Investigators: Prof James Moon, Dr Saidi Mohiddin, Dr Luis Lopes, Dr Konstantinos Moschonas.
We would like to kindly invite you to take part in our research study. Before you decide you need to understand why the research is being done and what it would involve for you. Please take time to read the following information carefully. Ask us if there is anything that is not clear or if you would like more information. Take time to decide whether or not you wish to take part.
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Summary of the research
Our research focuses on Apical Hypertrophic Cardiomyopathy (ApHCM). As you may know, this is a common inherited cardiac condition with thickening of the heart muscle at the bottom tip, or apex. Our research group has recently discovered that people with ApHCM have low blood flow to the apex (Figure 1). In fact, you may have taken part yourself in that research project.
This research study aims to understand why that happens and whether we can restore blood flow. This may lead to new treatments for individuals with ApHCM.
To do this, we would like to scan individuals with ApHCM with an MRI scan of the heart (also known as Cardiac Magnetic Resonance, CMR), an ultrasound scan of the heart (aka echocardiogram) and take some blood tests.
The study is divided in three parts. You do not have to participate in all three parts.
Part 1 involves having two CMR scans stressing the heart in different ways each time. In the first scan, we will use adenosine, a very commonly used medication, and on the second scan we would ask you to exercise on a stepper (similar to the one found in gyms). This will help us understand more about the low blood flow to the apex.
Part 2 involves having a CMR and an echocardiogram, then changing your medication for one to two week and repeating the CMR and echocardiogram. This will help us research if we can alter/restore blood flow to the apex with medication.
Part 3 is only for participants who took part in our initial research study and involves having one CMR and an echocardiogram. Having another scan will give us insight on how ApHCM changes over time.
You are free to choose in how many parts of the study you wish to take part. If you are still interested, you will find more information below and a detailed description of what it means to take part. Use the table of contents on the right side of the page to navigate more easily.
The 3 parts of the research study
To understand more about the low blood flow to the apex, we would like to tackle the problem in three parts:
Part 1 - Exercise
The low blood flow abnormality was observed when the heart was stressed with adenosine, a very commonly used medication. To understand more about this, we would like to stress the heart in a more natural way, without medications, by asking you to do some exercise.
Unfortunately, there are many limitations on what type of exercise can be done when inside a CMR scanner, for technical and safety reasons. We use a stepper, similar to the one you may have seen in the gym, which you operate while laying on the CMR table.
In this part of the study, we would invite you to have two CMR scans, one using adenosine and one using exercise as a way to stress your heart. Whenever possible, we will try to book both scans on the same day. However, exercise CMR scans have a lot of equipment to prepare and we can do them more easily at the end business hours.
If the low blood flow is also present during exercise and not just with adenosine, it implies that it is a more real problem of individuals with ApHCM and not just the side effect of medication.
Part 2 - Medication
In our experience, about 50% of individuals with ApHCM receive medication which may already influence this blood flow to the heart, but the evidence is weak. Specifically, we are interested in beta-blockers, such as bisoprolol, or calcium channel blockers, such as verapamil. Part 2 of the study aims to measure the effect of this medication to the blood flow.
If you are already taking bisoprolol or verapamil, we would invite you to have a CMR and an echocardiogram and then ask you to defer/stop the medication for one week, enough time for it to washout from your body. We will then like to repeat the CMR and echocardiogram and compare the results. In the end, you restart the medication.
If you are not taking any of the above medications, we would invite you to have a CMR and an echocardiogram and then assign you either bisoprolol or verapamil to take for one week. During that week, we would like to call you over the phone every other day, check how you are, check your heart rate and blood pressure (BP), and increase the dose as much as possible without causing side effects. We will then like to repeat the CMR and echocardiogram and compare the results. In the end, you can stop the medication.
We will cover the cost of the prescription for the week you will be taking part in the study.
We may also like to take some blood tests at the time of the scans.
Part 3 - Follow-up
If you took part in the initial research study, you would have had a CMR and an echocardiogram between 2017 and 2021. We would like to repeat a detailed, research CMR and an echocardiogram now to compare how ApHCM changes over time. This will allow us to compare the disease process 4.5 years later.
