Advanced cardiac imaging and haemodynamic assessment following isometric exercise training in heart failure with preserved ejection fraction

Hypertension is as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations; however, they are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported with traditional guideline-recommended exercise modes. However, IET has been largely limited to healthy participants and before the transition of IET into clinical practice can be justified and practically implemented, there are several important gaps in the current literature to address. As such, the overall aims of this thesis were to establish the comparative effectiveness, optimal application, and clinical transferability of IET into a heart failure with preserved ejection fraction (HFpEF) population. To do this, 5 empirical studies including 2 systematic reviews with meta-analyses and 3 randomised controlled trials were completed. Study 1 performed a large-scale comparative network meta-analysis against other traditional exercise approaches, establishing IET as the most effective mode in reducing resting BP. Study 2 aimed to then determine the most effective application of IET in a randomised cross-over study design comparing handgrip and wall squat IET approaches, which demonstrated the effectiveness of both modes in producing clinically meaningful BP adaptations, with the wall squat likely to produce the greater magnitude of BP reduction. Moving towards the transition of IET into clinical populations, study 3 aimed to explore the existing data and effectiveness of different exercise modes in heart failure patients, revealing that there are no IET trials in heart failure patients published to-date. Studies 4 and 5 involved a randomised controlled clinical trial investigating the acute and chronic effects of IET in patients with HFpEF. IE produced similar acute responses to that seen in healthy cohorts, providing mechanistic evidence for its effectiveness and safety in this clinical population. Following a subsequent 4-week exercise programme, IET produced significant haemodynamic, cardiac functional and mechanical improvements in participants with HFpEF, evidencing the clinical transferability of IET as a novel exercise approach for managing cardiovascular health.