Background Adjunctive coiling may improve occlusion outcomes when combined in a single stage with cerebral aneurysm flow diversion. This technique has not been well described.
Objective To present a series of aneurysm patients treated by single-stage flow diversion with adjunctive coiling, describing technical considerations and outcomes.
Methods This was a retrospective cohort study using an IRB-approved database of procedures performed at a single institution. Treatment selection was based on large aneurysm size, morphological irregularity, branch vessel location, and wide neck.
Results A total of 72 Pipeline with adjunctive coiling (PAC) procedures were performed on 69 patients. Average aneurysm size was 11.0 mm and 86% were wide-necked. Three progressively complex techniques were performed approximately equally: 27 sequential (38%), 23 jailed single-intermediate (32%), and 22 bifemoral jailed microcatheter (31%) cases. Aneurysm dome (P=0.0223) and neck size (P=0.001) increased with procedural complexity and there was a trend toward increased procedure length, radiation exposure, and stent thrombosis. A ‘light’ coil pack was used with an average packing density of 14% that did not vary by technique. Of the three major complications (4.2%), none were observed with the sequential approach (0%), one with the jailed single-intermediate (4.3%), and two with bifemoral cases (9.1%) (P=0.116). Complete occlusion was achieved in 85% of PAC cases at 6 months and 96% at 12-month follow-up angiography.
Conclusions There are multiple approaches to flow diversion with adjunctive coiling, each with technical challenges, suitable to different types of aneurysms. Flow diversion with coiling can expedite and improve occlusion outcomes without a significant increase in morbidity.
- flow diverter
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Adjunctive coiling was used in one of the first descriptions of the placement of a Pipeline Embolization Device (PED) for cerebral aneurysm.1 The PED has since been used primarily as an independent modality with occlusion outcomes and recurrence rates that compare favorably2 with coiling3 and stent-coiling.4 Single-stage flow diversion with adjunctive coiling is now used in specific clinical scenarios in which earlier occlusion is desired, including large or giant unruptured aneurysms, rare cases of subarachnoid hemorrhage (SAH) treated with flow diversion, and aneurysms demonstrating significant morphological irregularity.5 Although several small series exist,6–8 the flow diversion literature lacks a description of the multiple strategies that can be used for Pipeline with adjunctive coiling (PAC) and the unique challenges associated with each. Here we present a single-center series of 72 aneurysms treated by single-stage flow diversion with adjunctive coiling using three distinct techniques in equal proportions.
The study was a retrospective cohort using an Institutional Review Board-approved prospectively-collected database of aneurysm patients at a tertiary medical center. Patients were selected for flow diversion with adjunctive coiling based on: large or giant size, significant morphological irregularity, wide neck (>4 mm or dome:neck ratio <2), or associated branch vessels known to slow or hinder occlusion with PED alone. Consideration was given to conservative management, surgical clipping, and other endovascular treatments and patients were counseled that PAC represents an off-label use of PED, which was originally approved for use as a single modality to treat large proximal carotid aneurysms. Patients were started on dual antiplatelet therapy 7 days prior to intervention. Post-embolization, patients were maintained on therapeutic anticoagulation and monitored in the neurocritical care unit overnight. Demographic information, clinical history, and outcomes were collected from medical records. Anatomic and technical details were collected from intra-procedure events, angiograms, and operative reports. Follow-up consisted of catheter cerebral angiography at 6, 12, and often at 24 months post-embolization. Clopidogrel was discontinued at 6 months and aspirin was reduced to 81 mg daily at 12 months. End-embolization occlusion was graded based on the Raymond scale as aneurysm occlusion, neck filling, or dome filling.9 Coil packing density was calculated using the Cerebral Aneurysm Calculator (AngioCalc, http://www.angiocalc.com). Occlusion on follow-up digital subtraction angiography (DSA) was self-adjudicated and graded according to the O’Kelly–Marotta scale for flow diversion10 as complete, trace filling, entry remnant, or aneurysm filling. A subset of the patients in this study were included in prior publications on the safety11 and efficacy12 of flow diversion for anterior circulation aneurysms.
Embolization was performed through an 8F femoral short sheath and standard triaxial set-up with a long guide sheath (AXS Infinity, Stryker Neurovascular, Fremont, California, USA; Neuron MAX, Penumbra, Alameda, California, USA)13 and 5F intermediate catheter (Catalyst 5, Stryker Neurovascular; Navien 0.058 inch, Medtronic Neurovascular, Irvine, California, USA; Syphontrak, InNeuroCo, Sunrise, Florida, USA)14 brought into position over a 0.027 inch microcatheter (Via 27, MicroVention/Sequent Medical, Tustin, California, USA; Marksman, Medtronic Neurovascular; Phenom, Medtronic Neurovascular).15 The 0.027 inch catheter was removed and coiling was performed using a 0.0165 inch inner diameter microcatheter (SL 10, Stryker Neurovascular). PED deployment was then performed as described previously,16 17 with the initial portion of the device opened distal to the aneurysm and then dragged back into position across the aneurysm neck. On three occasions the sequential technique was performed with balloon-assisted coiling, in which case a 6F intermediate catheter (Navien 0.072 inch; Sofia Plus, MicroVention) was used with a parallel coiling microcatheter and compliant balloon (Transform, Stryker Neurovascular) (figure 1).
This is similar to the sequential technique, except that a 6F intermediate catheter was brought up over the 0.027 inch microcatheter alongside which a parallel coiling microcatheter was subsequently introduced. The PED was advanced within the 0.027 inch catheter distal to the aneurysm. The aneurysm was accessed and the microwire was replaced with a coil advanced to the level of the petrous internal carotid artery (ICA). The PED was opened distal to the aneurysm and then dragged back to the level of the aneurysm neck. PED deployment was completed without retracking the 0.027 inch catheter or recapturing the delivery wire. After light packing with coils through a 0.0165 inch inner diameter microcatheter, the aneurysm was deaccessed and the coiling microcatheter was removed. Only at this point was the 0.027 inch microcatheter tracked over the PED delivery wire to recapture the delivery wire and ‘bump’ the proximal end of the device for improved final wall apposition of the PED. Balloon angioplasty was performed as necessary to promote device apposition (figure 2).
The PED was delivered through a triaxial set-up identical to the sequential technique. Through a 5F sheath in the opposite femoral artery, a 5F Envoy catheter (Codman Neuro, Raynham, Massachusetts, USA) was brought up and positioned at the level of the guide sheath in the distal common carotid artery or proximal ICA. The 0.0165 inch inner diameter coiling microcatheter was brought up through the Envoy and embolization was performed in a jailed fashion similar to the single-intermediate technique. Given vessel caliber constraints, in the one posterior circulation case in which the bifemoral technique was performed, the two intermediate catheters were positioned in separate vertebral arteries (figure 3).
Data are presented as means and range for continuous variables and as frequency for categorical variables. Univariate analysis was carried out using unpaired t tests and ANOVA tests. A threshold of P<0.05 was used to determine significance. Statistical analysis was performed using Stata V.14.0 (College Station, Texas, USA).
A total of 72 single-stage PED with adjunctive coiling procedures were performed on 69 patients (3 with two separate procedures for distinct aneurysms). The population was 86% female with average age of 58 years. The average aneurysm size was 11.0 mm. There were 38 small (53%), 28 large (39%), and 6 giant (8%) aneurysms. The majority of the aneurysms (86%) were wide-necked. A minority of patients had a history of SAH (10%) or were previously treated (7%). Two-thirds of aneurysms were located along the ICA, 11% anterior cerebral artery (ACA), 7% middle cerebral artery (MCA), and 15% in the posterior circulation (table 1).
There was parity in terms of the technique employed with 27 sequential (38%), 23 jailed single-intermediate (32%), and 22 bifemoral jailed microcatheter (31%) cases. Aneurysm dome (P=0.022) and neck size (P=0.001) both increased with procedural complexity. There were progressive increases in fluoroscopy time and radiation exposure with added procedural complexity, which were not statistically significant. End-embolization Raymond grade showed greater thrombosis of sequentially-treated aneurysms (59% residual aneurysm) than single-intermediate (83%) or bifemoral cases (86%), but this was not statistically significant. Coil packing densities were 14–15% for all three techniques. Balloon angioplasty was used in 29% of PAC cases and platelet aggregation along the stent requiring treatment with intra-arterial abciximab was seen in 13% (table 1).
Procedural success was achieved in 70/72 cases (97%). Both failures were initially attempted as sequential PAC and were converted to successful single-modality flow diversion (cases 36 and 50). The average length of stay was 3.2 days, 46% were discharged on POD1, and 89% were discharged home or to the prior level of care. The major complication rate in PAC cases was 4.2% compared with 4.0% in single-modality flow diversion cases (P=0.980). The three major complications were strokes. Minor neurological complications were observed in two cases (3%), both transient ischemic attacks; minor non-neurological complications were observed in six cases (7%), including five groin hematomas and one asymptomatic dissection (table 1).
The major complications encountered were as follows: Case 12 had left ACA to ICA PED placed with additional coiling via the bifemoral technique for a 9 mm proximal left A1 aneurysm with a 5.8 mm neck. The patient experienced left MCA stroke on POD1 secondary to hypotension from a large retroperitoneal hematoma and ultimately died from the stroke. Case 53 underwent PAC via the single-intermediate technique of a 13 mm right MCA bifurcation aneurysm with 8 mm neck. At the end of the procedure mild platelet accumulation was observed within the PED and 5 mg intra-arterial abciximab was administered with normal anterograde filling of the right MCA throughout. The patient awoke with left-sided hemiparesis, MRI showed right basal ganglia infarct, and the patient had a modified Rankin Scale (mRS) score of 4 at last follow-up. Case 56 had PAC via the bifemoral approach of a 9 mm right A2–A3 junction aneurysm with a 5.4 mm neck. DSA following stent and coil deployment showed occlusion of the covered callosomarginal branch. The vessel opened with escalating doses up to 20 mg abciximab. The patient awoke with left lower extremity weakness and had punctate infarcts in the right ACA distribution on MRI but had an mRS score of 1 at last follow-up.
Complete aneurysm occlusion after PAC was observed in 85% at 6 months, 96% at 12 months, and 100% at 24 months. At last follow-up (9.6 months), complete occlusion was observed in 85% of PAC cases (table 2).
This is a large study of 72 endovascular treatments for cerebral aneurysm with flow diversion and adjunctive coiling performed in a single stage. Three distinct techniques were used in equal proportion. As illustrated by longer procedural times, increased rates of balloon angioplasty, and the more frequent observation of platelet aggregation, coiling adds complexity to the flow diversion procedure. However, it also has the potential to achieve earlier and more complete occlusion outcomes without a substantial increase in the rate of major complications.
Rationale for PAC
The most common rationale for combining coils with flow diversion, both in the present series and literature, is to reduce the risk of delayed aneurysmal SAH in a large or giant aneurysm. In a meta-analysis of 1654 aneurysms, the rate of delayed rupture resulting in SAH following flow diversion for cerebral aneurysm was 4%. Large and giant aneurysms were more susceptible to this phenomenon: the OR of delayed SAH associated with small or large size compared with giant was 0.10.18 Others have observed this phenomenon in smaller aneurysms, still typically larger than 10 mm.19 20 Proposed mechanisms for delayed rupture after flow diversion include hemodynamic shifts with inflow/outflow mismatch and intrathrombus enzymatic proteolysis of the aneurysm wall,21 although the exact etiology is not known. Multiple authors have recommended combining coils with flow diversion for large and giant aneurysms in order to stabilize thrombus and equilibrate hemodynamic stress within the aneurysm dome.7 19 Rates of delayed SAH after flow diversion appear to have gone down over time, but there is no study linking this to adjunctive coiling.
Other reasons for combining coils with flow diversion include expediting occlusion of morphologically irregular aneurysms and scaffolding support for the stent in giant aneurysms. Flow diversion is occasionally used to treat ruptured aneurysms, whenever possible with adjunctive coiling to secure the aneurysm dome.22 As its occlusion benefits have become recognized, adjunctive coiling has also been used to expedite occlusion of unruptured aneurysms demonstrating significant morphological irregularity thought to portend rupture.6 In giant aneurysms, coils can serve an essential architectural role, acting as a scaffold to prevent PED foreshortening and prolapse into the aneurysm. Lin et al reported foreshortening/migration in 4/75 (5%) PED-only treatments compared with 0/29 (0%) treatments with PED and coils.6
Efficacy and safety of PAC
Previous studies have suggested improved occlusion outcomes with PAC compared with single-modality flow diversion based on near-term follow-up and retreatment rates. Lin et al observed complete occlusion in 93% of 29 PAC treatments compared with 75% of 75 PED-only treatments at an average of 7 months follow-up. Retreatment rates were 3% in the PAC group and 16% in the PED-only group.6 Park et al likewise saw a need for retreatment in 1/65 PAC cases (1.5%) compared with 8/68 (11.8%) PED alone.7 It is important to note that both of these studies, like ours, included cases of single-stage flow diversion with adjunctive coiling; flow diversion for recurrent previously coiled aneurysms has a separate indication, risk profile, and corresponding literature. In the study by Park et al, the authors elected to re-treat aneurysms based on incomplete occlusion at 6-month follow-up vascular imaging, allowing the possibility that retreatment rates reflect prolonged latency before occlusion with single-modality flow diversion rather than material differences in eventual cure rates. The present study confirms improved occlusion outcomes with PAC at both early and intermediate follow-up intervals, with complete occlusion in 85% compared with 70% of single-modality flow diversion cases at 6-month DSA and 96% versus 76% at 12-month DSA. Multivariate analysis,12 which accounts for significant differences in aneurysm size and morphology, identified adjunctive coiling as the sole predictor of occlusion at 6- and 12-month angiography for anterior circulation aneurysms treated with flow diversion. The use of multiple telescoping devices is an alternative technique that others have used to augment occlusion outcomes; however, this was not a significant predictor of occlusion in our multivariate analysis and may be less appropriate with contemporary more distal treatments at branch vessel locations and across perforator-rich regions.
PAC is a technically challenging procedure typically reserved for larger more complex aneurysms, yet no study has shown statistically increased morbidity compared with single-modality flow diversion. In the study by Lin et al, the neurological morbidity rate was 10.3% in 29 PAC procedures compared with 8.0% in 75 PED-only procedures.6 Park et al reported a 3.1% major complication rate in 65 PAC procedures compared with 2.9% in 68 PED-only procedures in the Barrow Neurological Institute experience.7 In the present study, the major complication rate was 4.2% in 72 PAC cases compared with 4.0% in PED-only cases at our institution. Adjunctive coiling was not identified on univariate or multivariate analysis as a predictor of complications with anterior circulation flow diversion in our institutional series.11 Results from the Intreped registry represent the largest experience with PAC, including 109 aneurysms treated with PAC and 797 treated with single-modality flow diversion. Aneurysms treated with PAC were larger (13.6 mm vs 10.3 mm), less commonly located along the ICA (64% vs 77%), and required longer procedures (136 min vs 97 min). In the Intreped registry there was a trend toward increased neurological morbidity with pipe-coiling (12.5% vs 7.8%), which did not achieve statistical significance (P=0.13).5
Despite the overall similar morbidity to single-modality flow diversion, there are unique risks of single-stage PAC that have not been well described. Specifically, there is a significantly increased risk of intra-procedural stent thrombosis which will progress to symptomatic ischemia without expeditious recognition and treatment23. When platelet aggregation is recognized during the embolization procedure and treated to stabilization or reversal, symptomatic complications can be avoided in a majority (7/9, 78%) of cases. However, two of the three major complications encountered in this series began with the observation of platelet aggregation along the stent during the embolization procedure. The risk is greater following balloon angioplasty, which is used in a greater percentage of PAC cases than single-modality flow diversion cases. The risk also appears greater in the small caliber vessels of the distal anterior circulation, as both events were observed among the 13 patients with ACA or MCA aneurysms treated with PAC. We are particularly judicious in selecting distal anterior circulation aneurysms for treatment with this approach. We are hyper-vigilant in these cases, waiting a full 30 min post-embolization for final control angiography prior to ending the case. Siddiqui et al shared the case of a patient with a giant MCA aneurysm treated with flow diversion and dense coil packing in which the patient experienced acute post-procedural stent thrombosis and cautioned against densely packing the aneurysm with coils.24 We also use a light coil pack (14% packing density overall) and systemically heparinize these patients overnight following their procedure, all to limit the risk of acute stent thrombosis.
