Editor's Choice - Structured Computed Tomography Analysis can Identify the Majority of Patients at Risk of Post-Endovascular Aortic Repair Rupture.

OBJECTIVE: The main objective was to report mechanisms and precursors for post-endovascular aneurysm repair (EVAR) rupture. The second was to apply a structured protocol to explore whether these factors were identifiable on follow up computed tomography (CT) prior to rupture. The third objective was to study the incidence, treatment, and outcome of post-EVAR rupture. METHODS: This was a multicentre, retrospective study of patients treated with standard EVAR at five Swedish hospitals from 2008 to 2018. Patients were identified from the Swedvasc registry. Medical records were reviewed up to 2020. Index EVAR and follow up data were recorded. The primary endpoint was post-EVAR rupture. CT at follow up and at post-EVAR rupture were studied, using a structured protocol, to determine rupture mechanisms and identifiable precursors. RESULTS: In 1 805 patients treated by EVAR, 45 post-EVAR ruptures occurred in 43 patients. The cumulative incidence was 2.5% over a mean follow up of 5.2 years. The incidence rate was 4.5/1 000 person years. Median time to post-EVAR rupture was 4.1 years. A further six cases of post-EVAR rupture in five patients found outside the main cohort were included in the analysis of rupture mechanisms only. The rupture mechanism was type IA in 20 of 51 cases (39%), IB in 20 of 51 (39%) and IIIA/B in 11 of 51 (22%). One of these had type IA + IB combined. One patient had an aortoduodenal fistula without another mechanism being identified. Precursors had been noted on CT follow up prior to post-EVAR rupture in 16 of 51 (31%). Retrospectively, using the structured protocol, precursors could be identified in 43 of 51 (84%). In 17 of 27 (63%) cases missed on follow up but retrospectively identifiable, the mechanisms were type IB/III. Overall, the 30 day mortality rate after post-EVAR rupture was 47% (n = 24/51) and the post-operative mortality rate was 21% (n = 7/33). CONCLUSIONS: Most precursors of post-EVAR rupture are underdiagnosed but identifiable before rupture using a structured follow up CT protocol. Precursors of type IB and III failures caused the majority of post-EVAR ruptures.

A population-based study of post-endovascular aortic repair rupture during 15 years.

OBJECTIVE: The devastating event of a ruptured abdominal aortic aneurysm (rAAA) in patients who have survived a previous AAA repair, either elective or urgent, is a feared and quite uncommon event. It has been suggested to partly explain the loss of the early survival benefit for endovascular aortic repair (EVAR) vs open surgical repair (OSR). The main objective of this study was to report the national incidence rate, risk factors and outcome of post-EVAR ruptures. Secondarily, the national incidence rate of ruptures after OSR (post-OSR ruptures) was investigated. METHODS: We conducted a nationwide, population-based, retrospective cohort study using the inpatient and outpatient entries for all patients >40 years of age, receiving their first (index) surgical procedure for AAA, from 2001 to 2015. Only patients surviving their index procedure were included. The primary outcome was rAAA, registered after discharge from the index procedure (EVAR or OSR), identified in the Swedish National Patient Registry and the Cause of Death Registry. RESULTS: In total, 14,859 patients survived their primary (index) AAA procedure. There were 6470 EVAR procedures, 5893 for intact AAA (iAAA) and 577 for rAAA. Of the 6470 EVAR patients, 86 cases of post-EVAR rupture were identified, corresponding with a cumulative incidence of 1.3% over a mean follow-up time of 3.9 years. The incidence rate was 3.4 (95% confidence interval [CI], 2.7-4.2)/1000 person-years. The independent risk factors identified for post-EVAR rupture were rAAA at index surgery HR 2.4 (95% CI, 1.4-4.1, p 0.002) and age (hazard ratio, 1.1; 95% CI, 1.0-1.1; P < .001). Freedom from post-EVAR rupture was 99%, 98%, and 96% at 3, 5, and 10 years, respectively. Total and postoperative mortality after post-EVAR rupture were 42% and 17% (30 days), 45% and 22% (90 days), and 53% and 33% (1 year). The incidence rate of post-OSR rupture was 0.9/1000 person-years (95% CI, 0.7-1.2). CONCLUSIONS: Post-EVAR rupture is a rare complication that can occur at any time after the index EVAR procedure. This finding may have implications for the discussion of limited follow-up programs and for the choice of procedure in patients with an AAA with a long life expectancy. An rAAA as the indication for the index surgery and age were identified as risk factors for post-EVAR rupture. The mortality associated with post-EVAR rupture is high, but lower than that of primary rAAA. The much lower risk of post-OSR rupture was confirmed, but must not be neglected as a possible late complication.

