Sex Differences in Rupture Risk and Mortality in Untreated Patients With Intact Abdominal Aortic Aneurysms.
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ABSTRACT:
SUBMITTER: Talvitie M
PROVIDER: S-EPMC8174277 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A rupture risk assessment is critical to the clinical treatment of abdominal aortic aneurysm (AAA) patients. The biomechanical AAA rupture risk assessment quantitatively integrates many known AAA rupture risk factors but the variability of risk predictions due to model input uncertainties remains a challenging limitation. This study derives a probabilistic rupture risk index (PRRI). Specifically, the uncertainties in AAA wall thickness and wall strength were considered, and wall stress was predicted with a state-of-the-art deterministic biomechanical model. The discriminative power of PRRI was tested in a diameter-matched cohort of ruptured (n = 7) and intact (n = 7) AAAs and compared to alternative risk assessment methods. Computed PRRI at 1.5 mean arterial pressure was significantly (p = 0.041) higher in ruptured AAAs (20.21(s.d. 14.15%)) than in intact AAAs (3.71(s.d. 5.77)%). PRRI showed a high sensitivity and specificity (discriminative power of 0.837) to discriminate between ruptured and intact AAA cases. The underlying statistical representation of stochastic data of wall thickness, wall strength and peak wall stress had only negligible effects on PRRI computations. Uncertainties in AAA wall stress predictions, the wide range of reported wall strength and the stochastic nature of failure motivate a probabilistic rupture risk assessment. Advanced AAA biomechanical modelling paired with a probabilistic rupture index definition as known from engineering risk assessment seems to be superior to a purely deterministic approach.
| S-EPMC4707859 | biostudies-literature
Project description:BackgroundAbdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture.MethodsExperimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE - / - mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS).ResultsThe size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate.ConclusionPemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.
| S-EPMC9280056 | biostudies-literature
Project description:OBJECTIVES: Abdominal aortic aneurysm (AAA) rupture has a high mortality rate. Although the diagnosis of a ruptured AAA is usually straightforward, detection of impending rupture signs can be more challenging. Early diagnosis of impending AAA rupture can be lifesaving. Furthermore, differentiating between impending and complete rupture has important repercussions on patient management and prognosis. The purpose of this article is to classify and illustrate the entire spectrum of AAA rupture signs and to review current treatment options for ruptured AAAs. METHODS: Using medical illustrations supplemented with computed tomography (CT), this essay showcases the various signs of impending rupture and ruptured AAAs. Endovascular aneurysm repair (EVAR) and open surgical repair are also discussed as treatment options for ruptured AAAs. RESULTS: CT imaging findings of ruptured AAAs can be categorised according to location: intramural, luminal, and extraluminal. Intramural signs generally indicate impending AAA rupture, whereas luminal and extraluminal signs imply complete rupture. EVAR has emerged as an alternative and possibly less morbid method to treat ruptured AAAs. CONCLUSIONS: AAA rupture occurs at the end of a continuum of growth and wall weakening. This review describes the CT imaging findings that may help identify impending rupture prior to complete rupture. TEACHING POINTS: • AAA rupture occurs at the end of a continuum of growth and wall weakening. • Intramural imaging findings indicate impending AAA rupture. • Luminal and extraluminal imaging findings imply complete AAA rupture. • Some imaging findings are not specific to AAA ruptures and can be seen in other pathologies. • EVAR has emerged as an alternative and possibly less morbid method of treating ruptured AAAs.
