Mitral valve prolapse but no mitral annular disjunction is related to mitral regurgitation progression in patients with Marfan syndrome
Authors: Servato ML , Lopez-Sainz A , Valente F , Fernandez-Galera R , Casas-Masnou G , Gutierrez L , Galian-Gay L , Limeres J , Sao-Aviles A , Gonzalez-Alujas MT , Rodriguez-Palomares JF , Evangelista A , Teixido-Tura G 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

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 (1,2). It has been associated with mitral valve prolapse (MVP). Limited data is available regarding the impact of the presence of MVP on the evolution of mitral regurgitation in these syndromic entities.

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 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 the first echocardiogram were evaluated. Electronic medical records were reviewed to register the need for mitral surgery. The 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). The 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, MAD was significantly associated with MVP (p= &lt;0.001) (Table 1). Concretely, 73 (31.1%) of the MFS patients had the concurrence of MAD and MVP and 14 (6.0%) of patients had isolated MAD (Table 2). At baseline, significant MR was observed in 30 (12.8%) of the MFS and in 18 (24.7%) of patients with concurrent MAD and MVP. Interestingly, significant MR was absent in patients with isolated MAD (Figure 1). MVP (OR 16.85 CI 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 &gt; = 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 +- 3.2yrs, 10 patients required mitral surgery (6 prostheses, 4 valvuloplasties).
After adjustment for the presence of MVP and time of follow-up, MAD was not associated with progression of MR (p= 0.529) but MVP was (OR 5.2 IC 1.70 - 15.93). Similarly, MVP (OR 5.6 CI 1.23 - 25.86) but not MAD (P= 0.096) was associated with the need for mitral surgery .,
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 MVP but not MAD was associated with mitral regurgitation evolution and the need for mitral surgery. Abstract Table 1 Abstract Figure 1