Abstract
Heart failure is a serious, life-threatening condition. Despite significant advances in both pharmacological and device therapies, significant morbidity and mortality remain a reality. The ability to monitor, identify and intervene on those most at risk to prevent further clinical deterioration continues to be a goal of healthcare providers around the world.Despite their established role in the diagnosis and prognosis of heart failure, use of the B-type natriuretic peptides, BNP and NTproBNP to monitor patients with chronic heart failure has been disappointing. Such results have, in part, been attributed to the high biological variability of these peptides. Over the past decade numerous novel biomarkers associated with heart failure have been identified. Several of these have shown significant prognostic potential. Evidence supporting their use for monitoring remains lacking.
The aim of this thesis is to assess the potential of four novel biomarkers of heart failure for monitoring pharmacologically optimised, stable chronic heart failure patients, both in terms of their biological variability and how this translates into the ability for changes in serial measurements to predict cardiovascular admission. Mid-regional pro-adrenomedullin, apelin, soluble ST2 and galectin- 3 were chosen due to previous promising results with respect to prognosis and their range of reflection of several different underlying pathological processes.
The hypothesis was that that one or more of these biomarkers would have lower biological variability than NTproBNP and that this would translate into serial changes being better at predicting cardiovascular admission. This being so, it would then provide strong evidence to justify a randomised controlled trial of monitoring chronic heart failure patients using one or more of these novel biomarkers.
Results demonstrated that all four novel biomarkers show lower biological variability than that of NTproBNP. This, however, did not consistently translate into improved ability for serial measurements to predict cardiovascular admission. The use of biomarkers for monitoring may depend more on the pathophysiological process being measured and the association of any marker with that process. Biomarkers of hypertrophy and fibrosis, galectin-3 and sST2, appear to show the most potential for monitoring purposes. This thesis supports the development of randomised controlled trials to assess these markers in greater detail.
| Date of Award | 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Theresa Anne McDonagh (Supervisor) & Ajay Shah (Supervisor) |