Targeting long non-coding RNA NUDT6 enhances smooth muscle cell survival and limits vascular disease progression.

Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6) and its antisense target fibroblast growth factor 2 (FGF2) in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase of NUDT6, whereas FGF2 was downregulated. Targeting Nudt6 in vivo with antisense oligonucleotides in three murine and one porcine animal model of carotid artery disease and AAA limited disease progression. Restoration of FGF2 upon Nudt6 knockdown improved vessel wall morphology and fibrous cap stability. Overexpression of NUDT6 in vitro impaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another direct NUDT6 interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifies NUDT6 as a well-conserved antisense transcript of FGF2. NUDT6 silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.

Pathogenesis and management of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

Surface-Functionalized Stem Cell-Derived Extracellular Vesicles for Vascular Elastic Matrix Regenerative Repair.

Extracellular vesicles (EVs) are nanosized vesicles that carry cell-specific biomolecular information. Our previous studies showed that adult human bone marrow mesenchymal stem cell (BM-MSC)-derived EVs provide antiproteolytic and proregenerative effects in cultures of smooth muscle cells (SMCs) derived from an elastase-infused rat abdominal aortic aneurysm (AAA) model, and this is promising toward their use as a therapeutic platform for naturally irreversible elastic matrix aberrations in the aortic wall. Since systemically administered EVs poorly home into sites of tissue injury, disease strategies to improve their affinity toward target tissues are of great significance for EV-based treatment strategies. Toward this goal, in this work, we developed a postisolation surface modification strategy to target MSC-derived EVs to the AAA wall. The EVs were surface-conjugated with a short, synthetic, azide-modified peptide sequence for targeted binding to cathepsin K (CatK), a cysteine protease overexpressed in the AAA wall. Conjugation was performed using a copper-free click chemistry method. We determined that such conjugation improved EV uptake into cultured aneurysmal SMCs in culture and their binding to the wall of matrix injured vessels ex vivo. The proregenerative and antiproteolytic effects of MSC-EVs on cultured rat aneurysmal SMCs were also unaffected following peptide conjugation. From this study, it appears that modification with short synthetic peptide sequences seems to be an effective strategy for improving the cell-specific uptake of EVs and may be effective in facilitating AAA-targeted therapy.

Twenty Years of Studying AngII (Angiotensin II)-Induced Abdominal Aortic Pathologies in Mice: Continuing Questions and Challenges to Provide Insight Into the Human Disease.

AngII (angiotensin II) infusion in mice has been used to provide mechanistic insight into human abdominal aortic aneurysms for over 2 decades. This is a technically facile animal model that recapitulates multiple facets of the human disease. Although numerous publications have reported abdominal aortic aneurysms with AngII infusion in mice, there remain many fundamental unanswered questions such as uniformity of describing the pathological characteristics and which cell type is stimulated by AngII to promote abdominal aortic aneurysms. Extrapolation of the findings to provide insight into the human disease has been hindered by the preponderance of studies designed to determine the effects on initiation of abdominal aortic aneurysms, rather than a more clinically relevant scenario of determining efficacy on the established disease. The purpose of this review is to enhance understanding of AngII-induced abdominal aortic pathologies in mice, thereby providing greater insight into the human disease.

Cancer, cancer treatment and aneurysmatic ascending aorta growth within a retrospective single center study.

