Soluble Glycoprotein VI Predicts Abdominal Aortic Aneurysm Growth Rate and is a Novel Therapeutic Target.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.

Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms.

BACKGROUND: Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention. METHODS: TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr-/-) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3-/-). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA. RESULTS: Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3-/- mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK. CONCLUSIONS: These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.

International Collaborative Study Comparing Outcomes of Fenestrated Endovascular Aortic Repair in OCtogenarian vs Non-Octogenarian Patients: The FEVOC study.

OBJECTIVE: With an increasing life expectancy, more octogenarian patients are referred with complex aortic aneurysms (cAAA). The aim of this study was to evaluate short and mid-term outcomes following fenestrated aortic repair (FEVAR) in octogenarians. SUMMARY BACKGROUND DATA: Few studies looking at octogenarian-specific outcomes with diverging results. METHODS: Retrospective, multicentre cohort study including consecutive patients undergoing elective FEVAR for cAAAs or type IV thoracoabdominal aortic aneurysms between 2007-2022 in eight high-volume centres. Octogenarians vs. non-octogenarians were compared. The primary outcome was 30-day mortality. Secondary outcomes included 1, 2 and 5-year survival and reintervention rates. RESULTS: A total of 729 patients (median age of 74.8 years [IQR 69.2 - 79.14]) were included, 169 (23%) of which were octogenarians, with 316 (43.3%) patients undergoing juxta/pararenal aneurysm repair. Although octogenarians presented less complex but larger (61 mm vs. 58 mm) aneurysms, the number of fenestrations was similar across groups. No differences in in-hospital mortality (4.1 vs. 3.0%), MAE (16.6% vs 12.2%) or reintervention rates (11.2 vs. 10%) were found. Multivariable logistic regression of in-hospital mortality identified BMI (OR 0.66, 95% CI 0.51-0.95, P=0.003), chronic heart failure (OR 7.70, 95% CI 1.36-36.15, P=0.003) and GFR<45 ml/min/1.73 m2 (OR 5.25, 95% CI 1.20-22.86, P=0.027) as independent predictors. Median follow-up was 41 months. The 1, 2 and 5-year survival rates were 91.3%, 81.8% and 49.5% in octogenarians vs 90.6%, 86.5% and 68.8% in non-octogenarian patients (Log-rank: =0.001). Freedom from aortic-related death and freedom from reintervention at five-years were similar across groups (log-rank=0.94 and .76, respectively). Age>80 was not an independent predictor of 30-day or long-term mortality on multivariable and Cox regression analysis. CONCLUSIONS: Elective FEVAR in octogenarians appears to be safe, with similar outcomes as in younger patients. Future studies looking at improved patient selection methods to ensure long-term survival benefits in both octogenarians and younger patients are warranted.

Statin therapy after elective abdominal aortic aneurysm repair improves long-term survival.

BACKGROUND: Patients with abdominal aortic aneurysms are at high risk of cardiovascular events. Although statin therapy is indicated for most of these patients, no specific recommendation regarding the intensity of therapy exists. The aim of this study was to assess the possible effect of statin therapy on survival of patients undergoing abdominal aortic aneurysm repair and to investigate if high-intensity statin therapy was superior to low-moderate-intensity therapy. METHODS: Data from nationwide Swedish registers on hospital admissions, operations, and medications for patients undergoing elective abdominal aortic aneurysm repair from 2006 to 2018 were collected. The effect of statin use was evaluated in three separate propensity score matched cohorts: perioperative mortality was analysed according to whether patients were on statins before abdominal aortic aneurysm repair or not; long-term survival was assessed according to whether patients were on statins during follow-up or not; and, for those on statins after surgery, long-term survival was analysed according to whether patients were on high-intensity or low-moderate-intensity statin therapy. RESULTS: Preoperative statin use did not reduce 90-day perioperative mortality (OR 0.99, 95% c.i. 0.77 to 1.28), whilst there was a marked benefit regarding long-term survival for postoperative statin users (HR 1.43, 95% c.i. 1.34 to 1.54). High-intensity statin therapy had no advantage over low-medium-intensity statin therapy with regards to long-term survival (HR 1.00, 95% c.i. 0.80 to 1.25). CONCLUSION: In this nationwide propensity score matched cohort study, preoperative statin treatment had no benefit regarding 90-day perioperative survival, but postoperative statin treatment markedly improved long-term survival. No additional benefit regarding high-dose statin treatment could be confirmed in this analysis.

Six Years' Experience With a Novel Dissection-Specific Stent-Graft to Prevent Distal Stent-Graft-Induced New Entry.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) in chronic dissection is associated with a risk for distal stent-graft-induced new entry (dSINE) in up to a quarter of cases. We assess the mid-term outcome of a novel dissection-specific stent-graft (DSSG), which is a custom-made device based on the Cook Alpha platform, with a modified graft design and a distal endovascular elephant trunk without any supporting stent to reduce the radial force on the dissection membrane at the distal landing zone. METHODS: A retrospective single-center study of chronic dissection patients at high risk of dSINE who received an elective endovascular repair with DSSG from January 2017 to June 2023. The primary outcome is Kaplan-Meier (KM) estimated freedom from dSINE during follow-up. Secondary outcomes included technical success, aortic remodeling, and anatomical evaluation of the distal landing zone in cases with dSINE during follow-up versus those without. RESULTS: Thirty patients (24 males) with a median age of 66 years [range=31-78] underwent elective TEVAR with the DSSG. The majority, n=27 (90%), had previous aortic repair; 7 (23%) had established connective tissue disease, and 6 (20%) had established dSINE after previous stent-graft implantation as an indication for TEVAR. Technical success was achieved in n=29 (97%). Median follow-up was 38.5 months (4.3-76.4), and KM estimated freedom from dSINE at 1 and 3 years was 95.6% (SE 0.043) and 89% (SE 0.081), respectively Four cases developed dSINE during follow-up. The median distance from the distal stent-graft to the coeliac trunk was 74mm (range=18-123) in the dSINE group versus 26mm (range=0-74) in the non-dSINE group (p=0.049). Median proximal tangential aortic angulation in the distal landing zone was 38.5° (range=26°-50°) in the dSINE group compared to 21° (range=3-61°) in the non-dSINE group (p=0.052). CONCLUSIONS: The Use of a novel DSSG with low radial force for TEVAR in the setting of chronic dissection is safe and feasible, with remodeling outcomes comparable with standard TEVAR. The reduced distal radial force in the DSSG does not eliminate the risk for dSINE over time, with new entries occurring, particularly in cases where the distal landing zone is in a tortuous aortic segment and not close to the coeliac trunk. CLINICAL IMPACT: Using the novel dissection-specific stent-graft with reduced radial force is safe and feasible but does not completely eliminate the risk of dSINE occurring over time. The exact positioning of the distal stent-graft in a straight aortic segment, close to the coeliac trunk, may be of importance to further mitigate the risk.

A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets (COS) has been developed. COS, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. METHODS: Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. RESULTS: The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents) 15 questions were eliminated, and 11 further questions were eliminated after round 2 (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: death at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, five year survival, and continued sac growth. CONCLUSION: Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and to define instruments for cognitive functioning is needed.

Intravascular Ultrasound in the Detection of Bridging Stent Graft Instability During Fenestrated and Branched Endovascular Aneurysm Repair Procedures: A Multicentre Study on 274 Target Vessels.

