Preliminary report on a new concept stent prototype designed for venous implant

Abstract

Venous obstruction at iliocaval level in both forms, primary and secondary, is a significant cause of severe chronic venous insufficiency. A new therapeutic approach to this pathology emerged with the introduction of stenting procedures that proved effective, leading to good long-term results. However, at present, the majority of implanted stents have been designed for arterial implant and this can pose a limit in particular districts. The purpose of this preliminary acute study was to verify the deliverability and safety of a new stent specially designed for venous-vessel implant. We assess the safety and deliverability of two braided, self-expanding, nickel–titanium stents (Jotec GmbH, Hechingen, Germany) specially designed for endovascular implant in veins. The two stents, despite being based on the same concept, have a different design: stent A presents a proximal tapering shape specially designed to reduce migration, while stent B does not. Both of them are enlarged at their distal extremity and present variable radial force the length of the stent itself, the said force becoming very high in the intermediate segment. Stents were implanted in the internal jugular vein of a sheep, showing optimal deliverability. The completion venography showed the migration of stent B into the right atrium. Stent A maintained its location, confirmed by intravascular ultrasound examination. No scaffolding effect was detected and an adequate adherence and adaptability to the vein wall was obtained. In conclusions, the stent A design matches the characteristics required by vein implants. Stability is achieved even where difficult anatomical conditions apply, such as in the jugular vein. Deployment is easy and precise in a given landing zone. Radial resistive force is very high, as required in specific vein districts, but is also associated with good flexibility. Following this preliminary acute report, further studies are required.

Keywords

Chronic CerebroSpinal Venous Insufficiency (CCSVI)iliac stenting May–Thurner syndrome stents post-thrombotic syndrome

Background

Venous obstruction at iliocaval level in both forms, primary and secondary, is a significant cause of severe chronic venous insufficiency of the lower limbs.

A new therapeutic approach to this pathology emerged with the introduction of stenting procedures.

After pioneering procedures which addressed the central veins, mainly in malignant diseases,^1–3 the first endovascular procedure for iliac vein obstructive disease was performed in 1995.⁴ At present, the endovascular treatment of iliocaval obstruction is a well-established technique.⁵ While venoplasty alone has shown poor efficacy,⁶ venous stenting, both direct and after venoplasty, has proved effective, leading to good long-term results.⁷

However, the majority of implanted stents have been designed in origin for arterial use and this can pose a limit in particular districts as well as affecting outcomes.⁸ At present, only few recent experiences about the insertion of venous dedicated stents have been reported; medium- and long-terms outcomes are still lacking.^9,10

Veins present specific features, both physiological as well as pathological that differ from arteries in many respects. Veins present a physiologic variation in calibre and length due to vein wall compliance. Specific anatomic areas, frequently the left common iliac vein, are submitted to extrinsic compression. Obstructive vein lesions usually are determined by post-thrombotic fibrosis, which is different from atherosclerotic wall damage. Post-thrombotic lesions usually involve long segments, frequently overpassing the inguinal crease and can be very hard. Thus, an ideal vein stent should be flexible, resistant to compression and fracture especially in focal segments, long and wide.

The aim of this acute study was to show that placement of a new concept venous stent was feasible and that the new design fulfilled its purpose.

Materials and methods

Stent design and delivery system

The original characteristic of this stent is its tapered shape, combined with variable radial resistive force (RRF) all along its length. In fact, at the present, no tapered venous stents have been described, nor such a pattern of variation in RRF. We designed two prototypes of stent, named A and B, in order to verify whether the difference of their structure can influence a possible migration. Three segments with different features compose both stents. The stent’s characteristics are listed in Table 1. The stent A (Figure 1) is flared at both ends. The proximal end (upper part in the figure) presents a wide mesh structure with a lower RRF, created to fit the vein enlargement in order to fix the higher RRF part in the correct position, thus preventing slipping. This characteristic determines the conceptual difference between stent A and stent B. In fact stent B (Figure 2) is not flared at its upper end, but cylindrical. The distal part, which is the longer one, presents a progressively decreasing RRF coupled with a tapered structure, created to fit the whole length of the target vessel. This part is similar in both stents. The variations in diameter and RRF have been conceived to create congruence with the peculiar vein-segment features commonly found in the left common iliac vein, the common femoral vein, and the jugular vein. This characteristic, combined with the peculiarity of braided structures used to maintain a constant luminal diameter even when the stent is tightly bent, as well as the stent’s flexibility, seems to be particularly suitable to fit vein anatomy.

Figure 1.

Stent type A (the upper part defined as ‘proximal’ in the text).

Figure 2.

Stent type B (the upper part defined as ‘proximal’ in the text).

Table 1.

Characteristics of the implanted stents.

