Bicuspid Aortic Valve Disease and Associated Hemodynamics

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac valve anomaly, affecting approximately 1–2 per cent of the population worldwide. Rather than the normal three–leaflet configuration, the valve in BAV patients has only two cusps, often with fusion of right–left or right–non-coronary leaflets. This altered geometry not only predisposes to valvular dysfunction—stenosis or regurgitation—but also profoundly influences ascending aortic haemodynamics. Aberrant flow jets skew the distribution of wall shear stress (WSS) along the aortic wall, promoting asymmetric dilation and predisposing to aneurysm formation or dissection. Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) has revealed characteristic helical and vortical patterns in the ascending aorta of BAV patients, alongside elevated flow displacement and oscillatory shear index. The interplay of these disturbed flow metrics with genetic predisposition, involving genes such as NOTCH1, SMAD6 and GATA4, underpins a heterogeneous clinical course. Early identification of high‐risk flow signatures is central to patient stratification, guiding surveillance intervals and timing of surgical intervention. Clinicians and researchers are increasingly integrating advanced imaging, biomarker assessment and molecular profiling to personalise management and mitigate long-term complications of BAV-associated aortopathy.

Research from Nature Portfolio

Recent seminal work has identified regulatory variants near the cardiac transcription factor GATA4 that modulate valve morphogenesis, demonstrating that disruption of GATA4 in pluripotent stem cell–derived endothelial models impairs endocardial-to-mesenchymal transition, a critical process in valve development. These findings illuminate a direct molecular link between non-coding sequence variation and BAV formation, offering insight into the heritable component of the disease. The study also underscores how genetic alterations may indirectly shape postnatal aortic haemodynamics by altering cusp geometry.

Bicuspid Aortic Valve Disease and Associated Hemodynamics publication trend

The graph below shows the total number of articles in bicuspid aortic valve disease and associated hemodynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Bicuspid aortic valve (BAV): A congenital valve malformation in which the aortic valve has two functional leaflets instead of three.

4D flow cardiovascular magnetic resonance (4D flow CMR): An imaging technique that measures three-dimensional blood flow velocity over time.

Wall shear stress (WSS): The tangential force per unit area exerted by blood flow on the vessel wall.

Flow displacement: A measure of how far the centre of forward blood flow deviates from the vessel’s geometric centre.

Oscillatory shear index (OSI): A dimensionless indicator of directional changes in shear stress during the cardiac cycle.

Helical flow: A spiral or corkscrew-shaped blood flow pattern commonly observed in the ascending aorta.

References

1. Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI. Computer Methods and Programs in Biomedicine (2024).
2. Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease. Journal of Cardiovascular Magnetic Resonance (2018).
3. Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor. Frontiers in Physiology (2017).
4. Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve. Nature Communications (2017).
5. Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2genes in familial cases of bicuspid aortic valve. BMC Medical Genomics (2013).
6. Pathogenic Mechanisms of Bicuspid Aortic Valve Aortopathy. Frontiers in Physiology (2017).