Abdominal Aortic Aneurysm Growth Research Articles

Can Biomarkers and PET Imaging Predict Abdominal Aortic Aneurysm Growth Rate?

Background: Abdominal aortic aneurysm (AAA) is a life-threatening condition due to the risk of aneurysm growth and rupture. Biomarkers linked to AAA pathogenesis are attractive candidates for AAA diagnosis and prognosis. The aim of this study was to assess circulating biomarkers levels relationship with PET imaging positivity and their predictive value in AAA growth rate. Methods: A total of 164 patients with AAA had whole body [18F]FDG PET/CT examination and blood drawn for biomarkers analysis at inclusion. Of these, 121 patients had at least one follow-up imaging assessment for AAA progression. Median (quartiles) imaging follow-up period was 32.8 months (15.2-69.6 months). Results: At baseline, PET was visually positive in 28 (17%) patients. Among PET+ patients, female proportion was higher compared to PET-patients (respectively, n = 6, 21.4% vs. n = 11, 8.1%, p = 0.046). Biomarkers of inflammation (CRP, CCL18), of proteolytic activity (MMP9), of extracellular matrix, and calcification regulation (OPN, OPG) were all significantly increased in PET+ patients (p < 0.05). During follow-up, rapid AAA growth (increase in size ≥ 1 cm per year) was observed in 36 (29.8%) patients and several biomarkers (CRP, MMP9, OPN, and OPG) were increased in those patients compared to patients without rapid growth (p < 0.05). Conclusions: Although PET positivity at baseline was not associated with rapid growth, CRP levels showed a significant association.

In vivo bistatic dual-aperture ultrasound imaging and elastography of the abdominal aorta.

Introduction: In this paper we introduce in vivo multi-aperture ultrasound imaging and elastography of the abdominal aorta. Monitoring of the geometry and growth of abdominal aortic aneurysms (AAA) is paramount for risk stratification and intervention planning. However, such an assessment is limited by the lateral lumen-wall contrast and resolution of conventional ultrasound. Here, an in vivo dual-aperture bistatic imaging approach is shown to improve abdominal ultrasound and strain imaging quality significantly. By scanning the aorta from different directions, a larger part of the vessel circumference can be visualized. Methods: In this first-in-man volunteer study, the performance of multi-aperture ultrasound imaging and elastography of the abdominal aortic wall was assessed in 20 healthy volunteers. Dual-probe acquisition was performed in which two curved array transducers were aligned in the same imaging plane. The transducers alternately transmit and both probes receive simultaneously on each transmit event, which allows for the reconstruction of four ultrasound signals. Automatic probe localization was achieved by optimizing the coherence of the trans-probe data, using a gradient descent algorithm. Speckle-tracking was performed on the four individual bistatic signals, after which the respective axial displacements were compounded and strains were calculated. Results: Using bistatic multi-aperture ultrasound imaging, the image quality of the ultrasound images, i.e., the angular coverage of the wall, was improved which enables accurate estimation of local motion dynamics and strain in the abdominal aortic wall. The motion tracking error was reduced from 1.3 mm ± 0.63 mm to 0.16 mm ± 0.076 mm, which increased the circumferential elastographic signal-to-noise ratio (SNRe) by 12.3 dB ± 8.3 dB on average, revealing more accurate and homogeneous strain estimates compared to single-perspective ultrasound. Conclusion: Multi-aperture ultrasound imaging and elastography is feasible in vivo and can provide the clinician with vital information about the anatomical and mechanical state of AAAs in the future.

A highly selective mPGES-1 inhibitor to block abdominal aortic aneurysm progression in the angiotensin mouse model

Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E2 synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E2 (PGE2)—a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first time that a highly selective mPGES-1 inhibitor (UK4b) can completely block further growth of AAA in the ApoE−/− angiotensin (Ang)II mouse model. Our findings show promise for the use of a mPGES-1 inhibitor like UK4b as interventional treatment of AAA and its potential translation into the clinical setting.

Comment on: Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.

Comment on: Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.

