Osman O. Al-Radi

Chylothorax and pleural effusion in contemporary extracardiac fenestrated fontan completion

Background: We hypothesized that chylothorax could be a sign of intolerance to the Fontan physiology, and thus patients who develop chylothorax or pleural effusion have worse medium‐term to long‐term survival. Methods: A total of 324 patients who underwent the Fontan operation between 2000 and 2013 were included. Chylothorax was defined as ≥5 mL/kg/day of chylomicron‐positive chest drainage fluid no earlier than postoperative day 5 or drainage with >80% lymphocytes. Outcomes were compared between the chylothorax and non‐chylothorax groups by the Kaplan–Meier method and log‐rank test. Independent predictors of chylothorax and number of days of any chest drainage were analyzed with multivariable logistic regression and multivariable generalized negative binomial regression for count data, respectively. Results: Chylothorax occurred in 78 patients (24%). Compared with the non‐chylothorax group, the chylothorax group had a longer duration of chest tube requirement (median, 18 days vs 9 days; P < .000) and a longer length of hospital stay (median, 19 days vs 10 days; P < .000). Eight patients (10.3%) required thoracic duct ligation. The chylothorax group had lower freedom from death (P = .013) and from composite adverse events (P = .021). No predictor was found for chylothorax. Pulmonary atresia (P = .031) and pre‐Fontan pulmonary artery pressure (P = .01) were predictive of prolonged pleural effusion (>14 days). Conclusions: Occurrence of chylothorax following the Fontan operation can be a marker of poorer medium‐term clinical outcomes. It is difficult to predict occurrence of chylothorax owing to its multifactorial nature and involvement of lymphatic compensatory capacity that is unmasked only after the Fontan operation.

Induced pluripotent stem cell modelling of HLHS underlines the contribution of dysfunctional NOTCH signalling to impaired cardiogenesis

Abstract Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype. Our data indicate that HLHS-iPSC have a reduced ability to give rise to mesodermal, cardiac progenitors and mature cardiomyocytes and an enhanced ability to differentiate to smooth muscle cells. HLHS-iPSC-derived cardiomyocytes are characterised by a lower beating rate, disorganised sarcomeres and sarcoplasmic reticulum and a blunted response to isoprenaline. Whole exome sequencing of HLHS fibroblasts identified deleterious variants in NOTCH receptors and other genes involved in the NOTCH signalling pathway. Our data indicate that the expression of NOTCH receptors was significantly downregulated in HLHS-iPSC-derived cardiomyocytes alongside NOTCH target genes confirming downregulation of NOTCH signalling activity. Activation of NOTCH signalling via addition of Jagged peptide ligand during the differentiation of HLHS-iPSC restored their cardiomyocyte differentiation capacity and beating rate and suppressed the smooth muscle cell formation. Together, our data provide firm evidence for involvement of NOTCH signalling in HLHS pathogenesis, reveal novel genetic insights important for HLHS pathology and shed new insights into the role of this pathway during human cardiac development.

Extracorporeal Membrane Oxygenation in Postcardiotomy Pediatric Patients—15 Years of Experience Outside Europe and North America

Background The increasing complexity of congenital cardiac surgery has resulted in the increased use of extracorporeal membrane oxygenation (ECMO) support for children who cannot be weaned from cardiopulmonary bypass. The purpose of this research was to assess the mortality and morbidity in children requiring ECMO support after the repair of congenital heart defects (CHDs). Methods The hospital records of all patients with CHD who required ECMO after a cardiac surgical procedure between January 2001 and December 2016 were retrospectively reviewed. Various outcomes were reported and tested for any association with hospital death. Results A total of 113 children required ECMO for cardiopulmonary support after congenital cardiac surgery; 88 (77.9%) were placed on ECMO in the operating room. Median age of the patients was 3 months (range, 4 days‐15 years) and median weight was 3.5 kg (range, 2.2‐42.5). Forty‐two (37.2%) survived to hospital discharge. In children with single‐ventricle physiology, survival to discharge was 37.3% (19/51 patients) and for biventricular physiology, it was 37.1% (23/62 patients). Univariate analysis revealed number of days on ECMO support, renal failure, and stroke as risk factors for hospital mortality, while age and cross‐clamp time were found to be statistically nonsignificant. Conclusion Satisfactory results can be achieved in pediatric patients by using ECMO support for postoperative cardiac and pulmonary failure refractory to medical management. Prolonged ECMO support, renal failure, and stroke are risk of mortality.

Coronary-pulmonary arterial fistula in a neonate with pulmonary atresia—ventricular septal defect and single coronary artery

In cases of pulmonary atresia with ventricular septal defect (PA‐VSD), coronary‐pulmonary arterial fistula (CPAF) as the main source of pulmonary blood supply is extremely rare. These fistulae may arise from the left coronary artery, right coronary artery, or a single coronary artery. Fistulae from a single coronary artery are unusual. We are reporting a case of PA‐VSD with single coronary artery and CPAF as the main source of pulmonary supply in addition to two major aortopulmonary collateral arteries (MAPCAS). Successful surgical correction with VSD closure and right ventricle (RV) to the pulmonary artery (PA) conduit was made.

A Triple Challenge: Thrombocytopenia in a 7-Year-Old Girl With Unrepaired d-Transposition of the Great Arteries, Ventricular Septal Defect, and Pulmonary Hypertension

Thrombocytopenia can be a real challenge during cardiac surgery in children with cyanotic congenital heart disease. This report describes a 7-year-old girl with d-transposition of the great arteries, ventricular septal defect, pulmonary hypertension, chronic thrombocytopenia, polycythemia, and chronic renal impairment. The thrombocytopenia improved several days after splenectomy. The child then underwent a successful arterial switch operation with ventricular septal defect closure.