Flow-diverting stents (FDS) are a commonly used, minimally invasive option for difficult-to-treat aneurysms. In particular, FDS excel in addressing aneurysms that are not amenable to coiling because of their size or morphology,¹ and their utility for the treatment of pathologies such as blister, iatrogenic, and dissecting pseudoaneurysms has been documented.^2–5 A key limitation is the requirement for dual antiplatelet therapy (DAPT), which is particularly problematic in the setting of ruptured lesions. The development of novel surface modifications to improve the safety of FDS may represent a significant step forward for the treatment of these pathologies in patients who present with aneurysm rupture.

Pseudoaneurysms of the internal carotid artery (ICA) encompass a number of different subtypes of aneurysms with manifold etiologies: the common thread of these "false" aneurysms is that the aneurysm wall lacks the typical histological architecture. ICA blister aneurysms are relatively rare lesions, comprising approximately 6% of all aneurysms.⁶ They pose unique challenges in treatment given that the aneurysm wall lacks intima and media and consists only of a thin layer of adventitia.^7,8 Iatrogenic pseudoaneurysms, which are most often seen in the setting of direct injury from surgery, share a similar histological architecture. Dissecting pseudoaneurysms, which occur particularly in the setting of subadventitial dissections, may occur spontaneously or in a traumatic setting.⁹ Open microsurgical treatments for these pathologies, including clip wrapping, vessel sacrifice, and bypass, can be technically challenging and, particularly in the case of rupture, may result in unsatisfactory outcomes.¹⁰ Endovascular treatment can involve vessel deconstruction via parent vessel sacrifice; on the other hand, vessel preservation strategies including coil embolization of the target aneurysm can be difficult because of the thin aneurysmal wall and wide neck, imparting a high risk for aneurysm perforation.¹¹ FDS do not require intrasaccular manipulation, making them an excellent option for the treatment of blister, iatrogenic, and dissecting pseudoaneurysms.² In the context of ruptured pathology, however, patients may require CSF diversion with an external ventricular drain (EVD) or eventually need long-term airway or enteral access via tracheostomy or gastrostomy tube placement, which may be further complicated by DAPT.

The Pipeline Flex embolization device with Shield technology (PED-Shield) (Medtronic) has a phosphorylcholine surface modification that results in lower material thrombogenicity in vitro.¹² Subsequent ex vivo experiments that used an established nonhuman primate arteriovenous shunt model of stent thrombosis also demonstrated less platelet deposition and a decrement in fibrin deposition.¹³ However, since its approval for use by the U.S. Food and Drug Administration in June 2021, larger studies have yet to be conducted that examine the efficacy and outcomes of patients treated with PED-Shield in the context of ruptured pathology. Here, we have described a modern, multicenter experience with the use of PED-Shield for the treatment of 33 patients who presented with ruptured ICA pseudoaneurysms and report on the safety, efficacy, and clinical and radiographic outcomes.

Methods

Results

Discussion

Despite the advancement of endovascular technologies, ruptured blister, iatrogenic, and dissecting pseudoaneurysms have persistently posed a challenge given their wide neck, friable nature, and resulting propensity for rerupture and recurrence.⁶ For example, Park et al.¹⁴ described a series of 4 patients in whom blister ICA aneurysms were treated with coil embolization. All 4 demonstrated recurrence on follow-up imaging, and 2 experienced rebleeding.¹⁴ FDS are intended to bypass this issue by avoiding intrasaccular manipulation and the consequent potential for vessel perforation. The small pore size of FDS results in a decrement of blood flow into the target aneurysm and, moreover, provides a scaffold for neointimal growth.¹⁵ Thus, after FDS placement, the vessel undergoes structural remodeling, thereby excluding the aneurysm from flow and leading to thrombosis.¹⁵ However, the inherent thrombogenicity of FDS requires the patient to be placed on potent antiplatelet therapies to avoid thromboembolic complications.

