Abdominal Aortic Aneurysm Rupture Research Articles

Abstract 128: Nicotine Transgenerationally Alters Gene Methylation And Abdominal Aortic Aneurysm Risk

Significance: Both smoking and family history are major risk factors for abdominal aortic aneurysm (AAA). Smoking is a powerful modulator of DNA methylation, and nicotine alone can cause heritable epigenetic alterations in animal models and humans. Nicotine also increases aortic stiffness, predisposing towards AAA. We investigated the effects of parental nicotine exposure in mice on their offspring’s risk for experimental AAA and on transgenerational DNA methylation. Methods: Male and female Apo E-/- mice (F0) were exposed to subcutaneous nicotine (25 mg/kg/day) or saline infusion for 28 days. After treatment completion, mice were mated to untreated controls. F1 generation offspring underwent Angiotensin II infusion (1μg/kg/min) to induce AAA at age 10-weeks. Aneurysm growth was tracked via ultrasound over 28 days. Subgroups of F1 mice underwent ex-vivo pressure myography assessment of the abdominal aorta. Germ and aortic tissue from both F0 and F1 were evaluated using RRBS-Seq genome-wide DNA methylation analysis. Results: Parental nicotine augments model AAA formation, incidence, and rupture rates in their offspring. This effect was most significant in male offspring of nicotine-exposed females (vs. saline). Maternal nicotine exposure also increased F1 aortic stiffness. F0 nicotine exposure altered DNA methylation in multiple tissues, and led to numerous significant differentially methylated regions (DMRs) in their F1 offspring, many precisely conserved. Nicotine caused global DNA hypermethylation, altered maternally imprinted genes in F0 females, and had variable patterns depending on gender. Nicotine altered aortic methylation patterns in genes known to relate to AAA development, including lncRNAs/miRNAs. DMR pathway analysis revealed enrichment for transcription factors, suggesting that nicotine transgenerationally influences numerous genes through expression modulation. Conclusion: Nicotine exposure can augment experimental AAA growth and aortic stiffness across generations. These effects are accompanied by widespread epigenetic changes in germ tissue and aorta, including several key AAA modulator genes, with enrichment in transcription factors, including many targeting known AAA-related genes.

Abstract 129: BAF60c Prevents Abdominal Aortic Aneurysm Formation Through Maintaining Vascular Smooth Muscle Cell Homeostasis

Background: Abdominal aortic aneurysm (AAA) is a common and life-threatening vascular disease. Vascular smooth muscle cell (VSMC) dysfunction is involved in the dilatation and eventual rupture of AAA, with the precise epigenetic control of this process less studied. BAF60c, a unique subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, serves as a core modulator of physiological and pathological processes, yet little is known about its function in the vasculature and pathogenesis of AAA. Methods and Results: BAF60c is downregulated in AAAs from humans and mice with primary staining to the aortic VSMC, confirmed by single cell RNA sequencing. In vivo studies revealed that VSMC-specific knockout Baf60c markedly aggravated both AngII- and elastase-induced murine AAA formation, with significant increases of elastin degradation, inflammatory cell accumulation, VSMC phenotype switching, and apoptosis. In vitro studies showed that knockdown of BAF60c in human aortic smooth muscle cells resulted in the loss of contractile phenotype while upregulation of inflammatory genes and increased apoptosis. Chromatin immunoprecipitation followed by sequencing and qPCR, as well as CoIP assays showed that BAF60c maintained VSMC contractile phenotype by enhancing serum response factor association with its co-activator p300 and SWI/SNF complex, suppressed VSMC inflammation via precise control of the repressive state of NF-κB-target genes, as well as prevented VSMC apoptosis through transcriptional activation of KLF5-dependent BCL2 expression. Conclusions: Our study indicates that BAF60c is essential for SWI/SNF complex recruitment to chromatin and interaction with diverse transcription factors to precise epigenetic control of VSMC homeostasis and prevention of AAA formation.

