SVR III: Brain Connectome and Neurodevelopmental Outcomes
Condition: Congenital Heart Disease
MeSH terms: Heart Diseases; Heart Defects, Congenital
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): Magnetic Resonance Imaging; Neurodevelopmental Testing
Intervention type(s): Device; Behavioral
Intervention description(s): Brain MRI without Contrast; Validated battery of neurodevelopmental and psychological tests.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        SVR Survivor - male and female - 10 to 12 years of age
      
Keywords: Congenital Heart Disease; Magnetic Brain Resonance; CHD; MRI; Neurodevelopmental