High Wall Shear Stress can Predict Wall Degradation in Ascending Aortic Aneurysms: An Integrated Biomechanics Study
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ABSTRACT:
SUBMITTER: Salmasi M
PROVIDER: S-EPMC8558434 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBicuspid aortic valve-associated ascending thoracic aortic aneurysms (BAV-aTAAs) carry a risk of acute type A dissection. Biomechanically, dissection may occur when wall stress exceeds wall strength. Our aim was to develop patient-specific computational models of BAV-aTAAs to determine magnitudes of wall stress by anatomic regions.MethodsPatients with BAV-aTAA diameter greater than 4.5 cm (n = 41) underwent electrocardiogram-gated computed tomography angiography. Three-dimensional aneurysm geometries were reconstructed after accounting for prestress and loaded to systemic pressure. Finite element analyses were performed with fiber-embedded hyperelastic material model using LS-DYNA software (LSTC Inc, Livermore, CA) to obtain wall stress distributions. The 99th percentile longitudinal and circumferential stresses were determined at systole.ResultsThe 99th percentile longitudinal wall stresses for BAV-aTAAs at sinuses of Valsalva, sinotubular junction (STJ), and ascending aorta were 361 ± 59.8 kPa, 295 ± 67.2 kPa, and 224 ± 37.6 kPa, respectively, with significant differences in ascending aorta vs sinuses (P< 1 × 10-13) and STJ (P < 1 × 10-6). The 99th percentile circumferential wall stresses were 474 ± 88.2 kPa, 634 ± 181.9 kPa, and 381 ± 54.0 kPa for sinuses, the STJ, and the ascending aorta, respectively, with significant differences in the ascending aorta vs sinuses (P = .002) and STJ (P < 1 × 10-13).ConclusionsWall stresses, both circumferential and longitudinal, were greater in the aortic root, sinuses, and STJ than in the ascending aorta on BAV-aTAAs. These results fill a fundamental knowledge gap regarding biomechanical stress distribution in BAV-aTAA patients, which when related to wall strength may provide prognostication of aTAA dissection risk by patient-specific modeling.
| S-EPMC8598319 | biostudies-literature
Project description:ObjectiveGuidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts.MethodsPatients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress.ResultsBicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007).ConclusionsCircumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction.
| S-EPMC8447844 | biostudies-literature
Project description:ObjectivesThe study objective was to evaluate the aortic wall stress and root dilatation before and after the novel V-shape surgery for the treatment of ascending aortic aneurysms and root ectasia.MethodsClinical cardiac computed tomography images were obtained for 14 patients [median age, 65 years (range, 33-78); 10 (71%) males] who underwent the V-shape surgery. For 10 of the 14 patients, the computed tomography images of the whole aorta pre- and post-surgery were available, and finite element simulations were performed to obtain the stress distributions of the aortic wall at pre- and post-surgery states. For 6 of the 14 patients, the computed tomography images of the aortic root were available at 2 follow-up time points post-surgery (Post 1, within 4 months after surgery and Post 2, about 20-52 months from Post 1). We analysed the root dilatation post-surgery using change of the effective diameter of the root at the two time points and investigated the relationship between root wall stress and root dilatation.ResultsThe mean and peak max-principal stresses of the aortic root exhibit a significant reduction, P=0.002 between pre- and post-surgery for both root mean stress (median among the 10 patients presurgery, 285.46 kPa; post-surgery, 199.46 kPa) and root peak stress (median presurgery, 466.66 kPa; post-surgery, 342.40 kPa). The mean and peak max-principal stresses of the ascending aorta also decrease significantly from pre- to post-surgery, with P=0.004 for the mean value (median presurgery, 296.48 kPa; post-surgery, 183.87 kPa), and P=0.002 for the peak value (median presurgery, 449.73 kPa; post-surgery, 282.89 kPa), respectively. The aortic root diameter after the surgery has an average dilatation of 5.01% in total and 2.15%/year. Larger root stress results in larger root dilatation.ConclusionsThis study marks the first biomechanical analysis of the novel V-shape surgery. The study has demonstrated significant reduction in wall stress of the aortic root repaired by the surgery. The root was able to dilate mildly post-surgery. Wall stress could be a critical factor for the dilatation since larger root stress results in larger root dilatation. The dilated aortic root within 4 years after surgery is still much smaller than that of presurgery.
