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.

Surgical valve replacement in patients with severe calcific aortic valve disease using either bioprosthetic or mechanical heart valves is still limited by structural valve deterioration for the former and thrombosis risk mandating anticoagulant therapy for the latter. Prosthetic polymeric heart valves have the potential to overcome the inherent material and design limitations of these valves, but their development is still ongoing. The aim of this study was to characterize the hemodynamics and thrombogenic potential of the Polynova polymeric trileaflet valve prototype using a fluid-structure interaction (FSI) approach. The FSI model replicated experimental conditions of the valve as tested in a left heart simulator. Hemodynamic parameters (transvalvular pressure gradient, flow rate, maximum velocity, and effective orifice area) were compared to assess the validity of the FSI model. The thrombogenic footprint of the polymeric valve was evaluated using a Lagrangian approach to calculate the stress accumulation (SA) values along multiple platelet trajectories and their statistical distribution. In the commissural regions, platelets were exposed to the highest SA values because of highest stress levels combined with local reverse flow patterns and vortices. Stress-loading waveforms from representative trajectories in regions of interest were emulated in our Hemodynamic Shearing Device (HSD). Platelet activity was measured using our platelet activation state (PAS) assay and the results confirmed the higher thrombogenic potential of the commissural hotspots. In conclusion, the proposed method provides an in depth analysis of the hemodynamic and thrombogenic performance of the polymer valve prototype and identifies locations for further design optimization.

Bicuspid aortic valve (BAV), i.e. the fusion of two aortic valve cusps, is the most frequent congenital cardiac malformation. Its progression is often characterized by accelerated leaflet calcification and aortic wall dilation. These processes are likely enhanced by altered biomechanical stimuli, including fluid-dynamic wall shear stresses (WSS) acting on both the aortic wall and the aortic valve. Several studies have proposed the exploitation of 4D-flow magnetic resonance imaging sequences to characterize abnormal in vivo WSS in BAV-affected patients, to support prognosis and timing of intervention. However, current methods fail to quantify WSS peak values. On this basis, we developed two new methods for the improved quantification of in vivo WSS acting on the aortic wall based on 4D-flow data. We tested both methods separately and in combination on synthetic datasets obtained by two computational fluid-dynamics (CFD) models of the aorta with healthy and bicuspid aortic valve. Tests highlighted the need for data spatial resolution at least comparable to current clinical guidelines, the low sensitivity of the methods to data noise, and their capability, when used jointly, to compute more realistic peak WSS values as compared to state-of-the-art methods. The integrated application of the two methods on the real 4D-flow data from a preliminary cohort of three healthy volunteers and three BAV-affected patients confirmed these indications. In particular, quantified WSS peak values were one order of magnitude higher than those reported in previous 4D-flow studies, and much closer to those computed by highly time- and space-resolved CFD simulations.

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Congenital bicuspid aortic valve (BAV) consists of two fused cusps and represents a major risk factor for calcific valvular stenosis. Herein, a fully coupled fluid-structure interaction (FSI) BAV model was developed from patientspecific magnetic resonance imaging (MRI) and compared against in vivo 4-dimensional flow MRI (4D Flow). FSI simulation compared well with 4D Flow, confirming direction and magnitude of the flow jet impinging onto the aortic wall as well as location and extension of secondary flows and vortices developing at systole: the systolic flow jet originating from an elliptical 1.6 cm 2 orifice reached a peak velocity of 252.2 cm/s, 0.6% lower than 4D Flow, progressively impinging on the ascending aorta convexity. The FSI model predicted a peak flow rate of 22.4 L/min, 6.7% higher than 4D Flow, and provided BAV leaflets mechanical and flowinduced shear stresses, not directly attainable from MRI. At systole, the ventricular side of the non-fused leaflet revealed the highest wall shear stress (WSS) average magnitude, up to 14.6 Pa along the free margin, with WSS progressively decreasing towards the belly. During diastole, the aortic side of the fused leaflet exhibited the highest diastolic maximum principal stress, up to 322 kPa within the attachment region. Systematic comparison with ground-truth non-invasive MRI can improve the computational model ability to reproduce native BAV hemodynamics and biomechanical response more realistically, and shed light on their role in BAV patients' risk for developing complications; this approach may further contribute to the validation of advanced FSI simulations designed to assess BAV biomechanics.