Abstract 13285: Sensitivity to Beta-Adrenergic Stimulation in Pediatric Failing Single Ventricle Myocardium

Abstract

Introduction: Children with heart failure (HF) in the context of palliated single ventricle congenital heart disease (SV) are treated with various pharmacotherapies, all with limited efficacy. Specifically, outcomes with β-blockade for HF in SV children are disparate from those in adult HF, even with similar downregulation of β 1 -adrenergic receptors (AR) in both populations. Hypothesis: Downregulation of β 1 -AR in pediatric SV subjects results in a unique contractile phenotype. Methods: Hearts were obtained from SV children who underwent transplant between 2010-2020. Non-failing SV (SV-NF) subjects underwent primary transplantation and had no signs of HF at the time of transplant. Failing SV (SV-F) subjects required transplantation due to end-stage HF (including refractory protein losing enteropathy or plastic bronchitis). At the time of transplant, trabeculae are isolated from the right ventricle of the explanted SV heart and mounted in a multi-chamber muscle bath. Ex vivo contractile response of isolated trabeculae is measured in response to the non-selective β-agonist isoproterenol; only trabeculae with an appropriate isoproterenol response are included in analyses. Results: Although β 1 -AR density is decreased in both SV-NF and SV-F myocardium, trabecular contractility assessment demonstrates increased sensitivity to isoproterenol in SV-F compared to SV-NF. Maximal tension generation with isoproterenol is similar between SV-NF and SV-F. Isoproterenol sensitivity in SV-F is comparable to that of non-failing adult hearts (age <40, n=4). Conclusions: Pediatric SV-F trabeculae demonstrate increased sensitivity to β-adrenergic stimulation when compared to SV-NF, but is similar to that of non-failing adult hearts. The preservation of adrenergic responsiveness may suggest that chronic, adverse β 1 -AR signaling is not part of the pathophysiology of failing SV, which may limit the effectiveness of β-blockade for HF indications in this population.