15 FLOW DIVERTERS FOR BRAIN ANEURYSM TREATMENT: INTRAPROCEDURAL COMPLICATIONS AND MANAGEMENT
Abstract
The recent introduction of flow diverters in the neurointerventional armamentarium is revolutionary. The uniqueness of this technology consists of decreasing the blood flow into the aneurysm sac, which induces changes on the intrasaccular hemodynamics leading to aneurysm thrombosis. This new ability to treat and cure a brain aneurysm with low to no risk of recurrence has been very appealing. Mid- and long-term outcomes in multiple series have demonstrated the safety and effectiveness of flow diverters, especially for wide-necked, large or giant aneurysms that were otherwise challenging to treat by microsurgery or endovascular embolization. However, the neurointerventionalist may face complications at any point during the treatment of aneurysms with the use of this technology. For that reason, the purpose of this chapter is to review the advantages of a triaxial system to provide additional support for flow diverter placement within oftentimes tortuous vascular anatomy; the role of dual-antiplatelet therapy; and potential intraoperative complications, their management, and bail-out techniques.
15.1 Introduction
The concept of changing flow to treat brain aneurysms dates back from the technique of Hunterian ligation, when decreasing or stopping flow on the parent vessel would lead to aneurysm thrombosis. 1 There has been an evolution in the treatment of cerebral aneurysms from those early days of microsurgical clipping to endovascular techniques, such as coiling, balloon or stent-assisted coiling, and now flow diversion.
Flow diverters are a group of devices with metal-to-artery coverage of more than 30%, which induce changes on the intrasaccular hemodynamics often leading to thrombosis. Additionally, these devices have small struts and cells that provide a scaffold for endothelial cells to grow over the neck of the aneurysm and ultimately heal the parent vessel defect. 2 , 3 , 4
The purpose of this chapter is to review the intraoperative complications with use of flow diverters, as well as their prevention and management. We will cover events that are common to all flow diverters and also include device-specific issues. There are multiple flow diverter stents on the market today, with some more studied than others. The underlying concept is the same for all of these devices, which is to divert flow away from the aneurysm and to redirect the blood flow to the parent artery. The devices currently on the market for use include Pipeline Embolization Device (PED; Covidien/eV3, Irvine, CA), Silk flow diverter (SILK; Balt Extrusion, Montmorency, France), Flow Redirection Endoluminal Device (FRED; Microvention, Tustin, CA), Surpass (Surpass Medical/Stryker Medical, Miramar, FL), and p64 (Phenox, Bochum, Germany). To date, the PED is the most studied of these devices and the only one currently available in the United States. There have been more than 20,000 of PEDs implanted worldwide and more than 300 publications related to their use. However, the SILK was actually the first device in this category to become commercially available and has been used over 16,000 times worldwide with 48 publications ( Table 15.1).
15.2 Endovascular Access
15.2.1 Catheter Access
In our experience, a triaxial system should be employed when deploying a Pipeline flow diverter. This system consists of a proximal support long sheath, an intermediate catheter to provide additional support, and finally the delivery microcatheter. This progressive triaxial system allows for superior control and device placement when using a flow diverter in often tortuous cerebrovascular anatomy. Device and catheter control are critical in avoiding complications in the deployment of a flow diversion system.
15.2.2 Proximal Long Sheath
The proximal support lays the framework of support for the entire delivery system allowing navigation of oftentimes tortuous vascular anatomy and preventing buildup of forward tension on the system during catheter navigation. Although increased flexibility of the delivery system can offer superior trackability, this introduces the possibility of kinking the support catheter around a particularly tight corner. In this situation, a more robust support catheter becomes necessary.
Forward tension can also make delivery of any device treacherous. When pressure is applied for delivery, unsheathing, or recapturing of the device, the operator must apply additional stress on the support system. This can cause the catheters or device to become more difficult to control and move spontaneously or rapidly in an unintended manner due to the high forward tension within the system. Eliminating or reducing the forward tension is an important step in reducing potential complications and allows for superior control in device placement and apposition. This is particularly salient when attempting to avoid coverage over critical vessels while also maintaining an adequate margin of coverage on either side of the aneurysm neck.
