Physician-made pericardium stent graft as a potential endovascular alternative for infectious aortic disease – an ex-vivo proof-of-concept study

Abstract

Purpose.

The treatment of infectious aortic disease is still challenging with open surgical debridement and reconstruction using biological, preferably autologous material, being the treatment of choice. However, these procedures are associated with high morbidity and mortality. Endovascular therapy is often considered a bridging method only, since the biologically inactive fabric of the covered stent grafts usually cannot be treated sufficiently with anti-infective agents in the event of a (obligate) consecutive secondary graft infection. This study aims to prove the feasibility of a physician-made pericardium stent graft ex-vivo.

Technique.

A state-of-the-art TEVAR was modified by separating the fabric from the z-stents and suturing a hand-sewn bovine pericardium tube to the bare metal. Feasibility of preparation, re-sheathing, and delivery is demonstrated in an ex-vivo model.

Conclusion.

This first xenogeneic stent graft could be manufactured and deployed successfully. In the future this may provide a bridging alternative for high-risk patients with infected native aortic aneurysm or aortic fistulas, eventually followed by surgical or thoracoscopic/laparoscopic debridement. Further studies on simulators or animal models are needed to test the technique and investigate its long-term durability. Additionally, this study prompts reflection on whether materials currently used should be further developed to prevent graft infections.

Introduction

The treatment of infectious aortic disease, such as infected native aortic aneurysms or aortic fistulas is still challenging. Open surgical debridement and reconstruction using biological material is the treatment of choice. ¹ This includes, for example, autologous deep vein, cryopreserved cadaveric aorta or bovine pericardial prostheses. However, these procedures are associated with high morbidity and mortality. ¹ Thus, long-term antibiotic treatment together with the best supportive care measures avoiding invasive graft removal is being discussed more frequently. ²

Often, such high-risk patients present as emergencies with bleeding complications at risk of death. In these cases, a standard polyester stent graft can be implanted as a bridging procedure. After stabilisation, the stent graft is typically replaced by open means, as the biologically inactive fabric of the covered stent grafts cannot be effectively treated with current anti-infective agents and consequently becomes infected, too. ¹

The question arises whether other materials can be used as primary fabric in such detrimental situations, less susceptible to infections or on which anti-infective agents work better than on alloplastic materials. In addition, a better outcome due to reduced invasiveness might be achieved with an endovascular procedure using biologically covered stent grafts.

As demonstrated more than 20 years ago for cardiac stents, other materials, such as bovine pericardium can be used instead of polyester to cover stent grafts. ³ Here, successful implantation has been shown in animal experiments and in humans. ³

For this purpose, a novel proof-of-concept in an ex-vivo model elucidates, whether the preparation of such a “biological aortic stent graft” is possible at all.

Technique

1. Select a commercially available stent graft of the target size with an appropriate oversizing of 10–20%. We used a Zenith® TX2®, ZDEG-P-32–142-PF from Cook Medical, Bloomington, USA) (Supplemental Figure 1A).

2. Release the stent graft on a sterile back table (Supplemental Figure 1A).

3. Detach the stent graft from the delivery system by cutting the distal retaining suture from the trigger wire in the case a Zenith® TX2®graft is used. As the stent graft has no proximal fixation in the form of baresprings, it can be easily detached (Supplemental Figure 1A, Video S1).

4. Remove all synthetic coverage from the Z-stents (Supplemental Figure 1A).

5. Cut a bovine pericardium rectangle (thickness: 0.25–0.75 mm) to the required size: length * stent graft perimeter + 2 mm (for suture) (Supplemental Figure 1B). To calculate the perimeter use: P = 2r*π. We used a Peri-Guard from Synovis, St Paul, USA, with perimeter P = 32*π = 100.5 mm.

6. Create a tube graft with a polypropylene 5–0 running suture with stop sutures (Supplemental Figure 1C). We used Prolene^TM from Ethicon^TM, Georgia, USA.

7. Insert the Z-stents with appropriate spacing and fixate the Z-stents circularly with multiple single knots (Supplemental Figures 1D and 2A).

8. Put the pericardial graft onto the original delivery system and fixate it to the corresponding distal trigger wire of the delivery system with a polypropylene 3–0 loop (Supplemental Figure 1D, Video S1).

9. Re-Sheathing: The graft is either packed with multiple tourniquets or a sterile crimper, usually used for transcatheter aortic valve implantation (Supplemental Figure 2B, Video S1). Care must be taken to ensure that the graft is not torqued or dislodged and the delivery system is not damaged. Note: there must be a smooth finish at the tip.

10. Flush the delivery system adequately and prepare the graft according to the manufacturer's instructions for use.

We performed the implantation in a 3D ex-situ model, initially used as a prototype of a fenestrated stent graft. The pericardium stent graft could be unpacked and released without any problems. A proper positioning with sufficient sealing was achieved (Supplemental Figure 2C and D, Video S2).

Discussion

In this proof-of-concept experiment, we demonstrated that it is technically feasible to prepare a pericardium aortic stent graft and implant it successfully after re-sheathing in an ex-vivo model.

Applications of such a prosthesis could be numerous: For example, pericardial stent grafts could be implanted as a permanent solution in the case of infections in high-risk patients. Or, one could consider implanting this prosthesis primarily in patients with aortic fistulas who are at high perioperative risk, followed by either open surgical or endoscopic debridement, lavage, drainage and fistula closure. Even further modifications incorporating fenestrations or branches are thinkable. ⁴ Additionally, the prosthesis could be soaked in rifampicin or loaded with bacterial phage.

It is debatable whether there is enough time to create such a stent graft in emergency cases. In our experience, the time required for this corresponds to that of a physician-modified fenestrated prosthesis with approx. 2–3 fenestrations, for which we work with two teams. One team takes care of the patient (from positioning to washing and draping), the puncture and the wire placement. The other team creates the prosthesis. The duration to prepare such a graft naturally depends on experience and practice, which must be taken into account when fabricating such prostheses.

Further technical considerations include using staple sutures instead of hand-sewing. Re-sheathing could be facilitated by loading the stent graft to a large DrySeal sheath (W. L. Gore & Associate, Newark, USA) as described by the PERTINI method ⁵ (Video S3).

As an alternative to the technique described above, in urgent cases it is also possible to modify the pioneering work of Parody and colleagues from 1991 ⁶ : After preparation of the pericardial tube graft as described above (steps 1 to 6), Palmaz stents are loaded proximally and distally on valvuloplasty balloons and fixed to the pericardium by sutures. The graft can then be loaded on an appropriately sized sheath and deployed by retracting the sheath and inflating the balloons.

Limitations

This is an ex-vivo proof-of-concept experiment. The demonstrated technique has not yet been tested in-vivo. Animal experiments are necessary to explore the exact properties of sealing, migration properties, and long-term durability. It is crucial to test whether these are as durable as conventional physician-modified stent grafts. ⁷ Potential micro-damages that may occur to the material during re-sheathing must be further clarified, for example through microscopic testing.

Conclusion

The handmade creation of a bovine pericardium covered stent prosthesis as well as the re-sheathing and deployment is technically feasible. Further studies on simulators and animal models are required for verification of the technique and durability. This proof-of-concept should also encourage reflection on whether the materials used today should be further developed to prevent prosthetic infections.