Possible Prophylactic Effect of High-Dose Angiotensin II Type 1 Receptor Blockers on Pediatric Patients with Marfan Syndrome

Objectives: Due to a risk of dynamic dilatation of sinus of Valsalvae (SV) a prophylactic medical treatment is suggested also in pediatric patients with Marfan Syndrome (MFS). Based on pathogenesis of MFS with increasing transforming growth factor-β (TGFß) signaling, prophylactic medication with angiotensin II type 1 receptor blockers (ATII) was expected to be a treatment with high potential. Now first published large randomized trials demonstrate failing of ATII being superior to prophylaxis with beta-blockers (BB). In childhood dose of treatment with ATII is variable and dose related effect on aortic root dilatation in children has not been investigated yet. High dose of ATII may show a significant impact on growth of SV and could then be superior to BB treatment.

Methods: Since 2008 we investigated 329 patients (10.9 ± 5.8 years) with suspected MFS, whereas 125 patients were diagnosed with MFS. Thereby 79 showed indication for prophylactic treatment. ATII was used in 54 patients (BB, n = 25). To evaluate dose-related impact, we retrospectively divided those patients in ATII groups (A: 0.5–1.0, B: >1.0–1.5, C: >1.5 mg/kg/d) to measure progression of SV dilatation (Z-score) via echocardiography.

Results: Mean follow-up period in groups A (n = 23), B (n = 17), and C (n = 13) after initiation of therapy with ATII was 17.75 ± 14.19 months (BB 50.50 ± 43.01). Z-score decreased in all groups after follow-up period (Table 1). Using linear regression rate of change between the three groups did not show linear correlation.

Conclusion: Overall effect of BB and ATII were similar, whereas medication with ATII statistically seems to be more effective. Superiority of medium and high dose of AT II could not be demonstrated, because there may be a group of non-responders. Further investigations with larger pediatric patient groups and pharmacokinetic and pharmacodynamic models need to be done to finally estimate the effect of high dose ATII and to evaluate reasons for patients not responding to prophylaxis.