-43
..
35.
..
36.
First clinical studies describing treatment outcomes with the Pipeline embolization device. Nelson PK, Lylyk P, Szikora I, et al. The Pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 2011;32(1):34-40 First clinical studies describing treatment outcomes with the Pipeline embolization device. Szikora I, Berentei Z, Kulcsar Z, et al. Treatment of intracranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the Pipeline embolization device. AJNR Am J Neuroradiol 2010;31(6):1139-47
..
First clinical studies describing treatment outcomes with the Pipeline embolization device.
37.
Kan P, Siddiqui AH, Veznedaroglu E, et al. Early postmarket results after treatment of intracranial aneurysms with the Pipeline embolization device: a U.S. multicenter experience. Neurosurgery 2012;71(6):1080-8
38.
Saatci I, Yavuz K, Ozer C, et al. Treatment of intracranial aneurysms using the Pipeline flow-diverter embolization device: a single-center experience with long-term follow-up results. AJNR Am J Neuroradiol 2012;33(8):1436-46
Device Profile
40.
Briganti F, Napoli M, Tortora F, et al. Italian multicenter experience with flow-diverter devices for intracranial unruptured aneurysm treatment with periprocedural complications – a retrospective data analysis. Neuroradiology 2012;54(10):1145-52
.
Recent clinical studies documenting complications associated with the Pipeline embolization device.
41.
Piano M, Valvassori L, Quilici L, et al. Midterm and long-term follow-up of cerebral aneurysms treated with flow diverter devices: a single-center experience. J Neurosurg 2013;118(2):408-16
.
Recent clinical studies documenting complications associated with the Pipeline embolization device.
42.
Brinjikji W, Murad MH, Lanzino G, et al. Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis. Stroke 2013;44(2):442-7
..
Recent clinical studies documenting complications associated with the Pipeline embolization device.
43.
Leung GK, Tsang AC, Lui WM. Pipeline embolization device for intracranial aneurysm: a systematic review. Clin Neuroradiol 2012;22(4):295-303
..
Recent clinical studies documenting complications associated with the Pipeline embolization device.
44.
Lopes DK, Ringer AJ, Boulos AS, et al. Fate of branch arteries after intracranial stenting. Neurosurgery 2003;52(6):1275-9
45.
Wakhloo AK, Tio FO, Lieber BB, et al. Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response. AJNR Am J Neuroradiol 1995; 16(5):1043-51
46.
Puffer RC, Kallmes DF, Cloft HJ, Lanzino G. Patency of the ophthalmic artery after flow diversion treatment of paraclinoid aneurysms. J Neurosurg 2012; 116(4):892-6
47.
Siddiqui AH, Abla AA, Kan P, et al. Panacea or problem: flow diverters in the treatment of symptomatic large or giant fusiform vertebrobasilar aneurysms. J Neurosurg 2012;116(6):1258-66
39.
Arrese I, Sarabia R, Pintado R, Delgado-Rodriguez M. Flow-diverter devices for intracranial aneurysms: systematic review and meta-analysis. Neurosurgery 2013; 73(2):193-200
48.
Kulcsar Z, Houdart E, Bonafe A, et al. Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment. AJNR Am J Neuroradiol 2011;32(1):20-5
..
Recent clinical studies documenting complications associated with the Pipeline embolization device.
49.
Siddiqui AH, Kan P, Abla AA, et al. Complications after treatment with pipeline embolization for giant distal intracranial
149
Device Profile
Eller, Dumont, Sorkin et al.
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
aneurysms with or without coil embolization. Neurosurgery 2012;71(2): E509-13 50.
McAuliffe W, Wycoco V, Rice H, et al. Immediate and midterm results following treatment of unruptured intracranial aneurysms with the Pipeline embolization device. AJNR Am J Neuroradiol 2012; 33(1):164-70
51.
Berge J, Tourdias T, Moreau JF, et al. Perianeurysmal brain inflammation after flow-diversion treatment. AJNR Am J Neuroradiol 2011;32(10):1930-4
intracranial aneurysms in the anterior circulation: an outcome study. J Neurosurg 2008;109(6):1012-18 55.
Kattner KA, Bailes J, Fukushima T. Direct surgical management of large bulbous and giant aneurysms involving the paraclinoid segment of the internal carotid artery: report of 29 cases. Surg Neurol 1998;49(5):471-80
60.
Withers K, Carolan-Rees G, Dale M. device for the treatment of complex intracranial aneurysms: a NICE Medical Technology Guidance. Appl Health Econ Health Policy 2013;11(1):5-13
56.
Sughrue ME, Saloner D, Rayz VL, Lawton MT. Giant intracranial aneurysms: evolution of management in a contemporary surgical series. Neurosurgery 2011;69(6): 1261-71
.
A cost–benefit analysis of the Pipeline embolization device.
61.
Gao L, Hoi Y, Swartz DD, et al. Nascent aneurysm formation at the basilar terminus induced by hemodynamics. Stroke 2008; 39(7):2085-90
62.
Meng H, Xiang J, Liaw N. The role of hemodynamics in intracranial aneurysm initiation. Int Rev Thromb 2012;7:40-56
63.
Binning MJ, Orion D, Yashar P, et al. Use of the microangiographic fluoroscope for coiling of intracranial aneurysms. Neurosurgery 2011;69(5):1131-8
Drake CG, Peerless SJ. Giant fusiform intracranial aneurysms: review of 120 patients treated surgically from. 1965 to 1992. J Neurosurg 1997;87(2): 141-62
57.
53.
Gewirtz RJ, Awad IA. Giant aneurysms of the anterior circle of Willis: management outcome of open microsurgical treatment. Surg Neurol 1996;45(5):409-21
58.
Parkinson RJ, Eddleman CS, Batjer HH, Bendok BR. Giant intracranial aneurysms: endovascular challenges. Neurosurgery 2008; 62(6 Suppl 3):1336-45
54.
