In the present work, numerical simulations were conducted for a typical end-to-side distal graft anastomosis to assess the effects of inducing secondary flow, which is believed to remove unfavourable flow environment. Simulations were carried out for four models, generated based on two main features of 'out-of-plane helicity' and 'spiral ridge' in the grafts as well as their combination. Following a qualitative comparison against in vitro data, various mean flow and hemodynamic parameters were compared and the results showed that helicity is significantly more effective in inducing swirling flow in comparison to a spiral ridge, while their combination could be even more effective. In addition, the induced swirling flow was generally found to be increasing the wall shear stress and reducing the flow stagnation and particle residence time within the anastomotic region and the host artery, which may be beneficial to the graft longevity and patency rates. Finally, a parametric study on the spiral ridge geometrical features was conducted, which showed that the ridge height and the number of spiral ridges have significant effects on inducing swirling flow, and revealed the potential of improving the efficiency of such designs.

No abstract

Computational fluid dynamics is a tool capable of accurately measuring metrics currently used to predict the behaviour of cardiovascular diseases. This study quantifies the impact various commonly used inlet and outlet boundary conditions have on various shear rate-based haemodynamic metrics currently used for predicting the localisation of cardiovascular diseases. Simulations are conducted on an accurately represented rabbit aorta configuration and comparison has been made against available in vivo data. The boundary conditions studied include two different inlet profiles, three outlet boundary conditions, and steady-state versus pulsatile flow cases. Large variations were found in the results, particularly when using different outlet boundary conditions, and the discrepancies were evaluated both quantitatively and qualitatively. The results clearly highlight the importance of the type of boundary condition used when simulating complex cardiovascular models. By restricting the attention to the flow within the aorta and the intercostal branches, the results suggest that prescribing transient simulation and fully developed flow at the inlet are not required. Furthermore, assuming the widely accepted low wall shear stress theory of Caro, it was found that Murray's law-based outlet boundary condition returns the most physiologically accurate results when compared to in vivo data.

Endothelial erosion of atherosclerotic plaques is the underlying cause of approximately 30% of acute coronary syndromes (ACS). As the vascular endothelium is profoundly affected by the haemodynamic environment to which it is exposed, we employed computational fluid dynamic (CFD) analysis of the luminal geometry from 17 patients with optical coherence tomography (OCT)-defined plaque erosion, to determine the flow environment permissive for plaque erosion. Our results demonstrate that 15 of the 17 cases analysed occurred on stenotic plaques with median 31% diameter stenosis (interquartile range 28–52%), where all but one of the adherent thrombi located proximal to, or within the region of maximum stenosis. Consequently, all flow metrics related to elevated flow were significantly increased (time averaged wall shear stress, maximum wall shear stress, time averaged wall shear stress gradient) with a reduction in relative residence time, compared to a non-diseased reference segment. We also identified two cases that did not exhibit an elevation of flow, but occurred in a region exposed to elevated oscillatory flow. Our study demonstrates that the majority of OCT-defined erosions occur where the endothelium is exposed to elevated flow, a haemodynamic environment known to evoke a distinctive phenotypic response in endothelial cells.

No abstract

Endothelial erosion of atherosclerotic plaques and resulting thrombosis causes approximately 30% of acute coronary syndromes (ACS). As changes in the haemodynamic environment strongly influence endothelial function and contribute to plaque development, we reconstructed the coronary artery geometries of plaques with thrombi overlying intact fibrous caps from 17 ACS patients and performed computational fluid dynamic analysis. The results demonstrated that erosions frequently occur within areas of stenosis exposed to elevated flow. We recapitulated this flow environment in vitro, exposing human coronary artery endothelial cells to elevated flow and modelled smoking (a risk factor for erosion) by exposure to a combination of aqueous cigarette smoke extract and TNFα. This treatment induced endothelial detachment, which increased with pharmacological activation of the antioxidant system controlled by transcription factor Nrf2 (encoded by NFE2L2). The expression of Oxidative Stress Growth INhibitor genes OSGIN1 and OSGIN2 increased under these conditions and also in the aortas of mice exposed to cigarette smoke. Sustained high level expression of OSGIN1+2 resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and dysregulation of autophagy. Overexpression of either Nrf2 or OSGIN1+2 induced cell detachment, which did not depend on apoptosis, and could be partially rescued by inhibition of HSP70 using VER-155008, or AMP kinase activation using metformin. These findings demonstrate that under elevated flow, smokinginduced hyperactivation of Nrf2 can trigger endothelial cell detachment, highlighting a novel mechanism that could contribute to ACS involving endothelial erosion overlying stenotic plaques.

Purpose This computational fluid dynamics study investigates the necessity of incorporating heart failure severity in the preoperative planning of left ventricular assist device (LVAD) configurations, as it is often omitted from studies on LVAD performance. Methods A parametric study was conducted examining a common range of LVAD to aortic root flow ratios (LVAD/AR-FR). A normal aortic root waveform was scaled by 5-30% in increments of 5% to represent the common range of flow pumped by the left ventricle for different levels of heart failure. A constant flow rate from the cannula compensated for the severity of heart failure in order to maintain normal total aortic flow rate. Results The results show that LVAD/AR-FR can have a significant but irregular impact on the perfusion and shear stress-related haemodynamic parameters of the subclavian and carotid arteries. Furthermore, it is found that a larger portion of the flow is directed towards the thoracic aorta at the expense of the carotid and subclavian arteries, regardless of LVAD/AR-FR. Conclusion The irregular behaviour found in the subclavian and carotid arteries highlights the necessity of including the LVAD/ AR-FR in the preoperative planning of an LVAD configuration, in order to accurately improve the effects on the cardiovascular system post implantation.

defines a diagnostic yield of just 8/536 (6%) in this patient group, using known aortopathy gene panels. Surprisingly, none of these variants were found in probands under 30 at disease onset. There were 68 classic trios in this cohort (proband + mother and father). However, just one of these has a clearly pathogenic de novo variant identified (in MYH11). There were just 2 Tier 2 variants of uncertain significance (VUS) in aortopathy genes in other trios. 10 larger family structures have yielded no clear pathogenic candidates to date. The majority of the cohort are recruited as singletons. 75 Tier 2 variants have been identified to date in 19 aortopathy genes (see figure 1). Just 1 of these (in LOX) can be classified as likely pathogenic. The remainder are VUSs. Conclusion In this genetically pre-screened cohort with FTAAD, genetic diagnosis remains elusive. The variety of genes in which protein-altering variants are found highlights the genetic heterogeneity of this condition. We plan further systematic studies of the family structures available in the 100,000 Genomes Project and case:control studies to further elucidate the genetic architecture of FTAAD. The negative findings to date, particularly in probands with young-onset aortopathy, make it likely that responsible genes are yet to be discovered in many cases. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project.