Abstract
Accurate prediction of individuals at risk of ventricular arrhythmia and sudden cardiac death remains a major challenge. Beat-to-beat variability of ventricular action potential duration (APD) has long been proposed as a potential mechanism of arrhythmogenesis, however, studies examining the dynamics of this metric in humans are lacking and to date have been dependent largely on assessment of the QT interval. We hypothesised that increased beat-to-beat variability of APD would be seen in patients experiencing ventricular arrhythmia and that autonomic tone would play a significant role in the modulation of beat-to-beat variability of APD. These hypotheses were tested in a series of human experiments.In patients with heart failure and implanted cardiac resynchronization therapy defibrillator devices we demonstrated for the first time that increased left ventricular beat-to-beat variability of APD was associated with an increased risk of ventricular tachyarrhythmia.
Subsequently, through invasive electrophysiology studies we compared the behavior of local right and left ventricular APD with global body surface QT intervals. These results highlighted that although the body surface QT interval is representative of global repolarization, subtle regional inhomogeneity of repolarization would be missed by QT interval assessment alone.
Finally, a sequence of experiments in patients with heart failure and patients with structurally normal hearts demonstrated for the first time the ability of a sympathetic stimulus to increase the beat-to-beat variability of human ventricular APD, and the potentially important role of beta-adrenergic blocking agents in the suppression of this increase.
| Date of Award | 2021 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Jaswinder Gill (Supervisor) & Reza Razavi (Supervisor) |