More than twenty years after its introduction, endovascular

Transcription

1 J CAR DI O VASC SURG 2012;53: The use of Endurant stent-graft for abdominal aortic aneurysm: the story about extension of Instruction for Use with persistent good results of stent-graft latest generation Z. RANCIC 1, F. PECORARO 2, T. PFAMMATTER 3, I. BANZIC 1 H. KLEIN 1, K. KYRIAKIDIS 4, D. MAYER 1, M. LACHAT 1 The Endurant stent-graft (Medtronic, Inc., Minneapolis, MN, USA) is a latest generation device for the treatment of abdominal aortic aneurysm. The idea behind designing such a graft came from the intention to broad the instruction for use (IFU) and to enable it to treat more challenging anatomy including the 10mm neck lengths, and more severe suprarenal and infrarenal angulations. Endurant stent-graft has active fixation through suprarenal stent with anchoring pins to provide migration resistance, optimized heights of stents and spacing between them for improved flexibility and conformability, low-profile delivery system with hydrophilic coating and controlled simple deployment mechanism. Short term results are excellent. Technical and clinical success is confirmed in Regulatory trials (EU and USA), as well as in EN- GAGE and the Canadian registry. Many current publications record the use of Endurant stent-graft outside the Instruction for use. The results in a group of patients outside the instruction for use are comparable to those within instruction for use; with the exception of perioperative proximal endoleak type I. Mid-term results are consistent with short-term results. The long-term results are lacking. Key words: Stents - Endovascular procedures - Aortic aneurysm, abdominal. More than twenty years after its introduction, endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) still remains a matter of debate. Two main discussion points are: 1. in which patients is EVAR safer intervention than open repair, and 2. does EVAR really offer life-long protection against AAA rupture. Randomized trials 1-3 have shown a reduction in perioperative mortality and morbidity Corresponding author: Z. Rancic, Department of Surgery, Clinic for Cardiovascular Surgery, University Hospital Zurich Raemistrasse 100, 8091 Zurich, Switzerland. Zoran.rancic@usz.ch 1Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland 2Vascular Surgery Unit University of Palermo, Palermo, Italy 3Interventional and Diagnostic Radiology University Hospital Zurich, Zurich, Switzerland 4Department of Vascular Surgery Konstantopouleio General Hospital AgiaOlga Athens, Greece of endovascular repair of AAA, compared to open repair. Medicare patients cohort showed that late reinterventions related to abdominal aortic aneurysm are more common after endovascular repair, but are balanced by an increase in laparotomy-related reinterventions and hospitalizations after surgery. 4. For patients with high surgical risk, endovascular treatment is alternative to non-operative best medical treatment. 1 Based on anatomical and /or device suitability 20-60% of the patients are suitable for EVAR. Short infrarenal neck is responsible for half of AAAs unsuitable for EVAR, 5, 6 or even more, up to 74% (neck length <15 mm in 44%, neck diameter >26 mm in 25%, and tortuous/calcified neck in 5%). 7 Chairkof 8 identified and graded the factors that modify the outcome of EVAR. He showed that severe aortic neck is that one with length <10 mm, diameter >28 mm, and angulation >60, severe iliac artery is that one with calcification of >50% vessel length, diameter <7 mm, stenosis <7 mm in diameter and >3 mm in length. Generally, there is no consensus in the definition of short neck. In the Zenith trial, a neck length 15 mm was required. 9 Verhoeven et al. included necks 10 mm in their initial series o fenestrated stent-grafts 10. Vol No. 5 THE JOURNAL OF CARDIOVASCULAR SURGERY 579

2 RANCIC THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM Becquemin et al. proposed that a short neck should be between 15 to 10mm and a very short neck <10 mm. 11 Torsello et al. uses standard devices in off label situations outside the instruction for use if the neck is between 5 mm to 10 mm. 12 Hostile neck is defined as short neck with at least one of other characteristics: large diameter, infrarenal angulation >60, presence of thrombus, or bulge, or reverse taper shape and significant calcification. 13 There are several options to deal with short and angulated neck. Fenestrated or branched stent grafts are reported to be useful in juxta- or suprarenal aneurysm, thoracoabdominal 14 but also in infrarenal aortic aneurysms with short, conical or steeply angulated necks. 15 The stent grafts are custom made that is time consuming, the procedure needs substantial experience in canulation of visceral arteries and is technically demanding. Chimney graft is another possibility to extend the proximal sealing zone cranially from short aneurysm neck. Chimney graft is covered stent-graft implanted parallel and outside the aortic stent-graft in order to preserve flow into the target artery covered with aortic stent graft. This technique can be used in urgent cases, is technically relatively simple and less costly compared to fenestrated and branched graft. 16, 17 Combined open/endovascular repair including bypass surgery to the renal arteries, or even to superior mesenteric artery or celiac trunk, followed by endovascular exclusion of the aneurysm is an option for pararenal (juxta- and suprarenal) aortic aneurysm. This hybrid technique is less invasive than complete open surgical repair with suprarenal aortic clamp, but the complications related to laparotomy are still present. 18 Access issue could be challenged for EVAR, especially in women and patients with severe aortoiliac occlusive disease. If neglected, significant complications can occur with fatal haemorrhage. 19 Tortuous, angulated iliac arteries, with stenosis, occlusion, circumferential thrombosis or calcification make stent-graft tracking extremely difficult. Moreover, for proximal sealing of stent-graft is important to increase stent-graft fixation distally. 20, 21 In first and second generation stent grafts the access site complications were frequent fatal. Several possibilities were used to overcome access artery challenges: creation of iliac conduit 22, or preemptive angioplasty, 23 debulking, 24 in-situ sheath dilatation, 25 or endoconduit. 26 To overcome neck (short, angulated) and access issues related to stent grafts first and second generation, the Endurant stent-graft system (Medtronic, Inc, Minneapolis, MN) was designed. 