As mentioned above, you are free to choose in how many parts of the study you wish to take part. You will notice that all three parts of the study start with an adenosine CMR. This means that if you choose to participate in all three parts you will only have three CMR scans and two echocardiograms in total.
Cardiac Magnetic Resonance
You may already be familiar with CMR. The experience of undergoing a research CMR scan in this study is similar to having one as part of your clinical care.
CMR is very safe. It uses a magnet and radio-waves to create detailed images of your heart. It does not emit ionising radiation (see What are the risks of taking part?) We can assess the heart’s size, strength, blood flow, and if there is any scarring.
What will happen when you come for the scan
We kindly ask you to arrive 30 min before your scan appointment to get ready. When you arrive, we will repeat the safety questionnaire (see below If you wish to participate) and a brief assessment. You will then change into a hospital gown, as it is important not to bring any metal object into the scanner room, such as jewelry or belt buckles). A small cannula will be inserted into a vein by a qualified professional to collect the blood sample and be able to give adenosine and the contrast agent during the scan.
The contrast agent is called Gadolinium and is widely used in medicine. Side effects are very rare, in fewer than 1/100 people it can cause some mild headache and nausea.
The scan can take up to one hour. It involves lying on your back insider a large, open-ended tube (the magnet). We will attach a heart trace monitor and an antenna cover on your chest. During the scan, you will be asked to hold your breath several times for a small amount of time (between 2 to 15 seconds).
Halfway through the scan, we will give you an infusion of adenosine for about 4 minutes, to stress your heart. Adenosine in itself is very short acting, and washes out of your body within minutes of stopping the infusion, so it is very safe. However, it is not a pleasant experience. You are very likely to experience chest tightness, shortness of breath, racing heart, and feel generally uncomfortable. These are normal effects of the drug and do not mean that there is a problem. Also, they disappear immediately after stopping the infusion.
When you heart is stressed enough with adenosine, we will inject the contrast medication, take pictures of the blood flow to your heart and finish the scan within about 15 minutes.
Exercise CMR
Exercise CMR is similar to adenosine CMR, but instead of stressing your heart with adenosine we would ask you to do some exercise.
You will be attached to a stepped from the beginning of the scan. Halfway through the scan, you will start exercising to increase your heart rate. This can take longer than the 4 minutes needed with adenosine. When you heart is stressed enough, we will inject the contrast medication, take pictures of the blood flow to your heart and finish the scan within about 15 minutes.
Echocardiogram
Echocardiogram is an ultrasound scan of your heart. It does not emit ionising radiation and is risk free. It uses an ultrasound probe to take pictures and measurements of your heart from various points on your chest. Initially, during the examination, you will lay at 45 degrees on your left shoulder and later lay flat on your back.
What will happen when you come for the scan
Five minutes prior to the scan, you will be asked to change your top clothes with a hospital gown, which will open at the front but cover your upper body. You will then lay on the examination couch and a qualified professional will start the examination. They will use the ultrasound probe with some gel on your chest to take pictures and measurements of your heart from different parts. The examination lasts about 15-20 minutes and you can go home immediately after.
Practical information
Reimbursement
We will offer to reimburse your UK-based travel expenses to and from the research centre as well as your prescription for the one week you may be taking bisoprolol or verapamil.
Where will the study take place?
We have two research centres in the heart of London, both very easy to get to with public transport. Car parking is very limited around those areas and we do not recommend driving:
Do I need to fast before the scans?
No, you do not need to fast. However, we kindly ask you not to consume any caffeine up to 24 hours before the scan, as it naturally stresses your heart and may influence the results. This includes coffee, tea, energy drinks, caffeine found in some multi-vitamin, or some headache/flu tablets or sachets.
Safety & risks
What are the risks of taking part?
As mentioned above, in this study you will have CMR scans, echocardiograms, blood tests, and may be given a number of medications (adenosine, gadolinium, bisoprolol or verapamil).
CMR has no proven side effects and does not emit ionising radiation. Before each CMR, a qualified professional will guide you through a safety questionnaire to identify any potential dangers and contraindications. This is part of routine clinical practice and happens to all patients. Depending on your answers, they may need to postpone or cancel your CMR (e.g. immediately after a dental implant). Please note, we will also go through this questionnaire during our initial discussions in case you cannot have a CMR in the first place.
Echocardiography also has no side effects and does not emit ionising radiation. Individuals with mobility issues or musculoskeletal conditions may find it difficult to adopt the necessary positions. We can usually work around that, ensuring your comfort.
Adenosine is contra-indicated in the following conditions and such individuals will be excluded from the study:
An abnormally low heart rate - resting heart rate less than 40 bpm, or heart rhythm abnormality known as “second degree mobitz type 2 atriovetricular (AV) block” or “complete AV block”. All participants will have an ECG before the scan to screen for those conditions
Very low BP (systolic BP less than 90 mmHg)
Very high BP (more than 200/120 mmHg)
Asthma
Previous allergic reaction to adenosine
Gadolinium-based contrasts are the most commonly used contrast medication used in CMR and are very safe. We will use the same dose as in clinical practice (up to 2 mmol/kg). The risk of serious side effects is very low; less than 0.01%. Individuals with severe kidney disease will be excluded from the study (eGFR less than 30 mL/min/1.73m2).
Bisoprolol and verapamil are contra-indicated in the following circumstances and such individuals will be excluded from the study:
An abnormally low heart rate - resting heart rate less than 50 bpm, or heart rhythm abnormality known as “significant type 2 atriovetricular (AV) block” or “complete AV block”. All participants will have an ECG before the scan to screen for those condition.
Very low BP (systolic BP less than 90 mmHg)
Severe or acute heart failure. Those individuals will be excluded from the study.
Raynaud’s phenomenon
Severe lung disease
What happens if I do not want to carry on with the study?
You are entitled to withdraw from the study at any point. If you wish to do so, you can simply tell us and we won’t collect any more data about you (see Contact details). This includes electronic data from your file or scans.
You also have the right to decide what happens to the data we may have already collected about you by then – we could keep it and use it or disregard anything from the beginning of the study.
Please note that the CMR and echocardiograms will not be permanently deleted from your clinical records at Barts Health NHS Foundation Trust or Chenies Mews Imaging Centre. Nevertheless, it will be clearly stated on our research protocols and your clinical folder that they should not be used for research purposes. See below If you do not want to participate.
What if something goes wrong during the study?
Harm to a participant
Serious Adverse Events (SAEs) are defined as any event which requires hospitalisation or prolongation of existing inpatient hospitalisation, results in persistent or significant disability, or consists of a congenital anomaly or birth defect, is life-threatening, or results in death.
A SAE is extremely unlikely to occur in participants who undergo imaging research like this one, as we are not performing invasive procedures or surgery. Any SAE related to this research study will be reported to the Sponsor (i.e. UCL) within 5 working days by the Chief Investigator (CI).
Data breaches
Personal data breaches will be immediately reported to the UCL Information Security Group (ISG) and the UCL Data Protection Officer and Sponsor.
What if we find a new abnormality?
Any diagnostic test can potentially identify a new abnormality unintentionally. We will always inform you if that happens. Below is an outline of our method for analysing scans and ensuring any new abnormalities are dealt with appropriately.
CMR images the entire chest, lower neck, and the top part of the abdomen, such as the liver, spleen, stomach, and sometimes the kidneys. All CMRs will be analysed by the Research Fellow within close of business on the same day they were performed and by the CI within 48 hours (CHECK THIS). All echocardiograms will be analysed and reported by a professional with formal accreditation within close of business on the same day they were performed. The CI will always be notified of all incidental findings.
Findings that require emergent or urgent action will be dealth with promptly by the Research Team: escalated to the on-call team at Barts Health NHS Trust or referred urgently to the most appropriate medical team (e.g. a new lung abnormality that could be cancer will be referred to the Respiratory Team under a two-week wait cancer care pathway). The incident will be clearly documented in the participant’s medical records, and the clinical care team and GP will be notified within 24 hours.
Benefits of taking part
By participating in this research study, you will contribute to the advancement of medical knowledge regarding ApHCM and potential treatment strategies. Your participation may help improve the understanding and management of this condition in the future.
Throughout your participation, you will receive specialised medical attention from our experienced team. Your health and well-being will be closely monitored during the study, and you may gain valuable insights into your own condition.
