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AbstractThe role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications—which may be lethal—serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms.

A new appraisal of the management of acute aortic dissection is timely because of recent developments in diagnostic strategies (including biomarkers and imaging), endograft design, and surgical treatment, which have led to a better understanding of the epidemiology, risk factors, and molecular nature of aortic dissection. Although open surgery is the main treatment for proximal aortic repair, use of endovascular management is now established for complicated distal dissection and distal arch repair, and has recently been discussed as a pre-emptive measure to avoid late complications by inducing aortic remodelling.

Purpose To evaluate the performance of periscope and/or chimney grafts (CPGs) in the endovascular treatment of pararenal or thoracoabdominal aneurysms using off-the-shelf devices. Methods Between February 2002 and August 2012, 77 consecutive patients (62 men; mean age 73±9 years) suffering from pararenal aortic (n=55), thoracoabdominal (n=16), or arch to visceral artery aneurysms (n=6) were treated with aortic stent-graft implantation requiring chimney and/or periscope grafts to maintain side branch perfusion. CPGs were planned in advance and were not used as bailout. A standardized follow-up protocol including computed tomographic angiography, laboratory testing, and clinical examination was performed at 6 weeks; 3, 6, and 12 months; and annually thereafter. Results Technical success was achieved in 76 (99%) patients; 1 branch stent-graft became dislocated from a renal artery, which could not be re-accessed. Overall, 169 target vessels (121 renal arteries, 30 superior mesenteric arteries, 17 celiac trunks, and 1 inferior mesenteric artery) were addressed with the chimney graft configuration in 111 and the periscope graft configuration in 58. In total, 228 devices were used for the CPGs: 213 Viabahn stent-grafts and 15 bare metal stents. Over a mean 25±16 months (range 1–121), 9 patients died of unrelated causes. Nearly all (95%) of the patients demonstrated a decreased or stable aneurysm size on imaging; there was a mean 13% shrinkage in aneurysm diameter. Twenty patients had primary type I/III endoleaks at discharge; in follow-up, only 3 of these were still present (no secondary or recurrent endoleaks were noted). Additional endovascular maneuvers were required for CPG-related complications in 13 patients from intervention throughout follow-up. Overall, 4 CPGs occluded (98% target vessel patency); no stent-graft migration was observed. Renal function remained stable in all patients. Conclusion In this series, the use of CPGs has proven to be a feasible, safe, and effective way to treat thoracoabdominal and pararenal aneurysms with maintenance of blood flow to the renovisceral arteries. Nearly all of the aneurysms showed no increase in diameter over a >2-year mean follow-up, which supports the midterm adequacy of the CPG technique as a method to effectively revascularize branch vessels with few endoleaks or branch occlusions.

Background Although an association between elevated blood pressure and risk of aortic aneurysm is established, few studies have investigated the association with aortic aneurysm subtypes. We investigated the association between systolic and diastolic blood pressure and hypertension status with the risk of aortic aneurysm in the UK Biobank. Methods The analysis included 495,542 men and women aged 37–73 years at recruitment between 2006 and 2010. Aortic aneurysm cases were identified by linkage to hospitalization and mortality records. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between blood pressure and hypertension and risk of aortic aneurysm overall and for subtypes. Results During a mean follow-up of 12.3 years, 3,346 incident aortic aneurysm cases were identified. Hypertension vs. no hypertension was associated with increased risk (HR, 95% CI) of aortic aneurysm (1.17, 1.08–1.27), and for thoracic (1.23, 1.04–1.46), abdominal (1.16, 1.04–1.30), and non-ruptured (1.18, 1.08–1.28) aortic aneurysm, and suggestively with unspecified site aortic aneurysm (1.18, 0.96–1.46) and aortic aneurysm mortality (1.26, 0.87–1.82), but not ruptured aortic aneurysm (1.02, 0.67–1.58). Systolic blood pressure was not associated with risk of aortic aneurysm overall or for any subtype. Diastolic blood pressure was positively associated with aortic aneurysm (1.74, 1.26–2.41, p trend <0.0001) for ≥ 110 vs. <80 mmHg, abdominal aortic aneurysm (1.95, 1.28–2.96, p trend <0.0001), unspecified site aortic aneurysm (2.02, 0.94–4.33, p trend =0.005), non-ruptured aortic aneurysm (1.79, 1.29–2.47), and aortic aneurysm mortality (2.32, 0.56–9.58, p trend <0.0001), and with ruptured aortic aneurysm (2.48, 1.22–5.03, p trend <0.0001 for 100–109 vs. <80 mmHg), while the association with thoracic aortic aneurysm was less clear (1.30, 0.64–2.63). These associations were strengthened and positive associations emerged for systolic blood pressure and abdominal and non-ruptured aortic aneurysm in sensitivity analyses when excluding participants with prevalent ischemic heart disease, stroke, those using hypertension medications and the first 3 years of follow-up. Conclusion We found that hypertension status and higher diastolic blood pressure were associated with increased risk of aortic aneurysm overall and most aortic aneurysm subtypes. No association was observed for systolic blood pressure. Although further studies are needed on aortic aneurysm subtypes, these findings provide strong support that controlling blood pressure is important for reducing the risk of aortic aneurysm.

It has been documented that large-artery stiffness is independently associated with increased cardiovascular risk and may potentially lead to heart and kidney failure and cerebrovascular disease. A systematic review of studies investigating changes in arterial stiffness in patients undergoing endovascular repair of aortic disease was conducted. In addition, a review of the available literature was performed, analyzing findings from studies using the cardio-ankle vascular index (CAVI) as a marker of arterial stiffness. Overall, 26 studies were included in the present analysis. Our research revealed a high heterogeneity of included studies regarding the techniques used to assess the aortic stiffness. Aortic stiffness was assessed by pulse wave velocity (PWV), elastic modulus (Ep), and augmentation index (AI). Currently a few studies exist investigating the role of CAVI in patients having an aortic aneurysm or undergoing endovascular aortic repair. The majority of studies showed that the treatment of an abdominal aortic aneurysm (AAA) either with open repair (OR) or endovascular aortic repair (EVAR) reduces aortic compliance significantly. Whether EVAR reconstruction might contribute a higher effect on arterial stiffness compared to OR needs further focused research. An increase of arterial stiffness was uniformly observed in studies investigating patients following thoracic endovascular aortic repair (TEVAR), and the effect was more pronounced in young patients. The effects of increased arterial stiffness after EVAR and TEVAR on the heart and the central hemodynamic, and an eventual effect on cardiac systolic function, need to be further investigated and evaluated in large studies and special groups of patients.

Aortic aneurysms are potentially fatal focal enlargements of the aortic lumen; the disease burden is increasing as the human population ages. Pathological oxidative stress is implicated in the development of aortic aneurysms. We pursued a chemogenetic approach to create an animal model of aortic aneurysm formation using a transgenic mouse line, DAAO-TGTie2, that expresses yeast d-amino acid oxidase (DAAO) under control of the endothelial Tie2 promoter. In DAAO-TGTie2 mice, DAAO generated the ROS hydrogen peroxide (H2O2) in endothelial cells only when provided with d-amino acids. When DAAO-TGTie2 mice were chronically fed d-alanine, the animals became hypertensive and developed abdominal, but not thoracic, aortic aneurysms. Generation of H2O2 in the endothelium led to oxidative stress throughout the vascular wall. Proteomics analyses indicated that the oxidant-modulated protein kinase JNK1 was dephosphorylated by the phosphoprotein phosphatase DUSP3 (dual specificity phosphatase 3) in abdominal, but not thoracic, aorta, causing activation of Kruppel-like Factor 4 (KLF4)-dependent transcriptional pathways that triggered phenotypic switching and aneurysm formation. Pharmacological DUSP3 inhibition completely blocked the aneurysm formation caused by chemogenetic oxidative stress. These studies establish that regional differences in oxidant-modulated signaling pathways lead to differential disease progression in discrete vascular beds and identify DUSP3 as a potential pharmacological target for the treatment of aortic aneurysms.

Aortic aneurysm is a life-threatening disease with limited interventions that is closely related to vascular smooth muscle cell (VSMC) phenotypic switching. SLC44A2, a member of the solute carrier series 44 (SLC44) family, remains undercharacterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMC phenotypic switching in aortic aneurysm. Screening for Slc44a2 among aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evident in the aorta of both patients with abdominal aortic aneurysm and angiotensin II-infused (Ang II-infused) Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs toward a synthetic phenotype, while SLC44A2 overexpression attenuated VSMC phenotypic switching. VSMC-specific SLC44A2-knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2's interaction with NRP1 and ITGB3 activates TGF-β/SMAD signaling, thereby promoting contractile gene expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low-dose lenalidomide (LEN; 20 mg/kg/day) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal that the SLC44A2-NRP1-ITGB3 complex is a major regulator of VSMC phenotypic switching and provide a potential therapeutic approach (LEN) for aortic aneurysm treatment.

Abstract Objectives Hybrid repair of thoracoabdominal aortic aneurysms (TAAA), combining visceral debranching and thoracic endovascular aortic repair, is a less invasive alternative to open surgery. However, data on long-term outcomes, especially in patients with prior open abdominal aortic aneurysm (AAA) repair, are limited. This study compares outcomes of hybrid TAAA repair in patients undergoing concomitant AAA repair vs those with prior open AAA repair. Methods Between January 2007 and January 2024, 132 TAAA repairs were performed at our institution. We retrospectively analysed 80 patients who underwent hybrid TAAA repair. After excluding emergency cases and those without AAA repair, 67 patients were included: 50 with concomitant AAA repair (Group C) and 17 with prior open AAA repair (Group P). Perioperative outcomes, complications, and long-term survival and aortic event-free rates were compared between groups. Results The median age was 72.0 years (IQR: 65.0-80.8) in Group C and 75.0 years (IQR: 70.0-82.0) in Group P (P = .34). Hospital mortality was 3.0% overall, with no significant group differences. Mean follow-up was 5.0 ± 3.1 years. Five-year overall survival was 69% in Group C and 63% in Group P (P = .22). Freedom from aortic events at 5 years was 92% in Group C and 83% in Group P (P = .19). IPTW-adjusted analyses confirmed no significant differences between the groups. Conclusions Hybrid TAAA repair can be safely performed for patients with prior AAA open repair, with acceptable long-term outcomes after appropriate patient selection. Thoracoabdominal aortic aneurysms (TAAAs) represent a complex and life-threatening condition requiring meticulous surgical intervention to prevent catastrophic outcomes such as rupture or dissection. Graphical abstract

Objective To assess the three year clinical outcomes and cost effectiveness of a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair for patients with suspected ruptured abdominal aortic aneurysm.Design Randomised controlled trial.Setting 30 vascular centres (29 in UK, one in Canada), 2009-16.Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm, of whom 502 underwent emergency repair for rupture.Interventions 316 patients were randomised to an endovascular strategy (275 with confirmed rupture) and 297 to open repair (261 with confirmed rupture).Main outcome measures Mortality, with reinterventions after aneurysm repair, quality of life, and hospital costs to three years as secondary measures.Results The maximum follow-up for mortality was 7.1 years, with two patients in each group lost to follow-up by three years. After similar mortality by 90 days, in the mid-term (three months to three years) there were fewer deaths in the endovascular than the open repair group (hazard ratio 0.57, 95% confidence interval 0.36 to 0.90), leading to lower mortality at three years (48% v 56%), but by seven years mortality was about 60% in each group (hazard ratio 0.92, 0.75 to 1.13). Results for the 502 patients with repaired ruptures were more pronounced: three year mortality was lower in the endovascular strategy group (42% v 54%; odds ratio 0.62, 0.43 to 0.88), but after seven years there was no clear difference between the groups (hazard ratio 0.86, 0.68 to 1.08). Reintervention rates up to three years were not significantly different between the randomised groups (hazard ratio 1.02, 0.79 to 1.32); the initial rapid rate of reinterventions was followed by a much slower mid-term reintervention rate in both groups. The early higher average quality of life in the endovascular strategy versus open repair group, coupled with the lower mortality at three years, led to a gain in average quality adjusted life years (QALYs) at three years of 0.17 (95% confidence interval 0.00 to 0.33). The endovascular strategy group spent fewer days in hospital and had lower average costs of −£2605 (95% confidence interval −£5966 to £702) (about €2813; $3439). The probability that the endovascular strategy is cost effective was >90% at all levels of willingness to pay for a QALY gain.Conclusions At three years, compared with open repair, an endovascular strategy for suspected ruptured abdominal aortic aneurysm was associated with a survival advantage, a gain in QALYs, similar levels of reintervention, and reduced costs, and this strategy was cost effective. These findings support the increasing use of an endovascular strategy, with wider availability of emergency endovascular repair.Trial registration Current Controlled Trials ISRCTN48334791; ClinicalTrials NCT00746122.

Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM–VSMC network.