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    Innovations and mechanisms in pacing therapy for heart failure

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    Despite pharmacological advances, heart failure remains a major cause of mortality and morbidity. Pacing therapy for heart failure was achieved in the 1990s with the advent of biventricular pacing (BVP). BVP shortens ventricular activation time and has thus been referred to as ‘cardiac resynchronization therapy’ (CRT). However BVP has other effects including shortening of atrioventricular delay: the contributions of its effects to its overall benefit have yet to be elucidated. Ventricular activation is not normalised by BVP, indicating scope for more effective resynchronization. This thesis explores mechanisms and innovations in pacing therapy for heart failure through measurement of haemodynamic and electrical parameters with high precision and resolution during BVP, right ventricular pacing (RVP) and His bundle pacing (HBP), where the His-Purkinje conduction system is directly stimulated. HBP offers both an innovation in pacing and a model to study conventional pacing. HBP can deliver physiological CRT by overcoming left bundle branch block (LBBB) to normalise QRS appearances but its performance relative to BVP is not known. When performed proximally, or using lower energy, HBP can preserve intrinsic LBBB. In Chapter 3, the electro-mechanical effects of conventional BVP are compared with LBBB correction by HBP. Chapter 4 uses non-invasive electrical mapping to identify mechanisms and predictors of LBBB correction by HBP, comparing it with narrow QRS. Capture of the His bundle can be alone (selective HBP) or alongside myocardial capture (non-selective): the effect of this on HBP is studied in Chapter 5. In Chapter 6, the haemodynamic effects of proximal/low-energy HBP, where LBBB is preserved but atrioventricular timing can be optimised, is compared to BVP and RVP to measure the contribution of atrioventricular delay shortening to the overall benefit of BVP. By evaluating innovative therapies and improving our understanding of existing therapies, hopefully this thesis will advance pacing therapy for heart failure.Open Acces
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