| S-EPMC9159430 | biostudies-literature
Project description:Ascending thoracic aortic aneurysms (ATAAs) are anatomically complex in terms of architecture and geometry, and both complexities contribute to unpredictability of ATAA dissection and rupture in vivo. The goal of this work was to examine the mechanism of ATAA failure using a combination of detailed mechanical tests on human tissue and a multiscale computational model. We used (1) multiple, geometrically diverse, mechanical tests to characterize tissue properties, (2) a multiscale computational model to translate those results into a broadly usable form, and (3) a model-based computer simulation of the response of an ATAA to the stresses generated by the blood pressure. Mechanical tests were performed in uniaxial extension, biaxial extension, shear lap, and peel geometries. ATAA tissue was strongest in circumferential extension and weakest in shear, presumably because of the collagen and elastin in the arterial lamellae. A multiscale, fiber-based model using different fiber properties for collagen, elastin, and interlamellar connections was specified to match all of the experimental data with one parameter set. Finally, this model was used to simulate ATAA inflation using a realistic geometry. The predicted tissue failure occurred in regions of high stress, as expected; initial failure events involved almost entirely interlamellar connections, consistent with arterial dissection - the elastic lamellae remain intact, but the connections between them fail. The failure of the interlamellar connections, paired with the weakness of the tissue under shear loading, is suggestive that shear stress within the tissue may contribute to ATAA dissection.
| S-EPMC7104749 | biostudies-literature
Project description:Thoracic Aortic Aneurysm (TAA) is characterized by the dilation of the aorta and is fatal if not diagnosed and treated appropriately. The underlying genetic mechanisms have not been completely delineated, so better knowledge of the physiopathology of TAAs is needed to improve detection and therapy. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and are known to be involved in cardiovascular diseases (CVDs). The current study aimed to identify miRNAs that can be used as possible biomarkers for the early diagnosis of patients with ascending TAAs (ATAAs). MiRNA expression was profiled by NanoString nCounter technology using 12 samples including tissue and pre- and post-surgical plasma from ATAA patients. Four miRNAs were selected and further validated by real time polymerase chain reaction (RT-PCR) in 22 plasma samples from which three miRNAs (hsa-miR140-5p, hsa-miR-191-5p and hsa-miR-214-3p) showed significant expression level differences between the two types of plasma samples. Further analyses of the corresponding predicted target genes by these miRNAs, revealed two genes (Myotubularin-related protein 4 (MTMR4) and Phosphatase 1 catalytic subunit ? (PPP1CB)) whose expression was inversely correlated with the expression of their respective miRNAs. Overall, in this pilot study, we identified three miRNAs that might serve as potential biomarkers and therapeutic targets in ATAA.
| S-EPMC7385583 | biostudies-literature
Project description:An ascending aortic aneurysm (AscAA) is a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a potentially novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Additionally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 is sufficient to cause AscAA. RNA sequencing analysis of the Notch1.129S6+/- aortic root demonstrated gene expression changes consistent with AscAA. These findings are the first to our knowledge to demonstrate an SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.
