Biomarkers of neurohormonal activation, on-going myocardial damage, haemostasis and inflammation in patients with stable chronic heart failure due to left ventricular systolic dysfunction and potential novel treatment

Loh, Poay Huan

January 2014

Thesis or dissertation

© 2014 Poay Huan Loh. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

The prognosis of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) remains poor despite the progress in modern therapy. Btype natriuretic peptide (BNP) is a useful diagnostic and most consistent prognostic markers in CHF. However, treatment strategy guided by natriuretic peptides does not necessarily improve the outcome. In addition to myocardial remodelling, CHF is a systemic syndrome involving neurohormonal activation, inflammatory up-regulation, endothelial dysfunction and haemopoietic, haemostatic and haemorrheologic disturbance. In patients with CHF, the projects of this thesis investigated the potential prognostic role of some biomarkers which reflect these pathophysiological processes in addition to NT-proBNP.

The haemostatic markers investigated were D-dimer and fibrinogen for thrombogenesis; t-plasminogen activator and plasminogen activator inhibitor-1 for fibrinolysis, von Willebrand factor activity and soluble E-selectin for endothelial function, and soluble P-selectin for platelet activity. The role of white and red cell variables from routine full blood count was also explored. Heart-type fatty acid-binding protein (H-FABP), a sensitive marker for myocardial injury, was used as a marker for on-going myocardial damage/remodelling. The change in the level of these markers with time for dynamic risk stratification was also explored.

Coronary artery disease (CAD) is the commonest cause of CHF and conventional invasive revascularisation has not been proven to improve the prognosis of the patients. Enhanced external counterpulsation (EECP) has been shown to improved myocardial perfusion mainly in patients with CAD. Building on the experience from studies of patients with angina, potential role of EECP in improving myocardial function and perfusion in patients with LVSD and CAD was investigated. Its effects on some biomarkers were also investigated.

These studies confirmed the potential prognostic value of a few laboratory markers including H-FABP; whilst showing that EECP can improve regional myocardial function and perfusion with a short-term reduction in H-FABP.

Hull York Medical School, The University of Hull and the University of York
Qualification level
Qualification name
10 MB
QR Code