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Title: Novel biomarkers in paediatric dilated cardiomyopathy
Author: Panesar, Dilveer
ISNI:       0000 0004 7970 638X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Introduction: The pathophysiology of cardiomyopathy (CMP) is not fully understood in children. In this project, I analysed blood and imaging biomarkers to ascertain the importance of various processes in this condition. Remodelling, fibrosis, inflammation and vaso-reactivity were examined using circulating biomarkers. Diffuse fibrosis was quantified using T1 mapping and the calculation of extracellular volume (ECV) on magnetic resonance imaging (MRI). Methods: 76 children with CMP and a history of impaired left ventricular (LV) function underwent clinical assessment, 34 had blood biomarkers and 30 had cardiac MRI scans. 88 control subjects (7 adults) had an MRI performed and 25 had novel blood biomarkers measured. The biomarker panel consisted of: N-terminal pro-brain-natriuretic peptide (NT-proBNP), mid-regional atrial natriuretic peptide (MR-proANP), midregional adrenomedullin (MR-proADM), c-terminal endothelin-1 (CT-proET1), soluble suppression of tumorgenicity-2 ligand (sST2), growth differentiation factor-15 (GDF-15), high-sensitivity troponin I (hsTnI) and high-sensitivity Creactive protein (hsCRP). 29 patients with CMP had T1native (T1 time pre-contrast, ms) and 26 had ECV (%) measured. 14 control subjects had T1native and ECV measured (7 adults and 7 children). Circulating levels of blood biomarkers were measured in the 7 children. Results: NT-proBNP, MR-proANP, GDF-15, hsCRP and sST2 were significantly higher in patients with CMP versus control subjects (paediatric). Both T1native and ECV were significantly higher in patients with CMP and those with DCM versus control subjects (adult controls). Septal regions of the myocardium had significantly higher levels of T1native in patients compared to control subjects. Discussion: Blood biomarkers implicating fibrosis, inflammation, endothelial activation and apoptosis are elevated in paediatric heart failure, particularly idiopathic dilated cardiomyopathy (DCM) compared to control subjects. T1native and ECV values are higher in patients with CMP and DCM than control subjects. Septal values are especially high.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available