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

左心室辅助装置非脉动血流的神经血管后果

• 批准号: 10367076
• 负责人: Joshua Zebadiah Willey
• 金额: $ 59.97万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367076
• 关键词: Adverse event; Age; Anatomy; Angiography; Anticoagulants; Anticoagulation; Biological; Biological Markers; Blood - brain barrier anatomy; Blood Pressure; Blood Vessels; Blood flow; Blood-Retinal Barrier; Brain; Brain hemorrhage; Cardiac Output; Cause of Death; Cerebral hemisphere hemorrhage; Cerebrovascular Circulation; Cerebrum; Clinical; Cognition; Cognitive; Congestive Heart Failure; Device Designs; Disease; Endothelium; Event; Exercise Tolerance; Functional disorder; Gastrointestinal Hemorrhage; General Population; Generations; Goals; Heart Transplantation; Hemorrhage; Homeostasis; Human; Hypertension; Interdisciplinary Study; Investigation; Ischemic Stroke; Measures; Microcirculation; Morbidity - disease rate; Neuraxis; Neuropsychological Tests; Neuropsychology; Observational Study; Operative Surgical Procedures; Optical Coherence Tomography; Outcome; Participant; Pathologic Processes; Patients; Pattern; Permeability; Physiological; Physiology; Play; Population; Prevalence; Public Health; Reperfusion Injury; Research; Retina; Risk Factors; Role; Secondary to; Serum; Structure; Time; Transplantation; arterial stiffness; arteriole; blood-brain barrier disruption; blood-brain barrier permeabilization; cerebrovascular; clinically significant; cognitive change; design; endothelial dysfunction; implantation; improved; in vivo; in vivo imaging; indexing; individualized medicine; left ventricular assist device; lifetime risk; mechanical circulatory support; mortality; neurovascular; neurovascular unit; retinal imaging; risk stratification; stroke therapy

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.

项目摘要： 该项目将是一项观察性研究，其主要目标是检查非脉动的后果 在连续流动的左室辅助装置（CF-LVAD）下的流动在大脑循环上。公众 充血性心力衰竭（CHF）的健康负担很大，很少有治疗选择可供选择 在最后阶段的患者。不幸的是，心脏移植并不广泛，其中许多 患者依靠左心室辅助设备进行循环支持。最新一代设备是 专为耐用性而设计，因此提供非脉冲流。尽管CHF死亡率有所提高，但CF- LVAD与多种并发症有关，这些并发症是由非脉冲的影响源自 动脉内皮的流动，尤其是胃肠道出血，运动耐受性不佳。 CF-LVAD 患者随着出血转化（ISHT）的缺血性中风率异常高，其中之一是 这些患者的主要死亡原因。一般人群中的ISHT是由微循环产生的 功能障碍与血脑屏障（BBB）和脑内皮的破坏。非脉冲的影响 在人类CF-LVAD患者中尚未研究BBB和大脑内皮的流量，部分原因是 缺乏特定于大脑循环的标记。在AIM 1A中，我们将执行经颅多普勒（TCD） CF-LVAD植入之前和之后，以测量呼吸指数作为脑的生理标记 自动调节是大脑内皮的重要功能。在AIM 1B中，我们将研究非 - 血液视网膜屏障（与BBB的解剖学相似）上的脉冲流动流动流动层造影 血管造影和视网膜多普勒。在AIM 2中，我们将检查CF-LVAD参与者的认知变化 手术后与对照。该提案的总体目标是确定生理学和 在非脉冲流下大脑循环中发生的功能变化，这将允许改善 在CF-LVAD在末期CHF中应用的风险分层和量身定制的治疗方法。