CHOP Researchers Highlight Advances in Pediatric Heart Disease at 2016 AHA Scientific Sessions

Published on in CHOP News

Physician-researchers from the Cardiac Center at Children’s Hospital of Philadelphia (CHOP) presented new findings on pediatric cardiovascular disease at the American Heart Association’s Scientific Sessions 2016 in New Orleans. Among many studies presented were research on pediatric use of adult ventricular assist devices, the benefits of 3-D models in heart surgery, the effects of heart disease on growth and multiple organs, novel treatments for hazardous lymphatic fluid blockages, and racial disparities in bystander CPR methods in children with sudden cardiac arrest.

Heart defects have long-term effects on other organs and systems

Even as medical and surgical interventions have extended survival for most children with single ventricle, one of the most severe congenital heart defects, long-term complications remain in organs and body systems beyond the heart. In three studies, Dr. Jack Rychik, Director of CHOP’s Single Ventricle Survivorship Clinic, and colleagues reported on multiple challenges after children undergo the palliative Fontan operation for a severely underdeveloped ventricle. A cross-sectional analysis of 210 single-center patients reported significantly lower height and body mass density, and the occurrence of the hormonal disorder secondary hyperparathyroidism, sometimes with severe vitamin D deficiency. The authors say these findings are part of multiple, increasingly recognized collection of varied end-organ consequences that define a “Fontan circulatory syndrome” that merits further investigation.

A second study focused on Fontan-associated liver disease that occurs in single-ventricle patients and computational fluid modeling utilizing magnetic resonance imaging techniques. This study of 33 Fontan patients with liver fibrosis revealed an association between increased blood flow in the inferior vena cava and the degree of liver fibrosis. The research suggests that liver fibrosis, while due to elevated venous pressures, may itself place an additional burden on the circulation. A third study characterized changes in the gut microbiome in the days and months following the Fontan operation in 32 children. Using bacterial genomic sequencing, the authors found significant differences in the proportions of particular bacterial populations, possibly related to the Fontan circulation altering intestinal blood supply and intestinal oxygenation. Given the growing awareness of the role of gut microbiome on human health, the authors recommend continued research on the microbiome in older children and adults who are Fontan survivors.

Novel form of MRI visualizes hazardous lymph flow, predicts success of embolization

Patients with congenital heart disease are at risk of a rare but potentially fatal postoperative condition called chylothorax, an abnormal buildup of lymphatic fluid in the pleural cavity around the lungs. Dr. Jill Savla and colleagues from the Jill and Mark Fishman Center for Lymphatic Disorders performed a retrospective review of 25 patients with congenital heart disease and postoperative chylothorax. The team used dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL), a customized MRI technique developed at CHOP, to identify the cause of chylothorax.

Of the 25 patients, 16 patients had either pulmonary lymphatic perfusion (14 patients) or traumatic leak from a branch of the thoracic duct (two patients). All 16 of these patients underwent thoracic duct embolization, a procedure that seals off the abnormal lymphatic flow site of leakage; chylothorax resolved in all 16. The remaining nine patients had a central lymphatic flow disorder (CLFD), with abnormal lymphatic flow in multiple compartments. Lymphatic embolization to occlude the thoracic duct was unsuccessful in these nine patients with CLFD, who died.

The authors conclude that DCMRL is essential in determining the cause of chylothorax, and that lymphatic embolization should be considered first-line treatment.

Savla et al. Utilization of Magnetic Resonance Lymphangiography to Determine the Etiology of Chylothorax and Predict the Outcome of Lymphatic Embolization in Patients with Congenital Heart Disease

Single-ventricle children who receive tube-assisted feeding have lower growth patterns

Children with single-ventricle cardiac disease (SVCD) are known to have lower weight, length and head circumference than healthy peers through age 3. Tube-assisted feeding is thought to improve weight gain in these patients, but little is known about tube feeding’s long-term effects on growth. Researchers led by Dr. Arene Butto compared SVCD children who required tube-assisted feeding at the time of discharge from their initial cardiac surgery to those who did not, to assess growth trajectories and clinical factors.

This single-center cohort study examined 134 children who had surgery for SVCD over a 10 year period, of whom 44 were discharged on tube-assisted feeds and 90 were not. In every year from age 2 to age 6, tube-fed children had significantly lower weight and body mass index, and also had persistent failure to gain weight despite similar rates of postoperative complications and inter-stage hospitalizations. The tube-fed group also had longer cardiopulmonary bypass and deep hypothermic circulatory arrest times, as well as longer length of stay. The study team also did a sub-analysis of the 91 SVCD patients who had the Norwood operation. Those patients were more prevalent in the tube-fed group, and more likely to have suboptimal weight gain — suggesting a unique risk factor associated with the Norwood procedure.

Butto et al, Tube-Assisted Feeding Is Associated with Worse Longitudinal Growth in Children with Single-Ventricle Cardiac Disease

Conventional CPR is better for children than compression-only method, but racial disparities exist

In adults who suffer out-of-hospital cardiac arrest, bystander CPR using chest compression only is as effective as conventional bystander CPR, which uses both compressions and ventilations. Dr. Maryam Naim and colleagues evaluated outcomes in children, drawing on data from a large national registry. The team analyzed 3,900 cases of out-of-hospital cardiac arrest in children up to age 18; bystander CPR occurred in 1,814 (47 percent) of cases. For the 1,411 events in which type of CPR was recorded, children were equally likely to receive either conventional CPR or compression only CPR. Infants were more likely to receive conventional CPR than compression-only, and the conventional method improved their survival. Compression-only CPR was used more often in black children (56 percent) and Hispanic children (64 percent) than in white children (49 percent), although overall survival was higher in black children who received conventional CPR. Overall survival for all children was 17 percent for conventional CPR and 14 percent for compression-only CPR.

Both conventional and compression-only CPR were associated with overall survival to hospital discharge. However, only conventional CPR was associated with neurologically favorable survival. Compared to compression-only CPR, conventional CPR showed a 60 percent higher chance of overall survival and a 50 percent higher chance of neurologically favorable survival.

Naim et al, Comparison of Conventional and Compression Only Bystander CPR Following Pediatric Out of Hospital Cardiac Arrest in the United States: A Study from the Cardiac Arrest Registry to Enhance Survival (CARES)

Exome sequencing may ID genetic causes of sudden cardiac death and arrest

Exome sequencing identifies some gene mutations that cause sudden cardiac arrest or death (SCA/D), but many uncertainties remain. After a SCA/D occurs, proactive family screening may potentially lead to life-saving treatment and help identify other affected family members. Dr. Victoria Vetter and colleagues investigated 41 affected subjects (probands) in whom specific pathogenic mutations were unknown, along with 127 family members — parents, siblings and grandparents, both affected and unaffected. Among the 41 probands, the team identified nine with definitive pathogenic mutations, 17 with variants of uncertain significance, (10 of whom fit the phenotype or clinical presentation), and 14 negative cases. Of the nine gene-positive probands and 10 VUS probable probands, 90 percent had a positive parent and 47 percent had a gene mutation positive sibling. The authors conclude that exome sequencing is a helpful diagnostic tool for SCA/D, but that clinicians should be aware of current limitations in knowledge.

Vetter et al, Exome Sequencing for Genetic Etiology in Families with Sudden Cardiac Death or Arrest

Aortic reconstruction may raise risk for adverse events in the future

Patients with single-ventricle disease who undergo aortic reconstruction have increased stiffness in their aortas that reduces ventricular volumes at rest and at exercise, impeding their performance. In addition, this result suggests they also may be at higher risk of adverse events in the future. Dr. Mark A. Fogel and colleagues compared 18 single-ventricle patients who underwent aortic reconstruction with 30 single ventricle patients who had normal aortas, measuring heart performance, oxygen use and other variables during exercise, and a stress test. In single-ventricle patients, the aortic reconstruction is stiffer than a normal aorta and restricts exercise performance. The authors suggest that the distensibility of the descending aorta acts as an “energy sink” when it interacts with the stiffer ascending aorta in the aortic reconstruction patients. The authors conclude that their data may help in designing better aortic reconstructions to maximize exercise performance and improve outcomes in these patients.

Fogel et al, Aortic Stiffness and Its Relationship to Exercise and Ventricular Volumes After Surgical Reconstruction in Single Ventricle Patients

Contact: Joey McCool Ryan, The Children’s Hospital of Philadelphia, (267) 258-6735 or