Clinical trials

This study aims to evaluate a clinical tool called the Breathing Pattern Assessment Tool (BPAT), which is used by physiotherapists to assess breathing pattern disorder (BPD). BPD is a condition where breathing is inefficient or out of sync with the body's needs, leading to symptoms such as breathlessness. The study will investigate whether the BPAT is a reliable and accurate way to identify and assess BPD, and whether it can be used to monitor changes over time, particularly following physiotherapy treatment. It will also compare BPAT scores with other commonly used questionnaires that measure breathlessness and breathing symptoms. Participants will include patients with BPD, patients with asthma, and healthy individuals. Patients with BPD will attend physiotherapy sessions as part of their usual care, during which their breathing will be assessed using the BPAT at different time points, including before and after treatment. Healthy participants will attend a single assessment visit, and asthma participants' data will be collected from routine clinical care. The study will also explore whether BPAT scores change following treatment and whether these changes reflect improvements reported by patients and clinicians. In addition, a small number of patients and physiotherapists will be invited to take part in interviews to share their experiences of the assessment process and treatment. This will help understand whether the BPAT is acceptable and useful in clinical practice. Overall, this study aims to improve how breathing pattern disorder is assessed and monitored, which may help guide better treatment for patients in the future.

The specific aim of this study is to try to discover the diagnostic accuracy of SleepImage technology for detecting respiratory failure in patients with MND. Importantly, this research project is not about NIV, it is about what method can most efficiently decide when to start NIV. To do this we'd like to collect data about you and your breathing from the SleepImage device when you come in for your routine overnight sleep study. We will compare this against the data that we would collect anyway.

Sarcoidosis is an inflammatory condition affecting many different parts of the body but most commonly the lungs. It is not known what causes sarcoidosis. In some patients no treatment is needed but in other patients long term treatment may be required. One of the main medications used to manage this condition is corticosteroids. This medication has been shown to be very effective at reducing inflammation in this condition and many patients often remain on it for months to years. Unfortunately, there are many negative long-term side effects of corticosteroid use. This includes an increased risk of developing diabetes, reduced bone density, weight gain, high blood pressure and low muscle mass. Currently there are no guidelines for how steroids should be weaned in patients who have stable sarcoidosis. The investigators aim to undertake a study at the Royal Brompton Hospital which will be assessing two different steroid tapering regimens which will be allocated to participants in a randomised manner. This will be the first study to directly evaluate different steroid weaning regimens in sarcoidosis patients. The main aim of this study is to determine how many participants can reduce their prednisolone dose to less than 50% from their baseline dose. Additionally, the investigators will be recording how many participants require an increase in dose or an additional medication whilst on the prednisolone weaning regimen. The investigators will also see the tolerability of steroid withdrawal and assess for any symptoms of steroid withdrawal. In a small subset of participants the investigators will assess for any changes in body composition and muscle strength using bioelectrical impedance analysis and isometric muscle testing.

Sometimes it is very difficult to tell if someone has cystic fibrosis (CF), especially when they have rare CF genes. Without this certainty, they are unlikely to get the correct treatment so their health may be affected. More accurate ways to test for CF are therefore needed in this situation. The aim of this study is to develop a more accurate test using what are called "organoids" or "mini organs." Organoids are grown in the laboratory from a small piece of gut tissue. As they have the person's exact genes, they can show if the CF gene ("CFTR") is working correctly or not and thus if the person has CF. The investigators will compare the organoid response with the current more established tests, such as the sweat test and CF genetics, and other recognised specialist tests called nasal potential difference (NPD) and intestinal current measurement (ICM). The gut tissue is usually taken by a quick, relatively painless, outpatient procedure (rectal biopsy). The additional benefit of organoids is that they can also help us to work out the best treatment for that individual by testing how well the gut tissue responds to different drugs in the laboratory. The investigators wish to carry out this research to prove that gut organoids are a better way to test for CF in this situation. The goal will be to diagnose people faster and for them to get better treatment quicker, both key for leading a longer and healthier life.

