Mitral annular disjunction and its progression during childhood in Marfan syndrome

Abstract

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 and results: We included patients <21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia 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.

Keywords: Marfan syndrome; aortic root dilation; cardiac magnetic resonance imaging; children; echocardiography; mitral annular disjunction.

Graphical Abstract

Figure 1

Identifying MAD and ‘pseudo’ MAD in MVP. (A) ‘Pseudo’ MAD (arrows) in MVP in a patient with both MVP and MAD (double-ended arrow). (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.

Figure 2

Venn diagram of mitral valve prolapse (MVP) and mitral annular disjunction (MAD) in 185 patients <21 years old with Marfan syndrome.

Figure 3

Aortic root z-scores between Marfan syndrome patients with and without mitral annular disjunction (A) and among the four age quartiles (B). MAD, mitral annular disjunction.

Figure 4

The agreement between echocardiography (echo) and cardiac magnetic resonance (CMR) imaging on the separation distance between the left ventricular (LV) crest and mitral valve (MV) posterior hinge point (A) Pearson correlation and (B) Bland–Altman plot and inter-rater variability by echocardiography (C) and by CMR (D). ICC, intraclass correlation. 95% CI, 95% confidence interval.