Pathophysiology of Dilated Cardiomyopathy
This will be a cross-sectional, observational study.
There is no difference in the amount of extracellular volume (ECV or scarring) in the hearts of patients with heart failure as compared to control subjects.
Heart failure occurs when the heart muscle has become too weak to work properly. It is associated with an increase in the amount of connective tissue (collagen) which replaces dead heart muscle cells (scarring). Currently a biopsy of the muscle is the only way to measure the amount of scarring. This is invasive and rarely done in children. Because of this, it is difficult to measure the amount of scarring in a particular patient or disease process, which is important for improving our understanding and treatment of the disease.
Cardiac magnetic resonance imaging (MRI) is a non-invasive imaging tool which is routinely used to look at areas of local scarring in heart muscle. Because the scarring is so widespread in paediatric patients, we have not been able to use this method previously. Now new imaging techniques allow us to look at widespread scarring but these have not yet been validated in children.
We plan to use late gadolinium enhancement (T1 mapping) to measure the amount of scarring in patients with heart failure (we have evidence that their heart biopsies show increased amounts of scar tissue) and children having MRI scans for other reasons. We will use measures of function including echocardiography and 6 minute walk test to compare to the amount of scarring. This will help us to know whether the amount of scarring will be clinically useful.
We will look at the amount of various proteins in the blood of patients and control subjects which are related to the scarring and cell death processes. We already use blood tests to monitor heart failure and these tests may help us to refine our testing and improve timing of treatment (e.g. transplantation).
This study will help us to design further research in this field.
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||Using Novel Blood and Imaging Biomarkers to Better Understand the Pathophysiology of Paediatric Dilated Cardiomyopathy|
- Fibrosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]Higher fibrosis score (ECV) in heart failure patients in comparison to control subjects
- Biomarkers [ Time Frame: 6 months ] [ Designated as safety issue: No ]Significantly different pattern of blood biomarkers in heart failure patients as compared to control subjects
- Disease Severity [ Time Frame: 6 months ] [ Designated as safety issue: No ]Significant correlation between fibrosis score on MRI or biomarker profile and clinical parameters (including 6 minute walk test and disease severity).
Biospecimen Retention: Samples Without DNA
Blood plasma (>400 UL) will be collected in heparinised tubes plasma will be extracted and the cell fraction discarded. Plasma will be stored at 80°C prior to transport on dry ice, via protected courier.
|Study Start Date:||January 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Patients will be recruited from the heart failure clinic by their consultant. These will include patients who are due to have a MRI scan for clinical reasons and those who volunteer to participate. Voluntary subjects will be over 8 years.
Control subjects will be identified after being referred for an MRI scan and being allocated to a non-cardiac MRI with gadolinium contrast.
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|Great Ormond Street Hospital NHS Trust||Not yet recruiting|
|London, United Kingdom, WC1N 3JH|
|Contact: Emma Pendleton R&DGovernance@gosh.nhs.uk|
|Principal Investigator: Dilveer K Panesar, Mb ChB|
|Study Director:||Michael Burch, MD||Great Ormond Street Hospital|