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.