Investigating the Link between Alpha-1 Antitrypsin Deficiency and Abdominal Aortic Aneurysms

Alpha-1-Antitrypsin (AAT) is one of the major plasmatic protease inhibitors. In the last decade, an association between Alpha-1-Antitrypsin Deficiency (AATD) and Abdominal Aortic Aneurysms (AAA) has been hypothesized. Multiple factors may be involved in AAA's etiopathogenesis, and an underlying structural defect of the extracellular matrix (ECM) is always present. AATD could be a reasonable risk factor for AAA because it is related to protease/antiprotease imbalance and enhanced ECM degradation of the vessel wall. We performed genotyping of 138 patients hospitalized in the Vascular Surgery Division of the ASST-Spedali Civili di Brescia, Italy, for nontraumatic rupture of AAA. The second purpose was to observe the distribution of main nongenetic risk factors for AAA between patients with and without AATD. Out of 138 patients, 22 were found with AATD: 16 MS, 1 SS, 3 MZ, and 2 with a new rare AAT variant. When compared to the general Italian population, our cohort's frequency of deficient S allele was significantly higher (7.8 vs. 2.2% respectively, P < 0.01), whereas the deficient Z allele was similar (1.1 vs. 1.3% respectively, P > 0.05). Although we found no differences in age, gender, hypertension, diabetes, and smoke habits between AAA patients with and without AATD, hyperlipidemia was significantly less frequent in patients with AATD (46.4 vs. 12.5% respectively, P < 0.05). In our AAA patients' cohort, the S allele frequency was higher than in the general Italian population. Our results support the hypothesis that AATD might be a risk factor for AAA.

Evaluation of Aortic Tortuosity as a Negative Predictor of Abdominal Aortic Aneurysm Rupture

Traditionally, the maximal aortic diameter has been used as the key indication for the decision to repair an abdominal aortic aneurysm (AAA). Aortic tortuosity has been proposed as another consideration, and the reported data have suggested that ruptured AAAs (rAAAs) tend to be less tortuous than non-rAAAs at the same diameter. Our objective was to compare the degree of aortic tortuosity in patients with rAAAs with those who had undergone elective repair using two-dimensional computed tomography imaging.

Rupture Before the Age of Abdominal Aortic Aneurysm Screening—Another Example of Disparities in Vascular Surgery?

Area deprivation index (ADI) is a validated measure of socioeconomic disadvantage at the neighborhood level and is increasingly used to assess disparate outcomes across a broad variety of disease states. Cardiovascular diseases present earlier among minority and socioeconomically deprived patients. Screening at 65 years of age, diagnosis, and elective repair are vital in mitigating the risk of abdominal aortic aneurysm rupture (rAAA); however, the association of ADI with rAAA is poorly understood.

Outcomes and Predictors of Mortality in a Belgian Population of Patients Admitted with Ruptured Abdominal Aortic Aneurysm and Treated by Open Repair in the Contemporary Era

Abdominal aortic aneurysm (AAA) rupture is a serious condition that results in extremely high mortality rates. Some improvements in outcome have been reported during the last 2 decades. The objective of the present study was to determine the overall and operative (by open repair) mortality related to ruptured AAA in the contemporary era and to identify preoperative, intraoperative, and early postoperative parameters associated with poor outcomes. We performed a retrospective review of all consecutive patients admitted to our single institution with a diagnosis of ruptured AAA between 2004 and 2013. A total of 103 parameters, including demographic characteristics, medical history, clinical and biological parameters, cardiovascular risk factors, emergency level, diagnostic modalities, time from symptoms to diagnosis and treatment, type of operative procedure and postoperative complications, were analyzed. The primary endpoint considered in this study was the cumulative incidence rate of mortality. The secondary endpoint was the identification, by logistic regression methods, of risk factors for overall mortality as well as for operative, and postoperative mortality. Within our study period, 104 patients were admitted for a ruptured AAA. The majority of patients (84.6%) were male, and the AAA was known in 34.6% of the patients. Rupture occurred for a maximal diameter lower than 55 mm in 25% of the female population, compared to 5.7% of the male population (P = 0.030). The proportions of admitted patients who died before (preoperative mortality), during (intraoperative mortality) or after (postoperative hospital mortality) surgery was 17.3%, 16.3%, and 18.3%, respectively, yielding a cumulative in-hospital mortality of 51.9%. In the multivariate analysis, age ≥ 80 (P = 0.001), myocardial ischemia on the admission ECG (P = 0.046), and management by the physician response unit (P = 0.002) were the only preoperative parameters associated with a higher risk of hospital mortality. Four risk factors were found to be associated with a higher risk of postoperative mortality in the multivariate analysis, and all patients presenting with 3 or more of these risk factors (n = 5) died. The overall mortality of ruptured AAA in a contemporary cohort of patients who underwent open repair remains high and does not seem to have decreased during recent decades. Ruptures occur at smaller diameters in women than in men, supporting a lower threshold for intervention in women with known AAA. We developed risk scores to predict the mortality of patients with rAAA at different times of their hospital course. The validity of these scores should be assessed in prospective clinical studies.

