Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy

NCT04957147 | Completed

• 1 other identifier: 19IC5198
• Study Type: observational
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dilated Cardiomyopathy

Keywords

Dilated cardiomyopathy; Left ventricular reverse remodelling; Heart failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Left ventricular reverse remodelling

  12-months

• Left ventricular reverse remodelling

  12-months

• Major adverse cardiovascular events

  12-months

• Change in health status using Kansas City Cardiomyopathy questionnaire

  12-months

• Change in health status using SF-12 questionnaire

  12-months

Study Arms (2)

Group A: patients with dilated cardiomyopathy

Patients with recent-onset dilated cardiomyopathy

Other: 12 months of guideline-directed heart failure therapy

Group B: healthy volunteers

Healthy volunteers with no known heart disease

Interventions

12 months of guideline-directed heart failure therapy OTHER

Standard guideline-directed heart failure drug +/- device therapy

Group A: patients with dilated cardiomyopathy

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Imperial College London: lead
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (1)

Imperial College

London, SW3 6LY, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine samples

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Heart Failure

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Sanjay K Prasad

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: July 12, 2021
• Study Start: August 1, 2019
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)