The news offers hope that doctors may one day be able to investigate suspected kidney pathologies without carrying out invasive procedures such as biopsies, raising the tantalising prospect of earlier and simpler disease detection.

The impact of late detection of kidney disease can be severe and can lead to serious - and sometimes life threatening - complications.

The team led by University of Manchester scientists measured the levels of approximately 20,000 genes in each cellular sediment sample of urine using a technique called transcriptomics.

The British Heart Foundation-funded study benefited from access to the world's largest collection of human kidney samples collected after surgery or kidney biopsy conducted before transplantation, known as the Human Kidney Tissue Resource, at The University of Manchester.

They extracted both DNA and RNA from each sample and connected information from their analysis, together with data from previous large-scale analyses of blood pressure (called genome-wide association studies), using sophisticated computational methods.

Transcriptomics allows scientists to understand which genes are turned on or off in different situations so they can understand how cells respond to changes in their environment.

Such molecular-level understanding enhances the precision and effectiveness of diagnostic approaches, potentially improving patient care and outcomes.

The study, published in Nature Communications today (19/03/24) also showed that low levels of a specific gene in the kidney is likely to be one of the causes of high blood pressure.

The gene, called ENPEP, is an important part of the hormonal system which is essential for regulation of blood pressure, by making an enzyme called aminopeptidase A.

It was one of 399 genes identified by the researchers whose levels in the kidney are also causally related to either increasing or decreasing in blood pressure.

The study was led by Chair of Cardiovascular Medicine at The University of Manchester and Honorary Consultant Physician at 91ֱ�� University NHS Foundation Trust.

He is also Integrative Cardiovascular Medicine Co-Theme Lead at the National Institute for Health and Care Research (NIHR) 91ֱ�� Biomedical Research Centre (BRC), which supported the research.

He said: “This study shows that using cutting-edge technology we are able to combine different unique datasets together using genetics as a connector.

“One of the most exciting findings of that is we discover how cells harvested from urine have the potential to provide a glimpse into the molecular operation of the human kidney.

“That gives us an exciting avenue of research for non-invasive diagnostic testing.”

He added: “Persistent high blood pressure—or hypertension—can increase the risk of a number of serious and potentially life-threatening health conditions, such as heart disease, heart attacks and strokes.

“Our results also show that the gene ENPEP in the kidney is a new promising target for development of new blood pressure lowering medications.

“There are several classes of effective antihypertensives available, though the last new medication approved for management of high blood pressure was over a decade and a half ago.

“While for some people, they are effective, side effects make it difficult for others to take over the long term. That is why we need more choice.”

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “There is a well-known link between the heart and the kidneys in regulating blood pressure. This study uses cutting-edge scientific techniques to analyse genes present in kidney cells that are normally expelled in the urine. Analysing these cells could reveal which genes may be playing a key role in people with high blood pressure, and could potentially offer clinicians a new, non-invasive way to help diagnose those with kidney disease early on.

“High blood pressure is a major risk factor for heart disease and stroke, and this research has identified a gene called ENPEP that regulates important enzymes in the kidney that could be a promising target for blood pressure-lowering drugs. This study has demonstrated the power in using large sets of data and in doing so, shows how funding research like this can help us to improve treatment for people with high blood pressure.”

The paper Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates  new blood pressure and hypertension targets  is available . The DOI for the paper is 10.1038/s41467-024-46132-y

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

The study, led by Professor Holly Shiels from The University of Manchester and funded by the British Heart Foundation, is published in the influential  

Thanks to earlier work by Professor Shiels in conjunction with scientists at Stanford University, University of Bristol, Moscow State University and The National Oceanic and Atmospheric Association (NOAA), phenanthrene’s toxicity to the hearts of fish and crustaceans (crayfish) has been well established.

But now the team have discovered the change also occurs in healthy mouse hearts when directly exposed to phenanthrene, mimicking what happens when we breath in pollution.

She said: “We’ve known that phenanthrene is causally linked to cardiotoxicity in fish for many years-  scientists recognised this following the disastrous impact of the Exxon Valdez oil disaster in Alaska in 1989.

“But we now know this same effect occurs in mammals, and we are also able to show its causal mechanism.”

Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) that is present in crude oil and emitted into the air when fossil fuels are burnt.

“It is widely known that PAH’s in general are bad for human health, but no one really studied the impact of the lower molecular weight PAH’s” said professor Shiels.

Dr Sana Yaar, A British Heart foundation funded PhD student at The University of Manchester who is the lead author on the study, said: “Similar effects in humans could have serious health consequences which is why we need greater regulatory attention of this ubiquitous pollutant generated from fossil-fuel combustion.”

Phenanthrene is one of the compounds produced when fossil fuel is burned; it is present in the gas phase of air pollution and also adheres to the surface of particulate matter (PM).

It can be inhaled into the lung and then translocated into the bloodstream, eventually finding its way to the heart. Epidemiological evidence has long shown a positive association between PM2.5 concentration and the incidence of arrhythmias and both PM and diesel particles have been shown to trigger arrhythmias in rodents.

“Our findings suggest phenanthrene could be involved in these pathologies” says Prof Shiels.

In the study, when phenanthrene was applied to an isolated mouse heart, it caused monophasic tachycardia, which is when the heart starts to beat too quickly.

Tachycardia is a form of arrhythmia common in people who have scarring caused by a heart attack or past heart disease.

The researchers were able isolate single heart muscle cells known as myocytes to understand how electrical dysfunction arrhythmias were achieved.

They showed that phenanthrene disrupts the contractile and electrical function of the mouse heart by blocking ion channels required for synchronous beating of the heart. 

“Our study provides proof of concept that phenanthrene exposure can be proarrhythmic” says Prof Jules Hancox, co-author from the University of Bristol. “To understand the risk this poses to humans, more information is now needed on the levels phenanthrene can reach in the heart following occupational or environmental exposure.”

Co-author Ellie England and British Heart Foundation funded PhD student from The University of Manchester said: “If the effects of phenanthrene shown here for mice extend to humans, it could be particularly dangerous to people with existing heart problems, including the elderly.  Unfortunately, the authorities do not routinely measure the amount of PAHs or more specifically, phenanthrene, in the air.

“We think this is a mistake, as individuals who are vulnerable to heart disease would benefit from knowing the dangers of inhaling or ingesting phenanthrene”

She added: “If monitoring was in place there’s much doctors and public health officials could do to help vulnerable people reduce the risk of cardiotoxicity resulting from phenanthrene exposure.

“For example, at risk groups could stay indoors when there’s a spike in pollution, use air purifiers and avoid busier streets.”

Professor Shiels added: “As combustion engine technology improves, PM from car exhaust is reducing in many cities and that is beneficial to human health.

“But what many people don’t realise is that fossil fuel combustion also produces ultrafine PM, which has a greater capacity to enter the blood stream due to its small size, is rarely monitored.  And even electric cars that increase tire wear particle formation to their heavy weight, also impact our health. 

“That is why we should be routinely monitoring for phenanthrene and other PAHs in the air.”

The paper Global air pollutant, phenanthrene, and arrhythmic outcomes in a mouse model, is published in Environmental Health Perspectives

The MCT-PATHWAY and PATHWAY Beacons led by Professor Adrian Wells  secured the place at the prestigious awards ceremony, to be held later this year, for their outstanding  contribution to healthcare

The scheme was among a record-breaking 1456 entries received for this year’s Awards, with 223 projects and individuals reaching the final shortlist, making it the biggest awards programme its 43-year history.

Approximately 100,000 people attend cardiac rehabilitation each year in the UK. The NIHR-funded PATHWAY programme is the UK’s first successful group-based mental health intervention (Metacognitive therapy; MCT) that can be delivered alongside usual cardiac rehabilitation (CR). Group-MCT+CR was found to significantly improve anxiety and depression and halve the deterioration rate in comparison to usual care.

This is of vital importance as heart disease patients suffer significant anxiety and depression, which is not routinely treated in cardiac services and is linked to poorer health outcomes, greater mortality, greater healthcare use, and poorer quality of life. The follow-on NIHR-funded PATHWAY-Beacons project is currently evaluating the effect of implementation and roll-out of MCT-PATHWAY in the NHS.

"The team and I are thrilled to be shortlisted for the mental health innovation of the year award. A big thank you to the HSJ judging panel and to all our collaborators and participants whose dedicated work has improved the mental wellbeing of people living with heart disease"   said Professor Wells, Chief Investigator, from The University of Manchester and GMMH NHS Trust.

Patients who have received MCT as part of the roll-out of MCT-PATHWAY given it rave reviews: One patient, Angus told the research team:  “I truly do not know if I would still be alive if it was not for the course”

And another, Jan said: “Without this service I don't think I would have got to were I am now, they gave me confidence that I could live my life again and feel normal, easing all the anxiety I felt after my cardiac event.”

HSJ editor Alastair McLellan, said: “It always gives me great pleasure to congratulate our finalists at this stage of the judging process and this year is no exception as we acknowledge MCT-PATHWAY and PATHWAY Beacons for being shortlisted in the category of Mental Health Innovation of the Year.

“However, it’s always important to remember that the HSJ Awards are not just a celebration of success stories but also a platform to shape the future of the NHS.

“We can’t wait to welcome our finalists to the awards ceremony in November and to recognise and applaud such impressive achievements across the sector – as well as coming together to help mark the 75th birthday of our great NHS. Huge thanks also go to our new headline partner, Vodafone, who share our mission of driving the standard of healthcare excellence and creating better patient experiences.”

The 2023 awards judging panel was made up of a diverse range of highly influential and respected figures within the healthcare community, including; Crystal Oldman, Chief Executive, Queen’s Nursing Institute; Dr Habib Naqvi MBE, Chief Executive, NHS Race and Health Observatory; Anne-Marie Vine-Lott, Director of Health, Vodafone; Sir Jim Mackey, National Director of Elective Recovery, NHS England, as well as a range of esteemed Chief Executives from NHS Trusts across the UK.

The British Heart Foundation funded study, published today(2/09/21) in Circulation Research- the leading journal in its field - could have important implications on the management of the condition on humans.

In female sheep, the drug - also known as sildenafil - was able to suppress an arrythmia called Torsades de Pointes within 90 seconds by reducing the frequency of irregular heart rhythms caused by abnormal handling of calcium.

It also reduced the probability of Torsades de Pointes, which can lead to sudden cardiac death. However, the team believe the drug could treat other arrythmias as well.

Cardiac arrythmias often follow a heart attack, or result from heart disease. Though often benign , they can cause symptoms including palpitations, breathlessness, fainting and sometimes sudden death.

Treatments such as beta blockers and implantable defibrillators exist, though are not always effective.

Working on isolated sheep heart muscle cells known as myocytes, the research team were also able to measure their calcium stores- as well as their electrical properties.

Although calcium is a key driver of the heart’s pumping action, its overload can be a root cause of arrythmias. Viagra was able to suppress the mechanism in the cell which causes calcium overload.

When a small amount calcium enters a myocyte, it triggers the Sarcoplasmic Reticulum (SR)- a calcium store - to release a larger quantity of calcium.

When there is heart disease, the SR can become overloaded with calcium which in turn makes the heart beat at the wrong time- when it is supposed to be resting between beats.

The mechanism is part of an  enzyme pathway inside the cell involving PDE5 and activating a protein called protein kinase G which impacts on the arteries in the penis allowing blood to pump into it.

A similar mechanism exists around the muscle cells of the heart but has never been studied until now.

Dr David Hutchings is a lecturer at The University of Manchester. The paper’s lead author said: “Not only has this study demonstrated that Viagra has a powerful antiarrhythmic effect on living heart tissue, our cell studies have also uncovered the mechanism by which this happens.

“Though we studied the effect in sheep, we believe this discovery is likely to be relevant humans: the humans heart is a similar size to a sheep’s, as is its anatomy and associated electrical circuitry.

“So this discovery could one day unleash the potential for effective treatment on what can be a devastating problem.

“Clearly, anyone who has a cardiac arrythmia should not self-medicate and should consult their GP for advice on current treatment options.”

Principal Investigator Professor Andrew Trafford, from The University of Manchester said: “This exciting study builds on our previous work funded by The British Heart Foundation around the effect of Viagra on the heart.

“In 2016, our study of patients with diabetes showed that incidental use of Viagra was linked with reduced heart attack risk and improved heart attack survival.

“In 2019, we found that Viagra can slow or even reverse the progression of heart failure in sheep and this work dramatically extends those important findings providing another tool with which to beat heart disease.

“Much more work still needs to be done- but we feel we are getting closer to a effective and powerful alternative to current treatments.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “A better understanding of how heart rhythm disturbances occur could pave the way for better preventions and treatments for them.

“This study suggests that the enzyme PDE5, which is suppressed by Viagra, may also play a key role in causing abnormal heart rhythms that arise from an overload of calcium in sheep heart cells. This could be important because the electrical behaviour in these cells is similar to that of human heart cells.

“More research is needed, however, before Viagra and similar drugs can be repurposed for treating abnormal heart rhythms in patients.”

PDE5 inhibition suppresses ventricular arrhythmias by reducing SR Ca2+ content” is pub;ished in .

