The management of infants with congenital diaphragmatic hernia (CDH) receiving extracorporeal life support (ECLS) is complex. Significant variability in both practice and prevalence of ECLS use exists among centers, given the lack of evidence to guide management decisions. The purpose of this report is to review existing evidence and develop management recommendations for CDH patients treated with ECLS. This article was developed by the Extracorporeal Life Support Organization CDH interest group in cooperation with members of the CDH Study Group and the Children’s Hospitals Neonatal Consortium.

Early clinical outcomes data for adjunctive systemic sirolimus therapy (SST) for moderate to severe pediatric pulmonary vein stenosis (PVS) are promising but limited. The authors aimed to characterize a cohort of patients treated with SST to determine if SST was associated with a reduction in frequency of PVS interventions. Medical records of 45 patients with PVS treated with SST for ≥1 month from 2015 to 2022 were retrospectively reviewed. PVS intervention rates pre-SST and on-SST were compared using generalized Poisson mixed models, accounting for paired intervals within each patient. In addition to an unadjusted model, an adjusted model accounted for age at interval start, PVS type, sex, prematurity, and concurrent antiproliferative therapy. Mean number of PVS interventions per patient over time (mean cumulative function) were also compared for these intervals in an unpaired fashion. Kaplan-Meier estimates were used to quantify survival over time. Median per-patient PVS intervention rate (interventions/year) was 5 pre-SST and 1.7 on-SST, significantly lower on-SST in the unadjusted and adjusted models (P < 0.001, both). Patients accrued an increased cumulative number of interventions over time pre-SST compared to on-SST by mean cumulative function (P < 0.001). Median duration of SST was 1.7 years and median follow-up time from SST initiation was 2.7 years. There were 6 mortalities at a median of 1.1 years (range, 4.4 months-6.5 years) following SST initiation. SST was associated with a reduction in frequency of PVS interventions. Prospective studies are warranted to determine potential causality, delineate patient- and vein-level outcomes, and determine optimal therapeutic duration.

Heart failure is a life-changing diagnosis for a child and their family. Pediatric patients with heart failure experience significant morbidity and frequent hospitalizations, and many require advanced therapies such as mechanical circulatory support and/or heart transplantation. Pediatric palliative care is an integral resource for the care of patients with heart failure along its continuum. This includes support during the grief of a new diagnosis in a child critically ill with decompensated heart failure, discussion of goals of care and the complexities of mechanical circulatory support, the pensive wait for heart transplantation, and symptom management and psychosocial support throughout the journey. In this article, we discuss the scope of pediatric palliative care in the realm of pediatric heart failure, ventricular assist device (VAD) support, and heart transplantation. We review the limited, albeit growing, literature in this field, with an added focus on difficult conversation and decision support surrounding re-transplantation, HF in young adults with congenital heart disease, the possibility of destination therapy VAD, and the grimmest decision of VAD de-activation.

Background: Neonates with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction. These neonates frequently require vasoactive support and are at high risk for mortality and morbidity, including prolonged ventilator support, need for extracorporeal membrane oxygenation (ECMO), prolonged length of stay, and need for tracheostomy. However, identifying which infants are at increased risk can be challenging. In this study, we sought to investigate the utility of the inotropic score (IS) and vasoactive inotropic score (VIS) as tools to predict significant clinical outcomes and overall survival in patients with CDH. Additionally, we evaluated the correlation between IS/VIS and postnatal echocardiographic variables.Methods: This was a retrospective chart review of 57 patients with CDH whose postnatal care was based on a standardized institutional protocol. We calculated the IS/VIS at 6-, 12-, 24-, 48 hours of life (HOL), on the day of CDH repair and 24- and 48 hours after surgical repair. The association of these scores with postnatal echocardiographic markers was analyzed using Pearson's correlation and linear regression, while logistic regression was used for binary outcomes, and Cox proportional hazards regression was used to assess associations with survival.Results: We found that every one-unit increase in IS/VIS at 6 HOL was associated with 13% increase in the odds of ECMO (p = 0.034) and 10.1% increase in risk of death (p = 0.021). An increase in IS/VIS at 12-, 24- and 48-HOL was associated with posterior septal bowing in the first postnatal echocardiogram (p < 0.05 for all). Additionally, we noted an inverse relationship between IS (r = −0.281, p = 0.036) and VIS (r = −0.288, p = 0.031) on the day of repair and left ventricle (LV) systolic function in first postnatal echocardiogram. Increase in IS (r = −0.307, p = 0.024) and VIS (r = −0.285, p = 0.037) on the day of repair was associated with decreased LV function on the post-repair echocardiogram.Conclusion: This retrospective study showed a significant association between IS/VIS obtained at various time points with clinical outcomes and echocardiographic findings in CDH, which could be used to guide prognosis and management in this patient population.

Bronchopulmonary dysplasia and pulmonary hypertension, or BPD-PH, are serious chronic lung disorders of prematurity, without curative therapies. Hyperoxia, a known causative factor of BPD-PH, activates adenosine monophosphate-activated protein kinase (AMPK) α1 in neonatal murine lungs; however, whether this phenomenon potentiates or mitigates lung injury is unclear. Thus, we hypothesized that (1) endothelial AMPKα1 is necessary to protect neonatal mice against hyperoxia-induced BPD-PH, and (2) AMPKα1 knockdown decreases angiogenesis in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs). We performed lung morphometric and echocardiographic studies on postnatal day (P) 28 on endothelial AMPKα1-sufficient and -deficient mice exposed to 21% O₂ (normoxia) or 70% O₂ (hyperoxia) from P1–P14. We also performed tubule formation assays on control- or AMPKα1-siRNA transfected HPMECs, exposed to 21% O₂ or 70% O₂ for 48 h. Hyperoxia-mediated alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and PH were significantly amplified in endothelial AMPKα1-deficient mice. AMPKα1 siRNA knocked down AMPKα1 expression in HPMECs, and decreased their ability to form tubules in normoxia and hyperoxia. Furthermore, AMPKα1 knockdown decreased proliferating cell nuclear antigen expression in hyperoxic conditions. Our results indicate that AMPKα1 is required to reduce hyperoxia-induced BPD-PH burden in neonatal mice, and promotes angiogenesis in HPMECs to limit lung injury.

Despite advances in caring for neonates with congenital diaphragmatic hernia (CDH), mortality and morbidity continues to be high. Additionally, the pathophysiology of cardiac dysfunction in this condition is poorly understood. Postnatal cardiac dysfunction in neonates with CDH may be multifactorial with origins in fetal life. Mechanical obstruction, competition from herniated abdominal organs into thoracic cavity combined with redirection of ductus venosus flow away from patent foramen ovale leading to smaller left-sided structures may be a contributing factor. This shunting decreases left atrial and left ventricular blood volume, which may result in altered micro- and macrovascular aberrations affecting cardiac development in the prenatal period. Direct mass effect from herniated intra-abdominal contents restricting cardiac growth and/or reduced left ventricular preload may contribute independently to left ventricular dysfunction in the absence of right ventricular dysfunction and or pulmonary hypertension. With variable clinical phenotypes of cardiac dysfunction, pulmonary hypertension, and respiratory failure in patients with CDH, there is increased need for individualized diagnosis and tailored therapy. Routine use of therapy such as inhaled nitric oxide and sildenafil that induces significant pulmonary vasodilation may be detrimental in left ventricle dysfunction, whereas in a patient with pure right ventricle dysfunction, they may be beneficial. Targeted functional echocardiography serves as a real-time tool for defining the pathophysiology and aids optimization of vasoactive therapy in affected neonates. Key Points