Abstract 19198: Is Z-Score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aneurysm Disease?
Introduction: Aortic Z-score is widely used in cardiology to monitor aortic dilation in aortic diseases, including Marfan syndrome. Z-score has also been used in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan patients. We found a void in information regarding the natural, non-pharmacological change in Z-score over time as children age. We studied the natural changes in aortic Z-score in normal children and children with Marfan syndrome. We also studied the effect of obesity on aortic Z-score
Methods: (1) We compared mean aortic Z-scores in 4 pediatric age groups, for both ascending aorta and aortic root
(2) We compared mean Z-score in adolescents of different BMI ranges
(3) We studied the change of aortic Z-score over time (aging) in both normal children and children with Marfan syndrome (All children were on no cardiac medications). Data from our echo studies were entered into the Boston Children’s Hospital Z-score calculator
Results: (1) We identified 361 children with normal echo studies. For the ascending aorta, the mean Z-score showed a sequential decrease as age increased. For the root there were no significant changes between the 4 age groups
(2) We divided 168 children (Age 10-12 and 15-18) based on BMI into 3 groups. For both the ascending aorta and the root there was a decrease in the mean Z score with increasing BMI.
(3) We observed the change in Z-score over time in 27 children without aortic disease with more than a single echo. Mean follow-up time was 24.6 months. 19 of 27 (70%) showed a decrease of root Z-score and 24 (89%) showed a decrease of ascending Z-score.
We identified 25 untreated Marfan children with multiple echo studies. Mean follow-up was 28.5 months. We used each 2 sequential studies as one observation, achieving a total of 30 observations. 12 (40%) showed a decrease in root Z-score. 10 (33%) showed a decrease in ascending Z-score
Conclusion: Aortic Z-score is affected by other factors even in the absence of any aortic disease process or any medical intervention. Specifically, Z-score decreases spontaneously as children age. Obesity decreases the Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt
Author Disclosures: S. Elkinany: None. C. Weismann: None. A. Curtis: None. T. Smith: None. T. Breen: None. M. Tranquilli: None. B.A. Ziganshin: None. J.A. Rizzo: None. S.K. Mukherjee: None. J.A. Elefteriades: None.
- © 2016 by American Heart Association, Inc.