NIHRDataInsights/HRCSData huggingface dataset:
Title: The clinical and cost effectiveness of lead-I electrocardiogram (ECG) devices for detecting atrial fibrillation using single-time point testing in primary care
Funder: Department of Health and Social Care

Abstract: The aim of this assessment is to evaluate whether the use of lead-I electrocardiogram (ECG) devices to detect atrial fibrillation (AF) in people presenting to primary care with signs or symptoms of the condition and who have an irregular pulse represents a cost effective use of NHS resources compared with manual pulse palpation followed by a 12-lead ECG in primary or secondary care prior to initiation of anticoagulation therapy.

Lay abstract: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia (abnormal heart rate). People with AF are more likely to have a serious stroke or die compared with people without the condition. Many people go to their general practitioner (GP) with signs and symptoms commonly associated with AF such as feeling dizzy, being short of breath, feeling tired and having heart palpitations. At the moment, GPs check for AF by taking the patient’s pulse by hand. If the GP thinks the patient might have AF, the patient is referred for a 12-lead electrocardiogram (ECG). 12-lead ECGs use several pads stuck to the patient’s arms, legs and chest to measure how the heart is working. Sometimes a 12-lead ECG can be carried out in the GP practice on the same day as the original appointment. However, it may not be possible to get an appointment on the same day or the GP practice may not have its own 12-lead ECG. If the 12-lead ECG cannot be carried out on the same day, patients may have to travel to be tested and the arrhythmia may have subsided by the time the 12-lead ECG is recorded. Lead-I (i.e. one lead) ECGs can be an alternative to 12-lead ECGs for testing whether people may have AF. Lead-I ECGs are handheld devices with software that can detect AF. Testing patients using lead-I ECG devices during their GP appointment may mean that AF is detected earlier than if they were referred for 12-lead ECG. If that is the case, then using lead-I ECG devices in the GP surgery will allow people to receive treatment for their AF earlier than they do at the moment. This project will review the existing scientific evidence and will assess the cost effectiveness (costs and benefits) associated with the use of lead-I ECGs to detect AF in people going to their GP with signs and symptoms of AF.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR
Title: Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction
Funder: Department of Health and Social Care

Abstract: Heart failure affects ~ 900,000 people in the UK with incidence greater than 10% in those over 70 years (Petersen 2002, Mosterd 2007). The proportion of heart failure patients with preserved ejection fraction (HFpEF) is increasing with outcomes similar to those with reduced ejection fraction (HFrEF) (Owan 2006). Patients with HFpEF have frequently been excluded from heart failure trials and consequently there is relative lack of evidence to guide treatment (McMurray et al 2012). Beta blockade and renin-angiotensin-aldosterone system (RAAS) inhibition are well established to reduce mortality and morbidity HFrEF but not in HFpEF (McMurray 2012). Five randomised controlled trials (PEP-CHF n=850, CHARM-Preserved n=3020, I-PRESERVE n=4128, TOPCAT =3445, Aldo-DHF n=422) have investigated the efficacy of RAAS inhibition in HFpEF yet no single study has provided conclusive evidence for benefit (Pellicori 2014). Despite the lack of randomised evidence for benefit, HFpEF patients are often treated with RAAS inhibitors and beta-blockers (Lund 2012, Patel 2013). Guidelines offer no treatment recommendations for HFpEF beyond management of co-morbidity and NICE highlights an evidence synthesis as a research priority (NICE 2012). A sub-group analysis for the newly defined heart failure with mid-range ejection fraction (HFmrEF) will also be included in this review (Ponikowski 2016).


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: 'Mediterranean' dietary pattern for the primary prevention of cardiovascular disease, to change title due to expanded scope to 'Mediterranean' dietary pattern for the prevention and management of cardiovascular disease
Funder: Department of Health and Social Care

Abstract: In the UK over 7 million people currently live with CVD and CVD accounts for 26% of all deaths1. The original review has been cited in guidelines in the UK and US2. It formed one of 20 new reviews undertaken as part of a successful NIHR Cochrane Programme grant. The scope was therefore necessarily focused particularly with regard to the participants and comparison groups so the reviews were manageable. We intend to update this review and expand its scope so the findings are of use to a broader audience and explore heterogeneity further with an increased number of included studies. We will include participants with established CVD where evidence is currently limited, as well as those at risk. We will also consider any control group and stratify results based on this. We excluded many trials from the original review, notably a large primary prevention trial (PREDIMED, n=7447), and a recent updated search has identified 7591 citations to screen. We will collate all of this evidence, together with studies in participants with established CVD to produce a comprehensive review of the interventions in those at risk of and with established CVD to inform guidelines of both prevention and management of CVD.

Lay abstract: In the UK over 7 million people currently live with CVD and CVD accounts for 26% of all deaths1. The original review has been cited in guidelines in the UK and US2. It formed one of 20 new reviews undertaken as part of a successful NIHR Cochrane Programme grant. The scope was therefore necessarily focused particularly with regard to the participants and comparison groups so the reviews were manageable. We intend to update this review and expand its scope so the findings are of use to a broader audience and explore heterogeneity further with an increased number of included studies. We will include participants with established CVD where evidence is currently limited, as well as those at risk. We will also consider any control group and stratify results based on this. We excluded many trials from the original review, notably a large primary prevention trial (PREDIMED, n=7447), and a recent updated search has identified 7591 citations to screen. We will collate all of this evidence, together with studies in participants with established CVD to produce a comprehensive review of the interventions in those at risk of and with established CVD to inform guidelines of both prevention and management of CVD.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;6.7 PHYSICAL;7.1 INDIVIDUAL CARE NEEDS
Health categories: CARDIOVASCULAR
Title: Exercise-based cardiac rehabilitation for patients with stable angina
Funder: Department of Health and Social Care

Abstract: There is inconsistency in guideline and policy recommendations for the use of cardiac rehabilitation (CR) programs for stable angina patients. American College of Cardiology/American Heart Association (Fihn 2012) and European Society of Cardiology guidelines (Montalescot 2013) recommend CR for cardiac patients, including patients with stable angina. The 2017 British Association for Cardiovascular Prevention and Rehabilitation (BACPR) guidelines, recommend CR for people with established forms of cardiovascular disease, including stable angina (BACPR 2012). However, the National Institute for Health and Care Excellence (NICE) do not recommend CR in their clinical guidelines for the management of stable angina (CG126). In order to inform future national and international guidelines, we plan to undertake a new Cochrane Systematic Review to assess the impact of cardiac rehabilitation for this population. Number of patients affected: 1 in 12 men and 1 in 30 women (aged 55 – 64 yrs) have angina in England. This figure rises to 1 in 7 men and 1 in 12 women over 65 yrs. Degree of uncertainty: outlined above. Identified policy need: outlined above. Number and size of studies likely to be considered: Scoping searches confirm no existing systematic review assessing impact of CR instable angina patients and identified 6 relevant RCTs.

Lay abstract: There is inconsistency in guideline and policy recommendations for the use of cardiac rehabilitation (CR) programs for stable angina patients. American College of Cardiology/American Heart Association (Fihn 2012) and European Society of Cardiology guidelines (Montalescot 2013) recommend CR for cardiac patients, including patients with stable angina. The 2017 British Association for Cardiovascular Prevention and Rehabilitation (BACPR) guidelines, recommend CR for people with established forms of cardiovascular disease, including stable angina (BACPR 2012). However, the National Institute for Health and Care Excellence (NICE) do not recommend CR in their clinical guidelines for the management of stable angina (CG126). In order to inform future national and international guidelines, we plan to undertake a new Cochrane Systematic Review to assess the impact of cardiac rehabilitation for this population. Number of patients affected: 1 in 12 men and 1 in 30 women (aged 55 – 64 yrs) have angina in England. This figure rises to 1 in 7 men and 1 in 12 women over 65 yrs. Degree of uncertainty: outlined above. Identified policy need: outlined above. Number and size of studies likely to be considered: Scoping searches confirm no existing systematic review assessing impact of CR instable angina patients and identified 6 relevant RCTs.

Research activity codes: 6.7 PHYSICAL
Health categories: CARDIOVASCULAR
Title: Gene therapy for peripheral arterial disease
Funder: Department of Health and Social Care

Abstract: The burden of peripheral arterial disease (PAD) is increasing due to rising prevalence of diabetes and ageing population. About 20% of the UK population aged 55–75 years have evidence of lower-limb PAD, with 5% showing symptoms. Management involves exercise therapy, medical therapy for risk factor modification, pain relief, and surgery to relieve vascular obstruction. Because of co-morbidities and complex vascular anatomy many cases are not amenable to these interventions resulting in lower-limb amputations due to ulcers and infections. Gene therapy represents a new approach for PAD management. Gene therapy involves the transfer of genetic material into cells which initiate development of new blood vessels and restore the structure and function of affected areas, leading to improved blood flow and relief of symptoms negating the need for amputations and improve quality of life. The 2007 TASC-II guidelines concluded that gene therapy in PAD patients has shown promising results but further trials are warranted. A 2009 meta-analysis reported gene therapy for PAD management is safe and feasible, with some evidence of clinical improvement. However, since then studies have shown inconsistent results. A high-quality systematic review will identify whether investment in new trials is justified and if so, how to focus research.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: CARDIOVASCULAR
Title: Post-mortem computed tomography angiography (PMCTA) of the coronary arteries. Advancing knowledge of the diagnosis and interpretive significance of coronary artery stenosis in the living and the dead.
Funder: Health Education England

