Henry Timothy D, Pepine Carl J, Lambert Charles R, Traverse Jay H, Schatz Richard, Costa Marco, Povsic Thomas J, David Anderson R, Willerson James T, Kesten Steven, Perin Emerson C
Cedars-Sinai Medical Center, Los Angeles, California.
University of Florida, Gainesville, Florida.
Catheter Cardiovasc Interv. 2017 Feb 1;89(2):169-177. doi: 10.1002/ccd.26601. Epub 2016 Sep 23.
To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients.
Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions.
The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II-IV) or heart failure (NYHA Class II-III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo.
Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V0 max favored ADRCs (+45.4 ± 222 vs. -9.5 ± 137 mL/min) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (-21.6 + 13.9 vs. -5.5 + 23.8, P = 0.038).
A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in "no option" CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc.
评估自体脂肪来源的再生细胞（ADRCs）治疗慢性缺血性心肌病患者的安全性和可行性。
临床前和早期临床试验表明ADRCs在缺血性疾病方面具有巨大潜力。
雅典娜项目由两项平行、前瞻性、随机（2:1，活性治疗组：安慰剂组）、双盲试验组成，评估心肌内（IM）注射ADRCs[4000万个细胞，n = 28例（雅典娜试验）和8000万个细胞（雅典娜二号试验），n = 3例]。入选患者左心室射血分数（EF）≥20%但≤45%，患有多支冠状动脉疾病（CAD）且不宜进行血运重建，存在可诱导的心肌缺血，并且在最大药物治疗下有稳定型心绞痛（加拿大心血管学会分级II-IV级）或心力衰竭（纽约心脏协会分级II-III级）症状。所有患者均接受脂肪采集手术（≤450 mL脂肪）、现场细胞处理（Celution®系统，Cytori Therapeutics公司）、心脏电机械标测，并接受心肌内注射ADRCs或安慰剂。
由于与ADRCs无关的不良事件以及随后延长的入组时间，试验提前终止。共纳入31例患者（17例接受ADRCs治疗，14例接受安慰剂治疗），平均年龄65±8岁，基线左心室射血分数（LVEF）（%）分别为31.1±8.7（ADRCs组）和31.8±7.7（安慰剂组）。V0 max的变化有利于ADRCs组（+45.4±222 vs. -9.5±137 mL/min），但左心室功能或容积无差异。在12个月时，ADRCs组有2/17（11.7%）发生心力衰竭住院，安慰剂组有3/14（21.4%）发生。在12个月时，纽约心脏协会和加拿大心血管学会分级的差异有利于ADRCs组，明尼苏达心力衰竭生活质量问卷（MLHFQ）有显著改善（-21.6 + 13.9 vs. -5.5 + 23.8，P = 0.038）。
小体积脂肪采集、自动化局部处理以及心肌内注射自体ADRCs是可行的，提示对“无其他选择”的CAD患者有益。尽管样本量有限，但研究结果支持使用ADRCs治疗缺血性心肌病的可行性和可扩展性。© 2016威利期刊公司。
