The impact of Left Ventricular Assist Device Implantation on Cerebral Hemodynamics and Cognition - PROJECT SUMMARY The left ventricular assist device (LVAD) has revolutionized care for patients with advanced heart failure, but the impact on cerebral hemodynamics is poorly understood and represents an opportunity to optimize outcomes for this challenging patient population. Given organ scarcity and advances in LVAD technology, the majority of LVADs are now implanted as destination therapy. Neurologic complications have long been respected as the most significant contributor to bad clinical outcomes. Suboptimal brain perfusion increases the risk of stroke, cognitive decline, and brain atrophy, all of which are critical concerns in this patient population. Unfortunately, cerebral blood flow is not measured in routine clinical care, so it is not directly considered in LVAD management. In clarifying the relationship between LVAD physiology and neurovascular health, this proposal will identify hemodynamic metrics that will ultimately provide treatment targets by which we can personalize and improve long-term outcomes. Quantifying cerebral hemodynamics represents a significant challenge because LVADs are not MRI compatible. Other advanced imaging technique, including PET or CT provide only a snapshot in time. Transcranial Doppler ultrasonography is particularly well suited for this clinical scenario because it provides a continuous, non-invasive measure of cerebral blood flow (CBF) at the bedside. Though transcranial Doppler probes large trunk vessels, waveform morphologic features are informative of microvascular function, and these CBF data be leveraged to quantify two critical measures of cerebrovascular health: cerebral autoregulation and cerebrovascular reactivity. Autoregulation describes the relationship between blood pressure and CBF, while cerebrovascular reactivity quantifies the ability to augment CBF in times of demand. Both metrics are impaired in advanced heart failure and predict stroke risk and cognitive decline across a range of disease states. Our group recently reported improvement in autoregulation and cerebrovascular reactivity after LVAD implantation. The objective of this proposal is to build upon our recent studies to establish the relationship between LVAD and cerebral hemodynamics in long-term follow-up, correlating with cognition and brain atrophy over time. In clinical practice, LVAD speed and medication regimens are titrated to optimize cardiopulmonary hemodynamics and target a mean arterial blood pressure <90 mmHg. Our group recently demonstrated the sensitivity of CBF to LVAD pump speed, so with this proposal we will systematically explore the sensitivity of cerebral hemodynamic metrics to LVAD parameters by performing CBF monitoring during speed titration. Taken together, this proposal will reveal future opportunities to leverage cerebral hemodynamic metrics as treatment targets in long-term LVAD care, with the goal of optimizing neurologic outcomes.