Background: Multi-morbidity poses a substantial challenge for health care in an aging population. Recent studies did not provide evidence for general side effects of anti-cancer therapy regarding the growth rate of coincident abdominal aortic aneurysms, although it was suggested that specific therapeutic substances might accelerate growth. Aneurysm pathology, however, differs with respect to localization. Hence, we present the first ever analysis on the association of cancer and cancer therapy with growth alteration of aneurysms of the ascending aorta (AscAA). Patients and methods: A retrospective single-center identification of AscAA+cancer patients was performed in the institutional picture archiving and communication system (PACS). Included were all patients with ≥2 CT angiograms over ≥6 months and additional malignancy. Clinical data and aneurysm diameters were retrieved and analyzed for an association of cancer (stratified by tumor entity) or cancer therapy (stratified by several classes of chemotherapeutic agents and radiation therapy) with annual growth rate, respectively. Statistics included t-test, Wilcoxon test, and a linear regression model accounting for initial AscAA diameter and type of treatment. Results: From 2003 to 2021, 151 patients (median age 70 years; 85% male) with AscAA and coincident 163 malignancies were identified. Prostate (37%) and hematologic cancer (17%) were most frequent. One-hundred-eleven patients (74%) received chemotherapy and 75 patients (50%) had radiation. After exclusion of six patients with an initial AscAA diameter >55 mm, the average annual AscAA growth rate was 0.18±0.64 mm/year, with only 12 patients experiencing a growth rate >1mm/year. Neither tumor entity nor radiation or chemotherapy - alone or in combination - were significantly associated with an alteration of the annual AscAA growth rate. Likewise, a subanalysis for singular chemotherapeutic agents did not reveal a specific association with AscAA growth alteration. Conclusions: Growth rates of AscAA are low in this cohort with coincident malignancy. Cancer and/or chemotherapy or radiation are not associated with an alteration of the annual growth rate. Additional control examinations seem unnecessary.

Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.

Thoracic aortic disease affects people of all ages and the majority of those aged <60 years have an underlying genetic cause. There is presently no effective medical therapy for thoracic aneurysm and surgery remains the principal intervention. Unlike abdominal aortic aneurysm, for which the inflammatory/atherosclerotic pathogenesis is well established, the mechanism of thoracic aneurysm is less understood. This paper examines the key cell signaling systems responsible for the growth and development of the aorta, homeostasis of endothelial and vascular smooth muscle cells and interactions between pathways. The evidence supporting a role for individual signaling pathways in pathogenesis of thoracic aortic aneurysm is examined and potential novel therapeutic approaches are reviewed. Several key signaling pathways, notably TGF-ß, WNT, NOTCH, PI3K/AKT and ANGII contribute to growth, proliferation, cell phenotype and survival for both vascular smooth muscle and endothelial cells. There is crosstalk between pathways, and between vascular smooth muscle and endothelial cells, with both synergistic and antagonistic interactions. A common feature of the activation of each is response to injury or abnormal cell stress. Considerable experimental evidence supports a contribution of each of these pathways to aneurysm formation. Although human information is less, there is sufficient data to implicate each pathway in the pathogenesis of human thoracic aneurysm. As some pathways i.e., WNT and NOTCH, play key roles in tissue growth and organogenesis in early life, it is possible that dysregulation of these pathways results in an abnormal aortic architecture even in infancy, thereby setting the stage for aneurysm development in later life. Given the fine tuning of these signaling systems, functional polymorphisms in key signaling elements may set up a future risk of thoracic aneurysm. Multiple novel therapeutic agents have been developed, targeting cell signaling pathways, predominantly in cancer medicine. Future investigations addressing cell specific targeting, reduced toxicity and also less intense treatment effects may hold promise for effective new medical treatments of thoracic aortic aneurysm.

B Cell-Activating Factor Antagonism Attenuates the Growth of Experimental Abdominal Aortic Aneurysm.

B cell-activating factor (BAFF), part of a tumor necrosis factor family of cytokines, was recently identified as a regulator of atherosclerosis; however, its role in aortic aneurysm has not been determined. Here, the study examined the effect of selective BAFF antagonism using an anti-BAFF antibody (blocks binding of BAFF to receptors BAFF receptor 3, transmembrane activator and CAML interactor, and B-cell maturation antigen) and mBaffR-mFc (blocks binding of BAFF to BAFF receptor 3) on a murine model of abdominal aortic aneurysm (AAA). In a prevention strategy, the antagonists were injected before the induction of AAA, and in an intervention strategy, the antagonists were injected after the induction of AAA. Both strategies attenuated the formation of AAA. In the intervention group, BAFF antagonism depleted most of the mature B-cell subsets in spleen and circulation, leading to enhanced resolution of inflammation in AAA as indicated by decreased infiltration of B cells and proinflammatory macrophages and a reduced number of apoptotic cells. In AAA tissues, B cells and macrophages were found in close contact. In vitro, B cells, irrespective of treatment with BAFF, impaired the efferocytosis activity of macrophages, suggesting a direct innate role of B cells on macrophage function. Altogether, BAFF antagonism affects survival of the mature B cells, promotes resolution of inflammation in the aorta, and attenuates the growth of AAA in mice.

Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm is a pathologic condition with progressive abdominal aortic dilatation of 3.0 cm or more that predisposes the abdominal aorta to rupture. Most abdominal aortic aneurysms are asymptomatic until they rupture, although some are detected when an imaging study is performed for other reasons. The risk factors for abdominal aortic aneurysm include hypertension, coronary artery disease, tobacco use, male sex, a family history of abdominal aortic aneurysm, age older than 65 years, and peripheral artery disease. Abdominal ultrasonography is the preferred modality to screen for abdominal aortic aneurysm because of its cost-effectiveness and lack of exposure to ionizing radiation. Abdominal aortic aneurysm can be managed medically or surgically, depending on the patient's symptoms and the size and growth rate of the aneurysm. Medical management is appropriate for asymptomatic patients and smaller aneurysms and includes tobacco cessation and therapy for cardiovascular risk reduction. Surgical management, which includes open and endovascular aneurysm repair, is indicated when the aneurysm diameter is 5.5 cm or larger in men and 5.0 cm or larger in women. Surveillance of abdominal aortic aneurysm depends on the size and growth rate of the aneurysm. The most serious complication of abdominal aortic aneurysm is rupture, which requires emergent surgical intervention. The U.S. Preventive Services Task Force recommends that men with a history of smoking who are 65 to 75 years of age should undergo one-time abdominal aortic aneurysm screening with ultrasonography.

Hypoxia Marker Carbonic Anhydrase IX Is Present in Abdominal Aortic Aneurysm Tissue and Plasma.

Abdominal aortic aneurysms (AAA) are a significant cause of premature deaths worldwide. Since there is no specific treatment for reducing AAA progression, it is crucial to understand the pathogenesis leading to aneurysm wall weakening/remodeling and identify new proteins involved in this process which could subsequently serve as novel therapeutic targets. In this study, we analyzed the presence of the hypoxia-related proteins carbonic anhydrase IX (CA IX), hypoxia-inducible factor 1α (HIF-1α), and AKT as the key molecule in the phosphoinositide-3-kinase pathway in the AAA wall. Additionally, we used a blood-based assay to examine soluble CA IX (s-CA IX) levels in the plasma of AAA patients. Using western blotting, we detected CA IX protein in 12 out of 15 AAA tissue samples. Immunohistochemistry staining proved CA IX expression in the media of the aneurysmal wall. Evaluation of phosphorylated (p-AKT) and total AKT showed elevated levels of both forms in AAA compared to normal aorta. Using ELISA, we determined the concentration of s-CA IX >20 pg/mL in 13 out of 15 AAA patients. Results obtained from in silico analysis of CA9 and aneurysm-associated genes suggest a role for CA IX in aneurysmal wall remodeling. Our results prove the presence of hypoxia-related CA IX in AAA tissues and indicate a possible role of CA IX in hypoxia-associated cardiovascular diseases.

Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model.

BACKGROUND AND PURPOSE: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. METHODS: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. RESULTS: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P=0.008). CONCLUSIONS: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Validation of natural language processing to determine the presence and size of abdominal aortic aneurysms in a large integrated health system.

