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Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling.

ABSTRACT: Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group.

SUBMITTER: Cuomo F

PROVIDER: S-EPMC5333881 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Detecting Regional Stiffness Changes in Aortic Aneurysmal Geometries Using Pressure-Normalized Strain.

Project description:Transabdominal ultrasound elasticity imaging could improve the assessment of rupture risk for abdominal aortic aneurysms by providing information on the mechanical properties and stress or strain states of vessel walls. We implemented a non-rigid image registration method to visualize the pressure-normalized strain within vascular tissues and adapted it to measure total strain over an entire cardiac cycle. We validated the algorithm's performance with both simulated ultrasound images with known principal strains and anatomically accurate heterogeneous polyvinyl alcohol cryogel vessel phantoms. Patient images of abdominal aortic aneurysm were also used to illustrate the clinical feasibility of our imaging algorithm and the potential value of pressure-normalized strain as a clinical metric. Our results indicated that pressure-normalized strain could be used to identify spatial variations in vessel tissue stiffness. The results of this investigation were sufficiently encouraging to warrant a clinical study measuring abdominal aortic pressure-normalized strain in a patient population with aneurysmal disease.

| S-EPMC5562537 | biostudies-literature

Impact of age, sex, and global function on normal aortic hemodynamics.

Project description:PurposeTo examine the effects of age, sex, and left ventricular global function on velocity, helicity, and 3D wall shear stress (3D-WSS) in the aorta of N = 100 healthy controls.MethodsFifty female and 50 male volunteers with no history of cardiovascular disease, with 10 volunteers per age group (18-30, 31-40, 41-50, 51-60, and 61-80 years) underwent aortic 4D-flow MRI. Quantification of systolic aortic peak velocity, helicity, and 3D-WSS distribution and the calculation of age group-averaged peak systolic velocity and 3D-WSS maps ("atlases") were computed. Age-related and sex-related changes in peak velocity, helicity, and 3D-WSS were computed and correlated with standard metrics of left ventricular function derived from short-axis cine MRI.ResultsNo significant differences were found in peak systolic velocity or 3D-WSS based on sex except for the 18- to 30-year-old group (males 8% higher velocity volume and 3D-WSS surface area). Between successively older groups, systolic velocity decreased (13%, <1%, 7%, and 55% of the aorta volume) and 3D-WSS decreased (21%, 2%, 30%, and 62% of the aorta surface area). Mean velocity, mean 3D-3D-WSS, and median helicity increased with cardiac output (r = 0.27-0.43, all P < .01), and mean velocity and 3D-WSS decreased with increasing diameter (r > 0.35, P < .001). Arch and descending aorta systolic mean velocity, mean 3D-WSS, and median helicity increased with normalized left ventricular volumes: end diastolic volume (r = 0.31-0.37, P < .01), end systolic volume (r = 0.27-0.35, P < .01), and stroke volume (r = 0.28-0.35, P < .01).ConclusionHealthy aortic hemodynamics are dependent on subject age, and correlate with vessel diameter and cardiac function.

| S-EPMC7751625 | biostudies-literature

Aortic stiffness

Project description:BACKGROUND: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters. METHODS AND RESULTS: In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell. CONCLUSIONS: Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated. Keywords: other

2003-08-28 | GSE420 | GEO

Acute Effects of Transcatheter Aortic Valve Replacement on Central Aortic Hemodynamics in Patients With Severe Aortic Stenosis.

Project description:Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were increases in systolic, diastolic, mean, and pulse aortic pressures (all P<0.05). Post-TAVR reservoir pressure was unchanged (54.5±12.4 versus 56.6±14.0 mm Hg, P=0.30) whereas excess pressure increased 47% (29.0±10.9 versus 42.6±15.5 mm Hg, P<0.001). Wave intensity analysis (arbitrary units, au) demonstrated increased forward compression wave (64.9±35.5 versus 124.4±58.9, ×103 au, P<0.001), backward compression wave (11.6±5.5 versus 14.4±6.9, ×103 au, P=0.01) and forward expansion wave energies (43.2±27.3 versus 82.8±53.1, ×103 au, P<0.001). Subendocardial viability ratio improved with aortic function effectively unchanged post-TAVR. Increased central aortic pressure following TAVR relates to increased transmitted power and energy to the proximal aorta with increased excess pressure but unchanged reservoir pressure. These changes provide a potential mechanism for the improved prognosis associated with relative hypertension post-TAVR.

| S-EPMC7224985 | biostudies-literature

Characterization of hemodynamics in anomalous aortic origin of coronary arteries using patient-specific modeling.