The need for DAPT poses a challenge in the context of ruptured aneurysms, especially among patients who require placement of an EVD. This is particularly pertinent given that, in the presented series, 27 patients (81.8%) underwent EVD placement and 5 EVD-related complications occurred. Two of these 5 events consisted of intraparenchymal hemorrhages, with one requiring placement of a contralateral EVD and the other resulting in death. The other 3 events also required EVD replacement, which poses a significantly increased risk of hemorrhage in a patient on DAPT.¹⁶ Although fraught with similar challenges involving removal and replacement on DAPT, lumbar drain placement may serve as an alternative and possibly safer option for CSF drainage. Klimo et al.¹⁷ compared a series of 81 patients with thick cisternal hemorrhage after aneurysm rupture who underwent lumbar drain placement with 86 who did not. Patients who underwent lumbar drain placement had less vasospasm and associated ischemic injury, as well as greater frequency of discharge home and better Glasgow Outcome Scale score at 1- to 3-month follow-up. Elevated intracranial pressure (ICP) is a known sequela of aneurysmal subarachnoid hemorrhage that results in decreased cerebral perfusion and possibly herniation events if left untreated.¹⁸ The necessity of ICP monitoring is therefore apparent, and studies have been conducted to compare EVDs and parenchymal probes for monitoring. Baggiani et al.¹⁹ reported a multicenter prospective series of 423 patients with aneurysmal subarachnoid hemorrhage, of whom 295 (69.7%) underwent ICP monitoring. EVDs were used in 157 cases (54.9%), whereas parenchymal probes were used in 124 cases (43.4%). Patients treated with EVDs demonstrated a lower frequency of ICP spikes compared with those treated with parenchymal probes, and ICP monitor use was associated with significantly better overall outcomes at 6-month follow-up in critically ill patients.¹⁹ Although parenchymal ICP monitors are smaller in caliber than EVDs, their replacement and removal in the context of DAPT would likely have similar potential for hemorrhagic complication.

The compound phosphorylcholine is found on cell membranes²⁰ and has been used as a synthetic coating for coronary artery stents. With the objective of minimizing the thrombogenicity of FDS, the phosphorylcholine surface modification of the PED-Shield may decrease the potential for thromboembolic complications. In vitro studies have demonstrated that platelets and fibrinogen bind significantly less to materials coated with phosphorylcholine compared with those without, a principle known as biomembrane mimicry.²⁰ The principle of reduced material thrombogenicity is of particular importance in the context of subarachnoid hemorrhage due to aneurysmal rupture, because the proinflammatory state results in a greater potential for thromboembolic complications.²¹ Thus, the advantage of PED-Shield in the treatment of ruptured pathology may be twofold: decreased potential for thromboembolic complications in the immediate periprocedural period, as well as the possibility for earlier cessation of DAPT without leading to FDS thrombosis. Both of these principles were supported by the included series, given that no patients experienced thromboembolic complications in the immediate periprocedural period and none of the patients maintained on single antiplatelet therapy experienced FDS thrombosis.

Nearly half of the patients (48.5%) in our series underwent placement of 2 PED-Shield devices for aneurysm treatment. Of the patients treated with overlapping PED-Shield devices, 90.9% demonstrated complete aneurysm occlusion at latest follow-up, compared with 72.7% who underwent placement of a single PED-Shield. In addition, among the 5 patients who experienced complete aneurysm occlusion less than 1 month after treatment, 4 (80%) were treated with a construct of 2 overlapping PED-Shield devices. Previous reports have suggested that placement of multiple FDS can meaningfully alter the fluid dynamics and wall stress in the treatment area,²² and our experience supports this. Furthermore, delayed rupture in "undertreated" blister aneurysms has been described with FDS devices, although this was not observed in our series.²³

To date, several small studies have described the treatment of ruptured aneurysms with PED-Shield. Manning et al.²⁴ described a series of 14 patients with aneurysmal subarachnoid hemorrhage (2 of which were blister aneurysms) treated with PED-Shield and single antiplatelet therapy. They reported complete or near-complete occlusion in 85.7% of patients at early-acute follow-up. One patient experienced an in-stent thrombus, which was successfully treated with thrombectomy.²⁴ Although single antiplatelet therapy after PED-Shield placement was not the main objective of our study, 4 patients were maintained on aspirin therapy alone. None of these patients demonstrated evidence of in-stent thrombus/stenosis or distal embolic complication at follow-up. Additionally, all 4 patients demonstrated complete occlusion of the aneurysm on follow-up imaging.

