| Title | Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. | | Author(s) | Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC | | Institution | McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. | | Source | N Engl J Med 2008 Jun 26; 358(26):2787-95. | | MeSH | Adolescent
Adrenergic beta-Antagonists
Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors
Aorta
Biphenyl Compounds
Blood Pressure
Calcium Channel Blockers
Child
Child, Preschool
Drug Therapy, Combination
Female
Heart Rate
Humans
Infant
Linear Models
Losartan
Male
Marfan Syndrome
Prospective Studies
Tetrazoles
Transforming Growth Factor beta
| | Abstract | 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 beta (TGF-beta) that can be mitigated by treatment with TGF-beta 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. | | Language | eng | | Pub Type(s) | Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 18579813 |
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