Patel Amit N, Mittal Sanjay, Turan Goekmen, Winters Amalia A, Henry Timothy D, Ince Hueseyin, Trehan Naresh
University of Utah, Salt Lake City, Utah, USA; Heart Institute, Medanta MediCity, Gurgoan, India; Department of Cardiology, Rostock University Hospital, Rostock, Germany; Cedars-Sinai Heart Institute, Los Angeles, California, USA; Vivantes Klinikum, Berlin, Germany
University of Utah, Salt Lake City, Utah, USA; Heart Institute, Medanta MediCity, Gurgoan, India; Department of Cardiology, Rostock University Hospital, Rostock, Germany; Cedars-Sinai Heart Institute, Los Angeles, California, USA; Vivantes Klinikum, Berlin, Germany.
Stem Cells Transl Med. 2015 Sep;4(9):1021-7. doi: 10.5966/sctm.2015-0070. Epub 2015 Jul 27.
Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients.
This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery.
对于终末期心力衰竭且尽管接受了最佳药物治疗仍有持续症状的患者，细胞治疗是一种不断发展的选择。我们的目标是评估在缺血性心力衰竭（IHF）或非缺血性心力衰竭（NIHF）患者中逆行骨髓细胞递送的情况。这是一项前瞻性随机、多中心、开放标签研究，旨在评估逆行注入冠状静脉窦的骨髓抽吸浓缩物（BMAC）的安全性和可行性。60例患者按IHF和NIHF分层，并以4:1的比例随机分为接受BMAC输注或对照（标准心力衰竭治疗）两组。因此，24例受试者被随机分配至缺血性BMAC组，6例至缺血性对照组。同样，24例受试者被随机分配至非缺血性BMAC组，6例至非缺血性对照组。所有60例患者均成功纳入研究。治疗组接受BMAC输注，无并发症发生。接受BMAC治疗的患者左心室射血分数较基线有显著改善，NIHF组从筛查时的25.1%提高到12个月时的31.1%（p = 0.007），IHF组从26.3%提高到31.1%（p = 0.035）。非缺血性BMAC组的收缩末期直径从55.6 mm显著减小至50.9 mm（p = 0.020）。逆行BMAC递送是安全的。所有接受BMAC治疗的患者左心室射血分数均有改善，但只有NIHF患者的左心室收缩末期直径和B型利钠肽有所改善。这些结果为在心力衰竭患者中开展更大规模的临床试验提供了依据。
这项工作是首例在心力衰竭患者中通过逆行冠状静脉窦输注进行高剂量细胞治疗的前瞻性随机临床试验。这是一项跨国、多中心研究，具有新颖性、可转化性和可扩展性。基于该试验以及逆行冠状静脉窦输注的安全性，目前还有另外三项试验正在采用这种递送途径进行。
