SVR III: Brain Connectome and Neurodevelopmental Outcomes

Patients with hypoplastic left heart syndrome and other single right ventricle lesions who have undergone the Fontan procedure have a high risk of neurodevelopmental disorders that affect quality of life and adulthood employment. This study will leverage the ongoing National Heart, Lung, and Blood Institute (NHLBI)-funded Single Ventricle Reconstruction Study by using innovative graph measures of brain connectivity to elucidate how alterations of the "connectome" in children with critical congenital heart disease are associated with developmental disabilities and their associated clinical risk factors. Improved understanding of these interrelationships may facilitate development of targeted interventions to improve outcome in the soaring population of adult Fontan survivors.

With dramatic improvement in survival of patients with hypoplastic left heart syndrome and related forms of single right ventricle undergoing staged palliation to the Fontan operation, a high prevalence of neurodevelopment abnormalities has been exposed. The NHLBI-funded Pediatric Heart Network (PHN) Single Ventricle Reconstruction (SVR) III study, "Long-term Outcomes of Children with Hypoplastic Left Heart Syndrome (HLHS) and the Impact of Norwood Shunt Type," is a prospective follow-up study of an existing cohort of children with HLHS and other single RV anomalies who were enrolled in early infancy in a randomized clinical trial of the modified Blalock-Taussig shunt (MBTS) versus right ventricular to pulmonary artery shunt (RVPAS). The parent SVR III study seeks to determine if the shunt assignment at the time of the Norwood operation is associated with cardiac function, transplant-free survival, exercise function, and neurodevelopmental outcomes. The investigators here propose a neuroimaging ancillary study to the parent SVRIII study that leverages the neurodevelopmental follow-up of the SVR cohort at age 11 years. The investigators will combine state-of-the-art brain imaging techniques \[Resting-Blood Oxygenation Level Dependent (BOLD) and Diffusion Tensor Imaging\] in 140 SVR III patients and 100 referent subjects with innovative brain connectome or "graph" analyses to determine if brain connectivity graph measurements will provide novel neuroimaging biomarkers for neurodevelopmental disabilities and improve the investigators' understanding of their inciting mechanisms in the SVR survivors. The investigators' specific aims are: Specific Aim (SA) #1: To characterize the global brain network topology of the SVR III cohort; SA #2: To determine which neurocognitive and behavioral outcomes predict global brain network topology in the SVR III cohort. SA #3: To determine which patient factors (e.g., birth weight, gestational age, maternal education) and medical factors (e.g., intraoperative conduct during Norwood procedure, hemodynamic complications, types and number of interventions, and measures of global morbidity) predict global brain network topology in the SVRIII cohort. SA #4: To precisely characterize the specific relationships between global brain network topology, specific patient/medical factors, and adverse neurocognitive/behavioral outcomes in the SVRIII cohort. The investigators will use linear regression and mediation statistical methods to analyze associations of MRI graph measures with SVRIII neurodevelopmental measures and surgical/non-surgical clinical independent risk factors. Upon successful completion, these studies will elucidate the nature and basis of neurodevelopmental disability in single ventricle patients following Fontan palliation. This research will also contribute a novel and robust set of clinical/research tools in the form of neuroimaging biomarkers that can be used to help classify and predict outcomes in complex congenital heart disease (CHD).

Eligibility Criteria:
Inclusion Criteria:

* SVR Survivor:
* All SVR study cohort members will be contacted to assess for vital status
* Transplant free survivors will be approached to participate in the in-person assessment
* Healthy Controls: Males and females aged 10 - 12 at the time of enrollment and whose parent or legal guardian can provide consent for participation will be recruited for participation in this study. Study participants will also be asked to provide assent for participation in this study.

Exclusion Criteria:

* SVR Survivors: The investigators will exclude patients who have undergone cardiac transplantation or biventricular conversion from all outcomes other than vital status.
* Those patients with a contraindication to MRI (i.e., claustrophobia; metal screen failure; inability to lie still) will not be enrolled for participation in this study.
* Healthy Controls: Potential participants will be excluded for any of the following reasons:

  1. disorders that would prevent successful completion of the planned study testing (e.g., pacemaker, metal implants; claustrophobia; inability to lie still)
  2. other forms of congenital heart disease requiring surgical correction
  3. Lack of reading fluency in English by primary caregiver in English