OBJECTIVE: Previous studies of the natural history of abdominal aortic aneurysms (AAAs) have been limited by small cohort sizes or heterogeneous analyses of pooled data. By quickly and efficiently extracting imaging data from the health records, natural language processing (NLP) has the potential to substantially improve how we study and care for patients with AAAs. The aim of the present study was to test the ability of an NLP tool to accurately identify the presence or absence of AAAs and detect the maximal abdominal aortic diameter in a large dataset of imaging study reports. METHODS: Relevant imaging study reports (n = 230,660) from 2003 to 2017 were obtained for 32,778 patients followed up in a prospective aneurysm surveillance registry within a large, diverse, integrated healthcare system. A commercially available NLP algorithm was used to assess the presence of AAAs, confirm the absence of AAAs, and extract the maximal diameter of the abdominal aorta, if stated. A blinded expert manual review of 18,000 randomly selected imaging reports was used as the reference standard. The positive predictive value (PPV or precision), sensitivity (recall), and the kappa statistics were calculated. RESULTS: Of the randomly selected 18,000 studies that underwent expert manual review, 48.7% were positive for AAAs. In confirming the presence of an AAA, the interrater reliability of the NLP compared with the expert review showed a kappa value of 0.84 (95% confidence interval [CI], 0.83-0.85), with a PPV of 95% and sensitivity of 88.5%. The NLP algorithm showed similar results for confirming the absence of an AAA, with a kappa of 0.79 (95% CI, 0.799-0.80), PPV of 77.7%, and sensitivity of 91.9%. The kappa, PPV, and sensitivity of the NLP for correctly identifying the maximal aortic diameter was 0.88 (95% CI, 0.87-0.89), 88.8%, and 88.2% respectively. CONCLUSIONS: The use of NLP software can accurately analyze large volumes of radiology report data to detect AAA disease and assemble a contemporary aortic diameter-based cohort of patients for longitudinal analysis to guide surveillance, medical management, and operative decision making. It can also potentially be used to identify from the electronic medical records pre- and postoperative AAA patients "lost to follow-up," leverage human resources engaged in the ongoing surveillance of patients with AAAs, and facilitate the construction and implementation of AAA screening programs.

Incidence and natural history of isolated abdominal aortic dissection: A population-based assessment from 1995 to 2015.

BACKGROUND: Isolated abdominal dissection (IAD) is an uncommon clinical problem that is less well-understood than thoracic aortic dissection (AD). We performed a population-based assessment of the incidence, natural history, and treatment outcomes of IAD to better characterize this disease. METHODS: We used the Rochester Epidemiology Project to identify all Olmsted County, MN residents with a diagnosis of AD, intramural hematoma or penetrating ulcer (1995-2015). Diagnostic imaging of all patients was reviewed to confirm the diagnosis of IAD for inclusion. Presentation, treatment, and outcomes were reviewed. Survival of IAD patients was compared to age- and sex-matched population controls 3:1. RESULTS: Of 133 residents with aortic syndrome (AD, intramural hematoma, or penetrating ulcer), 23 were initially diagnosed with IAD. Nine were reclassified as having a penetrating aortic ulcer and were excluded, leaving 14 patients for review (10 male [71%]; mean age, 71 years). Three patients (21%) were symptomatic (abdominal pain, back pain, hypertension) and none had malperfusion or rupture. Prior aortic dilatation was present in eight patients (57%) and Marfan syndrome in one (7%). Two patients (14%) had iatrogenic IAD. Initial management was medical in 13 and endovascular aneurysm repair in one (symptomatic subacute, infrarenal dissection with small aneurysm). The median clinical and imaging follow-up was 6.7 years (range, 0-17 years). An abdominal aortic aneurysm occurred in eight (six at the time of IAD diagnosis, one at 2.9 years, and one at 5.2 years after diagnosis). The average growth in the entire cohort was 0.9 ± 0.4 cm, which translated to an average growth rate of 0.09 cm/year. Subsequent intervention was performed in two patients; for severe aortic stenosis with claudication in one (infrarenal aortic stenting) and increasing aortic size in one (open repair). One patient required reintervention (thrombolysis and stenting for endovascular aneurysm repair limb thrombosis). Survival for IAD at 1, 3, and 5 years was 93%, 85%, and 76%, respectively, compared with population controls at 98%, 85%, and 71%, respectively (long rank P = .38). Mortality was due to cardiovascular causes in three patients (21%) and no deaths were aortic related. Major adverse cardiac events occurred in five patients (36%) owing to heart failure. CONCLUSIONS: IAD is rare. The initial management for asymptomatic patients is medical. The aortic growth rate is slow, with no aortic-related mortality and a low rate of aortic intervention. The overall mortality is similar to population controls. Heart failure and cardiac-related death are prevalent, suggesting that close cardiovascular care is needed in this patient population.

