Ischemic heart diseases and heart attacks often cause irreparable damage in the heart muscle. The damage is caused by blockages in coronary arteries, which result in a lack of oxygen in the heart. These blockages can be treated with drugs, through catheterization or stenting, or a vein can be taken from another part of the body to bypass the blockages in a coronary artery bypass graft (CABG) surgery. 

However, opening of the blockages does little to repair the tissue damage or the scarring of the heart muscle and the heart failure. Tissue damage and related effects cause a significant number of premature deaths and, even in milder cases, the impact on the quality of life is significant. The need for more effective treatments is clear. A new regenerative treatment method known as Cardiac Micrograft Therapy™ has been developed to make the modern treatments more effective. 

The foundation for the treatment was established around fifteen years ago, when an optimal approach was being sought by the researchers of the University of Helsinki and the surgeons of Helsinki University Hospital. Experience was gained from stem cell therapies and practical implementation of cardiac surgeries, and ultimately epicardial application of atrial appendage micrografts emerged as the most potential mode of treatment. Laboratory tests have been completed over the years, as well as animal tests on small and larger animals and, most recently, a first-in-human study on six patients. The results have been encouraging in every phase and the safety of the treatment has been well established. The results gained from both animals and people indicate that the treatment has positive impacts. In the studies, the impact is visible in the walls of the heart chambers (ventricular wall), which have become stronger, in addition to which there are indications of a reduction in the volume of scar tissue and its replacement with healthy tissue.  

In the first study implemented on people, six patients were treated. The same study was also implemented on a comparison group of an equal size. Differences were observed between the treated patients and the comparison group in the thickness of the chamber wall, for example, which is critical for heart failure: Thickening was observed in all treated patients, the average growth being around 1 mm. In the comparison group, one person died of heart failure before the six-month control appointment, two manifested no change, and in three patients, the thickness of the chamber reduced (on average, by around 1.5 mm). Therefore, there are clear indications of positive impacts on the patients, but more extensive research is necessary to prove the effectiveness of the treatment reliably. 

Key research results have been published in respected international peer-reviewed publication series and summarized below on this page.  Case anecdotes from the first-in-human treatment was published by Lampinen et al.

The impact mechanism of the developed micrograft therapy is understood to be based on the fact that transplanted cells send signals through natural mechanisms and modulate inflammatory reactions. Various medicines and gene therapies are also being researched around the world that would enable similar effects. One approach is for example to utilize mRNA and plasmid DNA as messengers in the therapies. 

EpiHeart has the expertise and equipment to support the dosing of such medicines into the heart. Already existing product portfolio enables the handling of samples parallel to the cardiac surgery and efficient delivery of the treatment. In-house product development allows also tailoring the solution for customer specific needs. 

First-in-human clinical study

“Epicardial transplantation of AAMs was safe and feasible to be performed during CABG surgery. CMRI demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment. Transplantation of AAMs shows good clinical applicability as performed during cardiac surgery, shows initial therapeutic effect on the myocardium and has the potential to serve as a delivery platform for cardiac gene therapies.”

Nummi et al, 2021 , ' Epicardial Transplantation of Autologous Cardiac Micrografts During Coronary Artery Bypass Surgery ' , Frontiers in cardiovascular medicine , vol. 8 , 726889 . https://doi.org/10.3389/fcvm.2021.726889

LVAD + Cardiac Micrograft Therapy™ surgery with EpiHeart devices

Schmitto et al, 2023, ' Use of left atrial appendage as an autologous tissue source for epicardial micrograft transplantation during LVAD implantation ', Frontiers in cardiovascular medicine.

https://doi.org/10.3389/fcvm.2023.1143886

Pre-clinical research 

“In conclusion, our results demonstrate that the epicardially transplanted AAMs-enclosing matrix patch significantly improves myocardial function after ischemic damage. The composite graft’s therapeutic effect is mediated by a combination of mechanical support, via ventricular unloading, and an activation of myocardium-protecting pathways, cardio-regenerative signaling, and angiogenesis. These results strengthen the therapeutic profile of epicardial AAM patch transplantation as a cost-effective, clinically feasible cellular adjuvant therapy for myocardial rescue and repair.”

Xie et al, 2020 , ' Epicardial transplantation of atrial appendage micrograft patch salvages myocardium after infarction ' Journal of Heart and Lung Transplantation , vol. 39 , no. 7 , pp. 707-718 . https://doi.org/10.1016/j.healun.2020.03.023

Use of Left Atrial Appendage

"These studies consistently demonstrated that the LAA is a key reservoir of multiple types of progenitor cells. This is intuitive considering the unique embryonic development and fetal gene expression of the atrial appendages. The abundance of CPCs [cardiac progenitor cells] in the atrial appendages has therefore become the foundation of an evolving field of stem cell therapy: autologous atrial appendage transplantation. - AAMs [atrial appendage micrografts] activate several cardiogenic and cardioprotective pathways leading to enhanced contractility and reparative capabilities of the cardiomyocytes and decreased oxidative stress."

Alkhouli et al, 2023, 'Nonthrombogenic Roles of the Left Atrial Appendage: JACC Review Topic of the Week.' J Am Coll Cardiol. 2023;81(11):1063-1075. https://doi.org/10.1016/j.jacc.2023.01.017

“In conclusion, our results provide evidence of effectiveness and insight into the molecular mechanisms of left atrial appendage transplantation for heart failure. The therapy can easily be clinically administered, either as an epicardial tissue transplant or as epicardial left atrial appendage micrograft transplants, when mechanically minced during open heart surgery, as reported previously by us using the right atrial appendage. Given the excellent clinical applicability of atrial appendage epicardial therapy, further clinical trials evaluating therapy efficacy are warranted.”

Leinonen et al, 2022, Structural and Functional Support by Left Atrial Appendage Transplant to the Left Ventricle after a Myocardial Infarction. Int J Mol Sci. 2022 Apr 22;23(9):4661. https://doi.org/10.3390/ijms23094661