Since the first implantable device 60 years ago, cardiac device therapy for brady and tachy arrhythmias has shown continued progress. However, despite the substantial benefits that have been realized, they still exhibit significant limitations and pose risks to patients.
Despite the acute benefits that pacemakers confer by providing life-saving ventricular stimulation in patients with ventricular standstill, in the longer-term harm may arise. This harm can occur as both right ventricular pacing and biventricular pacing do not deliver normal physiological activation of the ventricles and a subsequent deterioration in cardiac outcomes can be seen in both observational and randomised studies.
Similarly, Implantable Cardioverter Defibrillators (ICDs) clearly save lives in patients with ventricular arrhythmias by terminating the rhythm disturbance. However, ICDs can also cause harm. Devices may deliver therapies when not absolutely needed. Some therapies may be inappropriate (i.e. the device has incorrectly interpreted the recorded electrogram as a ventricular tachyarrhythmia when it is not) or unnecessary (i.e. there is indeed a ventricular tachyarrhythmia, but the patient is tolerating it well and a therapy could have been withheld safely). Current available ICD therapies are painful (in the case of shocks) and may worsen the clinical state (in the case of anti-tachycardia pacing accelerating a ventricular arrhythmia).
Improvements in both the pacing and defibrillator sphere of cardiac devices may well have the potential to improve the lives of the one million individuals worldwide that receive new implantable cardiac devices each year.
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In Chapter 3, this thesis explores the rationale for delivering cardiac pacing through His bundle pacing. Furthermore, it provides data demonstrating the feasibility of permanent His bundle pacing though data from a large worldwide survey I have conducted.
In Chapter 4, haemodynamic experiments are performed to determine the potential physiological benefit that can be derived from His bundle pacing when compared to the standard bradycardia alternatives – dual chamber right ventricular pacing and pacing avoidance algorithms in a cohort of patients with intrinsic PR intervals longer than 200ms. This is a group of patients where currently a decision must be made between (a) shortening the atrio-ventricular delay but at the expense of creating ventricular dyssynchrony or (b) maintaining ventricular synchrony but at the expense of atrio- ventricular dyssynchrony. His bundle pacing may allow atrio-ventricular delay to be optimised whilst maintaining ventricular synchrony.
The physiological principles and knowledge derived from these prior chapters will be evaluated in the tachyarrhythmia setting and used to investigate the mechanisms by which ventricular tachyarrhythmias cause harm and subsequent consideration to novel mechanistically-targeted therapies.
In Chapter 5, invasive and non-invasive experiments are performed to determine how the loss of atrio-ventricular and biventricular synchrony contribute to the haemodynamic harm associated with ventricular tachycardias. This thesis then investigates how atrial pacing and His pacing during VT might mitigate this haemodynamic harm, preventing circulatory collapse and potentially allowing spontaneous termination of the ventricular tachycardia which could be a novel strategy for ICDs. In this chapter the first case series of His bundle pacing to terminate ventricular arrhythmias is presented.
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In Chapter 6, this thesis tests and investigates a novel algorithm that I have derived, combined with a potentially implantable haemodynamic sensor, namely laser Doppler, to augment the accuracy of arrhythmia detection and the need for therapy to reduce the incidence of potentially harmful inappropriate ICDs therapies.
This thesis elucidates the mechanisms by which anti-bradycardia pacing and ventricular tachycardia cause harm; investigates how the novel strategy of His bundle pacing can potentially overcome these; and provides a potential framework by which the next generation of devices could work to enhance the lives of the one million individuals who receive a device each year.