Abstract: The objective is to improve the ability of PMCT angiography to assess coronary artery stenoses by using state-of-the-art clinical systems. The study will use ex-vivo human heart as a model to develop and optimise techniques, including pressure wire measurements and optical coherence tomography. The findings will be translated to in-vivo work developing a straightforward protocol to assess the presence AND significance of stenoses.The immediate benefit is to reduce the number of cases that need autopsy after PMCT, to provide cause of death. The human heart model will also allow clinical research that would otherwise be performed in animal models.

Lay abstract: The objective is to improve the ability of PMCT angiography to assess coronary artery stenoses by using state-of-the-art clinical systems. The study will use ex-vivo human heart as a model to develop and optimise techniques, including pressure wire measurements and optical coherence tomography. The findings will be translated to in-vivo work developing a straightforward protocol to assess the presence AND significance of stenoses.The immediate benefit is to reduce the number of cases that need autopsy after PMCT, to provide cause of death. The human heart model will also allow clinical research that would otherwise be performed in animal models.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Investigating the sources of variation in outcomes from Out of Hospital Cardiac Arrest
Funder: Health Education England

Abstract: Reducing premature mortality is a key objective for the NHS. Cardiac arrest affects approximately 60,000 people each year in the UK; with a 5% survival rate it is a key target for improving health outcomes. To properly evaluate public health interventions (e.g. community CPR programmes), and NHS quality improvement initiatives, accurate data on patient outcomes are required. This PhD will define reliable, feasible and consistent methods for identifying cardiac arrest cases and for monitoring long term outcomes. The output will strengthen the use of the NHS Quality Indicators and Cardiac Arrest Registry to drive improvement in patient care and outcomes.

Lay abstract: Reducing premature mortality is a key objective for the NHS. Cardiac arrest affects approximately 60,000 people each year in the UK; with a 5% survival rate it is a key target for improving health outcomes. To properly evaluate public health interventions (e.g. community CPR programmes), and NHS quality improvement initiatives, accurate data on patient outcomes are required. This PhD will define reliable, feasible and consistent methods for identifying cardiac arrest cases and for monitoring long term outcomes. The output will strengthen the use of the NHS Quality Indicators and Cardiac Arrest Registry to drive improvement in patient care and outcomes.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Shared decision making for cardiovascular conditions: How can shared decision making for patients with hypertension and chronic heart failure be supported?
Funder: Department of Health and Social Care

Abstract: Shared decision making, where patients and health professionals both contribute to the decision making around treatment of a health condition, is essential for good clinical care but is difficult to achieve. This research aims to determine how best to implement shared decision making in primary care for two common problems: high blood pressure and heart failure. First, I will review, summarise and synthesise the available research evidence. Secondly, we will interview health professionals and patients and observe consultations to identify current practice and opportunities for improvement. These data will be combined to develop an intervention for future evaluation.

Lay abstract: Shared decision making, where patients and health professionals both contribute to the decision making around treatment of a health condition, is essential for good clinical care but is difficult to achieve. This research aims to determine how best to implement shared decision making in primary care for two common problems: high blood pressure and heart failure. First, I will review, summarise and synthesise the available research evidence. Secondly, we will interview health professionals and patients and observe consultations to identify current practice and opportunities for improvement. These data will be combined to develop an intervention for future evaluation.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CARDIOVASCULAR
Title: Magnetic resonance Guided Ablation System for Treatment of ventricular Tachycardia (MR-GAST-VT)
Funder: Department of Health and Social Care

Abstract: A child is born with CF every day in the UK. The median age at death is ~29 years (CF Trust Registry, 2013). People with CF typically suffer from repeated bacterial infections of the conducting airways leading to lung failure. Almost all current treatments provide only symptomatic relief and require hours of selfadministered therapy daily. NHS costs per patient range from £15-£50K per year, with an annual direct healthcare cost of ~£300M. Novel small molecules targeting CFTR, such as ivacaftor and lumacaftor (Vertex Pharmaceuticals), can significantly improve lung function, but only in patients with certain genotypes. To address the broader unmet need through gene therapy, we have developed vGM058, a nebulisable SIVbased lentiviral vector expressing CFTR which has been pseudotyped to promote high-efficiency uptake by airway epithelial cells. Following extensive preclinical studies on the vector backbone, we are ready to (i) transfer cGMP production to a CMO; (ii) carry out an MHRA-compliant murine toxicology study; and (iii) conduct a first-in-human Phase 1 trial in which escalating doses of vGM058 will be delivered to the nasal epithelium. An efficient gene therapeutic for CF would have a significant impact on patients' health and therefore reduce the economic burden of routine CF care.

