Bartunek Jozef, Terzic Andre, Davison Beth A, Behfar Atta, Sanz-Ruiz Ricardo, Wojakowski Wojciech, Sherman Warren, Heyndrickx Guy R, Metra Marco, Filippatos Gerasimos S, Waldman Scott A, Teerlink John R, Henry Timothy D, Gersh Bernard J, Hajjar Roger, Tendera Michal, Senger Stefanie, Cotter Gad, Povsic Thomas J, Wijns William
Cardiovascular Center, OLV Hospital, Moorselbaan 164, Aalst, B-9300, Belgium.
Department of Cardiovascular Medicine, Mayo Clinic, Center for Regenerative Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
ESC Heart Fail. 2020 Dec;7(6):3345-3354. doi: 10.1002/ehf2.13031. Epub 2020 Oct 23.
This study aims to explore long-term clinical outcomes of cardiopoiesis-guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial.
CHART-1 is a multinational, randomized, and double-blind trial conducted in 39 centres in heart failure patients (n = 315) on standard-of-care therapy. The 'active' group received cardiopoietic stem cells delivered intramyocardially using a retention-enhanced catheter. The 'control' group underwent patient-level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann-Whitney estimator 0.52, 95% confidence interval (CI) 0.45-0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow-up, patients with left ventricular end-diastolic volume of 200-370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16-0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09-0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years.
Longitudinal follow-up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long-term clinical follow-up thus offers guidance for future targeted trials.
本研究旨在探讨在充血性心力衰竭心脏再生治疗（CHART-1）试验中评估的心脏生成引导的干细胞治疗缺血性心力衰竭的长期临床结果。
CHART-1是一项在39个中心针对心力衰竭患者（n = 315）进行的多中心、随机、双盲试验，采用标准治疗方案。“活性”组通过使用保留增强导管心肌内注射心脏生成干细胞。“对照组”接受患者水平的假手术。对患者进行了长达104周的随访。在整个研究人群中，主要分层复合结局在第52周时保持中性[曼-惠特尼估计值0.52，95%置信区间（CI）0.45 - 0.59，P = 0.51]。里程碑分析表明，在左心室显著扩大且接受适当剂量治疗的患者中存在后期临床益处。具体而言，在随访超过100天时，接受≤19次心脏生成干细胞注射治疗且左心室舒张末期容积为200 - 370 mL的患者，死亡或心血管住院风险降低（风险比0.38，95% CI 0.16 - 0.91，P = 0.031），心血管死亡或心力衰竭住院风险降低（风险比0.28，95% CI 0.09 - 0.94，P = 0.040）。心脏生成干细胞治疗长期耐受性良好，与2年时的假手术相比，安全性读数无差异。
纵向随访证明心脏生成干细胞治疗总体安全，事后分析表明，在由晚期左心室扩大定义的缺血性心力衰竭亚组中，在可耐受的干细胞剂量下有获益。因此，长期临床随访为未来的靶向试验提供了指导。
