Neurovascular consequences of non-pulsatile flow from left ventricular assist devices

项目总结： 该项目将是一项观察性研究，主要目的是检查非脉动的后果。 连续血流下左心室辅助装置(CF-LVAD)对脑循环的影响。公众 充血性心力衰竭(CHF)造成的健康负担很大，可供选择的治疗方法很少 终末期患者。不幸的是，心脏移植并不是广泛可用的，其中许多 患者依靠左心室辅助装置进行循环支持。最新一代的设备是 设计经久耐用，因此提供无脉动流量。尽管CHF死亡率有所改善，但CF- LVAD与多种并发症有关，这些并发症被认为源于非搏动性的影响 动脉内皮细胞的血流，尤其是胃肠道出血，以及运动耐量增加不佳。CF-LVAD 伴有出血性转化(ISHT)的患者发生缺血性中风的几率异常高，这是 这些患者的主要死因。一般人群中的ISHT是微循环的结果 血脑屏障(BBB)和脑内皮细胞功能障碍。非脉动型的影响 在人类CF-LVAD患者中，血脑屏障和脑内皮细胞上的血流尚未被研究，部分原因是 缺乏脑循环特有的标志物。在目标1a中，我们将进行经颅多普勒(TCD)。 CF-LVAD植入前后屏气指数作为脑生理指标的检测 自我调节是脑内皮细胞的重要功能。在目标1b中，我们将研究非 用光学相干断层扫描技术研究血视网膜屏障(解剖上类似于血脑屏障)上的脉动流 血管造影术和视网膜多普勒。在目标2中，我们将检查CF-LVAD参与者在 以及手术后与对照组的对比。这项提案的总体目标将是确定生理和 在非脉动血流条件下发生的脑循环功能改变，这将允许改善 终末期充血性心力衰竭患者应用CF-LVAD的风险分层和个体化治疗方法。

Project summary: This project will be an observational study with the primary goal to examine the consequences of non-pulsatile flow under continuous flow left ventricular assisted devices (CF-LVAD) on the cerebral circulation. The public health burden from congestive heart failure (CHF) is substantial and few treatment options are available to those patients at the end-stage. Unfortunately, cardiac transplantation is not widely available and many of these patients rely on left ventricular assist devices for circulatory support. The newest generation devices are designed for durability and therefore deliver non-pulsatile flow. Despite improvements in CHF mortality, CF- LVAD is associated with multiple complications that are hypothesized to originate from the impact of non-pulsatile flow on arterial endothelium, notably gastrointestinal bleeding, and poor gains in exercise tolerance. CF-LVAD patients develop unusually high rates of ischemic stroke with hemorrhagic transformation (ISHT), one of the leading causes of death in these patients. ISHT in the general population results from microcirculatory dysfunction with disruption of the blood brain barrier (BBB) and cerebral endothelium. The impact of non-pulsatile flow on the BBB and cerebral endothelium has not yet been studied in human CF-LVAD patients, in part due to the lack of markers specific to the cerebral circulation. In aim 1a we will perform transcranial Doppler (TCD) before and after CF-LVAD implantation to measure the breath holding index as a physiological marker of cerebral autoregulation an important function of cerebral endothelium. In aim 1b we will examine the impact of non- pulsatile flow on the blood retina barrier (anatomically similar to the BBB) with optical coherence tomography angiography and retinal doppler. In aim 2 we will examine changes in cognition in CF-LVAD participants before and after surgery and versus controls. The overall goals of this proposal will be to identify physiological and functional changes which occur in the cerebral circulation under non-pulsatile flow which will allow for improved risk stratification and tailored treatment approaches in the application of CF-LVAD in end-stage CHF.