The DERIVO 2heal embolisation device: A technical report using single antiplatelet therapy for intracranial pseudoaneurysm treatment

Abstract

The novel DERIVO 2heal Embolisation Device (Acandis, Pforzheim, Germany) is a flexible, fully radiopaque flow-diverter with a fibrin-based nano-coating, which is supposed to make the device inert to the coagulation cascade. We report a case of pseudoaneurysm treatment with this device under single anti-platelet therapy (SAPT). A female patient underwent endoscopic surgery for chronic rhinosinusitis. During surgery, the lateral wall of the sphenoid wall and the adjacent internal carotid artery was injured, leading to massive hemorrhage, which was treated with compression and tamponades. Eleven days after the procedure, the patient developed a rapidly growing pseudoaneurysm at the injury site with a relevant risk of upcoming aneurysm rupture. The aneurysm was treated by implantation of a DERIVO 2heal. A SAPT regimen was chosen due to the recent massive hemorrhage and anticipating enhanced progressive aneurysm occlusion. There were no thromboembolic complications and there was no morbidity. After 5 days, the pseudoaneurysm was completely occluded. The observations of the presented case are promising and warrant further investigation of this device.

Introduction

Intracranial flow-diverters (FD) have revolutionized neuroendovascular treatment of intracranial aneurysms with potentially higher occlusion rates compared to conventional coiling or stent-assisted coiling. However, due to the high amount of metal exposure to the blood flow, flow-diverters are associated with a relevant risk of ischemic stroke, either by thromboembolism or by development of in-stent stenosis. ¹ In order to reduce these risks, dual anti-platelet therapy (DAPT) is currently recommended after flow-diverter implantation, whereas acetylsalicylic acid (ASA) monotherapy may be sufficient several months after the procedure. ² In acutely ruptured aneurysms, DAPT is detrimental, as it may increase the risk of aneurysmal rebleeding during the latency period until complete aneurysm thrombosis and as it potentially complicates upcoming surgical procedures.

To reduce the thrombogenicity of the devices, several manufacturers developed surface modification technologies such as electropolishing and annealing (BlueXide, Acandis, Pforzheim, Germany),^3,4 phosphatidylcholine coating (Shield Technology^TM, Medtronic, Irvine, CA) ⁵ and glycan-based hydrophilic polymer coating, pHPC (Phenox, Bochum, Germany). ⁶ The ultimate goal of these technologies is to allow for a reduced DAPT or a single anti-platelet therapy (SAPT) regimen after FD implantation without increasing the risk of thromboembolic complications.

The DERIVO 2heal Embolisation Device (Acandis, Pforzheim, Germany) is a novel flow-diverter featuring a novel surface modification with fibrin-based nano-coating, which is supposed to be less thrombotic than its uncoated counterpart. ⁷ In this paper, we report the first clinical case of DERIVO 2heal implantation under ASA monotherapy.

DERIVO 2heal embolisation device

The DERIVO 2heal Embolisation Device is based on the second-generation DERIVO Embolisation Device 2 (DED 2) by Acandis. The DERIVO 2heal is available for vessel diameters ranging between 1.5 and 8.0 mm. Depending on its diameter, the DERIVO 2heal consists of either 48 (diameters 2.5–4.5 mm), 52 (5.0–6.0 mm) or 64 (7.0 and 8.0 mm) nitinol composite wires. An illustrative photograph of these three device types is presented in Figure 1A. The devices with a diameter of 2.5–3.5 mm can be delivered via low-profile 0.0165”-0.017” microcatheters, 3.5–6.0 mm diameters via 0.027” microcatheters and 7.0–8.0 mm diameters via 0.039” microcatheters. The delivery system of DED flow-diverters allows subtotal resheathing and repositioning. As illustrated in Figure 1B, the drawn filled tubing (DFT) wires of the DERIVO 2heal exhibit a higher amount of platinum than the conventional DED 2 for increased fluoroscopic visibility of the entire device contour. In return, the additional radiopaque markers at the ends of the DED 2 were omitted. Both ends of the DERIVO 2heal are flared with a 25° angle in order to improve wall apposition.

