Noonan syndrome and pregnancy outcomes

Background: Noonan syndrome is a genetic disorder with high prevalence of congenital heart defects, such as pulmonary stenosis, atrial septal defect and hypertrophic cardiomyopathy. Scarce data exists regarding the safety of pregnancy in patients with Noonan syndrome, particularly in the context of maternal cardiac disease. Study design: We performed a retrospective chart review of patients at Yale-New Haven Hospital from 2012 to 2020 with diagnoses of Noonan syndrome and pregnancy. We analysed medical records for pregnancy details and cardiac health, including echocardiograms to quantify maternal cardiac dysfunction through measurements of pulmonary valve peak gradient, structural heart defects and interventricular septal thickness. Results: We identified five women with Noonan syndrome (10 pregnancies). Three of five patients had pulmonary valve stenosis at the time of pregnancy, two of which had undergone cardiac procedures. 50% of pregnancies (5/10) resulted in pre-term birth. 80% (8/10) of all deliveries were converted to caesarean section after a trial of labour. One pregnancy resulted in intra-uterine fetal demise while nine pregnancies resulted in the birth of a living infant. 60% (6/10) of livebirths required care in the neonatal intensive care unit. One infant passed away at 5 weeks of age. Conclusions: The majority of mothers had pre-existing, though mild, heart disease. We found high rates of prematurity, conversion to caesarean section, and elevated level of care. No maternal complications resulted in long-term morbidity. Our study suggests that women with Noonan syndrome and low-risk cardiac lesions can become pregnant and deliver a healthy infant with counselling and risk evaluation.

Transplacental treatment of foetal supraventricular tachycardia with triple antiarrhythmic combination to avoid intra-foetal intervention

Although a high percentage of foetuses with supraventricular tachycardia respond to single or dual antiarrhythmic therapy, on occasion when there is no response to these combination regimens, direct intra-foetal therapy remains the only choice, albeit such an approach carries a potential risk to the foetus. Data with regard to the safety and efficacy of triple antiarrhythmic combination have not been reported before. Here, we present a foetus with intractable tachycardia in whom arrhythmia termination was successfully achieved with triple oral antiarrhythmic therapy.

Cardiovascular manifestations of Hutchinson–Gilford progeria syndrome

Cardiovascular complications are the most frequent cause of death in patients with the Hutchinson–Gilford progeria syndrome. However, due to its rarity, studying the course of cardiac abnormalities has been a challenge. The cardiovascular phenotype helps to provide greater insight into the natural history of these abnormalities.

Biventricular non-compaction cardiomyopathy and tricuspid hypoplasia in a novel non-POU domain-containing octamer-binding gene variant

A maternally inherited novel pathogenic non-POU domain-containing octamer-binding gene variant c.767G>T, p.R256I [NM_001145408], manifested in a male infant as dilated cardiomyopathy with severe left ventricular dysfunction and dilation, biventricular non-compaction, tricuspid hypoplasia, and hydrocephaly. To the best of our knowledge, no previous non-POU domain-containing octamer-binding gene variants with biventricular non-compaction have been associated with tricuspid valve hypoplasia. Hence, this case introduces a new pathogenic variant observed in the non-POU domain-containing octamer-binding gene and adds to the range of cardiac phenotypes identified in non-POU domain-containing octamer-binding gene variants.

Prenatal diagnosis lowers neonatal cardiac care costs in resource-limited settings

Background: Prenatal diagnosis of critical CHDs and planned peripartum care is an emerging concept in resource-limited settings. Objective: To report the impact of prenatal diagnosis and planned peripartum care on costs of neonatal cardiac care in a resource-limited setting. Methods: Prospective study (October 2019 to October 2020). Consecutive neonates undergoing surgery or catheter-based interventions included. Patients were divided into prenatal (prenatal diagnosis) and post-natal (diagnosis after birth) groups. Costs of cardiac care (total, direct, and indirect) and health expenses to income ratio were compared between study groups; factors impacting costs were analysed. Results: A total of 105 neonates were included, including 33 in prenatal group. Seventy-seven neonates (73.3%) underwent surgical procedures while the rest needed catheter-based interventions. Total costs were 16.2% lower in the prenatal group (p = 0.008). Direct costs were significantly lower in the prenatal group (18%; p = 0.02), especially in neonates undergoing surgery (20.4% lower; p = 0.001). Health expenses to income ratio was also significantly lower in the prenatal group (2.04 (1.03–2.66) versus post-natal:2.58 (1.55–5.63), p = 0.01);, particularly in patients undergoing surgery (prenatal: 1.58 (1.03–2.66) vs. post-natal: 2.99 (1.91–6.02); p = 0.002). Prenatal diagnosis emerged as the only modifiable factor impacting costs on multivariate analysis. Conclusion: Prenatal diagnosis and planned peripartum care of critical CHD is feasible in resource-limited settings and is associated with significantly lower costs of neonatal cardiac care. The dual benefit of improved clinical outcomes and lower costs of cardiac care should encourage policymakers in resource-limited settings towards developing more prenatal cardiac services.

