The Medusa Multi-Coil Versus Alternative Vascular Plugs for Iliac Artery Aneurysm Embolization (MVP-EMBO) Study

Abstract: Transcatheter embolization has evolved from the use of autologous clot as the embolic agent, to stainless-steel coils, to braided-nitinol vascular plugs. However, there are disadvantages to platinum and metal coils, including procedural time, radiation exposure, mass effect, risk of distal embolization, recanalization, imaging artifacts, and cost. Therefore, a large vessel-occluding device is needed to mitigate these current disadvantages. The Medusa Multi-Coil (MMC; EndoShape, Inc) is a Food and Drug Administration (FDA)-approved embolization device constructed primarily of radioopaque coils with synthetic fibers to promote thrombogenicity, and a unique delivery platform with both proximal and distal attachment to assist with precise placement. We report our experience with the endovascular treatment of internal iliac artery aneurysms using platinum coils vs MMCs. 

J INVASIVE CARDIOL 2016;28(1):23-29

Key words: embolization, iliac artery aneurysm

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Transcatheter embolization (TE) was first performed with the use of an autologous clot in a patient who was a poor surgical candidate.¹ TE gradually progressed to the use of stainless-steel coils for large-vessel occlusion.^2,3 Over time, the development of platinum coils provided superior radioopacity and a denser coil pack,⁴ and the need for more accurate coil placement led to the development of detachable coils.^5-7 Ongoing technological advances for TE led to the braided-nitinol Amplatzer vascular plug (AVP; St. Jude Medical).⁸ However, significant disadvantages to platinum and metal coils remain, including: increased procedure time/radiation exposure; complexity; mass effect; distal embolization risk; and recanalization.^8-10 

The Medusa Multi-Coil (MMC; EndoShape, Inc) is a Food and Drug Administration (FDA)-cleared embolization device constructed primarily of coils made from a proprietary shape-memory polymer, with synthetic fibers attached to promote thrombogenicity. The polymer contains cross-linked iodine that makes the device radioopaque. Additionally, it has a unique delivery platform with both proximal and distal attachment to assist with precise placement. We report our experience with endovascular internal iliac artery aneurysm (IIAA) treatment using platinum coils or platinum coils with a nitinol plug vs MMCs.

Methods

Overall design. We report our experience with 8 patients who underwent endovascular treatment of their IIAA. Each patient underwent abdominal aortic aneurysm (AAA) screening ultrasound (US) or computed tomography (CT) imaging for suspected or known AAA that revealed IIAA (Figure 1A). The decision was made to occlude the IIAAs since it has been established that the natural progression of IIAAs is continual expansion with subsequent increase in risk of rupture. 

There were two prospective cohorts of 4 patients each based on the type of endovascular treatment for their IIAA. All patients were treated at Deborah Heart and Lung Center in Browns Mills, New Jersey. There was 1 patient in each cohort that had bilateral iliac aneurysms for a total of 10 treated IIAAs – 5 in each cohort. Cohort #1 consisted of 4 patients who had endovascular treatment of their IIAAs with platinum coils or platinum coils and 1 nitinol plug between March 2013 and February 2014. Cohort #2 consisted of 4 patients who had endovascular treatment of their IIAAs with MMCs between June 2014 and December 2014.

Patients were followed up for clinical evaluation and CT angiogram (CTA) at 30 days. The CTA was performed in order to confirm the location of the devices and classify the degree of occlusion. 

Safety variables. The primary safety variables were the occurrence, frequency, and severity of adverse events and adverse device effects. Specific adverse events associated with endovascular procedures that were evaluated included but were not limited to: blood vessel perforation or rupture; unintended thrombosis; adverse tissue reaction; thrombophlebitis; infection; hematoma formation at access site; and device migration.

Efficacy variables. The efficacy variables were related to the ability of the devices to embolize the target aneurysm and affect clinical outcome. 

Specifically, a CTA was performed at 30 days post embolization. The occlusion was graded based on a previously described grading scale¹¹ that was simplified as follows post embolization: (A) total filling; (B) subtotal filling; (C) entry remnant; or (D) no filling.