OBJECTIVE: The use of intravascular ultrasound (IVUS) reduces contrast medium use and radiation exposure during conventional endovascular aneurysm repair (EVAR). The aim of this study was to evaluate the safety and efficacy of IVUS in detecting bridging stent graft (bSG) instability during fenestrated and branched EVAR (F/B-EVAR). METHODS: This was a prospective observational multicentre study. The following outcomes were evaluated: (1) technical success of the IVUS in each bSG, (2) IVUS findings compared with intra-operative angiography, (3) incidence of post-operative computed tomography angiography (CTA) findings not detected with IVUS, and (4) absence of IVUS related adverse events. Target visceral vessel (TVV) instability was defined as any branch or fenestration issues requiring an additional manoeuvre or re-intervention. Any IVUS assessment that detected stenosis, kinking, or any geometric TVV issue was considered to be branch instability. All procedures were performed in ad hoc hybrid rooms. RESULTS: Eighty patients (69% males; median age 72 years; interquartile range 59, 77 years) from four aortic centres treated with F/B-EVAR between January 2019 and September 2021 were included: 70 BEVAR (21 off the shelf; 49 custom made), eight FEVAR (custom made), and two F/B-EVAR (custom made), for a total of 300 potential TVVs. Two TVVs (0.7%) were left unstented and excluded from the analysis. The TVVs could not be accessed with the IVUS catheter in seven cases (2.3%). Furthermore, 17 (5.7%) TVVs could not be examined due to a malfunction of the IVUS catheter. The technical success of the IVUS assessment was 91.9% (274/298), with no IVUS related adverse events. Seven TVVs (2.5%) showed signs of bSG instability by means of IVUS, leading to immediate revisions. The first post-operative CTA at least 30 days after the index procedure was available in 268 of the 274 TVVs originally assessed by IVUS. In seven of the 268 TVVs (2.6%) a re-intervention became necessary due to bSG instability. CONCLUSION: This study suggests that IVUS is a safe and potentially valuable adjunctive imaging technology for intra-operative detection of TVV instability. Further long term investigations on larger cohorts are required to validate these promising results and to compare IVUS with alternative technologies in terms of efficiency, radiation exposure, procedure time, and costs.

Editor's Choice - Systematic Review and Meta-Analysis of Contemporary Abdominal Aortic Aneurysm Growth Rates.

OBJECTIVE: To evaluate the contemporary growth rate of small abdominal aortic aneurysms (AAAs) in view of recent epidemiological changes, such as decreasing smoking rates and establishment of population screening programmes. DATA SOURCES: MEDLINE, CENTRAL, PsycINFO, Web of Science Core Collection, and OpenGrey databases. REVIEW METHODS: Systematic review following the PRISMA guidelines. In October 2021, databases were queried for studies reporting on AAA growth rates published from 2015 onwards. The primary outcome was contemporary AAA growth rates in mm/year. Data were pooled in a random effects model meta-analysis, and heterogeneity was assessed through the I2 statistic. GRADE assessment of the findings was performed. The protocol was published in PROSPERO (CRD42022297404). RESULTS: Of 8 717 titles identified, 43 studies and 28 277 patients were included: 1 241 patients from randomised controlled trials (RCTs), 23 941 from clinical observational studies, and 3 095 from radiological or translational research studies. The mean AAA growth rate was 2.38 mm/year (95% CI 2.16 - 2.60 mm/year; GRADE = low), with meta-regression analysis adjusted for baseline diameter showing an increase of 0.08 mm/year (95% CI 0.024 - 0.137 mm/year; p = .005) for each millimetre of increased baseline diameter. When analysed by study type, the growth rate estimated from RCTs was 1.88 mm/year (95% CI 1.69 - 2.06 mm/year; GRADE = high), while it was 2.31 mm/year (95% CI 1.95 - 2.67 mm/year; GRADE = moderate) from clinical observational studies, and 2.85 mm/year (95% CI 2.44 - 3.26 mm/year; GRADE = low) from translational and radiology based studies (p < .001). Heterogeneity was high, and small study publication bias was present (p = .003), with 27 studies presenting a moderate to high risk of bias. The estimated growth rate from low risk studies was 2.09 mm/year (95% CI 1.87 - 2.32; GRADE = high). CONCLUSION: This study estimated a contemporaneous AAA growth rate of 2.38 mm/year, being unable to demonstrate any clinically meaningful AAA growth rate reduction concomitant with changed AAA epidemiology. This suggests that the RESCAN recommendations on small AAA surveillance are still valid. However, sub-analysis results from RCTs and high quality study data indicate potential lower AAA growth rates of 1.88 - 2.09 mm/year, findings that should be validated in a high quality prospective registry.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Long-term Survival After Repair of Ruptured Abdominal Aortic Aneurysms Is Improving Over Time: Nationwide Analysis During Twenty-four Years in Sweden (1994-2017).