27 The Endurant stent-graft system: device description The Endurant Stent-graft System is an evolution of the Talent abdominal stent-graft and the latest innovation of the Medtronic, Inc, Minneapolis, MN, USA for endovascular treatment of infrarenal aortic aorta aneurysm. 28 The idea to design such a graft came from the intention to broad the instruction for use (IFU) and to accommodate it to more challenging anatomy including the 10 mm neck lengths. The Endurant stent-graft system consists of two components: the Endurant stent-graft and the Endurant Delivery System. Endurant stent-graft is a modular device made of multifilament polyester fabric (polyethylene terephthalate) supported by the electropolished Nitinol stents, a shape memory alloy, with a roughly equal percentage of titanium and nickel. Polyester is highdensity multi-filament graft material with lower porosity designed to resist porosity-related type IV endoleak. All stents are sewn outside of the graft fabric (exoskeleton). One exception is the contralateral leg of the bifurcated stent-graft component where the nitinol stents are sewn inside of the graft fabric (endoskeleton) with the aim to provide additional friction for higher separation forces after contralateral limb component deployment. The first stents of the stub and contralateral iliac are sewn together insuring the contralateral gate accessible in patients with angulated iliac arteries. All the stents are sewn to polyester fabric using very strong and ultrahigh-molecular-weight polyethylene suture designed to increase stent-to-graft attachment strength, thus providing a more durable proximal attachment. Nitinol stents construction consists of: suprarenal stents (with anchor pins) and the remaining skeleton. Suprarenal stents are laser cut from a nitinol tube. Remaining skeleton is formed from nitinol wire. Suprarenal stent is designed to have an active fixation mechanism reducing the risk of device migration with its dual anchor pin (2 pins per stent crown) fixation mechanism. The 580 THE JOURNAL OF CARDIOVASCULAR SURGERY October 2012

3 THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM RANCIC bare stent design of the suprarenal stent allows the Endurant stent-graft to be fixed above the renal arteries. In-vitro bench model testing defined the design of suprarenal stent and pins to maximize engagement with aortic wall: pin angulation, pin length, pin geometry, location along the suprarenal stent, and the take-off angulation. Dual pin design allows robust fixation in highly angulated necks where not all anchor pins way be fully engaged in the aortic wall. 29 Remaining skeleton is composed of: 1. proximal seal, 2. body, 3. contour, and 4. limb stents. The proximal seal stent is M-shaped, and is constructed to mate with the suprarenal stent in order to enhance wall apposition, minimize the risk of in-folding and provide a 5 mm sealing zone. The whole stent-graft has virtually no columnar strength, as a result of removal of the stent connecting bar and increased spacing between individual stents. The radial force of the sealing stent is maximized while ensuring that the device could be constrained to a low-profile delivery system. The heights of proximal seal stent and body stents (8mm), as well as the spacing between them (2 mm) are optimized to achieve a high degree of conformability, while maintaining the required radial force necessary to seal the device to the aortic wall. Reduced columnar strength is compensated through active suprarenal fixation. Limb stents and stent spacing are designed to prevent kinking and to obtain adequate distal limb seal. Distally, a sinusoidal stent design enhances device flexibility. In general super elastic Endurant nitinol stents through the main body and limbs provide high conformability (opposite to stiff stents) and design to adapt to straight and tortuous anatomies. Radiopaque markers facilitate accurate stent-graft placement and are sewn onto the fabric. There are four proximal radiopaque markers to facilitate positioning in relation to renal arteries, including e shaped marker which helps with anterior/posterior view and serves to identify the contralateral gate. There is also flow divider marker (one), contralateral gate marker, as well as distal end of stent-graft limb or the extensions. Nitinol stent skeleton is also visualized under fluoroscopy. Endurant stent-graft offers multiple options for patient customization. Stent-graft configurations include bifurcated main body with straight and flared limb, contralateral limb with tapered, straight and flared limb, iliac extension, aortic extension, and abdominal tube. The stent-graft is also available as Aorto-uni-Iliac configuration with a contralateral limb. The bifurcated devices have universal contralateral gates which work with all sizes of the contralateral limb for a simplified sizing. 28 Endurant Delivery System is a flexible low profile delivery system with a hydrophilic coating and deployment mechanism with control-release tip capture of the suprarenal stent. Available outer diameters are 18F and 20F for the main body component, and 14F and 16 F for contralateral iliac limbs and extensions components. Lubricious hydrophilic coating to the surface of the sheath reduces the friction and improves the tractability in the access vessels (especially important in patients with small, calcified, tortuous iliac vessels). There are two delivery systems: either for bifurcated (main body) and aortic extensions components, or contralateral and iliacextensions components. Delivery system enables controlled simple deployment with high accuracy. Suprarenal stent with anchoring pins is captured inside the tip cap to allow positioning adjustments before tip release. Balloon dilatation of the proximal neck, the docking zone, and the iliac limbs is often performed with a Reliant balloon (Medtronic Cardiovascular). 28 Endurant II Stent-graft System In January 2012 (after CE mark) begin the international launch of the Endurant II AAA Stent-graft system. In June 2012 Endurant II received approval from the U.S. Food and Drug Administration (FDA). The new system incorporates the proven clinical performance Endurant stent-graft platform, while adding advanced design features that enhance the device s ease of use. Three distinct features were included: 35% extended hydrophilic coating allows the 28 mm-diameter bifurcated component to fit inside an 18F outer diameter catheter (down from 20F with the original Endurant stent-graft system) (Table I). This was possible after removal of one peak of the suprarenal stent, which is one of a few modifications made to lower the profile of delivery system. Second, the addition of two new contralateral limb lengths (156 mm and 199 mm) enables more configuration options requiring fewer total pieces. The benefit lies Vol No. 5 THE JOURNAL OF CARDIOVASCULAR SURGERY 581

