Brief Title
The Boston Circulatory Arrest Study: Antecedents and Correlates of Well-Being in Adults With Congenital Heart Disease
Official Title
The Boston Circulatory Arrest Study: Antecedents and Correlates of Well-Being in Adults With Congenital Heart Disease
Brief 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.
Study Type
Observational
Primary Outcome
Quality of Life
Secondary Outcome
Mental health - Anxiety
Condition
Transposition Great Arteries
Intervention
Brain MRI, neurocognitive and psychological testing
Study Arms / Comparison Groups
TGA Case
Description: Brain MRI, Neurocognitive and psychological testing
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Diagnostic Test
Estimated Enrollment
150
Start Date
November 9, 2017
Completion Date
November 30, 2020
Primary Completion Date
June 30, 2020
Eligibility Criteria
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
Gender
All
Ages
24 Years - 30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Michelle Gurvitz, MD, 617-355-6508, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03073122
Organization ID
P00023574
Secondary IDs
1R01HL135061-01
Responsible Party
Principal Investigator
Study Sponsor
Boston Children's Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Study Sponsor
Michelle Gurvitz, MD, Principal Investigator, Boston Children's Hospital
Verification Date
August 2019