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Abstract
Background The Pipeline Flex embolization device has some peculiarities in comparison with the previous generation device. Despite recent reports of the modified delivery system, its safety is still unknown.
Objective To illustrate the intraprocedural and periprocedural complication rate with this new device in 30 consecutive patients.
Material and methods Clinical, procedural, and angiographic data, including aneurysm size and location, device or devices used, angiographic and clinical data were analyzed.
Results 30 patients harboring 30 aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end opened fully from the beginning with a complete wall apposition. In the remaining 11 devices, distal-end opening of the devices was instant but partial, but fully opened easily after recapture. Among the 30 procedures, recapture and reposition of the Pipeline Flex was performed four times owing to proximal migration/malposition of the device during delivery. Four intraprocedural/periprocedural complications occurred, of which 2 resulted in major complications, with neurologic deficits persisting for longer than 7 days. The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or parenchymal hemorrhage was seen.
Conclusions The Pipeline Flex embolization device allows more precise and controlled deployment than the first-generation device. The number of devices and the complication rate during the learning curve are lower than reported with the first-generation PED. The new delivery system and the resheathing maneuvers do not seem to increase the intraprocedural complication rate in comparison with the first-generation PED.
- Aneurysm
- Flow Diverter
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Introduction
The Pipeline embolization device (PED; ev3/Covidien Neurovascular, Irvine, California, USA) received conformité européenne (CE) mark of approval for the embolization of cerebral aneurysms in 2008 and US FDA approval in 2011 for the treatment of large and giant wide neck aneurysms in the internal carotid artery, from the petrous to the superior hypophyseal segments.1–5
Recently, the “Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial” (PUFS trial)6 and “International Retrospective Study of the PED: a multicenter aneurysm treatment study” (IntrePED study)7 have demonstrated a high rate of complete occlusion of aneurysms of the internal carotid artery and a reasonably low rate of major safety events using this type of flow diverter.
The new generation of PED, so-called Pipeline Flex embolization device (PFED), received the CE mark of approval in March 2014. Since then, only two reports8 ,9 have described it, with particular emphasis on the technical aspects. Although the stent has not changed, the new delivery system makes the device resheathable, theoretically allowing a more precise, safe and efficient deployment.
The aim of our study was to assess the technical success and the safety of this new delivery system by evaluating the intraprocedural and periprocedural complication rate after its use in several European tertiary institutions.
Material and methods
Clinical and radiological parameters were obtained prospectively from 30 consecutive patients presenting with unruptured aneurysms and treated with the new Pipeline Flex device at nine academic tertiary centers. The study was approved by each institutional review board. All procedures were performed after obtaining written informed consent.
Data collection included clinical presentation, aneurysm size and location, device or devices used, procedural and angiographic data. Angiographic and clinical data were analyzed. All complications were noted and reported during the time of hospitalization. Complications were defined as follows: (a) ‘major’ adverse event was considered to be an ongoing clinical deficit at 7 days after the event; (b) ‘minor’ adverse events were considered as events that resolved within 7 days with no clinical sequelae. All major adverse events are included in the neurologic morbidity and mortality rates. A modified Rankin Scale (mRS) score was assessed and reported by each treatment center at discharge to evaluate the clinical effect of any complications. After 30 days patients were telephoned by a member of staff to determine whether any adverse events had occurred since discharge.
Procedures
All procedures were performed/supervised by senior neurointerventionalists with more than 20 cases of first-generation PED experience (MM-G, AV, PR, JLC, PS, JCM, FD, PV, AR, AG).
Although all patients were premedicated with double antiplatelet therapy 5 days on average before the intervention, each institution followed its own protocol: 100 mg aspirin in 14 cases, 300 mg in 16 cases, and 75 mg clopidogrel in 30 cases.
Platelet function tests were not mandatory and they were performed only in 19 cases, showing one borderline responder to aspirin and three hyper-responders to clopidogrel (Plavix).
An initial 70–100 U/kg of heparin bolus was given and the activated clotting time was maintained at twice the patient's baseline level intraoperatively. Heparin was discontinued but not reversed at the end of the procedure. Dual antiplatelet therapy was continued after discharge.
Devices were deployed through a Marksman microcatheter (ev3, Irvine, California, USA) using a triaxial guide-catheter system in all cases.
The delivery consisted of 80% pulling the microcatheter and 20% pushing the wire, which differed substantially from the classic technique for PED; since one of the main modifications of the new device is the absence of a capture coil, ‘cigar-shape’ and torquing are not required anymore.
Any clinical events occurring postoperatively were noted.
