Bicuspid Aortic Valve: Identifying Knowledge Gaps and Rising to the Challenge From the International Bicuspid Aortic Valve Consortium (BAVCon)
Open accessAbstract
Since its estimated first description >500 years ago by Leonardo da Vinci,2 the bicuspid aortic valve (BAV) has progressively built a reputation; initially, as a curious valvular phenotype with a tendency to develop obstruction and insufficiency. In more contemporary times, however, the BAV is recognized as underlying almost 50% of isolated severe aortic stenosis cases requiring surgery,3 and has been extensively associated with ominous outcomes such as bacterial endocarditis and aortic dissection.4 These associations, coupled with the high prevalence of BAV in humans,5 have prompted investigative efforts into the condition, which although insightful, have generated more questions than answers. This review describes our current knowledge of BAV, but, more importantly, it highlights knowledge gaps and areas where basic and clinical research is warranted. Our review has 2 sections. The first section outlines the multifaceted challenge of BAV, our current understanding of the condition, and barriers that may hamper the advancement of the science. The second section proposes a roadmap to discovery based on current imaging, molecular biology, and genetic tools, recognizing their advantages and limitations.
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Bicuspid aortic valves have two functional leaflets often of unequal size and result from incomplete separation of commissures during embryonic development.
“Bicuspid aortic valves have two functional leaflets often of unequal size. This abnormality results from incomplete separation of commissures during embryonic development8.”
From Calcific aortic stenosis (2016) · cites this paper as [8]
The section “A Valvuloaortopathy With Varied Phenotypes and Unpredictable Outcomes” describes two aortic cusps that are usually asymmetrical, supporting the description of the leaflets. The “Pathobiology” section discusses embryological development but does not say that incomplete separation of commissures causes bicuspid aortic valves; that causal explanation, to which the citation is attached, is not supported by our copy. (LLM, conf=0.86)
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- Authors
- Michelena, H. I., Prakash, S. K., Della Corte, A., Bissell, M. M., Anavekar, N., Mathieu, P., Bossé, Y., Limongelli, G., Bossone, E., Benson, D. W., Lancellotti, P., Isselbacher, E. M., Enriquez-Sarano, M., Sundt, T. M., Pibarot, P., Evangelista, A., Milewicz, D. M., & Body, S. C.
- Affiliations
- From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (H.I.M., N.A., M.E.-S.); Division of Medical Genetics; Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX (S.K.P., D.M.M.); Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy (A.D.C.); Department of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (M.M.B.); Institut Universitaire de Cardiologie et de...
- Mayo Clinic (US)
- Children's Hospital of Wisconsin (US)
- ORCID
- Venue
- Circulation
- Published
- 2014-06-24
- Volume
- 129
- Issue
- 25
- Pages
- 2691-2704
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4145814
- OpenAlex
- W2023616993
- Cited by
- 442
- References
- 214
- Citations by year
- 2026: 28 · 2025: 27 · 2024: 32 · 2023: 36 · 2022: 46 · 2021: 59 · 2020: 39 · 2019: 32 · 2018: 35 · 2017: 44 · 2016: 35 · 2015: 17 · 2014: 8 · 2013: 1 · 2012: 3
- FWCI
- 23.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Corpus Université Laval (Université Laval) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- Funders
- British Heart Foundation (FS/10/43/28415)
- National Institutes of Health (UL1TR000371, UL1TR000170)
- National Heart, Lung, and Blood Institute (R01HL114823)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Aortic Disease and Treatment Approaches
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- bicuspid aortic valve, aortic stenosis, aortic valve obstruction, aortic regurgitation, bacterial endocarditis, aortic dissection, congenital heart disease, aortic valve imaging, genetic susceptibility, research gaps
- MeSH terms
- Bicuspid Aortic Valve Disease, Aortic Valve, Diagnostic Imaging, Cardiac Surgical Procedures, Heart Valve Diseases, Humans, Health Knowledge, Attitudes, Practice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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