Performance variables. The performance variables were related to the ability of the devices to demonstrate lack of artifacts on CTA. The degree of imaging artifacts was graded as follows: (0) none; (1) mild; (2) moderate; or (3) severe. In addition, cost analyses were performed on each cohort group.

Preembolization procedure. Angiography and embolization were performed in a cardiac catheterization suite. All patients received intravenous conscious sedation using midazolam and fentanyl. Each patient was anticoagulated with heparin to maintain an activated clotting time (ACT) of 200-250 seconds. All patients were accessed using a femoral approach via the ipsilateral or contralateral femoral artery. The access site was prepped and draped in the usual sterile fashion. A 7 Fr vascular introducer sheath (Terumo Medical) was placed in the femoral artery for access. Contrast-enhanced angiography was performed in the catheterization lab, providing both intraarterial subtracted and unsubtracted imaging of the iliac arteries (Figure 1B) using a 5 Fr pigtail catheter (Cook Medical). Anteroposterior (AP), contralateral oblique, and lateral imaging views were obtained as necessary throughout the procedures. 

Embolization procedure: cohort #1. The target internal iliac artery was engaged using a CXI support catheter (Cook Medical), which was positioned in the main trunk of the IIAA. Embolization was performed with Interlock- 35 fibered IDC occlusion system coils (Boston Scientific). Angiographic occlusion of the IIAA was determined at 5 minutes after the last coil was placed in order to determine occlusion grade. Endovascular stents were placed in order to occlude the ostium of the artery at the discretion of the operator if suboptimal occlusion was achieved with embolization. Poststent angiograms were taken at 5 minutes in order to determine occlusion grade. 

Embolization procedure: cohort #2. The target IIA was catheterized using a CXI support catheter, which was positioned in the main trunk of the IIAA. Embolization was performed with MMCs. Angiographic occlusion of the IIAA was determined at 5 minutes after the last MMC was deployed to determine occlusion grade. Endovascular stents were placed in order to occlude the ostium of the artery at the discretion of the operator if suboptimal occlusion was achieved with embolization. Poststent angiograms were taken at 5 minutes in order to determine occlusion grade.

Postembolization procedures. Heparin was discontinued following completion of the embolization procedure. Antiplatelet therapy was started on day 1. Patients were monitored in the postinterventional unit and discharged when stable, with follow-up at 4 weeks post embolization. Postprocedural CTA was performed at the follow-up visit. 

Results

Overview. Eight patients were found to have either unilateral or bilateral IIAAs on CT or US during screening for AAA. Table 1 provides an overview of the 8 patients who underwent endovascular treatment of their IIAA. At the time of screening, 6 of 8 patients (75%) were found to have an incidental finding of one IIAA and 2 of 8 patients (25%) were found to have bilateral IIAAs, for a total number of 10 IIAAs treated. There were two cohorts of 4 patients each based on the type of endovascular treatment. One patient in cohort #1 had bilateral aneurysms treated on the same day, while one patient in cohort #2 had bilateral aneurysms treated on separate occasions.

Patient demographic data and baseline clinical characteristics. There was 1 female in cohort #1 and all males in cohort #2. The mean age of the patients in cohort #1 was 7.8 years greater than in cohort #2. The ages ranged from 68-90 years. 

All 8 patients (100%) had dyslipidemia, hypertension (HTN), and coronary artery disease (CAD). In cohort #1, 1 of 4 separate patients (25%) had congestive heart failure (CHF) and diabetes mellitus (DM), and was a smoker. In cohort #2, a total of 2 of 4 patients (50%) had CHF, 1 of 4 patients (25%) had a history of stroke, 2 of 4 patients (25%) had DM, and 3 of 4 patients (75%) were smokers. 

