Defining the Genetics, Biomarkers and Outcomes for Dilated Cardiomyopathy

Finding new ways to diagnose and treat Dilated Cardiomyopathy (DCM) could improve the health and well-being of patients with this condition. The main aim of this research study is to help develop better ways of diagnosing and treating patients with DCM. The information that is collected may help develop tailored treatments for patients with this disease in the future. This research study will recruit patients with DCM from a number of centres across England and follow their health over a period of years. Patients will give some blood samples for a type of genetic test called whole genome sequencing (WGS) to look for genetic changes. Patients will also have a magnetic resonance imaging (MRI) scan of their heart to look for any changes in the heart such as scarring, and check their heart function. The aim of this study is to discover if using WGS and MRI can improve the diagnosis of DCM. Another aim of the study is to look at how genetic changes and scarring in the heart may affect the progress of the disease.

Studying patients with DCM may also help the investigators learn more about diagnosing and treating other diseases of the heart. The second aim of this study is to see whether using WGS and MRI scanning can also be useful in other types of heart diseases which might be affected by genetic changes or scarring in the heart.

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.

Eligibility Criteria:
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)