A mechanistic study of response to cardiac resynchronisation therapy

Student thesis: Doctoral ThesisDoctor of Philosophy


Cardiac resynchronisation therapy (CRT) is an effective intervention for symptomatic heart failure patients to reduce morbidity and mortality, but even in carefully selected cases approximately 30% of patients fail to benefit. In patients who respond, there is evidence of reverse left ventricular (LV) remodelling and increased cardiac output (CO) but it’s unknown whether there are additional changes in the vascular system or aortic and pulmonary wave intensity. Endocardial LV pacing has many advantages over conventional epicardial CRT and may be important with improving response rates. This thesis aims to further explore the physiology underlying CRT response and investigate how endocardial pacing may improve patient outcomes.
Initially, this thesis will investigate the physiological effects underpinning CRT response by using a combination of invasive and non-invasive wave intensity analysis and invasive haemodynamic assessments. Patients who improve following CRT have evidence of ventricular resynchronisation, reverse LV remodelling, increased CO and increased external work achieved by the heart. However, it’s unknown whether these physiological changes result purely from improved LV contraction thus increasing CO or whether there are also differences in loading conditions on the left ventricle and/or changes in dynamic and steady state components of systemic impedance following CRT. This is important to help understand how CRT benefits patients and may have implications for optimising therapy.
This thesis will explore how to optimise LV endocardial pacing with the WiSE-CRT system (EBR systems, CA, USA) using real-time cardiac computed tomography with dynamic perfusion image overlay. Targeting the latest mechanically and electrically activating segments whilst avoiding myocardial scar has been shown to improve outcomes. Identifying the optimal implantation sites for both the electrode and transmitter, whilst ensuring adequate acoustic intensity is vital to provide reliable right ventricular tracking and biventricular pacing. Additionally, identifying ways to reduce procedure-related complications is important to improve patient outcomes.
Finally, this thesis will investigate whether the WiSE-CRT system is beneficial in patients who are non-responders to conventional CRT. Endocardial pacing has a number of advantages over epicardial pacing including access to fast endocardial conduction, a more physiological activation pattern and access to multiple pacing sites which are unrestricted by the coronary sinus anatomy. Consequently, endocardial pacing may be beneficial in patients who are deemed non-responders to epicardial CRT.
Date of Award1 Mar 2021
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorChristopher Aldo Rinaldi (Supervisor) & Steven Niederer (Supervisor)

Cite this