Limb Graft Occlusion Following Endovascular Aneurysm Repair for Infrarenal Abdominal Aortic Aneurysm with the Zenith Alpha, Excluder, and Endurant Devices: a Multicentre Cohort Study.

OBJECTIVE: Limb graft occlusion (LGO) is a serious complication after endovascular aneurysm repair (EVAR) and while device development enables treatment of increasingly complex aortic anatomy, little is known about how endograft type affects the risk of occlusion. This observational study aimed to explore the incidence of LGO after EVAR for three major endograft systems. METHODS: All patients with standard EVAR as the primary intervention for infrarenal abdominal aortic aneurysm (AAA), between January 2012 and December 2018, at five Swedish vascular surgery centres, were included in this multicentre retrospective cohort study. LGO was defined as a total limb occlusion regardless of symptoms, or a treated significant stenosis. A nested case control (NCC) design with incidence density sampling of 1:3 was used for analysis of potential per-operative and morphological risk factors. Conditional logistic regression was used to estimate multivariable odds ratios (OR) with 95% confidence intervals (CI) RESULTS: A total of 924 patients were included. The majority were male (84%), the mean age was 76 years (± 7.5 SD), and median AAA diameter was 59 mm (IQR 55, 67). Patients were treated with Zenith Alpha (n = 315, ZISL limbs), Excluder (n = 152, PLC/PXC limbs), and Endurant (n = 457, ETLW/ ETEW limbs). During median follow up of 37 months (IQR 21, 62), 55 occlusions occurred (5.9%); 39 with Zenith Alpha (12.4%), one with Excluder (0.7%), and 15 with Endurant (3.3%). In the NCC analysis, the Zenith Alpha device (OR 5.31, 95% CI 1.97 - 14.3), external iliac artery (EIA) landing (OR 5.91, 95% CI 1.30 - 26.7), and EIA diameter < 10 mm (OR 4.99, 95% CI 1.46 - 16.9) were associated with an increased risk of LGO. CONCLUSION: Endograft device type is an independent risk factor for LGO after EVAR. Specifically, the Zenith Alpha demonstrated an increased risk of LGO compared with the Endurant and Excluder devices. In addition, a narrow EIA and landing zone in EIA are also risk factors for LGO.

Nationwide Study on Treatment of Mycotic Thoracic Aortic Aneurysms.

