Burkhoff Daniel, Klotz Stefan, Mancini Donna M
J. Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY 10962, USA.
J Card Fail. 2006 Apr;12(3):227-39. doi: 10.1016/j.cardfail.2005.10.012.
With improved technology, increasing clinical experience, 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. Early in the course of LVAD use as a bridge to transplant, it became evident that some patients exhibit substantial recovery of ventricular function, which led to the concept of reverse remodeling.
Herein we summarize and integrate insights derived from a multitude of studies that have investigated how LVAD support influences ventricular structural, cellular, extracellular matrix, molecular, biochemical, and metabolic characteristics of the end-stage failing heart. The focus includes a review of the extent and sustainability of reverse remodeling, the important advances in understanding of the pathophysiology of heart failure derived from these studies and the implications of these findings for development of new therapeutic strategies.
In brief, 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, when given sufficient mechanical unloading and restoration of more normal neurohormonal milieu, a relatively large degree of myocardial recovery is possible. Comparison of effects on right and left ventricles have provided mechanistic insights by implicating hemodynamic unloading as primarily regulating certain aspects of reverse remodeling, neurohormonal factors as regulating other aspects, and joint regulation of still other aspects. As such these observations have driven a shift of thinking of chronic heart failure as a progressive irreversible disease process to a potentially treatable entity.
随着技术的进步、临床经验的增加以及使用指征的扩大,左心室辅助装置(LVADs)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LVAD作为移植桥梁使用的早期过程中,很明显一些患者的心室功能有显著恢复,这就产生了逆向重构的概念。
在此,我们总结并整合了大量研究的见解,这些研究调查了LVAD支持如何影响终末期衰竭心脏的心室结构、细胞、细胞外基质、分子、生化和代谢特征。重点包括对逆向重构的程度和可持续性的综述,从这些研究中对心力衰竭病理生理学理解的重要进展,以及这些发现对新治疗策略开发的意义。
简而言之,对LVAD与心脏相互作用的研究使我们认识到,尽管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,但当给予足够的机械卸载并恢复更正常的神经激素环境时,相当程度的心肌恢复是可能的。对左右心室影响的比较通过表明血流动力学卸载主要调节逆向重构的某些方面、神经激素因素调节其他方面以及其他方面的联合调节,提供了机制上的见解。因此,这些观察结果推动了将慢性心力衰竭从一种进行性不可逆疾病过程的思维转变为一种潜在可治疗的实体。