| S-EPMC4035490 | biostudies-other
Project description:BackgroundThe UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK.MethodsAnonymized data from the UK National Vascular Registry (NVR) for patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co-variables were extracted for analysis by sex. The primary outcome measure was in-hospital mortality. Secondary outcome measures included mortality by 5-year age groups and duration of hospital stay. Logistic regression was performed to adjust for age, calendar time, AAA diameter and smoking status. NVR-based outcomes were checked against Hospital Episode Statistics (HES) data.ResultsA total of 23 245 patients were included (13·0 per cent women). Proportionally, more women than men underwent open repair. For elective open AAA repair, the in-hospital mortality rate was 6·9 per cent in women and 4·0 per cent in men (odds ratio (OR) 1·48, 95 per cent c.i. 1·08 to 2·02; P = 0·014), whereas for elective endovascular AAA repair it was 1·8 per cent in women and 0·7 per cent in men (OR 2·86, 1·72 to 4·74; P < 0·001); the results in HES were similar. For ruptured AAA, there was no sex difference in mortality within the NVR; however, in HES, for ruptured open AAA repair, the in-hospital mortality rate was higher in women (33·6 versus 27·1 per cent; OR 1·36, 1·16 to 1·59; P < 0·001).ConclusionWomen have a higher in-hospital mortality rate than men after elective AAA repair even after adjustment. This higher mortality may have an impact on the benefit offered by any screening programme offered to women.
| S-EPMC5655705 | biostudies-literature
Project description:Background Prior studies have suggested aortic peak wall stress (PWS) and peak wall rupture index (PWRI) can estimate the rupture risk of an abdominal aortic aneurysm (AAA), but whether these measurements have independent predictive ability over assessing AAA diameter alone is unclear. The aim of this systematic review was to compare PWS and PWRI in participants with ruptured and asymptomatic intact AAAs of similar diameter. Methods and Results Web of Science, Scopus, Medline, and The Cochrane Library were systematically searched to identify studies assessing PWS and PWRI in ruptured and asymptomatic intact AAAs of similar diameter. Random-effects meta-analyses were performed using inverse variance-weighted methods. Leave-one-out sensitivity analyses were conducted to assess the robustness of findings. Risk of bias was assessed using a modification of the Newcastle-Ottawa scale and standard quality assessment criteria for evaluating primary research papers. Seven case-control studies involving 309 participants were included. Meta-analyses suggested that PWRI (standardized mean difference, 0.42; 95% CI, 0.14-0.70; P=0.004) but not PWS (standardized mean difference, 0.13; 95% CI, -0.18 to 0.44; P=0.418) was greater in ruptured than intact AAAs. Sensitivity analyses suggested that the findings were not dependent on the inclusion of any single study. The included studies were assessed to have a medium to high risk of bias. Conclusions Based on limited evidence, this study suggested that PWRI, but not PWS, is greater in ruptured than asymptomatic intact AAAs of similar maximum aortic diameter.
| S-EPMC8174183 | biostudies-literature
Project description:An abdominal aortic aneurysm (AAA) is a permanent and irreversible dilation of the lower region of the aorta. It is a symptomless condition that, if left untreated, can expand until rupture. Despite ongoing efforts, an efficient tool for accurate estimation of AAA rupture risk is still not available. Furthermore, a lack of standardisation across current approaches and specific obstacles within computational workflows limit the translation of existing methods to the clinic. This paper presents BioPARR (Biomechanics based Prediction of Aneurysm Rupture Risk), a software system to facilitate the analysis of AAA using a finite element analysis based approach. Except semi-automatic segmentation of the AAA and intraluminal thrombus (ILT) from medical images, the entire analysis is performed automatically. The system is modular and easily expandable, allows the extraction of information from images of different modalities (e.g. CT and MRI) and the simulation of different modelling scenarios (e.g. with/without thrombus). The software uses contemporary methods that eliminate the need for patient-specific material properties, overcoming perhaps the key limitation to all previous patient-specific analysis methods. The software system is robust, free, and will allow researchers to perform comparative evaluation of AAA using a standardised approach. We report preliminary data from 48 cases.