Project description:The anomalous aortic origin of coronary arteries (AAOCA) is a congenital disease that can lead to sudden cardiac death (SCD) during strenuous physical activity. Despite AAOCA being the second leading cause of SCD among young athletes, the mechanism behind sudden cardiac death remains mostly unknown. Computational fluid dynamics provides a powerful tool for studying how pathologic anatomy can affect different hemodynamic states. The present study investigates the effect of AAOCA on patient hemodynamics. We performed patient-specific hemodynamic simulations of interarterial AAOCA at baseline and in the exercise state using our massively parallel flow solver. Additionally, we investigate how surgical correction via coronary unroofing impacts patient blood flow. Results show that patient-specific AAOCA models exhibited higher interarterial time-averaged wall shear stress (TAWSS) values compared to the control patients. The oscillatory shear index had no impact on AAOCA. Finally, the coronary unroofing procedure normalized the elevated TAWSS by decreasing TAWSS in the postoperative patient. The present study provides a proof of concept for the potential hemodynamic factors underlying coronary ischemia in AAOCA during exercise state.

| S-EPMC10712838 | biostudies-literature

Acute Effects of Short-Term Warm Water Immersion on Arterial Stiffness and Central Hemodynamics.

Project description:Warm water immersion (WWI) has a potentially favorable effect on vascular health. However, the effects of short-term WWI on vascular function and central hemodynamics remain unclear. The present study aimed to determine the acute effects of short-term WWI on arterial stiffness and central hemodynamics in healthy men. Ten healthy men (27-57 years, 44 ± 12 years of mean age) underwent 5-min WWI (40-41°C) at the heart level. Systemic hemodynamics and tympanic temperature were monitored during WWI. Furthermore, pulse wave velocity (PWV) and aortic hemodynamics were measured before and 10 min after WWI. Cardiac output (CO) (via the Modelflow method) increased (P = 0.037), whereas tympanic temperature did not change (P = 0.879) during WWI. After 5-min WWI, heart rate (HR) and brachial diastolic blood pressure (BP) were significantly decreased. Aortic and leg PWV were decreased by 7.5 and 3.1%, respectively (P = 0.006 and P = 0.040). Femoral arterial blood flow was increased by 45.9% (P = 0.002), and leg vascular resistance was decreased by 29.1% (P < 0.001). Regarding central hemodynamic variables (estimated by general transfer function), aortic BP and augmentation index (AIx) did not change significantly, but the subendocardial viability ratio (SEVR), an index of coronary perfusion, was increased (P = 0.049). Our results indicate that a short-term WWI acutely improves aortic and peripheral arterial stiffness and coronary perfusion. Further studies to determine the interaction between the residual effect of a single bout of short-term WWI and chronic change (e.g., adaptation) in arterial stiffness and central hemodynamics are needed.

| S-EPMC7890244 | biostudies-literature

Association between hemodynamics, morphology, and rupture risk of intracranial aneurysms: a computational fluid modeling study.

Project description:The objective of the study was to examine the correlations between intracranial aneurysm morphology and wall shear stress (WSS) to identify reliable predictors of rupture risk. Seventy-two intracranial aneurysms (41 ruptured and 31 unruptured) from 63 patients were studied retrospectively. All aneurysms were divided into two categories: narrow (aspect ratio ?1.4) and wide-necked (aspect ratio <1.4 or neck width ?4 mm). Computational fluid dynamics was used to determine the distribution of WSS, which was analyzed between different morphological groups and between ruptured and unruptured aneurysms. Sections of the walls of clipped aneurysms were stained with hematoxylin-eosin, observed under a microscope, and photographed. Ruptured aneurysms were statistically more likely to have a greater low WSS area ratio (LSAR) (P = 0.001) and higher aneurysms parent WSS ratio (P = 0.026) than unruptured aneurysms. Narrow-necked aneurysms were statistically more likely to have a larger LSAR (P < 0.001) and lower values of MWSS (P < 0.001), mean aneurysm-parent WSS ratio (P < 0.001), HWSS (P = 0.012), and the highest aneurysm-parent WSS ratio (P < 0.001) than wide-necked aneurysms. The aneurysm wall showed two different pathological changes associated with high or low WSS in wide-necked aneurysms. Aneurysm morphology could affect the distribution and magnitude of WSS on the basis of differences in blood flow. Both high and low WSS could contribute to focal wall damage and rupture through different mechanisms associated with each morphological type.

| S-EPMC5486504 | biostudies-literature

Data-driven Modeling of Hemodynamics and its Role on Thrombus Size and Shape in Aortic Dissections.

