Mitral annular disjunction in patients with syndromic hereditary aorthopaties
Authors: Servato M L , Lopez-Sainz A , Valente F , Fernandez-Galera R , Casas-Masnou G , Gutierrez L , Limeres J , Sao-Aviles A , Gonzalez-Alujas M T , Rodriguez-Palomares J F , Evangelista A , Teixido-Tura G 
Published: October 2021

Abstract

Background
Mitral annular disjunction (MAD) is a structural abnormality of the mitral annular fibrosus characterized by a separation between the atrial wall-mitral valve junction, and the left ventricular attachment (1). It has been associated with mitral valve prolapse (MVP) (2) but also, with arrhythmias and sudden cardiac death (SCD) (3). There is no evidence of its prevalence and clinical significance in patients with syndromic hereditary aortopathies.

Purpose
To evaluate the prevalence of MAD, PMV, and the combination of both in patients with syndromic hereditary thoracic aortic disease (HTAD) including Marfan (MFS), Loeys-Dietz (LDS) and vascular Ehlers-Danlos syndromes (vEDS), and its relationship with arrhythmias, SCD, mitral regurgitation (MR) severity and the need for mitral surgery at the follow-up.

Methods
Adult patients with syndromic HTAD seen at our specialized unit were retrospectively included. The presence of MAD, MVP, and significant MR at first echocardiogram were evaluated. Electronic medical records were reviewed to register the occurrence of arrhythmic events and the need of mitral surgery. Last echocardiogram available was also assessed to evaluate MR progression.

Results
A total of 295 patients were included (235 MFS, 42 LDS and 18 vEDS). Mean age at baseline was 39.0±14.4 and 52.9% were female. MAD was present in 87 (37.0%) of MFS, 6 (14.3%) of LDS and was not present in vEDS (p&lt;0.001). MVP was found in 105 (44.7%) of MFS, 6 (14.3%) of LDS and 0 in vEDS (p&lt;0.001).
In MFS, the presence of MAD was significantly associated with MVP (p≤0.001) (Table 1). However, 14 (6.0%) of patients had isolated MAD (Table 2). At baseline, significant MR was observed in 18 (24.7%) of patients with concurrent MAD and MVP and was not present in patients with isolated MAD (Table 2). MVP (OR 16.85 IC 4.43 – 64.07) but not MAD (p=0.607), was associated with significant MR in the multivariate analysis.
A second echocardiogram was available in 220 patients at ≥1 year (mean 4.1±1.4 years). Overall, 25 (11.4%) presented significant progression of MR, 0 in the isolated MAD group, 13 (19.4%) in the MAD/MVP group and 6 (20.0%) of the isolated MVP (p=0.007).
After a mean clinical follow-up of 7.5±3.2 years, 10 patients required mitral surgery (6 prosthesis, 4 valvuloplasty), 22 (9.4%) presented atrial fibrillation, flutter or supraventricular tachycardia (SVT), and 2 (0.9%) SCD.
After adjustment for the presence of MVP and time of follow-up, MAD was not associated with progression of MR (p=0.529) need for mitral surgery (p=0.096), atrial fibrillation-flutter or SVT (p=0.510) nor SCD. (p=0.997).

Conclusions
The prevalence of MAD in syndromic HTAD is high, especially in Marfan syndrome, and absent in vEDS. In this retrospective observational study, the presence of MAD in Marfan was not associated with mitral regurgitation evolution or arrhythmic events.

Funding Acknowledgement
Type of funding sources: None. Characteristics of MFS patientsPresence of significant MR by groups.