| S-EPMC5498605 | biostudies-literature
Project description:ObjectiveThere is a growing body of literature raising concerns about the long-term durability of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs), suggesting that long-term outcomes may be better after open AAA repair. However, the data investigating these long-term outcomes largely originate from early in the endovascular era and therefore do not account for increasing clinical experience and technologic improvements. We investigated whether 4-year outcomes after EVAR and open repair have improved over time.MethodsWe identified all EVARs and open repairs for intact infrarenal AAA within the Vascular Quality Initiative database (2003-2018). We then stratified patients by procedure year into treatment cohorts of four years: 2003-2006, 2007-2010, 2011-2014, and 2015-2018. We used Kaplan-Meier analysis and Cox proportional hazards models to assess whether the survival after EVAR or open repair changed over time. In addition, we propensity matched EVAR and open repairs for each time cohort to investigate whether the relative survival benefit of EVAR over open repair changed over time.ResultsWe included 42,293 EVARs (increasing from 549 performed between 2003 and 2006 to 25,433 between 2015 and 2018) and 5189 open AAA repairs (increasing from 561 to 2306). Four-year survival increased for the periods 2003-2006, 2007-2010, 2011-2014, and 2015-2018 after both EVAR (76.6% vs 79.7% vs 83.5% vs 87.3%; P < .001) and open repair (82.2% vs 85.8% vs 87.7% vs 88.9%; P = .026). After risk adjustment, compared with 2003-2006, hazard of mortality up to 4 years after EVAR was lower for those performed between 2011 and 2014 (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.59-0.87; P = .001) and for those performed between 2015 and 2018 (HR, 0.56; 95% CI, 0.46-0.68; P < .001). In contrast, the risk-adjusted hazard of mortality was similar between open repair cohorts (2011-2014: HR, 0.81 [95% CI, 0.61-1.08; P = .15]; and 2015-2018: HR, 0.86 [95% CI, 0.64-1.17; P = .34]). Finally, in matched EVAR and open repairs, there was no difference in mortality in the first three cohorts, whereas the hazard of mortality was lower for the 2015-2018 cohort (HR, 0.65; 95% CI, 0.51-0.84; P = .001).ConclusionsFour-year survival improved in more recent years after EVAR but not after open repair. This finding suggests that midterm outcomes after EVAR are improving, perhaps because of technologic improvements and increased experience, information that should be considered by surgeons and policymakers alike in evaluating the value of contemporary EVAR and open AAA repair.
| S-EPMC8025309 | biostudies-literature
Project description:ObjectiveMortality after open repair for emergent complex abdominal aortic aneurysm (AAA) is poorly defined. This study evaluated the 30-day mortality of open complex AAA repair performed for rupture or other emergent indication using a national surgical registry. We subsequently identified factors associated with mortality.MethodsThe targeted vascular module from the American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients undergoing open repair for juxtarenal and suprarenal AAAs or type IV thoracoabdominal aneurysms (TAAAs) for rupture or other emergent indication from 2011 to 2017. Univariate analyses were performed using the Fisher's exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Multivariable logistic regression was performed to identify factors independently associated with mortality.ResultsWe included 374 patients who underwent an emergent complex open AAA repair during the study period. There were 142 (38%) cases performed for rupture with hypotension, 141 (38%) for rupture without hypotension, 40 (11%) for symptomatic AAA, and 51 (14%) for another indication. The distribution by aneurysm type was 224 juxtarenal AAAs, 122 suprarenal AAAs, and 28 type IV TAAAs. Overall, there was a 30-day mortality of 32% (118 deaths). For those with juxtarenal AAA repair, 67 (30%) patients died within 30 days; there were 38 (31%) deaths within 30 days in those with suprarenal AAA, and 13 (46%) deaths within 30 days in those with type IV TAAA. On univariate analysis, preoperative variables associated with death were increasing age, use of a transperitoneal surgical approach, lower preoperative estimated glomerular filtration rate, low baseline albumin concentration (<3.5 g/dL), need for preoperative transfusion, low body mass index (<18.5 kg/m2), and hypotension at presentation. Intraoperative variables associated with mortality were supraceliac clamp location and concurrent renal revascularization. On multivariable analysis, factors independently associated with death included rupture with associated hypotension (reference: other emergent indication; adjusted odds ratio [AOR], 3.28; confidence interval [CI], 1.75-5.41; P < .001), age >60 years (reference: <60 years; AOR, 1.59; CI, 1.18-2.13; P = .002), longitudinal laparotomy incision (reference: retroperitoneal; AOR, 3.28; CI, 1.75-6.16; P < .001), and supraceliac cross-clamp (reference: clamp above one renal artery; AOR, 2.14; CI, 1.31-3.50; P = .003).ConclusionsNearly one-third of patients die within 30 days of emergent open complex AAA repair. Mortality is particularly high for patients with type IV TAAAs, approaching 50%. Predictors of 30-day mortality include rupture with associated hypotension, increasing age, supraceliac clamp location, and longitudinal transperitoneal repair approach. These results will help inform surgical decisions preoperatively and intraoperatively.
