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Title: The effect of cardiac resynchronisation therapy on left ventricular remodelling, plasma apelin and cytokine levels in patients with heart failure with systolic dysfunction
Author: Chandrasekaran, Badrinathan
ISNI:       0000 0004 2732 1664
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Aims: To investigate the human production of the vasodilating, inotropic peptide apelin in heart failure (HF) and the effect of cardiac resynchronisation therapy (CRT) on left ventricular remodelling (LVR), venous apelin, serum cytokines and their soluble receptors in humans. Methods: Plasma apelin and B-type natriuretic peptide (BNP) were measured in coronary sinus (CS), Aorta (Ao) and renal vein (RV) of patients with HF and healthy controls. In a population of patients who were eligible for CRT clinical parameters apelin, soluble ST2 (sST2), and an array of cytokines: Interferon (IFN)-γ, Interleukin (IL) -1b, IL-1ra, IL-6, Tumour necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, sTNFR2, IL-4 and IL-10 were measured at baseline, 6 and 12 months. LVR was assessed by radionuclide ventriculography. Results: Apelin was higher in CS compared to Ao in controls and this was not maintained in patients with HF. After 12 months of CRT clinical parameters and left ventricular ejection fraction (LVEF) improved. Apelin was unchanged in the whole group, but was decreased in those that failed to remodel at 6 months and LVEF was increased significantly more in individuals whose apelin rose early. sST2 was unchanged at 12 months, but changes correlated with change in BNP and negatively with changes in LVEF. In individuals where sST2 decreased, LVEF was significantly increased. IFN-γ, IL-10 and IL-6 were reduced following 12 months of CRT. In those that remodelled favourably IL-10 was reduced whereas in those who failed to remodel IFN-γ was reduced. Conclusions: Apelin is produced in the heart and myocardial apelin is reduced in HF. Early changes in apelin are associated with LVR post CRT. A reduction in sST2 post CRT is associated with favourable LVR and a fall in BNP. Following CRT there is a relative shift away from a TH2 towards a TH1 pattern of cytokines.
Supervisor: McDonagh, Theresa Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral