Genetic Determinants of Congenital Heart Disease Outcomes (GECHO)

• Contribution of genetic variation in oxidative stress management to differences in short term outcomes after repair for severe cardiac disease in the neonatal period [ Time Frame: Duration of initial perioperative hospitalization (~2-4 weeks) ] [ Designated as safety issue: No ]

  Genotyping will be performed on 10 variants in the oxidative stress response pathway and we will combine risk genotypes in order to evaluate the cumulative effect of both detrimental and beneficial alleles on post-operative outcomes.

  Composite short term outcome measure includes:

  ICU length of stay (days) Time to initial extubation (hours) Cardiac arrest or ECMO support (Y/N) Delayed sternal closure (Y/N) Serious adverse event (Y/N) Greater than 1 serious adverse event (Y/N)

  
  

• Contribution of genetic variation in oxidative stress management to differences in interstage mortality and pre-Stage II cardiovascular function in patients with single ventricle cardiac disease [ Time Frame: Interval from hospital discharge following stage I surgical palliation until hospital admission for stage II surgical palliation (~4-6 months of age) ] [ Designated as safety issue: No ]

  Composite outcome

  • Growth parameters (height, weight, head circumference)
  • AV valve insufficiency (By echocardiogram and cardiac catheterization) , Ventricular function (ejection fraction by echocardiogram and by cardiac catheterization), Central venous pressure and ventricular end diastolic pressure (by catheterization), Interstage Death (Y/N).
  
  

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.