Remodelling, remission and risk in non-ischaemic dilated cardiomyopathy
File(s)
Author(s)
Hammersley, Daniel John
Type
Thesis
Abstract
Background: Dilated cardiomyopathy (DCM) is a major contributor to the global burden of heart failure. Whilst outcomes of patients with DCM have historically been poor, some patients improve with modern treatments. Unmet clinical needs include more precise early identification of patients at risk of adverse outcomes across the full spectrum of disease and improved understanding of disease remission.
Methods & Results:
1. Prospective observational study characterised 254 patients with early-stage non-ischaemic cardiomyopathy (NICM) using cardiovascular magnetic resonance (CMR), found a quarter of patients had myocardial fibrosis. Over long-term follow-up, 11% experienced major adverse cardiovascular events (MACE). Myocardial fibrosis, non-sustained ventricular tachycardia and diabetes were important predictors of MACE.
2. Prospective observational study characterised 70 patients with recent-onset DCM, of which 31% reached a state of clinical remission after 12-months of treatment. While standard clinical variables were imprecise determinants of remission, molecular phenotyping using plasma proteomics offered enhanced prediction and mechanistic insight.
3. Prospective observational study of 727 patients with DCM found that diabetes mellitus was associated with lower LVEF and higher prevalence of myocardial fibrosis. Patients with DCM and diabetes treated with pharmacological therapy were at greater risk of cardiovascular death.
4. Two-centre observational study of 1,714 patients with NICM demonstrated that quantification of myocardial fibrosis and fibrosis entropy (a measure of scar texture heterogeneity) were incremental to the presence of myocardial fibrosis alone for predicting life-threatening arrhythmic events.
5. Prospective observational study of 90 patients with DCM found that measures of myocardial perfusion, derived from adenosine stress perfusion CMR, were associated with MACE and enhanced risk prediction beyond established prognostic markers.
Conclusion: Integration of advanced cardiac imaging with molecular phenotyping enhances risk prediction and understanding of early disease trajectory and remission in patients with DCM; this may provide a gateway to bespoke management and personalised therapies.
Methods & Results:
1. Prospective observational study characterised 254 patients with early-stage non-ischaemic cardiomyopathy (NICM) using cardiovascular magnetic resonance (CMR), found a quarter of patients had myocardial fibrosis. Over long-term follow-up, 11% experienced major adverse cardiovascular events (MACE). Myocardial fibrosis, non-sustained ventricular tachycardia and diabetes were important predictors of MACE.
2. Prospective observational study characterised 70 patients with recent-onset DCM, of which 31% reached a state of clinical remission after 12-months of treatment. While standard clinical variables were imprecise determinants of remission, molecular phenotyping using plasma proteomics offered enhanced prediction and mechanistic insight.
3. Prospective observational study of 727 patients with DCM found that diabetes mellitus was associated with lower LVEF and higher prevalence of myocardial fibrosis. Patients with DCM and diabetes treated with pharmacological therapy were at greater risk of cardiovascular death.
4. Two-centre observational study of 1,714 patients with NICM demonstrated that quantification of myocardial fibrosis and fibrosis entropy (a measure of scar texture heterogeneity) were incremental to the presence of myocardial fibrosis alone for predicting life-threatening arrhythmic events.
5. Prospective observational study of 90 patients with DCM found that measures of myocardial perfusion, derived from adenosine stress perfusion CMR, were associated with MACE and enhanced risk prediction beyond established prognostic markers.
Conclusion: Integration of advanced cardiac imaging with molecular phenotyping enhances risk prediction and understanding of early disease trajectory and remission in patients with DCM; this may provide a gateway to bespoke management and personalised therapies.
Version
Open Access
Date Issued
2023-11-13
Date Awarded
2024-05-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Prasad, Sanjay
Ware, James
Mayr, Manuel
Tayal, Upasana
Sponsor
National Heart & Lung Foundation
Grant Number
WHCC P76228
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)