Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium

Authors

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

Language

English

Publication Date

11-5-2024

Journal

Journal of the American Heart Association

DOI

10.1161/JAHA.124.036274

PMID

39424426

PMCID

PMC11935710

PubMedCentral® Posted Date

10-18-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Humans, Male, Female, Middle Aged, Mitral Valve Prolapse, Cross-Sectional Studies, Mitral Valve, Smad3 Protein, Mitral Valve Insufficiency, Registries, Aortic Aneurysm, Thoracic, Aged, Adult, Echocardiography, Genetic Predisposition to Disease, Aorta, Thoracic, Phenotype, Transforming Growth Factor beta, Prevalence, cardiovascular genetics, congenital heart disease, Loeys–Dietz syndrome, mitral valve, thoracic aortic aneurysms and dissections

Published Open-Access

yes

Recommended Citation

Asokan, Kishan L; Landes, Jennifer R; Renders, Wannes; et al., "Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium" (2024). Faculty, Staff and Student Publications. 6273.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6273