Evaluating growth patterns of abdominal aortic aneurysms among women

ObjectiveThough initially protected from vessel dilation by estrogen, women may experience rapid abdominal aortic aneurysm (AAA) growth post-menopause. The rate of growth has been poorly defined in prior literature. Here, we describe aneurysm growth in a cohort of women found through an AAA screening program. MethodsWomen with AAAs were retrospectively identified. Aortic imaging was reviewed, and measurements of maximum transverse and anterior-posterior diameters were completed. Growth was stratified by the type of aortic pathology (fusiform aneurysm, aortic ectasia, dissection with aneurysmal degeneration, saccular aneurysm) as well as size category (<3 cm, 3.0-3.9 cm, 4.0-4.9 cm, ≥5.0 cm) at diagnosis. ResultsA cohort of 488 women was identified; 286 had multiple scans for review. The mean age of the entire cohort was 75 ± 9.9 years. Stratified by type of pathology, the mean age was 76 ± 8.9 years in patients with a fusiform AAA, 74 ± 9.8 years in ectasia, 65 ± 13.7 years in dissection, and 76 ± 5.6 years in saccular aneurysms. The maximum growth was highest in women with fusiform AAAs, followed by dissection, ectasia, and saccular pathology (9.7 mm, 7.0 mm, 3.0 mm, and 2.2 mm, respectively; P < .001). Comparing mean growth by year, the highest mean growth was in fusiform AAAs (3.6 mm vs 1.75 mm in dissection; P < .001). The Shapiro-Wilk test demonstrated that mean growth per year was non-normally distributed with a right skew. Stratified by aortic diameter at the time of diagnosis, mean growth/year increased with increasing size at diagnosis in fusiform AAAs and dissection (0.91 mm for <3 cm, 2.34 mm for 3.0-3.9 cm, 2.49 mm for 4.0-4.9 mm, and 6.16 mm for ≥5.0 cm in patients with fusiform AAAs vs 0.57 mm, 0.94 mm, 1.87 mm, and 2.66 mm, respectively, for patients with dissection). Smoking history was associated with a higher mean growth/year (2.6 mm vs 3.3 mm; P < .001). Conversely, patients with a family history of AAA had a lower mean growth/year (3.2 mm vs 1.5 mm; P < .001). ConclusionsThe rate of aneurysm growth in women varies based on pathology and aneurysm size, and women experience rapid aneurysm growth at sizes greater than 4.5 cm. Current screening guidelines are inadequate, and our results demonstrate that the rate of growth of fusiform aneurysms in women is faster than in men at a smaller size and may warrant more frequent surveillance than current Society for Vascular Surgery recommendations to prevent risk of increased morbidity.

Association of metformin use with abdominal aortic aneurysm: A systematic review and meta-analysis.

Abdominal aortic aneurysm (AAA) is a cardiovascular disease characterized by a high mortality rate when ruptured. Some studies suggest a potential inverse correlation between AAA and diabetes patients, especially those undergoing metformin treatment. However, this relationship remains unclear. This paper offers a systematic review and meta-analysis with the objective of clarifying the influence of metformin on AAA. A search for relevant articles was performed across multiple databases including PubMed, ScienceDirect, Cochrane and Scopus. The focus was on studies that examined the comparative effects of metformin and non-metformin treatments on AAA patients. Data from appropriate studies were consolidated to estimate the effects. Our study encompassed 11 articles, comprising 13 cohorts that compared metformin (n = 32,250) with a control group (n = 116,339). The random effects meta-analysis revealed that metformin was associated with a slower growth rate (weighted mean difference (WMD) -0.86 mm; 95% CI: -1.21 to -0.52; p < 0.01; I2: 81.4%) and fewer AAA-related events (OR: 0.54; 95% CI: 0.34 to 0.86; p = 0.01; I2: 60.9%). The findings suggest that metformin may be linked to a reduced risk of aortic aneurysm. A meta-regression analysis indicated that the association between metformin and AAA growth was significantly influenced by male gender (p = 0.027), but not by age (p = 0.801), hypertension (p = 0.256), DM (p = 0.689), smoking history (p = 0.786), use of lipid-lowering agents (p = 0.715), or baseline diameter (p = 0.291). These results hint at a potential role for metformin in limiting annual AAA growth, AAA-related events, and the risk of AAA.

Endovascular aortic repair with sac embolization for the prevention of type II endoleaks (the EVAR-SE study): study protocol for a randomized controlled multicentre study in Germany

BackgroundBeyond a certain threshold diameter, abdominal aortic aneurysms (AAA) are to be treated by open surgical or endovascular aortic aneurysm repair (EVAR). In a quarter of patients who undergo EVAR, inversion of blood flow in the inferior mesenteric artery or lumbar arteries may lead to type II endoleak (T2EL), which is associated with complications (e.g. AAA growth, secondary type I endoleak, rupture). As secondary interventions to treat T2EL often fail and may be highly invasive, prevention of T2EL is desirable. The present study aims to assess the efficacy of sac embolization (SE) with metal coils during EVAR to prevent T2EL in patients at high risk.MethodsOver a 24-month recruitment period, a total of 100 patients undergoing EVAR in four vascular centres (i.e. Klinikum rechts der Isar of the Technical University of Munich, University Hospital Augsburg, University Hospital Dresden, St. Joseph’s Hospital Wiesbaden) are to be included in the present study. Patients at high risk for T2EL (i.e. ≥ 5 efferent vessels covered by endograft or aneurysmal thrombus volume <40%) are randomized to one group receiving standard EVAR and another group receiving EVAR with SE. Follow-up assessments postoperatively, after 30 days, and 6 months involve contrast-enhanced ultrasound scans (CEUS) and after 12 months an additional computed tomography angiography (CTA) scan. The presence of T2EL detected by CEUS or CTA after 12 months is the primary endpoint. Secondary endpoints comprise quality of life (quantified by the SF-36 questionnaire), reintervention rate, occurrence of type I/III endoleak, aortic rupture, death, alteration of aneurysm volume, or diameter. Standardized evaluation of CTA scans happens through a core lab. The study will be terminated after the final follow-up visit of the ultimate patient.DiscussionAlthough preexisting studies repeatedly indicated a beneficial effect of SE on T2EL rates after EVAR, patient relevant outcomes have not been assessed until now. The present study is the first randomized controlled multicentre study to assess the impact of SE on quality of life. Further unique features include employment of easily assessable high-risk criteria, a contemporary follow-up protocol, and approval to use any commercially available coil material. Overcoming limitations of previous studies might help SE to be implemented in daily practice and to enhance patient safety.Trial registration ClinicalTrials.gov NCT05665101. Registered on 23 December 2022.

Antiplatelet or Anticoagulant Therapy for Abdominal Aortic Aneurysms: Growth and Clinical Outcomes.

Intraluminal thrombi in the abdominal aortic aneurysms (AAA) were demonstrated to increase aneurysm growth. The effect of treatments on thrombus reduction upon AAA enlargement and clinical endpoints is uncertain Therefore, this study aimed to investigate the effect of antiplatelet and anticoagulant therapy on AAA growth and clinical outcomes. A total of 357 patients with AAAs were enrolled in this study. They were divided into 2 groups based on their medical therapies. Patients on antiplatelet and anticoagulant therapy were assigned to group 1 (n = 234) and group 2 (n = 92), respectively. The greatest reduction in thrombus diameter change was observed in patients with anticoagulant therapy (group 1, -2.26 mm; group 2, -8.16 mm; P =.001). The greatest aneurysmal enlargement was found in patients with antiplatelet therapy. There was less AAA progression with anticoagulant therapy than with the other therapy (group 1, 2.08 mm; group 2, 1.31 mm P =.027. The more operational need was observed in patients with antiplatelet therapy than in patients with anticoagulant therapy ( group 1 67, group 2 16, P =.036) Conclusion: In our study, it was revealed that anticoagulant therapy has been associated with decreased thrombus diameter and less aneurysmal enlargement compared with antiplatelet therapy. Furthermore, this beneficial effect on the thrombus size and aneurysmal diameter decreased the operational need in patients with anticoagulant therapy.

Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis.

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models. Mechanistically, colchicine increased global mRNA stability by inhibiting the METTL14/YTHDC1-mediated m6A modification, resulting in increased sclerostin (SOST) expression and consequent inactivation of the WNT/β-catenin signaling pathway in vascular SMCs from mouse AAA lesions and in cultured human aortic SMCs. Moreover, human and mouse AAA lesions all showed increased m6A methylation, decreased SOST expression, and skewed synthetic SMC de-differentiation phenotype, compared to those without AAA. This study uncovers a novel mechanism of colchicine in slowing AAA development by using the METTL14/SOST/WNT/β-catenin axis to control vascular SMC homeostasis in mouse aortic vessels and in human aortic SMCs. Therefore, use of colchicine may benefit AAA patients in clinical practice.

Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.

There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery. Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models. A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) -0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) -0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) -0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) -0.307(0.09) mm/year, P = 0.00078). The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates.

Role of Common Antihypertensives in the Growth of Abdominal Aortic Aneurysm at the Presurgical Stage.

Background: Whether drug therapy slows the growth of abdominal aortic aneurysms (AAAs) in the Japanese population remains unknown. Methods and Results: In a multicenter prospective open-label study, patients with AAA at the presurgical stage (mean [±SD] AAA diameter 3.27±0.58 cm) were randomly assigned to treatment with candesartan (CAN; n=67) or amlodipine (AML; n=64) considering confounding factors (statin use, smoking, age, sex, renal function), with effects of blood pressure control minimized setting a target control level. The primary endpoint was percentage change in AAA diameter over 24 months. Secondary endpoints were changes in circulating biomarkers (high-sensitivity C-reactive protein [hs-CRP], malondialdehyde-low-density lipoprotein, tissue-specific inhibitor of metalloproteinase-1, matrix metalloproteinase [MMP] 2, MMP9, transforming growth factor-β1, plasma renin activity [PRA], angiotensin II, aldosterone). At 24 months, percentage changes in AAA diameter were comparable between the CAN and AML groups (8.4% [95% CI 6.23-10.59%] and 6.5% [95% CI 3.65-9.43%], respectively; P=0.23]. In subanalyses, AML attenuated AAA growth in patients with comorbid chronic kidney disease (CKD; P=0.04) or systolic blood pressure (SBP) <130 mmHg (P=0.003). AML exhibited a definite trend for slowing AAA growth exclusively in never-smokers (P=0.06). Among circulating surrogate candidates for AAA growth, PRA (P=0.02) and hs-CRP (P=0.001) were lower in the AML group. Conclusions: AML may prevent AAA growth in patients with CKD or lower SBP, associated with a decline in PRA and circulating hs-CRP.

Abstract 18373: Differential Effects of Hypertension and Aneurysm on Stiffness Properties of the Abdominal Aorta

Introduction: The serum and glucocorticoid inducible kinase-1 (SGK-1) can contribute to matrix remodeling in murine models of hypertension (HTN) and abdominal aortic aneurysm (AAA), a potential biomechanical link between these aortopathies. Utilizing aortic stiffness as a marker of pathologic remodeling. Hypothesis: We hypothesize that HTN causes an SGK-1 dependent increase in aortic stiffness to amplify AAA growth. Methods: AngiotensinII (AngII) infusion induced HTN in C57Bl/6 mice (WT;1.46mg/kg/day) with subset groups treated + periadventitial CaCl2 to induce AAA and + infusion of the specific SGK-1 inhibitor EMD638683 (2.5mg/kg/day;n=2-4 each). Abdominal aortic ultrasound was conducted on Day 0 and Day 21 to measure stiffness parameters (radial strain(RS), distensibility(D), pulse propagation velocity(PPV)). Aortic diameter (AoD) was obtained by ultrasound and systolic blood pressures (SBP) were measured by Coda tail cuff. Results: This HTN model has consistently resulted in &gt;30% increase in SBP and AAA induction did not effect SBP. Although the WT+AngII+AAA mice had 66+8% increase in AoD, dilation was not amplified beyond that of the WT+AAA mice (72+7%, p=NS). Treatment with EMD had no impact on SBP, but did significantly reduce AAA growth (WT+AAA+EMD=29+5%; WT+AngII+AAA+EMD= 24+3%), therefore despite ongoing mechanical tension, SGK-1 inhibition abrogated a pathway necessary for degenerative remodeling. Accordingly, aortic stiffness was differentially altered in HTN versus AAA. As indictors of increased stiffness, D decreased with HTN (p&lt;0.05 vs Day 0) and RS decreased with AAA (p&lt;0.05 vs Day 0), but SGK-1 inhibition had no effect, indicating that the matrix remodeling driving these mechanical parameters was not SGK-1 dependent. Conversely, PPV was increased in both aortopathies (WT+AAA, WT+AngII, WT+AngII+AAA; each p&lt;0.05 vs Day 0) but EMD infusion prevented elevation in PPV, suggesting SGK-1-dependent preservation of contractility. Conclusions: Although concurrent induction of HTN and AAA did not amplify AAA growth, these aortopathies differentially impacted aortic stiffness. Tracking PPV as an indicator of pathologic SGK-1 activity may represent a pharmacological target to abrogate dysfunctional aortic remodeling.

