The Boston Circulatory Arrest Study: Antecedents and Correlates of Well-Being in Adults With Congenital Heart Disease
Condition: Transposition Great Arteries; Executive Dysfunction
MeSH terms: Heart Diseases; Heart Defects, Congenital; Transposition of Great Vessels
Study type: Observational

Summary: 
      In the landmark Boston Circulatory Arrest Study, neurologic and developmental status was
      measured following infant heart surgery and then prospectively at ages 1, 2.5, 4, 8, and 16
      years, with findings of significant neurocognitive deficits and brain MRI abnormalities
      regardless of operative management. To date, no study has evaluated the neuropsychological
      and neuroimaging antecedents and correlates of well-being in adults with congenital heart
      disease, a population now >1 million and projected to grow at 5% per year. The investigators
      propose to study the Boston cohort at ages 24-29 years to assess the associations of adult
      well-being with childhood and adolescent executive function, other measures of mental health
      and cognitive function, adolescent brain MRI findings, and clinical variables; findings will
      guide the design of interventions in childhood to optimize outcomes in adults with congenital
      heart disease.
    

Detailed description: 
      Previously lethal, critical congenital heart disease (CHD) can now be treated effectively
      with surgical, catheter, and medical interventions. The resulting dramatic improvement in
      life expectancy has brought a major demographic shift, so that adult patients with CHD now
      outnumber children with CHD, even for complex conditions. Adult survivors are at increased
      risk of anxiety, depression, social difficulties, lower educational attainment, and
      underemployment. These psychosocial morbidities may be associated with deficits in executive
      functions (EFs) and other neurocognitive abilities that are prevalent in children and
      adolescents with CHD. Deficits in EFs, represented by measures of inhibitory control, working
      memory, cognitive flexibility, and decision-making, are highly dependent on the integrity of
      cortical and subcortical neural networks that continue to develop into early adulthood and
      can have a major adverse impact on self-regulation and management. The goal of this proposal
      is to bridge the gap in knowledge between known executive function deficits in childhood CHD
      and adult well-being. The investigators propose to accomplish our goal by studying subjects,
      now age 24-29 years, who were enrolled as infants in the Boston Circulatory Arrest Study and
      then studied with respect to neuropsychological and developmental function at ages 1, 2.5, 4,
      8, and 16 years, as well as with brain MRI at 16 years. In Aim 1, the relationship of EFs to
      major dimensions of adult well-being will be explored. It is hypothesized that lower
      performance on EFs will be related to poorer overall well-being. The outcomes measured to
      determine well-being will be quality of life, neuropsychological function (e.g. social
      cognition, memory skills), mental health diagnosis and function (e.g. anxiety, depression),
      social relatedness, academic achievement, and adult independence (e.g. employment status,
      medical follow up). In Aim 2, the relationship of EFs to MRI-derived measures of brain
      structure, function, and connectivity will be determined. It is hypothesized that lower
      performance on EFs will be associated with lower global efficiency (integration) and higher
      modularity (segregation). The brain MRI outcomes will be measured using global white matter
      connectivity, regional cortical gray matter thickness, gray matter connectivity measured from
      interregional correlation in cortical thickness, and functional connectivity as defined by
      resting state functional magnetic resonance imaging. In Aim 3, longitudinal models will be
      used to analyze the association of adult well-being with earlier measures of EFs and other
      neurocognitive and mental health variables, as well as with earlier clinical variables and
      adolescent neuroimaging. The associations of adult well-being dimensions with childhood and
      adolescent EFs, other measures of mental health and cognitive function, adolescent brain MRI
      findings, and clinical variables will be explored. The ultimate goal is to identify early,
      modifiable risk factors for adult performance to guide the design of targeted treatment
      strategies that optimize educational achievement, employability, and quality of life in the
      burgeoning population of adults with CHD.
    

Intervention name(s): Brain MRI, neurocognitive and psychological testing
Intervention type(s): Diagnostic Test
Intervention description(s): MRI of the brain and multiple tests of neurocognitive and psychological function including executive function, anxiety and depression
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Study Group: All children enrolled in the original boston circulatory arrest study who are
        alive and living in the US will be invited to participate. We estimate that about 165
        adults will be eligible to participate as we will again attempt to contact those patients
        who did not participate in the 16 year follow-up.

        Controls (for MRI): A group of 50 normally-developed age- and sex-matched young adults ages
        24-30 years old who are able to provide informed consent to undergo the MRI portion of the
        study and limited neuropsychiatric (NP) evaluation. These controls will be recruited from
        the local metro-Boston area and we will frequency-match control patients to study patients
        by gender, integer age and handedness.