The University of Manchester has pledged to match the funding awarded by the BHF, taking the total investment in cardiovascular disease research at the University to £8 million.

Researchers at the University welcomed the announcement. Professor Bernard Keavney, BHF Professor of Cardiovascular Medicine at the University of Manchester, said: “This is a landmark moment for cardiovascular research in Greater 91ֱ��. We’re thrilled that the progress we have made in our research at The University of Manchester in recent years has been recognised with this award, alongside other top-ranking institutions nationally.

“We will focus particularly on science that will meet the needs of those who suffer disproportionately from cardiovascular disease because they are disadvantaged – be that by socio-economic status, race or ethnicity, geography or genetics. We are determined that this award will lead to positive health changes for our local population in the North West – who suffer the worst rates of cardiovascular illness and death in England – as well as nationally and internationally.”

Prof Keavney , will lead the Centre of Excellence at the University, along with Professor Maciej Tomaszewski from the University of Manchester.

The funding will support the university to cultivate a world-class research environment that encourages collaboration, inclusion and innovation, and where visionary scientists can drive lifesaving breakthroughs.

The award from the BHF is part of a much needed £35 million boost to UK cardiovascular disease research from the British Heart Foundation. The funding comes from the charity’s highly competitive Research Excellence Awards funding scheme. The award to the University of Manchester will support researchers to:

• Discover the reasons why some babies are born with heart problems (congenital heart disease) and find ways in which these problems could be better predicted, potentially avoided, and treated when they occur in families.
• Better understand the genetic drivers of high blood pressure, kidney disease, diabetes and other chronic conditions.
• Provide new insights into the causes and consequences of heart failure and identify new potential treatment strategies.
• Uncover the links between inflammation and inflammatory diseases (such as certain types of arthritis) and the higher risk of cardiovascular disease and stroke these patients carry and find ways to break these links.
• Use Artificial Intelligence on largescale datasets to identify how we can better identify and prevent disease in patients with cardiovascular diseases, including those suffering from other conditions such as cancer.

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “We’re delighted to continue to support research at the University of Manchester addressing the biggest challenges in cardiovascular disease. This funding recognises the incredible research already happening at the university and will help to cement its status as a global leader in the field.

“With generous donations from our supporters, this funding will attract the brightest talent, power cutting-edge science, and unlock lifesaving discoveries that can turn the tide on the devastation caused by heart and circulatory diseases.”

Research Excellence Awards offer researchers greater flexibility than traditional research funding, allowing scientists to quickly launch ambitious projects that can act as a springboard for larger, transformative funding applications.

The funding also aims to break down the silos that have traditionally existed in research, encouraging collaboration between experts from diverse fields. From clinicians to data scientists, biologists to engineers, the funding will support universities to attract the brightest minds, nurture new talent and foster collaboration to answer the biggest questions in heart and circulatory disease research.

The University of Manchester received a £1 million Accelerator Award from the BHF in 2019 to enable the university to develop its cardiovascular research programme. This funding has supported research that will lay the foundations for future breakthroughs, including:

• Development of a biodegradable gel that could help to . Researchers showed that the gel can be safely injected into the beating heart to act as a scaffold for cells to grow into new heart tissue. They hope that it could form a new generation of treatments to repair damage caused by a heart attack.
• Identifying how high blood pressure causes the small arteries in the brain to become constricted, reducing the blood flow through them and increasing the risk of developing vascular dementia. The mechanism could be the target of new drugs to prevent vascular dementia.
• Providing new biological insights into high blood pressure by studying the genes that influence differences in blood pressure in the kidney, the key organ controlling blood pressure. This work identified opportunities to repurpose drugs currently used for other conditions to better treat high blood pressure.

Its recent successful funding bid will now support the university to take the next steps towards internationally recognised excellence in cardiovascular disease research.

The highly interdisciplinary team used cutting-edge unsupervised deep learning to analyse over 50,000 three-dimensional magnetic resonance images of the heart from UK Biobank, a world-leading biomedical database and research resource.

The study, published in the leading journal , focused on uncovering the intricate genetic underpinnings of cardiovascular traits. The research team conducted comprehensive genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS), resulting in the discovery of 49 novel genetic locations showing an association with morphological cardiac traits with high statistical significance, as well as 25 additional loci with suggestive evidence.  

The study's findings have significant implications for cardiology and precision medicine. By elucidating the genetic basis of cardiovascular traits, the research paves the way for the development of targeted therapies and interventions for individuals at risk of heart disease.

The research was funded by the Royal Academy of Engineering (RAEng), The Royal Society, the British Heart Foundation (BHF), and the Argentinean National Scientific and Technical Research Council (CONICET) in an interdisciplinary collaboration involving a RAEng Chair, two BHF Professors, and an IBM Fellow.

The research was directed by , Director of the , the Bicentennial Turing Chair for Computational Medicine, and a Royal Academy of Engineering Chair in Emerging Technologies. The first author was Rodrigo Bonazzola, a PhD candidate, jointly co-supervised by Prof Frangi, (CONICET, Argentina) (IBM Fellow and Chief Scientist at IBM Research).

Prof Frangi said: “This is an achievement which once would have seemed like science fiction, but we show that it is completely possible to use AI to understand the genetic underpinning of the left ventricle, just by looking at three-dimensional images of the heart.

“Previous studies have only investigated association of traditional clinical phenotypes, such as left ventricular mass or stroke volume, limiting the number of gene associations detected for a given study size. However, this study used AI not only to delineate the cardiac chambers from three-dimensional medical images at pace but also to unveil novel genetic loci associated with various cardiovascular deep phenotypes.”