Preoperative and ICU Scoring Models for Predicting the In-Hospital Mortality of Patients With Ruptured Abdominal Aortic Aneurysms

ObjectivesThis study’s objective was to compare several preoperative and intensive care unit (ICU) prognostic scoring systems for predicting the in-hospital mortality of ruptured abdominal aortic aneurysms (RAAAs). DesignRetrospective cohort study. SettingSingle tertiary university center. ParticipantsThe study comprised 157 patients. InterventionsNone. Measurements and Main ResultsA total of 157 patients (82% male) presented with RAAA at Charité University Hospital from January 2011 to December 2020. The mean age was 74 years (standard deviation ten years). In-hospital mortality was 29% (n = 45), of whom nine patients (6%) died en route to the operating room, 13 (8%) on the operating table, and 23 (15%) in the ICU. A total of 135 patients (86%) were admitted to the ICU. All six models demonstrated good discriminating performance between survivors and nonsurvivors. Overall, the area under the curve (AUC) for RAAA preoperative scores was greater than those for ICU scores. The largest AUC was achieved with the Vascular Study Group of New England (VSGNE) RAAA risk score (AUC = 0.87 for all patients, AUC = 0.84 for patients admitted to the ICU), followed by Hardman Index (AUC = 0.83 for all patients, AUC = 0.81 for patients admitted to the ICU), and Glasgow Aneurysm Score (AUC = 0.74 for all patients, AUC = 0.83 for patients admitted to the ICU). The largest AUC for ICU scores (only patients admitted to the ICU) was achieved with Simplified Acute Physiology Score II (0.75), followed by Sepsis-related Organ Failure Assessment (0.73), and Acute Physiology and Chronic Health Evaluation II (0.71). ConclusionsPreoperative and ICU scores can predict the mortality of patients presenting with RAAA. In addition, the discriminatory ability of preoperative scores between survivors and nonsurvivors was larger than that for ICU scores.

Ultrasound-Based Fluid-Structure Interaction Modeling of Abdominal Aortic Aneurysms Incorporating Pre-stress.

Currently, the prediction of rupture risk in abdominal aortic aneurysms (AAAs) solely relies on maximum diameter. However, wall mechanics and hemodynamics have shown to provide better risk indicators. Patient-specific fluid-structure interaction (FSI) simulations based on a non-invasive image modality are required to establish a patient-specific risk indicator. In this study, a robust framework to execute FSI simulations based on time-resolved three-dimensional ultrasound (3D+t US) data was obtained and employed on a data set of 30 AAA patients. Furthermore, the effect of including a pre-stress estimation (PSE) to obtain the stresses present in the measured geometry was evaluated. The established workflow uses the patient-specific 3D+t US-based segmentation and brachial blood pressure as input to generate meshes and boundary conditions for the FSI simulations. The 3D+t US-based FSI framework was successfully employed on an extensive set of AAA patient data. Omitting the pre-stress results in increased displacements, decreased wall stresses, and deviating time-averaged wall shear stress and oscillatory shear index patterns. These results underline the importance of incorporating pre-stress in FSI simulations. After validation, the presented framework provides an important tool for personalized modeling and longitudinal studies on AAA growth and rupture risk.