OBJECTIVE: Mycotic aortic aneurysms are rare, life threatening, and complex. This nationwide study aimed to assess outcome after repair of mycotic thoracic aortic aneurysms (MTAAs). METHODS: Patients treated in Sweden for MTAAs between 2000 and 2016 were identified in the Swedish vascular registry (2010-16) and local patient registries (2000-09). Primary outcome was survival, and secondary outcomes included surgical strategy, rate of infection related complications (IRC), and re-operations. RESULTS: Fifty-two patients (median age 71 ± 8.1 years; 28 [54%] men, 13 [25%] ruptured) were identified (3.6% of all thoracic aortic aneurysm repairs in Sweden). Aneurysm location was aortic arch (n = 6; 11%), descending aorta (n = 42; 81%), and multiple locations (n = 4; 8%). Twenty-nine (56%) patients had positive cultures; the most prevalent agent was Staphylococcus aureus (n = 16; 31%). Operative techniques included thoracic endovascular aortic repair (TEVAR; n = 35 [67%]), fenestrated/branched TEVAR (n = 8; 15%), hybrid repair (n = 7; 14%), and open patch repair (n = 2; 4%). Survival was 92% (95% confidence interval [CI] 88-96) at 30 days, 88% (95% CI 84-93) at three months, 78% (73-84) at one year, and 71% (64-77) at five years. The mean follow up among survivors (> 90 days) was 45 months (range 4-216 months). Antibiotics were administered for a median of 15 weeks (range 0-220 weeks). IRCs occurred in nine patients (17%): sepsis (n = 3), graft infection (n = 3), recurrent mycotic aneurysm (n = 1), aorto-oesophageal/bronchial fistula (n = 2). Six (67%) IRCs were fatal; 80% occurred within the first year. Re-operations were performed in nine patients (17%). CONCLUSIONS: TEVAR was often used as treatment for MTAAs, with acceptable short- and long-term survival when compared with open cohorts in the literature. IRCs are of concern and warrant follow up and long-term antibiotic treatment.

Outcome After Endovascular Repair of Ruptured Descending Thoracic Aortic Aneurysm: A National Multicentre Study.

OBJECTIVE: The purpose of this multicentre study was to analyse the outcome of thoracic endovascular aortic repair (TEVAR) in patients with ruptured descending thoracic aortic aneurysm (rDTAA). METHODS: This is a nationwide retrospective study including all patients who underwent TEVAR for rDTAA at six major vascular university centres in Sweden between January 2000 and December 2015. Outcome measures were analysed using Kaplan-Meier estimator and multivariable Cox regression. RESULTS: There were 140 patients (age [mean ± SD] 74.1 ± 8.8 years; 56% men; aneurysm size 64.8 ± 19 mm), with rDTAA. In 53 patients (37.9%), the left subclavian artery was covered, and in 25 patients (17.9%) arch vessel revascularisation was performed. In total, 61/136 patients (45%) had a major complication within 30 days post TEVAR. Stroke (n = 20; 14.7%) was the most common complication, followed by paraplegia (n = 13; 9.6%) and major bleeding (n = 13; 9.6%). TEVAR related complications during follow up included endoleaks 22.1% (30/136; 14 type 1a, six type 1b, 10 not defined). In total, re-interventions (n = 31) were required in 27/137 (19.7%) patients. The median follow up time was 17.0 months (range 0-132 months). The Kaplan-Meier estimated survival was 80.0% at one month, 71.7% at three months, 65.3% at one year, 45.9% at three years, and 31.9% at five years. Age (HR 1.03; 95% CI 1.00-1.07; p = .046), history of stroke (HR 2.35; 95% CI 1.19-4.63; p = .014), previous aortic surgery (HR 2.11; 95% CI 1.15-3.87; p = .016) as well as post-operative major bleeding (HR 4.40; 95% CI 2.20-8.81; p = .001), stroke (HR 2.63; 95% CI 1.37-5.03; p = .004), and renal failure (HR 8.25; 95% CI 2.69-25.35; p = .001) were all associated with mortality. CONCLUSIONS: This nationwide multicentre study of patients with rDTAA undergoing TEVAR showed acceptable short- but poor long-term survival. Adequate proximal and distal aortic sealing zones are important for technical success. High risk patients and post-operative complications need to be further addressed in an effort to improve outcome.

Evaluation of calibration-free concentration analysis provided by Biacore™ systems.

