Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities

J Am Coll Cardiol. 2009 Dec 8;54(24):2312-8. doi: 10.1016/j.jacc.2009.07.044.


Objectives: The aim of this study was to decide whether bicuspid aortic valves (BAVs) with fused right and noncoronary leaflets (R-N) and BAVs with fused right and left leaflets (R-L) have different etiologies or are the product of a single diathesis.

Background: The BAV is the most common congenital cardiac malformation. The R-N and R-L BAVs are the most frequent BAV subtypes.

Methods: The study was carried out in adult and embryonic hearts of endothelium nitric oxide synthase knock-out mice and inbred Syrian hamsters with a high incidence of R-N and R-L BAVs, respectively. The techniques used were histochemistry, immunohistochemistry, and scanning electron microscopy.

Results: The R-N BAVs result from a defective development of the cardiac outflow tract (OT) endocardial cushions that generates a morphologically anomalous right leaflet. The left leaflet develops normally. The R-L BAVs are the outcome of an extrafusion of the septal and parietal OT ridges that thereby engenders a sole anterior leaflet. The noncoronary leaflet forms normally.

Conclusions: The R-N and R-L BAVs are different etiological entities. The R-N BAVs are the product of a morphogenetic defect that happens before the OT septation and that probably relies on an exacerbated nitric oxide-dependent epithelial-to-mesenchymal transformation. The R-L BAVs result from the anomalous septation of the proximal portion of the OT, likely caused by a distorted behavior of neural crest cells. Care should be taken in further work on BAV genetics because R-N and R-L BAVs might rely on different genotypes. Detailed screening for R-N and R-L BAVs should be performed for a better understanding of the relationships between these BAV morphologic phenotypes and other heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Valve / abnormalities*
  • Aortic Valve / embryology
  • Congenital Abnormalities / etiology
  • Cricetinae
  • Disease Susceptibility
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Scanning