NIHRDataInsights/HRCSData huggingface dataset:
Title: Increasing medication adherence among adults with atrial fibrillation: A Medical Research Council complex intervention framework development and feasibility study
Funder: Chief Scientist Office, Scotland

Abstract: Atrial fibrillation (AF) is a common abnormal heart rhythm affecting more than 1 million people in Scotland. People with AF are five-times more likely to have a stroke and twice as likely to die, compared to those without AF. Strokes caused by AF are more likely to be severely disabling than strokes of other causes, a devastating event for individuals and their families. A medication that prevents blood clots from forming (an oral anticoagulant), reduces this risk by two-thirds. 75% of people with AF do not take their medication as recommended either because they do not understand or believe in their medications, or forget. We aim to develop and evaluate a digital intervention that will help people take their recommended medications. We will involve people with AF at every stage of development and focus on how this intervention could reach the broadest range of people. We are working with policy makers, third sector representatives and clinicians which will help to make the intervention suitable for usual care. Successful delivery of this intervention could help more people take their medications as recommended This would help reduce risk of stroke, thereby preventing disability and death in people with AF.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: CARDIOVASCULAR
Title: Targeting investigation and treatment in patients with type 2 myocardial infarction (TARGET-Type 2): A pilot randomised controlled trial.
Funder: Chief Scientist Office, Scotland

Abstract: The heart can experience trauma when it is put under stress. This can happen if the heart beats too quickly, or if blood pressure or oxygen levels are too low. Often this happens during another illness or condition. Our research has shown that most patients who experience trauma to their heart muscle during another illness also have undiagnosed heart disease such as narrowed blood vessels or a weakened heart muscle. This can put patients at risk of future heart attacks or early death. We don’t know which treatments help people with this type of heart injury. We will ask these patients to take part in a trial. Half of patients will receive current care and half will get extra heart tests and treatments, aiming to improve symptoms and lifespan. This pilot study will inform the design of a large randomised controlled trial


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Optimizing Quality of Life for People Living with Heart Failure in Care Homes: Co-Design of a Digital Intervention
Funder: Public Health Agency, NI

Abstract: Heart failure (HF) affects at least 20% of residents living in care homes, leading to increased morbidity, increased mortality and impaired quality of life (QOL). There are limited educational interventions to improve care home staff understanding to better support their residents to live well with HF. Aim: To co-design a digital intervention to improve care home staff understanding of HF, and subsequently to optimise QOL for people living with HF within care homes. Methods: This will involve three work streams (WS). WS1 will involve a systematic review of the literature regarding HF interventions in care home settings. In addition, we will conduct 10-15 semi-structured interviews with care home staff about the current facilitators and barriers to providing care to residents living with HF. WS1 will inform WS2 which will focus on the co-development of the digital intervention using co-design methodology. In WS3 we will conduct a feasibility study across 10 care homes to test the novel intervention. Baseline and post questionnaires (3 months after intervention) will be completed by care home staff to evaluate data related to HF knowledge and self-efficacy. Focus groups will be held with staff to explore implementation processes and semi-structured interviews with HF residents will explore possible impacts of the intervention. Data will be analysed using descriptive statistics, paired t-tests and thematic analysis. HSC R&D funding will support the research team to carry out three additional activities which will strengthen the project. These a Delphi Study to strengthen intervention design during year one, embedding/evaluation of digital intervention within the undergraduate nursing curriculum and protected time to develop a suitable application for feasibility testing during year two.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CARDIOVASCULAR
Title: 2019 Doctoral Fellowship: A data mining approach to understanding heart failure: Retrospective and real time analysis of Northern Ireland heart failure databases to enhance patient outcomes.
Funder: Public Health Agency, NI

Abstract: Background: Cardiovascular disease which include heart failure (HF) is the leading cause of death in the United Kingdom (UK). There are approximately 900,000 people in the UK with HF. HF causes or complicates approximately 5% of all emergency adult hospital admissions. HF accounts for approximately 2% of total NHS expenditure. In Northern Ireland (NI) 4% of the population have Coronary Heart Disease with 1% having HF. There is no centralised registry for monitoring data on patients with HF in NI. Some health and social care trusts in NI have developed their own databases for monitoring the progress of HF patients. Data mining and data science technologies are underutilised for eliciting insights from patient databases but are likely to become an essential instrument for hospital management, medical research, epidemiology and for predicting patient outcomes. Aims: We will use data mining techniques to uncover ‘useful and actionable’ insights for improving the care of HF patients and will uncover bottlenecks in HF care by analysing real world clinical pathways and their variations from current guidelines. Methods: A rich dataset of HF patients is available from Southern, Belfast and Western HSC Trusts in NI. We will use the standard method of Cross-Industry Standard Process for Data Mining (CRISP-DM) to analyse and understand the bottlenecks and gaps in patient care pathways. CRISP-DM involves the following process: 1) business understanding, 2) data understanding, 3) data preparation including data cleaning, modelling, evaluation and 4) deployment of results. Outcome: The results of CRISP Data Mining process will allow development of predictive models to forecast future care of HF patients. The models will act as potential clinical decision support tools. Following detailed analysis of the data available to date, we will initiate a national NI HF data analytics dashboard to facilitate visual analytics and exploration of further hypotheses.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CARDIOVASCULAR
Title: US Ireland Partnership - Food based Biomarkers, diet quality and cardiovascular health
Funder: Public Health Agency, NI

Abstract: Coronary heart disease (CHD), a leading cause of deaths, is a preventable disease. Largely through smoking cessation promotion and improved control of hypertension and dyslipidemia through medications, we have witnessed a decline of CHD incidence and mortality in the past decades, although such a decline will likely reach a plateau. The role of other effective strategies, such as diet, in the prevention of CHD has become more critical for a further reduction in CHD incidence and mortality. However, further research is necessary to establish the optimal approaches to achieve dietary changes. Furthermore, epidemiological associations regarding major dietary components, such as animal proteins, is not entirely consistently observed across studies that mostly relied on food frequency questionnaires (FFQs) or other traditional instruments to assess diet. The validity of using FFQs to assess diet may be influenced by factors such as recall accuracy and bias. Novel instruments that are not subject to measurement errors are needed to substantiate the link between foods and dietary patterns and the risk of developing CHD. In this regard, metabolomic profiling technique, is instrumental in finding novel molecules that can serve as highly-specific, objective biomarkers of food intake. The present proposal will use these dietary biomarkers in large cohorts to determine the relationships with CHD risk. Furthermore, we will develop strategies for implementation of personalized nutrition approaches to improve CHD risk factors. Results from the present proposal have the potential to impact on the delivery of future healthcare through the provision of evidence based preventive programs.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CARDIOVASCULAR
Title: Mechanisms, target organ damage and innovative screening approaches in hypertension in sub-Saharan Africa
Funder: Wellcome Trust

Abstract: Most of our current understanding of the aetiological drivers, resultant phenotypes and treatment approaches of hypertension in native Africans are derived from studies in diaspora Africans. This is despite some evidence that the clinical manifestation of hypertension in native Africans differ from classical findings described elsewhere. The overall goal of this fellowship is to help decrease the substantial hypertension burden in sub-Saharan Africa. I will first use data from The Gambia National Eye Health Survey 2019 (GNEHS2019) to describe the prevalence of hypertension, its associated risk factors and comorbidities as well as demographic and socio-economic correlates. A sample of 500 individuals with hypertension as found in the GNEHS2019 with their age and sex-matched local controls will be re-examined to investigate the accuracy of using survey blood pressure measurements to classify individuals by hypertension status. I will then combine socio-demographic, clinical, laboratory, ECG, echocardiography and vascular function studies to explore whether hypertension phenotypes cluster into identifiable sub-groups that would better characterise the possible mechanism(s) of their hypertension. I will also investigate the burden, characteristics and associated factors of hypertension-mediated organ damage. Finally, I will validate the potential for AI-enabled ECG to screen for cardiac contractile dysfunction in low resource settings.

Lay abstract: The prevalence of hypertension in sub-Saharan Africa continues to escalate at an alarming rate. It is the leading risk factor for cardiovascular diseases including heart failure. Hypertension and associated organ damage has not been extensively studied in native Africans. Most of our understanding of the causes, features and treatment in this population are therefore derived from studies elsewhere, notably in African-Americans. In this fellowship, I will first describe the burden of hypertension, associated risk factors, comorbidities and demographic and socio-economic correlates. I will carry out detailed tests to explore clustering and mechanism of hypertension in native Africans. Finally, I will evaluate the validity of ECG, aided by novel artificial intelligence methods, to screen for left ventricular dysfunction. This proposed fellowship will increase understanding on key aspects related to the burden, mechanisms and complications of hypertension as well as validating a cheap, accessible tool for screening left ventricular dysfunction.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: The role of Wilms tumour 1 in the regenerating zebrafish myocardium
Funder: Wellcome Trust

