{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:14:45Z","timestamp":1760238885141,"version":"build-2065373602"},"reference-count":10,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Background: The vestibular atrial septal defect is an interatrial communication located in the antero-inferior portion of the atrial septum. Reflecting either inadequate muscularization of the vestibular spine and mesenchymal cap during development, or excessive apoptosis within the developing antero-inferior septal component, the vestibular defect represents an infrequently recognized true deficiency of the atrial septum. We reviewed necropsy specimens from three separate archives to establish the frequency of such vestibular defects and their associated cardiac findings, providing additional analysis from developing mouse hearts to illustrate their potential morphogenesis. Materials and methods: We analyzed the hearts in the Farouk S. Idriss Cardiac Registry at Ann and Robert H. Lurie Children\u2019s Hospital in Chicago, IL, the Van Mierop Archive at the University of Florida in Gainesville, Florida, and the archive at Johns Hopkins All Children\u2019s Heart Institute in St. Petersburg, Florida, identifying all those exhibiting a vestibular atrial septal defect, along with the associated intracardiac malformations. We then assessed potential mechanisms for the existence of such defects, based on the assessment of 450 datasets of developing mouse hearts prepared using the technique of episcopic microscopy. Results: We analyzed a total of 2100 specimens. Of these, 68 (3%) were found to have a vestibular atrial septal defect. Comparable defects were identified in 10 developing mouse embryos sacrificed at embryonic data 15.5, by which stage the antero-inferior component of the atrial septum is usually normally formed. Conclusion: The vestibular defect is a true septal defect located in the muscular antero-inferior rim of the oval fossa. Our retrospective review of autopsied hearts suggests that the defect may be more common than previously thought. Increased awareness of the location of the defect should optimize its future clinical identification. We suggest that the defect exists because of failure, during embryonic development, of union of the components that bind the leading edge of the primary atrial septum to the atrioventricular junctions, either because of inadequate muscularisation or excessive apoptosis.<\/jats:p>","DOI":"10.3390\/jcdd7030035","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:10:09Z","timestamp":1599729009000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification and Morphogenesis of Vestibular Atrial Septal Defects"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9116-2835","authenticated-orcid":false,"given":"Rohit S.","family":"Loomba","sequence":"first","affiliation":[{"name":"Division of Cardiology, Advocate Children\u2019s Hospital, Chicago, IL 60453, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8926-3752","authenticated-orcid":false,"given":"Justin T.","family":"Tretter","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Mohun","sequence":"additional","affiliation":[{"name":"Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5163-9021","authenticated-orcid":false,"given":"Robert H.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Kramer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane E.","family":"Spicer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1136\/heartjnl-2016-310660","article-title":"Development of the atrial septum in relation to postnatal anatomy and interatrial communications","volume":"103","author":"Jensen","year":"2017","journal-title":"Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1017\/S1047951104002197","article-title":"Surgical treatment of an unusual atrial septal defect: The vestibular defect","volume":"14","author":"Fukuda","year":"2004","journal-title":"Cardiol. Young"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1017\/S1047951103000349","article-title":"The vestibular defect: An interatrial communication due to a deficiency in the atrial septal component derived from the vestibular spine","volume":"13","author":"Sharratt","year":"2003","journal-title":"Cardiol. Young"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.gde.2011.07.004","article-title":"Imaging heart development using high-resolution episcopic microscopy","volume":"21","author":"Mohun","year":"2011","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_5","unstructured":"Ezon, D., Goldberg, J., and Kyle, W. (2015). Atlas of Congenital Heart Disease Nomenclature, Ezon Educational Services."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1161\/01.RES.82.6.645","article-title":"Formation of the atrioventricular septal structures in the normal mouse","volume":"82","author":"Webb","year":"1998","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0002-9149(02)03106-5","article-title":"Deficiency of the vestibular spine in atrioventricular septal defects in human fetuses with down syndrome","volume":"91","author":"Blom","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/dvdy.21074","article-title":"A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development","volume":"236","author":"Snarr","year":"2007","journal-title":"Dev. Dyn."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1017\/S1047951100008155","article-title":"The anatomy of interatrial communications\u2014What does the interventionist need to know?","volume":"10","author":"Martins","year":"2000","journal-title":"Cardiol. Young"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/ccd.20162","article-title":"Evaluation and treatment of abnormalities of the interatrial septum","volume":"63","author":"Wahl","year":"2004","journal-title":"Catheter. Cardiovasc. Interv."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/7\/3\/35\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:32Z","timestamp":1760177312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/7\/3\/35"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,10]]},"references-count":10,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["jcdd7030035"],"URL":"https:\/\/doi.org\/10.3390\/jcdd7030035","relation":{},"ISSN":["2308-3425"],"issn-type":[{"type":"electronic","value":"2308-3425"}],"subject":[],"published":{"date-parts":[[2020,9,10]]}}}