Hauck EF, Wohlfeld B, Welch BG, et al. Clipping of very large or giant unruptured
59.
Shankar JJ, Vandorpe R, Pickett G, Maloney W. SILK flow diverter for
52.
150
treatment of intracranial aneurysms: initial experience and cost analysis. J Neurointerv Surg 2013(5 Suppl 3):iii11-15
Velat GJ, Zabramski JM, Nakaji P, Spetzler RF. Surgical management of giant posterior communicating artery aneurysms. Neurosurgery 2012;71(1 Suppl Operative): 43-51
Expert Rev. Med. Devices 11(2), (2014)
The Pipeline embolization device for treatment of intracranial aneurysms Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Expert Rev. Med. Devices 11(2), 137–150 (2014)
Jorge L Eller1,5, Travis M Dumont1,5, Grant C Sorkin1,5, Maxim Mokin1,5, Elad I Levy1,2,4,5, Kenneth V Snyder1–5, L Nelson Hopkins1,2,4–6 and Adnan H Siddiqui*1,2,4–6 1 Department of Neurosurgery, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA 2 Department of Radiology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA 3 Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York Buffalo, NY, USA 4 Toshiba Stroke and Vascular Research Center, University at Buffalo, State University of New York, Buffalo, NY, USA 5 Department of Neurosurgery, Gates Vascular Institute, Kaleida Health, Buffalo, NY, USA 6 Jacobs Institute, Buffalo, NY, USA *Author for correspondence: Tel.: +1 716 218 1000 Fax: +1 716 859 7479 [email protected]
informahealthcare.com
Flow diversion is a new endovascular technique developed for treatment of intracranial aneurysms. It is based on stent-induced modification of blood flow within and around an aneurysm inflow zone, leading to gradual intra-aneurysmal thrombosis and subsequent atrophy, while preserving flow into the parent vessel and perforating branches. Flow-diversion technique is well-suited for the treatment of large, giant, wide-necked, and fusiform intracranial aneurysms because it does not rely on endosaccular packing with coils but rather on the strategy of placing a stent across the aneurysm “neck” or across the diseased segment of a vessel in case of a fusiform aneurysm. Over time, neointimal endothelium covers the flow diverter such that it becomes incorporated into the parent vessel wall and occludes the aneurysm from the circulation, effectively repairing the diseased parent vessel segment. This report describes in detail the Pipeline embolization device (ev3-Covidien, Irvine, California, USA), its mechanism of action and deployment technique, and reviews the pertinent literature regarding safety, efficacy and potential risks and complications associated with the use of this flow diverter. KEYWORDS: endovascular treatment . flow diversion . intracranial aneurysms . Pipeline embolization device
Intracranial aneurysms are acquired lesions with a prevalence of 5–10% estimated in the population [1]. Approximately 30,000 cases of subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms occur in the USA each year, leaving approximately 60% of victims dead or disabled [2]. The first surgical clipping of an intracranial aneurysm was performed by Walter Dandy in 1937 [3]. Developments in aneurysm surgery – including microsurgical techniques, new clip designs, development of brain protection, neuroanesthesia, neuromonitoring and bypass techniques – made surgical clipping the mainstay, time-tested treatment for intracranial aneurysms. In the early 1990s, the introduction of the Guglielmi detachable coil revolutionized the treatment of intracranial aneurysms by providing an endosaccular, endovascular alternative to surgical clipping [4], effectively paving the way for the new discipline of endovascular neurosurgery to emerge [5]. In the short timespan, since endovascular coiling has evolved to become the preferred treatment modality for most ruptured and unruptured intracranial aneurysms, with better survival and fewer poor outcomes in patients treated with
10.1586/17434440.2014.877188
this approach than with surgical clipping, as demonstrated by recent clinical trials [6,7]. The limitations of endovascular coiling, however, became apparent as time and experience accumulated. One of the main issues has been the long-term aneurysm occlusion rate, with significant numbers of aneurysms treated by coil embolization not angiographically cured at the time of mid-term follow-up assessment. For example, a single-center experience with 501 aneurysms treated endovascularly demonstrated a complete angiographic occlusion rate of only 38.3% at 1 year and, even after retreatment, approximately half the aneurysms required further intervention [8]. Additionally, the geometry of intracranial aneurysms determines the feasibility of effective treatment with endovascular coiling. Several adjunctive techniques and technologies have been advocated to improve angiographic and clinical outcomes associated with primary aneurysm coiling, including balloon-assisted coiling techniques, self-expanding intracranial stents for stent-assisted coiling and 3D, bioactive, and gel-coated coils. Despite these advancements, many aneurysms remain challenging to
2014 Informa UK Ltd
ISSN 1743-4440
137
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Device Profile
Eller, Dumont, Sorkin et al.
