Iron and the sympathetic nervous system in chronic heart failure

Student thesis: Doctoral ThesisDoctor of Medicine (MD)


Heart failure with reduced ejection fraction (HFrEF) is a common condition associated with considerable morbidity and mortality. The condition is characterised by a reduction in left ventricular function and subsequent derangement in autonomic function with increased activity of the sympathetic nervous system (SNS). Increased activity is associated with worse clinical outcomes. Many factors may drive this increased activity. A common comorbidity of HFrEF is iron deficiency. Treatment of this in HFrEF is associated with clinical improvements. This study sought to assess a link between iron status and SNS activity and whether any clinical improvements seen with iron therapy could be attributed to improvements in deleterious autonomic function. To achieve this muscle sympathetic nerve activity (MSNA) was assessed with microneurography at rest and with post exercise ischaemia (PEI) in iron deficient and non-iron deficient as well as non-invasive assessment of haemodynamic responses to exercise. Assessment of exercise was important as HFrEF is particularly associated with reduced exercise tolerance. A skeletal myopathy develops in the iron deficient HFrEF patient and it was hypothesised that these patients would have excessive activity of muscle based exercise reflexes including the metaboreflex. Post exercise ischaemia was used to isolate the metaboreflex. The first finding of this thesis is that MSNA differs between iron deficient and non-iron deficient participant at rest, being higher in the iron deficient state. Furthermore, there is potential that treatment of iron deficiency with intravenous iron may reduce this. It was not possible to assess changes in MSNA on exercise due to a limited sample size. Differences in haemodynamic responses were not seen between iron deficient and non-iron deficient participants. However, treatment of iron deficiency was associated with improvements in cardiac output and a suggestion, based on effect size of improvements in stroke volume and reduced total peripheral resistance.
Date of Award7 May 2024
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorAngus K Nightingale (Supervisor) & Emma C J Hart (Supervisor)

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