4 RANCIC THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM Table I. Features included. AAA ENDOGRAFTS Proximal stent graft diameter Catheter outer diameter (OD) Contralateral limb size (vessel size/od) Hydrophilic coating Endurant mm 18F mm 20F mm, 14-18F(OD) Yes Endurant II mm 18F mm, 14F(OD) mm 20F mm, 16F(OD) Yes Talenttm AAA mm 22F mm 24F 8-24 mm, 18-20F(OD) Yes Excluder C mm 20.4F 31 mm 22.8F mm, 12-18F(OD) No Anaconda mm 20.4F mm 22.5F mm, 18.3F(OD) Yes Aorfix Max.33 mm (inner-inner) 22F Max. 22 mm, 20F(OD) Yes Powerlink 25 mm 19F 28 mm 21F mm, 11-17F(OD) Yes in lower cost, and lowering the risk of modular disconnections. Finally, the radiopacity of the distal end of the bifurcated component s contralateral gate has been improved through placement of platinum-iridium markerband to enhance visibility and aid with limb insertion, placement and deployment. 29 The Endurant stent-graft system: trials and registries First-in-human trial A first-in-human prospective, non-randomized, multicenter, open label trial was performed at eight clinical sites in the Netherlands and Germany. In total 40 patients were enrolled and followed for 30 days. Six patients had infrarenal angulation 60 to 75, and suprarenal angulation 45 to 60. Technical success was achieved in 90.3%, 30 with no reported type I/III endoleaks, no loss of device integrity, no graft infection, thrombosis or occlusion, no conversion to open surgery, and no rupture. Three secondary endovascular procedures were recorded all due to bleeding access complications. No device-related death or devicerelated serious adverse events were recorded during the 30-day follow-up. Careful review of the adverse event revealed an acceptable safety profile even in highly angulated necks and tortuous anatomies. The regulatory trials followed, first in Europe, and later in USA. 31, 32 Regulatory trials European Trial of the Endurant stent-graft European trial of the Endurant stent-graft for Endovascular Abdominal Aortic Aneurysm Repair was the prospective, single arm, non-randomized, openlabel multicenter trial. 31 Between November 2007 and August 2008, 80 patients were enrolled in 10 European Centres for elective EVAR with the Endurant stent graft. The morphological inclusions criteria were within the instruction for use (Table II): 71 of Table II. Endurant stent graft instructions for use. One of the following criteria: Maximal AAA diameter >5 cm Maximal AAA diameter >4 cm and <5 cm, with increase 0.5 cm in past 6 month Maximal AAA diameter diameter 1.5 times the diameter of the referenced aorta AND One of the following criteria Proximal aortic neck length of 10 mm Infrarenal angulation 60 Suprarenal angulation 45 With non-significant calcification and/or non-significant thrombus Proximal neck length of 15 mm Infrarenal angulation 75 Suprarenal angulation 60 With non-significant calcification and/or non-significant thrombus AND All of the following criteria: Adequate iliac/femoral access Proximal AAA neck diameter 19 mm and 32 mm Distal iliac fixation site diameter 8 mm and 25 mm Distal non-aneurysmal iliac fixation length 15 mm bilaterally 582 THE JOURNAL OF CARDIOVASCULAR SURGERY October 2012

5 THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM RANCIC patients were with moderate ( 60 ), and nine with high (60-75 ) infrarenal aortic neck angulation. The device was successfully delivered and deployed in all patients: technical success was 100%. Specific technical observations included difficulties withdrawing the sheath (in two patients), or retracting the nose cone (5), which were uneventfully resolved during the procedure. All-cause mortality was 5% (4/80), but only one was classified as possibly device-related (in patient with occlusion of crural vessels treated with heparin infusion leading to massive GI bleeding). Serious adverse events were comparable between the moderate and high angulation group. There were no device migrations, stent fracture, aortic rupture, or conversion to open aortic repair. No type I or III endoleaks were registered. In total 28 endoleaks were observed (26 type II, and two undetermined). A total of three out of 80 patients underwent secondary endovascular procedures: one patient with complete limb occlusion treated successfully with recanalization and stent placement, one with stenosis of external iliac artery distal to limb of stent-graft treated with PTA, and in one patient it was necessary to extend the stent-graft and lengthen the distal sealing zone. The diameter of aneurysm showed: regression >5 mm in 42.7% of patients, no change in 54.6%; in 2.7% aneurysm sac showed an increase >5 mm compared to 1 month as baseline. During the follow-up, two more patients died, providing a survival rate of 95% after 1 year. The 1-year results of the trial supported the Conformité Européene (CE) marking for the Endurant in July Regulatory US IDE Trial Regulatory US IDE Trail 32 was the prospective, nonrandomized, single-arm, multicenter (26 sites) in USA. In total 150 patients were treated with the Endurant bifurcated stent-graft system from April 2008 to May The anatomical characteristics of the AAA were within the instruction for use. Technical success was 99.3%, with one failure due to inability to cannulate the contralateral gate, so that procedure was completed with aorto-uni-iliac stent-graft with femoro-femoral crossover. One patient developed a neck rupture during the procedure, but was still treated successfully. There was no mortality at 30 days, and major adverse events were noted in only six patients (4%): respiratory failure in 2 pa- tients (1.3%), bowel ischemia in 2 patients (1.3%), and myocardial infarction in one (0.7%), renal failure in one (0.7%), and stroke in one patient (0.7%). Serious adverse events, whether related to procedure or not, were registered in 43 patients (28.7%) within the first 30-days of follow-up. The most frequent were: cardiac (8.7%), respiratory (4.0%), and bleeding events (3.3%). Vascular events were noted in 4.0%. All five reinterventions were open surgical performed for arterial events. At one month followup, there were no endoleak type I and III; endoleak type II was present in 23/143 patients (16%). At 12 month follow-up there were no migrations, ruptures or conversion to open surgery. None of six late deaths was aneurysm related. No type I or III endoleaks were registered. 