Figure 1.

(A) The DERIVO 2heal embolisation device (Acandis Pforzheim, Germany) consists of 48, 52 or 64 (shown left to right) densely woven nitinol composite wires available in diameters between 3.5 and 8.0 mm for treatment of vessel diameters ranging between 1.5 and 8.0 mm. The device diameters ≤ 3.5 mm are compatible with a low-profile (0.017”) microcatheter. The ends of the DERIVO 2heal are flared of 25° in order to improve wall apposition. The nitinol wires of the DERIVO 2heal exhibit a higher amount of platinum than the conventional DED 2 resulting in increased fluoroscopic visibility of the entire device contour, as demonstrated by unsubtracted angiograms in (B). In return, the additional radiopaque markers at the ends of the DED 2 were left out. The photograph in (A) was provided by courtesy of Acandis. .

After production of the bare flow-diverter, the device receives a surface finishing with a fibrin-based nano-coating named “heal” coating (Acandis, Pforzheim, Germany). This is a step-by-step process, where fibrinogen is adsorbed on the entire surface of the bare stent. ⁸ Then, thrombin is attached to the binding centers of the adsorbed fibrinogen, converting fibrinogen to fibrin and growing a fibrin mesh. Thereafter, the surface is functionalized by a covalent binding to activated heparin which elicits the anticoagulant activity and the interaction with blood cells. ⁸ This fibrin/heparin-network mimicks the final step of the coagulation cascade and potentially encourages the attachment and proliferation of endothelial cells (neoendothelialization) and prevents thrombus formation.

Figure 2 shows electron microscopy images of the stent wires of an uncoated and a fibrin-coated DERIVO, indicating reduced fibrin deposit and platelet adhesion on the coated stent struts.

Figure 2.

The DERIVO 2heal received a surface finishing with fibrin-based nano-coating (“heal” technology). This surface technology converts fibrinogen molecules to fibrin and covers the entire surface of the flow-diverter with a fibrin network mimicking the final step of the coagulation cascade. Electron microscopy (500- and 1000-fold magnification) shows increased fibrin and platelet deposits at the stent wires of an uncoated compared to a fibrin-coated DERIVO stent after exposure to thrombin/antithrombin III complex and platelets. The images were provided by courtesy of Acandis. .

Case report

The reported case is illustrated in Figure 3. A 72-year old female patient underwent endoscopic sinus surgery for chronic rhinosinusitis at an external hospital. Intraoperatively, a massive arterial bleeding from the right sphenoid sinus occurred, which was temporarily stopped with a nasal tamponade. Emergency CT with arterial angiography showed a 5 mm large osseus defect in the lateral sinus wall adjacent to the cavernous internal carotid artery, indicating injury of the ICA. However, there were no direct signs of arterial bleeding on CT-A. The patient was transferred to our tertiary care hospital for further treatment. Subsequently, four-vessel digital subtraction angiography (DSA) including the right ICA was performed, which showed a regular vessel wall and no active bleeding. The nasal tamponade was removed under angiographic control. Again, no active bleeding was seen on DSA. The following days, the patient was surveilled under continuous control of hemoglobin levels and repeated inspection searching of active nasal bleeding. During the hospital stay, the hemoglobin levels remained stable at 10 g/dL.

Figure 3.

A 72-year old female underwent endoscopic sinus surgery for chronic rhinosinusitis. During the intervention, massive arterial bleeding from the right sphenoid sinus occurred, which was temporarily stopped with a nasal tamponade. Computed tomography with angiography showed an osseous defect at the lateral sinus wall adjacent to the clinoid segment of the internal carotid artery (A). Also, there were no signs of active bleeding in digital subtraction angiography and the vessel wall seemed regular (B). The tamponade was carefully removed under angiographic control without complications. Control CTA after 11 days showed a pseudoaneurysm (3 mm) of the ICA that protruded through the osseous defect into the sphenoid wing (C). On the following day, the aneurysm measured 5 mm on DSA (D). The aneurysm was treated with a DERIVO 2heal flow-diverter under single anti-platelet therapy. The non-subtracted angiogram shows the radiopaque contour of the device at its full length (E). Immediately after flow-diverter implantation, contrast stasis was seen inside the pseudoaneurysm (OKM A2, F). On 5-day angiographic follow-up, the aneurysm was completely occluded (G) and there was no in-stent stenosis, as shown in the rotational angiography scan (H).