treat surgically or endovascularly, such as large (>10 mm diameter) and/or giant (>25 mm diameter), wide-necked (aneurysms with a dome-to-neck ratio of 4 mm), had unfavorable dome-to-neck ratios (25 mm diameter) [33]. One patient enrolled in the study could not have the parent artery catheterized; therefore, PED placement was not attempted. Three patients died on postoperative Days 4, 11 and 14, respectively. Of the remaining 104 patients alive at 6 months, 97 patients had follow-up angiography demonstrating 73.6% complete occlusion at 6 months without major stenosis or use of adjunctive coils. Six patients (5.6%) experienced major ipsilateral stroke or neurological death at 6 months, five patients developed intraparenchymal hemorrhages distant from the aneurysm site and five patients presented with delayed parent vessel occlusions at the 1-year follow-up assessment. On the basis of the results of this trial, the FDA granted the aforementioned premarket approval for the PED for the endovascular treatment of adults (age 22 years or older) with large or giant wide-necked intracranial aneurysms in the ICA from the petrous to the superior hypophyseal segments. We have published the early results of a multicenter experience following the release of the PED in the US market [37]. A total of 62 procedures were performed to treat 58 aneurysms with PEDs. On average, two PEDs were used per aneurysm. Six postdeployment angioplasties were performed for maldeployment (kinking, stenosis or torsion). The major permanent procedural complication rate was 8.5%. Six postprocedural ischemic events were noted, five of which were in the posterior circulation and only one was permanent. There were four postprocedural hemorrhagic events (6.9%): three delayed ruptures and one distal parenchymal hemorrhage, all of which were fatal. Follow-up angiograms at 3 months were available for 19 patients; the rate of complete occlusion was 68% (13 patients). Although limited and early, this result compared favorably with alternate techniques given that only 17% of the aneurysms treated were small (50% of the perforator orifice is compromised by the PED, despite the presence of a flow gradient [44,45]. Nevertheless, long-term clinical follow-up data are lacking on this issue. Puffer et al. [46] reported that up to 25% of ophthalmic arteries would undergo thrombosis when covered with the PED. This may be due to competitive collateral flow from the external carotid artery that prevents a pressure gradient from developing, leading to occlusion of the proximal ophthalmic artery when covered by the PED. The need to place more than one PED in an overlapping fashion to provide enough metal coverage at the neck of an aneurysm and therefore enough flow diversion to initiate aneurysm thrombosis and occlusion has to be tempered by the need to allow enough flow across the stent pores to maintain perforating branch vessel patency. This delicate balance may be relatively straightforward in the ICA circulation – specifically within the ICA segments for which the device was granted FDA approval, namely, from the petrous to the superior hypophyseal artery; however, in the perforator-rich vertebrobasilar system, the situation is fairly different. Siddiqui et al. [47] recently published a case series of large or giant fusiform vertebrobasilar aneurysms treated with flow diversion. Four of seven patients treated with PEDs died. Two of those deaths were due to devastating brainstem strokes and two to postprocedural aneurysm rupture and SAH. In those patients who experienced ischemic events, the deployment of multiple, overlapping PEDs may have led to occlusion of perforating vessel branches. One must proceed with great care when using the PED in the posterior circulation and certainly attempt to place the least number of devices needed to disrupt aneurysm flow, preferably with only single PED coverage of perforator-rich territories. The risk of thromboembolism leading to Pipeline device occlusion or late in-stent stenosis is also important to consider. Although relatively uncommon, these are potentially devastating complications. The rate of PED thrombosis or stenosis was 1.9% in the PUFS trial [33] and approximately 5% in the Buenos Aires series [34]. Notably, one of the first two patients to undergo PED treatment in the USA under compassionate use (described above) later presented with occlusion of the treated vertebral artery just a few days after his antiplatelet medication was discontinued by another physician [32]. This fact underscores the likely need for at least single agent lifelong antiplatelet therapy to counteract the PED’s thrombogenic potential. Conversely, the risk of acute thrombosis must be weighed against the risk of immediate and/or delayed aneurysm rupture and SAH. Because aneurysm thrombosis and eventual occlusion after PED treatment are a gradual process, the risk of aneurysm rupture exists during the latency period following PED deployment. In a review of five prospective series of aneurysms treated with PED, the incidence of hemorrhage after flow diversion was 2% [26]. The underlying mechanism is unclear; among different hypotheses raised to explain these ruptures are redirection of flow within an ‘unstable’ aneurysm or inflammatory changes related to formation of an intra-aneurysmal clot 144
burden, with subsequent mural destabilization and rupture [26,43]. Kulcsar et al. [48] published a review of 13 cases from 12 centers worldwide of delayed aneurysm hemorrhage following flow diversion with the SILK device. All patients in their review had aneurysms with characteristics pertaining to a high risk of rupture, such as large size, symptomatic aneurysms and high aspect ratio (>1.6). However, treatment of these lesions with flow diversion may have led to changes in intraaneurysmal flow patterns that favored the formation of autolytic, aggressive thrombus associated with the presence of a persistent inflow jet into the aneurysm, ultimately leading to degradation of the aneurysm wall and rupture. This work underscores how much is still unknown about the effects of flow diversion in an individual patient and how parent vessel geometry and aneurysm flow configuration may influence its final outcome. A small cases series of complications related to giant distal intracranial aneurysms treated with the PED was reported by Siddiqui et al. [49]. In this report, these authors describe one case of aneurysm rupture within 24 h of PED implantation and another case of acute thrombosis of the PED–parent vessel within 6 h of PED implantation. They suggest loose packing of coils within large and/or giant aneurysms to reduce the likelihood of postprocedural aneurysmal rupture and, at the same time, avoid the possibility that a dense coil mass may result in thrombosis and/or acute occlusion of the PED. Another hemorrhagic complication of flow diversion is the occurrence of nonaneurysm-related intracerebral hemorrhages adjacent or within the dependent territories of the treated aneurysm, sometimes in the contralateral hemisphere within the anterior cerebral artery territory. In a systematic review of the PED literature, Leung et al. [43] estimated an incidence of 1.6% for this particular complication. The underlying etiology of these hemorrhages could be related to hemorrhagic