Prior descriptions of the PAC technique
While there are excellent descriptions of the various techniques used for stent-coiling, the PAC procedure differs significantly and there is no detailed description of the technique. In a report of 260 stent-coiled aneurysms, Spiotta et al described four techniques of stent-coiling, in decreasing order of frequency, as: ‘coil through’ (37%), ‘balloon stent’ (36%), ‘jailing’ (11%), and ‘coil stent’ (8%).25 The ‘coil through’ technique is not a possibility for PAC, given the challenge Spiotta et al acknowledge of accessing the aneurysm through a VRD with <10% metal density and the impossibility of access through a flow diverter with closer to 30% metal surface area. The simplest technique we use, the sequential technique used in 38% of cases, is analogous to Spiotta et al’s ‘balloon stent’ and ‘coil stent’ techniques and, while jailing was used in just 11% of Spiotta et al’s stent-coiling cases, either single intermediate jailing or bifemoral jailing was used in the majority of PAC cases (63%).
Similar to our experience, some variation of jailing appears in the literature to be the most often used technique for PAC. In the first report of PAC, Fiorella et al coiled through a jailed microcatheter to promote stasis within a large fusiform V4 aneurysm.1 In 27 aneurysms treated with PAC, Nossek et al relied exclusively on jailing with a coiling catheter brought up through an 8F guide parallel to a biaxial set-up of 044 DAC and Marksman used for PED deployment.8 Lin et al acknowledged ‘usually’ using a jailed technique,6 while Park et al used both a sequential technique and jailed microcatheter technique on 65 aneurysms treated with PAC, but did not give the frequency of each treatment.7
Technical considerations and pitfalls of the three PAC techniques
The three different PAC techniques involve escalating technical challenges and are best employed in differing clinical circumstances. The sequential technique (38%) was most often used for relatively narrow-necked, highly irregular aneurysms (figure 1, case 34). These aneurysms could be treated with single-modality flow diversion, but the addition of coils was chosen to provide immediate dome security. Whereas the analogous stent-coiling techniques of ‘balloon stent’ and ‘coil stent’ were commonly used only when unstable coil mass or herniation into the parent vessel was encountered in planned simple coiling procedures,25 the addition of a flow diverter was planned in these cases. While these aneurysms could likely be treated with coiling alone, adding a flow diverter enabled lighter packing and reduced the long-term risk of recurrence compared with coiling or stent-coiling. We eschewed jailing for these typically smaller aneurysms because it would limit the coiling microcatheter’s ability to paint and could heighten the risk of intra-procedural aneurysm rupture.
The single-intermediate jailed technique described in the Methods was used in wide-necked aneurysms with relatively straightforward parent vessel anatomy, as in case 7 of a woman in her mid-40s with an unruptured 10 mm PICA aneurysm with a 5 mm neck (figure 2). PAC was chosen for this patient because of the wide-necked nature of the aneurysm and the propensity for recurrence stent-coiling. This technique requires a larger, less mobile 6F intermediate catheter with more limited ability to wag or bump the PED, since any manipulation of the 0.027 inch microcatheter can translate to the parallel coiling microcatheter. We favor the 0.070 inch inner diameter Sofia plus over the 0.072 inch Navien for single-intermediate jailed cases because of its increased trackability, but recognize that its smaller inner diameter increases the risk of microcatheter rubbing. Where possible, looping the coiling microcatheter inside the dome of larger aneurysms can prevent dislodgment during PED deployment. Advancing a coil to the level of the petrocavernous junction inside the coiling microcatheter adds stability during PED deployment while limiting stiffness at the tip of the jailed microcatheter in single-intermediate jailed cases.
