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Investigation of Absolute Refractory Period Pacing to Prevent Lethal Arrhythmias in Humans

Santos, Diogo Reis; (2020) Investigation of Absolute Refractory Period Pacing to Prevent Lethal Arrhythmias in Humans. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Sudden cardiac death (SCD) is a major health issue, being the commonest cause of natural death in the industrialised world. SCD frequently results from the development of erratic heart rhythms which are usually preceded by repolarisation alternans (RA). Previous studies suggest that the abolishment of RA may prevent the onset of arrhythmia. In a recent swine study, absolute refractory period pacing (ARPP) showed promising results in RA modulation. However, the cellular mechanisms underlying this therapy and its efficiency in human patients remains unclear. Single cell in silico modelling showed that ARPP might be used to both increase or decrease action potential duration (APD) with the degree of modulation depending mainly on stimulus duration, magnitude and coupling interval. ICaL, IKr and IK1 were the main currents involved, and conductance of Ito and ICaL strongly influenced results. APD alternans was successfully reduced in a population of alternating models. In vivo results obtained using an epicardial sock during cardiac surgery showed significant changes in repolarisation when applying ARPP. However, elevated morphological signal alterations led to question the results’ validity. The investigation of signal processing methodology led to the acknowledgement of high-pass filter interference in signal morphology due to the ARPP artefact, resulting in altered markers. Further in vivo data showed no significant effect of ARPP on local RT at the whole heart level. Small effects on RT, spectral method and Tend markers close to the pacing site were observed, suggesting a localised effect. One dimensional in silico modelling showed a rapid decline of the ARPP effect, being limited to around 10mm from the pacing site, correlating with the in vivo results. These results provide important new knowledge regarding the effects of ARPP in the human ventricle at the cellular and organ level. It also provides relevant information for further development, analysis and translation of pacing based therapies.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigation of Absolute Refractory Period Pacing to Prevent Lethal Arrhythmias in Humans
Event: UCL
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10091035
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