Clinical InvestigationMarfan SyndromeEchocardiographic Methods, Quality Review, and Measurement Accuracy in a Randomized Multicenter Clinical Trial of Marfan Syndrome
Section snippets
Patients
Subjects enrolled in this trial2 were individuals aged 6 months to 25 years who met the original Ghent criteria for MFS,4 with a body surface area (BSA)–adjusted ROOTmax Z score > 3 and absolute ROOTmax < 5 cm. Patients with prior aortic surgery were excluded. A total of 608 subjects were enrolled between February 2007 and February 2011. The study protocol was approved by the institutional review board or institutional ethics board at each participating center, and informed consent and assent
Results
Imaging of the aortic root was graded as excellent in 203 (33%), good in 357 (59%), and fair in 47 (8%) patients. ROOTmax was measurable at least once in all echocardiograms and in triplicate in 95%.
Discussion
Aortic root size is a major determinant in the clinical diagnosis of MFS13 and is the best predictor of cardiovascular outcome.14 Varying methods to assess aortic root size by echocardiography have been reported, including M-mode versus 2D imaging, systolic versus diastolic measurements, and leading edge–to–leading edge versus inner edge–to–inner edge measurements.6, 15, 16, 17 Most adult echocardiography laboratories use the leading edge–to–leading edge method in diastole, as recommended by
Conclusions
The echocardiographic methodology, training, and quality review process used in this multicenter randomized clinical trial resulted in a robust evaluation of aortic root dimensions with excellent reproducibility despite the challenges of a multicenter study design and the imaging difficulties common in patients with MFS. This will optimize our ability to detect differences in treatment effects between atenolol and losartan in children and young adults with MFS.
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This study was supported by U01 grants HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, and HL085057 from the National Heart, Lung, and Blood Institute (Bethesda, MD) and the US Food and Drug Administration Office of Orphan Products Development (Silver Spring, MD). Additional support was provided by the National Marfan Foundation (Port Washington, NY), Merck & Co., Inc. (Whitehouse Station, NJ), and Teva Canada Limited (Mirabel, QC, Canada). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of National Heart, Lung, and Blood Institute or the National Institutes of Health.
The authors have no conflict of interest to disclose.
Benjamin W. Eidem, MD, FASE served as Guest Editor on this article.