Investigation of metabolomic biomarkers of heart failure

Cardiovascular disease, an overarching term for many diseases affecting the heart and vasculature, is the highest cause of death globally. Heart failure is a cardiovascular syndrome with many causes characterised by an inability of the heart to meet the demands of the rest of the body. The incidence of heart failure is set to increase in coming years with an ageing population. In addition to causing premature death, its treatment and management comes at a substantial cost to the economy. When a patient presents to the emergency department, a diagnosis of heart failure is made using a combination of measurements. To date, two plasma biomarkers are recommended for the diagnosis of heart failure: BNP and NT-proBNP. There are no prognostic biomarkers recommended for heart failure.

To identify potential biomarkers for the diagnosis or prognosis of heart failure requires analysis of the plasma metabolome. This thesis conducts an initial investigation of metabolites which differ between heart failure and healthy volunteer plasma samples in previous untargeted mass spectrometry datasets.

From this analysis, the identity of three metabolites: glutamine, lysophosphatidylcholine 17:0 and lysophosphatidylcholine 18:2 was reported which were lower in heart failure patients compared to healthy volunteers. The three metabolites were further investigated by targeted mass spectrometry. Two quantitative methods were developed to investigate the association of the metabolites with adverse events in a larger clinical cohort.

Results from the application of the two quantitative methods showed that lower glutamine was associated with a poorer prognosis. The combination of glutamine and glutamic acid also had significant prognostic ability. Lower levels of blysophosphatidylcholine 17:0 was associated with poor prognosis in the clinical cohort.

The results of this thesis present novel diagnostic and prognostic biomarkers which could, bwith further investigation, translate to being used in the clinic to aid clinicians treating heart failure patients.