Results
A total of 30 patients harboring 30 intracranial aneurysms (28 anterior circulation and two posterior circulation locations) were included between September 2014 and November 2014 (table 1).
Aneurysms and device characteristics, intra and periprocedural events, clinical outcome
Eighteen cases were asymptomatic incidental, one patient presented only with headache, four patients had diplopia, and one patient had transient pons compression. In five patients who were re-treated with a PED placement, four aneurysms had coils from the previous treatments and one stent plus coils. There were no cases of acute rupture.
In the anterior circulation, 12 cases were ‘small’ (<10 mm), 14 were ‘large’ (10–25 mm), one case was ‘giant’ (>25 mm), and one was ‘fusiform’.
Eight aneurysms were located at an internal carotid artery (ICA)-cavernous segment, one at an ICA-intracranial and cavernous segment, six at an ICA-ophthalmic, nine at an ICA-intracranial portion (segments included carotid cave, hypophyseal, choroidal, PCom) and four at a middle cerebral artery (MCA).
In the posterior circulation, one case was ‘small’ located at a V4 segment and one was ‘large’ at a mid-basilar portion.
Of the 30 cases, 23 were saccular, three dissecting, three segmental defects, and one fusiform.
A total of 39 stents were deployed properly in the 30 cases—that is, an average of 1.3 devices per case in this series. All devices were placed properly and no devices needed to be removed (figure 1). The distal portion of the device opened instantaneously in all cases (table 2).
Device size and technical aspects
DSA. (A) Case 24: treatment of a paraophthalmic recanalized aneurysm using a 4.5×20 mm Pipeline Flex embolization device. Note the absence of a capture coil (*). (A, B) Teflon flaps are not radiopaques. Resheathing marker (white arrow) and proximal bumper (black arrow) marks are noted. Since the modifications in the delivery system, technical maneuvers differ from those of the previous generation Pipeline embolization device.
Multiple PEDs were used in seven cases (23%). Of these seven cases, two devices were overlapped in five aneurysms with significantly mismatching arterial diameters (cases 1, 21, 23, 26, 29). In the case of the fusiform aneurysm (case 16), four devices were necessary to reconstruct the artery, and in one recanalized case, previously ruptured (case 12), the operator decided to superimpose two devices to accelerate the lumen occlusion.
In 28/39 cases (72%) the distal-end opened fully from the beginning with a complete wall apposition. In 11 cases (28%), distal-end opening of the device was instant but partial, and a resheathing maneuver was necessary since the device opened more easily after recapture. In five cases (cases 1–5) the operators decided to recapture the device despite an initial full opening, in order to improve the wall apposition and to achieve a more stable position for a precise deployment.
Among the 30 procedures, recapture and repositioning of the PFED was performed four times (cases 10, 21, 22 and 26) owing to proximal migration/malposition of the device during delivery.
The 30-day morbidity rate was 6.6%. Two major clinical events occurred (6.7%), but there were no minor events and no deaths. No aneurysm rupture or parenchymal hemorrhage was seen.
Both major neurologic events (cases 23 and 26) were ischemic infarcts at anterior choroidal arteries in large aneurysms, where two devices were overlapped (figure 2).
Major clinical events at the choroidal segment of an internal carotid artery (ICA). DSA. (A, B) Case 23 (dissecting ICA-supraclinoid aneurysm) and (C, D) case 26 (large saccular aneurysm), before and after deployment of stents. These complications were not unexpected given the size of the aneurysm and the inability to achieve good vessel wall apposition near the anterior choroidal artery.
There were two intraprocedural events with no clinical relevance. In case 25 (located at the M1 segment of the MCA), an acute occlusion of an early frontal branch of the MCA occurred during hypotension, which resolved after increasing the arterial pressure and an intra-arterial bolus (5 mg) of abciximab (Reopro). In case 28, an intraprocedural mild in-stent thrombus occurred in a patient with borderline-hyporesponse to aspirin, which resolved with an intra-arterial bolus of abciximab (10 mg) (by increasing the dose of aspirin from 100 to 300 mg daily a normal response range was achieved).
No aneurysm rupture or parenchymal hemorrhage occurred.
The mRS at discharge from hospital was the same as the mRS at admission, except in those patients who had a major event, where the mRS was 1 (cases 23 and 26).
A follow up-telephone call after 30 days showed that no worsening or any adverse event had occurred.
Discussion
Clinical experience with the first-generation PEDs has been widely reported since they obtained a European CE mark in 2008.1–5 Large clinical multicenter trials, such as the PUFS trial6 and IntrePED study,7 clearly described the safety and effectiveness of PEDs for the treatment of intracranial aneurysms.