As demonstrated in case 26, a woman in her mid-70s with 28 mm true ophthalmic aneurysm, an independent intermediate catheter plays an essential role in the manipulations required to deploy a PED across the neck of a giant aneurysm (figure 3). A jailed technique was selected to prevent coil herniation into the parent vessel, given the 9 mm neck of this aneurysm. This aneurysm was initially crossed with an omega-looped 0.0165 inch microcatheter that was then reduced before being exchanged for the 0.027 inch microcatheter for PED deployment. The bifemoral technique is always used when loop reduction is anticipated because it increases the risk of PED twisting during deployment. Significant wagging was required to open the device along the supraclinoid ICA, which resulted in the intermediate catheter tracking back to the petrocaverous junction, a manipulation that could not be done with a parallel coiling catheter in place. The proximal PED was then deployed partially into the intermediate catheter to progressively reduce an observed twist in the device. Finally, the 0.027 inch microcatheter was removed and balloon angioplasty was performed at regions of malapposition along the horizontal cavernous ICA, all before attention was turned to the relatively straightforward aneurysm coiling. Given the large to giant size and wide neck of most aneurysms treated with the bifemoral jailed technique, coiling catheter access is typically straightforward despite the proximal location of the Envoy in the distal common or proximal cervical ICA. Maintaining perfusion around multiple intermediate catheters requires a strict 120 mm Hg minimum systolic blood pressure throughout these cases and vigilance for vasospasm with a low threshold for the addition of Ca2+ blockers to the flush bag.
Overall packing density for PAC cases was 14.3% and did not differ based on the technique used. There was a trend toward lighter packing densities over time with 12.0% packing density in the final third of cases, but this was not statistically significant. This is considerably ‘lighter’ than the minimum of 20–25% packing density which previous studies show is associated with durable occlusion after both coiling26 27 and stent-assisted coiling.4 28 We have not gone to the extreme of Lin et al who recommended ‘one ortwo undersized coils’, although they did not publish packing densities in their series of 29 PAC cases.6 The decision to stop coiling is different for sequential and the two jailed techniques. Jailing stiffens the coiling microcatheter, limits its ability to paint, and eliminates the ability to re-access the aneurysm. Any resistance is typically a sign that coiling is finished, except in large or giant aneurysms where there may be sufficient microcatheter length to reposition by drawing back. The decision to stop coiling in the sequential technique is based on subjective assessment of having achieved a well-distributed light coil pack. Packing densities are not calculated mid-embolization. Finishing coils are not typically used.
This study was limited by its retrospective and observational nature. The small number of patients prevented meaningful statistical comparisons between the three techniques. Decision-making about which aneurysms warranted adjunctive coiling and which technique to use was at the discretion of the attending surgeon and was non-randomized. New developments in flow diverter and catheter technology over the course of this study influenced treatment decisions. Cost effectiveness of endovascular treatments (eg, stent coiling vs flow diversion,29 adjunctive coiling vs multiple PED7) is a relevant issue that we put deliberately outside our scope.
This is a large study of 72 patients with cerebral aneurysms treated with single-stage flow diversion with adjunctive coiling. There are multiple approaches to PAC, each with unique technical challenges, which are suitable to different types of aneurysms. Single-stage flow diversion with coiling can expedite and improve occlusion outcomes without a significant increase in morbidity.
Contributors All authors contributed significantly to conception, data acquisition, and analysis; all drafted and revised manuscript contents; and all approved the final version of the manuscript.
Competing interests ALC is a consultant and proctor for Medtronic, Stryker, and Microvention. GPC is a consultant for Medtronic and Microvention. L-ML is a proctor for Medtronic.
Patient consent Not required.
Ethics approval Johns Hopkins University School of Medicine Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The relevant anonymised patient level data are available on reasonable request from the authors.
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