Embolization procedure characteristics: cohort #1. Table 2 provides procedure characteristics for each patient in cohort #1. One of 4 patients (25%) had bilateral IIAAs and 3 of 4 patients (75%) had unilateral IIAAs. In total, there were 5 IIAAs treated in cohort #1 with coils. The mean baseline aneurysm diameter (n = 5) was 2.7 cm (range, 1.0-5.3 cm). The mean number of coils used to achieve adequate embolization was 7.2 coils (range, 3-13 coils). An AVP was used in 1 patient due to inadequate IIAA occlusion post coil deployment. Immediate postembolization angiography demonstrated subtotal filling (grade B) in 4 out of 5 cases (80%) and entry remnant (grade C) in 1 case (20%). In all 5 cases (100%), stents were placed in the common iliac artery (CIA) and external iliac artery (EIA) in order to occlude the ostium of the treated artery due to suboptimal embolization. The stents used in cohort #1 were AFX (Endologix), ICast (Atrium Med), Ovation (Trivascular), and Endurant (Medtronic). Following stent placement, all 5 cases (100%) demonstrated complete occlusion of the IIAA (grade D) on angiography (Figure 2). The mean duration of the procedure was 2.24 hours (range, 1.0-3.9 hours).

Follow-up: cohort #1. In cohort #1, a total of 4 out of 5 patients were placed on aspirin and clopidogrel (80%) and 1 patient was placed on aspirin alone (20%). 

Postembolization CTAs of the 3 cases that returned for follow-up (60%) demonstrated clinically significant occlusion with no contrast filling of the aneurysm (grade D). However, there were significant CT imaging artifacts in all 3 cases (100%) graded as severe (grade 3) (Figure 3). No further CTA imaging was obtained in these patients following complete occlusion. Two of the patients from cohort #1 died from non-cardiac causes prior to follow-up CTA. 

Embolization procedure characteristics: cohort #2. Table 3 provides procedure characteristics for each patient in cohort #2. One of 4 patients (25%) had bilateral IIAAs and 3 of 4 patients (75%) had unilateral IIAAs. In total, there were 5 IIAAs treated in cohort #2 with MMCs (Figure 4A). The mean baseline aneurysm diameter (n = 5) was 2.4 cm (range, 1.6-3.2 cm). The mean number of coils used to achieve adequate embolization was 2.6 MMCs (range, 2-3 MMCs). Immediate postembolization angiography demonstrated subtotal filling (grade B) in all 5 cases (100%) (Figure 4B). In 4 out of 5 cases (80%), stents were placed in the CIA and EIA in order to occlude the ostium of the treated artery due to suboptimal embolization. In 1 case, a stent was not placed at the operator’s discretion due to the lack of peripheral access for upsizing and stent placement. The stents used in cohort #2 were Ovation, Viabahn (Gore), and Endurant. Following stent placement, all 5 cases (100%) demonstrated complete occlusion of the IIAA (grade D) on angiography. The mean duration of the procedure was 1.86 hours (range, 0.9-2.8 hours).

Follow-up: cohort #2. In cohort #2, a total of 3 out of 5 patients were placed on aspirin and clopidogrel (60%), 1 patient was placed on aspirin and prasugrel (20%), and 1 patient was placed on aspirin alone (20%).

Postembolization CTAs of the 4 cases that returned for follow-up (80%) demonstrated clinically significant occlusion with no contrast filling of the aneurysm (grade D). None of the cases demonstrated any CT imaging artifacts (grade 0) (Figure 5). No further CTA imaging was obtained in these patients following complete occlusion. The last patient in this cohort had not yet returned for the follow-up CT at the time of this data collection. 

Safety. Table 4 shows the adverse events and length of stay (LOS) for each aneurysm case. There was no device migration, infection, thrombophlebitis, unintended thrombosis, acute blood vessel rupture, or perforation. The mean LOS was 1.3 days for cohort #1 and 0.8 days for cohort #2. Patient 01-03 required an intensive care unit stay secondary to bleeding at the access site. Two of the 8 patients (25%) died due to non-cardiac causes. One patient was readmitted to the hospital within 3 days of discharge secondary to exacerbation of heart failure symptoms. One patient was readmitted to the hospital within 22 days after discharge secondary to anemia and hematoma at the access site, requiring a blood transfusion.

Cost. Table 5 shows the device and hospital costs associated with each cohort. The mean coil cost in dollars was $6466.40 (range, $2632.00-$11,700.00). The mean MMC cost was $3630.00 (range, $3300.00-$4950.00), which is almost half the cost of the coils ($3630.00/$6466.40; 56.1%). The mean stent cost for cohort #1 was $7634.00 (range, $3380.00-$10,718.00). The mean stent cost for cohort #2 was $3778.00 (range, $0-$6420.00), which is less than half the cost of the stents used in cohort #1 ($3778.00/$7634.00; 49.5%). One patient from cohort #1 required an intensive care unit stay, at an additional cost of $3600.00. The mean total hospital cost for cohort #1 (n = 5) was $3300.00 (range, $2400.00-$6000.00). The mean total hospital cost for cohort #2 (n = 5) was $1920.00 (range, $1200.00-$2400.00), which was almost half the total hospital cost for cohort #1 ($1920/$3300; 58.2%).

Discussion

Peripheral vascular embolization techniques and devices have evolved over the past 40 years.^1-10 In particular, the use of different of metal alloy types such as nitinol, platinum, tungsten, and iridium have been configured in many different embolization designs. In addition, the delivery method for different embolization devices ranges from simple pushing to commercialized injection and detachment mechanisms.^12,13 Thus, there are dozens of endovascular options for physicians. However, despite advancements in the metal-based designs, disadvantages include technical complexity resulting in increased procedural time with associated radiation and intravenous contrast agent exposure, device migration, mass effects, and metal artifacts on radiological imaging. Depending on the type of metal alloy, such as platinum, and the specific size of the target anatomical region, cost may be substantially increased.¹⁴

The MMC was developed in order to eliminate many of the problems that exist with metal embolization devices, such as coils. The MMC is constructed from multiple 0.018˝ shape-memory polymer coils with synthetic fibers attached to promote thrombogenicity. This multiple-coil construct has both proximal and distal attachments, which offers the advantages of a denser coil pack positioned more precisely in a single deployment as opposed to the delivery of multiple individual coils. This unique single-delivery platform offers the potential for overall shorter procedural times and reduced exposure to radiation and dye load. In addition, the polymer material contains cross-linked iodine, which makes the device radioopaque, yet produces minimal to no artifact on radiologic imaging. 

In our series, we report the endovascular treatment of IIAAs using platinum coils and platinum coils with a nitinol plug (cohort #1) vs MMCs (cohort #2). This is the initial report of the use of MMCs for the treatment of vascular aneurysms, specifically IIAAs. Given their anatomical location within the pelvis, they are more frequently found incidentally upon imaging as opposed to physical examination, as 10%-20% of AAAs have associated IIAAs.¹⁵ This is consistent with the 10 IIAAs found incidentally during AAA screening using US or CT imaging for suspected or known AAA in our series. In our series, 25% of the patients had bilateral IIAAs, which is consistent with literature showing bilateral occurrence in up to 30%.^15-17 The natural progression of IIAAs is continual expansion with subsequent increase in risk of rupture. 

The common underlying pathophysiology in aneurysmal disease is related to systemic variables, with male gender and age as the lead demographic variables. Smoking is the most common environmental risk factor, and was seen in 50% of our patients.¹⁶ Degenerative atherosclerosis is the most common vascular abnormality, which is usually widespread throughout the vascular system and associated with additional co-morbid conditions such as CAD, hypertension, dyslipidemia, and cerebrovascular accidents.^16,17 The demographic data for the 8 patients in our series were representative of the published literature, as 7/8 patients were male and all patients were advanced in age (range, 68-90 years). The baseline characteristics of the patients in our series were consistent with elderly patients with associated aneurysmal and metabolic diseases, as all had CAD, dyslipidemia, and HTN. 

