Echocardiographic methods, quality review, and measurement accuracy in a randomized multicenter clinical trial of marfan syndrome

Background: The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. Methods: Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area-adjusted maximum aortic root diameter (ROOT_max) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOT _max Z score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. Results: Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOT_max measurements was independently associated (model R² = 0.15) with better image quality (P =.002) and later study reading date (P <.001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOT_max Z scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOT_max Z scores < 4.5. Conclusions: The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility.