In our study, we assessed the relation between aortic flow patterns and regional WSS components (magnitude, axial and circumferential) through the entire ascending aorta in a large BAV population. In order to avoid the effect of changes in flow dynamics and WSS secondary to aortic dilatation  or severe valvular disease, only BAV patients with non-severe valvular dysfunction and aortic diameters ≤45 mm were included. Also, the specific role of flow parameters and WSS components in the ascending aorta dilatation and morphotype was assessed by unadjusted and multivariable adjusted analysis.
The main findings of our study were that: 1) RL-BAV patients present a sustained flow towards the anterior and right-anterior aortic walls, whereas, RN-BAV present a predominantly posterior output flow that shifts towards the right and right-anterior walls in the mid and distal AAo inducing an increase in the IRF. This flow distribution reflects into regional WSS patterns. 2) Sex (male), normalized displacement and axial WSS in the proximal AAo are the main factors associated with the root-morphotype, whereas RN-phenotype, SFRR and circumferential WSS are the main factors related to the ascending-morphotype.
To our knowledge, this is the first large study conducted in BAV patients in which different patterns of axial and circumferential regional WSS maps were used to explain variations in the AAo dilatation morphotype. Previous studies have emphasized differences in flow variables and WSS between the RN- and RL-BAV [7, 10, 11, 13, 14] with little or no correlation with the aortic dilatation morphotype [7, 11]. In this regard, Mahadevia et al.  did not analyze rotational flow or WSS components when studying BAV aortopathy, while Bissell et al.  only showed an increased rotational flow at larger aortic diameters suggesting a potential causative role. Thus, it is of great interest to ascertain the main factors associated with aortic dilatation since aortic diameter and structural changes in the aortic wall are related to clinical events regardless of valve phenotype [6, 8].
Owing to the asymmetric valve opening, there is an increase in the jet angle and in the displacement of the center of velocities with respect to the center of the lumen that induces an asymmetric distribution of the WSS pattern as previously described [7, 11, 13, 14]. Similar to those of Mahadevia et al. , our results confirm that the jet angle is wider in RN-phenotype, whereas normalized displacement is greater in the RL-phenotype. Also, we demonstrated that these variables are greater at the proximal aorta with a progressive reduction at the distal AAo that suggests that flow tends to be more symmetric in the distal AAo. Our results differ from those of Mahadevia et al.  since they reported flow angle and displacement to be the main factors involved in AAo dilatation. However, they determined the absolute value of the displacement, whereas we report this value normalized by aortic diameter as suggested elsewhere .
In-plane rotational flow and SFRR
Similar to previous studies [11, 13, 30, 31], we found that BAV presented greater rotational flow compared to controls, with the RN-phenotype being greater than in RL- at the mid and distal AAo. This finding can be justified by the fact that the flow shifts from posterior towards anterior segments in RN-BAV. This rotational flow is not only significantly greater in RN-BAV but also in those with the ascending-morphotype. An increased rotational flow induces an increase in the circumferential WSS which justifies that both parameters were statistically significant in the ascending-morphotype on univariable analysis.
In our population, most of the BAV patients presented right-handed flow (98%). The lack of left handed helical flow seen in our study could be a sign of left handed helical flow being associated with severe/late disease process , and therefore, not seen in the benign aortopathy population (≤ 45 mm) included in our study.
The presence of retrograde flow at systole has been reported in patients with greater aortic diameters [29, 32, 33]. We found that higher values of SFRR are associated with the ascending-morphotype and not with the root-morphotype. An increase in the SFRR may induce an asymmetric increase and directional variations in the WSS contributing to dilatation. It is not clear whether this parameter is the cause or consequence of aortic dilatation; however, we observed that this cranio-caudal flow also exists in BAV with normal aortic diameters. This finding suggests that this flow may act as a causal agent of aortic dilatation and would increase as the aorta dilates, thereby perpetuating this process.
WSS and aortic dilatation
Our study is consistent with previous publications [7, 13] which suggest that the magnitude of WSS lacks significance since its value is similar in controls and BAV. However, controls present increased axial WSS because of predominant laminar flow, while helical flow in BAV increases circumferential WSS . Thus, the different WSS components (axial and circumferential) constitute an interesting parameter in the assessment of aortic dilatation .
A detailed analysis of WSS permitted us to use a 3D representation of axial and circumferential WSS maps along the AAo, showing asymmetrical patterns that may contribute to structural changes in the aortic wall (elastin and metalloproteinases) related to aortic dilatation . Furthermore, the presence of eccentric but uniform flow along the anterior AAo in the RL-phenotype determines that the axial component of WSS is greater in this subgroup of patients; however, the eccentric but helical flow in the RN-phenotype determines that the circumferential component of WSS is greater in this subgroup. This variation in WSS components may also influence the aortic morphotype. Thus, patients with a greater axial component exhibit more dilatation at the aortic root; however, greater circumferential WSS is associated with dilatation in the AAo.
Despite the correlations found here and elsewhere, the causative role of the observed flow disturbances need to be assessed in longitudinal studies. In particular, it has been mainly discussed in root only dilatation in BAV, which is thought to be a predominantly genetic form of BAV disease . Our data confirmed the previously found association between root (only) dilatation and male sex .
The association of male sex, normalized displacement, and axial WSS in the proximal aorta discriminated the root-morphotype with an AUC of 0.91. However, the combination of an RN-phenotype, circumferential WSS and SFRR discriminated the ascending-morphotype with an AUC of 0.89. Thus, we believe these parameters should be considered in the evaluation of BAV beyond aortic diameters. This additional information could identify patients at higher risk of aortopathy that may require a closer follow-up.
The prospective nature of our study determined the inclusion of more patients with the RL-phenotype than RN-; however, our cohort reflects the distribution of fusion phenotypes in the general BAV population.
Healthy subjects were recruited to match BAV patients for age and aortic diameters. Although aortic diameters were slightly larger in BAV, these differences were not statistically significant.
Owing to the limited spatial and temporal resolution of 4D-flow, WSS is known to be underestimated [25, 34, 35]. However, all acquisitions were made with the same imaging parameters and analyzed with the same methodology and previous work highlighted that regions of high/low WSS are matched despite different spatial and temporal resolutions . Additionally, manual segmentation causes intra- and inter-observer variability. Nevertheless, the robustness of WSS measurements employed in this study and their reproducibility has been previously demonstrated .
WSS estimation was limited to 8 slices in the AAo at peak systole. Thus, very localized regions of altered WSS may have been lost and temporal variations were not assessed. The use of a volumetric WSS method [37, 38], would allow a more detailed analysis.
Despite flow variables are likely to vary during the ejection phase, our measurements of jet angle, flow displacement, IRF and WSS were performed only at peak systole. Moreover, these measurements were performed averaging the results obtained at four successive time instants to reduce noise. Despite this approach has been used by several authors [7, 11, 13], and have proved high reproducibility , it may imply the loss of possible information contained in other systolic phases.
We conducted a cross-sectional study to evaluate the impact of flow dynamics in aortic dilatation in BAV. However, the real influence of these parameters on the concurrence of aortic dilatation needs to be determined in further longitudinal studies.