COBRA3 Congenital heart defects: Bridging the gap between Growth, Maturation,
Regeneration, Adaptation, late Attrition and Ageing

Congenital Heart Defect (ConHD) is the most common birth defect, affecting 0.8%
of live births. After invasive treatment, many ConHD patients survive with
relatively few problems for many years, despite abnormal loading conditions.
However, about 50% of patients with ConHD reaching adulthood die from heart
failure, arrhythmias or pulmonary hypertension, especially in diseases
affecting the right ventricle (RV). This morbidity and mortality in young
adulthood has created a new health care problem, affecting over 4 million
patients with ConHD in North-America and Europe.
Current progress in management, prognosis and therapy is hampered by our lack
of 1) mechanistic insight into the impact of ConHD on postnatal growth,
function and homeostasis of the heart, 2) ability to identify patients at risk
in an early stage and 3) specific therapies aimed to prevent or reverse heart
failure in the setting of ConHD.
The heart of children grows rapidly, proliferates, remodels and has the
potential to renew its
cells. Our hypothesis is that these properties are important factors in
preserving homeostasis in the context of ConHD and abnormal loading conditions
during childhood, keeping attrition at bay.

1. to gain mechanistic insight into the impact of ConHD on growth, renewal and
homeostasis of the heart, especially the RV
2. to improve identification of patients at risk for attrition of heart
function in ConHD
3. to establish the context to develop therapies to prevent or reverse heart
failure or arrhythmias in ConHD patients.

Prospective as well as cross-sectional patient-based study.

All clinical examinations, with the exception of myocardial biopsies, in the
participating patients are the same as are routinely performed during follow-up
of patients from the 4 diagnostic groups, including dobutamine stress MRI in
Fallot and Fontan patients. For the purpose of the research proposal
examinations will be clustered, and will be repeated before and after surgery,
catheter intervention or change in drug regimen, if
applicable. All examinations will be performed on the same day, unless the
patient prefers to participate on 2 consecutive days. The total duration of
these examinations is a maximum of 2,5 hours all the medical examinations
combined. Burden and risk are similar to those of regular clinical procedures
and follow-up, that apply to all children and adults in this research proposal.
During regular follow-up blood samples will be obtained with every check-up
related to the current research proposal. The amount of blood drawn and the
mode of acquisition will be in line with the local biobank protocol for study
specific biobanking.
Only in those patients in whom a clinical indication exists for cardiac
surgery, myocardial samples will be obtained according to clinical guidelines.
Blood and myocardial biopsies will be stored in local university hospital
biobanks for later use in the course of the current project.
Myocardial sampling is done strictly for scientific reasons. Samples will be
taken from the region of the heart that will need to be approached by surgery
for clinical reasons in tetralogy of Fallot patients and most patients with a
univentriculair heart. In patients with an ASD II, VSD and some univentriculair
heart patients with a body weight of > 8 kg, a surgical myocardial biopsy will
be taken from the right ventricle (ASD II / VSD) or from the dominant ventricle
in univentriculair heart patients strictly for scientific reasons.
Group-relatedness exists because the study cannot be done in adults with
similar disease types, since growth and growth related myocardial renewal and
homeostasis cannot be studied in subjects in whom growth has ceased.