ET1 Concentration, Metabolic Pathway Activation, and Pulmonary Blood Flow in Infants Undergoing Superior Cavo-Pulmonary Anastomosis

Study Overview
=================
Brief Summary
-----------------
This is a novel preliminary study of biomarkers of pathologic pre-operative pulmonary vascular development, elevated pre-operative Pulmonary Vascular Resistance Index (PVRi), and complications associated with decreased post-operative pulmonary blood flow in single ventricle patients undergoing superior cavo-pulmonary anastomosis (SCPA). The study will utilize a combined targeted and untargeted approach to both optimize translation of a promising existing biomarker and efficiently identify novel biomarkers and potential therapeutic targets in this population.

Detailed Description
-----------------
Overall Hypothesis: Endothelin-1 (ET1) and associated dysregulation of key metabolic pathways decrease pre-operative pulmonary blood vessel development and increase post-operative pulmonary blood vessel resistance leading to decreased pulmonary blood flow in patients undergoing SCPA. For enrolled patients, collected data will include: 3 mL blood sample (x2) at pre-SCPA catheterization. 3 mL blood samples at 2, 24, and 48 hours post-operative. Urine sample pre-operatively and post-operatively Collection of otherwise-discarded operative tissue sample from the pulmonary artery. Collection of clinical data, demographic data, and results of routine, post-operative hemodynamic monitoring.

Official Title
-----------------
ET1 Concentration, Metabolic Pathway Activation, and Pulmonary Blood Flow in Infants Undergoing Superior Cavo-Pulmonary Anastomosis

Conditions
-----------------
Single-ventricle, Pulmonary Vascular Resistance Abnormality, Superior Cavo-Pulmonary Anastomosis, Endothelin, Metabolomics

Intervention / Treatment
-----------------
* Other: Research Blood Sampling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Congenital heart disease patients undergoing catheterization for pre-SPCA evaluation or undergoing SCPA without plans for cardiac catheterization (utilizing data from a previously performed clinical catheterization). All patients will have age from 31 days to 2 years. Exclusion Criteria: Patients who will remain post-op with a pulsatile source of pulmonary blood flow in addition to the cavo-pulmonary anastomosis (so called 1.5 ventricle repair) will be excluded. Due to limitations in acceptable sample blood volumes for research, patients with weight <4kg will be excluded. Patients will not be excluded on the basis of gender, ethnicity, genetic diagnosis, gestational age at birth, non-cardiac comorbidity, or pre-operative medication regimen.

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 2 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Patients<br>Infants between 1 month and 2 years of age undergoing evaluation for SCPA candidacy. | Other: Research Blood Sampling<br>* Blood samples will be collected at specified time points and research assays will be performed.<br>|
| Control Patients<br>Infants between 3 months and 12 months of age with no known cardio-pulmonary disease, no active infection, and no known genetic abnormality undergoing elective surgery for a non-cardiac indication. | Other: Research Blood Sampling<br>* Blood samples will be collected at specified time points and research assays will be performed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in ET1 concentration between controls, study patients at pre-SCPA catheterization, and study patients in the post-operative period. |  | 48 hours post-operatively | 
| Difference in metabolomics profile between controls, study patients at pre-SCPA catheterization, and study patients in the post-operative period. |  | 48 hours post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between ET1 concentration at pre-SCPA catheterization in study patients and clinical metrics of pre-operative pulmonary adequacy. |  | 48 hours post-operatively | 
| Association between metabolomics profile in study patients and clinical metrics of pre-operative pulmonary adequacy. |  | 48 hours post-operatively |