He added: “This research exemplifies the power of multidisciplinary teams and international collaborations, bolstered by UK Biobank's valuable data. By marrying genetic data with cardiac imaging through advanced machine learning, we've gained novel insights into the factors shaping cardiovascular health.”

Early career scientist and rising star, Bonazzola, the study's lead author said: “Our research reveals genes that harbour mutations known to be detrimental to other organisms, yet the impact of common variations within these genes on cardiac structure across the human population had not been previously documented. For instance, the STRN gene, recognised for its harmful variants leading to dilated cardiomyopathy in dogs, exhibits a common variant in humans that seems to induce a subtle but detectable change in mitral orientation.”

Dr Ferrante said: “The study's core achievement is a robust method based on geometric deep learning for large-scale genetic and cardiac imaging data analysis, leading to ground-breaking genetic insights related to heart structure. These discoveries could revolutionize our approach to disease understanding, drug development, and precision medicine in cardiology. The study's thorough analysis and ensemble-based methods also enhance the discovery rates and the reliability of our findings.”

Prof Keavney, BHF Professor of Cardiovascular Medicine at The University of Manchester, emphasised the transformative methodology. He said: “Employing cutting-edge deep learning to integrate genetic and imaging data has shed light on the genetic underpinnings of heart structure. This approach is a beacon for future organ studies and understanding genetic influences on organ anatomy.”

Prof Plein, BHF Professor of Cardiovascular Imaging in Leeds, said: "Cardiovascular MRI plays a crucial role in understanding disease phenotypes, allowing us to uncover genetic associations that help stratify cardiovascular diseases, ultimately leading to better treatments and precision medicine."

Professor Frangi added: “Our publication marks a significant stride in correlating deep cardiovascular imaging traits with genetic data. It paves the way for revolutionary progress in cardiovascular research, clinical practices, and tailored patient care.”

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “This new research shows the huge power of big data linking genes to heart structure. Machine learning has made this possible by transforming how we process, analyse and gain insights from big data to tackle the biggest questions in cardiovascular research. This pioneering new method has uncovered many more genes that influence the structure and function of the heart, which will lead to new insights into why abnormal structure and function can lead to heart disease.

“Heart and circulatory diseases are still devastating millions of lives each year in the UK. AI could unlock more information about the genes that contribute to the structure of the heart. In future this could lead to real improvements for patients, including the development of tailored, precision treatments for people with heart problems.”

The paper Unsupervised ensemble-based phenotyping enhances discoverability of genes related to left-ventricular morphology is published in

Dr Kathryn Hentges and her team hope the two-year project, funded by a grant from the British Heart Foundation (BHF), will provide patients and clinicians with new knowledge on the causes of congenital heart diseases and provide families with options in reproductive choices.

Dr Hentges added that longer term she hoped the research could pave the way to future screening for these genes, and empower families with knowledge about the underlying causes of congenital heart conditions.

This project is also another step towards understanding how the heart can develop incorrectly and ultimately help to inform future research that it is hoped could eventually prevent heart defects in babies from happening at all.

Each day in the UK around 13 babies are diagnosed with congenital heart disease and some children will need one or more procedures to help their hearts function normally.

The grant of £140,951 is the latest BHF grant awarded to Dr Hentges and will build on her earlier work to better understand which specific genes cause heart defects.

Previous research by the team used machine learning to predict which genes are likely to be involved in the development of the heart. The new grant will allow the team to further analyse these genes using AI to find out if they are the same genes as those found with mutations in congenital heart disease.

“I’ve always had an interest in understanding the causes of birth defects in general and particularly why new gene mutations cause children to be born with these defects,” said Dr Hentges.

“In this research we are focusing specifically on the heart to understand if we can link particular genes which have a role in development to those that cause congenital heart defects.

“This project will help speed up the process to achieve a genetic diagnosis for people with congenital heart defects, because it will identify the genes that are the most likely to cause these defects.

“We hope it will be able to give people an understanding of why something has happened to them that makes then different, and we also hope it will give peace of mind to parents that it is nothing they did in pregnancy that has caused the harm.

“Speaking to clinicians I know this is a huge issue –parents often have a lot of guilt when children are born with congenital disease, a feeling that they must have done something wrong.

“So I think it will help a lot of people, helping parents know they didn’t do anything wrong as well as giving them a specific diagnosis so that in future they will understand the course of the disease progression and make sure they get the best care for their child as they grow up.”

BHF Research Advisor Dr Tian Yu said: “Today, thanks to research, more than eight out of 10 babies born with a congenital heart defect in the UK survive to adulthood. However, we don’t always know why their hearts haven’t developed properly, and understanding this better could improve the way we diagnose and treat these conditions.

“This research could help parents better understand why and how these defects occur and help them work with medical experts to ensure they can get the best care for their children as they grow up.”

The research is being presented at the British Cardiovascular Society conference in 91ֱ��.

Scientists have been looking for ways to introduce new cells into damaged hearts for years, as a way to repair it and reduce the risk of progression to heart failure. But historically, when cells have been injected directly into the heart, only one per cent have remained in place and survived.

Now, researchers from the University of Manchester have developed a new biodegradable gel that can be safely injected into the beating heart to act as a scaffold for cells to grow new tissue. The researchers hope their gel will become a key part of future regenerative treatments for damaged hearts.

Katharine King, a BHF-funded PhD student at the University of Manchester, led this research. She said: “The heart has a very limited ability to repair any damage it sustains. Our research has been looking for ways to overcome this so we can keep the heart in a healthier place for longer.

“While it’s still early days, the potential this new technology has in helping to repair failing hearts after a heart attack is huge. We’re confident that this gel will be an effective option for future cell-based therapies to help the damaged heart to regenerate.”

