Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity

Atkins, Samantha K.; Moore, Alison; Sucosky, Philippe

doi:10.4330/wjc.v8.i1.89

Cited by 18 publications

(12 citation statements)

References 58 publications

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“…Indeed, recent studies investigated the effects of BAV-related fluid-dynamic alterations in non-dilated and initially healthy aortas, isolating these alterations from possible concomitant pathophysiological factors (Atkins et al, 2014; Atkins, 2016; Cao et al, 2017; McNally et al, 2017). Morphotype-dependent flow alterations in the aorta proved to generate different mechanical stimuli on the aortic wall in terms of

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magnitude and directionality (Cao et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…These BAV-specific mechanical stimuli were different on the convexity and on the concavity of the ascending aorta. Interestingly, when applied in vitro to fresh specimens of healthy porcine aortas, these two region-dependent stimuli induced different responses: only when reproducing the

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pattern computed at the convexity significant alterations in the expression of MMP-2 and MMP-9, which are involved in medial degradation, were detected already after 48 h (Atkins et al, 2014; Atkins, 2016). Similar evidences of dysregulations in gene expression and metalloproteinase concentration were also reported at the sites of highest

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in BAV patients undergoing aortic resection, thus in presence of clinically-relevant aortopathy at the organ-scale length (Guzzardi et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

et al. 2017

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Bicuspid aortic valve (BAV) is the most common congenital cardiac disease and is a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of the associated aortopathies, BAV-related alterations in aortic fluid-dynamics, and particularly in wall shear stresses (WSSs), likely play a role in the progression of aortopathy, and may contribute to its pathogenesis. To test whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of phase-contrast cardiac magnetic resonance imaging (CMR) to quantitatively compare the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i) five prospectively enrolled young patients with normo-functional BAV and with no aortic dilation and (ii) ten age-matched healthy volunteers. Through the semi-automated processing of 4D Flow data, the aortic bulk flow at peak systole was quantified, and WSSs acting on the endothelium of the ascending aorta were characterized throughout the systolic phase in terms of magnitude and time-dependency through a method recently developed by our group. Variables computed for each BAV patient were compared vs. the corresponding distribution of values obtained for healthy controls. In BAV patients, ascending aorta diameter was measured on cine-CMR images at baseline and at 3-year follow-up. As compared to controls, normo-functional BAV patients were characterized by minor bulk flow disturbances at peak systole. However, they were characterized by evident alterations of WSS distribution and peak values in the ascending aorta. In particular, in four BAV patients, who were characterized by right-left leaflet fusion, WSS peak values exceeded by 27–46% the 90th percentile of the distribution obtained for healthy volunteers. Only in the BAV patient with right-non-coronary leaflet fusion the same threshold was exceeded by 132%. Also, evident alterations in the time-dependency of WSS magnitude and direction were observed. Despite, these fluid-dynamic alterations, no clinically relevant anatomical remodeling was observed in the BAV patients at 3-year follow-up. In light of previous evidence from the literature, our results suggest that WSS alterations may precede the onset of aortopathy and may contribute to its triggering, but WSS-driven anatomical remodeling, if any, is a very slow process.

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magnitude and directionality (Cao et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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in BAV patients undergoing aortic resection, thus in presence of clinically-relevant aortopathy at the organ-scale length (Guzzardi et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

et al. 2017

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“…Aortic dimension has been the most used marker of aortic dissection risk, yet it provides little prognostic information over the clinically important range of 40–55 mm (2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines For the Diagnosis and Management of Patients with Thoracic Aortic Disease Representative, Erbel et al, 2014 ; 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines For the Diagnosis and Management of Patients with Thoracic Aortic Disease Representative Members et al, 2016 ), while the majority of aortic dissections occur at dimensions less than these (Pape et al, 2007 ). This limitation has led to other approaches such as examining morphometry (Biaggi et al, 2009 ; Habchi et al, 2017 ), hemodynamic factors (Atkins et al, 2016 ; DeCampli, 2017 ; Raghav et al, 2017 ), the position and shape of the aneurysm (Schaefer et al, 2008 ; Della Corte et al, 2014b ), aortic growth rate (Elefteriades and Farkas, 2010 ), and aortic distensibility parameters (Benedik et al, 2013 ). To date, observed population-based associations are weak and are unlikely to provide any predictive value for the individual patient.…”

Section: Is There a Biomarker For Aortic Dissection?mentioning

confidence: 99%

Pathogenic Mechanisms of Bicuspid Aortic Valve Aortopathy

2017

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Bicuspid aortic valve (BAV) is the most common congenital valvular defect and is associated with ascending aortic dilation (AAD) in a quarter of patients. AAD has been ascribed both to the hemodynamic consequences of normally functioning and abnormal BAV morphology, and to the effect of rare and common genetic variation upon function of the ascending aortic media. AAD manifests in two overall and sometimes overlapping phenotypes: that of aortic root aneurysm, similar to the AAD of Marfan syndrome; and that of tubular AAD, similar to the AAD seen with tricuspid aortic valves (TAVs). These aortic phenotypes appear to be independent of BAV phenotype, have different embryologic origins and have unique etiologic factors, notably, regarding the role of hemodynamic changes inherent to the BAV phenotype. Further, in contrast to Marfan syndrome, the AAD seen with BAV is infrequently present as a strongly inherited syndromic phenotype; rather, it appears to be a less-penetrant, milder phenotype. Both reduced levels of normally functioning transcriptional proteins and structurally abnormal proteins have been observed in aneurysmal aortic media. We provide evidence that aortic root AAD has a stronger genetic etiology, sometimes related to identified common non-coding fibrillin-1 (FBN1) variants and other aortic wall protein variants in patients with BAV. In patients with BAV having tubular AAD, we propose a stronger hemodynamic influence, but with pathology still based on a functional deficit of the aortic media, of genetic or epigenetic etiology. Although it is an attractive hypothesis to ascribe common mechanisms to BAV and AAD, thus far the genetic etiologies of AAD have not been associated to the genetic etiologies of BAV, notably, not including BAV variants in NOTCH1 and GATA4.

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“…Disturbed flow has been shown to alter endothelial cell-smooth muscle cell communication and behavior in blood vessels (Ando and Yamamoto, 2011;Shav et al, 2014;Chistiakov et al, 2016). For example, ex vivo experiments with porcine tissue have shown that WSS magnitude overloads on the aortic wall secondary to valvular defects contribute to the loss of tissue homeostasis and the progressive degeneration of the tunica media Atkins et al, , 2016. In light of those observations, the increased WSS magnitude and temporal gradient captured on the septal wall may promote fibrosis and explain the frequent association between DSS and steep LVOTs documented in the literature (Cape et al, 1997;Yap et al, 2008;Foker, 2013;Massé et al, 2018).…”

Section: Potential Significance For Dss Pathogenesis and Secondary Armentioning

confidence: 99%

Impact of Aortoseptal Angle Abnormalities and Discrete Subaortic Stenosis on Left-Ventricular Outflow Tract Hemodynamics: Preliminary Computational Assessment

Shar

Brown

Keswani

et al. 2020

Front. Bioeng. Biotechnol.

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Discrete subaortic stenosis (DSS) is an obstruction of the left ventricular outflow tract (LVOT) due to the formation of a fibromuscular membrane upstream of the aortic valve. DSS is a major risk factor for aortic regurgitation (AR), which often persists after surgical resection of the membrane. While the etiology of DSS and secondary AR is largely unknown, the frequent association between DSS and aortoseptal angle (AoSA) abnormalities has supported the emergence of a mechanobiological pathway by which hemodynamic stress alterations on the septal wall could trigger a biological cascade leading to fibrosis and membrane formation. The resulting LVOT flow disturbances could activate the valve endothelium and contribute to AR. In an effort to assess this hypothetical mechano-etiology, this study aimed at isolating computationally the effects of AoSA abnormalities on septal wall shear stress (WSS), and the impact of DSS on LVOT hemodynamics. Two-dimensional computational fluid dynamics models featuring a normal AoSA (N-LV), a steep AoSA (S-LV), and a steep AoSA with a DSS lesion (DSS-LV) were designed to compute the flow in patient-specific left ventricles (LVs). Boundary conditions consisted of transient velocity profiles at the mitral inlet and LVOT outlet, and patient-specific LV wall motion. The deformation of the DSS lesion was computed using a two-way fluid-structure interaction modeling strategy. Turbulence was accounted for via implementation of the k-ω turbulence model. While the N-LV and S-LV models generated similar LVOT flow characteristics, the DSS-LV model resulted in an asymmetric LVOT jet-like structure, subaortic stenotic conditions (up to 2.4-fold increase in peak velocity, 45% reduction in effective jet diameter vs. N-LV/S-LV), increased vorticity (2.8-fold increase) and turbulence (5-and 3-order-ofmagnitude increase in turbulent kinetic energy and Reynolds shear stress, respectively). The steep AoSA subjected the septal wall to a 23% and 69% overload in temporal shear magnitude and gradient, respectively, without any substantial change in oscillatory shear

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Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity

Cited by 18 publications

References 58 publications

4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

Pathogenic Mechanisms of Bicuspid Aortic Valve Aortopathy

Impact of Aortoseptal Angle Abnormalities and Discrete Subaortic Stenosis on Left-Ventricular Outflow Tract Hemodynamics: Preliminary Computational Assessment

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