[I-S05-01] State of Art: Beta-receptor in Pediatric Heart Failure
Although the pathophysiology and treatment of adult heart failure (HF) are well studied, HF in children remains poorly understood. In adults, adrenergic receptor (AR)-mediated adaptation plays a central role in cardiac abnormalities in HF, and these patients respond well to β-blocker (BB) therapy. However, in children with HF, there is a growing body of literature suggesting a lack of efficacy of adult HF therapies. Due to these unanticipated differences in response to therapy and the paucity of data regarding the molecular adaptation of the paediatric heart, we investigated the molecular characteristics of HF in children. Explanted hearts from adults and children with idiopathic dilated cardiomyopathy and non-failing controls were used in the study. Our results show that the molecular characteristics of pediatric HF are strikingly different from their adult counterparts. There are differences in β1- and β2-AR expression, up-regulation of connexin43, phosphatase expression and in the phosphorylationof phospholamban. More recently we have discovered gender-based differences in β-AR expression patterns in pediatric HF. There is a different adaptation of β-AR and adrenergic signaling pathways in children with HF compared with adults. Our results begin to address the disparities in cardiovascular research specific to children and suggest that age-related differences in adaptation could influence the response to therapy. These findings could lead to a paradigm shift in the contemporary approach to and management of children with HF.