transformation of embolic infarctions related to complex manipulations with more robust access support and distal access catheters (especially in the face of dual antiplatelet therapy). Additionally, suggestions have been made that materials used to coat the microcatheters may be physically stripping and embolizing in the distal territories. Another hypothesis is that there are postflow diversion hemodynamic changes in the dependent vascular territory such as hyperperfusion syndrome. For example, after flow through a giant aneurysm that effectively functioned as a giant capacitance reservoir with relative dependent territory ischemia and chronic vasodilation is streamlined, breakthrough hemorrhage results because of disrupted autoregulation. Another hypothesis reflects that markedly increased metal surface area exposed to the blood stream in the intracranial circulation and the shear forces to which platelets are exposed when crossing the surface of the PED or traversing in and out of the PED result in platelet activation despite dual antiplatelet therapy, leading to embolic strokes with secondary hemorrhagic conversion. Mass effect-related symptoms are expected to subside once large and/or giant aneurysms regress after flow diversion Expert Rev. Med. Devices 11(2), (2014)
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
The Pipeline embolization device for treatment of intracranial aneurysms
Device Profile
therapy. However, there are reports of A B temporary worsening of mass effect symptoms immediately after PED implantation, likely secondary to an inflammatory cascade following aneurysm thrombosis. In the Buenos Aires cases series, Lylyk et al. [34] reported three cases of giant aneurysms causing cranial nerve palsies that worsened postoperatively. Similarly, in the series of unruptured aneurysms treated with the PED by McAuliffe et al. [50], neurological deficits in 3 of the 16 patients who presented with mass effect worsened after C D treatment, despite receiving steroids. These mass effect symptoms eventually improved over time once the inflammatory response subsided. Berge et al. [51] reported MRI findings of perianeurysmal changes in five of the seven patients with worsening mass effect symptoms following flow diversion. These aneurysms were large and embedded in brain parenchyma without interposition of cerebrospinal fluid. Therefore, despite lack of significant evidence, we routinely recommend starting patients who have giant aneurysms or present with mass effect on steroids and taper them off Figure 6. A 62-year-old woman presented with left-hand weakness. Diagnostic steroid use slowly over 3 to 4 weeks. angiogram reveals a giant right internal carotid artery fusiform aneurysm: (A) right ICA Finally, another issue to be kept in injection, anteroposterior view; (B) 3D reconstruction demonstrates complex right ICA mind is that the PED’s mechanism of fusiform aneurysm; (C) three Pipeline devices were placed in overlapping fashion, action relies on its apposition against the covering the entire diseased segment of the right ICA; (D) Two-month follow-up angiogram shows complete involution of the aneurysm and normal right ICA anatomy. vessel wall to direct flow away from the aneurysm. Therefore, aneurysms previously treated by means of stent-assisted coiling will be less ame- rates approach 30% [52–57], despite the development of skull nable to flow diversion therapy. In the series of Lylyk et al. [34], base approaches and surgical bypass strategies. Thus far, tradithe only aneurysm that remained patent at 12 months post- tional endovascular techniques have been unable to provide a PED implantation had been previously treated with stent- much better alternative for these lesions, with aneurysm occluassisted coiling. Therefore, the efficacy of the PED may be sion rates of only 57% and mortality rates varying between somewhat limited in cases of previously stented or stent-coiled 7.7 [58] and 11% [10–12]. Considering the poor natural history of giant aneurysms – 5-year cumulative rupture rates of 40% aneurysms. in the anterior circulation and 50% in the posterior circulation [9] – the search for alternative means of treatment Cost–effectiveness, alternative devices and/or becomes even more pressing. technology Despite the limitations and uncertainties described in the Alternatives to flow diversion treatment of large and/or giant, wide-necked and fusiform aneurysms include both surgical and preceding section, flow diversion appears to provide many endovascular options. From a surgical perspective, the options advantages in the management of large and/or giant intracranial are clipping, trapping, proximal (Hunterian) and/or distal par- aneurysms compared with surgical clipping and traditional ent vessel occlusion and wrapping, all of which are potentially endovascular options. Flow diversion aims at reconstructing the associated with the need for surgical bypass. From an endovas- diseased parent vessel segment and providing a scaffold for neocular perspective, one may find primary coiling, balloon- intimal growth and complete obliteration of the aneurysm, assisted coiling or stent-assisted coiling as viable options. How- regardless of the aneurysm fundus size or neck size, as opposed ever, all these alternative techniques fall short in providing an to traditional coiling strategies where these variables dictate the likelihood of success or failure and the risks and complications optimal solution to these challenging lesions. In the particular scenario of giant aneurysms, surgical mor- involved. As such, flow diversion seems particularly well suited tality rates remain as high as 10%, whereas surgical morbidity to treat these most complex aneurysms, with excellent occlusion informahealthcare.com
145
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Device Profile
Eller, Dumont, Sorkin et al.
rates and acceptable morbidity and mortality rates (FIGURE 6), as described above. Preliminary cost analyses of flow diversion so far have indicated that this treatment modality compares favorably with traditional endovascular stent-assisted coiling [59]; although in one study, it would become cost saving only in patients who would otherwise require treatment with 32 coils or more [60]. We expect that as other flow diversion strategies are introduced to the market place, such as the FRED and Surpass, the cost of each device will progressively decline. We similarly expect subsequent generations of these devices to perform in a safer and more effective fashion, bringing these previously poorly treated or untreated aneurysms into conformity with the current high standards of endovascular or microsurgical aneurysm treatment. Expert commentary