Ultrasound screening for abdominal aortic aneurysm in high-risk women

BackgroundPopulation-wide ultrasound screening programmes for abdominal aortic aneurysm (AAA) for men have already been established in some countries. Women account for one third of aneurysm-related mortality and are four times more likely to experience an AAA rupture than men. Whole-population screening for AAA in women is unlikely to be clinically or economically effective. The aim of this study was to determine the outcomes of a targeted AAA screening programme for women at high risk of AAA.MethodWomen aged 65–74 years deemed at high risk of having an AAA (current smokers, ex-smokers, or with a history of coronary artery disease) were invited to attend ultrasound screening (July 2016 to March 2019) for AAA in the Female Aneurysm screening STudy (FAST). Primary outcomes were attendance for screening and prevalence of AAA. Biometric data, medical history, quality of life (QoL) and aortic diameter on ultrasound imaging were recorded prospectively.ResultsSome 6037 women were invited and 5200 attended screening (86.7 per cent). Fifteen AAAs larger than 29 mm were detected (prevalence 0.29 (95 per cent c.i. 0.18 to 0.48) per cent). Current smokers had the highest prevalence (0.83 (95 per cent c.i. 0.34 to 1.89) per cent) but lowest attendance (75.2 per cent). Three AAAs greater than 5.5 cm were identified and referred for consideration of surgical repair; one woman underwent repair. There was a significant reduction in patient-reported QoL scores following screening.ConclusionA low prevalence of AAA was detected in high-risk women, with lowest screening uptake in those at highest risk. Screening for AAA in high-risk women may not be beneficial.

Choices of emergency treatment and surgical method for ruptured abdominal aortic aneurysms

Objective: To investigate the emergency management process of ruptured abdominal aortic aneurysm (RAAA), and analyze the perioperative mortality factors of different surgical methods. Methods: The emergency data and hospitalization data of 91 patients with ruptured abdominal aortic aneurysm in Xiangya Hospital of Central South University from June 2010 to June 2019 were retrospectively analyzed.Twelve of the patients died preoperatively due to excessive blood loss, and the remaining 79 patients were hospitalized for open surgery (OSR) or endovascular repair (EVAR).The differences in age, time to hospital arrival, emergency preparation time, first creatinine value, emergency infusion volume, preoperative drop in blood pressure, preoperative use of vasoactive drugs and iliac artery involvement were compared between preoperative death group (n=12) and preoperative survival group (n=79), OSR group (n=50) and EVAR group (n=29), postoperative death group (n=23) and postoperative survival group (n=56). Results: Seventy-nine patients received open surgery or endovascular repair, and 23 died after operation. Age, time to hospital arrival, first creatinine value and emergency infusion volume were (77±11) years, (18±5)h, (469±150) μmol/L, (4 140±1 743) ml in the preoperative death group and (70±10) years, (12±8) h, (228±174) μmol/L, (1 358±1 211) ml in the preoperative survival group, respectively, and the differences were statistically significant (all P<0.05). There were no significant differences in preoperative data, intraoperative treatment and postoperative perioperative mortality between the open surgery group and the endovascular repair group (all P>0.05). The intraoperative blood loss, operation time and aortic occlusion rate in the endovascular repair group were 100 (50, 175) ml, (3.2±0.9) h, 13.8%, respectively, which were better than that in the open surgery group 1700 (600, 3425) ml, (5.2±1.1) h, 100%. The differences were statistically significant (all P<0.05). Age, emergency preparation time, first creatinine value, emergency infusion volume, blood pressure decline rate and vasoactive drug utilization rate in the death group were (77±8) years, (4.1±1.7) h, (456±172) μmol/L, (2 024±1 687) ml, 100%, 100%, respectively, and (68±10) years, (2.7±2.2) h, (135±26) μmol/L, (1 085±825) ml, 21.4%, 12.5% in the survival group, respectively. The differences were statistically significant (all P<0.05). Conclusions: Age, emergency preparation time, first creatinine value, emergency infusion volume, decreased blood pressure and use of vasoactive drugs are all associated with perioperative death in patients with ruptured abdominal aortic aneurysm. EVAR surgery is a better choice if conditions exist.