For any successful treatment, a good blood supply will be vital for the injected cells to develop into new tissue. The researchers saw early signs of blood vessel growth into the gel, proving the technology could boost growth of new vessels.

They also showed that the gel can support growth of normal heart muscle tissue. When they added human cells that had been reprogrammed to become heart muscle cells into the gel, they were able to grow them in a dish for three weeks and the cells started to spontaneously beat.

In order to prove that this technology could work in a living heart, the team injected the gel with a fluorescent tag into the hearts of healthy mice. The fluorescent tag revealed that the gel remained in the heart for two weeks. Echocardiograms (ultrasounds of the heart) and electrocardiograms (ECGs, which measure the electrical activity of the heart) confirmed that the injection is safe for the heart.

The researchers now plan to trial this treatment in mice straight after a heart attack, to see whether the heart cells can develop new muscle tissue and help restore the heart’s ability to pump efficiently.

The gel is made of chains of amino acids called peptides, the building blocks of proteins. The bonds between the peptides mean that the gel can exist in different states. When it’s under stress the peptides disassemble and behave like a liquid, making it ideal for injecting. When the stress is removed the peptides re-assemble almost immediately and behave like a solid, holding the cells in place as they graft onto the heart.

Professor James Leiper, Associate Medical Director at the British Heart Foundation, said: “We’ve come so far in our ability to treat heart attacks and today more people than ever survive. However, this also means that more people are surviving with damaged hearts and are at risk of developing heart failure.

“This new injectable technology harnesses the natural properties of peptides to potentially solve one of the problems that has hindered this type of therapy for years. If the benefits are replicated in further research and then in patients, these gels could become a significant component of future treatments to repair the damage caused by heart attacks.”

The study compared recommended treatment (oral anticoagulation such as warfarin), less effective treatment (aspirin), and no treatment.

Compared to White patients, Black and other ethnic minorities patients were 22%, and 24% less likely to receive oral anticoagulation, respectively. These estimates have taken into account patient age, sex, comorbidities, residence deprivation (ranked 1 to 5, from least to most deprived), and bleeding risk factors.

The study of the heart condition, published in PLOS Medicine today (07/06/22), also identifies people from deprived neighborhoods as being less likely to receive the treatment.

Patients living in the most deprived areas were 15% less likely to receive oral anticoagulation, compared to patients living in the least deprived areas (on top of the ethnicity disparities).

For example, a black patient living in deprivation quintile 5 was 16% likely to be prescribed aspirin-only and 62% oral anticoagulants, while respective estimates for a white patient living in deprivation quintile 1 were 12% and 72%.

Adjusting for patient characteristics, practices in London, the North West, and Yorkshire and Humber generally performed worse than other regions, with a no treatment probability of around 18% compared to practices in the North East and the South West regions with a no treatment probability of around 14%.

And the team also identified an association between different comorbidities such as dementia, liver disease and cancer and under-prescribing.

Patients with dementia, liver disease, malignancy, and history of falls were associated a 48%, 42%, 26% and 18% lower prescribing rate of oral anticoagulation, respectively.

Patients with history of ischaemic heart disease were also more likely to receive aspirin-only, even though this is not considered best practice for stroke prevention.

The data also showed that incidence rates of atrial fibrillation rose by almost a quarter in England between 2009 and 2019, and were markedly higher in men than in women.

The researchers analysed almost 200,000 patients aged over 18 and registered with an English general practice between 2009 and 2019, contributing data to the UK Clinical Practice Research Datalink database.

However, they also showed there was an overall rise in the proportion of patients with AF prescribed oral anticoagulants increased substantially between 2011 and 2015.

But the increase, they said, may be related to a change in European Society of Cardiology guidelines in 2010, which recommended anticoagulation for all patients with AF at moderate-risk to high-risk of stroke.

That was followed by a 2012 update recommending avoidance of aspirin prescribing in low-stroke risk patients.

Lead author Alyaa Ajabnoor, a PhD researcher from The University of Manchester said: “Atrial fibrillation is associated with increased risk of stroke, cardiovascular comorbidities, and mortality, and currently accounts for 1% of the total healthcare expenditure in the United Kingdom.

“The treatment of choice is anticoagulation, however many patients with non-valvular atrial fibrillation -the most common form of the disease - are not receiving the therapy they need.

“Despite an increase in prescribing, we report important racial and socioeconomic inequalities in the prescribing of oral anticoagulants.

“People with low socioeconomic status and black or other non-white ethnicities were associated with the prescription of aspirin-only or no-treatment at all compared to white patients or those with higher socioeconomic status.”

Co-author Professor Evan Kontopantelis from The University of Manchester said: “Though this study depends on accurate recording of conditions by health professionals, we feel the overriding findings are robust and stark.

“Our findings suggest that to improve atrial fibrillation outcomes, these inequalities need to be addressed through equitable interventions to improve anticoagulant prescribing to prevent strokes and reduce mortality.”

The paper Incidence of non-valvular atrial fibrillation and oral anti-coagulant prescribing in England, 2009 to 2019: a cohort study is published in PLOS Medicine.

The implantable pacemakers and defibrillators contain multiple sensors that allow continuous monitoring of a patient’s heart health, 24 hours a day.

The study published in and funded by the is a collaboration between The University of Manchester, 91ֱ�� University NHS Foundation Trust (MFT), and – which manufactures implantable devices.

The research team examined remotely monitored health related data from 439 patients being cared for at , part of MFT, over two years.

The study reported a three-fold increase in the odds of mortality for patients who spent at least one day in ‘high-risk’ status. The risk status is determined by a combination of up to nine factors.

There was also a 26 per cent increase in the odds of mortality for patients who had 14 consecutive days or more in a high-risk status – compared with those whose high-risk episodes were shorter.

The researchers are currently investigating if integration of the remotely-monitored device data into healthcare pathways can reduce hospitalisations and mortality.

Dr Fozia Ahmed, Honorary Reader in Cardiovascular Sciences from The University of Manchester and Consultant Cardiologist at , part of the MRI, said: “Remote monitoring capabilities of modern-day cardiac devices enables continuous monitoring of health-related data in the patients’ own homes.

“The data can help identify when there is a potentially significant shift in a patient’s clinical condition, helping to predict future adverse clinical events, such as hospitalisation and death.

“Historically, cardiologists have seen patients at six to 12-month hospital-based appointments. If a patient with heart failure is unwell between appointments, then we rely on the patient getting in touch. But patients don’t always know they are unwell until it is too late.”

“We believe this technology could be a game-changer in the management of cardiac patients, particularly those with heart failure.

“In Greater 91ֱ��, based on the data from the research, we have started to use the device-derived alerts, which notify the care team when a patient is detected by the device as ‘high-risk’, prompting a telephone consultation with a specialist.

“The whole process from detection of a high-risk episode, through to assessment and follow-up is known as the TriageHF Plus care pathway – originally developed in 91ֱ��, it is now being used more widely.”

In recognition of their outstanding contribution to healthcare in the HealthTech Partnership of the Year category, announced in June at the HSJ Partnership Awards 2021.

Dr Camilla Sammut-Powell, from the at The University of Manchester and lead statistician for the research, said: “This is the first prospective study to show that remotely monitored cardiovascular implantable electronic device (CIED) data, summarised as a risk score, can be used to predict mortality.

“This routinely monitored data, automatically collected every day, can help discriminate between patients at high and low risk of death.

“Such information may personalise a clinician’s decision making towards ensuring that the patient is in receipt of therapies designed to improve their long-term prognosis.”

A spokesperson from Medtronic, the industry collaborators which manufactures the device, said: “The increased mortality identified in the evaluation justified the need for an industry and NHS collaboration in this space, to create a digital solution to that aims to ensure that the high risk notifications are sent direct to heart care teams who can take action as clinically indicated, based on the health-related data from the patient’s device and patient reported symptoms.”

The researchers, with support from the NIHR Applied Research Collaboration Greater 91ֱ��, are undertaking a follow-on study to evaluate the costs and resources of implementing the new heart failure care pathway, :

Remote Monitoring Data from Cardiac Implantable Electronic Devices Predicts All-cause Mortality is published in .

Trialled by University of Manchester and 91ֱ�� University NHS Foundation Trust doctors and scientists, in conjunction with Liverpool Clinical Trials Centre, pirfenidone could offer a much-needed viable treatment for heart failure with preserved ejection fraction (HFpEF).

But larger scale trials are needed to confirm the findings for the drug, produced by Roche Products Limited, before it can be licensed for use in the NHS.

The study, funded by the National Institute for Health Research, is published in Nature Medicine today (Thursday 12 August).

Heart failure means that the heart is no longer able to pump blood around the body properly, causing shortness of breath, swelling and extreme fatigue.

Around a million people in the UK live with heart failure, and many more are at risk of developing it.

Just under a third of 55-year-olds will develop heart failure, and 2 to 3 of every 10 people diagnosed die within a year.

In about half of patients with heart failure, the forward pumping function of the heart is normal. This is called heart failure with preserved ejection fraction, or HFpEF.

While a number of processes lead to heart failure, scarring - or fibrosis - of the heart muscle is thought to be an important mechanism in around half to two-thirds of patients with HFpEF and is associated with adverse outcomes.

Dr Chris Miller, National Institute for Health Research Clinician Scientist at The University of Manchester and Consultant Cardiologist at 91ֱ�� University NHS Foundation Trust led the study.

He said: “Heart failure is as devastating an illness as some of the most common cancers, however its profile its much lower and treatment options for HFpEF are very limited.

“Using cardiac MRI, we were able to select patients in whom heart scarring is important. Pirfenidone then reduced that scarring.”

Pirfenidone works by inhibiting the biological processes involved in scar formation.

The study enrolled patients with heart failure, normal forward pumping function of the heart and evidence of fluid retention.

Eligible patients had cardiac MRI scanning, and those who had evidence of heart scarring, as indicated by a measurement called ‘extracellular volume’, were randomly assigned to take pirfenidone or a placebo daily. 94 patients were randomised, with 47 assigned to each treatment group.

At one year, patients underwent a second cardiac MRI to measure change in heart scarring. Extracellular volume declined by 1.21% on average in patients who took pirfenidone compared with those receiving placebo.

“Based on data from previous studies, this amount of reduction in heart scarring could translate into a substantial reduction in rates of death and admission to hospital for heart failure, however larger trials are needed to determine this,” said Dr Miller.

Fluid retention, measured using a blood test called NT-proBNP, also improved in patients taking pirfenidone compared to those receiving placebo.

Dr Miller added: “Though further investigation is required, the associated improvement in fluid retention provides support for heart scarring having a causal role in heart failure and being an effective treatment target”.

The most common side effects were nausea, insomnia and rash, which are similar to that which lung patients can experience when taking Pirfenidone.

Dr Miller said: “These findings are exciting and suggest that pirfenidone could benefit patients with this condition, however further trials are required.”

The paper Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial is published in Nature Medicine

High blood pressure, known as “silent killer”, is one of the most common human diseases and remains the key risk factor for strokes and heart attacks.

High blood pressure - or hypertension- runs in families but the exact mechanisms through which genes influence individuals’ predisposition to hypertension is not clear.

The discoveries published in Nature Genetics, one of the world’s leading journals, shed new light on our understanding of genetic predisposition to high blood pressure.

