Pölzl Leo, Nägele Felix, Graber Michael, Hirsch Jakob, Lobenwein Daniela, Mitrovic Martina, Mayr Agnes, Theurl Markus, Schreinlechner Michael, Pamminger Matthias, Dorfmüller Christian, Grimm Michael, Gollmann-Tepeköylü Can, Holfeld Johannes
University Clinic of Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Clinical Trial Center, Medical University of Innsbruck, Innrain 52, 6020, Innsbruck, Austria.
Trials. 2020 May 30;21(1):447. doi: 10.1186/s13063-020-04369-0.
Coronary artery diseases (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodeling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave Therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function.
METHODS/DESIGN: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min Walk Test distance, improvement of symptoms and assessment of quality of life.
This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure.
ClinicalTrials.gov, ID: NCT03859466. Registered on 1 March 2019.
冠状动脉疾病（CAD）在西方世界仍然是一项严重的社会经济负担。冠状动脉阻塞及随后的心肌缺血会导致收缩性心肌逐渐被功能失调的纤维化瘢痕组织所取代。心肌梗死后重塑是左心室功能随之下降及心力衰竭致命综合征的病因。现有的神经体液治疗策略旨在改善症状。尽管进行了广泛研究，但包括（干）细胞治疗、基因治疗、细胞重编程或组织工程在内的心肌再生治疗选择仍纯属实验性。因此，临床上迫切需要新的治疗选择，以诱导缺血性心肌病的心肌再生并改善左心室功能。冲击波疗法（SWT）是一种成熟的再生工具，对治疗慢性肌腱炎、长骨不愈合和伤口愈合障碍有效。在临床前试验中，SWT通过诱导血管生成和减少纤维化瘢痕组织来再生缺血心肌，从而改善左心室功能。
方法/设计：在这项前瞻性、随机对照、单盲、单中心研究中，80例左心室射血分数降低（LVEF≤40%）的患者接受冠状动脉旁路移植术（CABG），并按1:1的比例随机分组，分别接受额外的心脏SWT（干预组；40例患者）或CABG假治疗（对照组；40例患者）。本研究旨在评估（1）心脏SWT作为CABG手术期间辅助治疗用于缺血心肌再生的安全性和（2）疗效。该研究的主要终点包括（1）主要心脏事件和（2）治疗后12个月左心室功能的变化。次要终点包括6分钟步行试验距离、症状改善情况和生活质量评估。
本研究旨在调查CABG手术期间心脏SWT用于心肌再生的安全性和疗效。诱导血管生成、减少纤维化瘢痕组织形成，进而改善左心室功能，可能会改善缺血性心力衰竭患者的生活质量和预后。因此，它可能成为第一种临床上可用的缺血心肌再生治疗策略，减轻心力衰竭的社会经济负担。
ClinicalTrials.gov，ID：NCT03859466。于2019年3月1日注册。
