|
|
Background Progressive enlargement of the aortic root, leading to dissection, is the main cause of premature death in patients with Marfan's syndrome. Recent data from mouse models of Marfan's syndrome suggest that aortic-root enlargement is caused by excessive signaling by transforming growth factor β (TGF-β) that can be mitigated by treatment with TGF-β antagonists, including angiotensin II–receptor blockers (ARBs). We evaluated the clinical response to ARBs in pediatric patients with Marfan's syndrome who had severe aortic-root enlargement.
Methods We identified 18 pediatric patients with Marfan's syndrome who had been followed during 12 to 47 months of therapy with ARBs after other medical therapy had failed to prevent progressive aortic-root enlargement. The ARB was losartan in 17 patients and irbesartan in 1 patient. We evaluated the efficacy of ARB therapy by comparing the rates of change in aortic-root diameter before and after the initiation of treatment with ARBs.
Results The mean (±SD) rate of change in aortic-root diameter decreased significantly from 3.54±2.87 mm per year during previous medical therapy to 0.46±0.62 mm per year during ARB therapy (P<0.001). The deviation of aortic-root enlargement from normal, as expressed by the rate of change in z scores, was reduced by a mean difference of 1.47 z scores per year (95% confidence interval, 0.70 to 2.24; P<0.001) after the initiation of ARB therapy. The sinotubular junction, which is prone to dilation in Marfan's syndrome as well, also showed a reduced rate of change in diameter during ARB therapy (P<0.05), whereas the distal ascending aorta, which does not normally become dilated in Marfan's syndrome, was not affected by ARB therapy.
Conclusions In a small cohort study, the use of ARB therapy in patients with Marfan's syndrome significantly slowed the rate of progressive aortic-root dilation. These findings require confirmation in a randomized trial.
Source Information
From the McKusick–Nathans Institute of Genetic Medicine and the Howard Hughes Medical Institute (B.S.B., J.P.H., N.P., B.L., H.C.D.), the Department of Surgery (B.S.B.), and the Department of Medicine and Cardiology (D.P.J.), Johns Hopkins University School of Medicine, Baltimore; and the Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium (B.L.).
Address reprint requests to Dr. Dietz at the McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 539 Broadway Research Bldg., 733 N. Broadway, Baltimore, MD 21205, or at hdietz{at}jhmi.edu.
Related Letters:
Angiotensin II Blockade in Marfan's Syndrome
Ahimastos A. A., Dart A. M., Kingwell B. A., Jiménez S. A., Rosenbloom J., van Dijk F. S., Meijers-Heijboer H., Pals G., Brooke B. S., Dietz H. C. III
Extract |
Full Text |
PDF
N Engl J Med 2008;
359:1732-1734, Oct 16, 2008.
Correspondence
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2008 Massachusetts Medical Society. All rights reserved. |
Previous