Clinical impact of subcutaneous treprostinil in trisomy 21 patient with pulmonary arterial hypertension associated with CHD

Subcutaneous treprostinil is commonly used to improve idiopathic pulmonary arterial hypertension in children. However, its effectiveness has not been reported in trisomy 21. We report the case of 9-year-old boy in trisomy 21 with CHD-pulmonary artery hypertension after surgical correction of CHD. Haemodynamics and exercise capacity dramatically improved with a transition from oral selexipag to subcutaneous treprostinil.

A left atrial hamartoma of mature cardiac myocytes

We present a case of a hamartoma of mature cardiac myocytes. This is an extremely rare tumour and the first reported paediatric case localised in the left atrium.

Evaluation of the selected parameters of the fetal diastolic functions in normally grown or macrosomic fetuses of gestational diabetic mothers with poor glycaemic control

Objective: This study aimed to investigate whether the third trimester fetal cardiac diastolic function measured by selected conventional Doppler indices is affected in appropriate-for-gestational-age or macrosomic fetuses of gestational diabetic mothers with poor glycaemic control. Methods: This cross-sectional study included 93 pregnant women divided into two groups. Group 1 included 45 appropriate-for-gestational-age or macrosomic fetuses from gestational diabetic mothers with poor glycaemic control (study group). Group 2 included 48 appropriate-for-gestational-age fetuses from gestational age-matched healthy mothers (control group). Functional fetal cardiac parameters and fetoplacental Doppler parameters were measured. Data were compared between the two groups. Results: Maternal characteristics did not differ significantly between the study and the control group. There were no significant differences in the early and late velocity, early/late velocity ratio of both mitral and tricuspid valves, the fetal pulmonary vein pulsatility index, and the ductus venosus pulsatility index between the study and the control group. Moreover, the rate of abnormal Doppler findings in pulmonary vein (pulmonary vein pulsatility index >95th centile), ductus venosus (ductus venosus pulsatility index >95th centile), and peripheral vessels (umbilical artery pulsatility index >95th centile, middle cerebral artery pulsatility index <5th centile, cerebra-placental index >95th centile) were comparable in both groups. Conclusions: The third trimester fetal diastolic functions measured by selected conventional Doppler techniques do not seem to be altered in appropriate-for-gestational-age or macrosomic fetuses of gestational diabetic mothers who have poor glycaemic control.

Self- and informant-reported executive function in young adults operated for atrial or ventricular septal defects in childhood

Background: Adults with simple congenital heart defects (CHD) have increased risk of neurodevelopmental challenges including executive dysfunction. It is unknown if the executive dysfunction is universal or if it is driven by dysfunction in specific clinical subscales and how it might affect psychosocial aspects of everyday life. Methods: The self-reported and informant-reported executive function of adults with an average age of 26 ± 5 (range 18–41) who underwent childhood surgery for atrial septal defects (n = 34) or ventricular septal defects (n = 32) and matched controls (n = 40) were evaluated using the Behavior Rating Inventory of Executive Functions - Adult version (BRIEF-A). Results: The CHD group reported having more executive dysfunction than controls in all BRIEF-A clinical subscales (p < 0.020) and more than their informants reported on their behalf (p < 0.006). The CHD group had received three times more special teaching (44% compared to 16%) and pedagogical psychological counselling (14% compared to none) and had a three times higher occurrence of psychiatric disorders than controls (33% compared to 11%). Lower educational levels and psychiatric disorders were associated with higher BRIEF-A scores (p < 0.03). Conclusions: Adults operated for septal defects in childhood report more challenges with all aspects of the executive functions than controls and more than relatives are aware of.

Condition notification assisted by virtual reality technology reduces the anxiety levels of parents of children with simple CHD: a prospective randomised controlled study

Purpose: This study explored the effects of condition notification based on virtual reality technology on the anxiety levels of parents of children with simple CHD. Methods: The subjects of the study were the parents of 60 children with simple CHD who were treated in our centre. The state anxiety scale was used to assess the anxiety status of the parents of the children before and after the condition notification in different ways (based on virtual reality explanations and written explanations). Results: In this study, a total of 55 parents of children with CHD successfully completed the survey. At the time of admission, there was no significant difference in the state anxiety scale scores of the parents between the two groups. The anxiety status of the virtual reality group was relieved after the condition notification assisted by virtual reality technology, and there was a significant difference compared with the control group. Conclusion: Condition notification based on virtual reality technology can effectively alleviate the anxiety of parents of children with simple CHD, which is worthy of clinical application.