Abstract 18814: Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms

Objective: Abdominal aortic aneurysms (AAA) frequently feature the formation of a nonocclusive intraluminal thrombus (ILT) along the site of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understand. Thus, we sought to investigate how platelet activation via the glycoprotein VI (GPVI) platelet receptor impacts the pathogenesis of AAA. Methods and Results: RNA sequencing of age-matched control human aortic tissue, AAA aortic tissue, and AAA ILT demonstrates that platelet transcripts comprised 25% of significantly enriched genes AAA thrombus compared to AAA tissue and control aortic wall, with GPVI increased by 9.1 Log2-FC (P = 3.21E -08 ). Examination of soluble GPVI (sGPVI), a specific marker of platelet activity, in 2 independent AAA patient cohorts is predictive of AAA case status, associates strongly with aneurysm growth rate, and better predicts the presence of a fast-growing AAA when compared to D-dimer. To determine if GPVI blockade ameliorates AAA progression, mice were subjected to either the angiotensin II (AngII) infusion or the topical elastase models of aneurysm formation. Following model initiation, aortic diameter was monitored by weekly ultrasounds. After two weeks, mice which developed an aneurysm (defined as an aortic diameter of &gt;1.2mm) were randomized into control (IgG-50μg) or treatment (JAQ1-50μg, monoclonal GPVI antibody) groups. Treatment with JAQ1 blunted GPVI mediated platelet activation, attenuated aneurysm progression, and increased survival in both murine AAA models versus control. Conclusions: The highly specific platelet activation biomarker soluble glycoprotein VI strongly predicts both AAA case status and growth rate with potential use in identifying high risk patients. Specific blockade of GPVI-mediated platelet activation attenuates progression of established aneurysms in two independent murine models. Thus, our work demonstrates that specific targeting of GPVI to blunt platelet activation in AAA could be a potential therapeutic for a pathology with no current pharmacological treatments.

Abstract 17672: Implications of Pcsk9 on Abdominal Aortic Aneurysm

Objective: Recent genome-wide association studies revealed a potential role of proprotein convertase subtilisin/kexin type9(Pcsk9) in the human abdominal aortic aneurysm(AAA) disease.Altered Pcsk9 gene expression and smaller AAA diameter were observed in murine AAA using the porcine pancreatic elastase(PPE) model in our lab. Pcsk9 increases plasma LDL-cholesterol,enhances tissue inflammation and induces vascular smooth muscle cell (VSMC) senescence, hallmarks in AAA.However, the exact cellular mechanisms of Pcsk9 in AAA disease remain unclear.Despite the absence of a pharmacological treatment for AAA, monoclonal Pcsk9 antibody therapies have proven effective against statin-resistant hypercholesterolemia.This study aimed to explore the impacts of Pcsk9 on aortic vascular inflammation and VSMC dedifferentiation with a view to better understanding AAA pathophysiology and providing a basis for future investigations into Pcsk9 inhibitors. Hypothesis: We hypothesized that local vascular injury escalates Pcsk9 expression,amplifying vascular inflammation and driving VSMC towards dedifferentiation that further advances AAA. Conversely,Pcsk9 inhibition will mitigate these processes. Methods: AAA was induced by PPE model in wildtype C57Bl/6 mice and Pcsk9 knock-out (KO)mice.Sonography was used to evaluate the aneurysm growth. Single-cell RNA sequencing was employed to examine local changes in the aortic wall. Local vascular Pcsk9,pro-inflammatory and VSMC marker gene/protein expression were quantified using qPCR and immunohistochemistry.VSMCs were treated with exogenous Pcsk9 in vitro to assess metabolism via Seahorse. Results: Reduced AAA diameters were observed in Pcsk9 KO mice compared to wildtype controls. Significant upregulation of local Pcsk9 expression accompanied AAA induction. Single-cell RNA sequencing revealed altered gene expression profiles across vascular cell populations. In vitro,VSMCs displayed changes in marker gene/protein expression after treatment with exogenous Pcsk9, alongside metabolic changes (Mann-Whitney Test). Conclusions: The findings suggest a significant role of Pcsk9 in AAA pathogenesis. Its inhibition appears to mitigate AAA growth,indicating a promising treatment target for AAA.

Abdominal aortic aneurysms volume growth patterns with three-dimensional ultrasound.

Three-dimensional ultrasound (3D-US) and computed tomography (CT) have proven abdominal aortic aneurysm (AAA) volume a more sensitive measure of growth than diameter. This proof-of-concept study aimed to investigate the clinical applicability of two-dimensional ultrasound and 3D-US for AAA diameter and volume growth pattern evaluation. AAA patients with at least three follow-ups within a minimum of 24 months were included prospectively and consecutively from the COpenhagen Aneurysms CoHort (COACH). Individual diameter and volume growth rates were categorized as rapid, slow, or no growth (>6.0, 3.8-6.0, and ≤3.7 mm/year for diameter. >17.4, 8.8-17.3, and ≤8.7 mL/year for volume). Similarly, diameter and volume growth patterns were categorized as as linear, exponential, staccato, and indeterminate growth, based from individual regressions. Thirty patients were included, of which 19 (63%) had no diameter growth, 10 (33%) had slow growth, and one (3%) had rapid growth. Regarding volume, 11 (37%) patients had no growth, 12 (40%) had slow growth, and seven (23%) had rapid growth. Growth patterns according to diameter showed that 18 (60%) patients had linear growth, none had staccato or exponential growth. Twelve (40%) were indeterminate. Volume growth patterns found 19 (63%) patients with linear growth, 3 (10%) with staccato, and none with exponential growth. Eight (27%) were indeterminate. Analysis of AAA volume growth patterns is a practical and safe modality that seems more sensitive at detecting growth patterns than AAA diameter. Volume also detects more AAA growth than diameter.

Radiation therapy for cancer is potentially associated with reduced growth of concomitant abdominal aortic aneurysm

PurposeCo-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency.MethodsA retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort.ResultsBetween 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association.ConclusionIn this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate /PP with the current AAA assessment methods of maximal diameter and growth rate. Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce /PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on /PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher /PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in /PP. When divided into terciles based on /PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). There was no correlation between AAA diameter and /PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of /PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of /PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.

Biomechanics of abdominal aortic aneurysm in the framework of Windkessel effect and fully-developed inflow velocity via two-way non-linear FSI

Abdominal aortic aneurysm (AAA) is a pathological condition characterised by localised dilation of the infrarenal aorta, which can be fatal if rupture occurs. Current diagnostic criteria for repair are not patient-specific, but computational modelling may help to predict the potential growth and risk of AAA rupture accurately. This paper highlights how important using the Windkessel effect and fully-developed inflow velocity framework for the biomechanical analysis of AAA is; in other words, this research investigates how different boundary conditions in modelling methods affect the ability to correctly represent the biomechanics of AAA with complex non-linear parameters using a two-way fluid–structure interaction (FSI) technique. Time-averaged wall shear stress (TAWSS) is highly sensitive to boundary conditions, so unrealistic or simplified boundary conditions can lead to very different TAWSS results. This study also revealed that the use of outflow 3-element Windkessel boundary conditions on pulsatile pressure affects the flow pattern and increases the flow recirculation period. By accounting for the Windkessel effect and preventing backflow in numerical studies of AAA, the maximum displacement found in the distal branches can also be reduced. Models assuming plug velocity profiles overestimate peak wall stress by approximately 20% compared with models using fully developed parabolic inlet velocity profiles. This study incorporated a three-layer anisotropic material model and non-Newtonian fluid properties into the simulation, providing a more realistic representation of the effect of boundary condition selection on AAA mechanics. The results summarised from the parametric study could contribute to better prediction of AAA growth and rupture risk, and have important implications for the development of improved treatment strategies for AAA patients.