The study, supported primarily by the British Heart Foundation and Kidney Research UK, was possible through access to huge datasets of human DNA and RNA from possibly the world’s largest repository of human kidney tissue-based “omics”.

The team led by Professor Maciej Tomaszewski at The University of Manchester characterised how information inherited in DNA translates into genetic predisposition to high blood through changes in activity of certain kidney genes.

These studies included comprehensive analyses conducted at various molecular “levels” of kidney tissue combining together DNA, RNA and other “layers” from the same set of kidney tissue samples.

They also used a statistical method –- called Mendelian randomisation – to screen for evidence of causal associations between thousands of variables and millions of genetic variants using the high-performance computing resources hosted at the University of Manchester.

Around 80 per cent of 179 genes discovered by the team have never before been associated with high blood pressure before. Some of these genes can be targeted by existing medicines creating new opportunities to treat high blood pressure.

Principal Investigator Maciej Tomaszewski, Professor of Cardiovascular Medicine and University of Manchester and a Consultant Physician said: “Hypertension is a key driver of coronary heart disease and stroke and the single most important cause of disability and premature death worldwide.

“Yet, our understanding of the role of genes in development of this condition has been incomplete.”

Professor Tomaszewski is also a member of Manchester Academic Health Science Centre (MAHSC), a partnership between academia and NHS organisations in Greater 91ֱ�� to drive health research, improve health education and transform patient care.

Professor Fadi J Charchar, a senior author from Federation University, added: “Our studies filled an important gap in our knowledge through uncovering new genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to genetic regulation of blood pressure and inherited susceptibility to hypertension.”

Professor Andrew Morris, from The University of Manchester, commented: “Through our unparalleled access to the kidney tissue resource, we provide evidence for the role of the kidney as the mediator of common genetic effects on blood pressure and a potentially causal role of blood pressure in the development of renal disease.”

First author: Dr James Eales from The University of Manchester said: “By explaining the molecular mechanisms of hypertension embedded in the kidney, our study will ultimately lead to advancements in patient-centred diagnostic accuracy in hypertension.

“It will also lead to new targeted strategies to lowering blood pressure, thereby accelerating progress in precision medicine.

Professor Tomasz Guzik, from the University of Glasgow, said: “These exciting discoveries uncover a range of new possible mechanisms of hypertension some related to blood vessels, kidneys but also – body immune defences and pave the way for the development of novel genetic therapies for blood pressure.”

Professor James Leiper, Associate Medical Director at the BHF said: “We have known for many years that the kidney is a major regulator of blood pressure, but our understanding of precisely how the kidney controls blood pressure is incomplete.

“The identification of this large set of genes that appear to directly affect blood pressure fills in an important missing piece of that puzzle. The researchers have also found a subset of these genes that are a potential new target for the treatment of hypertension.

“This is important because many people taking existing medications still struggle to control their blood pressure. If doctors have more tools to work with then it will help stop thousands of lives being lost each year from this potentially preventable condition.”

Professor Jeremy Hughes, kidney doctor and chair of trustees at Kidney Research UK said: "High blood pressure is both a cause and consequence of kidney disease and we need better treatments to protect patients from harm such as strokes and heart attacks. 

“This innovative study harnesses the power of a kidney tissue biobank and state-of-the-art genetic analysis to identify novel genes that link the kidney to high blood pressure. We hope this new knowledge will eventually lead to new treatments that benefit kidney patients."

A simple new heart-monitoring technique has been developed to help people self-monitor their conditions at home without the need for hospital visits.

University of Manchester researchers have developed a simple technique that allows people to monitor their own electrocardiogram (ECG) for a potentially life-threatening condition.

Previously people needed to have an ECG in hospital that was interpreted by a highly-trained expert. In new research published today in journal , scientists show that if you apply colour in the right way, people can easily monitor hospital-level health data themselves.

The ‘QT-interval’ is the time it takes for the heart to depolarise and recharge itself. Many common medications, including some prescribed for depression and cancer, can cause this to lengthen. The longer it gets, the more likely you are to suffer from a life-threatening arrhythmia that can cause sudden death.

An ECG shows complex signal data representing the heart’s electrical activity. It is vital for detecting cardiac pathologies, but extremely difficult to interpret, even for clinicians. Researchers at The University of Manchester have been working on a novel visualisation technique that makes it straightforward for members of the general public to understand ECG data.

Dr Caroline Jay from The University of Manchester said: “For decades we’ve assumed that only medical experts can interpret ECGs. We now have evidence that if you display an ECG in the right way, it can easily be interpreted by a patient.

“Here, we’ve shown that it is simple for lay people to understand when they might be at risk of long QT syndrome, which is important because it is caused by many common medications and can result in sudden death.

“Empowering people to understand and monitor their own ECG is a huge leap forward for public health, as it will reduce the number of times people have to go into hospital for routine check-ups, and ensure they get emergency medical attention as soon as they need it.”

The newly developed technique works on a 'single lead’ ECG, which is the heart reading available on a smart watch. A spectrum of colour is applied to the area under the ECG signal from blue to red. The more warm colours you can see, the greater the risk of long QT syndrome.Long QT syndrome often doesn’t cause symptoms, so an ECG is the only way to pick it up. Self-monitoring is particularly useful when someone starts taking a new form of medication, as they will be able to contact their doctor as soon as they notice an issue.

The ability to accurately self-monitor conditions with confidence at home has the potential to ease the number of people requiring trips to hospital, which could be particularly useful during the COVID-19 pandemic.The technique is currently being used as the basis for a new Artificial Intelligence approach that can detect QT-interval lengthening automatically. Because the algorithm uses a data representation that humans find easy to visually understand, it is not just explainable from a technical perspective, but also intuitively understandable.

