Atrial Appendage Micrograft Transplants to Assist Heart Repair After Cardiac Surgery
Recruiting · NCT05632432 · Interventional (participants receive a specific treatment) · Lead sponsor: Hospital District of Helsinki and Uusimaa
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
Ischemic heart disease (IHD) leads the global mortality statistics. Atherosclerotic plaques in coronary arteries hallmark IHD, drive hypoxia, and may rupture to result in myocardial infarction (MI) and death of contractile cardiac muscle, which is eventually replaced by a scar. Depending on the extent of the damage, dysbalanced cardiac workload often leads to emergence of heart failure (HF). The atrial appendages, enriched with active endocrine and paracrine cardiac cells, has been characterized to contain cells promising in stimulating cardiac regenerative healing. In this AAMS2 randomized controlled and double-blinded trial, the patient's own tissue from the right atrial appendage (RAA) is for therapy. A piece from the RAA can be safely harvested upon the set-up of the heart and lung machine at the beginning of coronary artery bypass (CABG) surgery. In the AAMS2 trial, a piece of the RAA tissue is processed and utilized as epicardially transplanted atrial appendage micrografts (AAMs) for CABG-support therapy. In our preclinical evaluation, epicardial AAMs transplantation after MI attenuated scarring and improved cardiac function. Proteomics suggested an AAMs-induced glycolytic metabolism, a process associated with an increased regenerative capacity of myocardium. Recently, the safety and feasibility of AAMs therapy was demonstrated in an open-label clinical study. Moreover, as this study suggested increased thickness of the viable myocardium in the scarred area, it also provided the first indication of therapeutic benefit. Based on randomization with estimated enrolment of a total of 50 patients with 1:1 group allocation ratio, the piece of RAA tissue is either perioperatively processed to AAMs or cryostored. The AAMs, embedded in a fibrin matrix gel, are placed on a collaged-based matrix sheet, which is then epicardially sutured in place at the end of CABG surgery. The location is determined by preoperative late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRI) to pinpoint the ischemic scar. The controls receive the collagen-based patch, but without the AAMs. Study blood samples, transthoracic echocardiography (TTE), and LGE-CMRI are performed before and at 6-month follow-up after the surgery. The trial's primary endpoints focus on changes in cardiac fibrosis as evaluated by LGE-CMRI and circulating levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Secondary endpoints center on other efficacy parameters, as well as both safety and feasibility of the therapy.
Who can take part
Inclusion criteria
- Informed consent obtained
- Left ventricular ejection fraction (LVEF) between ≥ 15% and ≤ 40% at recruitment (transthoracic echocardiography)
- New York Heart Association (NYHA) Class II-IV heart failure symptoms
Exclusion criteria
- Heart failure due to left ventricular outflow tract obstruction
- Acute myocardial infarction (AMI) within last 30 days
- 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 \<45 ml/min/1.73m2)
- Other disease limiting life expectancy
- Contraindications for coronary angiogram or LGE-CMRI
- Participation in some other clinical trial
- Screening Failure:
- After optimization of medications, no visible scar or LVEF ≥ 50% in preoperative LGE-CMRI
- Preoperative LGE-CMRI has not been performed prior scheduled CABG
Where it is running
1 location listed.
- Hospital District of Helsinki and Uusimaa, Helsinki University Hospital, Heart and Lung Center & Cardiac Unit - Helsinki, Uusimaa, Finland