Speckle tracking analysis of the left ventricular anterior wall shows significantly decreased relative radial strain patterns in dystrophin deficient mice after 9 months of age ΠPLOS Currents Muscular Dystrophy

Background: Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder with an incidence of 1 in 3,500 male births. Early treatment of DMD cardiomyopathy is under investigation and echocardiographic analysis of strain patterns may provide measures to better quantify early treatment outcomes. Methods: We compared cardiac function in 3, 9 and 12 month old dystrophin deficient mdx mice to wild type (C57BL10/J) using in vivo high frequency echocardiography (Vevo 770, VisualSonics, Inc., Toronto, CA) and 2D speckle tracking [Velocity Vector Imaging (VVI), Siemens Medical Solutions, Inc., Malvern, PA]. Mice were anesthetized with 1-2% inhaled isoflurane and images were obtained using a 30 MHz transducer in modified parasternal long and short axis views obtained at the level of the papillary muscles. Myocardial motion was analyzed using VVI in single-beat reconstructed images. Results: M-mode imaging showed significantly decreased shortening fraction in mdx mice compared to wild type at 12 months of age (SF% 26.6±3 vs. 32.2±2; p=0.002). Mdx mice showed significantly increased cardiac fibrosis at 12 months of age compared to controls (p<0.0001). Speckle tracking analysis of the left anterior mid ventricular wall segment showed significantly decreased relative radial strain in mdx mice at 9 and 12 months (4.5±1.3% vs. 8.4±0.7%; p=0.001). There were no significant differences in circumferential or longitudinal strain. Conclusion: Mdx mice show significantly decreased LV anterior mid wall radial strain with mild cardiomyopathy after 9 months of age compared to wild type. Speckle tracking analysis may provide novel outcome measures for preclinical cardiac drug treatment studies in DMD.