Objectives Bicuspid aortic valve (BAV), characterized by valve malformation and risk for aortopathy, displays profound alteration in systolic aortic outflow and wall shear stress (WSS) distribution. The present study performed 4-dimenstional flow MRI in BAV patients with right-left (R-L) cusp fusion, focusing on the impact of valve function upon hemodynamic status within ascending aorta. Methods Four-dimensional flow MRI was performed in 50 R-L BAV subjects and 15 age- and aortic size-matched controls with tricuspid aortic valve. BAV patients were categorized into 3 groups according to their aortic valve function as follows: BAV with no more than mild aortic valve dysfunction (BAV-CTL, n=20), BAV with severe aortic insufficiency (BAV-AI, n=15), and BAV with severe aortic stenosis (BAV-AS, n=15). Results All R-L BAV patients exhibited peak WSS at the right-anterior position of the ascending aorta (BAV vs. TAV at right-anterior position: 0.91±0.23 N/m2 vs. 0.43±0.12 N/m2, p<0.001) with no distinct alteration between BAV-AI and BAV-AS. The predominance of dilatation involving the tubular ascending aorta (82%, type 2 aortopathy) persisted, with or without valve dysfunction. Compared to BAV-CTL subjects, the BAV-AI group displayed universally elevated WSS (0.75±0.12 N/m2 vs. 0.57±0.09 N/m2, p<0.01) in the ascending aorta, which was associated with elevated cardiac stroke volume (p<0.05). The BAV-AS group showed elevated flow eccentricity in the form of significantly increased standard deviation of circumferential WSS, which correlated with markedly increased peak aortic valve velocity (p<0.01). Conclusions The location of peak aortic WSS and type of aortopathy remained homogeneous among R-L BAV patients irrespective of valve dysfunction. Severe aortic insufficiency or stenosis resulted in further elevated aortic WSS and exaggerated flow eccentricity.

An aggressive policy of preventive aortic interventions seemed appropriate in patients with BAV-AI during AVR, and BAV phenotype presenting as either insufficiency or stenosis should be taken into consideration when contemplating optimal surgical strategies for BAV aortopathy.

Bicuspid aortic valve (BAV) exhibits a clinical incline toward aortopathy, in which aberrant tensile and shear stress generated by BAV can induce differential expression of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). Whether stenotic BAV, which exhibits additional eccentric high-velocity flow jet upon ascending aorta and further worsens circumferential systolic wall shear stress than BAV with echocardiographically normal aortic valve, can lead to unique plasma MMP/TIMP patterns is still unknown. According to their valvulopathy and aortic dilatation status, 93 BAV patients were included in the present study. Group A (n = 37) and B (n = 28) comprised severely stenotic patients with or without ascending aorta dilatation; Group C (n = 12) and D (n = 16) comprised echocardiographically normal BAV patients with or without ascending aorta dilatation. Plasma MMP/TIMP levels (MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4) were determined via a multiplex ELISA detection system in a single procedure. Among patients with isolated severe aortic stenosis, plasma levels of MMP-2 and -9 were significantly elevated when ascending aortic dilatation was present (p = 0.001 and p = 0.002, respectively). MMP-2, however, remained as the single elevated plasma component among echocardiographically normal BAV patients with dilated ascending aorta (p = 0.027). Multivariate analysis revealed that MMP-2 and MMP-9 could both serve as independent risk factor for aortic dilatation in the case of isolated severe stenosis (p = 0.003 and p = 0.001, respectively), and MMP-2 in echocardiographically normal patients (p = 0.002). In conclusion, BAV patients with isolated severe aortic stenosis demonstrated a distinct plasma MMP/TIMP pattern, which might be utilized as circulating biomarkers for early detection of aortic dilatation.