Our understanding of the pathogenesis of intracranial aneurysms continues to evolve. We have developed a hemodynamic model of aneurysmal genesis, which results from bilateral ligation of rabbit carotid arteries forcing rapid changes in the rabbit basilar artery including tortuosity, hypertrophy, fusiformal dilatation and a basilar terminus aneurysm [19,61]. These are not the first reports of a hemodynamic relationship, but clinically it has been well recognized, such as in the instance of previous carotid ligation and with flow-related aneurysms associated with arteriovenous malformations. This is not to discount intrinsic factors, such as family history, genetics and environmental exposures (such as cigarette smoking), all of which work to lower the threshold of hemodynamic insult [62]. Compared with all previous endovascular or microsurgical solutions, flow diversion attempts to address the affected vessel segment in its entirety. Buttressing the vessel walls with a microfilament-braided mesh allows for growth of endothelium across the aneurysmal ostium, regardless of its shape, size or configuration. We have recognized from previous angiographic endovascular cures that this endothelial separation of the parent vessel lumen and aneurysm is the ultimate cure that we seek. Flow diversion affords this most reliably for the more difficult to treat aneurysms. However, this paradigm shift comes with its own set of challenges and complications. We are encountering delayed aneurysmal rupture on a low but regular basis. We are encountering distal parenchymal hemorrhages at a low but steady rate. Although we have detailed some speculative hypotheses above, quite frankly, we do not have any clarity in terms of the pathogenesis for either of these devastating complications. It would be interesting to see if the newer flow diverters, such as Surpass or FRED, are also associated with these phenomena. If they are not, then these events may be more related to the nuances of the construct or delivery of the PED. Conversely (and more likely), if these devices are associated with similar complications, then they may reflect the underlying inherent conflict associated with superlative flow diversion cures, with a small but clear propensity for devastating hemorrhagic complications. Although both complications are hemorrhagic, they likely reflect differing mechanisms. We feel that the delayed ruptures 146
fall into two categories based on timing, early or late. Early ruptures likely reflect hemodynamic alterations, such as a repositioned flow-vector ‘jet’ following PED placement or an endoleak-type phenomenon with a ball valve effect in which the rate of incoming and outgoing flow is slightly mismatched and overwhelms aneurysm wall elasticity. Delayed ruptures likely reflect a balance between complete aneurysm thrombosis (preventing any further flow within the aneurysm and sealed by endothelial overgrowth across the aneurysm ostium) versus thrombosis-mediated inflammatory disruption of the aneurysmal wall (in the presence of persistent – even limited – aneurysmal flow), leading to rupture. Distal parenchymal hemorrhages appear to be either hemorrhagic transformations of embolic events or hyperperfusiontype breakdown of circulatory autoregulation post-PED placement. There is some empiric association with either under- or over-responsiveness to clopidogrel response testing. This remains entirely unproven but has caused us to be extremely responsive to results on the P2Y12 assays by titrating underresponse with additional or alternate medications and overresponse with dose reduction. The other new element introduced by PEDs is the need for more complex access supportive devices. We are routinely using larger guides and more complex intermediate catheters to deliver these devices reliably. The effect of these additional developments on complications from these procedures remains unclear. Although the pertinent literature documents several limitations associated with flow diversion at present – such as reduced efficacy in previously treated aneurysms, need for dual antiplatelet therapy (which poses a problem for treatment of ruptured aneurysms or in patients who are noncompliant) and inability to treat distal and/or bifurcation aneurysms (such as MCA bifurcation or anterior communicating artery aneurysms) – as well as clear risks (such as delayed aneurysm rupture, thromboembolic complications, nonaneurysm-related intracranial hemorrhage and worsening of mass effect symptoms), flow diversion represents a paradigm shift in the treatment of intracranial aneurysms. Recently, Szikora presented the preliminary results from the IntrePED registry at the Leipzig Interventional Course Conference, Paris France (11–13 June 2013), which included consecutive patients enrolled at 17 sites in 6 countries. A total of 906 aneurysms of all types and locations were treated in 793 patients with 88% of patients having a follow-up of >12 months. In this highly heterogeneous group, these results included delayed rupture in nine patients (1%), intracerebral hemorrhage in 1.6%, ischemic stroke in 6.5%, in-stent stenosis in 1.5%, permanent cranial neuropathy in 0.3% and all-cause mortality in 4.1%. All-cause morbidity–mortality was 8.2%. Delayed ruptures and intraparenchymal hemorrhages were much more common in large and giant aneurysms. Although this data set needs to undergo peer review, it reflects the growing volume of experience, which as with any new technology, improves with operator experience and understanding of pitfalls, strategies and indications with time. Expert Rev. Med. Devices 11(2), (2014)
The Pipeline embolization device for treatment of intracranial aneurysms
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
Five-year view
The PED is a first-generation flow diverter intended for treatment of the most challenging intracranial aneurysms. Many of the problems and limitations encountered with this device will certainly be solved by further refinements and developments of this technology. For instance, deployment of the PED can sometimes be challenging, given the difficulty in navigating a relatively stiff device (especially the longer PEDs) through tortuous anatomy and the significant foreshortening of the device once deployed. It is expected that the next iterations of this device will have a much easier and predictable deployment system, minimizing the likelihood of maldeployment and the need for multiple devices. New iterations of the PED are being developed to counter some of the deployment issues noted above. In addition, newer devices such as the FRED are made of nitinol and therefore behave much more like laser cut stents with markedly less foreshortening. The next question will be whether the preciseness of delivery will take away from the success of the braided design. Additional strategies may be using coated stents to reduce or eliminate the need for dual antiplatelet therapy, thereby opening options for ruptured aneurysms. The question remains whether that will alter the rate of distal parenchymal hemorrhages. Moreover, it is likely that the science of flow diversion will evolve, with computational flow dynamic simulations and in vivo laboratory experiments shining light into the mechanisms of delayed aneurysm rupture, nonaneurysm-related intracerebral hemorrhage and the relationship of a particular aneurysm inflow zone and the application of flow diversion to its respective parent vessel. Once these relationships are well understood, it will be possible to predict aneurysm behavior as related to particular changes in flow brought about by a specific flow diverter device and therefore minimize or avoid altogether the occurrence of the aforementioned complications. There is the possibility that if we can design asymmetric stents with a particular surface acting as a flow diverter, then we could avoid perforator-related