Abstract: Heart attacks are caused by a coronary artery occlusion which leads to ischaemia, necrotic cardiac muscle cell (cardiomyocyte) death and scar formation. As mammals cannot resolve this non-contractile scar, the surviving tissue undergoes further pathological remodelling which can lead to heart failure. Unlike mammals, zebrafish retain the ability to resolve scarring and regenerate cardiac tissue into adulthood. While it’s known that zebrafish regenerate their hearts through the de-differentiation and proliferation of cardiomyocytes, the role of progenitor cells is less well understood. The epicardium is a single-cell layer of multipotent progenitors that contribute to the generation of many cardiac cell types during development. After injury, the epicardium re-expresses embryonic genes and is essential for zebrafish heart regeneration. In accordance with evidence from preliminary lineage tracing experiments, we hypothesise that after heart injury the zebrafish epicardium becomes “re-activated” and contributes to de novo cardiomyocyte generation and/or that wt1b re-expression plays a role in existing cardiomyocyte de-differentiation, to facilitate heart muscle regeneration. A range of imaging and biochemical techniques on genetically modified zebrafish will be used to investigate these hypotheses, with the aim of furthering our understanding of zebrafish cardiac regeneration to extrapolate to mammals and identify potential novel therapeutic approaches for patients.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CARDIOVASCULAR
Title: Elucidating the mechanisms underpinning vascular regeneration in the injured adult zebrafish heart
Funder: Wellcome Trust

Abstract: Heart attacks occur when blood vessels fail to deliver blood to an area of the heart, causing the surrounding heart muscle to die. While mammals cannot recover from this, zebrafish can. An important component of zebrafish heart regeneration is the growth of new blood vessels to deliver oxygen and nutrients to the area. Blood vessels are comprised of endothelial cells (EC); so the number of EC in the injured area increases rapidly to build new vessels. This process is not fully understood, but discovering which genes are switched on could guide human gene therapies. In this project, we will use a high-accuracy laser to induce an injury mimicking a heart attack in zebrafish hearts. We will image the vascular regeneration process to identify timepoints of maximal regeneration and use a cutting-edge “single-nuclear” approach to determine which genes are switched on at those times. We will compare these genes to those previously identified in mice before investigating whether they are switched on/off in tissues from human patients. Genes that are switched on during zebrafish regeneration but are off after mouse and human injury could be driving zebrafish vascular regeneration and could therefore guide future therapeutic strategies in humans after heart attacks.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: A GWAS of the progression of abdominal aortic aneurysms and simultaneous use of genetic and non-genetic information in the evaluation of screening and diagnostic testing pathways
Funder: Wellcome Trust

Abstract: In the UK, men aged 65 are invited to screening to check for an Abdominal Aortic Aneurysm (AAA). Untreated aneurysms may rupture, which is usually fatal, although many aneurysms do not progress to this stage. There are known risk factors for AAA such as smoking and family history. Evidence of genetic association with AAA has been found which means that some people are more at risk from birth of having an aneurysm. I plan to investigate the role of genetics in both the presence and progression of disease, utilising data from UKBiobank, the UK Aneurysm Growth Study and AAA-Express. These findings will be adopted into a hypothetical computer model. I will investigate the possibility of targeted screening for AAA. This involves identification of risk factors that will also consider the benefit of genetic data to identify individuals at high risk of AAA for screening invitation. I will then investigate an adapted clinical pathway after detection of aneurysm based on the risk of rupture. Incorporating genetic information may improve patient outcomes and the cost-effectiveness of the screening program by limiting screening to those most at risk and by ensuring that those diagnosed with an aneurysm have the most appropriate clinical intervention.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Functional characterisation of CYP2C9 variants of uncertain significance
Funder: Wellcome Trust

Abstract: The liver is the main site for the elimination of medicines taken by people (a process termed drug metabolism). There are many enzymes involved in drug metabolism – one of these is cytochrome P450 2C9 (CYP2C9). CYP2C9 metabolises approximately 13% of all clinically used medications. One example is warfarin [1]. The activity of CYP2C9 varies between individuals which can affect drug efficacy and increase the likelihood for adverse drug reactions [2–4]. This is due to several factors including concurrent disease and the intake of other medications. Genetic factors also affect the activity of CYP2C9 – these are termed genetic polymorphisms. The function (i.e. whether they increase or decrease activity of CYP2C9) of almost half of these polymorphisms is not well-defined [5]. Preliminary work performed in the Pirmohamed lab has identified 16 high impact (e.g. frameshifts), 159 moderate impact (e.g. missense variants) and more than 8000 non-coding variants. The key goals of the project are: 1. Correlate genetic variation in CYP2C9 to clinical outcomes using the UK BioBank, 100K Genomes Project and a well-characterised warfarin cohort 2. Assess the effect of genetic variants on metabolomic parameters 3. Prioritise variants for in vitro functional studies using CRISPR-Cas9, with effects on metabolism evaluated using LC-MS


