A preliminary analysis of late structural failures of the Navion stent graft in the treatment of descending thoracic aortic aneurysms

Objective: Patients in the Valiant Evo U.S. and international clinical trials had positive short-term outcomes; however, late structural failures, including type IIIb endoleaks have been recently discovered. Type IIIb endoleaks are serious adverse events because the repressurization of the aneurysm sac increases the risk of rupture. The purpose of the present study was to detail the imaging patterns associated with the structural failures with the aim of increasing awareness of failing graft presentation, early recognition, and prompt treatment. Methods: The Valiant Evo clinical trial was a prospective, single-arm investigation of a thoracic stent graft system. With the recent late structural failures, sites were requested to submit all available imaging studies to date to allow the core laboratory to assess for structural failures such as type IIIb endoleaks, stent ring fractures, and stent ring enlargement. Of the 100 patients originally enrolled in the trial from 2016 to 2018, the core laboratory assessed the imaging studies performed at $ 1 year for 83 patients. Results: No structural failures of the graft were reported through 1 year of follow-up. At 1 to 4 years, graft structural failures were detected in 11 patients with descending thoracic aortic aneurysms. Of the 11 patients, 5 had a type IIIb endoleak. Four of the ﬁ ve had imaging ﬁ ndings showing stent fractures consistent with the location of the graft seam and one had a type IIIb endoleak attributed to calcium erosion with no stent fracture or ring enlargement. Of the four patients with stent fracture in line with the graft seam, three underwent a relining procedure that successfully excluded the type IIIb endoleak. One of these three patients died 4 days later of suspected thoracic aortic rupture because the distal thoracic endovascular aortic repair extension had been landed in a previously dissected and fragile section of the aorta. The remaining six patients had had stent ring enlargement. One of the six patients had had persistent aneurysm expansion from the time of implantation onward and had died of unknown causes. The remaining ﬁ ve patients have continued to be monitored. Conclusions: Inthepresentpreliminaryanalysis,theimagingpatternsassociatedwithtypeIIIbendoleaks,stentfractures,and stent ring enlargement appearto berelated to the loss ofseamintegrity or detachmentof the stent rings fromthe surface of the graft material. The imaging patterns we have detailed should be closely monitored using computed tomography angiography surveillance to allow structural failures to be promptly identi ﬁ ed and treated. (J Vasc Surg 2021; - :1-10.)

The Valiant Navion thoracic stent graft system (Medtronic Inc, Santa Rosa, Calif) was designed with improved conformability and a lower profile, and the patient outcomes through the 30-day and 1-year points have generally been positive. 1,2Recently, however, unexpected late structural failures of the stent graft have been observed in the Valiant Evo U.S. and international clinical trials (ClinicalTrials.govidentifiers, NCT02625324 and NCT02652949). 3In response to these adverse events, the manufacturer decided to issue a voluntary global recall of the device in February 2021.
Stent graft failure modes can generally be grouped into fractures of the metallic stent rings, suture breakage, and other causes of fabric wear. 4Cyclical movement of the metal stents due to the pulsatile environment can lead to fatigue stress and fracture 4,5 ; however, the occurrence of stent fractures has been rare with modern grafts. 6,7he sutures in the graft can also fail by creating microleakage where the suture penetrates the fabric, 8 or a broken suture can lead to detachment of a stent ring 9,10 or fabric disruption if the suture had joined two edges of the fabric.][13] Identifying structural failures of a graft is imperative because failure can be associated with type IIIb endoleaks.Type IIIb endoleaks after thoracic endovascular aortic repair (TEVAR) are rare but have been documented in a few case reports. 14,15Even with abdominal endovascular aneurysm repair, both randomized control trials and large multicenter registries of current generation stent grafts have reported rates <2%. 11,16Although uncommon, type IIIb endoleaks are serious adverse events because they result in blood flow back into the aneurysm sac, resulting in a significant risk of rupture. 16,17hen diagnosed, a type IIIb endoleak can generally be successfully treated by relining the device. 18,19In the present report, we have summarized the recurring patterns in the imaging studies of patients with Navion stent graft failure with the aim of increasing physician awareness in the identification of possible failure modes, early recognition, and prompt treatment.

METHODS
Trial design and clinical and imaging follow-up extension.The patients identified with type IIIb endoleaks and other imaging findings were a part of the Valiant Evo U.S. and international clinical trials (Clinical-Trials.govidentifiers, NCT02625324 and NCT02652949).In brief, the trials were prospective, single-arm investigations of the Valiant Navion stent graft system for the treatment of pathologies, including descending thoracic aortic aneurysms (DTAAs) and penetrating atherosclerotic ulcers.More details on the trial design and the 30-day and 1-year outcomes have been previously reported. 1,2All the sites conducted the study in accordance with the clinical investigation protocol and received institutional review board or ethics committee approval, as applicable.All the patients in the trials provided written informed consent, and the trials were compliant with the Declaration of Helsinki (October 2013) and the laws and regulations of the countries in which the clinical trials were conducted.
The trials were originally designed with clinical and imaging follow-up, including independent core laboratory analysis (Syntactx, New York, NY) through 1 year.A total of 100 patients were enrolled between April 2016 and March 2018.With the recent observations of type IIIb endoleaks, the sponsor initiated an investigation in which all sites were asked to submit their follow-up imaging studies beyond 1 year to the core laboratory for review, including from patients who had withdrawn from the study.The request for the retrospective imaging review was made possible in the United States under a Health Insurance Portability and Accountability Act exception, given the urgency to assess patient safety, and was communicated to the related institutional review boards through the unanticipated adverse device effects letter.For the sites outside the United States, the unanticipated serious adverse device effects letter sent to the ethics committees included language regarding the core laboratory review of imaging studies from all the study patients in the interest of patient safety and specified how data privacy would be ensured for the patients who had withdrawn from the trial.
Valiant Navion thoracic stent graft design and relevance to imaging findings.The Valiant Navion stent graft is constructed from a sheet of multifilament polyester sewn into a cylindrical shape, resulting in a seam line running along the length of the graft (Fig 1).The graft also has a series of stent rings that are formed by joining two ends of a stent ring with a cylindrical crimp sleeve.The stent rings are formed at a larger diameter (w20%) than that of the graft fabric diameter and sewn to the outer surface of the graft fabric such that the crimp sleeve on each stent ring is oriented w180 from the seam line (Fig 1).

ARTICLE HIGHLIGHTS d
Type of Research: A multicenter, prospective, nonrandomized trial d Key Findings: Eleven patients with a descending thoracic aortic aneurysm from the Valiant EVO clinical trial were identified with structural failure in their thoracic stent grafts.Five patients had experienced type IIIb endoleaks, with four having stent fractures and loss of seam integrity, and six patients had stent ring enlargements.d Take Home Message: Late structural failures were identified with the thoracic stent graft in the Valiant Evo clinical trial.These can present as type IIIb endoleaks, stent fractures, and stent ring enlargement.Lifelong surveillance using computed tomography angiography is important to allow structural failures to be promptly identified and appropriately treated.
The stent graft has three radiopaque proximal markers placed 120 from each other at the proximal end of the fabric.One radiopaque side marker is sewn between the third and fourth stent rings, with two radiopaque markers at the distal end of the fabric.Both the side marker and the crimps can be identified using high contrast-enhanced computed tomography (CT) or radiography.Together, they can be used to determine the location of the seam because the side marker is approximately equidistant between the crimps and the seam.
Core laboratory image analysis.All core laboratory reviews were performed on fully de-identified images.The core laboratory assessed the images for evidence of type IIIb endoleaks, stent ring fractures, and stent ring enlargement, which were required to meet the following criteria: d Type IIIb endoleak: defined as blood flow through a fabric disruption with confirmation with CT angiography (CTA) d Stent fracture: stents were considered fractured if a visible gap was present in the ring, with be confirmation by CT or radiography d Stent ring enlargement: defined as an increase of the diameter of a nitinol stent ring >1 mm of the nominal graft diameter as measured by CT; the most conservative threshold was chosen to detect all possible events, with the understanding that false-positive results could also be identified

