FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 358:2787-2795 June 26, 2008 Number 26 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Pyeritz, R. E. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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 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.

Full Text of this Article

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:

• Pilop, C., Aregger, F., Gorman, R. C., Brunisholz, R., Gerrits, B., Schaffner, T., Gorman, J. H. III, Matyas, G., Carrel, T., Frey, B. M. (2009). Proteomic Analysis in Aortic Media of Patients With Marfan Syndrome Reveals Increased Activity of Calpain 2 in Aortic Aneurysms. Circulation 120: 983-991 [Abstract] [Full Text]  
• Matt, P., Schoenhoff, F., Habashi, J., Holm, T., Van Erp, C., Loch, D., Carlson, O. D., Griswold, B. F., Fu, Q., De Backer, J., Loeys, B., Huso, D. L., McDonnell, N. B., Van Eyk, J. E., Dietz, H. C., the GenTAC Consortium, (2009). Circulating Transforming Growth Factor-{beta} in Marfan Syndrome. Circulation 120: 526-532 [Abstract] [Full Text]  
• Braverman, A. C. (2009). Transforming Growth Factor-{beta}: A Biomarker in Marfan Syndrome?. Circulation 120: 464-466 [Full Text]  
• Gerhardinger, C., Dagher, Z., Sebastiani, P., Park, Y. S., Lorenzi, M. (2009). The Transforming Growth Factor-{beta} Pathway Is a Common Target of Drugs That Prevent Experimental Diabetic Retinopathy. Diabetes 58: 1659-1667 [Abstract] [Full Text]  
• Jarvelainen, H., Sainio, A., Koulu, M., Wight, T. N., Penttinen, R. (2009). Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy. Pharmacol. Rev. 61: 198-223 [Abstract] [Full Text]  
• Ramirez, F., Dietz, H. C. (2009). Extracellular Microfibrils in Vertebrate Development and Disease Processes. J. Biol. Chem. 284: 14677-14681 [Full Text]  
• Cassis, L. A., Gupte, M., Thayer, S., Zhang, X., Charnigo, R., Howatt, D. A., Rateri, D. L., Daugherty, A. (2009). ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice. Am. J. Physiol. Heart Circ. Physiol. 296: H1660-H1665 [Abstract] [Full Text]  
• Formigari, R., Michielon, G., Digilio, M. C., Piacentini, G., Carotti, A., Giardini, A., Di Donato, R. M., Marino, B. (2009). Genetic syndromes and congenital heart defects: how is surgical management affected?. Eur. J. Cardiothorac. Surg. 35: 606-614 [Abstract] [Full Text]  
• Grossfeld, P., Ye, M., Harvey, R. (2009). Hypoplastic Left Heart Syndrome: New Genetic Insights. J Am Coll Cardiol 53: 1072-1074 [Full Text]  
• De Backer, J. (2009). The expanding cardiovascular phenotype of Marfan syndrome. Eur J Echocardiogr 10: 213-215 [Full Text]  
• Carta, L., Smaldone, S., Zilberberg, L., Loch, D., Dietz, H. C., Rifkin, D. B., Ramirez, F. (2009). p38 MAPK Is an Early Determinant of Promiscuous Smad2/3 Signaling in the Aortas of Fibrillin-1 (Fbn1)-null Mice. J. Biol. Chem. 284: 5630-5636 [Abstract] [Full Text]  
• Tadros, T. M., Klein, M. D., Shapira, O. M. (2009). Ascending Aortic Dilatation Associated With Bicuspid Aortic Valve: Pathophysiology, Molecular Biology, and Clinical Implications. Circulation 119: 880-890 [Full Text]  
• Goland, S., Elkayam, U. (2009). Cardiovascular Problems in Pregnant Women With Marfan Syndrome. Circulation 119: 619-623 [Full Text]  
• Pyeritz, R. E (2009). Marfan syndrome: 30 years of research equals 30 years of additional life expectancy. Heart 95: 173-175 [Full Text]  
• Vahanian, A., Iung, B., Piérard, L., Dion, R., Pepper, J. (2009). CHAPTER 21 Valvular Heart Disease. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full Text]  
• Matt, P., Eckstein, F. (2008). eComment: Stabilizing aortic tissue after aortic root surgery in Marfan syndrome. ICVTS 7: 1166-1166 [Full Text]  
• Ahimastos, A. A., Dart, A. M., Kingwell, B. A., Jimenez, S. A., Rosenbloom, J., van Dijk, F. S., Meijers-Heijboer, H., Pals, G., Brooke, B. S., Dietz, H. C. III (2008). Angiotensin II Blockade in Marfan's Syndrome. NEJM 359: 1732-1734 [Full Text]  
• (2008). All you need to read in the other general journals. BMJ 337: a582-a582 [Full Text]  
• Pearson, G. D., Devereux, R., Loeys, B., Maslen, C., Milewicz, D., Pyeritz, R., Ramirez, F., Rifkin, D., Sakai, L., Svensson, L., Wessels, A., Van Eyk, J., Dietz, H. C. (2008). Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on Research in Marfan Syndrome and Related Disorders. Circulation 118: 785-791 [Full Text]  
• Pyeritz, R. E. (2008). A Small Molecule for a Large Disease. NEJM 358: 2829-2831 [Full Text]  
• (2008). Angiotensin-Receptor Blockers and Marfan Syndrome. Journal Watch Cardiology 2008: 1-1 [Full Text]