Abstract 10890: Aortic Stiffness Predicts Clinical Outcome and Rate of Aortic Root Growth in Marfan Syndrome
Background: The NHLBI Pediatric Heart Network randomized trial of atenolol vs. losartan in Marfan Syndrome demonstrated no significant treatment difference in the rate of change in body surface area adjusted maximum aortic root diameter z score (AoRz).
Objectives: To report trial results on aortic stiffness and to determine whether aortic stiffness predicts clinical outcome and change in AoRz.
Methods: 608 patients (6 mo - 25 yr) who met original Ghent criteria and had AoRz > 3 were enrolled. Echocardiograms obtained at 0, 6, 12, 24 & 36 months were centrally interpreted. Aortic dimensions were measured by 2D imaging, and stiffness indices were calculated for aortic root (AoR) and ascending aorta (AA). Where appropriate, stiffness measurements were indexed to 1/sqrt(R-R interval) to adjust for heart rate. Data were analyzed by multivariable mixed effects modeling and Cox regression.
Results: The rate of change over three years in heart rate-adjusted AoR stiffness index differed by treatment (p = 0.016), with a decrease in the atenolol group and no significant change in the losartan group (-0.29 ± 0.14 vs. 0.14 ± 0.14/year). There was no significant treatment effect on the rate of change for AA stiffness index or for elastic modulus (AoR and AA). In the entire cohort, baseline AoR but not the AA stiffness index predicted the rate of change in ARz, with above-average stiffness index (≥ 10) predicting a slower annual decline of AoRz (-0.08 ± 0.02 vs. -0.15 ± 0.01 for below-average stiffness, p < 0.001), even after adjusting for baseline age. Elastic modulus was not a significant predictor of rate of change in AoRz. AoR elastic modulus >122 kPA (75th %ile) independently predicted the composite outcome of AoR surgery, dissection or death (hazard ratio 2.17, 95% CI 1.02 - 4.63, p = 0.04), controlling for baseline age and AoRz. Crude 3-year event rates were 10.4% vs. 3.2% for higher vs. lower elastic modulus groups, respectively.
Conclusions: Atenolol reduced AoR stiffness over 3 years, while losartan did not. In this medically-treated cohort, higher baseline AoR stiffness was associated with a smaller decrease in AoRz, and a greater hazard of AoR dissection/surgery/death. These data suggest that aortic stiffness measures may identify patients at higher risk and guide management.
Author Disclosures: E. Selamet Tierney: None. J.C. Levine: None. L.A. Sleeper: None. M.J. Roman: None. T.J. Bradley: None. S.D. Colan: None. S. Chen: None. M. Campbell: None. M.S. Cohen: None. J. De Backer: None. H. Heydarian: None. A. Hoskoppal: None. W.W. Lai: None. A. Liou: None. E. Marcus: None. A. Nutting: None. A.K. Olson: None. G.D. Pearson: None. D. Parra: None. M.E. Pierpont: None. B.F. Printz: None. R.E. Pyeritz: None. W. Ravekes: None. A.M. Sharkey: None. S. Srivastava: None. L. Young: None. R.V. Lacro: None.
- © 2015 by American Heart Association, Inc.