Cardiac Resynchronisation Therapy (CRT) is a well-established pacing treatment for severe systolic heart failure. This is a condition which carries a poor prognosis if left untreated. Despite decades of work and a number of large prospective randomised controlled trials, conventionally implanted CRT is only effective in around 70% of patients. In a further group, implantation of the left ventricular (LV) resynchronisation pacing lead is not feasible. Optimised endocardial LV lead placement may overcome these obstacles.

In this thesis, I consider techniques to deliver optimised endocardial LV pacing. I validate and use a new electroanatomic three-dimensional (3D) mapping system and mapping catheter, in addition to a bias-resistant high precision haemodynamic assessment protocol. I use these to evaluate techniques for acute optimisation of endocardial biventricular pacing. Following this, I evaluate permanently implanting an endocardial LV lead at a selected ideal location.

Specifically I assess: (1) If there is variation in the atrioventricular (AV) delay that delivers the greatest acute improvement in systolic blood pressure when the LV lead is placed at different locations; (2) if there is variation in acute systolic blood pressure change when the LV lead is placed in different locations; (3) the correlation between the acute change in systolic blood pressure at a specific LV lead location and other targets including, LV and right ventricular (RV) lead tip separation, LV endocardial electrical activation, change in QRS duration and scar; (4) the difference in LV endocardial activation patterns between intrinsic depolarisation and RV pacing; and (5) the feasibility of implanting a permanent endocardial LV lead, guided by a 3D mapping system.

I report that (1) there is variation in the AV delay that delivers the best improvement in systolic blood pressure with the LV lead in different locations but that the haemodynamic impact is small; (2) between patients, there is variation in the LV location that increases acute systolic blood pressure the most, and constantly it was at an alternative location to the mid lateral wall; (3) the LV location that delivers the greatest acute change in systolic blood pressure cannot be predicted by LV and RV lead tip separation, LV endocardial activation time, change in QRS duration or pacing away from scar; (4) the location of latest LV endocardial depolarisation differs between intrinsic LV depolarisation in left bundle branch block and RV pacing; and (5) implanting a permanent endocardial LV lead guided by a 3D mapping system is feasible and associated with limited morbidity.