Lay abstract: A child is born with CF every day in the UK. The median age at death is ~29 years (CF Trust Registry, 2013). People with CF typically suffer from repeated bacterial infections of the conducting airways leading to lung failure. Almost all current treatments provide only symptomatic relief and require hours of selfadministered therapy daily. NHS costs per patient range from &pound;15-&pound;50K per year, with an annual direct healthcare cost of ~&pound;300M. Novel small molecules targeting CFTR, such as ivacaftor and lumacaftor (Vertex Pharmaceuticals), can significantly improve lung function, but only in patients with certain genotypes. To address the broader unmet need through gene therapy, we have developed vGM058, a nebulisable SIVbased lentiviral vector expressing CFTR which has been pseudotyped to promote high-efficiency uptake by airway epithelial cells. Following extensive preclinical studies on the vector backbone, we are ready to (i) transfer cGMP production to a CMO; (ii) carry out an MHRA-compliant murine toxicology study; and (iii) conduct a first-in-human Phase 1 trial in which escalating doses of vGM058 will be delivered to the nasal epithelium. An efficient gene therapeutic for CF would have a significant impact on patients' health and therefore reduce the economic burden of routine CF care.

Research activity codes: 5.3 MEDICAL DEVICES;6.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR
Title: Comprehensive molecular diagnostics for inherited cardiac disease
Funder: Department of Health and Social Care

Abstract: Some diseases of the heart and arteries run in families and can cause sudden death or heart failure. In the UK it is estimated that up to 10 children a week die from these diseases that also affect people of all ages. Although we know a lot about the genes that cause these diseases and healthcare experts around the world advise that genetic test should be used routinely to guide healthcare decisions, they are in fact used rarely and inequitably. In this project we will use cutting edge sequencing technology to test all the known genes that cause these diseases in a single test that can be used around the UK. The test will be quick, affordable and widely available and will change the way we treat patients and their families.

Lay abstract: Some diseases of the heart and arteries run in families and can cause sudden death or heart failure. In the UK it is estimated that up to 10 children a week die from these diseases that also affect people of all ages. Although we know a lot about the genes that cause these diseases and healthcare experts around the world advise that genetic test should be used routinely to guide healthcare decisions, they are in fact used rarely and inequitably. In this project we will use cutting edge sequencing technology to test all the known genes that cause these diseases in a single test that can be used around the UK. The test will be quick, affordable and widely available and will change the way we treat patients and their families.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Cardiovascular Disease
Funder: Department of Health and Social Care

Abstract: We aim to develop interventions for adults and children to prevent or treat short term complications and enhance longevity of coronary grafts and cardiac prostheses, by exploiting our world-leading strengths in cardiac surgery and discovery science (myocardial physiology, regenerative medicine; genomics, metabolomics and proteomics) to identify and probe mechanisms and design interventions to target them. Short term S1. Trial early haemofiltration in adults and per-operative sildenafil in children (workstream 2 (WS2)). S2. Identify protein and genotypic biomarkers that predict bleeding (WS1) and acute kidney injury (AKI; WS2); validate microemboli in the cerebral circulation by retinal angiography and cerebral diffusion-weighted MRI (WS3). S3. Characterise the HPA-axis in children (WS4); seeding patches with stem cells (WS5); cohort data collection for cardiac patients (WS6). S4. Translate novel platelet function analyser to clinical evaluation and commercial exploitation (WS1). Medium term M1. Optimize tranexamic acid dose (WS1), HPA-axis maturation and the response to surgery in children (WS4). M2. Trial strategies to reduce microemboli in CABG, AVR, TAVI patients (WS3). M3. Produce bioengineered grafts to GMP standards (WS5). M4. Establish proof-of-principle of deep phenotyping of patient cohorts to elucidate mechanisms underlying complications (WS6). Long term L1. Trial optimal tranexamic acid strategy (WS1), embolic protection of the brain using protection devices (WS3) and bioengineered conduits (WS5). L2. Evaluate accuracy of biomarkers to predict bleeding (WS1) and implement AKI biomarkers (WS2). L3. Identify targets to prevent modification of HPA-axis after surgery (WS4). L4. Evaluate mechanisms underlying complications in large cohorts and describe targets for novel therapies (WS6).


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CARDIOVASCULAR