The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

Abstract

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.

Fig. 1.

A: construction of the bicuspid aortic valve (BAV) model from a porcine aortic valve (AV): the valve was cut open between the left and right coronary leaflets; the aortic wall, sinus walls, and leaflets were trimmed as shown; the 2 trimmed leaflets were sutured together to simulate leaflet fusion; and the valve was sutured onto a plastic ring with 2 stents. B: construction of the trileaflet AV (TAV) model: trimming the native porcine AV without opening up the valve. The valve was sutured onto a ring with 2 stents.

Fig. 2.

Acrylic chambers with idealized sinus geometries used to house the valve models. A: schematic of the cross-section of BAV chamber at midsinus level. B: schematic of the cross-section of TAV chamber at midsinus level. C: photograph of an acrylic chamber.

Fig. 3.

Flow and pressure waveforms simulated in the pulsatile flow loop for the BAV model (A) and for the TAV (B). Ventr, ventricular; Pr, pressure.

Fig. 4.

En face view of the BAV model in the flow loop in the closed (A) and open (B) configuration. The fused leaflet dominates ∼60% of the channel cross-sectional area, has impaired mobility, and obstructs flow. These images compared well with the images of human BAVs in in vitro flow loops (C–F), reported by Robicsek et al. (35). C and D: closed and open configuration of 1 human BAV. E and F: same for another human BAV.

Fig. 5.

Particle image velocimetry (Vel) measurements downstream of the BAV model (A) and the TAV (B), as well as in the sinuses. The BAV model has an eccentric forward flow jet, whereas the TAV model has a straight forward flow. Forward flow moves from right to left.

Fig. 6.

A: shear stress measured at the central point of the fused leaflet [both streamwise (strm) and nonstreamwise (non-strm) shear stresses], nonfused leaflet of the BAV model (only streamwise shear stress), and a leaflet of the TAV model. B: streamwise shear stresses experienced by the central portion of the fused leaflet of the BAV over the cardiac cycle, and the 1 SD bounds of the shear stress.

Fig. 7.

Plots of instantaneous velocity less the ensemble average velocity (or the fluctuating component of velocities, u′) for velocities near (a) the TAV leaflet (A), the fused leaflet of the BAV (B), and the nonfused leaflet of the BAV (C). Data are presented such that temporally consecutive data points were joined by straight lines. Velocities near the BAV leaflets had greater variability and unsteadiness during systole than those near the TAV leaflet. D and E: plot of the absolute value of u′ at various time points during systole (D) and diastole (E) for all 3 leaflets. u′ is an indication of variability of velocity, showing that the BAV leaflets have higher velocity variability during systole than the TAV leaflet. *Significantly different from normal leaflet; #significantly different from BAV-fused leaflet.

Fig. 8.

SD of velocity or u′_RMS measured at the location 1 mm away from the leaflet when the leaflet is at the systolic position (A) and when the leaflet is at the diastolic position (B), plotted over time.

Fig. 9.

Power spectral density of velocities measured at the location of 1 mm away from the valve leaflets during systole: a comparison between the fused leaflet of the BAV, the nonfused leaflet of the BAV, and a leaflet of the TAV, derived using the sample and hold method (A) and the sample and hold method with refinement to the autocorrelation function (B).