Mitral annular disjunction and its progression during childhood in Marfan syndrome

European Heart Journal - Cardiovascular Imaging (2024) 25, 1306–1314 https://doi.org/10.1093/ehjci/jeae125 ORIGINAL PAPER Mitral annular disjunction and its progression during childhood in Marfan syndrome 1 Division of Cardiology, Texas Children’s Hospital, 6651 Main Street MC-E1920, Houston, TX 77030, USA; and 2Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Received 26 April 2024; revised 5 May 2024; accepted 5 May 2024; online publish-ahead-of-print 10 May 2024 Aims Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood. ................................................................................................................................................... Methods We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia and results lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram–CMR agreement. Bland–Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P < 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P < 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI −0.0002, +0.0005 mm/m/year). ................................................................................................................................................... Conclusion MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS. * Corresponding author. E-mail: The study was performed at Texas Children’s Hospital and Baylor College of Medicine in Houston, Texas, USA. The abstract received Top Investigator Award at the 34th Annual Scientific Sessions of the American Society of Echocardiography in National Harbor, MD, in 2023. † These authors contributed equally to this work. © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Tam T. Doan 1,2*†, Alejandra Iturralde Chavez1,2†, Santiago O. Valdes1,2, Justin D. Weigand1,2, James C. Wilkinson1,2, Anitha Parthiban1,2, Sara B. Stephens1,2, Ricardo H. Pignatelli1,2, and Shaine A. Morris1,2 Mitral annular disjunction and progression in pediatric Marfan syndrome 1307 Graphical Abstract Keywords mitral annular disjunction • Marfan syndrome • children • aortic root dilation • echocardiography • cardiac magnetic resonance imaging Introduction Mitral annular disjunction (MAD) refers to the anatomical separation between the posterior mitral valve (MV) annulus and the crest of the left ventricular (LV) myocardium.1–4 This condition is strongly asso ciated with mitral valve prolapse (MVP), a common feature in patients with Marfan syndrome (MFS).2,5 The presence of MAD has been asso ciated with higher rates of aortic events, mitral valve surgery, and ar rhythmia in patients with MFS.6–13 While previous studies have reported MAD to be more prevalent in children than adults with MFS,8 it remains unclear whether MAD was an acquired condition and how it progresses during childhood. Additionally, imaging methods used to measure LV–MV separation distance and the criteria used to define MAD are not consistent between studies.9,13–16 MAD has been identified using both echo cardiography and cardiac magnetic resonance imaging (CMR) in adults, although the agreement on MAD or correlation of LV–MV separation distance between the two modalities has not been wide ly studied. In this study, we developed a standardized method to measure LV– MV separation distance and evaluated its reproducibility and MAD agreement between two readers, as well as between echocardiog raphy and CMR. We then investigated the prevalence of MAD, its as sociation with MVP and aortic root dilation, and MAD progression during childhood in pediatric MFS. By doing so, we aimed to establish a foundation for a better understanding of MAD’s impact on children with MFS and further investigations into MAD in other pediatric populations. ................................................................................................................................................... 1308 T.T. Doan et al. row). (B) ‘Pseudo’ MAD in a patient with MVP without MAD. (C ) MAD in a patient with MVP, measured on echocardiogram at peak T-wave (arrow on the ECG tracing), between the LV myocardium and the posterior MV leaflet hinge point (arrowheads). (D) MAD in a patient with MVP, measured on cardiac magnetic resonance imaging. Two dotted lines were drawn, one crossing the two MV leaflet hinge points and a second one along the crest of LV myocardium. The distance between the two lines as they crossed the posterior wall was measured. LV, left ventricular; MAD, mitral annular disjunction; MV, mitral valve; MVP, mitral valve prolapse. Methods Study population This retrospective study included all patients with MFS under 21 years old seen at Texas Children’s Hospital who had an initial echocardiogram be tween January 2012 and December 2022. MFS was defined as meeting the 2010 Ghent criteria17 as well as either a pathogenic FBN1 variant or ec topia lentis and no other explanatory genetic conditions. Only patients with an initial echocardiogram prior to mitral valve surgery were included. Patient demographics, including age, sex, race, ethnicity were collected. We (...truncated)