Key factors for cardiac recovery in patients with left ventricular assist device for end stage heart failure

左心辅助装置(LVAD)为终末期心力衰竭患者提供机械负荷，以恢复自身的心功能。机械卸载导致反向重构，使左心室舒张期和收缩期内径减小，左心室射血分数增加。然而，我们发现有应答者和非应答者。34例患者行LVAD-OFF试验，9例成功恢复心功能，脱离LVAD。病理检查显示，9例患者纤维化程度较轻，细胞体积较小。因此，我们得出结论，心脏纤维化和心肌细胞大小是预测心脏功能改善程度和移植后持续恢复的重要指标。接下来，我们研究了细胞移植对因心力衰竭的原因而不能恢复自身心功能的患者。同时注射自体骨…在动物模型中，更多的骨髓细胞和骨骼肌母细胞被证明可以改善心脏功能。我们评估了这种联合细胞疗法在需要植入左心室辅助装置(LVAD)的严重缺血性心肌病患者中的潜在应用。研究对象是4名因严重缺血性心肌病而需要植入LVAD的患者(年龄范围43-69岁)。取大鼠大腿骨骼肌成肌细胞，同时采集骨髓单个核细胞，并在手术时进行纯化。这些细胞被以连续的方式直接注射到受损的心肌中。没有观察到致命的心律失常或主要的并发症。注射的成肌细胞数量为2.7×10(7)~3.0×10(8)，纯度为25%~96%。2名患者移植部位脑利钠肽水平下降，超声心动图改善，H(2)(15)O正电子发射断层扫描显示血流灌注增加，其中1名患者成功地脱离了LVAD。另一名患者的尸检组织学结果显示，注射区域有少量骨骼肌。另外两名患者只观察到轻微的改善。总之，关键是存活的心肌细胞对任何类型的治疗都有反应，如机械卸载和细胞移植。此外，细胞稳定性是细胞治疗成功的另一个重要因素。较少

Left ventricular assist device(LVAD) confers mechanical unloading to the patients in end stage heart failure to recover their own cardiac function. The mechanical unloading leads reverse remodeling which decreases LV diastolic and systolic diameter and increases LV ejection fraction. However, we found there are responders and non-responders. Among 34 patients who underwent LVAD-off test, 9 patients successfully recovered their own cardiac function and was weaned off from LVAD. The pathological examination revealed that less fibrosis and smaller cell size in these 9 patients. Therefore, we concluded that Cardiac fibrosis and myocyte size at the time of LVAD implantation were significant predictors of degree of improvement of cardiac function and the sustained recovery after the LVAD explantation.Next, we examined cell transplantation to the patients who were unlikely recovered their own cardiac function because of their etiology of heart failure.Simultaneous injection of autologous bone … More marrow cells and skeletal myoblasts has been demonstrated to improve cardiac function in animal models. We evaluated the potential application of this combination cell therapy in patients with severe ischemic cardiomyopathy who required left ventricular assist device(LVAD) implantation.Four patients(age range, 43-69 years) who required LVAD implantation due to severe ischemic cardiomyopathy were studied. Skeletal myoblasts were obtained from the thigh, while bone marrow mononuclear cells were collected and purified at the time of the operation. These cells were directly injected in a serial manner into the damaged myocardium.No fatal arrhythmias or major complications were observed. The number of injected skeletal myoblasts ranged from 2.7×10(7) to 3.0×10(8), and their purity ranged from 25% to 96%. Two patients showed decreased brain natriuretic peptide levels and echocardiographic improvements in the transplanted areas, as well as increased perfusion revealed by H(2)(15) O positron emission tomography, of whom one was successfully weaned from LVAD. Histological findings at autopsy of the other patient showed a small amount of skeletal muscle in the injected area. Only marginal improvements were observed in the other two patients.As a conclusion, the key is a viable myocytes to respond any kind of treatment such as mechanical unloading and cell transplantation. In addition, cell stability is another important factor for successful cell therapy. Less