Proteomic Profiling with Single Ventricle Heart Disease

Research study background  

Infants with single ventricle heart disease, a rare yet severe form of congenital heart disease, are born with only one pumping chamber that functions. There is no cure, and without surgical intervention, most infants won’t survive. The underlying pathobiology is not well understood.

This study was the first to evaluate if the proteome of single ventricle heart disease is different than healthy controls, how the proteome changes after stage 2 palliation, and if differences in the proteome after stage two palliation have predictive value in infants’ outcomes after surgery.

Proteomics can identify novel biomarkers and important pathways in complex disease. Researchers at the Children’s Hospital Colorado Heart Institute conducted a prospective cohort study of cardiovascular proteomic phenotyping in infants with single ventricle heart disease undergoing stage 2 palliation.

The study population included 29 infants with pre-stage 2 single ventricle heart disease and 25 healthy controls. Outcomes that were analyzed were postoperative hypoxemia and endotracheal intubation time. Serum samples were drawn pre-operative and 24 hours post-operative, and 184 cardiovascular proteins were analyzed.

Findings from the study:

• Patients with longer endotracheal intubation time had higher pre-operative pulmonary vein tissue inhibitor of metalloproteinase-1 and nidogen-1
• Patients with greater postoperative hypoxemia had higher post-operative matrix metalloproteinase 7 levels
• Proteomic analysis identified significant changes among infants with pre- and post-stage 2 single ventricle heart disease and healthy controls:
  • Single ventricle heart disease cases with greater morbidity had higher tissue inhibitor levels of metalloproteinase-1, nidogen-1 and matrix metalloproteinase 7
  • Suggests extracellular matrix production regulation plays an important role in changes

Study conclusions

Proteomic profiling may identify infants with high-risk single ventricle heart disease. It will be important to conduct future studies to validate these findings and explore their pathophysiologic significance.