Feature	Stent type A	Stent type B
Material	NiTi alloy (50.6% Ni, 49.2% Ti, and 0.24% Cr)	NiTi alloy (50.6% Ni, 49.2% Ti, and 0.24% Cr)
Design	Braiding of ø 0.15 mm wires Flared ends	Braiding of ø 0.15 mm wires Only distal flare end
Marker	Gold, at the distal end of the cylindrical segment	Gold, at the distal end of the cylindrical segment
Sample production	TS-Machine	Manual production
Stent length
Constrained	115 mm	138 mm
Unconstrained	51 mm	53 mm
Proximal stent segment	Conical	Cylindrical
Segment length/diameter	12 mm/ø 16 mm	10 mm/ø 12.5 mm
Middle stent segment	Cylindrical	Cylindrical
Segment length/diameter	10 mm/ø 12.5 mm	10 mm/ø 12.5 mm
Distal stent segment	Conical	Conical
Segment length/diameter	29 mm/ø 21.5 mm	33 mm/ø 20 mm
Catheter working length	1202 mm	1195 mm

Both stents were deliverable using a 9Fr deployment catheter, which provide a pull-back monorail technology. The deployment systems must be advanced to target the vessel position over a 0.035″ guidewire. The delivery system with an integrated push–pull movement allows precise positioning and deployment of the stent itself. The selected stent diameter was determined by measuring the calibre of the vein in the landing zone position. The landing zone is dictated by the need to deploy the high radial force part at the jugular ostium, whose diameter is assessed using intravascular ultrasound (IVUS).

Study design

Two stents were inserted using endoluminal percutaneous implant in the right and the left internal jugular veins of a sheep. The stent A was inserted on the right side, the stent B on the left one. Imaging was performed using venography and IVUS. After stent implantation, the sheep was immediately euthanized and necropsied.

The sheep jugular vein was selected because of its similarities with the human venous system, as demonstrated by previous authors.¹¹ In detail, we selected the sheep’s internal jugular vein as implant zone, since it is undoubtedly one of the most challenging district, due to its straight confluence in the brachio-cephalic vein, determining a high risk of migration, and to the calibre variations.

Surgical procedure

The study was performed in compliance with the Guidelines for Animal Experimentations laid down by the Animal Protection Committee of the local state. The surgical procedure was performed using standard aseptic techniques by an experienced surgeon, skilled in endovascular procedures. Heparin was administered intravenously at a dose of approximately 100 IU/kg. The left femoral vein was cannulated with a 10 Fr introducer (Cook Medical Inc., Bloomington, USA). A coated guide wire (Terumo Medical Corps., Somerset, NJ, USA) was conducted under angiographic control into the jugular vein and a diagnostic catheter (Cook Medical Inc., Bloomington, USA) was then introduced. A venography was performed (Siemens Avantic System Siemens, France; contrast media, Hexabrix® 320, Laboratoires Guerbet, France). The coated guide wire was replaced by a stiff guide wire and an IVUS probe (Visions PV 8.2 Digital IVUS Catheter, Volcano Corps) was introduced and connected to the ultrasound unit system (IVUS, Volcano corps). The diameter of the jugular vein was measured using IVUS at its proximal and distal parts, as well as at the ostium, to determine the exact size of the stent graft to be used. The IVUS scanning was also applied to define the stent-landing zone. The intravascular probe was removed and the catheter containing the appropriately sized stent graft was then introduced and placed at the selected location. The choice of the stent-landing zone was dictated by the need to achieve greater precision in positioning the higher radial-force segment of the stent on the jugular ostium. The stent B was deployed in the left jugular vein, and the catheter was then removed. The IVUS probe was introduced on the stiff guide wire to assess correct stent deployment (complete adherence to the vein wall, adequate landing zones). A completion venography was performed. The same procedure was repeated in the right jugular vein, where the stent A was implanted.

Terminal procedure

After implantation, the sheep was immediately euthanized by a lethal injection of a barbiturate.

After dissection of the jugular veins and before sampling, an in situ macroscopic examination of the external vessels (right and left jugular veins) was conducted. The implanted sites were then harvested and opened to evaluate possible local tissue damages. Macroscopic pictures of the implanted sites (in situ and harvested, open jugular veins) were taken.

Results

The stent was successfully implanted in both cases. No technical problems occurred at the deployment of the stents and during the retrieval of the delivery system.

Stent A showed, both at venography and IVUS, perfect adherence to the venous wall (Figures 3 and 4). The deployment was precise, located in the selected predefined landing zone. No scaffolding effect occurred. The stent showed full patency at necroscopic examination (Figures 5 and 6).

Figure 3.

Stent A after deployment: Venographic image. No scaffolding effect occurred.

Figure 4.

IVUS imaging showing the good adherence of the stent to the venous wall.

