Molecular Changes in Children with Heart Failure Undergoing Left Ventricular Assist Device Therapy

• Published in: The Journal of pediatrics 2017-03, Vol.182, p.184-189.e1
• Main Authors: Medina, Elizabeth, PhD, Sucharov, Carmen C., PhD, Nelson, Penny, MS, Miyamoto, Shelley D., MD, Stauffer, Brian L., MD
• Format: Article
• Language: English
• Subjects: Adolescent; Age Factors; Analysis of Variance; Atrial Natriuretic Factor - metabolism; Biomarkers - metabolism; Blotting, Western; Child; Child, Preschool; Female; G-Protein-Coupled Receptor Kinase 2 - metabolism; Heart Failure - diagnosis; Heart Failure - surgery; Heart-Assist Devices; Humans; Linear Models; Male; Myocardium - metabolism; pathological gene program; Pediatrics; phospholamban; Receptors, Adrenergic, beta - metabolism; Reference Values; Risk Assessment; RNA, Messenger - metabolism; Sampling Studies; Sensitivity and Specificity; Tissue Donors; β-adrenergic receptor
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2016.11.011

Objective To determine whether left ventricular assist device (LVAD) treatment in children with heart failure would result in the modification of molecular pathways involved in heart failure pathophysiology. Study design Forty-seven explanted hearts from children were studied (16 nonfailing control, 20 failing, and 11 failing post-LVAD implantation [F-LVAD]). Protein expression and phosphorylation states were determined by receptor binding assays and Western blots. mRNA expression was measured with real-time quantitative polymerase chain reaction. To evaluate for interactions and identify correlations, 2-way ANOVA and regression analysis were performed. Results Treatment with LVAD resulted in recovery of total β-adrenergic receptor expression and β1 -adrenergic receptor (β1 -AR) in failing hearts to normal levels (β-adrenergic receptor expression : 67.2 ± 11.5 fmol/mg failing vs 99.5 ± 27.7 fmol/mg nonfailing, 104 ± 38.7 fmol/mg F-LVAD, P  ≤ .01; β1 -AR: 52.2 ± 10.3 fmol/mg failing vs 83.0 ± 23 fmol/mg non-failing, 76.5 ± 32.1 fmol/mg F-LVAD P  ≤ .03). The high levels of G protein-coupled receptor kinase-2 were returned to nonfailing levels after LVAD treatment (5.6 ± 9.0 failing vs 1.0 ± 0.493 nonfailing, 1.0 ± 1.3 F-LVAD). Interestingly, β2 -adrenergic receptor expression was significantly greater in F-LVAD (27.5 ± 12; P