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| Name | Class |
|---|---|
| Royal Brompton & Harefield NHS Foundation Trust | OTHER |
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Approximately 30-40% of patients with non-ischaemic dilated cardiomyopathy (DCM) undergo significant left ventricular reverse remodelling in response to guideline-directed therapies. This is characterised by improvement in systolic dysfunction and regression of left ventricular dilatation. In some patients, extensive left ventricular reverse remodelling is accompanied by resolution of symptoms and normalisation of cardiac biomarkers, resulting in a state of clinical remission.
The mechanistic drivers behind left ventricular reverse remodelling and clinical remission are poorly understood. Current techniques to predict ventricular remodelling trajectory and clinical remission in patients with recent-onset DCM are limited.
The purpose of this study is to characterise predictors and markers of left ventricular reverse remodelling and clinical remission in patients with recent-onset DCM using molecular markers, genetics and advanced CMR imaging.
The REMIT-DCM study is a single-centre pilot observational cohort study. 70 patients with recent-onset DCM (Group A) and up to 40 healthy volunteers (Group B) will be recruited. Patients with DCM will be recruited over a 2-year period and will be followed up for 12 months. Subjects in Group A may be offered an optional further study visit at 24-48 months after enrolment in order to assess whether cardiac remodelling and clinical remission are sustained over the intermediate-term.
Patients with DCM (Group A) will attend 3 study visits at The Royal Brompton Hospital (baseline, 2-3 months and 12 months). Each study visit will involve a clinical consultation, blood sample collection (including routine clinical blood tests and sample storage for exploratory biomarkers), urine sample collection, 12-lead ECG, health questionnaire completion and a cardiovascular magnetic resonance scan (CMR). If patients are unable to have a CMR, 3D transthoracic echocardiography will be performed.
Healthy volunteers will attend a single study visit at The Royal Brompton Hospital. This will involve a clinical consultation, blood sample collection (including routine clinical blood tests and sample storage for exploratory biomarkers), urine sample collection, 12-lead ECG, health questionnaire completion and a CMR.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: patients with dilated cardiomyopathy | Patients with recent-onset dilated cardiomyopathy |
| |
| Group B: healthy volunteers | Healthy volunteers with no known heart disease |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 12 months of guideline-directed heart failure therapy | Other | Standard guideline-directed heart failure drug +/- device therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical remission | If all 3 of the following criteria are met at 12-month assessment: i. Increase in left ventricular ejection fraction (LVEF) by ≥ 10% to a value ≥ 50% and decrease in indexed left ventricular end diastolic volume (LVEDV) to within normal range according to age-/sex-corrected normograms. ii. NYHA class I. iii. NT-Pro BNP <250 ng/L. | 12-months |
| Measure | Description | Time Frame |
|---|---|---|
| Left ventricular reverse remodelling | Evaluated by changes in indexed left ventricular end systolic volume (LVESV), indexed LVEDV and LVEF between baseline and 12 months. | 12-months |
| Left ventricular reverse remodelling |
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For DCM cohort (Group A):
Inclusion Criteria:
Exclusion Criteria:
For healthy volunteer cohort (Group B):
Inclusion Criteria:
Exclusion criteria:
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Group A: There are 3 routes via which patients with DCM may be recruited:
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| Name | Affiliation | Role |
|---|---|---|
| Sanjay K Prasad | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imperial College | London | SW3 6LY | United Kingdom |
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| ID | Term |
|---|---|
| D002311 | Cardiomyopathy, Dilated |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006332 | Cardiomegaly |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D009202 | Cardiomyopathies |
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Blood and urine samples
Evaluated using a pre-specified threshold: patients with DCM will be divided into 2 groups at the 12-month timepoint:
i. Left ventricular reverse remodelling: an increase in LVEF by ≥ 10% to a value ≥ 40%; and a decrease in indexed LVEDV by ≥ 10%.
ii. No left ventricular reverse remodelling: no increase in LVEF by ≥ 10% to a value ≥ 40% and/or no decrease in indexed LVEDV by ≥ 10%.
| 12-months |
| Major adverse cardiovascular events | Composite of cardiovascular death, major heart failure or major arrhythmic events. | 12-months |
| Change in health status using Kansas City Cardiomyopathy questionnaire | Change in Kansas City Cardiomyopathy questionnaire scores from baseline to 12-months | 12-months |
| Change in health status using SF-12 questionnaire | Change in SF-12 questionnaire scores from baseline to 12-months | 12-months |
| Change in health status using EQ-5D questionnaire | Change in EQ-5D questionnaire scores from baseline to 12-months | 12-months |
| Sustained clinical remission at 24-48 months after enrolment | For those in clinical remission at 12-month timepoint, the proportion that have sustained clinical remission at 24-48 months after enrolment. | 48 months |
| D000083083 |
| Laminopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |