Abstract 19165: Regional Changes in Cellular and Molecular Pathology in Children With End-stage Dilated Cardiomyopathy: Correlation With Cardiac Performance

Dilated cardiomyopathy (DCM) carries poor prognosis in children, often needing heart transplant. Regional differences in left ventricular (LV) function suggest inhomogeneous expression of contractility related proteins. However, associations between myocardial performance and histological / molecular findings are poorly defined. We sought to investigate associations of regional myocardial performance with histological and molecular changes in hearts explanted from children with DCM, undergoing transplantation. Clinical and echo features (including tissue Doppler and strain) were correlated with histological and molecular findings in hearts explanted from 9 children [median age 2.8 years (range 4.4 months-17 years); 6 had LVAD]. Interstitial fibrosis, myocyte volume, and expression of proteins (western blot) implicated in fibrosis and function ( p38 , ERK , phospho- JNK , phospho- GSK , SMA , myosin heavy chain, cadherin, ILK , sarcoplasmic reticulum Ca 2+ -ATPase [SERCA2a], phospho- CamKII , phospholamban [PLN], and phospho-PLN) were correlated with speckle tracking strain from 11 regions per patient (basal and mid regions of anterior septum, anterior, lateral, posterior and inferior LV segments, and right ventricular [RV] free wall). On average, no significant difference was noted for the percentage of fibrosis and myocyte volume between the various LV segments, and between RV and LV. LV dimension, systolic and diastolic function were not related to interstitial fibrosis, myocyte volume or molecular signaling. Tricuspid annular plane systolic excursion was related to myocyte volume (r=0.89; p p p =0.05). Global longitudinal strain was related to expression of ILK and SERCA2a (ILK, r=0.78, p =0.02; SERCA2a, r=0.71, p =0.04). This study demonstrated association of regional cardiac function in children with DCM with expression of calcium-cycling and contractile proteins, as well as interstitial fibrosis. These findings have implications for diagnosis and therapeutic targets in pediatric DCM.