There are differences in diastolic parameters in childhood CKD that persist during dialysis and after transplantation. Systolic parameters are preserved, with significant improvement in systolic myocardial deformation following transplantation. The impact of persistent diastolic changes on long-term outcomes requires further investigation.

Objectives Adrenergic receptor (ADR) genotypes have been associated with adverse outcomes in heart failure. Our objective was to evaluate the association of ADR genotypes with post-Norwood outcomes in infants with hypoplastic left heart syndrome (HLHS). Methods Infants with HLHS participating in the Pediatric Heart Network Single Ventricle Reconstruction Trial underwent genotyping for four single nucleotide polymorphisms in three ADR genes: ADRB1_231A/G, ADRB1_1165G/C, ADRB2_5318C/G and ADRA2A_2790C/T. The association of genotype with freedom from serious adverse events (SAE) (death, transplant, extra-corporeal membrane oxygenation, cardiopulmonary resuscitation, acute shunt failure, unplanned re-operations, or necrotizing enterocolitis) during 14 months follow-up was assessed using Cox regression and the association with post-Norwood complications was assessed using Poisson regression. Models were adjusted for clinical and surgical factors. Results The study included 351 eligible patients (62% male; 83% White). The mean age at Norwood procedure was 5.6±3.6 days. 152 patients had SAEs during 14-month follow-up including 84 deaths and 10 transplants. ADRA2A_2790CC genotype had lower SAE-free survival compared to CT/TT genotypes during follow-up (Log rank test, p=0.02) and this association was independent of clinical and surgical risk factors (Adjusted Cox regression. HR 1.54 [1.04, 2.30] p=0.033). Post-Norwood complication rate did not differ by genotype. Conclusions Infants with HLHS harboring ADR genotypes that are associated with higher catecholamine release or sensitivity had lower event-free survival after staged palliation. Excess catecholamine activation may adversely affect cardiovascular adaptation after the Norwood procedure. Future studies should explore if targeting adrenergic activation in those harboring risk genotypes can improve outcomes. (ClinicalTrials.gov number, NCT00115934)

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Background The optimal management pathway for the dysfunctional right ventricular outflow tract (RVOT) is uncertain. We evaluated the long‐term outcomes and clinical impact of stent implantation for obstructed RVOTs in an era of rapidly progressing transcatheter pulmonary valve technology. Methods Retrospective review of 151 children with a biventricular repair who underwent stenting of obstructed RVOT between 1991 and 2017. Results RVOT stenting resulted in significant changes in peak right ventricle (RV)‐to‐pulmonary artery (PA) gradient (39.4 ± 17.1–14.9 ± 8.3; p < 0.001) and RV‐to‐aortic pressure ratio (0.78 ± 0.22–0.49 ± 0.13; p < 0.001). Subsequent percutaneous reinterventions in 51 children to palliate recurrent stenosis were similarly effective. Ninety‐nine (66%) children reached the primary outcome of subsequent pulmonary valve replacement (PVR). Freedom from PVR from the time of stent implantation was 91%, 51%, and 23% at 1, 5, and 10 years, respectively. Small balloon diameters for stent deployment were associated with shorter freedom from PVR. When additional children without stent palliation (with RV‐to‐PA conduits) were added to the stent cohort (total 506 children), the multistate analysis showed the longest freedom from PVR in those with stent palliation and subsequent catheter reintervention. Pulmonary regurgitation was well‐tolerated clinically. Indexed RV dimensions and function estimated by echocardiography remained stable at last follow up or before primary outcome. Conclusion Prolongation of conduit longevity with stent implant remains an important strategy to allow for somatic growth to optimize the risk‐benefit profile for subsequent surgical or transcatheter pulmonary valve replacement performed at an older age.

Introduction: Variants in adrenergic receptor (ADR) genes are associated with adverse clinical outcomes in patients with heart failure. We evaluated the association of variants in ADR receptor genes with outcomes in infants with single ventricle lesions. Methods: Infants with single ventricle lesions participating in the Pediatric Heart Network Single Ventricle Reconstruction Trial (randomized to Norwood with modified Blalock-Taussig shunt versus right ventricle-pulmonary artery shunt) underwent genotyping for 4 single nucleotide polymorphisms (SNPs) in 3 ADR genes: ADRB1-A/G (rs1801252), ADRB1-C/G (rs1801253), ADRB2-C/G (rs1042714) and ADRA2A-C/T (rs553668). Linear and logistic regression, deviance tests, t-tests and F-tests were used to analyze association of genotype with clinical outcomes including hospital length of stay (LOS) at Norwood, occurrence of serious adverse events (SAE), and transplant-free survival during 14 months follow-up using a dominant model. Results: The study included 347 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 6±3.6 days and median Norwood LOS was 8 days. During 14 months follow-up, 147 patients had SAEs, 94 patients died and 14 were transplanted. ADRB1 AA (rs1801252) genotype was associated with longer Norwood LOS. The difference in LOS between AA vs AG/GG was 7.99 days (confidence intervals, 0.27, 15.71; p=0.043). ADRA2A CC (rs553668) genotype was associated with higher odds of SAEs i.e. 103/216 (47.6%) in CC compared to 36/106 (34%) in CT/TT [Odds ratio 1.77 (confidence intervals, 1.09, 2.87), p=0.018]. Transplant-free survival was not different between genotype groups. Combined analysis of risk genotypes did not confer an additive risk of adverse outcomes. Conclusions: ADR genotypes known to cause adrenergic upregulation were associated with prolonged Norwood hospitalization and/or serious adverse events in infant single ventricles. This may be secondary to adverse effects of adrenergic overexpression on cardiac function and systemic hemodynamics. Analysis is ongoing to replicate these findings for utility as predictive markers for outcomes in infant single ventricles.