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Title: Renal denervation in heart failure with preserved ejection fraction
Author: Patel, Hitesh Chandrakant
ISNI:       0000 0004 5994 2422
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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There are no treatments proven to significantly reduce heart failure hospitalisations or mortality in patients with heart failure with preserved ejection fraction (HFpEF). Activity of the sympathetic nervous system (SNS) is elevated in heart failure regardless of ejection fraction and may be an important target in HFpEF. Renal denervation (RDT) is a percutaneous technique that seeks to attenuate SNS activity. The aim of this thesis was to investigate the role of RDT in patients with HFpEF. A randomised (2:1) open-controlled trial with blinded endpoint analysis was planned. 10 228 patients were screened for the Renal DenervaTion in heart failure with Preserved Ejection Fraction trial (RDT-PEF), and ultimately 25 were randomised (17 received RDT and 8 were allocated to the open control arm). The primary endpoint was an improvement in a minimum of three out of the following six surrogate endpoints: Minnesota Living with Heart Failure questionnaire score, peak oxygen uptake on exercise, B-type natriuretic peptide, E/e' from echocardiography, left atrial volume from cardiac magnetic resonance imaging (CMR) and left ventricular mass from (CMR). The primary endpoint was not met but the study was underpowered. On post-hoc analysis there was an improvement in a composite score of all six endpoint in the RDT arm compared to the control arm at three months but this did not persist to 12 months. The study satisfied its safety endpoints. However, two patients required balloon angioplasty during the RDT procedure for significant renal artery spasm/oedema. RDT had no effect on blood pressure, renal function, vascular function, renin-angiotensin system or SNS activity. In summary, this thesis has shown that HFpEF is not as prevalent as reported. RDT did not improve quality of life, exercise function, biomarkers and left heart remodelling in HFpEF. The procedure was safe though not without complications in patients with HFpEF.
Supervisor: Di Mario, Carlo ; Lyon, Alexander R. ; Rosen, Stuart D. Sponsor: National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral