Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium
Background Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a c...
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Wiley
2024-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.036274 |
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| author | Kishan L. Asokan Jennifer R. Landes Wannes Renders Laura Muiño Mosquera Julie De Backer David W. Jantzen Anji T. Yetman Gisela Teixido‐Tura Arturo Evangelista Richmond Jeremy Edward G. Jones Shaine Morris Tam Doan Maral Ouzonian Alan Braverman Guillaume Jondeau Olivier Milleron Dianna M. Milewicz Siddharth K. Prakash |
| author_facet | Kishan L. Asokan Jennifer R. Landes Wannes Renders Laura Muiño Mosquera Julie De Backer David W. Jantzen Anji T. Yetman Gisela Teixido‐Tura Arturo Evangelista Richmond Jeremy Edward G. Jones Shaine Morris Tam Doan Maral Ouzonian Alan Braverman Guillaume Jondeau Olivier Milleron Dianna M. Milewicz Siddharth K. Prakash |
| author_sort | Kishan L. Asokan |
| collection | DOAJ |
| description | Background Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross‐sectional analysis of 2014–2023 data in the Montalcino Aortic Consortium registry. Methods and Results MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) in transforming growth factor‐β pathway genes. The combination of MR and MVP was associated with mitral surgery and arrhythmias. In the subgroup with available images, MAD was enriched in SMAD3 PV compared with other transforming growth factor‐β PV (prevalence ratio 1.8 [1.1–2.8], P <0.02). Severe disjunction (>10 mm) was only observed in the transforming growth factor‐β subgroup and was further enriched in participants with SMAD3 PV (prevalence ratio 3.1 [1.1–8.6]). MVP (prevalence ratio 5.2 [3.0–9.0]) and MR (PR 2.7 [1.8–3.9]) were increased in participants with MAD, but MAD was not independently associated with adverse cardiac or aortic events. Conclusions Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor‐β pathway genes, particularly SMAD3. MR and MVP but not MAD are associated with adverse aortic and cardiac events. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for heritable thoracic aortic disease should be considered for such individuals, especially if they also have a family history of heritable thoracic aortic disease. |
| format | Article |
| id | doaj-art-6412c93cdefe495f925a1a5d4ad6db2b |
| institution | DOAJ |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-6412c93cdefe495f925a1a5d4ad6db2b2025-08-20T02:48:57ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-11-01132110.1161/JAHA.124.036274Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic ConsortiumKishan L. Asokan0Jennifer R. Landes1Wannes Renders2Laura Muiño Mosquera3Julie De Backer4David W. Jantzen5Anji T. Yetman6Gisela Teixido‐Tura7Arturo Evangelista8Richmond Jeremy9Edward G. Jones10Shaine Morris11Tam Doan12Maral Ouzonian13Alan Braverman14Guillaume Jondeau15Olivier Milleron16Dianna M. Milewicz17Siddharth K. Prakash18University of Texas Health Science Center at Houston TXUniversity of Texas Health Science Center at Houston TXGhent University Hospital Ghent BelgiumGhent University Hospital Ghent BelgiumGhent University Hospital Ghent BelgiumUniversity of Nebraska Medical Center Omaha NEUniversity of Nebraska Medical Center Omaha NEUniversity Hospital Vall d’Hebron Barcelona SpainUniversity Hospital Vall d’Hebron Barcelona SpainUniversity of Sydney AustraliaTexas Children’s Hospital Houston TXTexas Children’s Hospital Houston TXTexas Children’s Hospital Houston TXUniversity of Toronto CanadaWashington University School of Medicine St Louis MOHospital Bichat‐Claude Bernard Paris FranceHospital Bichat‐Claude Bernard Paris FranceUniversity of Texas Health Science Center at Houston TXUniversity of Texas Health Science Center at Houston TXBackground Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross‐sectional analysis of 2014–2023 data in the Montalcino Aortic Consortium registry. Methods and Results MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) in transforming growth factor‐β pathway genes. The combination of MR and MVP was associated with mitral surgery and arrhythmias. In the subgroup with available images, MAD was enriched in SMAD3 PV compared with other transforming growth factor‐β PV (prevalence ratio 1.8 [1.1–2.8], P <0.02). Severe disjunction (>10 mm) was only observed in the transforming growth factor‐β subgroup and was further enriched in participants with SMAD3 PV (prevalence ratio 3.1 [1.1–8.6]). MVP (prevalence ratio 5.2 [3.0–9.0]) and MR (PR 2.7 [1.8–3.9]) were increased in participants with MAD, but MAD was not independently associated with adverse cardiac or aortic events. Conclusions Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor‐β pathway genes, particularly SMAD3. MR and MVP but not MAD are associated with adverse aortic and cardiac events. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for heritable thoracic aortic disease should be considered for such individuals, especially if they also have a family history of heritable thoracic aortic disease.https://www.ahajournals.org/doi/10.1161/JAHA.124.036274cardiovascular geneticscongenital heart diseaseLoeys–Dietz syndromemitral valvethoracic aortic aneurysms and dissections |
| spellingShingle | Kishan L. Asokan Jennifer R. Landes Wannes Renders Laura Muiño Mosquera Julie De Backer David W. Jantzen Anji T. Yetman Gisela Teixido‐Tura Arturo Evangelista Richmond Jeremy Edward G. Jones Shaine Morris Tam Doan Maral Ouzonian Alan Braverman Guillaume Jondeau Olivier Milleron Dianna M. Milewicz Siddharth K. Prakash Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular genetics congenital heart disease Loeys–Dietz syndrome mitral valve thoracic aortic aneurysms and dissections |
| title | Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium |
| title_full | Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium |
| title_fullStr | Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium |
| title_full_unstemmed | Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium |
| title_short | Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium |
| title_sort | mitral annular disjunction in heritable thoracic aortic disease insights from the montalcino aortic consortium |
| topic | cardiovascular genetics congenital heart disease Loeys–Dietz syndrome mitral valve thoracic aortic aneurysms and dissections |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.036274 |
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