Are aortic biomechanical properties early markers of dilatation in patients with Marfan Syndrome? – A Systematic Review and Meta-Analysis

Abstract

AbstractBackgroundAlthough the stiffness of tissue is known to play an important role in aortic dilatation, the current guidelines for offering a preventative aortic surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in-vivo aortic stiffness measurements in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation.MethodsFollowing the PRISMA guidelines, we collected literature on diameter and three in-vivo stiffness measures: Pulse Wave Velocity (PWV),β-stiffness index and Distensibility, at five different aortic locations in patients with Marfan syndrome. Reported results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining extracted data from the reviewed literature. Regression with respect to age and statistical comparison were performed on the augmented dataset for all three measures at five different locations.Results30 articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be statistically higher in Marfan at most aortic locations, but only when the aorta is already dilated. Distensibility was found to be lower at all aortic locations even in non-dilated aortas, and its decrease has been associated with higher chances of developing aortic dilatation.β-stiffness index was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis based on a total 1197 datapoints, diameter was found to be higher only at the root (p <0.001). All stiffness measures showed a significant variation with age. PWV at the root and carotid-femoral region was not statistically different (p= 0.62 andp= 0.14 respectively), but was positively correlated with age at all locations. Distensibility andβ-stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation.ConclusionBased on the results in the literature,β-stiffness index and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further analysis based on combined aortic stiffness and diameter criteria is recommended to evaluate aortic disease in a comprehensive way and assist clinical decisions for prophylactic surgery.