The University of Manchester-led study found that long-term exercise in retired racehorses – the best available model of the athlete’s heart - and in mice, triggered molecular changes in a part of the heart known as the atrioventricular (or AV) node. 

The work is the latest in a series of studies conducted by the team, showing that endurance exercise directly impacts the electrical wiring system of the heart.

Despite well-recognised cardiovascular benefits, sustained endurance exercise in athletes, footballers and other sportspeople can lead to the development of abnormal heart rhythms - known as cardiac arrhythmias, including heart block.

While benign for many people, heart block - also known as AV block - can be a precursor to more serious heart problems.

The team is the first to research the physiology of the notoriously hard-to-study AV node in athletes. The expertise to investigate the structure and function of the AV node has been developed by the 91ֱ�� team with longstanding BHF funding.

The heart’s AV node is part of its electrical conduction system controlled by the autonomic nervous system and electrically connects the atria and ventricles.

The study, published in the leading journal , found that long-term training in both horses and mice caused a reduction in key proteins, known as ion channels, that control AV node conduction.

The expression and activity of the ion channels were then investigated in detail in mice that followed a program which modelled long-term exercise training to build their fitness.

The mice were used to explore mechanisms underlying heart block in detail using approaches that would not be possible in racehorses.

Training-induced heart block and underlying ion channel changes were reversible when the exercise was stopped or when mice were given a compound known as an anti-microRNA.

Lead author Dr Alicia D’Souza, a British Heart Foundation Intermediate Fellow from The University of Manchester, said: “It’s well known that athletes are predisposed to heart block which in itself is often benign.

“But clinical research suggests that this may be ‘a canary in a coalmine’: it can flag up the risk of abnormal heart rhythms which may for example necessitate the implantation of a pacemaker in some individuals.

“For the first time our research highlights the fundamental adaptations taking place. Because we found similar effects on both mice and racehorses, it’s fair to assume this mechanism is present in humans too.”

“It must be stressed that exercise is good for you – and its benefits far outweigh the risks.”

First author Dr Pietro Mesirca, a researcher from the Institute of Functional Genomics in Montpellier said: “Understanding the physiology of the athlete’s heart is incredibly helpful: it could help us develop new interventions for heart block as well as help doctors more effectively monitor heart rhythm disturbances in top-flight professional athletes.”

Equine cardiologist and co-author of the study, Professor Rikke Buhl Professor Rikke Buhl from University of Copenhagen said: “Like human athletes racehorses suffer from cardiac arrhythmias and unfortunately also sudden cardiac death during or immediately after racing. Therefore, the results of this study have provided new insight into exercise-related cardiac changes in horses, which is of highly relevance for horse welfare as well as for owners and trainers of horses.”

The  paper ‘Intrinsic electrical remodelling underlies atrioventricular block in athletes’ is published in 

These findings, published in the American Heart Association journal, , are a huge step towards better informed and well-rounded care for heart disease patients, with the potential to improve not only mental health, but also the physical health of those recovering from heart disease.

Cardiac rehabilitation (CR) services aim to improve heart disease patients’ health and quality of life, and reduce the risk of further problems with their heart. Around 90,000 patients attend CR every year in the UK.

After a serious cardiac event, such as a heart attack, it is common to develop mental health problems; and around one-third of patients accessing CR services experience anxiety and/or depression. Research shows that this type of distress reduces quality of life, and increases the risk of further heart problems and even death.

Whilst CR services do have an educational component and an exercise component, they don’t currently include any specific mental health treatment to support patients with symptoms of anxiety and depression.

Added to this, mainstream mental health treatments, such as Cognitive Behavioural Therapy (CBT), are not very effective at improving the mental health of heart disease patients. One of the reasons for this is that CBT focuses on challenging negative thoughts and beliefs, which can be completely valid and realistic in people suffering from chronic and life-threatening heart conditions.

In response to this, Professor Adrian Wells, Consultant Clinical Psychologist at GMMH and Professor of Clinical and Experimental Psychopathology at UoM, who had developed a mental health treatment called Metacognitive Therapy (MCT), adapted this treatment for cardiac patients. MCT helps people to manage worries and low mood through reducing unhelpful styles of thinking, such as rumination (dwelling on the past) and worry (concerns about the future). It helps people to discover new and more helpful ways to react to negative or distressing thoughts so they are less likely to dwell on them, resulting in improved anxiety and mood.

The PATHWAY study evaluated the effectiveness of delivering MCT, alongside normal CR services, in treating symptoms of anxiety and depression in heart disease patients, in comparison to just receiving normal CR services alone.

Half of the 332 participants were randomly allocated to MCT plus standard CR treatment, and the other half were allocated to the standard CR. For those who were allocated to MCT, the therapy was embedded into their regular CR, and delivered by CR staff such as CR nurses, occupational therapists, and physiotherapists.

This took place at 91ֱ�� University NHS Foundation Trust, East Cheshire NHS Trust, Stockport NHS Foundation Trust and Pennine Acute Hospitals NHS Trust.

Findings showed for the first time ever that MCT plus CR is significantly more effective in improving symptoms of anxiety and depression in heart disease patients.

It also proved to be more effective in helping patients reduce unhelpful thinking patterns and trauma symptoms.

Debra was referred to group Metacognitive Therapy, following open heart surgery. She said:

“I found the MCT to be very interesting, informative and beneficial. It's not a type of therapy I had experienced before; it was a very gentle and subtle therapy that, over several weeks, slowly changed my attitudes and beliefs around worrying and fretting. 

“It was very interesting and useful to hear how people's beliefs changed over the weeks. To see the differences at the end was quite impressive. 

“Although the therapy was quite some time ago, it has stayed with me and it's something I naturally practice now, almost subconsciously.

“Although it's human nature to have concerns about certain situations, I don't spend time worrying and fretting about things as I know that it's wasted energy that does not change the outcome.

“I think it's a very useful life skill that anyone would benefit from, but particularly those who have suffered from any traumatic event, be that physical or mental and those that suffer with anxiety.”

Effectiveness of the therapy was measured with the Hospital Anxiety and Depression Scale (HADS). The HADS questionnaire is often used to determine the levels of anxiety and depression in a person with physical health problems, using a scale of 0 to 21 for both anxiety and depression. A score of 0-7 is considered normal, with 8-10 being borderline, and 11 or over indicating clinical anxiety or depression.

The 163 individuals who were randomly allocated to MCT plus standard CR treatment showed a significant average decrease in their HADS score for anxiety and depression of 3.24 after 4 months and 2.19 after 12 months. This compares to the 169 who only received standard CR treatment, who had an average decrease of 0.52 after 4 months and 0.33 after 12 months.

Overall, there was an improvement in the mental health of one in three heart patients who received MCT alongside standard CR treatment, in comparison to only one in five of those who received standard CR treatment. A further finding was that MCT appeared to prevent some patients from developing mental health problems.

The link between mental and physical health has long been known, and these findings signal a major step in understanding and improving the overall recovery of heart disease patients.

Professor Adrian Wells, PATHWAY Chief Investigator said,

“Living with serious physical illness has profound effects on emotional wellbeing, how sufferers view themselves, their future and their quality of life.

“Through the generous time of patients, staff, co-investigators and service users, we have made a breakthrough in improving mental health outcomes in heart disease patients.

Metacognitive therapy offers an effective way of treating both anxiety and depression. We found that heart patients benefitted no matter whether they had mild or severe symptoms or a previous history of mental health issues, supporting the versatility of this treatment.

We have demonstrated that MCT can be translated to medical settings and this opens up the way for more effective integrated physical and mental health care with the potential to improve thousands of people’s lives”

Paula Bithell, Nurse Consultant at Pennine Acute NHS Hospitals Trust said:

“For some patients the psychological impact of being diagnosed with a heart condition can be just as significant as the physical implications.

“MCT is a method to address the thoughts patients may have following their cardiac event in a familiar environment, in a group setting with patients who are experiencing similar thoughts and feelings to themselves. It is delivered by their recognised health care professionals who are experienced in cardiac care.

“My colleagues and I found that patients benefited hugely from the group therapy, with patients reporting that attending the group MCT supported them in overcoming the psychological barriers that were preventing them from resuming normal activities.

“Following the treatment, patients reported feeling more confident to go out and socialise again, resume hobbies and employment.”

Professor Kathryn Abel, NIHR Clinical Research Network National Specialty Lead for Mental Health and Domain Lead for Mental Health at NIHR Clinical Research Network Greater 91ֱ��, said:

"Findings from this research are incredibly encouraging and present the first evidence that a psychological treatment may both prevent development of common mental disorder in cardiovascular disease as well as be effective in reducing psychological symptoms once developed in cardiac patients recovering from heart disease. Understanding the links between mental and physical disorders is an incredibly important aspect of the research endeavour for the NIHR mental health specialty and a priority for the Medical Research Council (MRC) Mental Health Research Framework.

I would like to thank all the study participants and research team members who have made this research possible."

The British Heart Foundation funded study ‘completely changes our understanding’ of the heart’s anatomy and has important implications on the work of cardiologists and heart surgeons.

As part of the study, published in Frontiers in Physiology, University scientists carried out research involving 15 goats.

Subsequent data analysis found that a ‘subsidiary atrial pacemaker’ (SAP) takes over from the nearby sinoatrial, or SA Node, the primary way the heart generates electrical signals that make it beat, when it fails.

Lead author Dr Halina Dobrzynski, from The University of Manchester, said: “This study completely reshapes our understanding of the how the heart works and is tremendously exciting. It builds on our work on the human heart over many years and we hope will make an important contribution to future treatments.”

Co-author, Dr Gwilym Morris, a clinical researcher at The University of Manchester and a Consultant Cardiologist at 91ֱ�� Royal Infirmary, part of Manchester University NHS Foundation Trust, (MFT), worked on the data analysis strand of the project.

He said: “Not only will this knowledge improve our understanding of the anatomy of the heart – which is crucial for clinicians – it will give patients the full facts so they can make a more informed choice about ablation.”

The SA node in human, goat and other mammalian species is a group of cells located in the wall of the right atrium of the heart which have the ability to spontaneously produce the electrical impulses to make our hearts beat.

The team are confident the discoveries are highly relevant to the human heart, as the organ in goats has similar anatomy and physiology, producing a similar heart rate.

When the SA node doesn’t work as it should, the heart rate can slow down causing breathlessness and blackouts.

However, when the malfunctioning SA node is removed by cardiologists in a procedure known as ablation, the new structure discovered by the team carrying out the research in goats took over as the dominant pacemaker, which also drives electrical activity of the heart.

And even though electrocardiograms (ECGs) – which provide an electrical map of the heart – have slightly different shapes for each natural pacemaker, the heart still functioned normally when using the SAP.

The study also explains why ablation of the SA node - sometimes performed by cardiologists to treat a fast heartbeat called inappropriate sinus tachycardia - is often unsuccessful.

The research shows that the SA node is difficult to completely destroy using ablation and even if a few cells of the SA node are left, they find, it will continue to function as the heart’s pacemaker.

Dr Morris added: “I’m excited that we also intend as a team to produce a 3D reconstruction of the whole heart, which will depict the new structure. And that will be a helpful tool for helping patients to understand the pros and cons of having an ablated SA node.”

Dr Zoltan Borbas, a clinical scientist who conducted the study while at The University of Manchester said: “It was fascinating to see how the structure of the sinus node and SAP area in the goat gradually emerged. Getting closer, step by step, to understand the complexity of it was thrilling.”

Co-author Dr Luca Soattin, from The University of Manchester, said: “Before this study, it was thought the sinoatrial node was the primary activation site in the heart. When that failed, the atrioventricular node nearer to the ventricle was thought to kick in.

“But now we know of another site, the subsidiary atrial pacemaker’, which kicks in after the SA node fails. We believe this is a remarkable discovery.”

Dr Dobrzynski added: “I’m also hugely grateful to the NHS anaesthetists, surgeons and cardiologists who worked with us on this ground-breaking project.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation (BHF), said: “The heart is a wonderfully complex organ that contains many different types of specialist cells serving distinct functions. These include the cells in the heart’s own ‘pacemaker’, which generates the electrical signal triggering each heartbeat.

“This detailed study improves our understanding of how the heartbeat continues to be generated when the normal pacemaker is damaged. The findings will inform future work to better understand and treat human diseases associated with abnormal pacemaker activity.”

Figure shows:

• The heart will still function normally when it is using the SAP (Figure C).
• The SA node in a human (Figure A, red) and a goat (Figure B, yellow)
• Before and after ablation of the heart

The ‘walk through’ 3D video for the first time allows a precise anatomical classification of the disease and has important implications on future treatment for many of the heart defects humans- and animals - are born with.

The study, now published in the , started by chance when a Japanese veterinary researcher at contacted the team at 91ֱ��.

When the pet cat Dr Shu Nakao had been treating called Mi-ke sadly died, Dr Nakao had not been able to make an accurate diagnosis post mortem and decided to ask for the 91ֱ�� team’s help.

According to Dr Nakao, vets in Japan and beyond are not able to detect and report this type of congenital heart diseases in domestic animals.