11% of patients have endoleaks at 6 and 12 months, almost all type II. Ten reinterventions were performed during the first year: four endovascular and six open. Three of these procedures were for vascular problems, two for treatment of endoleak type II, and five for limb stenosis (one) or occlusion (four). The cause for limb occlusion was compression of the limb is the small aorta or kinked iliac artery. The diameter of aneurysm showed: regression >5 mm in 51% of patients, no change in 49%; no one aneurysm sac showed an increase >5 mm compared to 1 month as baseline. US Trial at 2 years showed consistent clinical results. There were no type I endoleak, no migration, conversion to open surgery, aneurysm related mortality, postoperative rupture. Stent-graft integrity was 100% (Endurant 2011 Annual Physician Clinical Update). 33 Secondary interventions (endovascular and open) were necessary in 1.4% of patients. Aneurysm sac diameter decreased or remained stable in 98.3% of patients. ENGAGE registry ENGAGE (Endurant Stent-graft Natural selection Global postmarket registry) is the multicenter, nonrandomized, single arm prospective study of the Endurant stent-graft device The ongoing worldwide study (begin 2009 with expected enrolment completion 2013) includes more than 1200 patients at 79 high-volume sites in Asia, Canada, Europe, Middle East, South Africa and Latin America. The eligibility criteria for site are more than 20 AAA stentgraft procedures per year, the ability to enrol more Vol No. 5 THE JOURNAL OF CARDIOVASCULAR SURGERY 583

6 RANCIC THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM than 10 patients per year, and adequate experience to implant the Endurant stent-graft system defined as more than three prior successful implants. Additionally, the site must be able to provide follow-up documentation for patients up to 5 years.. The registry wants to examine the use of single stent-graft system (Endurant) in a multiple real world population. 34 In order to reach that goal, the inclusions criteria are limited: patient must be older than 18 years, and have indications for elective repair of AAA strictly in accordance with the applicable guidelines on endovascular interventions and the instruction for use (IFU) of the Endurant stent-graft system, intention to electively implant the Endurant Stent-graft System, and willingness to participate. The exclusion criteria are the patients with probability that the follow-up will not be possible, and current participation in the concurrent trial which may confound result. In order to reflect the real world practice ENGAGE registry allowed that the implant procedure is to be performed according to standard clinical practice at each site, but the documentation of physician s preferred treatment choices must be documented: type of anaesthesia, use of antibiotics, use of heparin during the procedure, as well as the sole procedure: from cut down or percutaneous access, to final closure of all access sites. On the other side real world practice requires rigorous data entry, review, correction and monitoring for carefully defined endpoints. Creation of database is of utmost importance, so that all data can be pooled and/or compared within other data bases on the Endurant Stent-graft or other stent-graft systems. There are no strict requirements regarding followup protocol, or type of imaging technique. Most sites scheduled follow up at 30 days, 12 months, and yearly thereafter. The final follow-up control should be at 5 year. There are different types of imaging: the majority of sites use computed tomography angiography. Böckler et al. reported the first results of 180 elective patients with 30-day follow-up, out of 579 enrolled in ENGAGE registry between March 2009 and February The overall deployment success was 99.4% of, with single failure occurred in a patient with intention to deploy the main body through the first deployed iliac graft extension. The stent-graft moved cranial and unintentional covered both renal arteries: the patient was converted to open surgery. Within 30-days there were no type I and type III endoleak; endoleak type II was reg- istered in 13% of patients after the procedure, with 3.9% detected at 30-day follow-up control; type IV endoleak was detected after procedure in two patients: in one resolved, the other patient missed the follow-up control. There were no losses of stent integrity, stent-graft thrombosis, or graft stenosis/occlusion. In one patient stent-graft thrombosis detected at first postoperative day was left untreated and did not cause problem, nor was reported during the further follow-up controls. Two secondary endovascular procedures occurred within the first 30-days: thrombectomy and relining of the iliac stent-graft at day 5 after the initial operation, and in another patient 6 weeks after the initial procedure. All-cause mortality was 1.75% (3/180 patients), and were classified as procedure-, but not as device-related. These technical and clinical outcomes were very promising, having in mind extended instruction for use. Stokmans et al. reported the perioperative outcome and 30-day results of all 1200 enrolled patients in ENGAGE registry between March 2009 and December Technical success was 99.1%. Clinical success was 97.7%, with 17 cases of type I and/ or III endoleaks at the end of initial procedure and 11 technical failures. There were no intra-operative deaths. Within 30-days after stent-graft deployment 16 patients died (1.3%). The occurrence of one or more MAEs (major adverse events) including mortality was 4.1% in all cohorts of patients. 1-year follow-up is available on first 500 patients and showed no migration, no rupture, and 0.6% conversion. Only one (0.2%) aneurysm-related death occurred after the 30-days, what represents an aneurysm-related mortality rate of 1.4% at 1 year. The rate of secondary procedures to correct type I/III endoleak at 1 year was 1.2%, and the overall rate of secondary procedures was 4.6%. At 1- year, type II endoleak was present in 8% of patients. 33, 39 Longer follow-up for ENGAGE patients will be reported through the expected completion of registry data collection in CANADIAN multicenter prospective registry Canadian prospective registry recorded 111 patients treated from September 2008 until January All patients were treated on the elective basis. The indication for AAA treatment, procedure planning, and device selection were at the discretion of treating surgeon. Opposite to ENGAGE 34 and 584 THE JOURNAL OF CARDIOVASCULAR SURGERY October 2012

