FOXC1 haploinsufficiency due to 6p25 deletion in a patient with rapidly progressing aortic valve disease.

6p25 deletion is a rare but well-known entity. The main clinical features include an abnormal facial appearance, developmental delay, and ocular anomalies. Cardiac anomalies are frequently seen but remain poorly delineated. We describe a 4-year-old girl with 6p25.3 deletion, which includes the FOXC1 gene, typical dysmorphic features associated with developmental delay and oculo-motor anomalies. Aortic valve dysplasia was diagnosed early in life. The cardiac lesion progressed very rapidly between the age of 3 and 4 years requiring aortic valve replacement. Genomic analysis of blood and excised valve tissue showed down-regulation of FOXC1 but also FOXC2 expression in the diseased aortic valve. This allows us to speculate on the potential role of FOXC1 in aortic valve anomalies.

Impact of cardiac surgical timing on the neurodevelopmental outcomes of newborns with Complex congenital heart disease (CHD).

Background: More than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD. Methods: We hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay. Implications and Dissemination: This research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille - AP-HM - to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

Accuracy of prenatal screening for congenital heart disease in population: A retrospective study in Southern France.

Congenital heart diseases (CHDs) are the most common congenital malformations. The objective of our study was to evaluate the prenatal screening accuracy of congenital heart disease (CHD) in Southern France and to evaluate the impact of a prenatal diagnosis on pregnancies outcomes and neonatal outcomes. We performed a bicentric, retrospective observational study in the southern region over 4 years was conducted between 1 January 2014 and 31 December 2017. All foetuses and children under one year of age with CHD monitored in the UTHs (University Teaching Hospitals) in Marseille and Nice were included. CHD cases were divided into 3 groups: group 1, those with no possible options for anatomical repair; group 2, those with anatomical repair possibilities but that may require neonatal cardiologic management; and group 3, those with anatomical repair possibilities that do not require an emergency neonatal procedure. Among the 249070 deliveries during the study period, 677 CHD cases were included in the study. The overall prenatal screening rate was 71.5%. The screening rates were 97.8%, 63.6%, and 65.9% for groups 1, 2 and 3, respectively. Among group 2 CHD cases, 80% of the transpositions of the great arteries, 56% of the aortic coarctations, and 20% of the total anomalous pulmonary venous returns were detected during the prenatal period. A genetic anomaly was found in 16% of CHD cases. The overall mortality rate was 11.3% with a higher death rate in cases of prenatal screening (17.2% versus 2.1%; p < 0.001). However, when focusing only on children who died of CHD, prenatal screening did not create an impact (56.6% versus 100%, p = 0,140). Our data showed that the prenatal screening rate of CHD appears satisfactory in Southern France. Nevertheless, it could be improved for some CHD. This study did not find any benefit in terms of mortality from prenatal screening for CHD.

Percutaneous pulmonary valve implantation in small conduits: A multicenter experience.

BACKGROUND: Guidelines allow percutaneous pulmonary valve implantation (PPVI) in conduits above 16mm diameter. Balloon dilatation of a conduit to a diameter>110% of the original implant size is also not recommended. We analyzed patients undergoing PPVI in such conditions. METHODS AND RESULTS: Nine patients (May 2008-July 2016) from 8 institutions underwent PPVI in conduits <16mm diameter. Five patients with 16-18mm conduit diameter underwent PPVI after over-expansion of the conduit>110%. Mean age and weight of the 14 patients was 12.1 (7.7 to 16) years and 44.9 (19 to 83) kg. Median conduit diameter at PPVI was 12 (10 to 17) mm. Median systolic right ventricular pressure was 70 (40 to 94) mmHg. Procedure was successful in all cases. A confined conduit rupture occurred in 7 patients (50%) and was treated with covered stent in 6. One patient experienced dislocation of 2 pulmonary artery stents that were parked distally. The post-implantation median systolic right ventricular pressure was 36 (28 to 51) mmHg. A fistula between right-ventricle outflow and aorta was found in one patient, secondary to undiagnosed conduit rupture. This was closed surgically. After a median follow-up of 20.16 (6.95 to 103.61) months, all the patients are asymptomatic with no significant RVOT stenosis. CONCLUSIONS: PPVI is feasible in small conduits but rate of ruptures is high. Although such ruptures remain contained and can be managed with covered stents in our experience, careful selection of patients and high level of expertise are necessary. More studies are needed to better assess the risk of PPVI in this population.

A new technique for interrupted aortic arch repair: the Neville tube.

We have developed a new technique for interrupted aortic arch repair in which the pulmonary artery anterior wall is cut off and tailored so as to re-establish aortic continuity with an autologous tube. We are describing this method herein, with an 8-year follow-up of the first patient.