200,000 adults are admitted to intensive care in the UK each year. Many of these patients need help with their breathing and are put on a machine called a ventilator. Research shows that many patients using a ventilator quickly develop weakness in their main breathing muscle, called the diaphragm. This weakness can cause a longer time on the ventilator, a longer hospital stay, and higher chances of health problems or death. Inspiratory muscle training is a breathing exercise where the patient breathes against resistance through a small device (like breathing through a straw). It aims to improve the strength of the diaphragm and reduce how long patients are on the ventilator. Why is this research needed? Research shows that current breathing exercise programmes do not help patients come off the ventilator or go home quicker. This may be because these breathing exercises strengthen the wrong muscles (those in the chest and neck, that are not efficient). These exercises can also be distressing for patients. What will be done in this research? This research aims to develop a breathing exercise programme that focusses on strengthening the diaphragm. We will also make sure patients do not find the breathing exercise too distressing. This research will measure how the breathing muscles respond to four different levels of breathing exercise and ask patients to feedback on each level. 1. At each breathing exercise level, the effort of the breathing muscles will be measured using a small tube inserted into the nostril and small sticky patches on the chest and neck. We aim to find the level where the diaphragm is being pushed to work hard but other muscles in the chest and neck are not. 2. After each breathing exercise level patients will be asked how they found it - for example, easy, pleasant, scary. This procedure will be repeated 1-3 times over seven days with at least 24 hours between each measurement

To assess the impact on body mass composition from anti-fibrotic medications used in fibrotic lung disease by using BIA and muscle ultrasound

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia affecting over one million people in the UK. It is associated with increased cardiovascular morbidity and mortality and costs the NHS between £1.4 billion and 2.5 billion annually. Current methods to detect AF include opportunistic pulse palpation, single time point 12-lead electrocardiograms (ECGs), ambulatory Holter monitoring, and implantable loop recorders (ILRs). The more widely used intermittent monitoring methods, such as ECGs and Holter monitoring, are limited in terms of duration and have lower detection yields of atrial arrhythmias. At the other end of the spectrum, the ILR can give continuous and accurate arrhythmia detection but is invasive and requires specialist expertise to implant, monitor, and analyse. In recent years, the use of wearable mobile health (mHealth) devices has emerged as a direct-to-consumer option for monitoring parameters such as heart rate and activity levels. From a clinical perspective they potentially offer a less invasive and cost-effective investigative approach, with remote monitoring solutions to possibly predict and detect AF. This technology has significant potential in terms of passive, non-invasive and continuous monitoring to aid the early diagnosis and management of AF. The original REMOTE-AF study (NCT05037136) developed novel methodology to detect AF using PPG-dervived data from a wearable. This study will further enhance this foundational work by recruiting patients to develop a AI-enabled, multi-parametric algorithm using PPG-derived data to detect AF.

In this study, investigators aim to study in detail the physical (including nutritional and pulmonary) and mental health of females with cystic fibrosis (CF) planning a pregnancy, during pregnancy, and in the early parenthood period. Additionally the health of offspring in infancy and early life will be studied to understand if further screening investigations or clinical care models should be part of clinical guidelines

This observational study will follow patients requiring implantation of leadless pacemaker for 5 years after implantation. The main goal is to evaluate the long term safety and efficacy of AVEIR™ leadless pacemaker device in the usual clinical settings within the UK National Health Service. In addition, the study will collect data to understand patient characteristics receiving this type of pacemaker.

The goal of this observational study is to evaluate exercise testing and daily physical activity in children and adolescents who are diagnosed with an inherited arrhythmia. The main question it aims to answer is: Does maximum heart rate during controlled exercise tolerance testing accurately reflect maximum heart rate and peak exercise levels during free living daily physical activity in children and adolescents diagnosed with an inherited arrhythmia? Participants will: * Complete routine exercise tolerance testing * Record daily physical activity and exercise over two weeks, while wearing an activity and heart rate monitor and digit diary. * Complete a physical activity questionnaire at the end of two weeks.