Editor's Choice - Decrease in Mortality from Abdominal Aortic Aneurysms (2001 to 2015): Is it Decreasing Even Faster?

OBJECTIVE: The early twenty first century witnessed a decrease in mortality from abdominal aortic aneurysms (AAA), which was associated with variations in the prevalence of cardiovascular risk factors. This study investigated whether these trends continued into the second decade of the twenty first century. METHODS: Information on AAA mortality (2001 - 2015) using International Classification of Diseases codes was extracted from the World Health Organization (WHO) mortality database. Data on risk factors were extracted from the Institute of Health Metrics and Evaluation and WHO InfoBase, and data on population from the World Development Indicators database. Regression analysis of temporal trends in cardiovascular risk factors was done independently for correlations with AAA mortality trends. RESULTS: Seventeen countries across four continents met the inclusion criteria (Australasia, two; Europe, 11; North America, two; Asia, two). Male AAA mortality decreased in 13 countries (population weighted average: -2.84%), while female AAA mortality decreased in 11 countries (population weighted average: -1.64%). The decrease in AAA mortality was seen in both younger (< 65 years) and older (> 65 years) patients. The decrease in AAA mortality was more marked in the second decade of the twenty first century (2011 - 2015) compared with the first decade (2001 - 2005 and 2006 - 2010). Trends in AAA mortality positively correlated with smoking (males: p = .03X, females: p = .001) and hypertension (males: p = .001, females: p = .01X). Conversely, AAA mortality negatively correlated with obesity (males: p = .001, females: p = .001), while there was no significant correlation with diabetes. CONCLUSION: AAA mortality has continued to decline and seems to have declined at an even faster rate in the second decade of the twenty first century, albeit with heterogeneity among countries. These variations are multifactorial in origin but further efforts targeting smoking cessation and blood pressure control will probably contribute to continued reductions in AAA mortality.

Prospective, Randomised Two Centre Trial of Endovascular Repair of Abdominal Aortic Aneurysm With or Without Sac Embolisation.

OBJECTIVE: The benefit of aneurysm sac coil embolisation (ASCE) during endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) remains unclear. This prospective randomised two centre study (SCOPE 1: Sac COil embolisation for Prevention of Endoleak) compared the outcomes of standard EVAR in patients with AAA at high risk of type II endoleak (EL with EVAR with ASCE during the period 2014-2019. METHODS: Patients at high risk of type II EL were randomised to standard EVAR (group A) or EVAR with coil ASCE (group B). The primary endpoint was the rate of all types of EL during follow up. Secondary endpoints included freedom from type II EL related re-interventions, and aneurysm sac diameter and volume variation at two year follow up. Adverse events included type II EL and re-interventions. CTA and Duplex ultrasound scans were scheduled at 30 days, six months, one year, and two years after surgery. RESULTS: Ninety-four patients were enrolled, 47 in each group. There were no intra-operative complications. At M1, 16/47 early type II EL occurred (34%) in group A vs. 2/47 (4.3%) in group B (p < .001). At M6, 15/36 type II EL (41.7%) occurred in group A vs. 2/39 (4.26%) in group B (p < .001). At M12, 15/37 type II El (40.5%) occurred in group A vs. 5/35 (14.3%) in group B (p = .018). At 24 months, 8/32 type 2 El (25%) occurred in group A vs. 3/29 (6.5%) in group B (p = .19). Kaplan-Meier curves of survival free from EL and re-interventions were significantly in favour of group B (p < .001). Aneurysm sac volume decreased significantly in group B compared with group A at M6 (p = .081), at M12 (p = .004), and M24 (p = .001). CONCLUSION: For selected patients at risk of EL, ASCE seems effective in preventing EL at one, six, and at 12 months. However, the difference was not statistically significant at 24 months. ASCE decreases the re-intervention rate two years after EVAR. A significantly faster aneurysm volume shrinkage was observed at one and two years following surgery. (SCOPE 1 trial: NCT01878240).

Outcomes of Small Incidental Abdominal Aortic Aneurysms in Octogenarian and Nonagenarian Patients in Northern Spain.

OBJECTIVE: Greater population life expectancy and consistent improvement in diagnostic techniques have increased the diagnosis of abdominal aortic aneurysms (AAAs) in the elderly population. The aim was to study the natural history of small (< 55 mm) incidental AAAs in octogenarian and nonagenarian patients to assess the need for follow up and/or invasive treatment. METHODS: This was a retrospective analysis of a prospective registry. Patients ≥ 80 years old at the time of diagnosis of a < 55 mm AAA in 1988-2018 were selected. Clinical and anatomical characteristics were registered. Patients were divided in three groups: 30 - 39 mm, 40 - 49 mm, and 50 - 54 mm AAA. The outcome variables were aorto-iliac rupture, AAA reaching a surgical threshold (≥ 55 mm), and death. A descriptive statistical analysis was performed and life tables, Kaplan-Meier curves, and uni- and multivariable Cox regression were used. RESULTS: Three hundred and ten patients were included, 256 (82.6%) men, with mean index age of 84.5 years (standard deviation [SD] 3.5), and median follow up of 37.9 months (interquartile range [IQR] 18.2 - 65.4). Eighteen (5.8%) AAAs ruptured; four of these patients were operated on and only one survived. Sixty-two (20%) AAA reached a surgical size; eight were repaired electively, with 0% early mortality. The survival rates were 81%, 70%, and 38% at one, two, and five years. The rupture rates were 1%, 2%, and 6% and the AAAs reaching surgical threshold were 1%, 4%, and 19% for the same time periods. AAA size < 40 mm was an independent protective factor from rupture (0.13; 95% confidence interval [CI] 0.03 - 0.48), reaching surgical threshold (0.08; 95% CI 0.04 - 0.16) and death (0.63; 95% CI 0.42 - 0.95). CONCLUSION: The risk of late rupture of small incidental AAA diagnosed in octogenarian and nonagenarian patients is very small, especially when the AAA is < 40 mm in diameter. In contrast, global mortality is high. Conservative management seems sensible, with strict selection of the patients who would benefit from follow up and eventual repair.

Abdominal Aortic Aneurysm - Disease or a Defect - Patients' Perceptions of Aortic Aneurysm in the Presence of Multimorbidity.

OBJECTIVES: Abdominal aortic aneurysm is associated with substantial comorbidity and significant long-term mortality. Reduction of cardiovascular risk factors and smoking cessation improves prognosis, but implementation of recommendations is suboptimal. Patient's disease-awareness and level of multimorbidity are important factors affecting treatment- adherence. This study explored the perception of disease in patients with abdominal aortic aneurysms and multimorbidity. METHODS: In a qualitative design we assessed patients' perception of aortic aneurysms in the presence of multimorbidity and cardiovascular risk factors. We conducted a workshop including patients from the aneurysm ultrasound-surveillance-program at a tertiary vascular department. Data from the workshop were analyzed using a qualitative exploratory design with an inductive approach. RESULTS: A total of 10 patients with abdominal aortic aneurysm and multimorbidity participated in the workshop. Three categories describing the patient's perception of disease emerged from the analysis. (1) Abdominal aortic aneurysm is not a disease; it is a defect, (2) Someone else is in control, (3) Abdominal aortic aneurysm is an isolated condition. CONCLUSION: Patients with abdominal aortic aneurysms and multimorbidity did not perceive their aneurysm as a disease, but merely as a bodily defect. Growth and rupture of the aneurysm were the main concerns related to the condition, and the participants relied solely on the health professionals to control this by regular ultrasound-surveillance. Consequently, the participants did not perceive abdominal aortic aneurysm as a motivation for cardiovascular risk factor modification by optimization in medication or smoking-cessation.

Incidental abdominal aortic aneurysms are largely undocumented and unmonitored.

BACKGROUND: In countries without organized population screening, incidental detection remains the major form of abdominal aortic aneurysm (AAA) diagnosis. Despite the presumed homogeneity in AAA prevalence, its rate of repair is highly variable, with Portugal treating 2 to 6 times fewer AAA per habitant than other western countries. OBJECTIVES: To evaluate the detection rate and monitoring of incidental AAA in a multicentre cohort from Portuguese hospitals. METHODS: All abdominal CT scans performed in men ≥ 65 years old in three major Portuguese hospitals between January and June 2018 were selected for review. CT scans prescribed by the Vascular Surgery or Emergency Departments were excluded. Patients with previously known AAA were also excluded. Subjects with newly detected aneurysms were assessed for the two primary outcomes: the description of the finding by the radiologist in the written report; the effective follow-up recommendations by the prescriber of the CT or by the general practitioner (GP). Patients with newly found AAA that met criteria for monitoring or treatment and failed to be given guidance were contacted and included in surveillance programs. RESULTS: Overall, 3292 abdominal CT scans were selected for review. A total of 133 newly found aneurysms were detected (4.2% prevalence in the cohort). Of those, 48 cases (36%) were not described by the radiologist in the written report. Further 42 patients (32%) were not successfully oriented by the ordering physician or GP, despite having had their AAA mentioned. Overall, only 32% (n = 42) of the newly diagnosed AAA were correctly identified and referred to monitoring. CONCLUSIONS: Incidental AAA is a common occurrence in in-hospital abdominal CTs. A significant number is not documented by the radiologist and the vast majority is not referred to monitoring. This could be a major reason for the low elective treatment rate of AAA in Portugal.

Tailored Sac Embolization During EVAR for Preventing Persistent Type II Endoleak.

