Annals of Biomedical Engineering

, Volume 42, Issue 5, pp 986–998 | Cite as

Architectural Trends in the Human Normal and Bicuspid Aortic Valve Leaflet and Its Relevance to Valve Disease

  • Ankush Aggarwal
  • Giovanni Ferrari
  • Erin Joyce
  • Michael J. Daniels
  • Rachana Sainger
  • Joseph H. GormanIII
  • Robert Gorman
  • Michael S. SacksEmail author


The bicuspid aortic valve (AV) is the most common cardiac congenital anomaly and has been found to be a significant risk factor for developing calcific AV disease. However, the mechanisms of disease development remain unclear. In this study we quantified the structure of human normal and bicuspid leaflets in the early disease stage. From these individual leaflet maps average fiber structure maps were generated using a novel spline based technique. Interestingly, we found statistically different and consistent regional structures between the normal and bicuspid valves. The regularity in the observed microstructure was a surprising finding, especially for the pathological BAV leaflets and is an essential cornerstone of any predictive mathematical models of valve disease. In contrast, we determined that isolated valve interstitial cells from BAV leaflets show the same in vitro calcification pathways as those from the normal AV leaflets. This result suggests the VICs are not intrinsically different when isolated, and that external features, such as abnormal microstructure and altered flow may be the primary contributors in the accelerated calcification experienced by BAV patients.


Microstructure Aortic stenosis Calcific aortic valve disease Early disease stage Fiber structure Valve interstitial cells 



Aortic valve


Tricuspid aortic valve


Bicuspid aortic valve


Aortic stenosis


Aortic valve sclerosis


Calcific aortic valve disease


Valve interstitial cell


Aortic valve area


Extra cellular matrix


Small angle light scattering


Hematoxylin and Eosin


Modified Movat Pentachrome


Dulbecco’s modified Eagle’s medium


Smooth muscle actin


Glyceraldehyde 3-phosphate dehydrogenase


Root mean square distance


Magnetic resonance imaging


Orientation index



This work was supported by the following sources—National Institute of Health (grant number grant numbers HL63954, HL103723 and HL73021 to R.C.G. and J.H.G.) and Moncrief Chair funds (M.S.S.). Help from Vanessa Aguilar in carrying out several of the experiments is greatly appreciated. American Heart Association Postdoctoral Fellowship Award 14POST18720037 to A.A.

Conflict of interest

None declared.

Supplementary material

10439_2014_973_MOESM1_ESM.docx (1.5 mb)
Supplementary material 1 (DOCX 1534 kb)


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Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Ankush Aggarwal
    • 1
  • Giovanni Ferrari
    • 2
  • Erin Joyce
    • 3
  • Michael J. Daniels
    • 4
  • Rachana Sainger
    • 2
  • Joseph H. GormanIII
    • 2
  • Robert Gorman
    • 2
  • Michael S. Sacks
    • 1
    Email author
  1. 1.Center for Cardiovascular Simulation, Institute for Computational Engineering Sciences and the Department of Biomedical EngineeringThe University of Texas at AustinAustinUSA
  2. 2.Gorman Cardiovascular Research GroupUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of BioengineeringUniversity of PittsburghPittsburghUSA
  4. 4.Division of Statistics & Scientific Computation and Department of Integrative BiologyUniversity of Texas at AustinAustinUSA

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