Umeå University's logo

Objective: Abdominal aortic aneurysm (AAA) epidemiology differs significantly between the sexes; the biological factors behind this are mostly unknown. MicroRNAs (miRNAs) are short RNA molecules providing post-transcriptional regulation of protein synthesis. Several miRNAs have been associated with the development and growth of AAA, but only in men. We investigated whether the associations between some selected miRNAs and aortic size differ by sex and the possible target pathways for such differences.

Methods: A cross-sectional study included subjects with AAA (30–58 mm) and normal aortas. Clinical data were collected through questionnaires. Abdominal aortic diameters were measured using ultrasound. The levels of 17 miRNAs were measured in plasma. The association between miRNA levels, aortic diameter, and sex were analysed using multivariable linear regression.

Results: A total of 242 subjects were included, with 85 women and 157 men. In the group with aortic diameters below 30 mm were 122 men (15–29 mm) and 50 women (13–29 mm). There were 35 men (30–54 mm) and 35 women (30–58 mm) with AAA. The associations between six miRNAs and aortic diameter were influenced by sex: miR-125 (p = 0.013), miR-128–1 (p = 0.017), miR-24 (p = 0.013), miR-26a (p = 0.022), miR-93 (p = 0.0015), and miR-194 (p = 0.013). Bioinformatic analysis indicated Hippo and TGF-beta as the two signalling pathways most likely affected by these differences.

Conclusions: This exploratory study found sex differences in the associations between miRNA levels and aortic diameter, involving signalling pathways that control organ size and maintain tissue homeostasis by regulating cell proliferation, survival, and differentiation.

Objective: Different zone 0 endograft designs have been introduced. This study sought to assess postimplantation hemodynamic changes induced by zone 0 endografts, with varied configuration of side branches, using computational models.

Methods: Twenty-nine patients who underwent zone 0 endovascular repair with single-, double-, or triple-branched endografts (n = 7, n = 11, n = 11, respectively), using different configurations of antegrade (A) and retrograde (R) branches, were included. Computational simulations were used to assess postimplantation changes in peak flow rate, systolic blood pressure (SBP) and time-averaged wall shear stress (TAWSS) at the innominate artery (IA), right subclavian artery, right common carotid artery (CCA), left CCA (LCCA), left subclavian artery (LSA), and distal aortic arch, as well as the total displacement force (DF) of the endograft.

Results: Regardless of orientation, IA side branch implantation increased the IA peak flow rate across all endograft designs, an effect significant only in single-branched devices (+70%, P = .02). This increase was accompanied by a significant decrease in peak flow in the LCCA and LSA for single- ( P = .02 and P = .02, respectively) and double-branched devices ( P = .01 and P < .001, respectively), whereas no such effect was observed with triple-branched devices. Notably, the two antegrade branches supplying the IA and LCCA and one retrograde branch to the LSA- and three retrograde branches (3R)-triple-branched designs had the opposite effect on LCCA blood flow (+8.3% vs −6.7% [ P = .02], respectively), although their impact on LSA flow did not differ significantly (−7.5% vs −8.1% [ P = .92], respectively). This resulted in disparate effects on distal arch flow (−0.3% vs +6.3% [ P = .02], respectively). Postimplantation alteration in distal arch flow was progressively attenuated with more branches. The preimplantation to postimplantation SBP differences in the IA, LCCA, and LSA mirrored the corresponding changes in peak flow. Elevated peak flow in the IAs led to a significant postimplantation increase in the TAWSS across all device designs. In contrast, the LSA side branches with retrograde orientation in the two antegrade branches supplying the IA and LCCA and one retrograde branch to the LSA-triple-branched and 3R-triple-branched endografts demonstrated marked increases in TAWSS (36.1% vs 50.2%, respectively), despite there being no significant change in the mean flow rate. Although maximum DF varied between devices (single-branched, 32.8 N; double-branched, 23.9 N; 2A+1-triple-branched, 22.9 N; 3R-triple-branched, 28.9 N), a post hoc analysis showed that branch configuration did not significantly influence DF.

Conclusions: The hemodynamic stability within the aortic arch improves with a greater number of endograft side branches. Retrograde branch orientation does not significantly affect flow rates or SBP in the supra-aortic vessels. Among the evaluated designs, the triple-retrograde-branched configuration demonstrated the most favorable flow characteristics.