BACKGROUND: Persistent type II endoleaks (ELIIp) occur in 8-23% of patients submitted to endovascular aneurysm repair (EVAR) and may lead to aneurysm progression and rupture. Intraoperative embolization of the abdominal aortic aneurysm (AAA) sac is effective to prevent their occurrence, however a method to achieve complete sac thrombosis has not been standardized yet. Aim of our study was to identify factors associated with prevention of ELIIp after intraoperative embolization, in order to optimize technical details. METHODS: Patients at high risk for ELIIp, who underwent EVAR with AAA - sac coil embolization were prospectively collected into a dedicated database from January 2012 to March 2015. The endoluminal residual sac volume (ERV), not occupied by the endograft [ERV= AAA total volume (TV) - (AAA-thrombus volume (THV) + endograft volume (EgV)] was calculated on preoperative computed tomography and the concentration of coils implanted (CCoil= n coils implanted/ERV) for each patient was evaluated. AAA volumetric evaluation was conducted by dedicated vessels analysis software (3Mensio). ELIIp presence was evaluated by contrast-enhanced ultrasound at 6 and 12-month. Patients with ELIIp at 12 months (Group 1) were clustered and compared to patients without ELIIp (Group 2), in order to evaluate the incidence of ELIIp in patients undergone to preventive AAA-sac embolization, and identify the predictors of ELIIp prevention. Morphological potential risk factors for ELIIp such as TV, THV, VR% and EgV were also considered in all patients. Statistical correlation was assessed by Fisher Exact Test. RESULTS: Among 326 patients undergone to standard EVAR, 61 (19% - M: 96.7%, median age: 72 [IQR: 8] years, median AAA diameter: 57 [IQR: 7] mm) were considered at high risk for ELIIp and were submitted to coil embolization. The median AAA total volume (TV) and median ERV were 156 (IQR: 59) cc and 46 (IQR: 26) cc, respectively. The median number and concentration of coils (IMWCE-38-16-45 Cook M-Ray) positioned in AAA-sac were 5 (IQR: 1) coils and 0.17 coil/cm3 (range 0.02-1.20). Among this high-risk population, the incidence of ELIIp was 29.5% and 23% at 6 and 12-month, respectively. Fourteen patients (23%) were clustered in Group1 and 47 (77%) in Group 2. Both groups were homogeneous for clinical characteristics and preoperative morphological risk factors. There were no differences in the preoperative median TV, AAA-thrombus volume (THV), %VR, EgV and number of implanted coils between Group1 and Group2. Patients in Group1 had a significantly higher ERV (59 [IQR: 13] cm3 vs. 42 [IQR: 27] cm3, P = 0.002) and lower CCoil (0.09 [IQR: 0.03] vs. 0.18 [IQR: 0.21], P = 0.006) than patients of Group2. ELIIp was significantly related to the presence of ERV > 49 cm3 (86 % vs. 42 %, Group1 and Group2 respectively, P = 0.006) and CCoil < 0.17coil/ cm3 (100% vs. 68%, Group1 e Group2 respectively, P = 0.014). CONCLUSION: According with our results, Coil concentration and endoluminal residual volume can affect the efficacy of the AAA - sac embolization in the prevention of ELIIp, moreover CCoil ≥0.17coil/ cm3 maight be considered to determine the tailored number of coils.

The Association of Spondylitis and Aortic Aneurysm Disease.

OBJECTIVES: The aim of this study is to assess any relation between spondylitis and aortic aneurysmal disease by reviewing the current literature. METHODS: A systematic search was undertaken using MEDLINE, EMBASE and CENTRAL databases till May 2019, for articles reporting on patients suffering from spondylitis and aortic aneurysm. RESULTS: The most involved aortic segment was infrarenal aorta (56.9%). The lumbar vertebrae were more frequently affected (79.7%). Commonest symptoms were back pain (79.1%), fever (33.7%) and lower limb pain (29.1%). 55.8% of cases were diagnosed using computed tomography. The pathology was attributed to infectious causes in 25.1% of cases. 53.4% of patients were treated only for the aneurysm, 27.9% for both pathologies, while two patients solely for the vertebral disease. Endovascular aneurysm repair was chosen in 12.8% of cases. The 30-day mortality was 8.1% (7/86); mostly from vascular complications. CONCLUSIONS: A synchronous spondylitis and aortic aneurysm may share common etiopathology, when an infectious or inflammatory cause is presented. The lumbar vertebrae are more frequently affected. Low quality data do not allow safe conclusion to suggest the best treatment option.

Amplatzer Vascular Plug Embolization in Two Patients with Ruptured Infrarenal Aortic Aneurysm and Aortoiliac Occlusive Disease.

Mortality for ruptured abdominal aortic aneurysm (AAA) is known to be high. When left untreated, it is nearly always fatal. Standard treatment options include open surgery and endovascular aneurysm repair (EVAR), but both techniques have limitations. Owing to comorbidities and anatomical constraints, some patients are deemed unsuitable for both open surgery and EVAR. In these patients, alternative treatment strategies can be of special interest. To our knowledge, these are the first two cases reported using an Amplatzer Vascular Plug II for aortic embolization in patients with coexisting aneurysmatic and aorto-bi-iliac occlusive disease requiring urgent treatment for contained AAA rupture. Successful aneurysm exclusion was noted at follow-up ranging from 5 months to 3 years, and no procedure-related complications occurred. We therefore believe that in selected patients, this could be an elegant alternative in life-threatening situations with sustained occlusion in the mid-term.