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: The Role of SEMA3G in the Maintenance of Pulmonary Vascular Integrity
Funder: Wellcome Trust

Abstract: Pulmonary arterial hypertension (PAH) is a fatal disease in which the blood vessels of the lung thicken and narrow, causing an increase in blood pressure and eventually right heart failure. In order to develop new therapies for PAH the mechanisms underlying the progression of lung vessel damage must be determined. Many PAH cases are caused by a mutation of one of many components of the bone morphogenetic protein signalling pathway, however the effect of these mutations on blood vessel stability is still unknown. This project aims to examine the role of semaphorin 3G (SEMA3G), a protein that we have shown to be regulated by the bone morphogenetic protein (BMP) signalling pathway, in maintaining blood vessel integrity. Endothelial dysfunction is central to a number of pulmonary pathologies including PAH. I will investigate the role of BMP9 and BMP10 in regulating SEMA3G expression in the endothelium and specifically the functional role the protein plays in endothelial and mural cell interactions. In order to determine this, I will develop 3D co-culture assays using pulmonary microvascular endothelial cells and pericytes. These studies will further our understanding of the mechanisms controlling vascular homeostasis and potential pathways that can be targeted in the treatment of PAH.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Computational investigation into the interplay between pro-arrhythmic and mechanical abnormalities
Funder: Wellcome Trust

Abstract: Cardiac electrical activity and contractile output have a complex relationship – electrical activity signals contraction and contractile output can then affect electrical signalling via feedback mechanisms. Computational modelling allows us to understand this relationship further, particularly regarding two important applications. Cardiac toxicity is a leading reason behind pharmaceuticals being withdrawn during development, but current screening methods centred on animal testing raise concerns with ethics and accuracy. Recent developments have suggested computational testing is a viable alternative, outperforming animal models in predicting risk from dangerous arrhythmias. I will incorporate contractile mechanics into our drug testing pipeline such that we can also assess their effect on contractile output. Sudden cardiac death (SCD) is a leading cause of mortality worldwide, usually caused by arrhythmias. Various treatments exist to prevent SCD, but accurate risk stratification tools are needed to identify those at high risk for developing arrhythmias causing SCD. Measures of contractile output, such as ejection fraction (EF), are used, but the relationship between them and arrhythmic risk is currently unclear, as most people experiencing SCD have preserved EF. I will use an electromechanical model to investigate the mechanisms underlying this relationship so that we can more effectively identify and treat this high-risk population.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Inferring structural properties of the myocardial substrate from multipolar electrogram recordings using deep learning
Funder: Wellcome Trust

Abstract: The contraction of the heart muscle is caused by the propagation of electrical signal throughout the heart. This signal is propagated from cell to cell through proteins called ion channels and gap junctions. Physiological and pathological heterogeneities and changes in the expression of these proteins, result in the conductivity field of the heart tissue being non-homogeneous and anisotropic. This can result in electrical waves that propagate abnormally and can cause atrial fibrillation, which is an irregular beat in the upper chambers of the heart, the atria, and one of the most common cardiovascular diseases. The aim of this project is to test the hypothesis that data from electrograms, recorded by electrodes in direct contact with the heart, can be used to estimate the conductivity field of the cardiac tissue. Deep learning methods will be used to solve this inverse problem, first applied in synthetic data, and then validated in a biological setting. By reconstructing the conductivity field of the heart muscle from electrograms, the currently-low success rate of the treatment of atrial fibrillation through ablation will be increased, since the clinicians will have a better indication of the position of the low-conductivity tissue that has to be ablated.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Examining the role of endothelial derived galectins in vascular inflammation
Funder: Wellcome Trust

Abstract: The inflammatory response is a sophisticated mechanism used by the body to protect against injury and invading microorganisms and requires the trafficking of disease-fighting immune cells from the bloodstream to the site of injury. Resolution of the inflammatory response involves removal of immune-related infiltrate which if left unresolved can lead to chronic inflammatory pathologies. Carbohydrate-binding proteins called galectins, are expressed by cells that line the blood vessels and play fundamental roles in both the initiation and resolution of the inflammatory response. Changes in the frictional force generated by blood flow through the blood vessels can be detected by these cells which leads to subsequent changes in gene expression and release of these immune-modulating proteins. We aim to investigate and characterise the factors that regulate the endogenous expression of galectins from endothelial cells lining the blood vessels and the functional role they play in vascular inflammation. We aim to use a combination of inventive in vitro, ex vivo and in vivo experiments that combine physiological flow conditions and inflammatory mediators, to study the role of endothelial galectins in vascular inflammation and the mechanisms that underlie this.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR