Background: Cardio-regenerative cell therapies offer additional biologic support to coronary artery bypass surgery (CABG) and are aimed at functionally repairing the myocardium that suffers from or is damaged by ischemia. This non-randomized 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 transplantation. Data from 30 elective CABG patients was collected for a center- and time-matched control group. The AAMs were processed during the operation from a biopsy collected from the right atrial appendage. They were delivered epicardially onto the infarct scar site identified in preoperative late gadolinium enhancement cardiac magnetic resonance imaging (CMRI). The primary outcome measures at the 6-month 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 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 during CABG surgery. CMRI demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment.

Conclusions and Relevance: 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.

Trial Registration:ClinicalTrials.gov, identifier: NCT02672163.

背景：心脏再生细胞疗法为冠状动脉搭桥手术（CABG）提供额外的生物支持，旨在功能性修复遭受缺血或受损的心肌。这项非随机开放标签研究评估了接受 CABG 手术的患者进行心耳微移植 (AAM) 心外膜移植的安全性和可行性。

方法：本研究纳入了 12 名连续接受 CABG 手术的患者。 6 名患者在手术期间接受了 AAM，另外 6 名患者接受了 CABG 手术但未移植 AAM。收集了 30 名选择性 CABG 患者的数据，作为中心和时间匹配的对照组。 AAM 是在手术过程中从右心耳采集的活检中进行处理的。它们通过心外膜递送到术前晚期钆增强心脏磁共振成像（CMRI）中确定的梗塞疤痕部位。 6 个月随访的主要结果指标是 (i) 随着时间的推移，患者在血流动力学和心脏功能方面的安全性，以及 (ii) 在临床环境中进行治疗的可行性。次要结果指标包括左心室壁厚度、心肌疤痕组织体积变化、左心室射血分数变化、N 端 B 型利钠肽原血浆浓度、NYHA 分级、住院天数以及生活质量。

结果：在CABG手术中进行AAM心外膜移植是安全可行的。 CMRI 显示接受 AAM 治疗的患者梗塞部位的存活心脏组织有所增加。

结论和相关性：AAM 移植在心脏手术期间表现出良好的临床适用性，对心肌显示出初步的治疗效果，并有潜力作为心脏基因治疗的传递平台。

试验注册：ClinicalTrials.gov，标识符：NCT02672163。