Defining the Genetics, Biomarkers and Outcomes for Dilated Cardiomyopathy

This study will recruit patients from a number of hospitals in England and study them over a number of years. The study will be divided in 2 parts. Part 1 will recruit patients with a diagnosis of DCM, Part 2 will recruit patients diagnosed with other heritable cardiovascular disorders. Family members of patients may be invited to take part in the study. Children may also be approached to take part in the study.

Patients will attend for a baseline visit for a cardiovascular magnetic resonance (CMR) scan, completion of quality of life questionnaires, collection of blood samples for whole genome sequencing and biomarker analysis, and collection of clinical data. Collection of health information via national registries including Office of National Statistics (ONS) and Hospital Episodes Statistics (HES) will be continued over the patients's lifetime. This will not require any direct contact with the participant.

Recruitment will take place over a 3 year period, with annual completion of questionnaires at patients scheduled hospital visits. If the patient is not scheduled to attend the hospital for regular follow up, then patients may complete the questionnaires via an online system or over the telephone. Patients will be asked to complete questionnaires annually for 5 years. Sub-sets of patients may be invited for additional tests including exercise testing, and stress perfusion scans. These tests will not form part of the core tests for the study, and patients may choose not to have them. Separate informed consent will be obtained from participants for any additional tests.

If patients are having clinical diagnostic tests that involve the removal of tissue, they may be asked to donate any surplus tissue sample, or be asked to provide their consent to collect an additional tissue sample. Separate informed consent will be obtained from participants for donation of additional tissue samples.

Where patients are scheduled to have a CMR scan as part of their routine clinical care, an additional CMR scan for research purposes may not be required.

Children will not be asked to complete any annual questionnaires, health information will be collected via ONS and HES.

Family members of patients who take part in the study will only be asked to donate a blood or saliva sample, and provide consent to collection of their health information via ONS and HES records. They will not have any clinical tests such as CMR.

PART 1

Inclusion criteria

• Male or female participants of any age
• Capacity to provide informed consent
• Patients with a confirmed diagnosis of DCM
• Affected family members of patients meeting diagnostic criteria for DCM

Exclusion criteria

• DCM attributed to chemotoxicity (from chemotherapeutic agents, drugs of abuse)
• DCM attributed to systemic inflammatory myopathies (eg sarcoid, systemic lupus erythematosus)
• Patients who lack capacity to consent for themselves
• Patients with a confirmed history of coronary artery disease, assessed using standard UK clinical practice guidelines, defined as one or more of the following:-

• >50% narrowing, any major epicardial coronary artery on invasive or computed tomography coronary angiography
• CMR suggestive of previous myocardial infarction of ≥2 segments of ≥50% infarction of the LV wall
• Previous percutaneous coronary intervention or coronary bypass surgery
• 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)

PART 2

Inclusion criteria

• Males or females of any age
• Capacity to provide informed consent
• Patients with hypokinetic non-dilated cardiomyopathy, or
• Family members of DCM patients with possible or probable DCM or
• Patients with a confirmed diagnosis of heritable cardiovascular disease or
• Family members of patients with heritable cardiovascular disease, both affected and unaffected

Exclusion criteria

• Patients who lack capacity to consent for themselves
• Patients with a confirmed history of coronary artery disease, assessed using standard UK clinical practice guidelines, defined as one or more of the following:-

• >50% narrowing, any major epicardial coronary artery on invasive or computed tomography coronary angiography
• CMR suggestive of previous myocardial infarction of ≥2 segments of ≥50% infarction of the LV wall
• Previous percutaneous coronary intervention or coronary bypass surgery
• 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)