The degree of vessel tortuosity often dictates the amount of support necessary for successful navigation of the delivery system. It is incumbent on the operators to have knowledge of the properties and use of a versatile set of delivery catheters. The senior authors (E.S. and R.H.) generally utilize a 6F proximal long sheath, along with an intermediate catheter, such as the 058-inch Navien (Covidien/eV3, Irvine, CA) to offer additional distal support, followed by a 0.027-inch microcatheter (Marksman 027 or Phenom 27). The Arrow-Flex (Teleflex Inc, Wayne, PA) sheath also offers reasonable support for PED placement with moderately more support compared to the Neuron 070 delivery catheter (Penumbra Inc, Irvine, CA). A 6F Shuttle guide sheath (Cook Group; Bloomington, IN) and Fubuki 6F sheath (Asahi Intecc, Aichi, Japan) are even stiffer, more supportive sheaths that allow excellent proximal support. In relatively straightforward access cases for posterior circulation aneurysms, we have found the 6F Neuron 070 or Penumbra Benchmark (Penumbra Inc) to be useful catheters.
15.2.3 Intermediate Catheters
The use of intermediate catheters allows for even more distal support beyond that of the delivery catheter. This additional support is particularly important when the distal arterial anatomy is tortuous, or if the flow diverter device is being placed around a tight turn, such as the carotid siphon. The extra support afforded by an intermediate catheter allows for a more controlled deployment of the device. The intermediate catheter that bridges the gap between the delivery catheter and the distal tip of the microcatheter reduces the amount of forward tension that builds up in the system.
Additionally, if a device becomes distorted or does not deploy in the manner in which an operator intended, it may become necessary to recapture the flow diverter. If the microcatheter has difficulty recapturing the device around serpiginous or nonlinear anatomy, an intermediate catheter can be employed to recapture both the microcatheter and the device. In these instances, the operator will be very thankful for having the foresight to employ an intermediate catheter.
15.2.4 Microcatheters
There are many different options when it comes to selecting a microcatheter to use in the delivery of flow diverter devices. For instance, the Pipeline Flex flow diverter (Covidien/eV3, Irvine, CA) requires a 0.027-inch inner diameter microcatheter. While the Marksman microcatheter has been a popular choice, different microcatheters may be used depending on one′s needs. With particularly tortuous anatomy over long distances, friction on the inside of the microcatheter during device deployment may cause the microcatheter to stretch. This can result in “lock-up” of the device, which can become so pronounced that the device becomes completely lodged in the microcatheter.
Certain rescue strategies are required with this particular complication when the device is partially deployed. It may not be feasible to simply drag the microcatheter and device into the intermediate catheter without risking avulsion or dissection of the parent artery. In this case, the intermediate catheter could be advanced over both the microcatheter and the device, recapturing both at once. Newer microcatheters have certain attributes, which work well with the new Pipeline Flex delivery system′s increased pushability and resheathability. More supportive microcatheters, such as the Via 27 (Sequent Medical, Aliso Viejo, CA) and the Phenom 27 (Cathera, Inc.; Mountain View, CA), have been introduced and, in the authors’ estimation, seem to perform better when resheathing the Pipeline Flex. Ultimately, user preference and comfort level will influence an operator′s choice of microcatheter for delivery of a flow diversion device.
15.3 Platelet Inhibition
Platelet inhibition is a crucial component to the successful use of intravascular stents in the treatment of vascular disease throughout the body. The stakes are often high, particularly with the use of flow diversion in the treatment of aneurysms, where the amount of exposed bare metal is significantly higher compared to other stents. For example, the PED is constructed of a closed-cell woven mesh with 48 strands (75% nitinol, 25% platinum), and typically provides 30 to 35% metal coverage depending on device sizing and vessel curvature. 5 For comparison, the open-cell Neuroform (Stryker Neurovascular, Fremont, CA) and closed-cell Enterprise (Cordis Neurovascular, Miami, FL) stents provide 6.5 to 9.5% metal coverage. This increased metal coverage of flow diverters creates a much larger thrombogenic surface area compared with non–flow diversion stents.
The use of flow diverters comes with the need for dual-antiplatelet use, to prevent acute stent thrombosis, occlusion, and stroke. Patients are typically placed on both aspirin and a P2Y12-receptor antagonist. Patients on standard doses of aspirin and clopidogrel (or any another oral anti-P2Y12 medication) can have a supratherapeutic response, theoretically leading to a higher likelihood of hemorrhage, or a subtherapeutic effect, potentially leading to a higher likelihood of thrombotic events. To this end, platelet function assays have been developed to measure the therapeutic effect of the P2Y12 receptor antagonist. It has been studied in carotid 6 and coronary stenting 7 with positive correlation between high platelet response unit (PRU) values (low level of platelet response to the drug) and thromboembolic events.
Despite this evidence, 8 , 9 , 10 the overall usefulness of bedside P2Y12 monitoring has come into question. This was particularly true with the ARCTIC trial, 11 a prospective randomized trial of 2,440 coronary stenting patients with or without P2Y12 response monitoring and medication adjustments. Interestingly, the ARCTIC study showed no improvement in clinical outcomes (primary endpoints: death, MI, in-stent thrombosis, stroke, or urgent revascularization) despite P2Y12 monitoring and medication adjustments compared with standard medication dosing without monitoring or medication adjustments. The monitoring cohort reached the primary endpoint in 34.6% of patients, while the nonmonitoring cohort reached 31.1%. Furthermore, there were no differences in major hemorrhagic events between the two groups. Although the cardiac and carotid stenting literature can offer useful direction with respect to P2Y12 response testing, the overall generalizability of this literature to flow diversion must be approached with caution.
The use of platelet-inhibition testing in flow diversion remains controversial. In the initial Pipeline for Uncoilable or Failed Aneurysms (PUFS) 12 trial, 6 of the 107 patients (5.6%) in the study experienced a major ipsilateral stroke or neurologic death. However, in the study, all patients received a standard dose of aspirin and clopidogrel without routine use of platelet inhibition monitoring. A retrospective analysis of complication rates in patients who underwent platelet testing versus those who did not undergo platelet testing from the International Retrospective Study of Pipeline Embolization Device registry (IntrePED) 13 , 14 found that platelet testing was associated with higher morbidity. Patients who underwent platelet testing had higher rates of intracranial hemorrhage (2.3 vs. 0% in those with no platelet testing). Neurologic morbidity was 8.2% in those who had platelet testing versus 2.1% in those who did not. Interestingly, the use of multiple devices was also higher in the platelet testing group (38 vs. 27.8%), which potentially increased the density of metal coverage in this group.
In the neurosurgical literature, one retrospective study that examined hemorrhagic and thromboembolic complications during flow diversion demonstrated a combined major complication rate of 9.6% (4% hemorrhagic, 5.6% thromboembolic) in 248 aneurysms treated in 231 patients. Based on their data, the authors concluded that the ideal range for the PRU assay was 70 to 150. A PRU less than 60 was a significant predictor of hemorrhagic complications, whereas a PRU higher than 240 was a predictor of thromboembolic events. 15 These findings are echoed in other smaller retrospective studies, which also demonstrate a higher risk of symptomatic thromboembolic events in patients with elevated PRU test results (indicating lower platelet inhibition) and a higher risk of intracranial hemorrhages in patients with PRU less than 60. 15 , 16 , 17
Hemorrhagic complications following flow diversion while on dual-antiplatelet medication can be potentially devastating, particularly when trying to negotiate a delicate balancing act between hemorrhage prevention and device thrombosis. This particular conundrum is true with the use of any bare-metal stent placed, which requires pretreatment with dual-antiplatelet therapy prior to treatment. Our protocol involves at least 3 months of continuous aspirin and clopidogrel or ticagrelor following flow diversion. 18 , 19 Following that, patients generally remains on aspirin for the rest of their life.
In our practice, we routinely check a P2Y12 level preoperatively in all patients. Those patients with an elevated P2Y12 (> 200), despite at least 5 days of an aspirin and clopidogrel regimen, are typically switched to ticagrelor. In those patients who have had less time to take the aspirin/clopidogrel regimen and have a borderline P2Y12 level (200–240), we typically redose an additional oral bolus of clopidogrel (150–450 mg) followed by recheck of the P2Y12 levels. With supratherapeutic levels (30–60), the authors suggest dose adjustment, occasionally with doses as low as 5 mg of clopidogrel daily, to decrease hemorrhagic complications. Despite this, the use of platelet-inhibition testing remains controversial, likely due to our inadequate understanding of the mechanisms behind both stent-induced thrombosis and posttreatment hemorrhagic complications. Prospective analyses of these certainly seem warranted.
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