RESULTS
Through 1 year, no structural failures or type IIIb endoleaks were detected. 2Of the 100 patients originally enrolled, the core laboratory assessed the imaging studies at $1 year for 83 patients, including some patients who had withdrawn from the clinical trials.Through the retrospective core laboratory review, four patients who had been treated for a DTAA were identified with late type IIIb endoleaks concomitant with stent fracture and stent ring enlargement detected 36 to 49 months after the initial TEVAR implantation (Table I).Two of the four patients were asymptomatic and had undergone a complete relining procedure that successfully excluded their endoleak.One of the four patients was asymptomatic and the reintervention had been scheduled.Patient 1 underwent a relining procedure that successfully excluded the type IIIb endoleak; however, the patient died 4 days later.According to the investigator review, the death was likely secondary to aortic rupture at the level of the distal TEVAR extension, which had been landed in a previously dissected aortic segment.However, the cause of death could not be confirmed because the family refused an autopsy.
Patient 5 did not have any stent fractures but experienced a type IIIb endoleak that the core laboratory suspected had resulted from fabric wear near a region of calcification.The patient underwent a successful secondary procedure to treat the type IIIb endoleak but died 3 months later of noneaortic-related causes.Finally, six patients with a DTAA were identified with stent ring enlargement without any stent fracture or type IIIb endoleak.The stent ring enlargements measured by the core laboratory were all beyond the margin of error that could have resulted from imaging modality limitations or interobserver variability.Patient 6 underwent successful reintervention for type Ia and Ib endoleaks within the first year, 2 and the core laboratory reported no endoleaks after the secondary procedure.However, patient 6 experienced had persistent aneurysm expansion and died of unknown causes.The other five patients have continued to be monitored without reinterventions planned.None of the patients treated for a penetrating atherosclerotic ulcer presented with signs of structural failure of the graft at the last follow-up examination.
Patient 1 (type IIIb endoleak, stent fractures along seam line, stent ring enlargement).Patient 1 was a 66year-old man and had a saccular DTAA with a diameter of 59 mm.The patient was treated with a Valiant Navion stent graft (40 mm, 40 mm, 225 mm) successfully advanced and deployed in zone 4. The completion angiography showed a type Ib and type II endoleak that was resolved by balloon dilation.One day later, the patient presented with acute back pain.The CTA scan revealed a focal aortic dissection at the distal end of the graft that extended distally for 4.6 cm.The stent graft still appeared to be positioned normally, without a sign of an endoleak.Because the patient's pain resolved without further treatment, he was discharged 10 days after procedure.
The patient was admitted 44 months after the index procedure for acute left chest pain.CTA showed a type IIIb endoleak (Fig 2, A) and an aneurysm sac increase of >1 cm.Angiography confirmed blood flow outside of what should have been the cylindrical stent graft boundary (Fig 2, B).A secondary procedure was performed to reline the graft, and the type IIIb endoleak was successfully excluded with no evidence of any endoleaks.Four days after the secondary procedure, the patient was found unresponsive after an episode of left flank pain and pronounced dead, with the family refusing an autopsy.A retrospective review of the imaging studies b Information on secondary procedures determined from site and/or investigator communication because the information was not entered in the database.
c Subject withdrew from the study and did not provide consent for long-term follow-up in the trial; thus, data >1 year were either not available or reported from site and/or investigator communication instead of the clinical study electronic case report form for these subjects.d Subject 9 did not have 1-month imaging studies available; thus, we reported the preprocedure imaging measurement.e Officially reported by the core laboratory as ring deformation owing to an inability to locate the peaks to measure ring enlargement, although both the core laboratory and the investigators reviewed imaging studies and believe the findings indicate ring enlargement.
determined that the aortic rupture was likely related to placement of the distal TEVAR extension device in a previously dissected and fragile portion of the aorta (Supplementary Fig 1 , online only).
From the combination of CTA scans and angiography, it was evident that the stent graft fractures coincided with the location of the seam line of the graft.On the angiogram (Fig 2, B), the side marker was identified in the middle of the aorta, with the crimps visible along the inner curvature.This confirmed that the seam line was on the outer curvature where the stents had fractured.The three-dimensional CTA reconstructions (Fig 3), performed between 24 and 41 months after the index procedure, showed that four stent rings had fractured, with an additional stent ring fracture that occurred between 41 and 44 months.Stent ring enlargement had occurred as early as 24 months after initial treatment.