Acorai is developing the Acorai Heart Monitor, a handheld electronic device for monitoring pressures inside the heart in a non-invasive manner, by placing the device on the chest of a patient. Currently these intracardiac pressures are measured in an invasive way, during a right heart catheterisation procedure. This procedure carries risks to the patient. There is a clinical need for a non -invasive, easy to use, tool to monitor patients that suffer from heart failure. The study aim is to use the Acorai device to collect the intracardiac pressure measurements from patients admitted to hospital with heart failure and who are awaiting discharge home. Using the data, we will assess the feasibility of the Acorai derived cardiac output measurements, and assess what data best predicts survival, death, or major adverse cardiac events (MACE)

A heart attack (myocardial infarction) occurs when an artery supplying blood to the heart is suddenly blocked resulting in damage to the heart muscle. Patients presenting to hospital with a heart attack undergo an immediate angiogram (x-ray of the arteries in the heart) and are usually treated immediately with a balloon and stent to open their blocked artery. This procedure is called "primary percutaneous coronary intervention" (or primary PCI for short). An angiogram is a routine procedure that involves insertion of fine plastic tube (catheter) into either the groin or wrist under local anaesthetic. The tube is passed into the artery in the heart and X-ray pictures are taken to find out if the arteries are blocked. Blocked arteries can usually be opened by passing a small balloon into the artery, via the fine plastic tube followed by placement of a stent (a fine metal coil) into the artery to prevent it from blocking again. Although this treatment is very successful, it can result in damage to the heart muscle when the artery is opened. Cooling the entire body has been shown to reduce heart muscle damage during heart attacks in some patients but not in others; however, it is uncomfortable due to the shivering, expensive and can result in delays in opening the blocked artery. The investigators are conducting a series of research studies to find out if cooling the heart muscle directly through the catheter being used for the normal primary angioplasty treatment using room temperature may be effective in preserving heart muscle, without the shortcomings of entire body cooling. The investigators have already published an initial series of ten cases in which this treatment appeared to be feasible without causing significant clinical problems. The present study is a pilot study designed to assess the rate of patient recruitment and feasibility of this new treatment while exploring some detailed outcomes measuring the restoration of blood flow within the coronary artery at the end of the procedure. Ultimately if the present pilot study is successful, the investigators plan to go on to undertake a much larger randomised outcome study to determine definitively whether this treatment can help reduce heart attack size.

