Local ethics committee concern

The goal of this multi center prospective observational study is to evaluate the iliac patency rate during the time in patients treated with "AFX (Endologix, Irvine Calif)" unibody stent-graft for aorto-iliac occlusive disease The main question it aims to answer is if The Unibody AFX (Endologix) endograft could be in a large and real-world cohort of patients effective solution for the less-invasive treatment of the aortoiliac occlusive disease (AIOD).

Participants affected by AIOD with an indication of endovascular treatment will be prospectively enrolled and treated as our clinical practice. The requested follow-up did not differ from the one suggested by the most recent guidelines

In the last two decades there was a general shift from conventional open surgery to endovascular mini-invasive interventions, particularly towards patients with iliac and aortic occlusive disease (AIOD). However, while iliac artery angioplasty and stenting increased 8.5 fold from 1996 to 2000, aorto-bifemoral bypass fell by only 15%1,2. Indeed, according to European Society of Vascular Surgery/European Society of cardiology guidelines, open surgery remains the preferred choice for the most complex lesions to address by in endovascular fashion (TransAtlantic Inter-Society Consensus [TASC II] type C and D lesions). The reason is the good long-term patency of aorto-bi-iliac or aorto-bifemoral bypass among endovascular devices. Surgery, however, is associated with a high burden of early and late morbidity and mortality, and this aggressive approach is limited by the patient's age and comorbidity. In 1991 the kissing stent technique emerged as an alternative for bilateral aortoiliac occlusive disease. Even if the reported technical success rates varied between 89% and 100% with a 1-year primary patency between 76% and 98%, outcomes may be worse in more complex lesions owing to radial size mismatch between stents and certain stent configurations within the distal aorta. In addition, heavy calcified or thrombus-filled aorta could increase technical complexity and risk of limb and life-threatening procedural complications such as dissections, aortic rupture, and peripherical embolizations. Covered stents may increase patency rates in extensive disease, as shown by The Covered vs Balloon Expandable Stent Trial (COBEST) and confirmed in various case series but did not address the problem of a potential radial size mismatch that can lead to re-circulation, turbulence, and stasis of blood, which in turn, may cause thrombus formation and intimal neohyperplasia. Another endovascular procedure for the treatment of AIOD is the CERAB technique. A CERAB is defined as an "endovascular reconstruction of the aortic bifurcation" using at least one covered stent-graft for the infrarenal aorta (flared proximally) and 2 stent-grafts deployed within the aortic stent and into the common iliac arteries. This particular configuration leads to the reduction of the radial mismatch, which is defined as the discrepancy between the stented lumen and the vessel lumen after stent placement and, as a result, to more favorable flow conditions. In addition, it protects against potentially fatal aortoiliac rupture during the dilatation of heavily calcified lesions. However, the radial mismatch is increased if the limbs are placed higher than the nonflared aortic stent. In addition, while the CERAB technique does recreate the aortic bifurcation, future crossover interventions may be more difficult. This is similar to most bifurcated aortic stent-grafts where the angle of engagement at the flow divider makes up-and-over access more challenging. Finally, dead space outside the proximal aortic stent can result in cases of aortic diameters > 20 mm. The aortic stent is then left protruding mal-opposed in a dilated aorta. Hence, this technique may not be indicated in the setting of even mild proximal aortic dilation.

One potential alternative to treat the disease of both the distal aorta and the iliac arteries is the use of unibody stent-grafts. The AFX (Endologix) stent-graft is a unibody, low-profile endograft aimed to treat abdominal aortic aneurysms. The particular configuration of this device and its so-called anatomical fixation make it potentially an optimal solution to overcome the issue reported before inherent to AIOD treatment. This device presents a unique design with its long main body and two innate limbs and is designed to be deployed and sits on the native aortoiliac bifurcation and represents the only one-piece bifurcated endograft designed to use anatomical fixation for endograft stabilization. The AFX device consists of a main bifurcated body and a proximal aortic extension, which fix firmly to the aorta and provides sealing while reducing the possibility of stent's migration at the same time. The skeleton of the device is made of a cobalt-chromium alloy in a multilinked self-expanding unibody. External to the stent, the fabric is made of multilayer ePTFE material (STRATA). The stent is attached only to the proximal and distal ends at the proximal aortic extension and allows ePTFE to move independently and conform to abnormal surfaces, facilitating the sealing of the sac. According to published literature, the unibody device seems to represent a valid choice in the treatment of abdominal aortic aneurysms, but this particular device would seem to satisfactorily perform even in the treatment of occlusive pathologies and recently has become part of our clinical practice.

