Klotz Stefan, Jan Danser A H, Burkhoff Daniel
Department of Thoracic and Cardiovascular Surgery, University Hospital Muenster, Albert-Schweitzer-Str. 33, Muenster, Germany.
Prog Biophys Mol Biol. 2008 Jun-Jul;97(2-3):479-96. doi: 10.1016/j.pbiomolbio.2008.02.002. Epub 2008 Feb 12.
With improved technology and expanding indications for use, left ventricular assist devices (LVADs) are assuming a greater role in the care of patients with end-stage heart failure. Following LVAD implantation with the intention of bridge to transplant, it became evident that some patients exhibit substantial recovery of ventricular function. This prompted explantation of some devices in lieu of transplantation, the so-called bridge-to-recovery (BTR) therapy. However, clinical outcomes following these experiences are not always successful. Patients treated in this fashion have often progressed rapidly back to heart failure. Special knowledge has emerged from studies of hearts supported by LVADs that provides insights into the basic mechanisms of ventricular remodeling and possible limits of ventricular recovery. In general, it was these studies that spawned the concept of reverse remodeling now recognized as an important goal of many heart failure treatments. Important examples of myocardial and/or ventricular properties that do not regress towards normal during LVAD support include abnormal extracellular matrix metabolism, increased tissue angiotensin levels, myocardial stiffening and partial recovery of gene expression involved with metabolism. Nevertheless, studies of LVAD-heart interactions have led to the understanding that although we once considered the end-stage failing heart of patients near death to be irreversibly diseased, an unprecedented degree of myocardial recovery is possible, when given sufficient mechanical unloading and restoration of more normal neurohormonal milieu. Evidence supporting and unsupporting the notion of reverse remodeling and clinical implications of this process will be reviewed.
随着技术的改进和使用指征的扩大,左心室辅助装置(LVAD)在终末期心力衰竭患者的治疗中发挥着越来越重要的作用。在植入LVAD以作为过渡到移植的桥梁后,很明显一些患者的心室功能有显著恢复。这促使一些装置被取出而不是进行移植,即所谓的过渡到恢复(BTR)治疗。然而,这些经验后的临床结果并非总是成功的。以这种方式治疗的患者常常很快又进展回心力衰竭状态。对由LVAD支持的心脏进行的研究产生了一些特殊知识,这些知识为心室重塑的基本机制和心室恢复的可能限度提供了见解。一般来说,正是这些研究催生了现在被认为是许多心力衰竭治疗重要目标的逆向重塑概念。在LVAD支持期间心肌和/或心室特性未恢复正常的重要例子包括细胞外基质代谢异常、组织血管紧张素水平升高、心肌僵硬以及与代谢相关的基因表达部分恢复。尽管如此,对LVAD与心脏相互作用的研究使人们认识到,虽然我们曾经认为濒临死亡的患者的终末期衰竭心脏是不可逆转地患病,但如果给予足够的机械卸载和恢复更正常的神经激素环境,心肌恢复到前所未有的程度是可能的。本文将综述支持和不支持逆向重塑概念的证据以及这一过程的临床意义。