Retrospective Analysis of the Effect of Angiotensin II Receptor Blocker Versus Β-Blocker on Aortic Root Growth in Paediatric Patients With Marfan Syndrome

Study Questions:

How does therapy with an angiotensin II receptor blocker (ARB) compare with therapy with a beta-adrenergic antagonist (beta-blocker) for aortic root dilation among pediatric patients with Marfan syndrome?

Methods:

A cohort of 215 patients with Marfan syndrome (9.0 ± 5.7 years) was followed in a standardized clinical diagnostic program at a single institution. Of 82 untreated and unoperated patients, ARB (n = 22) or beta-blocker (n = 18) therapy was started in 40 patients. Aortic root diameter at the sinuses of Valsalva (SOV) was followed by echocardiography. The effect of treatment was measured by comparison of z scores of SOV diameter before and after treatment initiation.

Results:

Compared to no therapy, treatment with either an ARB or a beta-blocker was associated with significantly less SOV dilation (p < 0.05). The deviation of SOV enlargement from normal, expressed by the rate of change in z score, was significantly reduced by a mean difference of (z score) −0.56 ± 0.71 (p < 0.001) with ARB therapy and by a mean difference of −0.35 ± 0.68 (p < 0.05) with beta-blocker therapy. The prophylactic effect of ARB and beta-blocker therapies on aortic root dilation was similar in both groups (p > 0.05).

Conclusions:

The authors concluded that the effect on aortic root enlargement of ARB and beta-blocker therapy among pediatric patients with Marfan syndrome is similar. They reported that this is the first study that addresses the comparison of ARB and beta-blocker therapy in previously untreated pediatric patients with Marfan syndrome, and that both treatment strategies are beneficial in pediatric and adolescent patients.

Perspective:

Despite fairly limited supportive data, beta-blocker therapy has become an entrenched part of therapy in an attempt to reduce the rate of aorta dilation. Recently, studies in a mouse model of Marfan syndrome suggest that a deficiency of extracellular matrix fibrillin-1 leads to excess transforming growth factor-beta (TGF-ß) signaling that is responsible for progressive aortic root enlargement. The effect of ARBs on inhibition of TGF-ß signaling suggests that these might be beneficial in mitigating aortic root dilation in patients with Marfan syndrome. This study was a single-center retrospective review of a very small number of patients, with significant confounding factors (beta-blocker therapy was predominantly used prior to 2010, whereas ARBs were used from 2010-13; some beta-blocker patients crossed over to ARB therapy; and ARB therapy was added to beta-blocker therapy in other patients). At a minimum, its small sample sizes do not appear to allow for meaningful comparison between groups.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Aortic Surgery, Cardiac Surgery and CHD & Pediatrics, Congenital Heart Disease

Keywords: Transforming Growth Factor beta, Sinus of Valsalva, Extracellular Matrix, Dilatation, Pathologic, Receptors, Angiotensin, Marfan Syndrome


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