Surface Plasmon Resonance biosensors measure the interaction between a molecule in solution and its interaction partner attached to a sensor surface. Under certain conditions, the observed binding rate can be used directly to obtain the concentration of the molecule in solution, without the use of any standard. This type of assay is referred to as Calibration Free Concentration Analysis, CFCA. By examining experimental conditions, including immobilization levels and temperature, for a range of analytes, and by using global analysis of several sample dilutions, conditions that gave the most robust results were identified. These conditions provided the concentration values that were on average ∼15% lower than those obtained using other methods. The accuracy of the concentration determined may be related to how the analyte is distributed in the dextran matrix and to its distance from the gold surface, and may thereby depend on the conversion of the SPR signal to mass. A good precision of CFCA, ∼8% (n = 21), was demonstrated when this method was used to efficiently guide purification procedures of Interferon α-2a. In this paper, the theory behind CFCA and the future developments, as well as the application of CFCA for absolute and relative concentration measurements (including the assessment of the potency of a biotherapeutic medicine) are discussed, and new evaluation tools that broaden the range of applications, are introduced.

Endovascular Closure of Chronic Dissection Entries in the Aortic Arch Using the Amplatzer Vascular Plug II as a Sealing Button.

PURPOSE: To present a new endovascular technique to avoid open surgical arch reconstruction in selected patients with aneurysmal dilatation due to small chronic dissection entries in the aortic arch. TECHNIQUE: The true and the false lumen of the aortic arch are catheterized from the femoral arteries. An Amplatzer Vascular Plug II (AVP II) is advanced through the proximal entry from the false lumen side and deployed as a sealing button in the entry hole, with 1 disc in the true lumen and the remaining 2 discs in the false lumen. This technique was used in 4 patients with chronic dissection involving the aortic arch, three of whom had had previous surgery for acute type A aortic dissection. In 3 patients, the false lumen of the thoracic aorta was successfully obliterated, with thrombosis and aortic diameter reduction during follow-up. In 1 patient, false lumen flow persisted, and he was subsequently treated with a total arch reconstruction and frozen elephant trunk. CONCLUSION: Endovascular closure of small proximal dissection entries in the aortic arch with an AVP II used as a sealing button is feasible and may be an alternative to open surgical arch reconstruction in selected patients with chronic aortic dissection and secondary aneurysm expansion.

Re-interventions after endovascular aortic repair for infrarenal abdominal aneurysms: a retrospective cohort study.

BACKGROUND: Early morbidity and mortality are generally lower after endovascular aortic repair (EVAR), than after open repair but re-interventions and late complications are more common. The aim of the present study was to make a detailed description of re-interventions after EVAR-including incidence, indications, procedures, and outcome-with special reference to non-access-related re-interventions. METHODS: This is a retrospective single-center cohort study of re-interventions after standard EVAR with special reference to non-access-related re-interventions. Consecutive patients (n = 405) treated with standard EVAR for non-ruptured (n = 337) or ruptured (n = 68) infrarenal aneurysms between 2005 and 2013 were analysed. Median follow-up was 29 months (range 0-108). RESULTS: Eighty-nine patients (22 %) underwent 113 re-interventions during follow-up. Twenty-seven patients (7 %) had 28 access related re-intervention, 65 patients (16 %) had 85 non-access related reinterventions. Non-access related re-interventions were more common in ruptured aneurysms than in unruptured aneurysms (22 vs. 15 %, p = 0.002). The most frequent indications were endoleak type I (n = 19), type II (n = 21), or type III (n = 5); stent graft migration (n = 9); and thrombosis (n = 14). The most frequent procedures were embolization of endoleak type II (n = 21), additional iliac stent graft (n = 19), proximal extension (n = 12), thrombolysis (n = 8), iliac limb bare-metal stenting (n = 6), and stent graft relining (n = 7). Endovascular technique was used in 83 % of re-interventions. Thirty-day mortality after non-access-related re-interventions was 15 % when initiated from symptoms (rupture or infection) and 0 % when initiated from follow-up findings (p = 0.014). Cumulative survival five years after EVAR was 72 % in patients with a re-intervention and 59 % in patients without (p = 0.21). CONCLUSIONS: Non-access-related re-intervention rates are still considerable after EVAR and more frequent after ruptured aneurysms. Endoleak embolization is the most frequent procedure, followed by additional iliac stent grafts. Outcomes after re-interventions are generally good, except when initiated by rupture or infection.

Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.

BACKGROUND: Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival. METHODS AND RESULTS: All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39-86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella-positive culture as predictors for late infection-related death. CONCLUSIONS: Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella-positive blood cultures were more likely to die from late infection.

EVAR Guided by 3D Image Fusion and CO2 DSA: A New Imaging Combination for Patients With Renal Insufficiency.

PURPOSE: To present a new combination of imaging techniques that helps reduce the use of iodinated contrast during endovascular aneurysm repair (EVAR) procedures in patients with renal insufficiency. TECHNIQUE: Relevant anatomical structures are marked in the preprocedure computed tomography (CT) angiogram. A 3D-3D image fusion between the preprocedure CT and an intraprocedure cone-beam CT is performed in order to overlay anatomical information on live fluoroscopy. Verification of the correct overlay matching (or adjustment if necessary) is based on carbon dioxide (CO2) digital subtraction angiograms (DSA) instead of iodine DSA. The stent-graft is placed and deployed based on the overlaid information. Correct device placement is finally verified with conventional contrast angiography. CONCLUSION: The combination of 3D image fusion of a preoperative CT with live fluoroscopy and CO2 DSA verification is feasible and sufficient for guidance of abdominal EVAR. This method minimizes the use of iodinated contrast media, protecting residual function in the setting of preexisting renal insufficiency.

Endovascular plugs to occlude proximal entries in chronic aortic dissection.

OBJECTIVES: Patients with expanding chronic aortic dissection and patent proximal entries are sometimes poor candidates for open surgery or TEVAR. Occlusion of proximal entries with endovascular plugs has previously been suggested in selected patients, but clinical results over time are unknown. This study analyses aortic remodelling and clinical outcome after proximal entry occlusion. METHODS: Between 2007 and 2016, 14 patients, with expanding chronic aortic dissection, considered poor candidates for standard treatment, were treated with endovascular plugs in proximal entries located in the arch (n = 6) or descending aorta (n = 8). The Amplatzer™ Vascular Plug II was used for entries ≤4 mm and the Amplatzer™ Septal Occluder or Amplatzer™ Muscular VSD Occluder for entries 5-16 mm. Patients were followed for 0.5-13 years (median 7.3) with clinical visits and computed tomography. Diameters and cross-sectional areas along the aorta were measured. RESULTS: Occlusion of proximal entries was achieved in 10/14 patients (71%), including 4 patients with an adjunctive reintervention needed for complete seal in the segment. Unchanged or reduced maximum thoracic aortic diameter was observed in all 10 patients with successful occlusion. In 4 patients, proximal occlusion was not achieved and early conversion to FET (n = 1), FET/TEVAR (n = 2) or TEVAR (n = 1) was performed. Two aorta-related deaths occurred during follow-up, both after early conversion. CONCLUSIONS: Endovascular occlusion of proximal dissection entries of expanding chronic aortic dissections can induce favourable aortic remodelling and may be considered in selected patients with expanding chronic aortic dissection who are poor candidates for open surgery or stent graft repair.

Deep Femoral Vein Reconstruction of the Abdominal Aorta and Adaptation of the Neo-Aortoiliac System Bypass Technique in an Endovascular Era.