OBJECTIVE: To investigate long-term survival after ruptured abdominal aortic aneurysms (rAAA) repair in Sweden during twenty-four years (1994-2017). SUMMARY BACKGROUND DATA: Management of rAAA has seen significant changes in the past decades, with the shifting from open (OAR) to endovascular (EVAR) being the most striking, thereby enabling treatment of elderly patients with multiple comorbidities. METHODS: A registry-based nationwide cohort study was performed, and three 8-year periods (1994-2001, 2002-2009, 2010-2017) were compared for crude long-term survival with Kaplan-Meier and multivariable Cox proportional hazards analyses. Relative survival compared to matched general population referents was estimated. RESULTS: Overall, 8928 rAAA repair subjects were identified (1994-2001 N = 3368; 2002-2009 N = 3405; 2010-2017 N = 2155). The proportion of octogenarians (20.6%; 27.5%; 34.0%; P < 0.001), women (14.3%; 18.5%; 20.6%; P < 0.001), and EVAR procedures (1.5%; 14.9%; 35.5%; P < 0.001) increased over time. The crude 5-year survival was 36%; 44%; 43% (P < 0.0001). Multivariable Cox proportional hazard analysis displayed a decreasing mortality hazard ratio (HR) over time (1.00; 0.80; 0.72; P < 0.001). Use of EVAR was associated with reduced hazards of crude long-term mortality (HR = 0.80, P < 0.001). Relative survival for patients surviving the perioperative period (ie, 90 days) was lower than matched general population referents, and was stable over time (relative 5-year survival: 86% vs 88%, vs 86% P < 0.001). CONCLUSIONS: Nationwide analysis of long-term outcomes after repair of rAAA in Sweden during 24 years (1994-2017) has revealed that, despite changes in the baseline population characteristics as well as in the treatment strategy, long-term survival improved over time.

European Multicentric Experience With Fenestrated-branched ENDOvascular Stent Grafting After Previous FAILed Infrarenal Aortic Repair: The EU-FBENDO-FAIL Registry.

OBJECTIVE: To report the mid-term outcomes of fenestrated-branched endovascular aneurysm repair (F-BEVAR) following a failed previous endovascular aneurysm repair (pEVAR) or previous open aneurysm repair (pOAR). METHODS: Data from consecutive patients who underwent F-BEVAR for pEVAR or pOAR from 2006 to 2021 from 17 European vascular centers were analyzed. Endpoints included technical success, major adverse events, 30-day mortality, and 5-year estimates of survival, target vessel primary patency, freedom from reinterventions, type I/III endoleaks, and sac growth >5 mm. BACKGROUND: Treatment of a failed previous abdominal aortic aneurysm repair is a complex undertaking. F-BEVAR is becoming an increasingly attractive option, although comparative data are limited regarding associated risk factors, indications for treatment, and various outcomes. RESULTS: There were 526 patients included, 268 pOAR and 258 pEVAR. The median time from previous repair to F-BEVAR was 7 (interquartile range, 4-12) years, 5 (3-8) for pEVAR, and 10 (6-14) for pOAR, P <0.001. Predominant indication for treatment was type Ia endoleak for pEVAR and progression of the disease for pOAR. Technical success was 92.8%, pOAR (92.2%), and pEVAR (93.4%), P =0.58. The 30-day mortality was 6.5% overall, 6.7% for pOAR, and 6.2% for pEVAR, P =0.81. There were 1853 treated target vessels with 5-year estimates of primary patency of 94.4%, pEVAR (95.2%), and pOAR (94.4%), P =0.03. Five-year estimates for freedom from type I/III endoleaks were similar between groups; freedom from reintervention was lower for pEVAR (38.3%) than for pOAR (56.0%), P =0.004. The most common indication for reinterventions was for type I/III endoleaks (37.5%). CONCLUSIONS: Repair of a failed pEVAR or pOARis safe and feasible with comparable technical success and survival rates. While successful treatment can be achieved, significant rates of reintervention should be anticipated, particularly for issues related to instability of target vessels/bridging stents.

Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms.

OBJECTIVE: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs). BACKGROUND: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described. METHODS: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair. RESULTS: A total of 2603 patients (69% males; mean age 72±10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P <0.001) and rates of MAEs (34% vs 20%, P <0.001). Median follow-up was 15 months (interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50±4% vs 70±1% and 21±3% vs 7±1%, P <0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality (hazard ratio, 1.92; 95% CI] 1.50-2.44; P <0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P <0.001). CONCLUSIONS: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.

An updated systematic review and meta-analysis of pre-emptive aortic side branch embolization to prevent type II endoleaks after endovascular aneurysm repair.

OBJECTIVE: Pre-emptive embolization of aortic side branches may be effective in preventing type II endoleaks (T2EL) based on a previous systematic review and meta-analysis by our group. Data up to 2019 was, however, only based on retrospective studies. The aim of the current study was to update the meta-analysis and evaluate the current evidence on this treatment strategy. METHODS: A systematic literature search was performed with the same keywords and strategies used in the previous study. The complementary search included all articles published from January 1, 2019, through May 29, 2022. The incidence of aneurysm sac growth was the primary outcome of interest. RESULTS: Four new studies were identified, including one randomized controlled study and one nationwide registry-based retrospective study. Overall, the incidence of sac size enlargement was 4.3% in the embolization group compared with 6.8% in the control group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.26-0.55), the incidence of T2EL was 19.7% vs 37.4% (OR, 0.38; 95% CI, 0.30-0.47), and the incidence of reintervention for T2EL was 1.2% vs 11.2% (OR, 0.12; 95% CI, 0.06-0.23). CONCLUSIONS: Current evidence confirms lower incidence of aneurysm sac growth, T2EL, and reinterventions when pre-emptive embolization of aortic side branches is performed in conjunction with endovascular aneurysm repair, compared with no embolization. However, a higher level of evidence is still required to support a broad change of practice, including data on cost-effectiveness and on the potential effect on rupture.

Spinal drain-related complications after complex endovascular aortic repair using a prophylactic automated volume-directed drainage protocol.

OBJECTIVE: A common measure to lower the risk for spinal cord ischemia (SCI) during complex endovascular aortic repair (cEVAR) is prophylactic cerebrospinal fluid drainage (CSFD). This method has caused controversy because of drain-related complications. Spinal drains are usually pressure directed. The objective of this study was to evaluate the risk of CSFD-related complications and SCI within the context of an automated volume-directed drain protocol. METHODS: This is a retrospective, single-center study of all cEVARs with CSFD at a tertiary vascular center between January 2014 and December 2020. Demographics, complications, and spinal drain data were recorded. All drainages were volume based using an automatic drainage system (LiquoGuard7; Möller Medical GmbH). Spinal drain complications were categorized as disabling and nondisabling according to the modified Rankin scale. The primary end point was any CSFD-related complication. RESULTS: A total of 448 cEVAR patients were identified, of whom 147 (32.8%) had prophylactic CSFD. The mean age was 69 years (63% male). The most common pathology (61%) was thoracoabdominal aortic aneurysm, and the most common procedure was branched EVAR (55.1%). Eighteen (12.2%) patients developed a CSFD-related complication, whereof three (2%) were disabling. Nineteen (13%) patients developed SCI: 12 (8.4%) paraparetic, 5 (3.4%) paraplegic, and 2 (1.4%) paresthesias. Of these, 13 (68%) had full reversal of symptoms, whereas 6 patients (4%) had residual symptoms and were deemed disabling. Drain-related complications were more common in patients with SCI (31.6%) compared with those without (9.4%, P = .014). In the latter group, only two patients (1.6%) developed a disabling drain-related complication. CONCLUSIONS: Selective use of prophylactic, automated volume-directed CSFD in patients at high risk for SCI was associated with a high incidence of complications and should be used with caution. Among those developing SCI, reversal was achieved frequently with increased CSFD volume, but at the price of more bleeding complications.

Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs). METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM). RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively. CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.

Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms.

OBJECTIVE: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs). METHODS: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single- or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality. RESULTS: A total of 1947 patients (65% male; mean age, 71 ± 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9±1.3% vs 79.6±1.7%) and 3 years (72.7±2.1% vs 64.2±2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach. CONCLUSIONS: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years.

Contemporary outcomes after treatment of aberrant subclavian artery and Kommerell's diverticulum.

OBJECTIVE: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset. METHODS: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders. We report the early and mid-term clinical outcomes including stroke and mortality, technical success, and other operative outcomes including reintervention rates, patency, and endoleak. RESULTS: Overall, 285 patients were identified during the study period. The mean patient age was 57 years; 47% were female and 68% presented with symptoms. A right-sided arch was present in 23%. The mean KD diameter was 47.4 mm (range, 13.0-108.0 mm). The most common indication for treatment was symptoms (59%), followed by aneurysm size (38%). The most common symptom reported was dysphagia (44%). A ruptured KD was treated in 4.2% of cases, with a mean diameter of 43.9 mm (range, 18.0-100.0 mm). An open procedure was performed in 101 cases (36%); the most common approach was ASA ligation with subclavian transposition. An endovascular or hybrid approach was performed in 184 patients (64%); the most common approach was thoracic endograft and carotid-subclavian bypass. A staged operative strategy was employed more often than single setting repair (55% vs 45%). Compared with endovascular or hybrid approach, those in the open procedure group were more likely to be younger (49 years vs 61 years; P < .0001), female (64% vs 36%; P < .0001), and symptomatic (85% vs 59%; P < .0001). Complete or partial symptomatic relief at 1 year after intervention was 82.6%. There was no association between modality of treatment and symptom relief (open 87.2% vs endovascular or hybrid approach 78.9%; P = .13). After the intervention, 11 subclavian occlusions (4.5%) occurred; 3 were successfully thrombectomized resulting in a primary and secondary patency of 95% and 96%, respectively, at a median follow-up of 39 months. Among the 33 reinterventions (12%), the majority were performed for endoleak (36%), and more reinterventions occurred in the endovascular or hybrid approach than open procedure group (15% vs 6%; P = .02). The overall survival rate was 87.3% at a median follow-up of 41 months. The 30-day stroke and death rates were 4.2% and 4.9%, respectively. Urgent or emergent presentation was independently associated with increased risk of 30-day mortality (odds ratio [OR], 19.8; 95% confidence interval [CI], 3.3-116.6), overall mortality (OR, 3.6; 95% CI, 1.2-11.2) and intraoperative complications (OR, 8.3; 95% CI, 2.8-25.1). Females had a higher risk of reintervention (OR, 2.6; 95% CI, 1.0-6.5). At an aneurysm size of 44.4 mm, receiver operator characteristic curve analysis suggested that 60% of patients would have symptoms. CONCLUSIONS: Treatment of ASA/KD can be performed safely with low rates of mortality, stroke and reintervention and high rates of symptomatic relief, regardless of the repair strategy. Symptomatic and urgent operations were associated with worse outcomes in general, and female gender was associated with a higher likelihood of reintervention. Given the worse overall outcomes when symptomatic and the inherent risk of rupture, consideration of repair at 40 mm is reasonable in most patients. ASA/KD can be repaired in asymptomatic patients with excellent outcomes and young healthy patients may be considered better candidates for open approaches versus endovascular or hybrid modalities, given the lower likelihood of reintervention and lower early mortality rate.

