Investigation of the pro-arrhythmic effects of heart failure in 3D electromechanical models of canine ventricles

Abstract

Heart failure (HF) is one of the most common cardiac diseases that are associated with increased susceptibility of ventricular arrhythmia and mechanical failure causing morbidity and mortality. Previous studies have found that HF causes a series of electrical and structural remodelling in the heart, which may be responsible for arrhythmogenesis and cardiac dysfunction. However, it is still unclear how these remodelling contribute to ventricular arrhythmias and mechanical failure. The aim of this study is to determine the predominant factor of HF-induced remodelling responsible for ventricular arrhythmias and mechanical failure.In part I, 3D electrophysiological models of canine normal and failing ventricles are developed. The anatomical geometry of normal and failing ventricles, which was reconstructed from DTMRI data, is incorporated along with previously developed heterogeneous single myocyte models. Then ventricular arrhythmias are induced by three common conditions including supraventricular premature stimulus, sinus tachycardia and sudden external stimulus in order to investigate the arrhythmogenic effects of HF-induced remodelling. Further studies are conducted to investigate the predominant factor that may be responsible for sustainability of ventricular arrhythmias. Potential therapeutic targets for preventing ventricular arrhythmias in the failing heart are also proposed.In part II, 3D electromechanical coupling models of canine normal and failing ventricles are developed. The role of each HF-induced structural and electrical remodelling on impairing ventricular ejection fraction is investigated in a failing ventricle model.In part III, the impact of different types of left bundle branch block (LBBB) on normal ventricles and failing ventricles are investigated. We also investigate the therapeutic effects of alternative configurations of ventricular pacing therapy in this part including right-ventricular pacing, bi-ventricular pacing, multiple sites pacing (MSP) and bio-pacemaker pacing. Bi-ventricular pacing therapy is recommended for short-term treatment of heart failure patients with LBBB, as it improves cardiac output and relieves symptoms.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jian Lu (Supervisor) & Henggui Zhang (Supervisor)