Autologous Atrial Appendage Derived Cells in the Treatment of Heart Failure

Study Overview
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Brief Summary
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This study aims to evaluate the safety and clinical feasibility of epicardially delivered autologous atrial appendage micrografts in the treatment of heart failure. The micrografts consisting atrial-derived cells and their extracellular matrix, are placed on an infarction scar during CABG surgery.

Detailed Description
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The atrial appendages are a tissue reservoir for cardiomyocyte stem and precursor cells. During coronary artery bypass graft (CABG) surgery part of the right atrial appendage can be excised upon insertion of the right atrial cannula of the heart-lung machine. This study aims to address the surgical feasibility and patient safety of epicardially delivered atrial appendage micrografts during CABG surgery. Autologous cardiac cells are harvested from right atrial appendage during CABG of six patients. Micrografts consisting atrial appendage-derived cells (AADCs) and their extracellular matrix (ECM) of the atrial appendage are mechanically processed. The cells are placed on a tissue-engineered sheet with fibrin gel and tissue clue and further delivered epicardially on top of a infarction scar. Parameters including echocardiography reflecting cardiac insufficiency are studied pre- and post-operatively as well as at three and six months of the follow-up. Cardiac functional magnetic resonance imaging is performed preoperatively and at six-months follow-up. 20 patients will be recruited to serve as a control group. They are scheduled for elective CABG and are treated according to the normal hospital protocol, without the ECM sheet.

Official Title
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Epicardial Delivery of Autologous Atrial Appendage Micrografts During Coronary Artery Bypass Surgery - Safety and Feasibility Study

Conditions
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Heart Failure

Intervention / Treatment
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* Procedure: CABG surgery
* Procedure: AADC therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained Left ventricular ejection fraction (LVEF) between ≤50% and ≥15% New York Heart Association (NYHA) Class II-IV heart failure symptoms Exclusion Criteria: Heart failure due to left ventricular outflow tract obstruction History of life-threatening and possibly repeating ventricular arrhythmias or resuscitation, or an implantable cardioverter-defibrillator Stroke or other disabling condition within 3 months before screening Severe valve disease or scheduled valve surgery Renal dysfunction (GFR <84 ml/min/1.73m) Other disease limiting life expectancy Contraindications for coronary angiogram or MRI Participation in some other clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AACD-Therapy group<br>6 patients are recruited to the AADC-therapy group. Autologous atrial appendage derived cells (AADCs) are harvested from the appendage tissue removed during the venal cannulation of bypass. The cells and their extracellular matrix are placed with tissue clue to Cormatrix-sheet and further on top of the myocardium in the area of infarction scar. The procedure is done simultaneously with CABG surgery. The patients will be carefully monitored after the operations and cardiac MRI and echocardiogram will be performed previously to surgery as well as during the follow ups. | Procedure: CABG surgery<br>* Elective CABG surgery<br>Procedure: AADC therapy<br>* Atrial appendage derived cells are placed on the site of a infarct scar with matrix sheet<br>|
| Active Comparator: Control group<br>20 patients are recruited to form the control group. They are patients scheduled for elective CABG surgery and they meet the same inclusion and exclusion criteria as the therapy group. There patients are followed as the hospital protocol with out any additional imagination or blood tests. | Procedure: CABG surgery<br>* Elective CABG surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety; need for vasoactive medication | For assessing haemodynamics during the operation and at the intensive care unit | 6 months | 
| Safety; cardiac index in l/min/m | For assessing haemodynamics during the operation and at the intensive care unit | 6 months | 
| Safety; hemoglobin in g/l | For assessing haemodynamics during the operation and at the intensive care unit | 6 months | 
| Safety; oxygen saturation in the pulmonary arterial blood (SvO2) in % | For assessing haemodynamics during the operation and at the intensive care unit | 6 months | 
| Safety; serum potassium level in mmol/l | For assessing haemodynamics during the operation and at the intensive care unit | 6 months | 
| Safety; blood glucose level in mmol/l | For assessing haemodynamics during the operation and at the intensive care unit | 6 months | 
| Safety; Left ventricular ejection fraction (EF) in % | For assessing cardiac function during and after the operation by echocardiogram | 6 months | 
| Safety; pericardial effusion in mm | For assessing cardiac function after the operation by echocardiogram | 6 months | 
| Safety: telemetric monitoring of rhythm | For assessing cardiac function after the operation | 6 months | 
| Feasibility: Success in completing the delivery of the cell sheet to the myocardium | Measured in 0= success, 1= no success | 6 months | 
| Feasibility: Waiting time in minutes for the cell sheet | Waiting time in minutes for the finished cell sheet to be placed on the myocardium after doing all the required anastomoses | 6 months | 
| Feasibility: Waiting time in minutes for the heart | Waiting time in minutes for the the heart after doing all the anastomoses and before the cell sheet is finished | 6 months | 
| Feasibility: Closing the right atrial appendage | Closing the right atrial appendage after removing the standardized tissue piece for preparing the cell sheet. According to the hospital protocol, appendage is closed with purse string suture. 0 = no additional suturing needed, 1 = additional suturing needed. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular wall thickness | Measured by MRI | 6 months | 
| Change in the amount of myocardial scar tissue | Measured by MRI | 6 months | 
| Change in left ventricular ejection fraction | Measured by MRI | 6 months | 
| Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels |  | 6 months | 
| New York Heart Association class |  | 6 months | 
| Days in hospital |  | 1 month | 
| Changes in the quality of life. | measured by questionnaire | 6 months | 
| Change in movement and diastolic function of left ventricular wall | Measured by MRI | 6 months | 
| Local changes in systolic and diastolic function | Measured by echocardiogram | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous micrografts, heart failure, coronary artery bypass surgery, cell therapy, atrial appendage, epicardial cell delivery