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

左室辅助装置（Left ventricular assist device， LVAD）为终末期心力衰竭患者提供机械卸荷以恢复自身心功能。机械卸荷导致左室舒张和收缩内径减小，左室射血分数升高。然而，我们发现有反应者和无反应者。34例患者行LVAD off试验，9例患者自行恢复心功能，顺利脱离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在LVAD植入时是心脏功能改善程度和LVAD移植后持续恢复的重要预测指标。接下来，我们检查了由于心力衰竭病因而不太可能恢复自身心功能的患者的细胞移植。在动物模型中，更多的骨髓细胞和骨骼肌细胞已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。我们研究了4例因严重缺血性心肌病而需要LVAD植入的患者（年龄43-69岁）。从大腿处获得成骨骼肌细胞，同时在手术时收集并纯化骨髓单个核细胞。将这些细胞连续注射到受损心肌中。无致死性心律失常及重大并发症。注射的骨骼肌母细胞数量为2.7×10(7) ~ 3.0×10(8)，纯度为25% ~ 96%。2例患者显示脑利钠肽水平下降，移植区超声心动图改善，H(2)(15) O正电子发射断层扫描显示灌注增加，其中1例成功脱离LVAD。另一名患者尸检的组织学结果显示，注射区有少量骨骼肌。在另外两名患者中，仅观察到轻微的改善。综上所述，关键是有活力的肌细胞对机械卸载和细胞移植等任何治疗作出反应。此外，细胞稳定性是细胞治疗成功的另一个重要因素。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