complications. However, we currently do not have fluoroscopic abilities to fully harness design modifications that would allow us to reliably deploy directional stents. Microangiographic fluoroscopy may hold the key to such strategies [63]. Following the same line of reasoning, the need for adjunctive aneurysm coiling together with PED implantation will also be better understood and its effects predicted in flow dynamic simulations, making the utilization of devices such as the PED safer and associated outcomes more predictable. The inflammatory reaction associated with intra-aneurysmal thrombosis will also be better understood, leading to proper management strategies to avoid degradation of the aneurysm wall and rupture as well as minimization of mass effect symptoms. Also, further refinements in the device will likely minimize the risk of perforating vessel occlusion and the incidence of thromboembolic complications, making this device safer and effective in treating posterior circulation aneurysms as well. As further experience is gained worldwide with the utilization of the PED in the treatment of various types of aneurysms informahealthcare.com
Device Profile
and the device itself is further refined and developed by industry, it is likely that flow diverters will have an ever-widening range of applications including the treatment of ruptured aneurysms, blister aneurysms, dissecting aneurysms, perforatorrich territory aneurysms and bifurcation aneurysms. Acknowledgements
The authors thank N Aronoff, MLS, at the Kaleida Health Libraries for providing literature search and reference retrieval assistances and PH Dressel, BFA, for assistance with preparation of the illustrations and DJ Zimmer for editorial assistance (both at University at Buffalo Neurosurgery). Financial & competing interests disclosure
TM Dumont, JL Eller and GC Sorkin report no financial relationships. LN Hopkins receives grant/research support from Toshiba; serves as a consultant to Abbott, Boston Scientific, Cordis, Micrus and Silk Road; holds financial interests in AccessClosure, Augmenix, Boston Scientific, Claret Medical, Endomation, Micrus and Valor Medical; holds a board/trustee/ officer position with Access Closure and Claret Medical; serves on Abbott Vascular’s speakers’ bureau; and has received honoraria from Bard, Boston Scientific, Cleveland Clinic, Complete Conference Management, Cordis, Memorial Health Care System and the Society for Cardiovascular Angiography and Interventions (SCAI). EI Levy receives research grant support, other research support (devices) and honoraria from Boston Scientific and research support from Codman & Shurtleff, Inc. and ev3/Covidien Vascular Therapies; has ownership interests in Intratech Medical Ltd. and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman & Shurtleff, Inc.; serves as a consultant per project and/or per hour for Codman & Shurtleff, Inc., ev3/Covidien Vascular Therapies and TheraSyn Sensors, Inc.; and receives fees for carotid stent training from Abbott Vascular and ev3/Covidien Vascular Therapies. EI Levy receives no consulting salary arrangements. All consulting is per project and/or per hour. M Mokin has received an educational grant from Toshiba. AH Siddiqui has received research grants from the National Institutes of Health (co-investigator: NINDS 1R01NS064592-01A1; not related to present device review) and the University at Buffalo (Research Development Award); holds financial interests in Hotspur, Intratech Medical, StimSox, Valor Medical and Blockade Medical; serves as a consultant to Codman & Shurtleff, Inc., Concentric Medical, Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Inc., Stryker Neurovascular and Pulsar Vascular; belongs to the speakers’ bureaus of Codman & Shurtleff, Inc. and Genentech; serves on National Steering Committees for Penumbra, Inc. 3D Separator Trial and Covidien SWIFT PRIME Trial; serves on an advisory board for Codman & Shurtleff and Covidien Vascular Therapies; and has received honoraria from American Association of Neurological Surgeons’ courses, Annual Peripheral Angioplasty and All That Jazz Course, Penumbra, Inc. and from Abbott Vascular and Codman & Shurtleff, Inc. for training other neurointerventionists in carotid stenting and for training physicians in endovascular stenting for aneurysms. AH Siddiqui receives no consulting salary arrangements. All consulting is per project and/or per hour. KV Snyder serves as a consultant and a member of the speakers’ bureau for Toshiba and has received honoraria from Toshiba. He serves as a member of the speakers’ bureau for and has received honoraria from ev3 and The Stroke Group. 147
Device Profile
Eller, Dumont, Sorkin et al.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Key issues .
Endovascular coiling, with or without balloon or stent assistance, has become the preferred treatment modality for most intracranial aneurysms.
.
Large, giant, wide-necked and fusiform intracranial aneurysms remain particularly challenging, with low aneurysm occlusion rates and significant morbidity and mortality associated with surgical or endovascular treatment.
.
Flow diversion represents a paradigm change in endovascular aneurysm treatment, whereby the diseased segment of the parent vessel is reconstituted with a high metal, low-porosity stent that diverts flow away from the aneurysm, leading to aneurysm thrombosis, shrink-
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
age and neointimal parent vessel remodeling. .
Because flow diversion does not rely on endosaccular filling of the aneurysm with coils, the size of the aneurysm sac or neck is less relevant to its effectiveness; therefore, it seems a well-suited technique for the treatment of large, giant or fusiform aneurysms for which no optimal treatment alternative exists.
.
Notwithstanding the limitations and potential complications associated with flow diversion, it offers a promising new technique in the field of endovascular neurosurgery.
(ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 2005;366(9488):809-17
References Papers of special note have been highlighted as: . of interest .. of considerable interest 1.
Caranci F, Briganti F, Cirillo L, et al. Epidemiology and genetics of intracranial aneurysms. Eur J Radiol 2013;82(10): 1598-605
intracranial aneurysms. Neurosurgery 2008; 63(4):662-75 13.
Li MH, Li YD, Fang C, et al. Endovascular treatment of giant or very large intracranial aneurysms with different modalities: an analysis of 20 cases. Neuroradiology 2007;49(10):819-28
14.
Nakase H, Shin Y, Kanemoto Y, et al. Long-term outcome of unruptured giant cerebral aneurysms. Neurol Med Chir (Tokyo) 2006;46(8):379-86
15.
Nanda A, Sonig A, Banerjee AD, Javalkar VK. Microsurgical management of giant intracranial aneurysm: a single surgeon experience from Louisiana State University. Shreveport. World Neurosurg 2012;[Epub ahead of print]
.
Recent clinical trials demonstrating better survival and fewer poor outcomes of endovascular coiling when compared to surgical clipping in the treatment of intracranial aneurysms.
8.
Dandy WE. Intracranial aneurysm of the internal carotid artery: cured by operation. Ann Surg 1938;107(5):654-9
Raymond J, Guilbert F, Weill A, et al. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 2003;34(6):1398-403
9.
16.