A control CT-A scan at day eleven after admission revealed a 3 mm large pseudoaneurysm at the ventromedial wall of the clinoid segment of the ICA that protruded through the osseous defect of the sphenoid sinus. In this case, endovascular coiling of the aneurysm sac may have avoided aneurysm rupture but would not have covered the injured vessel wall. Hence, reconstructive treatment of the ICA with flow-diverter implantation was planned for the following day. After groin puncture, the patient received a bolus of 5.000 IU heparin and a loading dose of ASA 250 mg intravenously. Pre-interventional diagnostic DSA showed that the maximum pseudoaneurysm diameter increased to 5 mm from 3 mm on the day before indicating a fragile vessel and aneurysm wall and a high risk of aneurysm rupture in the near future. This situation could potentially lead to life-threatening massive hemorrhage into the sphenoid sinus, which might be reinforced under DAPT. As flow-diversion does not provide immediate aneurysm occlusion, we further speculated that complete aneurysm thrombosis might occur faster under single compared to dual anti-platelet therapy. Under these circumstances, we selected the DERIVO 2heal assuming ASA monotherapy sufficient due to the nanocoating. The flow-diverter was implanted across the aneurysm neck with the ends of the flow-diverter reaching from the supraclinoid to the cavernous ICA segment. Initially after detachment of the flow-diverter, proximal unfolding of the device was incomplete, however, unfolding completed within a few minutes under observation. Immediate angiographic control after the procedure showed total filling, but moderate contrast stasis within the pseudoaneurysm (O’Kelly-Marotta [OKM] grading scale score A2). There were no procedural thromboembolic complications. After the procedure, the patient was transferred to the normal ward for further surveillance. Life-long ASA monotherapy was prescribed. Five-day angiographic control showed progressive pseudoaneurysm thrombosis with complete occlusion (OKM D). There was no in-stent thrombosis. The patient was discharged 20 days after admission without morbidity. At three-month clinical follow-up, the patient was in good physical condition without evidence of delayed thromboembolic events.

Discussion

Flow-diversion under a SAPT regimen represents the next stage in the development of flow-diversion therapy, however, it is still uncommon and indication should be strict, since experience is scarce. This is due to the comparatively high thrombogenicity of flow-diverters as they exhibit a relatively high metal exposure to the blood flow, which may lead to downstream thromboembolic stroke. To date, the most extensive data on adverse events and associated morbidity after flow diverter implantation is available for the Pipeline Embolization Device (PED). In the International Retrospective Study of the Pipeline Embolization Device (IntrePED), the ischemic stroke rate was 4.7% and overall morbidity occurred in 8.4% after PED implantation. ¹

Aiming to reduce thrombogenicity of flow-diverters, several surface technologies such as phosphatidylcholine coating, glycan-based polymer coating and electropolishing and annealing have been developed.^4–6 These surface modifications mainly reduce platelet adhesion. ⁷

In a clinical study on the DED with BlueXide finishing under DAPT, the cumulative ischemic stroke rate was 3.4% and the morbidity rate was 1.7% at 1 year. ⁹ In a registry study, Taschner et al. reported ischemic stroke in 4.2% and morbidity in 3.1%. ¹⁰ These safety results compare favourably to uncoated flow-diverters and may be in part explained by the BlueXide coating, which has been shown to reduce thrombogenicity in animal studies. ¹¹ However, implantation of the second-generation DED with BlueXide coating under a SAPT regimen has not yet been reported.