Inhibition of Peptidyl Arginine Deiminase 4-Dependent Neutrophil Extracellular Trap Formation Reduces Angiotensin II-Induced Abdominal Aortic Aneurysm Rupture in Mice.

Objective: Neutrophil infiltration plays an important role in the initiation and development of abdominal aortic aneurysm (AAA). Recent studies suggested that neutrophils could release neutrophil extracellular traps (NETs), leading to tissue injury in cardiovascular diseases. However, the role of NETs in AAA is elusive. This study aimed to investigate the role and underlying mechanism of NETs in AAA development.Methods and Results: An angiotensin II (Ang II) infusion-induced AAA model was established to investigate the role of NETs during AAA development. Immunofluorescence staining showed that citrullinated histone 3 (citH3), myeloperoxidase (MPO), and neutrophil elastase (NE) (NET marker) expressions were significantly increased in Ang II-infused ApoE−/− mice. The circulating double-stranded DNA (dsDNA) level was also elevated, indicating the increased NET formation during AAA. PAD4 inhibitor YW3-56 inhibited Ang II-induced NET formation. Disruption of NET formation by YW3-56 markedly reduced Ang II-induced AAA rupture, as revealed by decreased aortic diameter, vascular smooth muscle cell (VSMC) apoptosis, and elastin degradation. Apoptosis of VSMC was evaluated by TUNEL staining and Annexin V-FITC/PI staining through flow cytometry. Western blot and inhibition experiments revealed that NETs induced VSMC apoptosis via p38/JNK pathway, indicating that PAD4-dependent NET formation played an important role in AAA.Conclusions: This study suggests that PAD4-dependent NET formation is critical for AAA rupture, which provides a novel potential therapeutic strategy for AAA disease.

Silencing IL12p35 Promotes Angiotensin II-Mediated Abdominal Aortic Aneurysm through Activating the STAT4 Pathway.

Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe−/−) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe−/− mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe−/− mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.

Targeting Tyrosine Hydroxylase for Abdominal Aortic Aneurysm: Impact on Inflammation, Oxidative Stress, and Vascular Remodeling.

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Risk Factors, Dynamics, and Clinical Consequences of Aortic Neck Dilatation after Standard Endovascular Aneurysm Repair

Aortic neck dilatation (AND) occurs after endovascular aneurysm repair (EVAR) with self expanding stent grafts (SESs). Whether it continues, ultimately exceeding the endograft diameter leading to abdominal aortic aneurysm (AAA) rupture, remains uncertain. Dynamics, risk factors, and clinical relevance of AND were investigated after EVAR with standard SESs. All intact EVAR patients treated from 2000 to 2015 at a tertiary institution were included. Demographic, anatomical, and device related characteristics were investigated as risk factors for AND. Outer to outer diameters were measured at a single standardised aortic level on reconstructed computed tomography (CT) images. A total of 460 patients were included (median follow up 5.2 years, interquartile range [IQR] 3.0, 7.7 years; CT imaging follow up 3.3 years, IQR 1.3, 5.4). Baseline neck diameter was 24 mm (IQR 22, 26) and increased 11.1% (IQR 1.5%, 21.9%) at last CT imaging. Endograft oversizing was 20.0% (IQR 13.6, 28.0). AND was greater during the first year (5.2% [IQR 0, 11.7]) decreasing subsequently (two to four years to 1.4%/year [IQR 0.0, 4.5%], p ≤ .001) and was associated with suprarenal fixation endografts (t value = 7.9, p < .001) and oversizing (t value = 4.4, p < .001). AND exceeding the endograft was 3.5% (95% CI 2.2% – 4.8%) and 14.4% (95% CI 11.0% – 17.8%) at five and eight years, respectively. Excessive AND was associated with baseline neck diameter (OR 1.2/mm, 95% CI 1.05 – 1.41) while the Excluder endograft had a protective effect (OR 0.15, 95% CI 0.04 – 0.58). Excessive AND was associated with type 1A endoleak (HR 3.3, 95% CI 1.1 – 9.7) and endograft migration > 5 mm (HR 3.1, 95% CI 1.4 – 6.9). AND after EVAR with SES is associated with endograft oversizing and radial force but decelerates after the first post-operative year. Baseline aortic neck diameter and suprarenal stent bearing endografts were associated with an increased risk of AND beyond nominal stent graft diameter. However, it remains unclear whether patient selection, differences in endograft radial force or the suprarenal stent are accountable for this difference.

Two Decades of Abdominal Aortic Endovascular Repair With the Anatomical FiXation at the Aortic Bifurcation in a Large Single-Center Experience

Objective: The introduction of new endograft models improved long-term results of abdominal aortic aneurysm (AAA) endovascular repair (EVAR), but most of them maintained an old and unchanged design: a short body and long legs shifting up the flow divider. This study assessed the long-term results of EVAR with unimodular endoprosthesis fixed at the aorto-iliac bifurcation (Anatomical FiXation), in a large, unselected cohort. Materials and Methods: In a single-center, retrospective cohort study, 623 patients selectively treated between 1999 and 2016, were analyzed. Follow-up protocol included at least a computed tomography angiography within 3 months and a duplex ultrasound and clinical exam yearly. All enrolled patients were analyzed by 2020. The primary outcomes were technical success, clinical success, and survival. Secondary outcomes included survival-free from late-open-conversion (LOC), reintervention, and endoleaks. Results: Median age was 74±11 years and the follow-up 93±54 months. The technical success was achieved in 99.4% and the 30-day clinical success was 98.4%. A 5-year clinical success of 97.7% was registered and at 10 years success was 96.7%. The overall survival at 1, 5, 10, and 15 years was 92.4%, 79.5%, 64.9%, and 45.5%, respectively. Six (0.98%) AAA-related death were registered, 3 caused by infection of the endograft and 3 for secondary rupture. LOCs were 9 (1.47%) and reintervention-free survival at 1, 5, 10, and 15 years were 88.4%, 78.0%, 76.2%, and 74.6%, respectively. Freedom from endoleaks was 88.8% at 1 year and 72.7% at 15 years. A total of 63 high-flow endoleaks were registered (43 type I, 7 type IIIa, 12 type IIIb, and 1 type Ib+IIIb). No migrations were recorded, and the graft limb thrombosis rate was 1.14%. From a multivariate analysis resulted that long-term clinical success appeared to be reduced in patients affected by diabetes [odds ratio (OR) 0.24; p=0.04] and in presence of calcified and thrombotic iliac accesses (OR 0.16; p=0.006). Conclusion: EVAR with the Anatomical FiXation was confirmed to be safe, feasible, and effective to prevent AAA rupture in the long term as well. However, the overall survival remains afflicted by cardiovascular accident. The original concept of unibody bifurcated design allowed a very low rate of graft thrombosis and zeroed the risk of migration and related reintervention.

Influence of perioperative risk factors on the development of transmural colonic ischemia after open repair of ruptured abdominal aortic aneurysm.

Development of colonic ischemia (CI) after ruptured abdominal aortic aneurysm (RAAA) treatment is a lethal complication with perioperative mortality reported to be high as 50%. Therefore, the main goal of this study was to identify pre-, intra- and postoperative risk factors associated with CI in patients undergoing open repair (OR) due to RAAA, that might help to select patients who are more prone to develop CI. This was a single-center prospective cohort study on patients with RAAA undergoing OR between January 1st 2018 and July 1st 2019, at the Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia. During this period 89 patients were treated due to RAAA and all were included in the study. The primary endpoint was grade III CI, or transmural necrosis, diagnosed by laparotomy. Out of 89 patients operated due to RAAA, CI was diagnosed in 14 (15.73%). During the operation, patients with CI had a longer duration of hypotension (42.86±35.82 vs. 24.13±23.48, P=0.021) and more common significant hypotension (54.54% vs. 14.66%, P=0.024). In the postoperative course, patients with CI had more common signs of abdominal compartment syndrome (71.42% vs. 25.33%, P=0.001) and higher mortality rate (78.57% vs 29.33%, P=0.001). The univariate regression model showed that one of the most significant factors that were associated with CI were age higher than 75 years, significant hypotension lasting more than one hour, organ lesion, development of abdominal compartment syndrome and higher potassium values on third and fourth quartile. Grade III colon ischemia (transmural) remains the important cause of mortality after ruptured abdominal aortic aneurysm repair. We identified pre- and intraoperative and postoperative risk factors that could improve the selection of patients for primary open abdomen treatment or early exploratory laparotomy in order to prevent or timely diagnose colon ischemia.

