Genetic Determinants of Congenital Heart Disease Outcomes

For physicians caring for children with congenital cardiac defects, perhaps the greatest
challenge is to improve the survival and functional outcomes of patients with severe defects
requiring surgical repair or palliation in the first month of life. These cardiac defects can
be associated with 5 year mortality rates of up to 30% with significant disabilities in many
of the survivors. As with every medical condition, patient outcomes depend on the complex
interaction of the disease process, the medical and surgical interventions to treat the
disease, and the inherent capacity of the patient to respond to both the disease and its
treatment.

For patients with severe cardiac defects, the greatest risk for morbidity and mortality
occurs during and shortly after their neonatal surgical repair. During surgery to repair
severe cardiac defects, the body is cooled and the heart is stopped. In many cases, blood
flow to the vital organs is interrupted or restricted for a significant period of time while
the aortic arch is reconstructed. This process places profound stress on the patient's
capacity to tolerate these insults without sustaining irreversible injury to tissues such as
the heart, brain, and kidneys. That there is such a wide range of outcomes after this
surgery, even between patients with similar clinical features, suggests that there are
important individual differences in patients' abilities to respond to this stress that is
determined by differences in their genetic traits.

The importance of the interaction between the controlled trauma of the surgical environment
and a patient's genetic background in determining patient outcomes has led to the new
discipline of "peri-operative genomics." In this study, we will examine the contribution of
gene-environment interactions to perioperative and short-term outcomes in neonates with
severe congenital cardiac defects.

Inclusion Criteria:

- d-transposition of the great arteries or single ventricle cardiac disease

- Less than or equal to 30 days of age

- Planned arterial switch operation or stage I surgical palliation (Norwood)with aortic
arch reconstruction

Exclusion Criteria:

- Known trisomy 13, 18, or 21

- Any major non-cardiac anomaly that precludes the patient from cardiac surgery