Establishing state-of-the-art non-invasive magnetic resonance imaging techniques for the study of the cardiovascular system of individuals with heart disease and individuals with conditions that occur together with heart disease

Possible investigations during the research visits are: - Cardiovascular magnetic resonance imaging; without or with use of (Gadolinium-based or Manganese-based) contrast agent; without or with pharmacological (Adenosine or Dobutamine) or physiological stress; - 6-minute walk test - Blood sampling - Echocardiography - Quality-of-life (QoL) assessment Participants may undergo each of these investigations up to a total of 4 times within this study, except for scans including contrast or pharmacological stress agents, which participants will undergo a maximum of 2 times. These assessments involve the following for the participants: Cardiovascular magnetic resonance imaging (MRI): MRI is a test which produces detailed pictures of internal organs by putting participants within a strong magnetic field. MR scans can vary in length (in this study, between 30 and 105 minutes), so participants will be told beforehand how long theirs will approximately take. The participant lies in a short 'tunnel', which holds a large magnet. Short bursts of magnetic fields and radio waves from the MRI scanner allow images to be created. They will hear periodical loud “banging” noises while we are acquiring the images of the heart; ear plugs and headphones will be provided for protection of the ears. We will remain in communication throughout the scan. The participant will need to lie very still on their back as movement can blur the images. For some parts of the scan they will be asked to breathe in and out and hold your breath for several seconds. MRI with use of contrast agent: In MRI scans using a contrast agent, a cannula (small plastic tube) will be inserted into a vein in the arm, through which a contrast dye will be administered. MRI with use of pharmacological stress: During the MRI scan, using a cannula inserted into a vein in the arm, the participant will be given a medication for about 5-9 minutes whilst images are taken and blood pressure measured within the scan. The medication increases the heart rate, mimicking exercise activity. MRI with use of physiological stress: In MRI scans using physiological stress, participants will be asked to carry out exercise during the scan using exercise equipment designed for use with the scanners. To do this, while lying in the scanner, the participant will exercise their legs using a cycle ergometer, similar to a home exercise bike. Blood sampling: Blood samples (c. 20mL) will be taken before the MRI scan. If the MRI scan involves contrast or stress agent, blood will usually be taken at the same time as the cannula insertion before the MRI scan. 6-minute walk test: The participant will be instructed to walk along a 30-meter corridor and cover the maximum distance in 6 minutes. At the end of 6 minutes the distance walked will be measured in meters. Echocardiography: An ultrasound scan of the heart with a probe positioned on the participant’s chest (c. 15 minutes). Questionnaires: Safety questionnaires will be taken before all MRI scans. Participants may further be asked to complete one or more questionnaires which address their health and well-being (up to c. 10 minutes). This study will involve one or more study visits (up to 6). The number of study visits will be determined prior to the consenting process and clearly communicated and recorded. Each participant will be scanned no more than 4 times. Participants will undergo scans including contrast or pharmacological stress agents a maximum of 2 times. Scans may be separated by up to 12 months. The minimum length of a participant’s involvement is a single study visit (for one MRI scan and additional investigations). The maximum involvement for a participant is 36 months (4 scans separated by 12 months). Participants will be informed prior to consenting what exact number of scans, and therefore what duration of involvement they are invited to. Validating cardiovascular magnetic resonance imaging (MRI) sequences in healthy volunteers and patient cohorts by demonstrating their reproducibility and sensitivity, using this information for sample size calculations for future studies, and assessing their associations with the clinical parameters (determined by blood sampling; 6-minute walk test; QoL questionnaires) or traditional imaging parameters (by echocardiography). New scan sequences are continually being developed for MRI scanning (for example, shortening the time required for a scan), and existing scan sequences are re-applied to different patient cohorts (for example, by establishing expected ranges for individuals with specific conditions). Using the combination of investigations described above, the MCMR study will be able to evaluate existing scan sequences in new cohorts, as well as test new scan sequences.