Autologous cardiac micrografts as support therapy to coronary artery bypass surgery

Objectives Cardio-regenerative cell therapies offer additional biologic support to coronary artery bypass surgery (CABG) for treating the myocardium suffering from or damaged by ischemia. This phase 1, open-label study assessed the safety and feasibility of epicardial transplantation of atrial appendage micrografts (AAMs) in patients undergoing CABG surgery. Methods Twelve consecutive patients destined for CABG surgery were included in the study. Six patients received AAMs during their operation and six patients were CABG-operated without AAMs treatment. Data from 30 elective CABG patients was collected for a conjunctive control group. The AAMs were processed during the operation from a biopsy collected from the right atrial appendage. They were delivered epicardially on the infarct scar site identified in preoperative CMR. The primary outcome measures at six-months follow-up were i) patient safety in terms of hemodynamic and cardiac function over time and ii) feasibility of therapy administration in a clinical setting. Secondary outcome measures were left ventricular wall thickness, change in myocardial scar tissue volume, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, NYHA class, number of days in hospital and changes in the quality of life. Results Epicardial transplantation of AAMs was safe and feasible to be performed in conjunction with CABG surgery. CMR demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment. Conclusion Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can additionally serve as a delivery platform for cardiac gene therapies. Trial Registration [ClinicalTrials.gov][1] identifier [NCT02672163][2] ### Competing Interest Statement A.N and E.K. are stakeholders in EpiHeart Ltd developing medical devices for the operating room. H.S. is the developer of the 15D. Other authors declare no competing interests for this article.  ### Clinical Trial ClinicalTrials.gov identifier [NCT02672163][2] ### Funding Statement This work was supported by A.H, M.K, A.V, and AN by Finnish Government Block Grants for Clinical Research (grant numbers TYH Y2016SK013, TYH2016211, TYH2015311, TYH2019266, Y1016SK017), E.K by Finnish Funding Agency for Technology and Innovation (grant number 40033/14) and A.N by Finnish Society of Angiology. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Surgical Ethics Committee of the Hospital District of Helsinki and Uusimaa (number 180/13/03/02/13). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data available on request due to privacy/ethical restrictions * AB-BE : Arterial astrup base excess AAMs : Autologous atrial appendage micrografts ARB : Angiotensin receptor blocker BMI : Body Mass Index CABG : Coronary artery bypass grafting CCB : Calcium channel blockers CMR : Cardiac magnetic resonance imaging COPD : Chronic Obstructive Pulmonary Disease CVP : Central venous pressure ECG : Electrocardiogram ECM : Extracellular matrix EDV : End diastolic volume ESV : End systolic volume EF : Ejection fraction FWHM : Full-width at half-maximum GFR : Glomerular filtration rate Hb : Hemoglobin LA : Left atrium LBBB : Left bundle branch block LV : Left ventricle LVEDD : Left ventricular end diastolic diameter MAP : Mean arterial pressure MRA : Mineralocorticoid receptor antagonists NYHA : New York Heart Association NT-PRO-BNP : N-terminal pro-B-type natriuretic peptid PCI : Percutaneous coronary intervention. SD : Standard deviation above the mean SI : signal intensity SPO2 : Peripheral capillary oxygen saturation STRM : signal threshold versus reference mean [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02672163&atom=%2Fmedrxiv%2Fearly%2F2021%2F03%2F12%2F2021.03.05.21252995.atom