The Boston Circulatory Arrest Study: Antecedents and Correlates of Well-Being in Adults With Congenital Heart Disease

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.

Study Group:

Inclusion Criteria

1. Prior participation in the Boston Circulatory Arrest Study

2. Informed consent

Exclusion Criteria

1. Disorders that would prevent successful completion of the planned study testing
(severe developmental impairment to prevent answering surveys and participating in
interviews)

2. Participants lack of reading fluency in English, which is the only language for which
we have the ability to do neuropsychology testing, and for which questionnaires have
been validated

3. Women who are currently pregnant will be excluded from the MRI portion of the study
only

Control Group:

Control Inclusion Criteria

1. Age 24-30 years at the time of enrollment

2. Informed consent

Control Exclusion Criteria

1. Conditions that would prevent successful completion of the planned study testing (MRI)
(e.g., pacemaker, metal implants, orthodontia)

2. Congenital heart disease requiring surgical correction

3. Lack of reading fluency in English, the only language for which questionnaires have
been validated

4. Because we purposefully wish to compare d-TGA patients with those in optimal
neurodevelopmental health, we will use the exclusion criteria for the NIH-funded
project, "MRI study of normal brain development."

5. Current pregnancy