Clinical Relevance: Using patient-specific computational fluid dynamics simulations, this study compared the postimplantation local hemodynamic effects of single-, double-, and triple-branched endografts, using different configurations of antegrade and retrograde branches, in complex zone 0 aortic arch repair. Our study suggests two key findings: first, more branching improves hemodynamic stability by steadying blood flow, and second, the specific orientation of retrograde side branches does not affect the supra-aortic arteries. Properly validated, these findings may help to optimize branched endograft selection, ensuring stable hemodynamics for long-term patient success and device durability.

Objective: To evaluate the ethics of introducing the Endo-Bentall (a novel high risk procedure) in the context of compassionate care and to make practical recommendations to support its incorporation into practice.

Methods: A seven step ethical framework was systematically applied to three clinical vignettes involving the Endo-Bentall procedure. Ethical issues identified across cases were synthesised and used to develop practical recommendations for clinical practice.

Results: Decision making regarding the Endo-Bentall procedure is challenging in the absence of robust outcome data. Patients amenable to treatment represent a highly heterogeneous population, with a high degree of variability in procedural risk, likelihood of technical success, consequences of failure, and uncertainty of long term durability. Despite this, ethical justification may be achievable in carefully selected cases where anticipated benefits proportionately outweigh risks, particularly in the context of otherwise limited therapeutic alternatives.

Conclusion: Ethical implementation of the Endo-Bentall procedure is possible in select patients. However, structured safeguards are necessary. These include enhanced informed consent processes with explicit disclosure of the learning curve, limited validation, and unknown long term outcomes; mitigation of potential conflicts of interest through independent or external case review; formal oversight mechanisms despite its classification as compassionate or innovative care; and integration within a learning health system framework with ongoing data reporting and outcome monitoring.

The ascending aorta and aortic root remain challenging areas for endovascular repair. While open surgical repair or replacement remains the gold standard, a proportion of the patients with ascending and/or root pathology are inoperable or at prohibitive surgical risk. Repair using conventional tubular ascending endografts is limited by anatomical constraints, especially inadequate proximal landing zones near the sinotubular junction (STJ), further complicated by the proximity of the coronary ostia. Therefore, endovascular strategies that enable anchoring in the aortic root may be required. To address these limitations, valve-carrying conduit concepts such as Endo-Bentall and Endo-Wheat have been proposed. These configurations integrate a transcatheter aortic valve with an ascending endograft, enabling coronary perfusion through fenestrations, branches, or uncovered segments. Early clinical experience is limited to a few published case reports to date, with heterogeneous techniques and no standardized procedural strategy. Although early technical success and short-term safety appear acceptable, conclusions are constrained by small sample size, selection bias, and limited follow-up. Proof-of-concept investigations, including ex vivo and in vivo animal studies, biomechanical modeling, and bench-top experiments using patient-specific three-dimensional (3D) anatomical models have been reported. These studies suggest stable deployment with preserved coronary perfusion; however, they do not establish clinical efficacy or safety in patients. At present, this approach should be considered an evolving strategy reserved for carefully selected patients with life-threatening aortic pathology where conventional surgery is not an option, pending robust evidence of safety, efficacy, and durability.

Objective: Aortic endograft infection (AeGI) is a rare complication following complex endovascular aortic repair (cEVAR). Data on its incidence, risk factors, and outcomes are limited to very small case series. This study aimed to retrospectively determine the incidence and risk factors for AeGI after cEVAR and to describe treatment strategies and outcomes in a high volume aortic centre.

Methods: Patients undergoing cEVAR with fenestrated or branched endografts at Uppsala University Hospital, Sweden, between September 2010 and May 2024 were identified retrospectively and crosschecked with the Swedish vascular registry (Swedvasc). AeGI was defined according to the Management of Aortic Graft Infection Collaboration (MAGIC) criteria. Risk factors were assessed using multivariable Cox regression. Outcomes included incidence, microbiology, treatment strategies, survival, and long term infection status.

Results: Among 527 patients (542 cEVARs, median follow up 47.4 months), 19 developed MAGIC diagnosed AeGI. The 5 year incidence was 3.87% (3.16% for non-infected aortic pathology and 23.5% for cEVAR treated primary infected aortic pathology [MAA]) adjusting for mortality as a competing risk using the cumulative incidence function. Independent risk factors to develop AeGI were MAA as index pathology (hazard ratio 10.2, 95% confidence interval 3.1 – 33.2) and late aortic related re-interventions (hazard ratio 3.0, 95% confidence interval 1.1 – 7.9). Six patients (32%) had a secondary fistula, associated with poor median survival (4.0 vs. 41.5 months). Treatment strategies were predominantly graft persevering: antimicrobial therapy alone in 11 of 19 (58%) or combined with image guided drainage and or surgical debridement in seven of 19 (37%). At last follow up, remission or cure was achieved in 56%, and treatment failure in 44%, mainly due to AeGI related death.

Conclusion: AeGI after cEVAR is more common than previously reported. Risk is further increased by MAA as the index pathology and late aortic re-interventions. Prognosis is poor in patients with secondary fistula. Endograft preserving strategies may achieve infection remission and survival in selected patients, not amenable to explantation, without fistula.

Aim: To explore how factors in the complex aortic surgical care context can affect care provision towards patients' postoperative recovery.

Design: Secondary qualitative analysis.

Methods: Results about patients' recovery after complex aortic surgery was presented in focus groups with healthcare professionals in 2022. Reflexive thematic analysis, using the Fundamentals of Care framework, was conducted to explore contextual factors affecting care provision.

Results: Healthcare professionals' descriptions resulted in one main theme: Care provision is challenged by discrepancies in values, goals and norms and unclear responsibilities within the context, and two subthemes: Values, goals and norms determine what care is provided; Taking responsibility for care requires resources, evaluation and feedback.

Conclusion: Healthcare professionals describe care provision as affected by a dynamic integration of contextual factors. Healthcare professionals need to be made aware of their own role in this context. Care provision needs to be guided by feedback from patients and healthcare professionals, and work with patients' resources at both an individual, system and societal level.

Implications for the Profession: The results provide knowledge regarding how contextual factors in dynamic integration can affect care provision in a complex surgical context. Healthcare professionals, leaders and policy makers all have responsibility to focus on patients' values and goals, and empower adequate care through feedback loops and resource management.

Impact: The context-of-care dimension of the Fundamentals of Care framework has been scarcely described. Our results illustrate how an integration of factors affects care provision, where values, goals, and norms affect what care is provided, and responsibility for care belongs to everyone in the care system. The results can contribute to the description of the context-of-care dimension within the framework and enable professionals to understand how they, as part of the context, could affect care towards patient recovery.

Reporting Method: This study adhered to the Equator research reporting checklist: Consolidated criteria for reporting qualitative research: a 32-item checklist for interviews and focus groups.

Patient or Public Contribution: No patient or public contribution.

Thoracic endovascular aortic repair (TEVAR) is standard for descending thoracic aortic disease. When disease involves the proximal arch (zones 0-3), left subclavian artery (LSA) coverage is often required, increasing stroke and spinal cord ischaemia risk if unrevascularized. Guidelines recommend routine LSA revascularization, traditionally via surgical bypass, though with notable morbidity. Endovascular alternatives include fenestrated/branched devices, chimneys, and in-situ fenestration. This narrative review aims to provide a summary of existing knowledge on laser in-situ fenestration (ISLF) and radiofrequency fenestration for LSA revascularization. ISLF provides high technical success, durable patency, and low perioperative risk, with expanding use in urgent and complex cases. Long-term durability, however, remains uncertain and requires further study.

Objective: – To determine the contemporary cost per quality-adjusted life year(QALY) gained for abdominal aortic aneurysm (AAA) repair in current practice and assess the optimal threshold for intervention.

Summary Background Data: – The widely accepted 5.5cm threshold for elective AAA repair in men remains largely consensus-based. However, contemporary evidence suggests that size-associated rupture risk may be lower than previously assumed, calling into question whether this threshold is cost-effective.

Methods: – A Markov-chain estimated the cost-utility of endovascular AAA repair(EVAR) and open surgical repair(OSR) compared with surveillance. Social Security Administration lifetables informed survival, while Vascular Quality Initiative and Medicare data informed complication rates, reinterventions, and late rupture. Quality-adjusted life years(QALYs) were derived from published estimates. Two willingness-to-pay(WTP) thresholds were evaluated:$100, 000/QALY(U.S.) and $40, 000/QALY(UK-NICE equivalent). Given uncertainty in size-specific rupture risk, a range of annual rupture probabilities was modeled. The base-case analysis considered a 70-year-old man over a 10-year time horizon.

Results: – At a WTP threshold of $100, 000/QALY, immediate EVAR became cost-effective when annual rupture risk was ≥2.2%, whereas OSR became cost-effective at ≥3.4%. At a $40, 000/QALY threshold, the rupture risk thresholds were ≥5.0% for EVAR and ≥6.8% for OSR. Assuming an annual rupture risk of 0.4% (as reported in a contemporary study), the cost per QALY gained with EVAR was $1, 233, 000, while OSR was associated with a loss of QALYs.

Conclusions: – The cost-effectiveness of AAA repair is highly dependent on rupture risk. Given that contemporary data suggest lower rupture rates than previously assumed, the current 5.5 cm repair threshold in men may not be optimally cost-effective from a population health perspective.

Background: The pathophysiological mechanisms of Abdominal Aortic Aneurysm (AAA) are not elucidated. Alterations in mitochondrial function, such as a reduction in oxidative phosphorylation (OXPHOS), have been observed at genome level and functionally in vascular smooth muscle cells. Metformin reduces AAA development and growth in diabetic patients, but the precise mechanisms are not known. In this paper we aim to demonstrate the feasibility of measuring mitochondrial functional capacity ex vivo in intact murine aneurysmal tissue and confirm a decrease in OXPHOS, and to determine if the protective effect of metformin on AAA is mediated by mitochondrial function.

Methods: AAA was induced in ApoE KO mice by administration of angII (1000 ng/kg/min) through osmotic minipumps. Metformin was administered in drinking water at a dose of 100 mg/kg/day. The abdominal aorta was isolated in situ and mitochondrial functional capacity was analyzed ex vivo in whole permeabilized tissue by high-resolution respirometry.

Results: Mitochondrial respiration was successfully measured ex vivo in whole aneurysmal tissue. Mitochondrial function was impaired in angII-treated mice, with decreased fold change in Complex I and Complex I+II oxygen consumption, relative to basal levels. Complex II oxygen consumption was also decreased in angII-treated mice. Rescue treatment of mice with metformin did not affect or restore mitochondrial function.

Conclusions: Mitochondrial function can be evaluated in murine whole aneurysmal tissue, providing a method for a physiological approach to the study of mitochondrial function in AAA. Mitochondrial function is impaired in AAA. However, rescue treatment with metformin is not sufficient to recover mitochondrial function and seems not to be the mechanism behind prevention of aneurysm.

BACKGROUND: Complex endovascular repair has emerged as a minimally invasive alternative for thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to assess the short- and mid-term outcomes of endovascular TAAA repair in Sweden.

METHODS: All endovascular TAAA repairs performed during 2018-2023 were identified in the Swedish Vascular (Swedvasc) Registry. Patient characteristics, operative details, and outcomes were analysed. The primary outcome was survival; secondary outcomes included complications and thoracoabdominal aortic life-altering events (TALEs). Predictors of mid-term outcomes were assessed in multivariable analysis.

RESULTS: Some 339 patients were treated for TAAAs, which included 476 repairs (366 elective repairs and 110 emergency repairs) across 11 centres (94% concentrated in 5 centres). Elective patients (235 patients; mean diameter 64 mm) had 30-day, 90-day, and 1-year mortality of 2.6%, 3.5%, and 12.4% respectively. Major complications, vascular complications, and TALEs occurred in 16.2%, 9.8%, and 14% respectively. The use of prophylactic spinal drainage declined over time (from 68% to 14%) and the incidence of spinal cord ischaemia declined over time (from 20% to 2.3%). Mean(s.e.) 1-year and 4-year Kaplan-Meier survival estimates were 89.3%(2.1%) and 73.5%(3.7%) respectively. Emergency patients (104 patients; mean diameter 73 mm) had 30-day, 90-day, and 1-year mortality of 12.5%, 17.6%, and 26.9% respectively. Major complications, vascular complications, and TALEs occurred in 20.2%, 12.5%, and 24% respectively. Mean(s.e.) 1-year and 4-year Kaplan-Meier survival estimates were 75.2%(4.3%) and 56.5%(6.2%) respectively. Perioperative myocardial infarction was the strongest predictor of 1-year mortality after both elective and emergency repair.

CONCLUSION: Endovascular TAAA repair in Sweden is associated with significant complication rates, but acceptable mid-term survival. Further research should focus on perioperative refinements, especially with regard to preserving organ function.