Abstract 19633: Comparison of Angiotensin II Receptor Blocker versus Beta-blocker Therapy in Genetically Classified Children With Marfan Syndrome

Abstract

Background: Children with Marfan syndrome (MFS) treated with angiotensin II receptor blocker (ARB) or beta-blocker (BB) therapy show a reduction in the rate of aortic root (AR) growth, yet substantial variability in effect remains. Adult data suggests that patients with haploinsufficient (HI) mutations may be more responsive to ARBs compared with dominant negative (DN) mutations. This study sought to assess the effect of genotype on the rate of AR growth in children treated with either ARB or BB. Methods: A retrospective review of all individuals with MFS assessed at our institution since 1980 was undertaken; those with ≥2 echocardiograms a minimum of 1 year apart and a documented disease-causing fibrillin-1 (FBN1) mutation were included. One patient with infantile MFS was excluded given extremely AR growth. Genotypes were classified by predicted protein effect as either HI or DN. Multivariable longitudinal linear regression analysis was used to compare average rate of AR growth by genotype and medical therapy using serial echocardiographic data. Results: Overall 41 children were included, including 18 with HI and 23 with DN mutations. Males comprised 58%. There was no difference in median age at first echo (HI 5.4 years, IQR 3.9-9.3 vs. DN 5.2 years, IQR 3.4-10.6 years, p=0.97), follow-up time (HI 5.8 years, IQR 4.6-8.2 vs. DN 4.9 years, IQR 3.3-8.7, p=0.35), AR dimension (HI 26 mm, IQR 23-29 vs DN 26 mm, IQR 22-37, p=0.81), or AR z-score (HI 3.0, IQR 2.3-4.0 vs DN 3.4, IQR 2.4-4.2, p=0.58). AR growth rate was greater in children with DN mutations (z-score annual change HI -0.04 vs DN +0.07, p<0.0001). When evaluating AR growth only in patients on ARB or BB monotherapy, patients on ARB with DN mutations grew significantly faster than those on BB therapy with DN mutations (p=0.02). Conclusions: In our cohort, patients with MFS and DN mutations had slower growth on BB therapy compared to those on ARB therapy. Genetic testing may play an important role in targeted medical therapy in MFS.