7 THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM RANCIC USA regulatory trial, 32 Canadian registry included patients with more challenging anatomy, sometimes outside the instruction for use. Out of 111 patients, 37 patients had challenging aortic anatomy: in 22 patients attributed to proximal neck, in 21 to access vessels; in 6 patients was present challenging anatomy in both locations. Challenging proximal neck anatomy was presented as large diameter (>28 mm, range mm) in four patients, short neck (<15 mm, range 8-14 mm) in 17 patients, and angulated neck (>60, range ) in three patients; two patients had both short and angulated neck. In 21 patients diameter of iliac artery was smaller than defined in IFU (<7 mm, range mm). Technical success of the procedure was 100%. During the procedure in 9 patients occurred unplanned events which required adjunctive procedures to fix it: in 4 patients graft kinking or stenosis were treated with bare metal stent, in one patient (with the proximal neck length of only 8mm), type Ia endoleak was resolved with proximal extension, in one patient type III endoleak was treated with additional iliac limb deployment, in one patients failure to cannulate contralateral gate necessitated conversion to aorto-uni-iliac graft with femoro-femoral bypass, in one patient loss of femoral access guide wire required transbrachial approach. Finally, unintentional occlusion of one internal iliac artery occurred in one patient. Perioperative additional 5 (4.5%) vascular complications occurred: access site pseudoaneurysm (2) treated with covered stent in one patient, and with open surgery in another one; EVAR limb thrombosis (3) with leg ischemia was treated with thrombectomy, thrombendarterectomy with patch plastic and femoro-femoral crossover in patient with external iliac artery dissection. The patient with surgical thrombectomy of limb thrombosis died at day five due to MOSF (0.9% procedure related mortality). The clinical follow up over the 6 months (range 1-6 months) were available in 107 patients (96.4%). There were no deaths related to aneurysm rupture. Overall patients survival at 6 months was 95.4%. Postoperative CT angiography was available in 99 patients (89%) and showed the resolution of four (out of 9) type II endoleak. Three patients (3%) developed new graft limb thrombosis but there was no graft kinking/stenosis identified on follow-up imaging: two did not require any interventions, and in one patient limb was revascularized (femoro-femoral bypass) due to acute limb ischemia 3 months after EVAR. There were no graft migrations, postoperative aneurysm enlargement, and secondary interventions for endoleak, aneurysm rupture, or conversion to open surgery. It is interesting subanalysis of the 37 patients with challenging proximal neck or access vessel anatomy vs. those without challenging anatomy. Mortality was higher in the subgroup with challenging anatomy (four of 37), though without statistical significance owing to the small numbers. Only one death was due to technical complications; the others were related to underlying comorbidity. There was no significant relationship between intraoperative adjunctive procedures, perioperative vascular complications, or late graft limb thrombosis and the presence of challenging proximal neck or access vessel anatomy. The registry did not report the tortuosity, degree of calcification, thrombosis or degree of arterial occlusive disease. In the series of almost 20% access vessels <7mm in diameter (some as small as 4.5mm), the importance of the low profile, flexible hydrophilic delivery system of the stent-graft could not be neglected. The Endurant stent-graft system for symptomatic and ruptured AAA The Endurant stent-graft system for symptomatic AAA Traditionally, patients with symptomatic AAA have worse outcome compared to non-ruptured elective patients. Nowadays, in the endovascular era perioperative care, operator skills result in less operative trauma. Stokmans et al. compared the differences in perioperative outcome after endovascular repair of symptomatic abdominal aneurysms (S-AAA) and elective non-symptomatic abdominal aneurysm (E-AAA) included in ENGAGE registry. 38 Out of 1200 ENGAGE registry patients, 185 (15.4%) were presented as symptomatic. Symptomatic patients were younger. Elective patients were more likely to be in ASA classes III and IV than symptomatic (P=0.001), and had larger aneurysms on average. Technical success in the symptomatic patients was 100%; in the elective group 98.9% (1004/1015). The EVAR was terminated due to access problems caused by stenosis/tortuous iliac arteries (4 patients), unintentional coverage of both renal ar- Vol No. 5 THE JOURNAL OF CARDIOVASCULAR SURGERY 585

8 RANCIC THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM teries (one patient) with, immediate conversion to open surgery, and entrapment of suprarenal strut in the delivery system (one patient). In the remained 5 patients the internal iliac artery was unintentionally covered. Initial clinical success in the symptomatic patients was 99.5% (184/185): one patient was with proximal endoleak type I. In the elective patients clinical success was 97.3% (988/1015): there were 16 endoleak type I and/or type III at the end of initial procedure, as well as 11 technical failures. No differences in the occurrence of major adverse events including mortality, within the 30- day post-implantation were seen between symptomatic and elective patients respectively, 3.2% and 4.2% (P=0.572). The authors concluded that there is no difference in outcome between symptomatic AAA and elective non-symptomatic AAA patients if treated with endovascular techniques. The Endurant stent-graft system for ruptured AAA There is a lack of data of use Endurant stentgraft system in treatment of ruptured AAA. The real world practice and the real world population EN- GAGE registry did not enroll the patients with ruptured aneurysm. 34 Troisi et al. reported three patients (1.9%) treated with Endurant stent-graft system: one ruptured AAA was associated with giant thoracic aneurysm, in another the rupture was in duodenum with aortoduodenal fistula. 41 Two of three patients died within 30-days. Urgent intervention significantly affected 30-day mortality in univariate, but not in multivariate analysis. Moreover urgent intervention significantly impacted 30-day morbidity in univariate, but also in multivariate analysis. Hyhlik Dürr et al. reported the use of Endurant stent-graft system in two patients with contained rupture in the emergency settings. 42 There was no graft related complications in this patients. In one patient with preexisting renal insufficiency renal function deteriorated, but the dialysis was not necessary. The Endurant stent-graft system: use outside the instruction for use Even though the anatomic inclusion criteria for the Endurant stent graft, according to the instruction of use are wider compared to other stent-grafts, the operators found the system hostile-neck and access-friendly and extend the indication for use for more challenging AAA. Van Keulen et al. reported 100 elective AAA patients treated at three Holland vascular cooperating centres (Utrecht, Nieuwegein, and Rotterdam) of the 100 (21%) included patients had at least one anatomic characteristic that was considered outside of the IFU: in 3 patients an aneurysm neck diameter exceeded 32 mm, one patient had a suprarenal neck angulation exceeding 60, and 10 patients had infrarenal neck angulation exceeding 75. One patient had aneurysm neck length of 9 mm, one aneurysm neck of 12 mm along with an infrarenal angulation exceeding 60. Three patients had suprarenal neck angulation exceeding 60 in combination with infrarenal neck angulation exceeding 75. There were also 5 patients with more than 50% of the aneurysm neck lumen lined by thrombus or calcification. In the group of patients treated out-ifu the bifurcated stent-graft was placed successfully with technical success of 100%. Among the out-ifu there were no deaths within the 30-days, no migration, no EL I or III. One-year postoperative analysis showed in the out-ifu group no Endoleak type I (one EL type I was registered in group of patients treated within the IFU), no graft migration (one migration was registered in the group of IFU group of patients). Georgiadis et al. reported 77 patients treated in two Greek centres (Thessaloniki and Alexandroupoulis). 44 Two groups were identified: friendly group (43 patients) and hostile group (34 patients). Hostile profile was defined for aneurysm with some (or combination) of the following criteria: proximal neck length between 5-12 mm, proximal infrarenal angulation >60, and any iliac axis angle >60 degrees but 90. In the hostile group of patients treated outside of IFU the stent-graft was placed successfully with technical success of 100%. Completion angiography after deployment of stent-graft in this group showed three proximal type I endoleak, four distal type I, and one type II. Patients with proximal type I endoleak had neck length, angulation and shape as follows: 15/20/9 mm, 84 /82 /73, and reverse conical/cylindrical/ cylindrical. In two of them EL was successfully managed with aortic cuff deployment. In the remaining case balloon angioplasty at the proximal anchoring zone successfully sealed endoleak. No 586 THE JOURNAL OF CARDIOVASCULAR SURGERY October 2012

9 THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM RANCIC one patient died within 30-days. During the followup period there were no stent fracture, migration, or thrombotic limb occlusion in the hostile group (opposite to 4 patients in the friendly group, who were treated with femoro-femoral crossover bypass). No new EL type I or III were identified during the follow-up period. Freedom from any type of endoleak at 12 months in the hostile group 86% (statistically non-significant compared to friendly group, with 93.2%). Freedom from any reinterventions at 12 months was 93.4% in hostile group (statistically non-significant compared to friendly group, with 87.1%). Goncalves et al. identified 45 elective patients treated with Endurant stent-graft system with severe angulation of the proximal neck and compared them to a control group without significant angulation. 45 Patients with severe angulation were those with infrarenal angle >75 and /or suprarenal angle >60 combined with neck length of 15mm, or infrarenal angle >60 and/or suprarenal angle >45 combined with neck length of >10mm. These cut-offs correspond to the limits of proximal neck angulation allowed by the IFU for Endurant. 23 patients were included only due to infrarenal angulation, 14 were included due to both infra- and suprarenal angulation, and 8 due to suprarenal angulation. The patients in the angulated group had larger aneurysms, with shorter necks, less cylindrical, and were sicker. The mean infrarenal aortic angle was The control group of 65 patients was selected from the sample of elective infrarenal EVARs. Primary technical success in the angulated group was 97.8%, but primary assisted technical success was 100%. Primary adjunctive procedures were performed in seven patients. In one patient it was necessary to deploy extension cuff to resolve the proximal endoleak type I (patient had suprarenal angulation of 64, the infrarenal angulation of 78, and also a 11mm short neck). Oversizing was 12% which according to authors may contribute to the primary failure. No type I endoleaks were detected at 30 days in each group (angulated and non-angulated). Moreover endoleaks were detected intraoperatively in almost one fifth of the patients and all were type II. Combined in-hospital/30-day mortality was 2.2% in the angulated group (one patient) and 3.1% in the non-angulated group (statistically non-significant). The patient died due to renal complications aggravated after endovascular treatment. The combined in-hospital/30 day morbidity was 6.7% for the angulated and 6.2% for the non-angulated group (non-significant). The distance from the lowest renal artery to beginning of the stent-graft was within 2.5 mm in both groups and not significantly different, demonstrating the controlled accuracy and conformability of the Endurant stent graft. Hyhlik-Dürr et al. reported consecutive series of 50 patient treated in three German clinics (Heidelberg, Oldenburg, Ludwigsburg) with challenging anatomy (48 patients were elective, two were emergent). 42 Patients had short ( 15 mm) aortic necks, severe suprarenal/infrarenal angulation, and /or small (<8 mm), calcified, severely angulated, or tortuous iliac or femoral access vessels. In the 31 patients (62%) the median proximal aortic neck length was 10 mm (range mm). In 16 patients (32%) severe tortuosity of iliac arteries was present; 27 patients (54%) had narrowed and calcified iliac arteries, with a median iliac diameter in those patients of just 5.8 mm. Sixty six percent of patients had a combination of both challenging neck and difficult vascular access. This group of patients was compared to 40 patients without challenging anatomies, who were included in ENGAGE registry within the IFU. Primary technical success in the challenging group was 92%. There were four technical failures: 1) proximal deployment of stent-graft resulted in occlusion of one renal artery, and after failure to stent it, the patient was managed conservatively, with complete renal function recovery; 2) canulation of contralateral gate failed, as well as crossover manoeuvre and attempt to antegrade cannulate it through the brachial access, so that the procedure was completed with aorto-uni-iliac stent-graft with a femoro-femoral bypass; 3) proximal endoleak type I in patient with 8mm short proximal aneurysm neck; and 4) unintentional covering of internal iliac artery, without ischemic buttock claudication. Overall mortality within 30 days in the challenging group was 2% (1/50). Intraoperative angiogram revealed two proximal type I, one distal type I endoleaks and all were initially treated by balloon dilatation. There were no type III endoleak. The persistent EL type I was treated with a fenestrating graft. Out of 5 type II endoleaks, one occluded spontaneously. Within the 30-days graft limb thrombosis occurred in two patients: in both surgical thrombectomy was necessary Vol No. 5 THE JOURNAL OF CARDIOVASCULAR SURGERY 587

10 RANCIC THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM with creation of femoro-femoral bypass because of critical limb ischemia. Complete thrombosis of aorto-uni-iliac stent-graft was corrected with transfemoral thrombectomy and ballooning of severe calcified and angulated aortic neck. Compared to the excellent 30-day results with the Endurant stent-graft in non-challenging anatomies (no type I endoleak, no graft limb occlusion, all-cause mortality 1.7% in group of first 180 ENGAGE patients), procedurerelated complications in challenging anatomies are increasing. Even in challenging anatomies Endurant is safe, and the results are encouraging. Torsello et al. reported several series of patients treated with Endurant stent graft. 46 The first 45 patients were treated at 3 European vascular centres. The majority of patients (38.84%) had hostile neck: 31% had neck <10 mm in length, and 58% had neck angulation > 60. Most of patients had at least 2 adverse neck characteristics. At discharge only one patient (2.2%) had a proximal type I endoleak, which was successfully treated with an aortic extension. At one year follow-up freedom from type I endoleak was 97.8%. Freedom from secondary interventions at one year was 93.3%. Torsello et al. published the biggest case series of patients treated outside the Instruction for use for the proximal aortic neck, or in off label situations. 12 In total there were 56 patients: 27 (48.2%) had a proximal aortic neck <10 mm, 22 (39.3%) had an infrarenal angulation of the proximal aortic neck >75 and the remaining 7 (12.5%) showed both features. This group of patients were compared to 121 patients treated within the IFU. Off label group had a larger aneurysm size, and had more complex aortoiliac anatomy in length/angulation of the proximal aortic neck and angulation of the iliac axis. Technical success intraoperative was 100% (both groups). No intraoperative conversion, migration, type I or III endoleak, or death were recorded. In completion angiography a type II endoleak were recorded in 8 patients in the off label group. Intraoperative 13 adjunctive procedure were performed: iliac stenting for limb stenosis (in 8 patients), proximal aortic cuff extension (one patient), embolization of internal iliac artery (three), and a femoro-femoral crossover bypass (in patient where the aorto-uni-iliac stentgraft was planned). 30-days results do not differ between the IFU and off label patients. 30-day CT angiography showed a proximal type I endoleak in two patients (opposite to none in IFU group). Uni- variate and multivariate analysis confirmed that no one of preoperative or intraoperative factors affected early outcome. Follow-up was available in 95.5% of patients in both groups (range 1-24 months, overall median 6 months). There was one aneurysm related death in the off label group secondary to a late type I endoleak diagnosed 3 months after the procedure. There were further three reinterventions in the off label group: two femoro-femoral crossover prosthetic bypasses for limb graft thrombosis and one proximal aortic cuff extension for a type I endoleak. The estimated survival at 1 year (95.3%), estimated freedom from any device related reinterventions at 1 year (91.7%), and estimated freedom from graft thrombosis (94.4%) in the off label group did not differ with IFU group. Finally, estimated 1-year freedom from type I endoleak was 100% in the IFU group vs. 93.3% in the off label group (P=0.01). Univariate and multivariate analysis demonstrated that none of the preoperative or intraoperative factors could be considered as an independent predictor of poor outcome at 1 year in the off label group. Troisi and Torsello reviewed 156 patients treated from November 2009 to December patients (67.9%) had a hostile proximal aortic neck: short neck 10mm (46 patients, 29.5%), neck bulge as focal dilatation of the neck 3 mm within the first 15 mm of the neck (3 patients, 1.9%), tapered neck defined as gradual enlargement 2 mm of the neck within the first 10 mm (48 patients, 30.8%), infrarenal neck angulation 60 (61 patients, 39.1%), and neck thrombus covering >50% of the circumference of the neck (27 patients, 17.3%). Technical success intraoperatively was 100%. In total 44 intraoperative adjunctive procedures were necessary (from the paper it was not possible to extract distribution between the groups with hostile neck, and IFU group). In particular, in 14 patients (9%) the authors used chimney technique to extend the proximal landing zone. No intraoperative conversion, migration, major complication, or death were encountered. The overall 30-day technical and clinical success rates were 98.7% and 95.5%, respectively. Four patients died within the 30 days; two of them underwent urgent operation due to rupture. Six patients required reinterventions (3.8%): two graft limb thrombosis were treated with a femoro-femoral crossover bypass, and thrombectomy with stenting, one in-stent thrombosis after 588 THE JOURNAL OF CARDIOVASCULAR SURGERY October 2012

11 THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM RANCIC deployment of chimney in left renal artery required an iliaco-renal bypass, two femoral artery access false aneurysm were treated with open suture, and in two patients with the proximal type I endoleak one was treated immediately, and other due to comorbidities with delay. 13/17 endoleak type II seen at the end of the procedure persisted. During a mean 9-month follow-up (range 1-24), three patients died (one of them with ruptured AAA). Estimated survival, freedom from types I/III endoleak, freedom from graft thrombosis, and freedom from any device-related reinterventions at 2 years were 94.7%, 96.9%, 97.8%, and 92.6%, respectively. The results showed that use of Endurant stent-graft system is safe and effective, even in patients with hostile aortoiliac anatomy. Collected experience of use of Endurant stentgraft system outside the instruction of use is extracted from above presented published series. 12, The experience from Münster, even though represents the biggest series of patients treated outside the IFU (106) could not be analyzed, because it is not possible to follow the results in IFU and outside IFU patients separately. 41 In total were identified 204 patients treated outside the IFU (Table III) and this patients are compared to patients treated within the IFU 40, 44, 46, two of them within the EU 31 und USA 32 regulatory trials. There is no difference in 30-day mortality, reinterventions rate, and 1-year mortality. There is only one statistically significant difference between IFU and outside IFU patients: intraoperative endoleak type I or III is more frequent in the group of patients outside the IFU. Of particular interest is that there is no difference in new onset of endoleak type I and III compared to IFU group (Table IV). The explanation might be the safety profile of Endurant stent graft. Endurant stent-graft system and use of chimney grafts Troisi et al. used in 14 patients (9%) chimney technique to extend the proximal landing zone in patients Table III. Patients treated outside the IFU. Current published study Author, Year of publication Number of patients IFU Number of patients Non IFU Makaroun, Rouwet, Kvinlaug, Torsello, van Keulen, Hyhlik-Dürr, Torsello, Georgiadis, Goncalves, Overall Table IV. New onset of endoleak type I and III compared to IFU group. Outcome IFU Non IFU P (χ 2 ) Patients d Mortality (%) 5 (1.16) 2 (0.98) Gate collaps (%) 6 (1.39) 8 (3.92) Reintervention (%) 28 (6.52) 9 (4.41) Patients year Mortality (%) 17 (3.96) 13 (7.03) Patients Intraoperative endoleak I/III 5 (2.51) 11 (5.39) Patients day endoleak I/III 3 (0.61) 3 (1.47) Patients months endoleak I/III 4 (1.14) 3 (2.22) Vol No. 5 THE JOURNAL OF CARDIOVASCULAR SURGERY 589

12 RANCIC THE USE OF ENDURANT STENT-GRAFT FOR ABDOMINAL AORTIC ANEURYSM There are several reports on unusual ure of Endurant stent-graft system. Donas et al. reported the percutaneous use of Enwith short neck: in 11 patients chimney was deployed in one renal artery, in three patients in both. The indication for chimney graft was straightforward, and in no patient chimney was a bail-out procedure. 41 The chimney technique proved useful in obtaining the immediate technical success even in patients with proximal necks <5 mm; however, in these 14 patients, one proximal endoleak type I was identified at discharge CT. The authors advice that in case when the neck is 2-5mm in length the chimney technique can be of use. Two centres (Münster and Zürich) reported prospectively collected technical and clinical experience of use chimney grafts in the treatment of pararenal aortic pathologies, presenting the largest consecutive series in the literature. 47 The technical success rate for preservation of target vessel in the Münster group with balloon expandable covered stent (46 stents in 37 patients) and in Zurich group with self-expanding covered stent (81 stents in 35 patients) was 97.8% and 100%, respectively. Flexible device with low profile such as Endurant stent-graft system performed very well in combination with balloon expandable covered stents, and the suprarenal fixation did not preclude its use. In the balloon-covered expandable stent grafts the Endurant stent-graft trapped the chimney grafts with only one registered low-flow proximal type I endoleak, which disappeared during the follow-up. The suprarenal fixation of Endurant stent-graft system might be responsible for additional fixation of chimney grafts. On the other side the same excellent results are in cases when the aortic stent grafts with infrarenal fixation are used. Endurant stent-graft system and learning curve Some papers addressed the possibility of influence of learning curve on technical success of Endurant stent-graft system use. Van Keulen et al. extensively used the predecessor of the Endurant stent graft, and they do not believe that learning curve of the use of the Endurant stent-graft will be of much influence on the results. 43 But also, they pointed out that interim analysis of the results of first implanted Endurant stent grafts was the core stone for the decision to treat all significant stenoses in the aortoiliac area detected on completion angiography by PTA (percutaneous transluminal angioplasty) to prevent future iliac limb occlusion. Endurant stent-graft system and quality of life in octogenarians Elective treatment of AAA in octogenarians demonstrated acceptable perioperative mortality rate after open surgery 7.5%, and after EVAR 4.6%. 48, 49 Furthermore, one must consider effects on quality of life. Stokmans et al. compared 274 octogenarians with 926 patients younger than 80 years treated for AAA with Endurant stent grafts system within EN- GAGE registry. 38 Octogenarians had larger aortic aneurysm, left iliac artery diameters and greater infrarenal neck angulation. Technical success rate was equal in both groups > 99.6%. The 30-day all-cause mortality was comparable between two groups (four deaths in octogenarians), there was no significant difference in major adverse events, but in the octogenarians was higher incidence of myocardial infarction (2.6%). There was no difference in the number of secondary endovascular procedures or aneurysm rupture at 30-days. However, a significantly higher incidence of proximal type I endoleak was recorded in octogenarians (12.1%, or in 33/273 patients, compared to 4.6% or 42/921 in patients younger than 80 years). Quality of life was assessed using the EuroQoL 5-Dimensions Questionnaire (EQ-5D) index score. At the preoperative assessment quality of life was similar in the octogenarians and younger than 80 years group. At discharge, both groups had reduced health status dimensions, except anxiety/depression, when compared with baseline. At 30 days, the octogenarians group had a lower EuroQoL 5-Dimenssions Questionnaire index compared with the younger indicating a slower recovery. The study showed that octogenarians can safely be treated by EVAR with a high rate of technical success, low short term morbidity and mortality, and good recovery of quality of life shown at 30-day postoperative time point. Increased applicability of Endurant stent-graft system will offer EVAR to more octogenarians, having in mind wider instruction for use comparing to other devices. Endurant Stent-graft System and unusual use 590 THE JOURNAL OF CARDIOVASCULAR SURGERY October 2012