Guglielmi G, Vinuela F, Dion J, Duckwiler G. Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: preliminary clinical experience. J Neurosurg 1991;75(1):8-14
International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms – risk of rupture and risks of surgical intervention. N Engl J Med 1998;339(24):1725-33
Colby GP, Paul AR, Radvany MG, et al. A single center comparison of coiling versus stent assisted coiling in 90 consecutive paraophthalmic region aneurysms. J Neurointerv Surg 2012;4(2):116-20
.
17.
5.
Guglielmi G. History of the genesis of detachable coils. A review. J Neurosurg 2009;111(1):1-8
First landmark trial describing risk of aneurysm rupture as it relates to aneurysm size and location.
10.
6.
McDougall CG, Spetzler RF, Zabramski JM, et al. The Barrow ruptured aneurysm trial. J Neurosurg 2012;116(1): 135-44
Biondi A, Jean B, Vivas E, et al. Giant and large peripheral cerebral aneurysms: etiopathologic considerations, endovascular treatment, and long-term follow-up. AJNR Am J Neuroradiol 2006;27(8):1685-92
Piotin M, Blanc R, Spelle L, et al. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 2010; 41(1):110-15
18.
.
Recent clinical trials demonstrating better survival and fewer poor outcomes of endovascular coiling when compared to surgical clipping in the treatment of intracranial aneurysms.
Aenis M, Stancampiano AP, Wakhloo AK, Lieber BB. Modeling of flow in a straight stented and nonstented side wall aneurysm model. J Biomech Eng 1997;119(2):206-12
19.
Hoi Y, Ionita CN, Tranquebar RV, et al. Flow modification in canine intracranial aneurysm model by an asymmetric stent: studies using digital subtraction angiography (DSA) and image-based computational fluid dynamics (CFD) analyses. Proc Soc Photo Opt Instrum Eng 2006;6143:61430J
2.
3.
4.
7.
Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 2012;43(6):1711-37
Molyneux AJ, Kerr RS, Yu LM, et al. International subarachnoid aneurysm trial
148
11.
12.
Hauck EF, Welch BG, White JA, et al. Stent/coil treatment of very large and giant unruptured ophthalmic and cavernous aneurysms. Surg Neurol 2009;71(1):19-24 Jahromi BS, Mocco J, Bang JA, et al. Clinical and angiographic outcome after endovascular management of giant
Expert Rev. Med. Devices 11(2), (2014)
The Pipeline embolization device for treatment of intracranial aneurysms
20.
Wakhloo AK, Schellhammer F, de Vries J, et al. Self-expanding and balloon-expandable stents in the treatment of carotid aneurysms: an experimental study in a canine model. AJNR Am J Neuroradiol 1994;15(3): 493-502
21.
Lawson MF, Newman WC, Chi YY, et al. Stent-associated flow remodeling causes further occlusion of incompletely coiled aneurysms. Neurosurgery 2011;69(3): 598-604
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
22.
23.
24.
25.
26.
Benndorf G, Herbon U, Sollmann WP, Campi A. Treatment of a ruptured dissecting vertebral artery aneurysm with double stent placement: case report. AJNR Am J Neuroradiol 2001;22(10):1844-8 Vanninen R, Manninen H, Ronkainen A. Broad-based intracranial aneurysms: thrombosis induced by stent placement. AJNR Am J Neuroradiol 2003;24(2):263-6 Wanke I, Forsting M. Stents for intracranial wide-necked aneurysms: more than mechanical protection. Neuroradiology 2008;50(12):991-8 Kim M, Levy EI, Meng H, Hopkins LN. Quantification of hemodynamic changes induced by virtual placement of multiple stents across a wide-necked basilar trunk aneurysm. Neurosurgery 2007;61(6): 1305-13 D’Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial aneurysms: a review. Stroke 2011;42(8): 2363-8
..
Excellent review of hemodynamic and structures properties of flow diverters.
27.
Liou TM, Li YC. Effects of stent porosity on hemodynamics in a sidewall aneurysm model. J Biomech 2008;41(6):1174-83
28.
29.
30.
31.
Kallmes DF, Ding YH, Dai D, et al. A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke 2007;38(8):2346-52 Kallmes DF, Ding YH, Dai D, et al. A second-generation, endoluminal, flow-disrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 2009;30(6):1153-8 Wong GK, Kwan MC, Ng RY, et al. Flow diverters for treatment of intracranial aneurysms: current status and ongoing clinical trials. J Clin Neurosci 2011;18(6): 737-40 Fiorella D, Lylyk P, Szikora I, et al. Curative cerebrovascular reconstruction with the Pipeline embolization device: the emergence of definitive endovascular therapy for intracranial aneurysms. J Neurointerv Surg 2009;1(1):56-65
informahealthcare.com
32.
Fiorella D, Woo HH, Albuquerque FC, Nelson PK. Definitive reconstruction of circumferential, fusiform intracranial aneurysms with the Pipeline embolization device. Neurosurgery 2008;62(5):1115-21
.
First clinical studies describing treatment outcomes with the Pipeline embolization device.
33.
Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013;267:858-68
..
First clinical studies describing treatment outcomes with the Pipeline embolization device.
34.
Lylyk P, Miranda C, Ceratto R, et al. Curative endovascular reconstruction of cerebral aneurysms with the Pipeline embolization device: the Buenos Aires experience. Neurosurgery 2009;64(4):632-43
..
35.
..
36.
First clinical studies describing treatment outcomes with the Pipeline embolization device. Nelson PK, Lylyk P, Szikora I, et al. The Pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 2011;32(1):34-40 First clinical studies describing treatment outcomes with the Pipeline embolization device. Szikora I, Berentei Z, Kulcsar Z, et al. Treatment of intracranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the Pipeline embolization device. AJNR Am J Neuroradiol 2010;31(6):1139-47
..
First clinical studies describing treatment outcomes with the Pipeline embolization device.
37.
Kan P, Siddiqui AH, Veznedaroglu E, et al. Early postmarket results after treatment of intracranial aneurysms with the Pipeline embolization device: a U.S. multicenter experience. Neurosurgery 2012;71(6):1080-8
38.