Using cutting edge technology which carries out Micro-Computed Tomography (Micro CT) – one of only 2 places in the UK where it is done- the team were able diagnose a rare but distressing condition called common arterial trunk.

Micro CT can create an intricately detailed scan of the heart at a resolution of 40 microns - a quarter the width of a human hair.

Treated with heart surgery, it is found in humans and domestic animals such as cats and dogs.

Less than 1 in 10,000 babies are born with common arterial trunk– which causes acute breathlessness over the first month or so after birth; around 95 out of every 100 babies who have surgical repair will survive.

In common arterial trunk, instead of leaving the heart as two separate arteries, a single large artery divides to form the aorta and the pulmonary artery.

There is also a large hole - called a ventricular septal defect- between the two main pumping chambers ventricles of the heart causing a mixing of blood flowing to the lungs and blood flowing to the rest of the body.

Dr Andrew Atkinson said: “This scan not only provides the most detailed ever anatomical description of the condition, but also demonstrates that it can be used for any congenital problem of the heart.

“Micro-computed tomography improves our understanding of the complex morphology in congenital heart diseases which cannot be seen by the naked eye.

“And that can contribute to precise disease classification and treatment decision-making for surgeons and cardiologists.

“In animals , it’s particularly hard to diagnose and treat, so this research will be of invaluable use to vets as well.”

Dr Halina Dobrzynski said: “Not only is this technology invaluable clinically, it could be of enormous benefit to the parents of new born babies who are struggling to come to terms with these rare but distressing conditions.

“Congenital heart disease it difficult to understand, so having this as an aid to explain what is going on would be incredibly helpful.

”Now we have the tools to do this, we are inviting clinicians and veterinary surgeons to get in touch if they wish to work with us to help map these conditions.”

The paper Common arterial trunk in a cat: a high-resolution morphological analysis with micro-computed tomography is published in the

The Virtual reality video showing the heart and vessels in collaboratio0n with VR software company SyGlass courtesy of Dr Lindsey Marshall of SyGlass.

The vagus nerve - one of the nerves of the autonomic nervous system which supplies internal organs including the heart - has long been thought to be responsible for the slower night-time heart rates.

But the University of Manchester-led study on mice and rats discovered that the vagus nerve is unlikely to be directly involved and instead the sinus node - the heart’s natural pacemaker - has its own clock, a biological clock.

The sinus node, they find, knows when it is night and slows the heart rate accordingly.

The British Heart Foundation funded findings, published in Heart Rhythm, shine new light on this fundamental biological question of why the heart rate is slower at night and why dangerously slow heart rates - called bradyarrhythmias - can occur when we’re asleep.

The team behind the study demonstrated that changes in the ‘funny channel’ – also known as HCN4, a key protein that controls the heart rate - at different times of the day and night can explain the changes in heart rate.

The team found that blocking the funny channel with ivabradine, an angina treatment, removed the difference in heart rate between day and night.

The team found a role for the clock gene called BMAL1 as a regulator of the funny channel and this could one day lead to a treatment for dangerous bradyarrhythmias when we’re asleep.

Though the research was carried out in mice and rats, funny channels and clock genes play similar roles in all mammals – including humans - which is why the research has a universal significance.

Lead author Dr Alicia D’Souza, a British Heart Foundation Intermediate Fellow from The University of Manchester said: “The heart slows down when we sleep and there can even be pauses between heart beats. Strangely, this is especially true in elite athletes. The longest documented pause is 15 seconds – a very long time to wait for your next heartbeat!

“For the very first time, we have tested an alternative hypothesis that there is a circadian rhythm in the intrinsic pacemaker of the heart - the sinus node.

“Our study shows that in mice, this is indeed the case and that explains why the heart rate is slower at night.

“These basic mechanisms of heart rate regulation are conserved in mammals - including humans - and therefore widely accepted concepts that are taught in schools may one day need to be revised.”

The sinus node – sometimes known as the sinoatrial node - generates electrical impulses which cause the heart to beat. It consists of a cluster of cells in the upper part of the right upper chamber of the heart.

Previous assumptions about the vagus nerve’s impact on the heart were based on a technique-called ‘heart rate variability’.

There are over 26,000 scientific papers based on heart rate variability published over 60 years. But the team’s previous British Heart Foundation-funded work demonstrated that heart rate variability is fundamentally flawed and says nothing about the vagus nerve.

In the present study the authors used a range of measurements to assess electrical activity and genes in the heart’s pacemaker. These included studying heart rhythm and activity levels and further exploration of ionic currents, proteins and regulatory proteins called transcription factors.

Cali Anderson, a British Heart Foundation-funded PhD student and co-author added: “It is well known that the resting heart rate in humans varies over 24 hours and is higher during the day than at night.

“But for over 90 years, the daily changes in our heart rate has been - and we believe over simplistically - assumed to be the result of a more active vagus nerve at night.

“In the future these findings could have important therapeutic potential in the way we are able to understand and treat heart rhythm disturbances.”

Dr Noel Faherty, Senior Research Advisor at the BHF, said: “This research challenges a near century old consensus on how heart rate is regulated.

“A slower heart rate at night by itself is quite normal in most people, but understanding the mechanisms that govern the heart’s basic functions are crucial building blocks for tackling more complicated questions about heart rhythm disturbances.

“Worryingly, our ability to fund research like this in the future is threatened by the devastating fall in income caused by coronavirus. It is more important than ever that the public continue to support our work so that we can continue to make progress in treating and preventing heart and circulatory disease in the UK.”

The paper: A circadian clock in the sinus node mediates day-night rhythms in Hcn4 and heart rate is published in Heart Rhythm  is published in Heart Rhythm

Poor awareness of a condition known as Heart Failure with preserved Ejection Fraction (HFpEF) – the cause of a half of all cases of heart failure in England – could be hindering opportunities to improve care for patients, say researchers from the Universities of Cambridge, 91ֱ��, and Keele.

HFpEF – pronounced ‘heff peff’ – is a condition whereby heart muscles are too stiff, preventing the organ’s chambers from filling properly with blood. Symptoms include shortness of breath, swelling in the legs, ankles, feet or in the lower back or abdomen, and extreme tiredness. It affects half of the 920,000 people in the UK with heart failure but frequently goes undiagnosed.

The National Institute of Clinical Excellence (NICE) recommends that ‘integrated’ care should be provided for HFpEF, bringing together specialist clinicians with GPs and primary care, and including support for patients to help them manage their condition.

In a new study published today in the British Journal of General Practice, the researchers argue that the problems they have identified may help to explain why the condition is difficult to diagnose and why there is a persistent gap between the national guidance on managing the condition and the kind of service patients receive.

The problems were uncovered in a study carried out in the East of England, Greater 91ֱ�� and the West Midlands, in which 50 people with HFpEF, nine carers and 73 clinicians, were interviewed. The clinicians included GPs and nurses from 26 GP practices, as well as heart failure specialist nurses and cardiologists from nine hospitals.

The team used a theoretical framework known as Normalisation Process Theory to make sense of the large amount of data generated by the interviews. The theory considers how healthcare interventions are integrated into routine practice, or ‘normalised’.

For any intervention to be routinely adopted, there needs to be a clear understanding – and differentiation between – aspects of the illness, tests and treatments, for example. The team found that this understanding is often missing for the clinicians dealing with patients experiencing HFpEF. In addition, some patients described how they were not aware they had the condition despite severe symptoms and, in some cases, multiple hospital admissions, and were unclear on how the condition can be best managed.

The data confirmed that diagnosis and treatment of HFpEF is not part of everyday practice in general practice, and that the condition was not widely visible, understood, or diagnosed within primary care. The researchers identified three clear tensions that contributed to this.

First, diagnosis of HFpEF is difficult and often delayed. A common method for identifying heart disorders is through the use of an echocardiogram, but in patients with HFpEF, the ‘ejection fraction’ – the percentage of blood leaving the heart each time it contracts – often appears normal or almost normal, confusing diagnosis. Many clinicians indicated a need for specialist opinion but referral systems were varied and inconsistent.

Patients’ descriptions of their diagnoses frequently conveyed a convoluted and protracted series of hospital admissions or visits to specialist clinics. Diagnosis was often slowed down by the presence of other co-existing health conditions, non-specific symptoms and breathlessness.

Second, there are varying perceptions of this complex condition and the data show little shared understanding between clinicians, patients and carers. Several clinicians indicated there is professional scepticism with the label of HFpEF, and most expressed a need for more knowledge and understanding of the condition.

Many patients had partial or incomplete knowledge of the condition, which often related to existing heart problems. Few patients provided a clear understanding of their heart failure.

Finally, once patients are diagnosed, the services they can access are variable. Roles and responsibilities are not well understood and there are big gaps in care. A sense of clinical inertia was revealed within some patient and clinician accounts, apparently due to a lack of evidence-based practice and a feeling that there was little that could be done.

“Our research paints a picture of a cloud of clinical uncertainty surrounding the diagnosis and treatment of HFpEF, which often leads to a failure to manage the condition,” said lead author Dr Emma Sowden from the University of Manchester. “Patients’ descriptions of their diagnoses suggest they are far more convoluted than the clinical guidelines spell out, leading to a protracted series of hospital admissions or specialist visits.”

Professor Christi Deaton, Chief Investigator from the Department of Public Health and Primary Care at the University of Cambridge, added: “We heard some clinicians asking: what’s the point of diagnosis if there is no specific treatment? But identification of HFpEF is critical if we are going to develop new treatments and ways for patients to better manage their condition, and there are actions that we can take now.”

The study is part of a larger programme of work on HFpEF, which aims to improve the management of people with HFpEF in primary care. The programme is funded by the NIHR School for Primary Care Research.

Living with HFpEF: Mike and Anna

Mike and Anna, who live in Mossley, Greater 91ֱ��, are, in their own words, glass-half-full people. But Mike has heart failure with HFpEF.

Until he retired on health grounds two years ago, aged 66, Mike was a police community support officer, a job that he loved. Anna, his wife of 17 years, is a retired health visitor and nurse midwife – “It’s a good thing I have medical knowledge,” she said. “I’ve needed it.”

HFpEF comes on slowly, Mike explained. He has had heart problems for 24 years and despite a pacemaker and later a stent, and now a regime of 13 different medications a day, his symptoms don’t seem any better. He is tired all the time, breathless and his activity is severely limited.

“From a personal point of view it is so frustrating to go from being someone who swam three times a week and walked 8 miles a day to being all washed up,” said Mike.

“My GP says it’s multifactorial. But no matter what you say to a consultant, [they say] it’s because I eat too much. You do get a condescending attitude about food. I get conflicting advice from various professionals about what I should and shouldn't be doing. They say exercise and lose weight but I set all the alarms off on the monitors when the cardiac physiotherapist was assessing me and she told me to stop right there.

“I do end up asking: why am I taking all these medications and I still feel so bad? I’m treading water just waiting for the next consultation.”

Anna is determined to help Mike get access to treatment that might improve his quality of life. As she saw it, things didn’t add up.

“I’m like a dog with a bone,” said Anna. “I said, why is he still breathless if he has the stent and all the medications? I think I was the one who found out about the possibility of HFpEF, and I researched the medical terminology, like diastolic dysfunction and what ejection fraction means.

“HFpEF seems to be classed as a second class citizen of heart failure. The medics don’t tell you that you have it and they don’t tell you it’s serious. It’s frustrating for the doctors too, because the test results are not clear and they don’t know how to treat it. But we have had to fight for every little bit [of help].”

Sowden, E et al. Understanding the management of Heart Failure with Preserved Ejection Fraction: a qualitative multi-perspective study. BJGP; 3 Nov 2020; DOI: 10.3399/bjgp20X713477

A drug has shown potential to improve heart function in women diagnosed with preeclampsia during their pregnancy, research carried out by and The University of Manchester (UoM) – has found.

The results of the ‘Postnatal enalapril to Improve Cardiovascular fUnction following preterm Preeclampsia’ (PICk-UP) feasibility trial were published in the peer-reviewed journal, , today.

is a medicine already available on the NHS, and is used to reduce high blood pressure and to prevent or treat heart failure. is a condition that affects some pregnant women, the main symptom of which is . 

High blood pressure in pregnancy is associated with future , a general term for conditions affecting the heart or blood vessels. Because of this, researchers from the , at Saint Mary’s Hospital, saw an opportunity to identify women who could benefit from targeted treatment at an early stage.

The PICk-UP study focused on the highest-risk group – women with pre-term preeclampsia – who have an eight-fold risk of developing serious CVD in future.

60 women receiving care at Saint Mary’s Hospital – part of MFT – consented to take part in the six-month pilot study, funded by the . Results indicate that those who received enalapril showed improved heart function, compared with those receiving a placebo.

Enalapril was given to women after birth, as the drug is not safe to take during pregnancy, but is safe in breastfeeding mothers.

Dr Laura Ormesher, a Clinical Research Fellow at the Tommy’s 91ֱ�� Maternal and Fetal Health Research Centre – a partnership between MFT and The University of Manchester – is the lead author of the PICk-UP study.