The average size and range of the IIAAs in cohort #1 was slightly larger than cohort #2, as mean baseline aneurysm diameter was 2.7 cm in cohort #1 (range, 1.0-5.3 cm) and 2.4 cm in cohort #2 (range, 1.6-3.2 cm). However the average number of coils used to achieve adequate embolization in cohort #1 (mean, 7.2 coils; range, 3-13 coils) was >2.5x greater than the mean number of MMCs in cohort #2 (mean, 2.6 MMCs; range, 2-3 MMCs). In addition, in cohort #1, an AVP was used in 1 patient due to inadequate IIAA occlusion post coil deployment. This translated to a longer overall average procedure time for cohort #1 compared with cohort #2 The multiple-coil polymer construct of the MMC contributes to the ability to treat a larger anatomical area in one delivery vs the introduction of multiple individual coils. This contributes to the overall shorter procedure time, reduced radiation exposure, and reduced dye load, which are important factors when treating an elderly population. In addition, the multiple loops of soft polymer produce a dense coil pack without the typical gaps seen with metal coils. These design features contributed to the use of a smaller number of MMCs per aneurysm vs metal coils used in our series. 

The lightness of the multi-coil polymer becomes more important as the anatomical region to be treated increases and the subsequent need for an increased metal burden increases. The mass effects vary by location and position within the surrounding parenchyma.^18,19 The MMC offers a new alternative for embolization if there is concern regarding an overwhelming metal burden. 

The metal burden is another concern for follow-up radiographic imaging. Currently, there is no CT or magnetic resonance imaging method that is optimal for follow-up evaluation after endovascular embolization with metal embolic devices due to the metallic artifacts.²⁰ More-invasive imaging procedures such as CTA are often used for evaluation after endovascular treatment, such as in our series. However, these are suboptimal as well due to the required need for radiation exposure and use of contrast agent. In addition, the assessment of aneurysms after metal-coil embolization is hindered by the metal-coil mass, which can obscure neck recanalizations and compaction. In cohort #1, the metal artifacts on the follow-up CTAs were severe (grade 3) in all 3 cases. However, in cohort #2, there were no significant CTA artifacts present in the 4 cases that returned for follow-up. The lack of imaging artifacts offers a more safe and efficacious imaging method for follow-up evaluations after endovascular procedures. This is especially important in elderly populations with many co-morbidities, where procedural time, radiation dose, and contrast agent exposure are more problematic.

Overall, cohort #1 had more adverse events, including 2 deaths and more days spent in the hospital (including an intensive care unit admission) vs cohort #2. This translated into higher total hospital costs for cohort #1. The total cost for metal coils was almost double the cost of the MMCs, which is consistent with the fact that more than 2.5x more coils were necessary to achieve adequate aneurysm embolization vs MMCs.

Study limitations. This study has significant limitations, primarily attributable to the small sample size of the cohort groups. Therefore, the analyses within the study (including performance variables and cost analyses) have little power to make definitive encompassing claims. However, there are significant trends suggesting positive attributes of the MMCs that will need to be validated in larger studies.

Conclusion

Our initial experience using MMCs for embolization of IIAAs demonstrates the potential for significant advantages over the use of metal coils. The unique multi-coil polymer MMC design with proximal and distal attachments allows the creation of a dense coil pack with the ability to control the positioning of the distal portion in a single step. This has the potential to simplify the overall embolization procedure, and to reduce procedural time, exposure to radiation, and amount of contrast media. The shape-memory polymer has cross-linked iodine to produce radioopacity on imaging, but without the obstructive artifacts seen with metal embolization devices. Longer-term follow-up on the MMC is indicated to assess the efficacy and durability of occlusion.

References

1.    Lubarsky M, Ray C, Funaki B. Embolization agents — which ones should be used when? Part 1: large vessel embolization. Semin Interv Radiol. 2009;26:352-357.

2.    Gianturco C, Anderson JH, Wallace S. Mechanical devices for arterial occlusion. Am J Roentgenol Radium Ther Nucl Med. 1975;124:428-435.

3.    Wallace S, Gianturco C, Anderson JH, Goldstein HM, Davis LJ, Bree RL. Therapeutic vascular occlusion utilizing steel coil technique: clinical applications. AJR Am J Roentgenol. 1976;127:381-387.