In spite of recent initiatives, in particular, the introduction into clinical practice of donation after circulatory death (DCD), there is a persistent mismatch between the demand for donor hearts for transplantation and their supply \[1\]. This mismatch is accentuated by the relatively low rate of utilisation of hearts donated for transplantation, i.e. the proportion of organs transplanted divided by the number of donations. In the UK between 2016 and 2018 this ranged from 25.7 to 30.8% \[2\]. For the year 2022/23, a total of 207 heart transplants (DBD and DCD) were performed out of 1429 donations giving a utilisation rate of 14.5% \[3\]. The rigorous assessment of donor heart quality prior to, and during donor organ retrieval, which is a crucial determinant of recipient outcome, accounts for the low utilisation rate. In both the donation after brain(stem) death (DBD) and DCD settings, pre-retrieval echocardiography is the principal method of anatomical and functional assessment. In the DCD setting, where normothermic organ perfusion (either in situ or ex situ) is mandatory to restore myocardial function, additional functional and biochemical assessments are available. In addition to recipient risk factors, donor age and comorbidity burden continue to limit the applicability and effectiveness of heart transplantation. Older donors are both associated with an increased comorbidity burden and prevalence of coronary artery disease (CAD). Donor-transmitted CAD is of particular concern due to the significant association with early graft dysfunction when multi-vessel disease is present \[4,5\]. Guidelines recommend that donor hearts with obstructive CAD in any major coronary artery be declined for transplantation \[4\]. However, there is evidence that single vessel CAD neither alters short- nor long term recipient prognosis \[6\]. The short and long term risks to the recipient of donor heart CAD needs to be carefully evaluated in relation to the risk of a transplant candidate remaining on the waiting list \[7,8\]. None of the methods currently available in the UK for the assessment of potential heart donors allows adequate characterisation of coronary artery disease (CAD). Instead, retrieval surgeons place a heavy reliance on an indirect assessment of CAD, i.e. direct visualisation and palpation of the large epicardial coronary arteries with the aim of identifying occlusive lesions. The discovery of such lesions is the justification for declining a donor organ otherwise deemed to be suitable for transplantation. In other countries, access to coronary artery imaging prior to heart donation is an established option, where indicated. Indeed, the Association of Organ Procurement Organizations Consensus Statement, supported by the Society of Critical Care Medicine and the American College of Chest Physicians recommends coronary angiography in all older donors (\>40 years) and in younger patients with risk factors for CAD. In the proposed study we seek to perform coronary angiography at Harefield Hospital on donated hearts where our retrieval team has declined the organ solely on the grounds of visible/palpable CAD. In so doing we aim to better understand the diagnostic utility of the assessment method. An internal audit of heart retrieval has revealed that of the donated hearts offered to Harefield since 2020 between 8 to 13 are declined per annum on the grounds of visible/palpable coronary artery disease, i.e. approx. 10 per annum. Assuming a study enrolment rate of 1:3 of donated hearts with CAD identified at the time of retrieval, we therefore anticipate that this study will take 36 months to complete. This investigation forms part of a broader research/service improvement initiative which aims to not only enhance the assessment of CAD in potential donors but also to better understand the pathogenesis of CAD in heart transplant recipients. The ultimate goals are to reduce the risks associated with transplantation and increasing donor organ availability. We propose to initiate this investigation as a single centre study but would welcome the participation of other UK centres who would like to collaborate. We believe this research initiative is well aligned with the strategic objectives of the NHS BT Business Plan 2022-23 \[9\]. 1. Hsich E. Circ. Heart. Fail. 2016 Apr. 9(4) e002679. 2. Rushton and Hogg March 2019 NHSBT/CAG, CHARH(19)25. 3. NHS-BT Annual Activity Report:Section 7, Cardiothoracic activity. 2022-23. 4. Ivanes F et al. Int J Cardiol. 2019 277;71-8. 5. Kotloff RM et al. Crit Care med. 2015;43:1291-325. 6. Dorent et al. Arch. Cardiovasc. Dis. 2018;111:126-39. 7. Kilic A et al. J Thorac Dis. 2014;6:1097-104. 8. Estevz-Loureiro R et al. Transplant. Proc. 2010;42:2987-91. 9. NHS BT Business Plan 2022-23, July 2022.

This pilot study aims to assess whether 18F-FDG PET CT imaging has the potential in diagnosing cardiac rejection. The investigators aim to recruit 20 heart transplant subjects within two groups of 10 subjects each. One group will have participants with definite rejection and the other group will have participants with definite no rejection. Subjects will be placed into study groups based on their heart muscle biopsy, echocardiogram, clinical symptoms, ECG, and presence or absence of donor specific antibodies. Each group will then undertake a 18F-FDG PET CT scan to identify whether this imaging modality has a role in identifying cardiac rejection. The study subjects and the research team will be blinded to the results of the PET CT until the end of the study.

In this project the investigator's plan to collect blood during a patient's routine angiogram procedure which they will have due to having suffered a heart attack. Data from the patients' routine procedures for this condition, including but not exclusively, ECG, Echocardiogram, MRI scans, will be collected. The aim of the research project is to analyse the blood samples and identify novel biomarkers and clinical parameters associated with acute coronary syndromes. The investigator's will particularly focus on markers of inflammation and micro-organism activity. The investigator's hope that this will help to gain more knowledge about what causes heart disease and how various conditions can be treated more efficiently. The investigator's will follow-up and collect further research data via a questionnaire at the routine 6 weeks and 6 months follow-up appointment after the angiogram procedure. Participants will also be telephoned at one-year post procedure, to update any events and medication status and data will thereafter be collected form data held by the hospital without having to contact the participant. Remaining blood samples will be stored securely for further analysis into blood and other markers.