Abstract P3016: Pathologic Matrix Markers Are Differentially Modulated By VSMC-Specific SGK-1 Activity In Hypertension And Abdominal Aortic Aneurysm

Introduction: The VSMC switch to synthetic phenotype promotes aortic pathology such as hypertension (HTN) and abdominal aortic aneurysm (AAA). Mechanical activation of serum and glucocorticoid inducible kinase-1 (SGK-1) alters the VSMC synthetic profile to promote remodeling. Plasma biomarkers may represent opportunities to assess VSMC function in aortic disease, and we hypothesize that analysis of a panel of plasma pathologic matrix markers (PMM) representing synthetic VSMC phenotype can reflect SGK-1-dependent activity. Methods: HTN was induced in wild-type C57Bl/6 (WT) and smooth muscle cell specific SGK-1 knockout (SMC-SGK-1KO +/- ) mice with AngiotensinII infusion (1.46mg/kg/day, n=4-6). Separate mice underwent AAA induction by peri-adventitial CaCl 2 application (n=4-6). Terminal procedure included collecting systolic blood pressure (SBP), aortic diameter (AoD), and plasma. ELISA for PMMs included Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), Cathepsin S (CtsS), and Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). Impact of the panel was evaluated by a composite T-score. Statistics included T-test and ANOVA. Results: WT+HTN had &gt;30% increased SBP and elevation of IL-6, CtsS, CysC, and TNC (p&lt;0.05). SMC-SGK-1KO +/- +HTN had equally elevated SBP, but no change in PMMs, suggesting that SGK-1 contributed to HTN-induced VSMC synthetic activity. WT+AAA had &gt;65% increased AoD and elevation of all PMMs (p&lt;0.05). Alternatively, SMC-SGK-1KO +/- +AAA had abrogated growth (29.4 + 3.6%, p&lt;0.05 vs WT and WT+AAA) with IL-6, CtsS, CysC, and TNC returning to baseline, suggesting that SGK-1-dependent production of these PMMS was necessary for true AAA growth. Composite T-scores differed between Control, HTN, and AAA in WT mice (0.78 + 0.08 vs 2.91 + 0.29 vs 7.11 + 0.71 respectively, p&lt;0.05). In SMC-SGK-1KO +/- mice, T-score normalized in HTN but remained elevated in AAA (2.19 + 0.21, p&lt;0.05 vs Control and WT+AAA), attributable to the elevations in MMP-9 and OPG, peptides produced by inflammatory infiltrate. Conclusion: A panel of PMMs can be scored to reflect synthetic activity of VSMCs in aortic pathology, as well as response to inhibition, and warrants further investigation for the clinical care of patients with vascular disease.

Comparing maximum diameter and volume when assessing the growth of small abdominal aortic aneurysms using longitudinal CTA data: cohort study.

Monitoring of abdominal aortic aneurysms (AAAs) is currently based on serial measurements of maximum aortic diameter. Additional assessment of aneurysm volume has previously been proposed to possibly improve growth prediction and treatment decisions. To evaluate the use of supplementing volume measurements, the authors aimed to characterise the growth distribution of AAA volume and to compare the growth rates of the maximum diameter and volume at the patient level. Maximum diameter and volume were monitored every 6 months in 84 patients with small AAAs, with a total of 331 computed tomographic angiographies (with initial maximum diameters of 30-68mm). A previously developed statistical growth model for AAAs was applied to assess the growth distribution of volume and to compare individual growth rates for volume and for maximum diameter. The median (25-75% quantile) expansion in volume was 13.4 (6.5-24.7) % per year. Cube root transformed volume and maximum diameter showed a closely linear association with a within-subject correlation of 0.77. At the surgery threshold maximum diameter of 55mm, the median (25-75% quantile) volume was 132 (103-167)ml. In 39% of subjects, growth rates for volume and maximum diameter were equivalent, in 33% growth was faster in volume and in 27% growth was faster in maximum diameter. At the population level, volume and maximum diameter show a substantial association such that the average volume is approximately proportional to the average maximum diameter raised to a power of three. At the individual level, however, in the majority of patient's AAAs grow at different pace in different dimensions. Hence, closer monitoring of aneurysms with sub-critical diameter but suspicious morphology may benefit from complementing maximum diameter by volume or related measurements.