4.    Prasad V, Chan RP, Faughnan ME. Embolotherapy of pulmonary arteriovenous malformations: efficacy of platinum versus stainless steel coils. J Vasc Interv Radiol. 2004;15(2 Pt 1):153-160.

5.    Nemoto S, Iwama J, Mayanagi Y, Kirino T. Coil embolization of cerebral aneurysms. Experience with IDC and GDC. Interv Neuroradiol. 1998;4 Suppl 1:159-164.

6.    Kinoshita A, Ito M, Skakaguchi T, et al. Mechanical detachable coil as a therapeutic alternative for cerebral aneurysm. Neurol Res. 1994;16:475-476.

7.    Marks MP, Chee H, Liddell RP, Steinberg GK, Panahian N, Lane B. A mechanically detachable coil for the treatment of aneurysms and occlusion of blood vessels. AJNR Am J Neuroradiol. 1994;15:821-827.

8.    Ratnam LA, Walkden RM, Munneke GJ, Morgan RA, Belli AM. The Amplatzer vascular plug for large vessel occlusion in the endovascular management of aneurysms. Eur Radiol. 2008;18:2006-2012. Epub 2008 Apr 17. 

9.    White HA, Travis SJ. The Amplatzer vascular plug. Cardiovasc Intervent Radiol. 2008;31:448-449.

10.    Widlus DM, Moeslein FM, Richard HM 3rd. Evaluation of the Amplatzer vascular plug for proximal splenic artery embolization. J Vasc Interv Radiol. 2008;19:652-656. Epub 2008 Mar 17.

11.    O’Kelly CJ, Krings T, Fiorella D, Marotta TR. A novel grading scale for the angiographic assessment of intracranial aneurysms treated using flow diverting stents. Interv Neurorad. 2010;16:133-137.

12.    Hui FK, Fiorella D, Masaryk TJ, Rasmussen PA, Dion JE. A history of detachable coils: 1987–2012. J Neurointerv Surg. 2014;6:134-138. Epub 2013 Feb 13.

13.    Vaidya S, Tozer KR, Chen J. An overview of embolic agents. Semin Intervent Radiol. 2008;25:204-215.

14.    Zander T, Medina S, Montes G, Nunez-Atahualpa L, Valdes M, Maynar M. Endoluminal occlusion devices: technology update. Med Devices. 2014;7:425-436.

15.    Scheinert D, Schroder M, Steinkamp H, Ludwig J, Biamino G. Treatment of iiac artery aneurysms by percutaneous implantation of stent grafts. Circulation. 2000;102:253-258.

16.    Normal PE, Powell JT. Site specificity for aneurysmal disease. Circulation. 2010;121:560-568.

17.    Sakamoto I, Sueyoshi, E, Hazama S, et al. Endovascular treatment of iliac artery aneurysms. Radiographics. 2005;25:S213-S227.

18.    Malisch TW, Guglielmi G, Vineula F, et al. Unruptured aneurysms presenting with mass effect symptoms: response to endosaccular treatment with Guglielmi detachable coils. Part I. Symptoms of cranial nerve dysfunction. J Neurosurg. 1998;89:956-961.

19.    Bilbao J, Martiz-Cuesta A, Urtasun F, Cosin O. Complications of embolization. Semin Intervent Radiol. 2006;23:126-142.

20.    Tulsyan N, Kashyap VS, Greenberg RK, et al. The endovascular management of visceral artery aneurysms and pseudoaneurysms. J Vasc Surg. 2007;45:276-283.

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From the Division of Interventional Cardiology and Endovascular Medicine, Deborah Heart and Lung Center, Browns Mills, New Jersey.

Funding: The authors received research grant support from Endoshape for the completion of this study. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr George reports consultant fees from EndoShape. Dr Kovach reports a small (0.7%) stock purchase. The remaining author reports no conflicts of interest regarding the content herein.

Manuscript submitted April 23, 2015, provisional acceptance given June 29, 2015, final version accepted September 15, 2015.

Address for correspondence: Jon C. George, MD, Deborah Heart and Lung Center, 200 Trenton Road, Browns Mills, NJ 08015. Email: jcgeorgemd@gmail.com