Developing Markers of Mechanical Dyssynchrony in Heart Failure: Implications for Research and Clinical Practice in Cardiac Resynchronisation Therapy

Abstract

This thesis studies techniques for maximising the effects of Cardiac Resynchronisation Therapy (CRT) which is a modern therapy for chronic heart failure. The ability of echocardiographic parameters of mechanical dyssynchrony to identify suitable candidate patients for CRT, and subsequently to optimise the interventricular delay, is disputed. In this study, I initially perform a systematic review to clarify the nature and extent of this problem. I then perform detailed mathematical simulations to understand what is feasible in an ideal setting. I then evaluate the realistic potential of several non-invasive approaches of optimising CRT devices by formal evaluation head-to-head. A fundamental requirement for any marker in optimisation of CRT devices, or in selection of patients for implantation, is that the marker must be reproducible and must change when the amount of dyssynchrony changes. I perform detailed experiments in patients where I interrogated a panel of echocardiographic parameters to answer the questions relating to the sensitivity of each parameter and looked at methods to improve this. I look at the effect of spontaneous variability, and the impact on each echocardiographic method including 3D echocardiography, tissue Doppler imaging and pulsed Doppler techniques including velocity time integrals and pre-ejection times. Finally, I perform an invasive study of the beat to beat physiological changes which occur after intra cardiac timings are altered, to evaluate alternative approaches to changes in cardiac performance that might be easier to automate.