| S-EPMC5752295 | biostudies-other
Project description:There has been increasing evidence that ascending thoracic aortic aneurysms (TAAs) protect against atherosclerosis. However, there have been no studies examining the relationship between ascending TAAs and clinical endpoints of atherosclerosis, such as stroke or peripheral arterial disease. In this study, we aim to characterize the relationship between TAAs and a specific clinical endpoint of atherosclerosis, myocardial infarction (MI). We compared prevalence of coronary artery disease (CAD) and MIs in 487 patients who underwent surgical repair for ascending TAAs to 500 control patients who did not have an ascending TAA. Multivariate binary logistic regression was used to calculate the odds of having MI if a patient had an ascending TAA versus any of several MI risk factors. There was a significantly lower prevalence of CAD and MI in the ascending TAA group than in the control TAA group. The odds of having a MI if a patient had a MI risk factor were all > 1 (more likely to have a MI), with the lowest statistically significant odds ratio being 1.54 (age; p = 0.001) and the highest being 14.9 (family history of MI; p < 0.001). The odds ratio of having a MI if a patient had an ascending TAA, however, was near 0 at 0.05 (p < 0.001). This study provides evidence that ascending TAAs protect against MIs, adding further support to the hypothesis that ascending TAAs protect against atherosclerotic disease.
| S-EPMC4169096 | biostudies-other
Project description:The bicuspid aortic valve is the most common congenital cardiac anomaly in developed nations. The abnormal bicuspid morphology of the aortic valve results in valvular dysfunction and subsequent hemodynamic derangements. However, the clinical presentation of bicuspid aortic valve disease remains quite heterogeneous with patients presenting from infancy to late adulthood with variable degrees of valvular stenosis and insufficiency and associated abnormalities including aortic coarctation, hypoplastic left heart structures, and ascending aortic dilatation. Emerging evidence suggests that the heterogeneous presentation of bicuspid aortic valve phenotypes may be a more complex matter related to congenital, genetic, and/or connective tissue abnormalities. Optimal management of patients with BAV disease and associated ascending aortic aneurysms often requires a thoughtful approach, carefully assessing various risk factors of the aortic valve and the aorta and discerning individual indications for ongoing surveillance, medical management, and operative intervention. We review current concepts of anatomic classification, pathophysiology, natural history, and clinical management of bicuspid aortic valve disease with associated ascending aortic aneurysms.
| S-EPMC3503270 | biostudies-other
Project description:Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the enlargement of the infrarenal segment of the aorta. A ruptured AAA can cause internal bleeding and carries a high mortality rate, which is why the clinical management of the disease is focused on preventing aneurysm rupture. AAA rupture risk is estimated by the change in maximum diameter over time (i.e., growth rate) or if the diameter reaches a prescribed threshold. The latter is typically 5.5 cm in most clinical centers, at which time surgical intervention is recommended. While a size-based criterion is suitable for most patients who are diagnosed at an early stage of the disease, it is well known that some small AAA rupture or patients become symptomatic prior to a maximum diameter of 5.5 cm. Consequently, the mechanical stress in the aortic wall can also be used as an integral component of a biomechanics-based rupture risk assessment strategy. In this work, we seek to identify geometric characteristics that correlate strongly with wall stress using a sample space of 100 asymptomatic, unruptured, electively repaired AAA models. The segmentation of the clinical images, volume meshing, and quantification of up to 45 geometric measures of each AAA were done using in-house Matlab scripts. Finite element analysis was performed to compute the first principal stress distributions from which three global biomechanical parameters were calculated: peak wall stress, 99th percentile wall stress and spatially averaged wall stress. Following a feature reduction approach consisting of Pearson's correlation matrices with Bonferroni correction and linear regressions, a multivariate stepwise regression analysis was conducted to find the geometric measures most highly correlated with each of the biomechanical parameters. Our findings indicate that wall stress can be predicted by geometric indices with an accuracy of up to 94% when AAA models are generated with uniform wall thickness and up to 67% for patient specific, non-uniform wall thickness AAA. These geometric predictors of wall stress could be used in lieu of complex finite element models as part of a geometry-based protocol for rupture risk assessment.
| S-EPMC6610879 | biostudies-literature
Project description:ObjectiveThe need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress.MethodsSerum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair.ResultsPro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue-and serum MMP-2 isoforms, nor any indication that pro-MMP-2 functions as a common marker of high aortic wall stress.
| S-EPMC5089694 | biostudies-literature