Dr Ormesher said: “We are extremely grateful to the women who took part in PICk-UP. Our results have shown early potential to improve maternal health in the postnatal period, with a safe and affordable medicine.

“We now plan to take this further, aiming to expand the study across the UK and are very excited about the next steps.”

Jenny Myers, Consultant Obstetrician at Saint Mary’s Hospital, Professor of Obstetrics and Maternal Medicine at UoM and Chief Investigator of the study said: “This is fantastic work from Dr Ormesher and the multidisciplinary team that delivered this study.

“Women diagnosed with preterm preeclampsia are eight times more likely to develop serious cardiovascular disease in future – to date there are no treatments which have been proven to reduce this risk. This study is the first step towards an acceptable treatment for women, which if shown to be effective in larger studies, could dramatically improve the long-term health of the women affected by this common pregnancy complication.

“This pilot has confirmed the feasibility of this treatment, and we are now ready to plan a larger clinical trial at other hospitals nationally, which is one of many great examples MFT leading the way with our cutting-edge research and innovation.”

A new research project funded by the British Heart Foundation (BHF) at the University of Manchester aims to find a way to slow down the progression of heart failure.

Heart failure is a life-threatening condition that affects 920,000 people in the UK. For people with severe heart failure, everyday tasks like going upstairs or walking to the shops can become impossible.

Problems with the heart’s natural recycling system can result in the onset and development of heart failure. Autophagy, which means ‘self-eating’, is a way for the heart to dismantle cell contents and proteins it no longer needs, and recycle useful parts such as glucose and amino acids. However, if the heart becomes stressed for too long, for example as a result of high blood pressure, autophagy may fail to work normally. As a result, either toxins accumulate or healthy cell contents are over-digested in heart cells. These cells gradually stop working and die, contributing to heart failure.

Researchers at the University of Manchester have identified a novel protein which is involved in the regulation of autophagy in the heart, and believe it plays a key role in causing heart failure. They will now investigate this protein in mice to identify whether it could be a target for slowing down the progression of the condition.

This two-year project, which has been awarded £178,000 by the BHF, could result in new treatment targets that will potentially offer longer and better-quality life to people living with heart failure.

“The longer autophagy is balanced, the longer heart cells can survive and heart failure can be slowed down,” said Dr Wei Liu, who is leading the study. “In preliminary data we found that, in end stage heart failure, the level of the identified protein is dramatically increased, which indicates that this protein may contribute to the progression of heart failure. If we find that keeping this protein at a lower level limits the progression of heart failure, it could provide an exciting new target for therapies.”

Subreena Simrick, Senior Research Advisor at the British Heart Foundation, said: “Heart failure is a devastating condition, affecting a growing number of people in the UK.

“This project at the University of Manchester, while at an early stage, could offer a new target for slowing down heart failure. Further research will need to be carried out in humans to see if this research will result in longer, healthier lives for those living with the condition.

“Funding for this research has only been made possible by the generosity of the people who support us, in our aim to beat heartbreak forever.”

Analysis from the BHF shows that hospital admissions for heart failure in the North West rose by almost half between 2013/14 and 2018/19 (8,600 to 12,700 -- a 48% increase). (1)

As the number of people living with heart failure rises, the BHF has launched the new £1million Hope for Hearts Fund to find innovative ways of caring for people with heart failure that can be trialled immediately. The charity is also continuing to invest in research into regenerative medicine, which could lead to new treatments within a decade.

Elaine Harris, 54, from Billinge in Wigan was diagnosed with heart failure following a heart attack in 2014. Elaine said, “I really welcome this new investment in research into my condition. Living with heart failure can leave you weak, tired and unsure about what the future holds. It’s reassuring to know that the BHF is funding research which could slow heart failure down and give people like me longer to live.”

A study at The University of Manchester will analyse heart patients’ activity levels through their pacemakers, to determine which people are at the highest risk of frailty and help them avoid long hospital stays.

The British Heart Foundation-funded study, supported by Medtronic, aims to help older people living with heart disease and heart failure. By identifying predictors of illness, it is hoped that doctors will be able to treat patients in the community before they become acutely ill. Older cardiac patients with frailty have high rates of long-term and often unsuccessful hospital admissions, and helping them to recover at home could relieve pressure on the NHS.

Cardiac monitoring devices, such as pacemakers and implantable cardioverter defibrillators (ICDs), can record and store data on patients’ physical activity which can be transmitted via a Bluetooth connection. Many patients are able to upload this data from home.

The researchers at The University of Manchester, led by Dr Adam Greenstein, will download this data, and use it to analyse whether patients with lower levels of physical activity are more likely to be hospitalised. This may be because they have a virus or infection, or have suffered a fall. If that is the case, in the future it may be possible to intervene before a patient’s health deteriorates to the point of needing to be hospitalised, for example by sending out a community nurse.

The clinical fellowship was awarded £123,000 by the BHF and will last two years, involving 150 patients aged 60 and older, recruited from 91ֱ�� Royal Infirmary.

The University of Manchester recently received a £1million Research Accelerator Grant from the BHF to support world-leading research into heart and circulatory diseases, which kill more than one in four people in the UK.

Jim Standing, 75, from Clayton le Dale in the Ribble Valley is one of those taking part in the study. In May 2016, Jim was travelling back from 91ֱ�� with his wife from a show when he suffered a cardiac arrest. Fortunately, there was a nurse on the train who gave Jim CPR until paramedics arrived with a defibrillator.

Jim said: “I got on the train, sat down, and simply died. It was terrifying for my wife. I had always been fit and healthy, but my dad died from cardiac ischaemia at the age of 63 and that was always a shadow hanging over me.

“Following a poor prognosis I spent three weeks in 91ֱ�� Royal Infirmary and that’s when I started to realise just how lucky I had been. During this time I often wondered what my future might hold, would I be around for my wife's mother's 100th birthday, see my grandson graduate or be able to celebrate our golden wedding anniversary?

“I had an ICD fitted and nine months later I had a quadruple bypass. There has been a steady improvement since my bypass operation and I now feel fine. I’ve equipped my garage with a couple of exercise machines, walk most days and make sure I’m active as possible.

“I'll be forever grateful for all the help and support I’ve received – from the people on the train who saved me, to the doctors and nurses in the NHS. I feel like I owe it to them and to my family to do my best to stay healthy and active, take part in research, and enjoy life.”

Dr Joanne Taylor, the Clinical Research Fellow who is the study’s principal investigator, said: “In geriatric medicine we spend a lot of time with older people trying to work out how mobile they are and how frail. An older person might get a minor illness such as a virus or infection, but it has a disproportionate impact on their physical functioning. They may become unable to look after themselves, and that’s a common reason for people to end up in hospital. We see this particularly with heart failure patients.