If you are not currently on verapamil or bisoprolol and choose to participate in Part 2 of the study, you will have a chance to try these medications. If you notice an improvement in your symptoms or quality of life with the medication, you may wish to continue them long term. In that case, we will have a detailed discussion about the risks and benefits of these medication in your individual case and also communicate with your clinical team.
Privacy & Confidentiality
Will my participation in the study be confidential?
Yes, your participation will be strictly confidential. Only the clinical team and we will know that you took part in the study. All data collected during the course of the research will be kept strictly confidential at Barts Heart Centre or University College London, in a similar manner as your clinical information. Any data transferred outside the hospital or university will be first anonymised and untraceable to you. Anonymised data may be shared with our collaborators subject to Ethical approval.
The study is compliant with the requirements of General Data Protection Regulation (2016/679) and the UK Data Protection Act (2018). All investigators and study site staff will comply with the requirements of the General Data Protection Regulation (2016/679) with regards to the collection, storage, processing and disclosure of personal information, and will uphold the Act’s core principles.
What will happen to the results of the study?
To make a significant impact to the care of individuals with ApHCM, it is important to communicate research effectively. We intend to publish and disseminate the results of the study in a variety of ways, via:
Scientific publications in peer-reviewed journals
Presentations and discussions in scientific conferences
Discussing the findings with patients we encounter in our clinical practice
Websites intended for a diverse audience not limited to healthcare professionals, such as the BHF website.
Final doctoral (PhD) thesis publicly available from UCL in the end of the study.
All code for data and statistical analysis will be available publicly at a github repository. The main data-set containing your data, however, will not be available publicly in accordance with our Ethics agreement.
Can I get notified of the results of the study?
Absolutely, we would be delighted to keep you informed and updated about all our endeavours to communicate science. In your consent form, you can opt in to email updates.
Who is organising the study?
The CI of the study if Professor James Moon, Professor of Cardiology and Director of CMR at Barts Health NHS Foundation Trust. University College London (UCL) is the sponsor of the study and data controller.
The study is funded by the British Heart Foundation under grant number FS/CRTF/22/24394.
Who has reviewed the study?
This research study has been assessed by a Research Ethics Committee (REC) in conjunction with the Health Research Authority (REC number <<insert final No here>>).
How can I make a complaint?
In the first instance, we would encourage you to discuss your concerns with Dr Moschonas or the CI. If you still with to make formal complaint after that, you can contact:
UCL, research-incidents@ucl.ac.uk
The Patient Advice and Liaison Service (PALS) at Barts Health NHS Foundation Trust (02034655919, SBHpals.bartshealth@nhs.net)
What next?
Before deciding if you want to take part, take some time to think about the information provided here. Sleep it over, talk to friends, family, or anyone else whose opinion you trust.
We would love to hear from you, understand your thoughts, impressions, reservations, answer any questions you may have to the best of our abilities and help you make an informed decision.
Even if you decide not to take part, talking with you will make us better researchers and will teach us a lot about what it means to live with ApHCM. And, from our side, we love to explain to anyone what we do and what medical research is all about.
Contact details
| Research Fellow | Chief Investigator |
|---|---|
Dr Konstantinos Moschonas 07597942338 k.moschonas@nhs.net |
Prof James Moon james.moon1@nhs.net |
Cardiac Imaging department, St Bartholomew’s Hospital, West Smithfield, London, EC1A 7BE
If you wish to participate
If you wish to participate, please get in touch with Dr Moschonas on the contract details above. We would then like to arrange a time that suits you for a brief phone call to:
Answer any questions or clarifiy what will happen on the day.
Go through the MRI safety questionnaire to ensure it is safe for your to have a CMR.
Discuss the consent form
<Here> you can find the consent form. It may be useful to you even if you do not wish to take part in the study.
If you do not wish to participate
It is absolutely OK not to want to participate. In that case, please let us know and we will not disturb you any longer.
Helpful resources
If you wish to learn more, these resources may be useful to you:
Booklet with information about living with Hypertrophic Cardiomyopathy, by the British Heart Foundation.
The main scientific publication of our research group explaining the discovery that individuals with ApHCM have reduced blood flow to the apex. This is open source and freely available to all.
Patient Data and Research Leaflet, by the Health Research Authority.