Cardiac Remodeling and Circulating Biomarkers in Pediatric Left Ventricular Pressure Loading Lesions

Study Overview
=================
Brief Summary
-----------------
This study is designed to learn more about children who have blockage of the left side of their heart. The goal is to determine how much the heart muscle has thickened before surgery and how it changes in the months after surgery. Investigators are also looking for blood tests that may help them predict which patients will have the most thickening pre-operatively and the best return towards normal after surgery. The findings of this study will help the investigators develop new tests to monitor affected patients and develop new therapies to help minimize heart thickening.

Official Title
-----------------
Cardiac Remodeling and Circulating Biomarkers in Pediatric Left Ventricular Pressure Loading Lesions

Conditions
-----------------
Coarctation of Aorta, Aortic Stenosis, Cardiac Hypertrophy

Intervention / Treatment
-----------------
* Procedure: Echocardiogram
* Biological: Serology


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Congenital heart disease patients with the following diagnoses undergoing surgical repair: Coarctation of the aorta (CoA), aortic stenosis (AS), subaortic membrane (sub-AS), supravalvar aortic stenosis (supra-AS). All patients will have age from birth through 18 years of age. While we will generally not enroll patients with other co-morbid heart disease that would alter the cardiac physiology (see exclusion criteria), patients with patent foramen ovale, atrial septal defect, and patent ductus arteriosus specifically will be allowed. Exclusion Criteria: Patients with lesions not listed in inclusion criteria (including but not limited to hypoplastic left heart syndrome, Shone's complex, mitral valve stenosis or regurgitation greater than trivial, non-restrictive ventricular septal defect, interrupted aortic arch, atrio-ventricular canal defect) Corrected gestational age at time of surgery <34 weeks Weight at time of surgery <2000g. Patients who will not be seen for any follow-up care at Children's Hospital Colorado

Ages Eligible for Study
-----------------
Maximum Age: 18 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Persistent hypertrophy<br>Elevated cardiac mass at follow-up time point as measured by Echocardiographic and Serologic evaluations. | Procedure: Echocardiogram<br>* 2 and 3-dimensional echocardiographic images will be obtained to estimate LV mass, ejection fraction (Simpson's biplane), fractional shortening (M mode Doppler), and pulse-wave estimated pressure gradient across the outflow obstruction.<br>* Other names: Diagnostics;Biological: Serology<br>* protein analysis targeting several potential protein biomarkers for cardiac remodeling and hypertrophy as well as targeting known miRNAs.<br>* Other names: Diagnostics;|
| Normal geometry<br>Normal cardiac mass at follow-up time point as measured by Echocardiographic and Serologic evaluations. | Procedure: Echocardiogram<br>* 2 and 3-dimensional echocardiographic images will be obtained to estimate LV mass, ejection fraction (Simpson's biplane), fractional shortening (M mode Doppler), and pulse-wave estimated pressure gradient across the outflow obstruction.<br>* Other names: Diagnostics;Biological: Serology<br>* protein analysis targeting several potential protein biomarkers for cardiac remodeling and hypertrophy as well as targeting known miRNAs.<br>* Other names: Diagnostics;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular mass | Left ventricular mass will be measured by 2D echocardiography at 1 year after surgical correction. | 1 year after surgery | 
| Change in left ventricular mass | Left ventricular mass will be measured by 2D echocardiography prior to surgery, immediately after surgery, and will be compared to that measured at 1 year after surgical correction. | Within 1 week prior to surgery, 24-72 hrs after surgery, 1 year after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative wall thickness | A more detailed measure of relative wall thickness (RWT) will be assessed by echocardiography at 1 year after surgical correction. | 1 year after surgery | 
| Left ventricular mass | Left ventricular mass will be measured by 3D echocardiography at 1 year after surgical correction. | 1 year after surgery | 
| Change in relative wall thickness | Relative wall thickness will be measured by 2D echocardiography prior to surgery and at 1 year after surgical correction. | Within 1 week prior to surgery and 1 year after surgery | 
| Change in relative wall thickness | Relative wall thickness will be measured by 2D echocardiography 24-72 hours and at 1 year after surgical correction. | 24-72 hours and 1 year after surgery | 
| Change in left ventricular mass | Change in left ventricular mass will be measured by 3D echocardiography 24-72 hours and 1 year after surgical correction. | 24-72 hours and 1 year after surgery | 
| Change in left ventricular mass | Change in left ventricular mass will be measured by 3D echocardiography prior to surgery and at 1 year after surgical correction. | Within 1 week prior to surgery and 1 year after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coarctation of aorta, aortic stenosis, biomarkers, cardiac hypertrophy