Percutaneous Left Ventricular Unloading for Cardiogenic Shock: Beyond Acute Hemodynamic Support

项目概要： 心源性休克发生在7-10%的急性心肌梗塞（MI）患者中，并且具有高的 死亡率为50- 70%。短期左心室（LV）卸载是一个新概念，已成为现实 最近出现了功能强大的经皮左心室辅助装置（pLVAD）， 显著改善心源性休克患者的预后。几个临床和预- 临床研究表明，使用这些器械可明显改善血液动力学，但无临床 迄今为止的研究表明，30天的临床结果有所改善。目前的数据表明，pLVAD改善了 血流动力学和非常急性的临床结果（约24小时），但在LV期间受损心脏的功能恢复 在装置被移除后，支撑通常不足以维持血液动力学， 减缓死亡。 大量的研究集中在短期左室负荷的急性血流动力学变化上 以及何时、如何以及向谁介绍这些设备。相反，很少有人研究我们如何退出 这些设备疗法。在这里，为了最大限度地发挥pLVAD用于心源性休克的益处，我们 建议研究可能影响LV卸载后自体心脏功能恢复的关键因素， pLVAD。具体而言，我们建议研究1）LV再负荷的影响，2）心脏分子 与LV卸载相关的改变，和3）促进心脏功能恢复的连续方法。 我们的中心假设是，LV卸载和重新加载的开始对 心脏功能，需要额外的治疗来改善患者的临床结局， 用pLVAD治疗心源性休克。为了检验我们的核心假设，我们提出以下具体目标。 具体目标1。定义LV重新加载的影响 具体目标2。定义LV卸载对关键翻译后修饰的影响 心肌蛋白 具体目标3。应用基因治疗促进心肌恢复 我们的研究将增加对左室去负荷和再灌注后心脏分子变化的理解。 加载中由于我们预见pLVAD在心源性休克患者中的使用会增加， 危害和发展的方式，以改善目前的低生存与短期低压卸荷具有重大意义 临床影响。

PROJECT SUMMARY: Cardiogenic shock develops in 7-10% of patients with acute Myocardial Infarction (MI), and has a high mortality ranging 50-70%. Short-term Left Ventricular (LV) unloading is a new concept that became a reality with the recent emergence of powerful percutaneous Left Ventricular Assist Devices (pLVAD)s, which offers significant promise for improving the outcomes of the patients with cardiogenic shock. Several clinical and pre- clinical studies demonstrated clear improvement in hemodynamics using these devices, however no clinical studies have so far shown improvement in 30-day clinical outcome. Current data suggest that pLVADs improve hemodynamics and very acute clinical outcome (~24hr), but the functional recovery of injured heart during LV support is often not sufficient to maintain the hemodynamics after the devices are removed, resulting in only slowing of the death. Large amount of research focus on short-term LV unloading is on the acute changes in hemodynamics and when, how, and to whom we introduce these devices. In contrast, little is studied on how we exit from these device therapies. Here, in order to maximize the benefit of pLVADs use for cardiogenic shock, we propose to study key elements that may influence functional recovery of native heart after LV unloading with pLVADs. Specifically, we propose to study 1) impact of LV re-loading, 2) impact of cardiac molecular alterations associated with LV unloading, and 3) adjunctive approach to boost cardiac functional recovery. Our central hypothesis is that initiation of LV unloading as well as re-loading negatively influence cardiac function, and additional therapy is required to improve the clinical outcomes of patients with cardiogenic shock treated with pLVADs. To test our central hypothesis we propose below Specific Aims. Specific Aim 1. Define the impact of LV re-loading Specific Aim 2. Define the impact of LV unloading on post-translational modification in key cardiac proteins Specific Aim 3. Use gene therapy to promote myocardial recovery Our study will increase the understanding of molecular changes in the heart after LV unloading and re- loading. As we foresee increase in pLVADs use for patients with cardiogenic shock, identifying the potential harm and developing ways to improve current low survival with short-term LV unloading has a significant clinical impact.