Mokin et al.² described a series of patients with blister aneurysms treated with flow diversion. Of 49 patients, 43 were treated with PED and 42 were placed on DAPT postoperatively (1 had postoperative hemorrhage that interrupted the use of DAPT).² Of note, the specific PED used by the group was a previous iteration of the device that lacked Shield Technology. The authors reported 5 (11.6%) intraprocedural thromboembolic complications in patients who underwent PED treatment: in-stent thrombosis occurred in 2 cases and distal thromboembolism in 3 cases, whereas none of the patients in our series experienced these complications. The in-hospital mortality rate reported in the previous series was 18.6%, and 68% of patients who had clinical follow-up at 3 months had an mRS score of 0–2. Our patients experienced a lower in-hospital mortality rate of 9.09% and had better clinical outcomes, as 93.8% of our patients with 3-month follow-up had an mRS score of 0–2. Finally, the previous study demonstrated similar rates of complete occlusion at follow-up compared with our series (88% vs 82.6%, respectively).

Conclusions

Ruptured blister, iatrogenic, and dissecting pseudoaneurysms pose challenges for cerebrovascular surgeons. The reduced material thrombogenicity of PED-Shield appears to improve the safety of minimally invasive endovascular flow diversion treatment of these pathologies. Our series represents the largest report of ruptured ICA pseudoaneurysms treated with PED-Shield and the first to report the use of single antiplatelet therapy in this population without thromboembolic complication. The efficacy of PED-Shield reported in this series, particularly with placement of two overlapping devices, demonstrates its potential as a first-line treatment option for these pathologies and provides evidence supporting ongoing evaluation in larger trials.

Disclosures

Dr. Seinfeld reported personal fees for consultant work from Medtronic outside the submitted work. Dr. Grossberg reported grants from GRA, EMCF, and Neurosurgery Catalyst, and stock options from Cognition outside the submitted work. Dr. Nerva is a medical advisor for and shareholder of Midwest Interventional Systems Inc. and a shareholder of Synchron LLC, Bendit Technologies Ltd, and Borvo Medical Inc. Dr. Burkhardt reported personal consulting fees from MicroVention, Cerenovus, Stryker, Medtronic, Longeviti Neuro Solutions, and Q’Apel Medical outside the submitted work. Dr. Gooch reported consulting fees from Stryker outside the submitted work. Dr. Jabbour reported grants from Medtronic during the conduct of the study. Dr. Tjoumakaris reported money paid to an institution from MicroVention outside the submitted work. Dr. Ortega Gutierrez reported personal fees from Stryker Neurovascular, Medtronic, MicroVention, and VizIA outside the submitted work and NIH funding and investigator-initiated funding from Medtronic, Stryker, MicroVention, and methinks. Dr. Levitt reported grants from Medtronic and Stryker; equity interest from Proprio, Hyperion Surgical, Synchron, Fluid Biomed, and Cerebrotech; and consultant fees from Metis Innovative and Stereotaxis; and is an advisor for Aeaean Advisers outside the submitted work. Dr. Mascitelli reported consultant fees from Stryker outside the submitted work. Dr. Kilburg reported personal fees from Medtronic Neurovascular and Cerenovus outside the submitted work. Dr. Gross reported consultant fees from Medtronic, MicroVention, and Stryker outside the submitted work. Dr. Grandhi reported personal fees from Medtronic Neurovascular, Cerenovus, and Balt Neurovascular outside the submitted work.

Author Contributions

Conception and design: Grandhi, Bounajem, Joyce, Scoville, Grossberg, Tjoumakaris, Kilburg. Acquisition of data: Grandhi, Bounajem, Joyce, Scoville, Seinfeld, Hoffman, Grossberg, Waiters, White, Nerva, Burkhardt, Tonetti, El Naamani, Jabbour, Ortega Gutierrez, Levitt, Ares, Desai, Mascitelli, Budohoski, Gross. Analysis and interpretation of data: Grandhi, Bounajem, Joyce, Scoville, Seinfeld, Nerva, Burkhardt, Tjoumakaris, Ortega Gutierrez, Levitt, Ares, Mascitelli, Budohoski. Drafting the article: Grandhi, Bounajem, Nerva, Mascitelli. Critically revising the article: Grandhi, Bounajem, Joyce, Scoville, Seinfeld, Grossberg, Tonetti, Gooch, Jabbour, Ortega Gutierrez, Levitt, Lang, Mascitelli, Kilburg, Budohoski, Couldwell, Gross. Reviewed submitted version of manuscript: Grandhi, Bounajem, Joyce, Seinfeld, Grossberg, White, Burkhardt, Tonetti, Gooch, Ortega Gutierrez, Levitt, Ares, Desai, Kilburg, Budohoski, Couldwell, Gross. Approved the final version of the manuscript on behalf of all authors: Grandhi. Administrative/technical/material support: Joyce. Study supervision: Grandhi, Joyce, Jabbour.

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