Theoretical advantages of AFX (Endologix) are:

• Unibody design preserves aortic bifurcation, thanks to its anatomical fixation, as described previously. Unlike kissing stents (covered or uncovered), which can often protrude into the native aorta, disrupting flow and functionally raising the aortic bifurcation, a unibody device sits on and preserves the native bifurcation. This makes future "up-and-over" interventions to the lower extremities less technically challenging. Compared to CERAB, by using fewer stents in the narrow aorta, this technique has the added advantage of minimizing potential flow disturbances introduced by multiple covered stents.
• Graft fabric reduces neointimal hyperplasia: there is some evidence, including the randomized COBEST trial, that covered stents may be less likely to restenose or occlude than bare metal stents, particularly in TASC C and D lesions. This may be because the graft fabric represents a direct barrier to tissue ingrowth from neo-intimal hyperplasia.
• No limb competition in narrow bifurcation, thanks to its unibody design.
• Unibody stent-graft is protective in cases of potential ruptures, such as in heavily calcified lesions.
• Coverage of the entire diseased aorta may reduce atheroembolic risk. Using this covered graft and positioning it proximal and distal to the limits of disease effectively traps atherosclerotic material that could potentially embolize during device deployment, reducing atheroembolic risk.

As with any new treatment alternative, this treatment strategy has limitations.

• Compared with the placement of kissing stents, or even the CERAB technique, the AFX (Endologix) device requires a larger profile sheath (17-Fr ipsilateral sheath, 9-Fr contralateral).
• Placing a stent-graft also has a higher potential for coverage of collateral vessels.
• The procedure is more time-consuming and requires a higher level of endovascular technical skill.
• Finally, while cost-effectiveness cannot be evaluated without robust efficacy data and will fluctuate based upon local differences in costs, use of the AFX (Endologix) unibody stent-graft is likely to be more expensive than kissing stent placement.

The aim of the study is to evaluate the patency rates, safety, and efficacy of the AFX unibody stent-graft for the treatment of aortoiliac occlusive disease (AIOD), which may represent an additional technique in the endovascular treatment of this disease.

The results will demonstrate whether the AFX (Endologix) stent graft is effective for the treatment of AIOD, in particular in more complex lesions (TASC C and D). The effectiveness will be evaluated in terms of patency (primary, assisted and secondary), technical success, clinical success, and quality of life improvement. Other objectives are the evaluation of procedure-related adverse events and re-interventions, as well as operative details.

Nowadays, kissing stenting (KS) technique and the CERAB technique are considered the standard of care in the endovascular treatment of AIOD. However, patency rates and clinical success of the endovascular treatment, especially in the mid- and long- term, are still lower than the classic aorto-femoral bypass. Many aspects like the preservation of the aortic bifurcation, neointimal hyperplasia, limb competition, potential rupture, and atheroembolic risk are challenging problems that the endovascular surgeon has to face to improve the outcomes of the endovascular treatment. In vitro studies have investigated hemodynamic aspects15 but only three other groups have previously discussed their experience with this technique showing encouraging early- and mid-term results.

Compared to other endovascular procedures, AFX (Endologix) unibody endograft shows many risks and disadvantages:

• It is a more invasive procedure with a larger introducer (19F+7F), which may need a surgical access
• The cost of the procedure is higher if compared to KS (but similar to CERAB)
• The endograft has a risk of fabric laceration with high calcium volume
• Very low chronic outward force (COF) of the Elgiloy stent

Inclusion Criteria:

• Age >18;
• Both sex;
• Preoperative 2.5mm CTA available;
• Written informed consent;
• Patients affected by AIOD classified as TASC B (with aortic involvement) C or D involving aortic bifurcation and or the first 5mm of one of both common iliacs;
• Treated in the coordinator center or in one of the study's participating center's;
• With a calcium volume in target zone based on real lumen of less than 20% and absence of circumferential calcifications;
• Minimum follow-up requested: 3-months, 12-18 months and 5-years CTA; clinical and DUS examination at 6- and 12- and 36-months after the intervention and yearly thereafter.

Exclusion Criteria:

• Age<18;
• No preoperative 2.5mm CTA available;
• Refused to sign the informed consent;
• Treated outside the coordinator centers or in one of the study's participating centers;
• Refusal to adhere to the requested follow-up;
• Patients affected by AIOD classified as TASC A or not involving aortic bifurcation or the first 5mm of one of both common iliacs;
• With a calcium volume in target zone based on real lumen of more than 20% and presence of circumferential calcifications;

Patients affected by AIOD classified as TASC B, C or D involving aortic bifurcation and or the first 5mm of one of both common iliacs with indication to endovascular treatment enrolled at the Unit of Vascular Surgery of the Ospedale Civile di Baggiovara (Azienda Ospedaliero-Universitaria di Modena) and fulfilling the previous inclusion criteria. The Investigators (3 experts Vascular surgeons) will screen the patients for inclusion. Once the patient's eligibility will be stated, informed consent will be collected and the study could take place.