Postoperative imaging follow-up at 2 years as a predictor of long-term outcomes after endovascular aneurysm repair

ObjectiveLifelong imaging follow-up remains the reference standard after endovascular aneurysm repair (EVAR). Because the number of EVARs has been increasing, an individually optimized follow-up protocol is desirable. The aim of the present study was to investigate the possibility of creating such a protocol by evaluating patients' follow-up images and to compare the findings with their freedom from reintervention and abdominal aortic aneurysm (AAA) rupture. MethodsFrom 2000 to 2010, 282 patients with an AAA had undergone elective EVAR with the Zenith stent-graft. The patients were followed up annually until the end of 2019. The patients were categorized into two groups according to the presence of any endoleak or sac shrinkage at 2 years. Group A included those with no detectable endoleak plus aneurysm sac shrinkage of ≥5 mm (n = 137; 63%), and group B included those with any type of endoleak and/or no significant aneurysm sac shrinkage (<5 mm; n = 82; 37%). ResultsThe mean follow-up was 83 months (range, 0-229 months), and the overall survival at 2 years was 84% (n = 237). No significant difference was found in overall survival between groups A and B (P = .73). However, a significant difference was found in freedom from AAA rupture at 12 years, favoring group A (group A, 100%; group B, 91%; P = .002). Furthermore, in group A, the freedom from reintervention was 95% at 12 years compared with only 31% in group B (P < .001). The sensitivity of the categorization was 89% and the specificity was 74% for the finding of a complication requiring a reintervention during long-term follow-up. ConclusionsPatients without an endoleak and a reduction of ≥5 mm in aneurysm size at 2 years had significantly fewer late reinterventions and ruptures during long-term follow-up compared with their counterparts using the Zenith stent-graft (Cook Medical, Bloomington, Ind). This finding suggests that, for these patients, the follow-up interval can be personalized and safely extended after 2 years.

Granzyme K - A novel marker to identify the presence and rupture of abdominal aortic aneurysm

BackgroundImmune inflammatory dysfunction is a hallmark of abdominal aortic aneurysm (AAA). Granzyme K (GZMK) is involved in the regulation of inflammation. However, the correlation between GZMK expression and AAA risk remains unknown. MethodsThis case-control study included 112 AAA patients and 112 controls. Serum GZMK levels were determined by enzyme-linked immunosorbent assay and immunohistochemistry was utilized to determine GZMK expression in aortic tissues. ResultsCompared with controls, AAA patients had higher levels of serum GZMK, and GZMK expression in AAA tissues was increased and positively associated with its serum levels (r = 0.688, P = 0.019). A positive association of serum GZMK levels with CRP or AAA diameter was confirmed, while there was a relationship between tissue GZMK expression and AAA diameter. The AUC of serum GZMK for AAA diagnosis was 0.78 with the sensitivity and specificity of 62.5% and 81.2%, whereas AUC for rupture detection was 0.76 with a sensitivity of 90.0% and specificity of 51.3%. A combination of clinically used inflammatory parameters with serum GZMK could enhance the accuracy of WBC or CRP alone in detecting AAA or rupture type. Multiple logistic analyses revealed an association of per unit increase of serum GZMK with AAA presence (OR = 1.046, P < 0.001) and its rupture risk (OR = 1.015, P = 0.048) after adjusting for confounding factors. ConclusionsOur study provides proof that elevated GZMK expression both in serum and tissues is correlated with the presence of AAA, and serum GZMK may be a useful non-invasive marker that helps to identify AAA and its rupture risk in clinical practice.