Figure 5.

Stent A placed in the right jugular vein.

Figure 6.

Harvested right jugular vein with stent placed in.

Regarding stent B, in which the specific proximal enlargement characteristic of the A design stent was absent, migration into the right atrium was observed immediately after implantation.

Discussion

This acute study was designed to test the specific features of a new concept design stent created to solve problems related to venous implant. The analysis of the problem arising during venous procedures, both in our clinical practice and described in literature, allowed us to identify key elements in the structure of a venous dedicated stent.¹²

Firstly, we considered the braided structure as the best option, due to its flexibility. On the other hand, braided stents present a risk of slipping and migration, especially in specific areas, such as the caval confluence of the left common iliac vein, where focal external compression may determine stent squeezing. The new concept consists in creating a stent with variable calibre capable of fixing the stent itself in anatomic areas where the risk of slipping is high.

The final design leads to the creation of a tower-shaped stent with asymmetric distribution of the above-mentioned features, reversible up-side down, depending on the implantation district.

The most frequent implant site is the left common iliac vein when treating primary obstruction (May–Thurner syndrome).¹³ The problems related to this specific site are linked to the very high RRF required in the cross point by the right common iliac artery, or the aortic bifurcation, and the risk of downward migration due to slipping. To avoid this problem, a straight braided stent should protrude into the cava; however, the length of the protrusion is defined empirically thus determining a possible jailing of the controlateral outflow and consequently increased thrombotic risk. The alternative could be to implant a new venous dedicated non-braided stent, but medium- and long-term outcomes are at the present not available. In this new concept stent, the enlarged (short) proximal part was designed to avoid downward migration and to fix the highest RRF part of the stent in exactly the required position. The highest RRF segment has to be precisely matched to the diameter and length of the vein in its landing zone, in order to avoid braiding geometry variation that can induce a decrease in radial force itself. To this end, we strongly recommend calibre assessment by means of IVUS.¹⁴ In a hypothetical use in treating primary iliac vein obstruction, the highest RRF part should be precisely deployed at the arterial cross point, and the shorter flared should provide fixation without protrusion in cava. The distal part of the stent, which is the longer one, presents a progressively increasing diameter, thus fitting the iliac anatomy and allowing flexibility and adaptability of the stent itself during movement.

When stents are implanted in post-thrombotic obstruction, to allow efficient inflow from the leg, the common femoral vein should be treated in most cases. In fact, in post-thrombotic disease, the common femoral vein is frequently involved in the obstructive process, and leaving it untreated may lead to failure due to occlusion of the whole implant. To extend the stent implant into the common femoral vein requires bridging the inguinal ligament, which exerts a very high force.¹⁵ Due to this element, laser-cut stents designed for arterial system are usually not employed in this area, given the risk of fracture; the behaviour of the new vein-dedicated nitinol mesh stents has to be assessed. In the hypothesis of implanting the new stent in this area, the highest RRF part must be located beneath the inguinal ligament. To this end, the stent has to be placed upside down. The short-flared segment will adapt easily to the common femoral vein without risk of barring the deep femoral vein junction.

The anatomy of the internal jugular vein junction in sheep is one of the sites where the risk of migration can be accurately assessed, and the precision of deployment subsequently tested.

The A design, provided with two tapered ends, satisfied both requirements. Moreover, the completion venography and IVUS examination showed a snug fit with the vein wall without the scaffolding effect, which can be a potential complication in braided-stent implantation.

This application may be a possible option in treating obstructed flow in jugular veins in humans, where the challenge is to resolve the ostium stenosis determined by malfunctioning valves, while maintaining the physiologic venous compliance of the jugular vein.¹⁶ The jugular vein fills in the supine position and collapses in the standing position. The only vein segments which do not change, as shown in IVUS examination, are the junction where the valve is located. The above-mentioned issues can be resolved by fixing the part which exerts the highest RRF at the junction of the jugular vein (Figure 7).

Figure 7.

Hypothetical placement of the stent A, with its higher RRF segment in correspondence of the valve insertion. (a) In supine position, the jugular vein is filled. (b) In standing position, the jugular vein can collapse as in physiology.

This stent prototype represents the first realization of the concept that variation in calibre and in RRF could better match venous features than cylindrical stents, disregarding they are braided or laser cut. The reported diameters and segment lengths have been chosen to match the sheep jugular vein anatomy and consequently must be changed to match human anatomy.

Conclusions

Differences between arterial and venous systems justify research into designing specifically vein-dedicated stents.

Future animal studies will establish whether the new concepts applied in creating this stent are effective in achieving a match in variable vein conformations, thus sanctioning its clinical application.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors disclose they will receive royalties from the company (Jotec) that holds patents relating to the device described in the manuscript.

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