Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy (REMIT-DCM)

The REMIT-DCM Study: Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy

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.

Study Overview

• Status: Completed
• Conditions: Dilated Cardiomyopathy
• Intervention / Treatment: Other: 12 months of guideline-directed heart failure therapy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6LY
    • Imperial College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Group A: There are 3 routes via which patients with DCM may be recruited:

1. Patients from the Royal Brompton & Harefield NHS Trust clinical service (inpatients, patients from clinics and patients referred for a CMR).
2. Patients with DCM may also be recruited from collaborating district general hospitals, defined as Patient Identification Centres (PICs). Clinicians at these sites have agreed to identify suitable patients encountered within their routine practice.
3. Patients will be able to self-refer via The Heart Hive for consideration by the study team. The Heart Hive (https://www.thehearthive.org/) is an online platform that offers patients with cardiomyopathy and healthy volunteers the opportunity to connect with researchers regarding participation in research studies.

Description

For DCM cohort (Group A):

Inclusion Criteria:

• Age ≥16.
• Able to give informed consent.
• Confirmed DCM with symptom-onset within the last 6 months and LVEF ≤ 45%. The diagnosis of DCM will be confirmed using the European Society of Cardiology definition, based on reduced LVEF and elevated LV end-diastolic volume indexed to body surface area, compared to published age- and sex-specific reference values

Exclusion Criteria:

• Significant coronary artery heart disease, defined as a stenosis of >50% of an epicardial coronary artery affecting the proximal or mid-portion of the vessel on invasive angiography or computed tomography coronary angiography (CTCA), previous percutaneous coronary intervention, CMR late gadolinium enhancement pattern suggestive of previous myocardial infarction of ≥ 2 segments of ≥ 50% transmural infarction of the LV wall.
• High suspicion of concomitant hypertrophic cardiomyopathy, amyloidosis, Fabry disease, sarcoidosis, active myocarditis, Chagas disease or hemochromatosis.
• History of primary valvular heart disease or congenital heart disease.
• Severe, untreated or untreatable hypertension (systolic blood pressures routinely >180 mm Hg and/or diastolic blood pressures >120 mm Hg)
• Pregnancy and/or breastfeeding.
• Severe renal disease (GFR <15 mls/min).

For healthy volunteer cohort (Group B):

Inclusion Criteria:

• Age ≥16.
• Able to give informed consent.

Exclusion criteria:

• Participants with any clinically significant cardiovascular or metabolic disease.
• Participants taking prescription medicines for significant cardiovascular or metabolic disease.
• Female subjects if they are pregnant or breastfeeding at the time of recruitment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A: patients with dilated cardiomyopathy; Patients with recent-onset dilated cardiomyopathy	Other: 12 months of guideline-directed heart failure therapy; Standard guideline-directed heart failure drug +/- device therapy
Group B: healthy volunteers; Healthy volunteers with no known heart disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Royal Brompton & Harefield NHS Foundation Trust
• Investigators: Principal Investigator: Sanjay K Prasad, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): May 1, 2023
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: June 22, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Heart failure; Dilated cardiomyopathy; Left ventricular reverse remodelling
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: 19IC5198

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No