University of Manchester scientists have discovered that removing immune cells from donor hearts using a new technique can reduce the risk of acute rejection after heart transplant surgery - even without the use of powerful immunosuppressant drugs.

The method- called ex-vivo heart perfusion - protects and restores the heart once it has been removed from the donor, and extends the current preservation time for the organs from 4 to 24 hours.

EVHP was developed by a team led by Professor Stig Steen from Lund University in Sweden.

The new 91ֱ�� and Lund study – published in the journal sheds light on how acute rejection is triggered.

Immune cells in the donor heart, they show, migrate into the transplant recipient’s body and are recognised as foreign. The recipient’s immune system is then programmed to destroy the transplanted organ.

Dr James Fildes from The University of Manchester lead the team that analysed donor hearts from pigs before and after EVHP, and reported that the resident immune cells were significantly depleted.

He is also a Principal Scientist at Wythenshawe Hospital – part of Manchester University NHS Foundation Trust (MFT)

They also found the molecular health of the tissue was excellent, resulting in less inflammation.

The hearts were analysed, preserved and transplanted in pigs using the new technique, and compared with the current method, which involves storing the heart in ice before transplantation.

After, EVHP there was little evidence of rejection, even in the absence of immunosuppression, whereas the non EVHP hearts showed signs of severe rejection very quickly.

Currently when patients receive a transplant, they need lifelong immunosuppression to prevent their own immune system from destroying the transplanted organ, a process called acute rejection.

, runs the Ex-Vivo Lab at the University of Manchester and the Transplant Research Lab at 91ֱ�� Foundation NHS Trust

He said: “Historically, the most common and rapid complication following heart transplantation has been acute rejection.

“With the advent of modern immunosuppression, it is now rare for a transplant recipient to die of acute rejection, but these medicines are inherently toxic, and leave the patient susceptible to infections, cancer, and kidney disease.”

He added: “The technique developed by Prof Steen is a major advance in heart transplantation, as organs can be stored for longer, with incredible preservation.

“What we show in this study is that the technique modifies the heart by removing donor immune cells which we know drive acute rejection. It also improves the state of the tissue, which reduces inflammation.

“So this technique has the potential to be a game changer in heart transplant surgery.”

This work comes as the availability of transplant organs in the UK has plummeted during lockdown, leaving many patients waiting for surgery. The drop exacerbates an already acute shortage of donor hearts.

The technique is now being evaluated in humans in a clinical trial across Sweden.

The paper, Hypothermic cardioplegic perfusion induces immunodepletion of donor hearts resulting in diminished graft infiltration following transplantation, is published in

Air pollution is associated with detrimental effects on human health, including increased risk of heart disease and stroke. Research published today in The Journal of Physiology by researchers at The University of Manchester shows that the knowledge we have about how pollution harms the hearts of marine species can be applied to humans, as the underlying mechanisms are similar. In other words, knowledge gained from the marine ecosystem might help protect the climate and health of our planet, whilst also helping human health.

Around 11,000 coronary heart disease and stroke deaths in the UK each year are attributable to air pollution, specifically due to particulate matter (PM), or small particles in the air that cause health problems. PM2.5 is one of the finest and most dangerous type of PM, is a compound for which the UK has failed to meet EU limits.

Researchers of this study looked across all vertebrates and particularly focused on a set of compounds that binds to the surface of PM, called polycyclic aromatic hydrocarbons (PAH) as the amount of PAH on PM is a associated with the detrimental affect air pollution has on the heart.

While air pollution is known to be dangerous to humans, it actually only became a widely-researched topic in the past five years or so. In marine species however, the mechanism of how PAH pollution causes heart problems is well understood.

Studies after the 1999 Exxon Valdez oil spill showed that the ecosystem still has not recovered 20 years on. In 2010, research on fish after the Deepwater Horizon oil spill, which released large quantities of PAHs into the marine environment, showed that the heart’s ability to contract was impaired.

Dr Holly Shiels, senior author on the study, from The University of Manchester said:

“Pollution affects all of us living on Planet Earth. Due to the conserved nature of cardiac function amongst animals, fish exposed to PAH from oil spills can serve as indicators, providing significant insights into the human health impacts of PAHs and PM air pollution.”

Dr Jeremy Pearson, Associate Medical Director at the British Heart Foundation, which partly funded the research presented in this review, commented:

“We know that air pollution can have a hugely damaging effect on heart and circulatory health, and this review summarises mechanisms potentially contributing to impaired heart function. Reducing air pollution is crucial to protecting our heart health, which is why the BHF is calling on the next Government to commit to reducing air pollution to within WHO limits.”

A drug used to treat erectile dysfunction has been found by University of Manchester scientists to slow or even reverse the progression of heart failure in sheep.

The British Heart Foundation funded study is a breakthrough in the treatment for the disease in which five year survival rates are lower than most common cancers.

The study of Tadalafil – which is in the same class as Viagra – proves that the drug is biologically effective as a treatment for heart failure in sheep.

However, lead author Professor Andrew Trafford argues the effect is likely to also be shown in humans. The study is published in the journal Scientific Reports.

Heart failure is a devastating condition, occurring when the heart is too weak to pump enough blood to meet the body's needs.

It also causes a build-up of fluid that backs up into the lungs, resulting in breathlessness as well as fluid retention, resulting in swelling of different parts of the body.

Most current treatments are ineffective.

“This discovery is an important advance in a devastating condition which causes misery for thousands of people across the UK and beyond,” said Professor Trafford.

“We do have limited evidence from human trials and epidemiological studies that show Tadalafil can be effective in treating heart failure.

“This study provides further confirmation, adds mechanistic details and demonstrates that Tadalafil could now be a possible therapy for heart failure.