| S-EPMC7606433 | biostudies-literature
Project description:In the event of abdominal aortic aneurysm (AAA) rupture, the outcome is often death. This paper aims to experimentally identify the rupture locations of in vitro AAA models and validate these rupture sites using finite element analysis (FEA). Silicone rubber AAA models were manufactured using two different materials (Sylgard 160 and Sylgard 170, Dow Corning) and imaged using computed tomography (CT). Experimental models were inflated until rupture with high speed photography used to capture the site of rupture. 3D reconstructions from CT scans and subsequent FEA of these models enabled the wall stress and wall thickness to be determined for each of the geometries. Experimental models ruptured at regions of inflection, not at regions of maximum diameter. Rupture pressures (mean+/-SD) for the Sylgard 160 and Sylgard 170 models were 650.6+/-195.1mmHg and 410.7+/-159.9mmHg, respectively. Computational models accurately predicted the locations of rupture. Peak wall stress for the Sylgard 160 and Sylgard 170 models was 2.15+/-0.26MPa at an internal pressure of 650mmHg and 1.69+/-0.38MPa at an internal pressure of 410mmHg, respectively. Mean wall thickness of all models was 2.19+/-0.40mm, with a mean wall thickness at the location of rupture of 1.85+/-0.33 and 1.71+/-0.29mm for the Sylgard 160 and Sylgard 170 materials, respectively. Rupture occurred at the location of peak stress in 80% (16/20) of cases and at high stress regions but not peak stress in 10% (2/20) of cases. 10% (2/20) of models had defects in the AAA wall which moved the rupture location away from regions of elevated stress. The results presented may further contribute to the understanding of AAA biomechanics and ultimately AAA rupture prediction.
| S-EPMC2857518 | biostudies-literature
Project description:Current clinical practice for the assessment of abdominal aortic aneurysms (AAA) is based on vessel diameter and does not account for the multifactorial, heterogeneous remodeling that results in the regional weakening of the aortic wall leading to aortic growth and rupture. This study was conducted to determine correlation between a novel non-invasive surrogate measure of regional aortic weakening and the results from invasive analyses performed on corresponding ex vivo aortic samples. Tissue samples were evaluated to classify local wall weakening and likelihood of further degeneration based on non-invasive indices. A combined, image-based fluid dynamic and in-vivo strain analysis approach was used to estimate the Regional Aortic Weakness (RAW) index and assess individual aortas of AAA patients prior to elective surgery. Nine patients were treated with complete aortic resection allowing the systematic collection of tissue samples that were used to determine regional aortic mechanics, microstructure and gene expression by means of mechanical testing, microscopy and transcriptomic analyses. The RAW index was significantly higher for samples exhibiting lower mechanical strength (p = 0.035) and samples classified with low elastin content (p = 0.020). Samples with higher RAW index had the greatest number of genes differentially expressed compared to any constitutive metric. High RAW samples showed a decrease in gene expression for elastin and a down-regulation of pathways responsible for cell movement, reorganization of cytoskeleton, and angiogenesis. Please note that the sample 'characteristisc: strain' represents the in-vivo strain corresponding to each section of aorta, which is measured from dynamic CT images of patient AAA using a proprietary software.
2021-01-26 | GSE165470 | GEO