There are few case series that reported FD implantation under SAPT, mainly for FDs with HPC coating. However, these published results have been rather ambivalent so far.

Using the p48 and p64 with pHPC coating, there were no symptomatic complications or in-stent stenoses in 10 patients in the study by Lobsien et al. ¹² Likewise, Bhogal et al. observed no complications in 5 patients treated with the p48 HPC flow-diverters under prasugrel monotherapy. ¹³ Furthermore, Bender et al. reported successful implantation of the uncoated Pipeline Flex embolization device in 2 cases. ¹⁴

In contrast to these favourable results, de Castro-Afonso et al. reported 4 ischemic events among 21 patients treated with the p48 MW HPC under prasugrel monotherapy. ¹⁵ Likewise, Manning et al. reported ischemic complications in two of 14 patients treated with the Pipeline shield flow-diverter. ¹⁶

Given these inconsistent results, there is a need for further refinements of FD surface technologies and studies that evaluate appropriate indications for SAPT.

In this context, the heal coating is a refinement of the currently existing coating technologies. This nanocoating technique covers the FD surface with a fibrin network, which is potentially inert to coagulation and may encourage neoendothelialization.

For the fibrin-based heal coating, Mühl-Benninghaus et al. reported similar blood and tissue compatibility compared to non-coated counterparts and there were no adverse effects on neo-endothelialization under DAPT in the histological analysis, which is necessary for the clinical efficacy of FD treatment. ⁷

In this report, we used the DERIVO with heal coating for the emergency treatment of a rapidly growing extradural ICA pseudoanerysm, which carried a very high rupture risk with consecutive potentially life-threatening hemorrhage, assuming a reduced thrombogenicity of this device. FD treatment under a SAPT regimen was favored assuming 1) faster progressive aneurysm occlusion due to reduced anti-thrombogenic efficiency and hence reduced risk of aneurysm rupture and 2) a potentially less pronounced hemorrhage and a better surgical control in case of aneurysm rupture. There are further treatment options for such a case with individual advantages and disadvantages. Implantation of a conventional flow-diverter would require DAPT. Implantation of a covered stent results in immediate aneurysm occlusion but technical and/or symptomatic complications are frequent. ¹⁷ Coil sacrifice of the parent artery represents the definitive method for managing massive, uncontrolled bleeding, but has a relatively high thromboembolic complication rate.^17,18

Similar to the second-generation DEDs with BlueXide surface modification, the DERIVO 2heal was fully visible under fluoroscopy and the navigability was facilitated by the flexible device structure. Unfolding of the device was complete, while wall adaption was initially incomplete, yet acceptable at a tortuous part of the ICA. Besides the chronic rhinosinusitis, the patient had no pre-existing illnesses and we did not test for coagulation disorders. During the intervention and at follow-up, no thromboembolic complications and no in-stent stenosis was observed. At three-months clinical follow-up, the patient was in good clinical condition without any neurological deficits.

The concept of flow-diversion is characterized by intra-aneurysmal hemostasis and progressive thrombosis of the aneurysm sac over time. In a previous study on the conventional DED, complete and near-complete aneurysm occlusion were 70.5% and 88.7% at 6-month follow-up, respectively, and 82.2% and 100% at 1-year follow-up, respectively. ⁹ Whether the heal coating affects aneurysm thrombosis has not yet been evaluated in detail, but a similar biocompatibility of the DERIVO 2heal to uncoated counterparts indicate a similar treatment efficacy. ⁷ In the presented case, the 5 mm large pseudoaneurysm was completely occluded within 5 days after treatment. Progressive aneurysm thrombosis might have been accelerated by SAPT compared to DAPT. As we only present a single case, a general conclusion on the heal coating in terms of procedural safety and angiographic outcome cannot yet be drawn, especially not regarding SAPT. Nevertheless, we consider the DERIVO 2heal as a promising new candidate for intracranial aneurysm treatment that warrants investigation by further studies. In this context, a SAPT regimen may be chosen for a carefully selected subset of patients, especially in an emergency setting, when DAPT is deemed unfavourable.