BACKGROUND:: Primary infection of the abdominal aorta is a rare pathology that may threaten the integrity of the aortic wall, while secondary aortic prosthesis infection represents a devastating complication to open surgical and endovascular aortic surgery. Curative treatment is achievable by removal of all infected prosthetic material followed by a vascular reconstruction. DESIGN AND METHODS:: Twelve consecutive patients treated with the neo-aortoiliac system bypass (NAIS) procedure were reviewed. Nine were treated for a secondary aortic prosthesis infection (tube graft n = 3, bifurcated graft n = 4, endovascular aortic repair (EVAR) stent graft n = 1, and fenestrated EVAR [FEVAR] stent graft n = 1), while 3 patients underwent NAIS repair due to an emergent primary mycotic aortoiliac aneurysm. PRIMARY RESULTS:: Ten of 12 patients survived 30 days. Three patients were operated on acutely, and 9 patients had elective or subacute NAIS surgery. Two of 3 patients operated acutely died within 30 days, whereas no 30-day or 1-year mortality was observed in patients undergoing elective or subacute surgery. The median time from primary reconstruction to the NAIS procedure was 11 months (range: 0-201 months). Stent grafts (n = 5 of 12) were in 4 cases explanted using endovascular balloon clamping. Of the explanted endografts, 2 patients presented with a secondary graft infection after EVAR/FEVAR, while 3 patients had been emergently treated with endovascular cuffs as a "bridge-to-surgery" procedure due to aortoenteric fistula (AEF). Patients who received a "bridge-to-surgery" regimen were treated with the NAIS procedure within 8 weeks (median 27 days, range: 27-60) after receiving emergency stent grafting. PRINCIPAL CONCLUSIONS:: Aortic balloon-clamping during explantation of infected aortic prosthetic endografts is feasible and facilitates complete endograft removal. Endovascular bridging procedures could be beneficiary in the treatment of AEF or anastomotic dehiscence due to graft infection, offering a possibility to convert the acute setting to an elective definitive reconstructive procedure with a higher overall success rate.

Ethylene vinyl alcohol copolymer (Onyx) to seal type 1 endoleak. A new technique.

The aim of this study was to investigate whether the liquid embolic agent Onyx, an ethylene vinyl alcohol copolymer, can be used to seal type 1 endoleaks during endovascular aortic repair (EVAR). Six patients with large aortic aneurysms and remaining type 1 endoleaks during or after EVAR were treated with Onyx embolization through a microcatheter placed in the proximal neck in five cases and in the distal neck in one case. Four of the patients were treated using the chimney technique. The type 1 endoleak was primarily sealed by Onyx in all six patients. There was no distal embolization. Two patients had complications during follow-up. One patient had occlusions of chimney grafts to the renal arteries and to one leg extension. These occlusions were not anatomically related to Onyx embolization. One patient had late stentgraft migration of the Onyx-treated distal neck with aneurysm rupture 18 months after treatment. Early experience of Onyx embolization as a bailout solution of type 1 endoleaks after complicated EVAR is promising. However, effective seal with Onyx does not prevent late stentgraft migration. More reported patients and longer follow-up are necessary to evaluate this new technique.

Biosensor-based characterization of serum antibodies during development of an anti-IgE immunotherapeutic against allergy and asthma.

Antibody responses, induced in Cynomolgus monkey by recombinant IgE-derived immunotherapeutic protein against atopic allergies and asthma, were characterized using label-free, real-time protein interaction analysis. The effects of two different immunotherapeutic proteins were compared. Active concentrations of specific anti-IgE antibodies formed were determined in sera sampled at multiple time points, using conditions of total mass transport limitation that were proved to exist on the sensor surface. These concentrations varied from about 0.4 to 35 microg/ml among the monkeys and throughout the immunization period. Based on these concentrations, the rate and affinity constants for the binding of antibody populations to the antigen could be determined. The apparent equilibrium dissociation constant decreased during the immunization period, for all the monkeys, by a factor between 6 and 50, ending at values from approximately 2 x 10(-9) to approximately 2 x 10(-11) M among the animals. This affinity maturation was attributable to the changes in both rate constants, although the magnitude of the contribution of each constant depended partly on specimen, but primarily on the immunotherapeutic used. The immunotherapeutic proteins examined showed excellent immunogenic properties, providing the basis for a new and effective treatment for allergy and asthma.