Partnering With Stakeholders to Inform the Co-Design of a Psychosocial Intervention for Prenatally Diagnosed Congenital Heart Disease

Input from diverse stakeholders is critical to the process of designing healthcare interventions. This study applied a novel mixed-methods, stakeholder-engaged approach to co-design a psychosocial intervention for mothers expecting a baby with congenital heart disease (CHD) and their partners to promote family wellbeing. The research team included parents and clinicians from 8 health systems. Participants were 41 diverse parents of children with prenatally diagnosed CHD across the 8 health systems. Qualitative data were collected through online crowdsourcing and quantitative data were collected through electronic surveys to inform intervention co-design. Phases of intervention co-design were: (I) Engage stakeholders in selection of intervention goals/outcomes; (II) Engage stakeholders in selection of intervention elements; (III) Obtain stakeholder input to increase intervention uptake/utility; (IV) Obtain stakeholder input on aspects of intervention design; and (V) Obtain stakeholder input on selection of outcome measures. Parent participants anticipated the resulting intervention, HEARTPrep, would be acceptable, useful, and feasible for parents expecting a baby with CHD. This model of intervention co-design could be used for the development of healthcare interventions across chronic diseases

Rendimiento acad\ue9mico y dificultades conductuales despu\ue9s de intervenci\uf3n quir\ufargica cardiaca neonatal y durante la lactancia

Aunque los avances en las \ue1reas m\ue9dica y quir\ufargica han proporcionado la capacidad para "rehabilitar" a ni\uf1os que nacen con cardiopat\ueda cong\ue9nita, el n\ufamero cada ve/ mayor de sobrevivientes ha creado una cohorte de ni\uf1os con dificultades acad\ue9micas potenciales. En este art\uedculo se revisa la comprensi\uf3n actual de los resultados neurol\uf3gicos a mediano plazo de ni\uf1os en quienes se practic\uf3 intervenci\uf3n quir\ufargica cardiaca neonatal y durante la lactancia. Las lesiones que se comentan con transposici\uf3n de las grandes arterias, tetralog\ueda de Fallot, s\uedndrome de hemicardio izquierdo hipopl\ue1sico. conexi\uf3n venosa pulmonar an\uf3mala total, y lesiones- de ventr\uedculo \ufanico que requieren paliaci\uf3n de Fontan y trasplante cardiac

Internal loop mutations in the ribosomal protein L30 binding site of the yeast L30 RNA transcript

Yeast ribosomal protein L30 binds to an asymmetric, purine-rich internal loop in its transcript to repress its own splicing and translation. The protein-bound form of the stem-internal loop–stem RNA is an example of a kink-turn RNA structural motif. Analysis of kink-turn motifs reveals that in (2 + 5) internal loops, the identities of five nucleotides are very important, while the remaining two may be varied. Previous SELEX experiments on the L30 binding site showed an identical pattern of sequence variation with five nucleotides highly conserved and two positions variable. In this work, internal loop residues were mutated and tested for protein binding in vitro and in vivo. The two sheared G-A pairs, which cannot be mutated without severely weakening L30 binding, make sequence specific contacts with other portions of the RNA and L30 protein. In contrast, the lone nucleotide that protrudes into the protein and an unpaired adenosine make no sequence-specific contacts, and may be mutated without compromising L30 binding. The internal loop allows the formation of a very tight bend that brings the two stems together with cross-strand stacking of two adenines and an interhelical ribose contact. Replacement of a ribonucleotide with a deoxynucleotide adjacent to the internal loop weakens protein binding significantly. In the absence of L30, some of the internal loop residues involved in the formation of the kink-turn motif are protected from chemical modification, indicating that some elements of kink-turn structure may form in the free L30 RNA

The Infant with Aortic Arch Hypoplasia and Small Left Heart Structures: Echocardiographic Indices of Mitral and Aortic Hypoplasia Predicting Successful Biventricular Repair.

In infants with aortic arch hypoplasia and small left-sided cardiac structures, successful biventricular repair is dependent on the adequacy of the left-sided structures. Defining accurate thresholds of echocardiographic indices predictive of successful biventricular repair is paramount to achieving optimal outcomes. We sought to identify pre-operative echocardiographic indices of left heart size that predict intervention-free survival in infants with small left heart structures undergoing primary aortic arch repair to establish biventricular circulation (BVC). Infants ≤2 months undergoing aortic arch repair from 1999 to 2010 with aortic and/or mitral valve hypoplasia, (Z-score ≤-2) were included. Pre-operative and follow-up echocardiograms were reviewed. Primary outcome was successful biventricular circulation (BVC), defined as freedom from death, transplant, or single ventricular conversion at 1 year. Need for catheter based or surgical re-intervention (RI), valve annular growth, and significant late aortic or mitral valve obstruction were additional outcomes. Fifty one of 73 subjects (79%) had successful BVC and were free of RI at 1 year. Seven subjects failed BVC; four of those died. The overall 1 year survival for the cohort was 95%. Fifteen subjects underwent a RI but maintained BVC. In univariate analysis, larger transverse aorta (p = 0.006) and aortic valve (p = 0.02) predicted successful BVC without RI. In CART analysis, the combination of mitral valve (MV) to tricuspid valve (TV) ratio ≤0.66 with an aortic valve (AV) annulus Z-score ≤-3 had the greatest power to predict BVC failure (sensitivity 71%, specificity 94%). In those with successful BVC, the combination of both AV and MV Z-score ≤-2.5 increased the odds of RI (OR 3.8; CI 1.3-11.4). Follow-up of non-RI subjects revealed improvement in AV and MV Z-score (median AV annulus changed over time from -2.34 to 0.04 (p \u3c 0.001) and MV changed from -2.88 to -1.41 (p \u3c 0.001), but residual mitral valve stenosis and aortic arch obstruction were present in one-third of subjects. In this cohort of infants requiring initial aortic arch repair with concomitant small left heart structures, successful BVC can be predicted from combined echocardiographic indices. In this complex population, 1 year survival is high, but the need for RI and the presence of residual lesions are common

Guidelines for the management of neonates and infants with hypoplastic left heart syndrome: The European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC) Hypoplastic Left Heart Syndrome Guidelines Task Force

The IPCCC is a standardized international system of paediatric and congenital cardiac nomenclature that should be used in all registries, databases and research studies in the domain of paediatric and congenital cardiac care, including those related to HLHS. This recommendation is level 1 class C [15, 16, 700]. Multi-institutional databases and registries allow benchmarking of data concerning death, patterns of practice, morbidity and postoperative length of stay [540]. As a level 1 class C recommendation, all paediatric and congenital cardiac teams should routinely assess their own data against national and international benchmarks using multi-institutional databases and registries [540, 697–699, 701]

Results of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial.

Background: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus -9±193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold