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

项目概要： 该项目将是一项观察性研究，主要目标是检查非搏动性心脏病的后果。 连续流左心室辅助装置（CF-LVAD）下的血流对脑循环的影响。公众 充血性心力衰竭（CHF）造成的健康负担是巨大的， 患者在末期。不幸的是，心脏移植并不广泛可用，并且这些移植中的许多都是心脏移植。 患者依靠左心室辅助装置来进行循环支持。最新一代的设备是 设计用于耐久性，因此提供非脉动流。尽管CHF死亡率有所改善，但CF- LVAD与多种并发症相关，假设这些并发症源于非搏动性心脏瓣膜的影响。 动脉内皮血流，特别是胃肠道出血，运动耐量增加不佳。cf-LVAD 患者发生缺血性卒中伴出血性转化（ISHT）的发生率异常高， 这些患者的主要死因。一般人群中的ISHT是由微循环系统引起的。 功能障碍，伴有血脑屏障（BBB）和脑内皮细胞破坏。非脉动的影响 尚未在人类CF-LVAD患者中研究BBB和脑内皮上的血流，部分原因是 缺乏脑循环的特异性标记在目标1a中，我们将进行经颅多普勒（TCD） 在CF-LVAD植入前后测量屏气指数，作为脑血管病的生理标志物， 自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术测量血视网膜屏障（解剖学上类似于BBB）上的脉动流 血管造影和视网膜多普勒。在目标2中，我们将检查CF-LVAD参与者在治疗前的认知变化。 手术后和对照组。该提案的总体目标是确定生理和 在非脉动流下脑循环中发生的功能变化， 在终末期CHF中应用CF-LVAD的风险分层和定制治疗方法。

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.