DISCUSSION
Type IIIb endoleaks are serious adverse events owing to repressurization of the aneurysm sac, which puts patients at an increased risk of rupture. 16In the literature, the incidence of type IIIb endoleaks has been reported to be <2%. 11,16At the time of the present analysis of the Valiant Evo clinical trial, five patients had been identified with late type IIIb endoleaks.Four of these patients had stent fractures coincident with the seam and the fifth endoleak was attributed to calcium erosion.The observations of stent fractures and type IIIb endoleaks led the manufacturer to initiate a voluntary global recall of the Navion devices in the interest of patient safety.
1][22] At the time of our report, four patients had undergone a relining procedure, and all reinterventions had successfully sealed the type IIIb endoleak.However, for patient 1, the distal end of the relining graft might have induced aortic rupture, because the distal landing was in a previously dissected and fragile aortic segment (Supplementary Fig 1

, online only).
The multiple stent fractures in line with the seam was a different pattern from the typical description of stent ring fractures from case reports of other grafts. 4,10,23rom this image analysis, one could hypothesize that the finding of stent fractures along the same longitudinal line as the seam, opposite the stent crimps, is highly suspicious for the loss of integrity of the seam.A significant loss of seam integrity might allow for unanticipated loading and/or displacement of the stent rings, which might, in turn, result in an increased risk of stent ring fracture.Although previous reports have also concluded that excessive mechanical stress can make stent rings more prone to failure, 23,24 this does not explain the cause of the loss of seam integrity, which is still under investigation.
Stent ring enlargement was also identified as a failure mode in our retrospective analysis and believed to result from detachment of the stent from the surface of the graft material.Although it is not common practice to measure stent ring enlargement, we would emphasize the importance of assessing the stent ring sizes along the length of the graft from the cross-sectional CT images (Fig 5).The detachment of stent rings from grafts after suture breakage has been previously reported with other grafts, 9,10,20 and the additional movement of a detached ring could result in stent fracture. 23,24Although no cause has been identified for stent ring enlargement, one possibility is the loss of suture fixation integrity.
Because suture failure could lead to the development of endoleaks, 10 compliance with follow-up imaging recommended.
We would emphasize that the root cause analysis of the structural failures is still ongoing, and the results will be reported when available.A number of engineering design factors can contribute to structural failure, including the design, material, construction, and use of the component.Several different design elements, materials, and manufacturing methods are unique to the Valiant Navion device compared with those used in previous generations of devices such as the Valiant Captivia (Medtronic Inc).No cases of stent fracture or type IIIb endoleak were reported through 5 years in the VALOR II (the Valiant thoracic stent graft system clinical study), 21 Dissection, 22 and RESCUE (study to determine if the Valiant stent graft is safe and effective in treating patients who have a blunt thoracic aortic injury) 25 clinical trials with the Valiant Captivia device.
Strict adherence to lifelong surveillance with a minimum of annual CTA is important for the timely identification of any structural failure of stent grafts. 26If a patient presents with a line of stent fractures, further interrogation is required to assess for type IIIb endoleaks.Strict imaging follow-up with CTA should be suggested for patients found with a single stent fracture without endoleaks and for patients identified with single stent ring enlargement.In accordance with the Society for Vascular Surgery guidelines, 27,28 lifelong surveillance is warranted because a single stent fracture and suture breakage can lead to fabric degradation over time. 8,9inally, a retrospective review of previous imaging studies might be beneficial because the patterns of graft failure we have described are difficult to assess and could be overlooked initially.
