Abstract 13317: Optimization of Left Ventricular Assist Device Therapy: A Combined in vitro and in silico Strategy to Reduce Thromboembolic Adverse Events via Evidence-Based Surgical Configuration and Medical Management

Abstract

Introduction: Left Ventricular Assist Devices are growing in frequency and importance in the treatment of medical-refractory heart failure. The incidence of thromboembolic events is a principal cause of mortality and morbidity for these patients, despite third generation pumps greatly reducing in-pump thrombosis. Hypothesis: To understand this problem, we hypothesize that LVAD-induced hemodynamics precondition platelets to activate and aggregate, leading to incipient thrombus formation which may propagate throughout the circulation, explaining the high incidence of thromboembolic events in the absence of in-pump thrombosis. Methods: A combined computational and in vitro modeling approach is used to simulate blood flow in the left ventricle, LVAD inflow cannula, outflow graft and aortic arch, with the goal of understanding the role of LVAD therapy in hemodynamics. Results: A systematic optimization of surgical parameters (inflow cannula angle, inflow cannula insertion depth, outflow graft anastomosis angle, outflow graft diameter) and medical management (LVAD speed, blood pressure, aortic valve opening frequency) based on Lagrangian metrics confirmed that the thrombogenicity of LVAD therapy can be potentially be significantly reduced. These metrics allow for quantitative comparisons of device management. Guidelines of optimum ranges of therapy configurations, and definition of “high risk” surgical configurations to avoid have been proposed. Conclusions: Reducing thrombogenicity and improving hemocompatibility is the next frontier in durable LVAD therapy for advanced heart failure. Risk-benefit analysis of many surgical configurations and medical management strategies can be quantitatively analyzed. Systematic analysis can serve as the rationale for future clinical trials that will optimize patient outcomes and reduce complications.