Saatci I, Yavuz K, Ozer C, et al. Treatment of intracranial aneurysms using the Pipeline flow-diverter embolization device: a single-center experience with long-term follow-up results. AJNR Am J Neuroradiol 2012;33(8):1436-46
Device Profile
40.
Briganti F, Napoli M, Tortora F, et al. Italian multicenter experience with flow-diverter devices for intracranial unruptured aneurysm treatment with periprocedural complications – a retrospective data analysis. Neuroradiology 2012;54(10):1145-52
.
Recent clinical studies documenting complications associated with the Pipeline embolization device.
41.
Piano M, Valvassori L, Quilici L, et al. Midterm and long-term follow-up of cerebral aneurysms treated with flow diverter devices: a single-center experience. J Neurosurg 2013;118(2):408-16
.
Recent clinical studies documenting complications associated with the Pipeline embolization device.
42.
Brinjikji W, Murad MH, Lanzino G, et al. Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis. Stroke 2013;44(2):442-7
..
Recent clinical studies documenting complications associated with the Pipeline embolization device.
43.
Leung GK, Tsang AC, Lui WM. Pipeline embolization device for intracranial aneurysm: a systematic review. Clin Neuroradiol 2012;22(4):295-303
..
Recent clinical studies documenting complications associated with the Pipeline embolization device.
44.
Lopes DK, Ringer AJ, Boulos AS, et al. Fate of branch arteries after intracranial stenting. Neurosurgery 2003;52(6):1275-9
45.
Wakhloo AK, Tio FO, Lieber BB, et al. Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response. AJNR Am J Neuroradiol 1995; 16(5):1043-51
46.
Puffer RC, Kallmes DF, Cloft HJ, Lanzino G. Patency of the ophthalmic artery after flow diversion treatment of paraclinoid aneurysms. J Neurosurg 2012; 116(4):892-6
47.
Siddiqui AH, Abla AA, Kan P, et al. Panacea or problem: flow diverters in the treatment of symptomatic large or giant fusiform vertebrobasilar aneurysms. J Neurosurg 2012;116(6):1258-66
39.
Arrese I, Sarabia R, Pintado R, Delgado-Rodriguez M. Flow-diverter devices for intracranial aneurysms: systematic review and meta-analysis. Neurosurgery 2013; 73(2):193-200
48.
Kulcsar Z, Houdart E, Bonafe A, et al. Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment. AJNR Am J Neuroradiol 2011;32(1):20-5
..
Recent clinical studies documenting complications associated with the Pipeline embolization device.
49.
Siddiqui AH, Kan P, Abla AA, et al. Complications after treatment with pipeline embolization for giant distal intracranial
149
Device Profile
Eller, Dumont, Sorkin et al.
Expert Review of Medical Devices 2014.11:137-150. Downloaded from informahealthcare.com by Emory University on 04/21/15. For personal use only.
aneurysms with or without coil embolization. Neurosurgery 2012;71(2): E509-13 50.
McAuliffe W, Wycoco V, Rice H, et al. Immediate and midterm results following treatment of unruptured intracranial aneurysms with the Pipeline embolization device. AJNR Am J Neuroradiol 2012; 33(1):164-70
51.
Berge J, Tourdias T, Moreau JF, et al. Perianeurysmal brain inflammation after flow-diversion treatment. AJNR Am J Neuroradiol 2011;32(10):1930-4
intracranial aneurysms in the anterior circulation: an outcome study. J Neurosurg 2008;109(6):1012-18 55.
Kattner KA, Bailes J, Fukushima T. Direct surgical management of large bulbous and giant aneurysms involving the paraclinoid segment of the internal carotid artery: report of 29 cases. Surg Neurol 1998;49(5):471-80
60.
Withers K, Carolan-Rees G, Dale M. device for the treatment of complex intracranial aneurysms: a NICE Medical Technology Guidance. Appl Health Econ Health Policy 2013;11(1):5-13
56.
Sughrue ME, Saloner D, Rayz VL, Lawton MT. Giant intracranial aneurysms: evolution of management in a contemporary surgical series. Neurosurgery 2011;69(6): 1261-71
.
A cost–benefit analysis of the Pipeline embolization device.
61.
Gao L, Hoi Y, Swartz DD, et al. Nascent aneurysm formation at the basilar terminus induced by hemodynamics. Stroke 2008; 39(7):2085-90
62.
Meng H, Xiang J, Liaw N. The role of hemodynamics in intracranial aneurysm initiation. Int Rev Thromb 2012;7:40-56
63.
Binning MJ, Orion D, Yashar P, et al. Use of the microangiographic fluoroscope for coiling of intracranial aneurysms. Neurosurgery 2011;69(5):1131-8
Drake CG, Peerless SJ. Giant fusiform intracranial aneurysms: review of 120 patients treated surgically from. 1965 to 1992. J Neurosurg 1997;87(2): 141-62
57.
53.
Gewirtz RJ, Awad IA. Giant aneurysms of the anterior circle of Willis: management outcome of open microsurgical treatment. Surg Neurol 1996;45(5):409-21
58.
Parkinson RJ, Eddleman CS, Batjer HH, Bendok BR. Giant intracranial aneurysms: endovascular challenges. Neurosurgery 2008; 62(6 Suppl 3):1336-45
54.
Hauck EF, Wohlfeld B, Welch BG, et al. Clipping of very large or giant unruptured
59.
Shankar JJ, Vandorpe R, Pickett G, Maloney W. SILK flow diverter for
52.
150
treatment of intracranial aneurysms: initial experience and cost analysis. J Neurointerv Surg 2013(5 Suppl 3):iii11-15
Velat GJ, Zabramski JM, Nakaji P, Spetzler RF. Surgical management of giant posterior communicating artery aneurysms. Neurosurgery 2012;71(1 Suppl Operative): 43-51
Expert Rev. Med. Devices 11(2), (2014)