Novel Experimental Technique to Create Size-Controlled Retroperitoneal Bleeding in the Infrarenal Aorta of Anesthetized Pigs.

Rupture of abdominal aortic aneurysm (rAAA) with a contained retroperitoneal hematoma is potentially fatal. Physiological studies are difficult to perform in patients suffering from life-threatening conditions such as rAAA. A translational model of the condition is therefore needed. The aim was to develop and validate an endovascular animal model for retroperitoneal bleeding of the abdominal aorta with contained hematoma. In anesthetized pigs, a puncture hole was made in the posterolateral portion of the infrarenal aorta by an Outback re-entry catheter device. The hole was gradually enlarged using angioplasty balloons to a specific diameter of either 4 mm (n = 6), 6 mm (n = 7), or 8 mm (n = 6). Onset of bleeding was verified by angiography and macroscopically examined on completion of the experiments. Survival up to 180 min was the primary outcome. Hemodynamic and metabolic markers in arterial blood were secondary outcomes. Aortic injury with a contained retroperitoneal hematoma was achieved in all animals. Survival rate at 180 min after onset of bleeding was higher in the 4 mm group compared to the 6 mm (P = 0.021) and 8 mm groups (P = 0.002), but not when comparing the 6 mm and 8 mm groups. Systemic hypotension, arterial acidosis, and lactatemia were provoked in the 6 mm and 8 mm groups but not in the 4 mm group. A porcine model for a controlled contained left posterolateral retroperitoneal bleeding was created using endovascular methods and validated. This model makes it possible to study the pathophysiology of a retroperitoneal hematoma.

Risk Factors, Dynamics, and Clinical Consequences of Aortic Neck Dilatation after Standard Endovascular Aneurysm Repair

Aortic neck dilatation (AND) occurs after endovascular aneurysm repair (EVAR) with self expanding stent grafts (SESs). Whether it continues, ultimately exceeding the endograft diameter leading to abdominal aortic aneurysm (AAA) rupture, remains uncertain. Dynamics, risk factors, and clinical relevance of AND were investigated after EVAR with standard SESs. All intact EVAR patients treated from 2000 to 2015 at a tertiary institution were included. Demographic, anatomical, and device related characteristics were investigated as risk factors for AND. Outer to outer diameters were measured at a single standardised aortic level on reconstructed computed tomography (CT) images. A total of 460 patients were included (median follow up 5.2 years, interquartile range [IQR] 3.0, 7.7 years; CT imaging follow up 3.3 years, IQR 1.3, 5.4). Baseline neck diameter was 24 mm (IQR 22, 26) and increased 11.1% (IQR 1.5%, 21.9%) at last CT imaging. Endograft oversizing was 20.0% (IQR 13.6, 28.0). AND was greater during the first year (5.2% [IQR 0, 11.7]) decreasing subsequently (two to four years to 1.4%/year [IQR 0.0, 4.5%], p ≤ .001) and was associated with suprarenal fixation endografts (t value= 7.9, p < .001) and oversizing (t value= 4.4, p < .001). AND exceeding the endograft was 3.5% (95% CI 2.2% - 4.8%) and 14.4% (95% CI 11.0% - 17.8%) at five and eight years, respectively. Excessive AND was associated with baseline neck diameter (OR 1.2/mm, 95% CI 1.05 - 1.41) while the Excluder endograft had a protective effect (OR 0.15, 95% CI 0.04 - 0.58). Excessive AND was associated with type 1A endoleak (HR 3.3, 95% CI 1.1 - 9.7) and endograft migration > 5 mm (HR 3.1, 95% CI 1.4 - 6.9). AND after EVAR with SES is associated with endograft oversizing and radial force but decelerates after the first post-operative year. Baseline aortic neck diameter and suprarenal stent bearing endografts were associated with an increased risk of AND beyond nominal stent graft diameter. However, it remains unclear whether patient selection, differences in endograft radial force or the suprarenal stent are accountable for this difference.