Reversible Pulmonary Artery Banding as Simplified Management of End-stage Dilated Left Ventriculopathy in Early Life

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to: 1) Remodel and restore left ventricular geometry and function. 2) Avoid the need for mechanical circulatory support (MCS) and/or cardiac transplantation (CT). 3) Confirm the outcomes of a pilot study completed in Germany and reported in The Journal of Heart and Lung Transplantation in May 2013.

Detailed Description
-----------------
The study infant will undergo cardiac catheterization and myocardial biopsy before pulmonary artery banding and at appropriate intervals during follow-up surveillance by the interventional cardiologist. Patients will be listed for heart transplantation, and rPAB will be applied in lieu of mechanical circulatory support or as an alternative to already existing mechanical circulatory support, in the form of extracorporeal mechanical oxygen (ECMO). Myocardial biopsies will be flash frozen for storage and eventual probing for cell type (mature or stem) as part of a separate study. The addition of afterload rPAB to a normal-functioning right ventricle (in the setting of end-stage dilated cardiomyopathy) shifts the inter-ventricular septum toward the midline, thus significantly improving left ventricular geometry and function. It permits the infant or young child to operate from a much improved position on Starling's curve with gradual resolution of congestive heart failure and the potential for lethal ventricular dysrhythmia. An abundance of progenitor myocytes known to exist within the myocardium of this patient age group may then contribute to permanent left ventricular restoration. A sternotomy incision is used for application of the rPAB. The band is tightened under echocardiographic control until the inter-ventricular septum becomes a midline structure. Myocardial function is augmented with inotropic and vasodilator agents. These agents are weaned off gradually over a period of 2-4 weeks. The infant is separated from mechanical ventilation within the first post-rPAB week, and enteric feeding is resumed. The infant is discharged on oral medications, and is kept under frequent clinical surveillance. As the infant grows, the rPAB becomes relatively more obstructive to right ventricular outflow. Based on a finding of increasing right ventricular dilation, onset or worsening tricuspid valve regurgitation, or a gradual late increase in plasma B-type natriuretic peptide (BNP) levels, the band may be loosened in stages as a balloon catheter-based procedure. Band enlargement may be accomplished in stages, ultimately opting for a mild residual right ventricle-main pulmonary artery pressure gradient of 15-30 mmHg. The infants' short- and long-term surveillance will include clinical examination, height, weight, cardiac catheterization, electrocardiogram, echocardiogram, chest x-ray, and plasma BNP levels.

Official Title
-----------------
Reversible Pulmonary Artery Banding as Simplified Management of End-stage Dilated Left Ventriculopathy in Early Life

Conditions
-----------------
Acute on Chronic Systolic Congestive Heart Failure

Intervention / Treatment
-----------------
* Procedure: Reversible Pulmonary Artery Banding
* Procedure: GORE-TEX DualMesh EMERGE PLUS Biomaterial


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 0-4 years Isolated, idiopathic left-ventricular end-stage dilated cardiomyopathy or a Left Ventricular End-Diastolic Diameter (LVEDD) Z-score > 4.5; Ejection Fraction (EF) < 30% Acceptable candidate for mechanical circulatory support and/or cardiac transplantation Preserved right-ventricular function Clinical functional status IV (hospitalized) Parental consent Exclusion Criteria: Biventricular end-stage dilated cardiomyopathy Proven or suspected myocarditis Concomitant structural (congenital) heart disease Moderate-severe tricuspid valve regurgitation Pulmonary hypertension out of proportion with left-ventricular end-stage cardiomyopathy Hereditary disease associated with bi-ventricular dysfunction Age greater than 4 years No parental consent

Ages Eligible for Study
-----------------
Maximum Age: 4 Years

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

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

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

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reversible Pulmonary Artery Banding Procedure<br>The addition of afterload Reversible Pulmonary Artery Banding to a normal-functioning right ventricle (in the setting of end-stage dilated cardiomyopathy) shifts the inter-ventricular septum toward the midline, thus significantly improving left ventricular geometry and function. It permits the infant or young child to operate from a much improved position on Starling's curve with gradual resolution of congestive heart failure and the potential for lethal ventricular dysrhythmia. An abundance of progenitor myocytes known to exist within the myocardium of this patient age group may then contribute to permanent left ventricular restoration. | Procedure: Reversible Pulmonary Artery Banding<br>* A sternotomy incision is used for application of the rPAB. Tightening is under echocardiographic control until the inter-ventricular septum becomes a midline structure. Myocardial function is augmented with inotropic and vasodilator agents that are weaned after 2-4 weeks. The infant is separated from mechanical ventilation within the first week, and enteric feeding is resumed. The infant is discharged on oral medications, with follow-ups. Band enlargement is in stages as a balloon catheter-based procedure if a finding of increasing right ventricular dilation, onset or worsening tricuspid valve regurgitation, or a gradual late increase in plasma B-type natriuretic peptide (BNP) levels, opting for a mild residual right ventricle-main pulmonary artery pressure gradient of 15-30 mmHg.<br>* Other names: rPAB;Procedure: GORE-TEX DualMesh EMERGE PLUS Biomaterial<br>* The study is being conducted to evaluate the procedure, not the materials being used. The study uses the patch as materials to create the band around the pulmonary artery which is currently done routinely off label. The patch is approved as a cardiovascular patch. FDA 501(k) K032168.<br>* Other names: Gortex Cardiovascular Patch;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical Success | positive surgical outcome, the survival of the patient, the lack of a need for mechanical circulatory support or heart transplant, and improved left ventricular function | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Mortality | Total number of deaths due to non-cardiac open vs minimally invasive thoracic surgery. | 5 years | 
| Persistent Heart Failure | Described as having an NYHA of greater than II. | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infant Cardiac Transplantation, End-stage Idiopathic Dilated Cardiomyopathy, Mechanical Circulatory Device, End Stage Dilated Left Ventriculopathy, Acute-on-Chronic Left Ventricular Failure