The second-generation PED, PFED, comprises the same clinically proven implant and a new delivery system which makes the device resheathable.
The main differences and technical modifications have been extensively described in two recent reports.8 ,9 Since the stent design has not changed, it would be expected that the results of long-term follow-up would be similar to those previously reported. However, the safety of the new delivery system is still unknown.
The complication rate using the first-generation PED is strongly associated with the number of the devices and complex maneuvers, especially during the learning curve.10–12
Thus, considering our patient population as part of the initial learning curve with this new resheathable device, we focused on studying two main variables: (1) the average number of devices, and (2) the complication rate associated with recapture and repositioning maneuvers.
Jabbour et al10 showed that during deployment of the first 37 devices the operators used 1.6 devices for each procedure and later, the average number dropped to 1.2–1.3 for the same operators. Also, by using fewer devices and maneuvers, the rate of complications decreased from 16% (first 37 devices) to 5.6% (experience with more than 74 devices). Tan et al11 showed that the average number of PEDs used in patients with aneurysms <10 mm was 1.19 compared with an average of 2.32 PEDs in patients with aneurysms >10 mm. They identified two statistically significant risk factors for neurologic changes due to thromboembolic events: longer procedure time (>116 min) and multiple PED deployment (>1 stent).
Recently, in the IntrePED study,7 multiple PEDs were used in 308 cases (34.2%). Patients with ICA aneurysms >10 mm had the highest rate of multiple PED use (46.0%, 143/311) and were significantly more likely to receive treatment with multiple PEDs than the other groups. IntrePed7 had a neurologic morbidity and mortality rate of 8.4% and most adverse events were ischemic strokes from thromboembolic complications. These were substantially more common in large, anterior circulation aneurysms and posterior circulation aneurysms than in small, anterior circulation aneurysms. The ischemic stroke rate was 4.7% (37/793), with most strokes occurring within 30 days of treatment (26/793, 3.3%).
To our knowledge, there are only two previous reports8 ,9 about the new PFED. In both series, although the authors made a valuable technical description of the new delivery system, the number of cases was too small for any clinical conclusion to be drawn.
In the series of six PFED cases by Martínez-Galdámez et al,8 one device was repositioned after malpositioning and two devices were telescoped in two different dissecting aneurysms. In another patient, full opening was achieved after recapturing a partially opened device. One major event occurred but no minor events and no deaths were reported. Pereira et al9 recaptured the PFED in five of 10 cases (50%) in order to reposition it more precisely, to improve apposition, especially in tight curves or complex loops, or because it had migrated proximally during deployment. They described two minor events, no major events and no deaths.
In our PFED series, the average number of devices for each procedure was 1.3. Moreover, excluding the fusiform and dissecting cases, the average number of devices was 1.
Our criterion for overlapping devices was a significant mismatch in arterial diameter in order to avoid delayed migration and achieve a homogeneous vessel reconstruction, which has been previously reported with the use of the first-generation PED.13 ,14
Our clinical results correlate with previous reports of flow diverters.15 Two major clinical events (6.7%) occurred but no minor event or death (0%) in the 30 days after treatment, with no morbidity or deaths in the subgroup of patients with anterior circulation aneurysms <10 mm. In our series 18/39 (46%) devices were resheathed as described above and no dissections or thromboembolic events occurred related to them.
These results show that this new delivery system allows a precise and easy device deployment. During this learning curve, the average number of devices and the complication rates were lower than in a similar experience with first-generation PEDs.10
Despite the inherent limitation of studies with a small sample size and the variety of aneurysm characteristics, the results appear promising. Larger and more uniform series of cases are needed to corroborate the effectiveness and safety of this treatment method and its superiority to other techniques.
Conclusion
The PFED may allow more precise and controlled deployment than first-generation devices. The number of devices and the complication rates during the learning curve are lower than reported with the first-generation PED. Resheathing maneuvers may not be associated with intraprocedural complications.
References
Footnotes
Contributors Study concept and design: MM-G; acquisition of data: all the authors; analysis and interpretation of data: MM-G; drafting of the manuscript: MM-G; critical revision of the manuscript for important intellectual content: MM-G and SO-G; administrative, technical, and material support: MM-G; study supervision: MM-G.
Competing interests MM-G is a proctor for the Pipeline embolization device and a consultant for Covidien Neurovascular.
Patient consent Obtained.
Ethics approval Institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data from this study is contained in this paper.