Morphological factors associated with progression of subaneurysmal aortas.

BACKGROUND: The aim of this population-based cohort study was to assess the association between aortic morphological baseline factors in 65-year-old men with subaneurysmal aortic diameter (25-29 mm) and risk of later progression to abdominal aortic aneurysm (AAA) generally considered to be at a diameter for repair (at least 55 mm). METHODS: Men with a screening-detected subaneurysmal aorta between 2006 and 2015 in mid-Sweden were re-examined using ultrasonography after 5 and 10 years. Cut-off values for baseline subaneurysmal aortic diameter, aortic size index, aortic height index, and relative aortic diameter (with respect to proximal aorta) were analysed using receiver operating characteristic (ROC) curves, and their associations with progression to AAA diameter at least 55 mm evaluated by means of Kaplan-Meier curves and a multivariable Cox proportional hazard analysis adjusted for traditional risk factors. RESULTS: Some 941 men with a subaneurysmal aorta and median follow-up of 6.6 years were identified. The cumulative incidence of AAA diameter at least 55 mm at 10.5 years was 28.5 per cent for an aortic size index of 13.0 mm/m2 or more (representing 45.2 per cent of the population) versus 1.1 per cent for an aortic size index of less than 13.0 mm/m2 (HR 9.1, 95 per cent c.i. 3.62 to 22.85); 25.8 per cent for an aortic height index of at least 14.6 mm/m (58.0 per cent of the population) versus 2.0 per cent for an aortic height index of less than 14.6 mm/m (HR 5.2, 2.23 to 12.12); and 20.7 per cent for subaneurysmal aortic diameter 26 mm or greater (73.6 per cent of the population) versus 1.0 per cent for a diameter of less than 26 mm (HR 5.9, 1.84 to 18.95). Relative aortic diameter quotient (HR 1.2, 0.54 to 2.63) and difference (HR 1.3, 0.57 to 3.12) showed no association with development of AAA of 55 mm or greater. CONCLUSION: Baseline subaneurysmal aortic diameter, aortic size index, and aortic height index were all independently associated with progression to AAA at least 55 mm, with aortic size index as the strongest predictor, whereas relative aortic diameter was not. These morphological factors may be considered for stratification of follow-up at initial screening.

Off-the-Shelf Single-Fenestrated Endograft for Emergent Juxtarenal and Pararenal Abdominal Aortic Aneurysm.

INTRODUCTION: Endovascular solutions to emergent juxtarenal and pararenal abdominal aortic aneurysms (AAAs) are complicated. Endovascular aortic repair (EVAR) with in situ laser fenestration (ISLF) is promising but requires a period of visceral ischemia. With an off-the-shelf, single superior mesenteric artery (SMA)-fenestrated device mesenteric ischemia is avoided and renal ischemia decreased. The aim was to develop an optimized design of such an endograft suitable for >90% of juxtarenal and pararenal AAAs. METHODS: Single-center analysis on 44 consecutive preoperative CTs for previously elective fenestrated EVARs for juxtarenal and pararenal aneurysms. Anatomical characteristics were analyzed to define: (1) shortest aortic coverage above SMA fenestration to achieve ≥4 cm seal; (2) feasibility of a scallop for the celiac artery; (3) shortest distance between the SMA and lowest renal, to facilitate renal ISLF in a straight endograft; (4) distance from the lowest renal to the aortic bifurcation, to allow an overlapping zone >40 mm with a bifurcated stent graft; (5) aortic diameter in the sealing zone, for optimal proximal stent graft diameter with 10% to 30% oversizing; (6) the final design was then tested on individual level. RESULTS: (1) The stent graft needs to start 40 mm above the SMA fenestration to achieve a 4 cm sealing zone in >90% of cases. (2) A proximal sealing zone of 40 mm without a scallop covers 77% of celiac arteries. With an addition of a 20 mm deep, 20 mm wide scallop at 12:30, the stent graft still covers 27% of celiacs. This suggests that a scallop would not be practically feasible. (3) In >90% of cases, the lowest renal was <31 mm from the SMA, suggesting that the tapering should start 30 mm below the SMA. (4) The distance from the lowest renal to the aortic bifurcation ranged from 82 to 166 mm. This allows for a 20 mm tapering and 50 mm straight part in all cases. (5) The 5th and 95th percentile of the aortic diameter in the sealing zone was 22 and 31 mm, respectively. Thus, 2 different stent graft diameters (28 and 34 mm) would fit >90% of cases. (6) The final design was suitable in 91% cases. CONCLUSIONS: Two sizes of a single-fenestrated aortic stent graft without scallop cover >90% of juxtarenal and pararenal anatomies. CLINICAL IMPACT: Emergent juxta- and pararenal aortic aneurysms is a difficult clinical scenario that continuously challenges physicians. An endovascular option is in situ laser fenestrated endografts. One risk with these is the complete visceral ischemia occurring before the fenestrations are completed. An off-the-shelf single-fenestrated stent graft facilitates the treatment by removing the ischemia time for the SMA and reducing the ischemia time for the celiac and renal arteries thus decreasing the risk of visceral ischemia complications.

Common Designs of Custom-Made Fenestrated Arch Devices and Applicability of an Off-the-Shelf Design.

OBJECTIVES: To analyze device designs, similarities and overlaps of custom-made fenestrated arch endografts intended for mid/distal arch thoracic endovascular aortic repair. MATERIALS AND METHODS: A multicenter cross-sectional study analyzing custom-made anonymized graft plans was performed. Graft plans were included from a cohort of mid/distal aortic arch repairs using custom-made fenestrated aortic endografts treated at 8 centers. Grafts targeting >2 arteries were excluded. No patient/clinical data were analyzed. A descriptive analysis was performed followed by an analysis of overlap of the designs to reach a common design in which the greatest number of grafts would overlap. RESULTS: One hundred thirty-one graft plans were included. All grafts were custom-made grafts from the COOK Medical Fenestrated arch platform. Ninety-four (71.8%) had a scallop-and-single-fenestration design, 33 (25.2%) had a single fenestration and 4 (4.3%) a single scallop. For analysis purposes, these latter 4 grafts were excluded. Two main graft plans (Plans 1 and 2) were proposed after analysis with similar configuration (1 scallop with 30 mm width, 20 mm height, 12:00 position; 1 preloaded fenestration with 8 mm diameter, 26 mm from the top of the graft and 12:00 position; tapered, with a 193 mm length and 32 mm distal diameter) but with 2 different proximal diameters of 38 mm (Plan 1) and 44 mm (Plan 2), reaching an overall feasibility of 85.8% (n=109), being 47.2% (n=60) and 38.6% (n=49) for each design, respectively. CONCLUSION: The degree of overlap between the studied fenestrated and/or scalloped thoracic endovascular aneurysm repair (TEVAR) graft designs was high. Future studies analyzing these designs in a real-world cohort of patients are needed to further address off-the-shelf feasibility. CLINICAL IMPACT: In a multicenter study analyzing 127 fenestrated aortic arch endograft plans from 9 aortic centers, we found that the degree of overlap between the studied fenestrated and/or scalloped arch graft designs was high and that 2 proposed graft designs would be theoretically applicable in 85.8% of cases. Future studies analyzing these designs in a real-world cohort of patients are needed to further address off-the-shelf feasibility.