Beyond the Sinus of Valsalva: Positive Effect of Angiotensin II Receptor Blockers on Mitral Valve Prolapse in a Retrospective Analysis of Pediatric Patients with Marfan Syndrome

Objectives: In recent years, treatment with AT-II-receptor-blockers (ARB) in patients with Marfan syndrome (MFS) has been well established. All studies, so far, focused on the growth development of the aortic root. Until now, no study has focused on the effect on the also regularly appearing mitral valve prolapse (MVP) in MFS. The aim of our study was to retrospectively analyze the treatment effect of ARB on the degree of MVP in pediatric patients with MFS.

Methods: Since 2008, we investigated 381 patients (11.4 ± 5.5 years) with suspected MFS. 139 patients were diagnosed with MFS. 61 patients showed MVP. We retrospectively analyzed database data and 2D-echocardiograms. Because of the high error measuring the actual MVP in millimeter mitral anular diameter (MAD) was used as a surrogate parameter for MVP in Marfan patients (Pini R, 1989, Circulation). Patients in the treatment group received oral Valsartan, control patients had no treatment. Patients taking β-blockers or having being operated on the aorta were excluded to clearly indicate group allocation.

Results: Prevalence of MVP in pediatric Marfan patients was 43,8%. In the control group the z-score of the MAD did not change significantly during the observation period. In patients treated with an ARB the z-score of the MAD was significantly reduced. Detailed data are shown in Table 1.

Table 1 Demographic and mitral valve before therapy initiation or at first visit (t0) and at last follow up (t1) in patients with MFS without treatment (control) or treated with an angiotensin receptor blocker (ARB)

	control group n = 12 (3 female)			ARB group n = 8 (4 female)
Demographic data and mitral anular diameter.
Demographic data
Age (years) at treatment initiation / first visit (years)	8.2 ± 4.75			12.3 ± 3.61
Follow up period in years	2.4 ± 1.93			3.4 ± 2.08
Mitral valve prolapse	t0	t1	p-value	t0	t1	p-value
z-score of mitral anular diameter	2.23	2.04	0.5121	2.59	2.21	0.0336
ARB, angiotensin II receptor blocker

Conclusion: Prevalence of MVP in children with MFS is 40 times higher than in a healthy population (Sattur S, 2010, Exp Clin Cardiol). In our study treatment with an ARB in pediatric patients with MFS leads to a significant reduction of the mitral anular diameter as a surrogate parameter for MVP. This first data suggests another positive effect of ARB treatment in MFS patients beyond the growth restrictive effect on the aorta. Future studies will have to analyze greater numbers of patients, the long term effect and develop better imaging methods for the detailed analysis of MVP e.g., MRI.