Patient-Pump Interaction with Centrifugal Continuous Flow Left Ventricular Assist Devices

Abstract

The use of newer generation centrifugal continuous flow left ventricular assist devices (cfLVADs) in supporting patients with refractory heart failure mandates understanding aspects of patient-pump interactions, which are studied in the course of this thesis. Hypertrophic cardiomyopathy traditionally precludes LVAD use due to small ventricular cavity; we report favourable short to medium term outcomes with centrifugal cfLVADs. We identified excess angiodysplasia and bleeding with third generation centrifugal cfLVAD support (7.6%) when compared the general population (0.8%). Thus, we advocate evaluation for angiodysplasia prior to support with centrifugal cfLVADs. Pump thrombosis related to LVADs is only partially mitigated by antiplatelet and anticoagulation use; we demonstrate successful treatment with intravenous thrombolysis. We longitudinally assessed the interplay between centrifugal cfLVADs and the haemostatic milieu; centrifugal cfLVAD use is associated with longitudinal changes in haemostasis. Additionally, we studied the effect of pulsatility on von Willebrand factor (VWF) studies and bleeding; pulsatility may contribute to recovery of VWF profile, and thereby potentially lower bleeding risk. Better understanding of pump physiology and its interaction with patient physiology fuels pump design innovation. We examined the effect of increasing pump speed at rest and with exercise on invasively measured central haemodynamics. Pump flow increases with up-titration of pump speed and with exercise. Though increased pump speed decreases filling pressures at rest, the benefit is not seen with exercise despite concurrent up-titration of pump speed. We performed two parallel studies to tease out the individual contribution of heart rate and venous return on pump output.Centrifugal cfLVAD flows are only significantly affected by changes with body position and passive filling, suggesting that previously demonstrated exercise-induced changes in pump flows may be related to altered loading conditions, rather than changes in heart rate. Our final study encompassed a multi-modal assessment of reverse remodelling following centrifugal cfLVAD support. We demonstrate its presence at multiple levels (regression of cardiomyocyte hypertrophy; improvement in ventricular ejection fraction measured by 3-D echocardiography), in the absence of changes in the microRNA transcriptome. As a whole, this thesis provides insights into understanding the complex interaction between the patient and the third generation centrifugal cfLVAD