Project description:Aortic dissection is a pathology that manifests due to microstructural defects in the aortic wall. Blood enters the damaged wall through an intimal tear, thereby creating a so-called false lumen and exposing the blood to thrombogenic intramural constituents such as collagen. The natural history of this acute vascular injury thus depends, in part, on thrombus formation, maturation, and possible healing within the false lumen. A key question is: Why do some false lumens thrombose completely while others thrombose partially or little at all? An ability to predict the location and extent of thrombus in subjects with dissection could contribute significantly to clinical decision-making, including interventional design. We develop, for the first time, a data-driven particle-continuum model for thrombus formation in a murine model of aortic dissection. In the proposed model, we simulate a final-value problem in lieu of the original initial-value problem with significantly fewer particles that may grow in size upon activation, thus representing the local concentration of blood-borne species. Numerical results confirm that geometry and local hemodynamics play significant roles in the acute progression of thrombus. Despite geometrical differences between murine and human dissections, mouse models can provide considerable insight and have gained popularity owing to their reproducibility. Our results for three classes of geometrically different false lumens show that thrombus forms and extends to a greater extent in regions with lower bulk shear rates. Dense thrombi are less likely to form in high-shear zones and in the presence of strong vortices. The present data-driven study suggests that the proposed model is robust and can be employed to assess thrombus formation in human aortic dissections.

| S-EPMC5802786 | biostudies-literature

Heritable changes in regional cortical thickness with age.

Project description:It is now well established that regional indices of brain structure such as cortical thickness, surface area or grey matter volume exhibit spatially variable patterns of heritability. However, a recent study found these patterns to change with age during development, a result supported by gene expression studies. Changes in heritability have not been investigated in adulthood so far and could have important implications in the study of heritability and genetic correlations in the brain as well as in the discovery of specific genes explaining them. Herein, we tested for genotype by age (G ×A) interactions, an extension of genotype by environment interactions, through adulthood and healthy aging in 902 subjects from the Genetics of Brain Structure (GOBS) study. A "jackknife" based method for the analysis of stable cortical thickness clusters (JASC) and scale selection is also introduced. Although additive genetic variance remained constant throughout adulthood, we found evidence for incomplete pleiotropy across age in the cortical thickness of paralimbic and parieto-temporal areas. This suggests that different genetic factors account for cortical thickness heritability at different ages in these regions.

| S-EPMC4205107 | biostudies-literature

Orthostatic blood pressure adaptations, aortic stiffness, and central hemodynamics in the general population: insights from the Malmo Offspring Study (MOS).

Project description:PurposeArterial stiffness is independently associated with orthostatic hypotension in older individuals. The relationship between orthostatic blood pressure adaptation and aortic stiffness has not been thoroughly examined in a younger population. We investigated the relationship between orthostatic blood pressure adaptations, central aortic hemodynamics, and aortic stiffness in a cohort of predominantly younger and middle-aged adults.MethodsWe analyzed an observational, population-based study of 5259 individuals living in Malmö, Sweden. We related aortic stiffness and central hemodynamics assessed by carotid-femoral pulse wave velocity and pulse wave analysis at the arteria radialis using Sphygmocor to orthostatic blood pressure adaptation after 3 min standing.ResultsThe mean age of the population was 41.9 ± 14.5 years, and 52.1% were women. We observed the highest aortic stiffness and central aortic blood pressure measurements in the lowest and highest quartiles of orthostatic systolic blood pressure differences (p < 0.001). Aortic stiffness and central aortic blood pressure gradually decreased across increasing quartiles of orthostatic diastolic blood pressure difference (p < 0.001). After full adjustment, orthostatic diastolic blood pressure remained significantly associated with aortic stiffness (p = 0.001) and central aortic blood pressure (p < 0.001), whereas orthostatic systolic blood pressure was significantly associated only with central aortic systolic blood pressure (p = 0.009). No significant associations were found between subclinical orthostatic hypotension, aortic stiffness, and central hemodynamics.ConclusionsOur findings demonstrate that altered blood pressure responses to orthostatic challenges, both blood pressure reductions and blood pressure increases, are independently and inversely associated with markers of aortic stiffness (vascular aging) in a predominantly young to middle-aged population.

| S-EPMC9984326 | biostudies-literature

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