“It’s entirely possible that some patients taking it for erectile dysfunction have also unwittingly enjoyed a protective effect on their heart.”

Sheep were used by the team as the physiology of their hearts is similar to human hearts.

When the animals had heart failure – induced by pace makers – which was sufficiently advanced to need treatment, the team administered the drug. Within a short period the progressive worsening of the heart failure was stopped and, importantly, the drug reversed the effects of heart failure.​

The biological cause of breathlessness in heart failure – the inability of the heart to respond to adrenaline – was almost completely reversed.

The dose the sheep received was similar to the dose humans are given when being treated for erectile dysfunction.

Tadalafil blocks an enzyme called Phosphodiesterase 5 or PDE5S for short, which regulates how our tissue responds to hormones like adrenaline.

The research team found that in heart failure, the drug altered the signalling cascade – a series of chemical reactions in the body – to restore the hearts ability to respond to adrenaline.

And that increases the ability of the heart to force blood around the body when working harder.

Professor Trafford added: “This is a widely used and very safe drug with minimal side effects.

“However we would not advise the public to treat themselves with the drug and they should always speak to their doctor if they have any concerns or questions.

“Tadalafil is only suitable as a treatment for systolic heart failure – when the heart is not able to pump properly – and there may be interactions with other drugs patients are taking.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said:

"Viagra-type drugs were initially developed as potential treatments for heart disease before they were found to have unexpected benefits in the treatment of erectile dysfunction. We seem to have gone full-circle, with findings from recent studies suggesting that they may be effective in the treatment of some forms of heart disease – in this case, heart failure.

“We need safe and effective new treatments for heart failure, which is a cruel and debilitating condition that affects almost a million people in the UK. The evidence from this study – that a Viagra-like drug could reverse heart failure – should encourage further research in humans to determine if such drugs may help to save and improve lives."

‘Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure’ is published in the journal Scientific Reports.

Results from a large clinical trial indicate that patients with rheumatoid arthritis are likely to experience the same level of cardiovascular benefits from statins as other individuals, without additional risks. The findings appear in , an official journal of The American College of Rheumatology.

The paper’s lead author is Professor George Kitas of Dudley Group NHS Foundation Trust, while co-senior authors are Professor Jill Belch of the University of Dundee and Professor Deborah Symmons of the University of Manchester.

Patients with rheumatoid arthritis have an approximately 50 percent higher risk of experiencing cardiovascular events such as heart attack and stroke compared with the general population. By lowering LDL cholesterol, statins are known to help prevent cardiovascular events in certain high-risk individuals, but it’s unclear whether they are safe and effective for patients with inflammatory conditions such as rheumatoid arthritis.

To investigate the potential risks and benefits of statins in moderate risk patients with rheumatoid arthritis, researchers designed the Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (TRACE RA), a multi-center, randomized, double-blind trial comparing the statin atorvastatin with placebo.

The trial included 3,002 patients with rheumatoid arthritis who were over aged 50 years or had rheumatoid arthritis for more than 10 years, without clinical atherosclerosis, diabetes, or myopathy. Patients were randomized to receive atorvastatin 40mg daily or placebo.

During a median follow-up of 2.5 years, 1.6 percent of patients who received atorvastatin and 2.4 percent of patients receiving placebo experienced cardiovascular death, heart attack, stroke, transient ischemic attack, or any arterial revascularization. After adjustments, there was a 40 percent lower risk of cardiovascular events for patients taking atorvastatin, although the difference was not statistically significant. This was because the overall rate of events was low.

At the end of the trial, patients taking atorvastatin had significantly lower LDL cholesterol as well as significantly lower levels of C-reactive protein, a marker of inflammation, compared with patients taking placebo. Adverse events in the atorvastatin and placebo groups were similar.

The paper’s lead author is Professor George Kitas of Dudley Group NHS Foundation Trust, while co-senior authors are Professor Jill Belch of the University of Dundee and Professor Deborah Symmons of the University of Manchester.

“The trial found that the statin reduced levels of cholesterol by similar amounts as has been seen in other populations studied. The results also show that it is as safe for patients with rheumatoid arthritis to take statins as for the general population,” said Prof. Symmons. “In addition, because of the low overall rate of cardiovascular events in the trial population, there is no indication for all patients with rheumatoid arthritis to be prescribed a statin. This is unlike diabetes where the great majority of patients are recommended to take a statin.”

The study authors recommend that patients with rheumatoid arthritis be prescribed statins according to national or local guidelines for managing cardiovascular risk in the general population.

An accompanying editorial notes that the study provides information that will be useful for researchers and clinicians who focus on rheumatoid arthritis, and the results may be helpful when considering cardiovascular risk across other rheumatic diseases.

“Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (Trace Ra): A Multicenter, Randomized, Placebo Controlled Trial.” George D. Kitas, Peter Nightingale, Jane Armitage, Naveed Sattar, Jill J.F. Belch, and Deborah P.M. Symmons, on behalf of the TRACE RA consortium. Arthritis & Rheumatology; Published Online: April 15, 2019 (DOI: 10.1002/art.40892) is published .

Patients with some of the most common lung diseases are substantially more likely to suffer a heart attack and develop other major heart problems according to new research.

The team of heart and lung doctors from the University of Manchester and Aston Medical School found people with asthma, chronic obstructive pulmonary disease (COPD) and lung fibrosis, were more likely to develop, and die from, heart disease and heart failure.

The study of nearly 100,000 people with lung disease in the North West of England who were followed up for up to 14 years is published in the .

The increased risk was in addition to the risk posed by other common conditions such as diabetes and high blood pressure.

However, despite the association, the team found that patients with lung disease were less likely to receive heart bypass surgery or angioplasty.

First author Dr Paul Carter, part of the ACALM 91ֱ�� Unit, Aston Medical School said: “The most striking findings were that the risk of coronary heart disease was increased by 50% in patients with asthma, 60% in patients with lung fibrosis and 70% in patients with COPD. Furthermore, having COPD more than doubled the risk of developing heart failure.”

Dr Rahul Potluri, founder of the ACALM 91ֱ�� Unit, Aston Medical School, said: “Despite the increased risk of heart disease, patients with lung diseases were less likely to receive heart treatments. Potential reasons include difficulties in diagnosis due to similar symptoms, and heart treatments having higher rates of complications in patients with lung diseases. Further work is required to understand this finding in more detail and how it could be addressed.“

Dr Chris Miller, senior author of the study from The University of Manchester said; “Research into why lung disease is associated with heart disease and the underlying disease mechanisms, is urgently required. If we could understand that, then we could potentially develop treatments that target these disease pathways.”

An international research team led by investigators from Massachusetts General Hospital (MGH), the , including the Universities of Bristol and 91ֱ��, has identified 57 gene regions associated with symptoms of insomnia. Their report, which also indicates a causal link between insomnia and coronary artery disease, is receiving advance online publication in s.

“Our findings confirm a role for genetics in insomnia symptoms and expand upon the four previously found gene loci for this condition,” says Jacqueline M. Lane, PhD, of the and the , lead author of the paper. “All of these identified regions help us understand why some people get insomnia, which pathways and systems are affected, and point to possible new therapeutic targets.”

Insomnia affects around 10 to 20 percent of the population, and twin and family studies have suggested that about a third of the risk of insomnia is inherited. While evidence has suggested that insomnia increases the risk of anxiety disorders, alcohol use disorder, major depression and cardiometabolic disease, little has been known about the mechanisms involved.

A 2017 Nature Genetics study led by Lane and Richa Saxena, PhD, MGH Anesthesia and Center for Genomic Medicine, who is senior author of the current report, identified three gene sites associated with self-reported insomnia symptoms among more than 112,500 participants in the UK Biobank study. For the current study the team analyzed data from more than 450,000 UK Biobank participants, 29 percent of whom reported frequent insomnia symptoms.

The analysis associated 57 gene sites with self-reported insomnia, associations that were not affected by known risk factors such as lifestyle, caffeine consumption, depression or recent stress. The genomic regions identified include genes involved in ubiquitin-mediated proteolysis – a process by which proteins are tagged for destruction – and those expressed in several brain regions, skeletal muscles and the adrenal gland. While some of these genes imply connections between insomnia symptoms, restless leg syndrome and coronary artery disease, the identified regions did not include neurotransmission genes known to be involved in sleep regulation.

To test whether the UK Biobank results generalize to other populations, the researchers analyzed data from the HUNT study – an epidemiologic study based in Norway – and from the Boston-based Partners Biobank. The comparisons of 15,000 HUNT study participants who reported insomnia symptoms with more than 47,600 controls and of 2,200 Partners Biobank participants with clinical diagnoses of insomnia with 14,240 controls confirmed the UK Biobank findings.

Data from a subset of almost 85,000 UK Biobank participants who had worn motion-detecting devices called accelerometers for up to seven days suggested that the insomnia-associated gene regions lowered sleep efficiency – a measure of the quality of sleep – and the duration of sleep and increased day-to-day variations in sleep duration. Shared genetic factors associated with insomnia and restless leg syndrome support previous work from the MGH team and suggest that undiagnosed restless leg syndrome may underlie insomnia for some patients.

An analysis technique called Mendelian randomization, which can reveal whether one of two traits present in individuals may cause the other, indicated that increased insomnia symptoms were causative of coronary artery disease – almost doubling the risk – symptoms of depression and a reduced sense of well-being. Co-lead author Samuel Jones, PhD, of the University of Exeter, says, “Insomnia has a really significant impact on millions of people worldwide. We’ve long known there’s a link between insomnia and chronic disease. Now our findings suggest that depression and heart disease are actually a result of persistent insomnia.”

MGH investigator Lane adds, “All of these identified regions are possible new therapeutic targets for insomnia, and 16 of these regions contain known drug targets. As well, the new causal relationships indicate the potential usefulness of insomnia therapeutics as possible treatments for coronary artery disease and depression.”

Co-senior author Michael Weedon, PhD, University of Exeter, adds, “There are problems with current treatments for insomnia – including issues with accessibility, addiction and side effects. We hope that understanding more about the underlying processes involved in insomnia will pave the way for better and more personalized treatments, which in turn could reduce the number of people suffering from insomnia and improve the long-term health of those that do.”

Co-senior author Dr Martin Rutter from The University of Manchester said: “We highlight a causal link between genetic risk for insomnia and coronary heart disease and feel this is particularly important. Our work suggests that improving sleep quality could have important public health benefits by reducing the burden of heart disease in the population. It’s important to point out that many people with insomnia will not get heart disease. But by identifying the potential risks, this research will encourage people who do have difficulty sleeping to seek help and find ways to address it. We can now start to investigate the potential molecular pathways linking sleep disturbance to heart disease to understand this process more fully.”

An associate professor of Anesthesia at Harvard Medical School, senior author Saxena says, “Next comes the hard work of figuring out how we get from genetic changes to insomnia. This requires studies in human cells, mice, fruit flies, zebrafish and other model organisms. In addition, detailed studies that more precisely define the causal links of insomnia to clinical outcomes are imperative. None of this work is possible without large collaborative studies across multiple institutes and countries. The UK Biobank is a transformative study in scope and scale, and we need more studies like it, particularly in groups that are underrepresented in genetic studies.”