To detect these late graft structural failures (Table II), we would recommend high quality CTA imaging studies, and, ideally, the stent diameter should be sized in planes orthogonal to the graft's main longitudinal axis to assess for stent ring enlargement.Using these same images, the outside of the stent graft boundaries should be carefully examined for any presence of contrast.Moreover, threedimensional reconstructions with the centerline should be obtained from CTA scans to identify stent breakage. 5,23These can also be found by careful evaluation of plain radiographs of the graft, 31,32 although overlapping stents can sometimes render the fractures difficult to ascertain.][35] The guidelines at present recommend treatment for type I and III endoleaks or type II endoleaks with aneurysm expansion. 26,29,30If an endovascular aortic reintervention is planned for any disease progression in a patient previously implanted with a Valiant Navion stent graft, we would suggest relining the previously treated areas, even without the diagnosis of other failures.In contrast to the reported data in which type IIIb endoleaks are often treated with spot relining using cuffs or limb extensions to exclude the endoleak, 11,36 we would suggest complete relining of the graft similar to the method used by Lemmon et al 37 to avoid future potential complications.
Finally, the distal seal has generally been discussed in the context of type Ib endoleaks. 2,38,39However, reported studies have also suggested the loss of fixation and Journal of Vascular Surgery migration will result in increased movement of the graft and fatigue stress on the stent rings. 5,23Aortic elongation will be more pronounced at the distal end of the thoracic aorta, 40,41 and the morphologic changes in the anatomy will affect the structural integrity of grafts. 2,4Furthermore, angulation is a well-discussed risk factor for graft migration and a compromised seal. 42,43All these factors could have played a role in the structural failures seen in our patient 4. Consistent with the present guidelines, which recommend endovascular treatment of all type III endoleaks, 26,29,30 we believe it is imperative to have a good seal zones to minimize the risk of further complications.
Study limitations.One limitation of the present retrospective analysis was that the original trial protocol was concluded at 1 year.Thus, clinical information on secondary procedures and mortality was not available for patients who had withdrawn from the study despite the core laboratory assessing the images from 83 patients.Also, if the CT images are not orthogonal to the main axis of the graft, a margin of error will be introduced into the calculation of the stent ring diameter.The 1-mm threshold beyond the nominal graft diameter as the definition for stent ring enlargement was conservatively chosen to identify all possible events, with the understanding that potential false-positive results would be found.Although a 1-mm threshold might be too strict a criterion to apply in the clinical setting because of imaging modality limitations or interobserver variability, stent ring enlargement resulting from detachment from the graft material can be expected to be >1 mm owing to the oversizing of the stent rings relative to the stent fabric.Likewise, without explanted devices to examine, the structural graft failures identified using the various imaging techniques could not be fully confirmed.

CONCLUSIONS
In the present preliminary analysis, several late structural graft failures occurred in the Valiant Evo U.S. and international clinical trials.We have described the imaging patterns associated with the type IIIb endoleaks, stent fractures, and stent ring enlargements seen in the present study and appear to be related to the loss of seam integrity or detachment of the stent rings from the surface of the graft fabric.In accordance with society guidelines, [26][27][28] lifelong surveillance for these imaging trends should be performed with CTA to allow structural failures to be promptly identified and treated.The complete understanding of the mechanisms of failure requires further investigation, which is underway.

Fig 1 .
Fig 1. A, Construction of the Valiant Navion stent graft with the cross-section view showing the stent rings sewn with the crimps located w180 from the graft seam.Also, a radiopaque side marker is nearly equidistant between the seam and crimps (red circle).B, View of a graft with the seam running down the length of the graft (blue arrows).C, View showing a line of crimps on the other side of the graft (green arrows).

Patient 3 (
type IIIb endoleak, stent fractures along seam line, stent ring enlargement).The details and images from patient 3 are shown in Supplementary Fig 2 (online only).Patient 4 (type IIIb endoleak, distal stent fractures along seam line, stent ring enlargement).Patient 4 was a 74-year-old woman with a fusiform DTAA with a diameter of 56 mm.The patient was implanted with two Valiant Navion stent grafts (proximal device, 34 mm, 34 mm, 225 mm; distal device, 43 mm, 43 mm, 175 mm) with a zone 3 proximal landing.The patient tolerated the procedure well and was discharged in 2 days.The CTA imaging studies at 1 and 12 months showed that the distance between the distal end of the graft and the distal edge of the celiac artery had increased by 17 mm (from 19 mm to 36 mm; Fig4, A and B).The core laboratory did not consider this a distal migration owing to the corresponding increase in the centerline length of the thoracic aorta.At 49 months, the patient had new findings of pulmonary malignancy and was referred for further evaluation.In the 49-month imaging study (Fig4, C), stent rings 9, 10, and 11 of the distal graft were found to have fractured, coincident with the location of the graft seam line.The findings was further confirmed by the 51-month chest radiograph (Fig4, D).Because the patient elected to undergo partial pneumonectomy and adjuvant therapy, reintervention for the stent fractures and type IIIb endoleak was deferred.At the last follow-up visit, the patient was scheduled for additional imaging studies and a planned endovascular reintervention.Patient 11 (single stent ring enlargement).Patient 11 was an 84-year-old man with a fusiform DTAA with a diameter of 60 mm.The patient had two Valiant Navion stent grafts placed with the proximal device (43 mm, 43 mm, 225 mm) landed in zone 3 and the distal device (46 mm, 46 mm, 175 mm) in zone 4. The patient tolerated the procedure well and was discharged in 2 days.Between 12 and 48 months, stent ring enlargement was suspected because, although the flow was contained within the boundary of the stent fabric, a focal stent ring detachment from the fabric on the upper edge was

Fig 2 .
Fig 2. Patient 1. A, Computed tomography angiography (CTA) at 44 months after treatment showing contrast outside the stent graft profile (blue arrow) indicative of a type IIIb endoleak.B, Angiogram showing the side marker (red circle) identified and crimps evident along the inner curvature (green arrows).These findings indicate the graft seam is on the outer curvature and coincident with the location of the fractured stents (blue arrows).

Fig 3 .
Fig 3. Patient 1. Three-dimensional computed tomography angiography (CTA) reconstructions over time with the stent rings numbered starting from the proximal end of the graft and showing no stent fractures at 24 months.At 41 months, four stent fractures (red numbers) were found, coincident with the seam line, with an additional stent fracturing by 44 months.The individual stent ring diameters over time showed ring enlargement (yellow numbers) as early as 24 months.

Fig 4 .
Fig 4. Patient 4. A,B, Three-dimensional computed tomography angiography (CTA) reconstruction showing the distance between the distal edge of the graft and distal edge of the celiac artery had increased by 17 mm by the 12-month imaging follow-up.The bottom three stent rings had fractured by the 49-month CTA study (C), and the fractured stents were also clear on the 51-month chest radiography (D).

Fig 5 .
Fig 5. Patient 11.Computed tomography angiography (CTA) showing stent ring enlargement that occurred between 12 and 48 months.The stent appears to have detached from the fabric, although this did not lead to a type IIIb endoleak.The nominal stent graft diameter was 43 mm; the seam location is marked by blue arrows.

Table I .
Core laboratoryereported baseline characteristics and outcomes of subjects with imaging findings F, Female; M, male; MAD, maximum aneurysm diameter; NA, not applicable; Pt.No., patient number.a Type IIIb endoleak, fracture, and/or ring enlargement.