Reverse remodeling with left ventricular assist devices: a review of clinical, cellular, and molecular effects.
Reverse remodeling with left ventricular assist devices: a review of clinical, cellular, and molecular effects.
复制标题
DOI：
10.1161/circheartfailure.110.959684
复制
发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Buttrick PM
中科院分区：
文献类型：
--
作者：
Ambardekar AV;Buttrick PM
在过去的20年里，医学治疗的许多进步改善了心力衰竭（HF）患者的预后。然而，仍有相当数量的患者进展为终末期心衰，其治疗选择主要限于心脏移植。由于患者对移植的需求持续超过可用器官的供应，机械辅助装置-特别是左心室辅助装置(LVAD) -最初被引入作为心脏移植的桥梁。lvad有两个重要的有益作用。首先，lvad与左心室平行放置，造成左心室的压力和容积卸载。其次，lvad恢复心输出量和随后的器官灌注。由于这两种作用，很明显，一些患者在LVAD放置后左室功能得到了实际改善。“反向重构”一词被用来描述在看似终末期疾病的患者中观察到的心肌功能的改善。随着逆向重构，HF治疗的新希望诞生了——利用lvad作为恢复的桥梁；然而，到目前为止，这一承诺在很大程度上尚未实现。这可能反映了这样一个事实，即机械性心室卸载的后遗症相当复杂，似乎涉及竞争性生物途径的参与，包括心肌细胞肥大的消退和进行性细胞萎缩。尽管心室恢复的希望仍然存在，但其实现将等待对这些相互竞争的生物过程进行更全面的解剖。本文将讨论LVAD支持的有益临床效果，以及对机械卸载的细胞和分子反应以及反向重构的机制进行综述。主要研究成果总结于表中。
Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table.