Heart Failure
Conditions
Keywords
autologous micrografts, heart failure, coronary artery bypass surgery, cell therapy, atrial appendage, epicardial cell delivery
Brief summary
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
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.
Interventions
PROCEDURECABG surgery
Elective CABG surgery
PROCEDUREAADC therapy
Atrial appendage derived cells are placed on the site of a infarct scar with matrix sheet
Sponsors
Helsinki University Central Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility: Closing the right atrial appendage | 6 months | 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. |
| Safety; oxygen saturation in the pulmonary arterial blood (SvO2) in % | 6 months | For assessing haemodynamics during the operation and at the intensive care unit |
| Safety; serum potassium level in mmol/l | 6 months | For assessing haemodynamics during the operation and at the intensive care unit |
| Safety; blood glucose level in mmol/l | 6 months | For assessing haemodynamics during the operation and at the intensive care unit |
| Safety; Left ventricular ejection fraction (EF) in % | 6 months | For assessing cardiac function during and after the operation by echocardiogram |
| Safety; pericardial effusion in mm | 6 months | For assessing cardiac function after the operation by echocardiogram |
| Safety: telemetric monitoring of rhythm | 6 months | For assessing cardiac function after the operation |
| Feasibility: Success in completing the delivery of the cell sheet to the myocardium | 6 months | Measured in 0= success, 1= no success |
| Feasibility: Waiting time in minutes for the cell sheet | 6 months | Waiting time in minutes for the finished cell sheet to be placed on the myocardium after doing all the required anastomoses |
| Feasibility: Waiting time in minutes for the heart | 6 months | Waiting time in minutes for the the heart after doing all the anastomoses and before the cell sheet is finished |
| Safety; need for vasoactive medication | 6 months | For assessing haemodynamics during the operation and at the intensive care unit |
| Safety; cardiac index in l/min/m | 6 months | For assessing haemodynamics during the operation and at the intensive care unit |
| Safety; hemoglobin in g/l | 6 months | For assessing haemodynamics during the operation and at the intensive care unit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular wall thickness | 6 months | Measured by MRI |
| Change in the amount of myocardial scar tissue | 6 months | Measured by MRI |
| Change in left ventricular ejection fraction | 6 months | Measured by MRI |
| 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. | 6 months | measured by questionnaire |
| Change in movement and diastolic function of left ventricular wall | 6 months | Measured by MRI |
| Local changes in systolic and diastolic function | 3 months | Measured by echocardiogram |
Countries
Finland
Outcome results
None listed