Autologous cardiac micrografts as support therapy to coronary artery bypass surgery

Abstract

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.

Use of left atrial appendage as an autologous tissue source for epicardial micrograft transplantation during LVAD implantation

“…Similar therapy utilizing a small piece of the RAA has already been evaluated in conjunction with coronary artery bypass grafting (CABG) surgeries (9,11). With increased amounts of tissue, for example from the LAA, available for processing, larger areas can be treated, and increased doses can be administered.…”

“…During LVAD implantation surgery, autologous cardiac tissue can be harvested for the purpose of cell therapy generation from, for example, atrial appendages and left ventricular tissue. Recent data have shown that epicardial transplantation of autologous right atrial appendage (RAA) micrografts is clinically safe and feasible and is associated with beneficial structural and functional effects on ischemic myocardium (9)(10)(11).…”

Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives

“…In addition, such follow-up of the IHD cohorts (STEMI I and CABG II) can be expected to provide biomarkers with prognostic properties. Moreover, the ability of epitranscriptomics-based blood biomarkers to reflect the responses to both current and novel cardiovascular therapies may extend their clinical applicability even further [ 114 , 115 , 173 ].…”