“We noticed that cardiac devices are measuring daily physical activity in older people – like a Fitbit in your heart, that’s always on. This data can show us how a person’s activity levels correlate with their likelihood of being hospitalised for frailty, and that means we can treat them in their home before they get so ill that they need to be in hospital.”

BHF Senior Research Advisor Noel Faherty said: “The results of this study could help the thousands of people in the UK who have cardiac devices to avoid having to go to back to hospital for relatively minor illnesses. This would remove a significant burden from the NHS, as well as improving people’s quality of life.

“The British Heart Foundation is the UK’s largest independent funder of research into heart and circulatory diseases, such as heart attack and stroke, and the risk factors which cause them, such as diabetes. Our vision is a world free from the heartbreak caused by these conditions, and we rely on the support of the public to help us get there.”

Margaret Long, 77, from Prestbury in Cheshire had a pacemaker fitted in May 2018. In 2008 Mags began suffering from atrial fibrillation, an abnormal heartbeat. She visited her GP who performed an ECG and a diagnosis came back within half an hour. Mags had two cardioversion procedures – where an electric shock is sent to the heart to restore a normal rhythm – followed by an ablation, where the piece of heart tissue which is causing the abnormal rhythm is destroyed. In 2012 Mags had a stroke, which is more common in people with atrial fibrillation.

In 2016 Mags had a pacemaker fitted to make sure her heart is beating at the right pace. She said: “All those years I had atrial fibrillation, I had to go to Macclesfield A&E so many times. Since having the pacemaker fitted I’ve been able to stay out of hospital. I can be more active – I’ve played a full season of bowls, I can walk a mile in 20 minutes. My cardiologist can see how well I look. I’m so grateful for what’s been done. Life is wonderful. I’m catching up on so many physical things that were nigh on impossible before.

“I usually upload data from my pacemaker every three months and am seen once a year. For me, taking part in this study is a way to help other people in my situation.”

University of Manchester and University of North Texas scientists are the first to show that an embryonic living heart can be programmed to survive the effects of a low oxygen environment in later life.

The BBSRC funded study of juvenile Common Snapping Turtles for the first time explains the heart’s biological mechanisms which help Turtles to uniquely survive up to 6 months without oxygen.

And according to the team, it’s the exposure to low levels of oxygen during embryonic development which programmes the animals’ hearts to be more resilient to what is known as hypoxia for the rest of their lives.

The study led by Dr Ilan Ruhr and Dr Gina Galli from The University of Manchester could one day be translated into treatments which alleviate damage to the heart caused by hypoxia. It is published in the journal Proceedings of the Royal Society B.

Hypoxia occurs during a heart attack and can also damage a heart during transplant surgery.

According to the team, exposure to hypoxia during development causes epigenetic changes to the genome that can turn genes on or off, which are key to the remarkable ability of the turtle heart cells to tolerate zero oxygen.

“Turtles are incredible creatures that can uniquely survive for long periods of time under ice or at depths where there is little oxygen,” said Ilan Ruhr, who is a postdoctoral researcher at The University of Manchester.

“We’re excited to be the first to show that it is possible to change the degree of tolerance that turtles have for low oxygen environments by early exposure to hypoxia during development”

“Now we hope to isolate those epigenetic signatures which help turtles to survive for so long without oxygen with a hope to developing epigenetic drugs that can switch on tolerance to low oxygen environments in human hearts.”

The team are studying heart, rather than other organs in the body, as it is one of the organs most at risk of damage from hypoxia.

T

They isolated heart muscle cells from juvenile turtles which lived as embryos in either normal levels of Oxygen at - 21% O_{2 -} or half the levels of Oxygen 10%.

The procedure mimicked what happens in nature: eggs at the bottom of turtles’ nests are more exposed to hypoxia.

And they subjected the juvenile turtles to lower levels of oxygen while measuring intracellular Calcium- which binds to the contractile proteins of the heart, known as the myofilaments - pH, and reactive oxygen species -a molecule we all have which can become toxic when tissue reoxygenates too quickly.

Dr Gina Galli from The University of Manchester said: “Heart cells in turtles and humans are anatomically quite similar, so if we can learn to understand what factors allow them to survive in an oxygen free environment, we’d hope to be able to apply that to a medical scenario.

“Our study showed that early exposure to hypoxia in these animals both reduces the amount of Reactive Oxygen Species that could protect their myofilaments from damage and allows them to contract normally in the complete absence of O₂.

“A drug which is able to switch on mechanisms to protect the human heart from Oxygen deprivation would be of enormous benefit

“It could, for example protect individuals at risk of heart attack or protect organs for transplantation.”

The paper ‘Developmental plasticity of cardiac anoxia-tolerance in juvenile common snapping turtles (Chelydra serpentina)’ is published in Proceedings of the Royal Society B.

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.”

Scientists at the University of Manchester have this week published research, funded by the British Heart Foundation (BHF) which shows, for the first time, possible genetic causes of a serious congenital heart condition, Tetralogy of Fallot (ToF).

People born with ToF have four specific structural abnormalities in the heart, which mean they often have to undergo open heart surgery early in life. Many patients will have several surgeries and procedures throughout their lifetime. ToF is a very complex congenital heart condition, and in the majority of cases the cause is unknown.

Although most children who have had Tetralogy of Fallot corrected will go onto lead normal lives, there can be complications later in life including the need for further operations, and the development of heart rhythm disorders.

In this study, led by BHF Professor Bernard Keavney, the team used a technique called “whole exome sequencing” to look at specific regions of the DNA of ToF patients. The BHF also funded young investigator Dr Donna Page, who was first author on the paper.

The DNA of 829 ToF patients was analysed, making this the largest genetic study of patients with this condition ever conducted. To collect these volunteer families, the researchers worked with 7 UK children’s heart centres, and colleagues in Belgium and Australia.

The research identified two genes called NOTCH1 and FLT4, which were associated with rare and damaging DNA changes in ToF patients. Using experiments on cells grown in the laboratory, the team showed that some of the changes identified caused abnormal function of the genes involved. The study showed that the DNA changes in these two genes are present in around 7% of ToF patients, making them the two most important genes that contribute to the condition.

Further research is now required to discover additional genes. It is hoped this may lead to the DNA testing of grown-up patients with ToF who are considering having a family, to give them better information on the how likely it is that they will have a child with this condition. It would also shed some light on why they themselves developed the condition whilst in the womb.

Eight year old Callum Peace, from Liverpool, was born with a range of conditions, including ToF. His mum Jo said:

“When I was pregnant, I knew nothing of Callum’s conditions. The doctors had told me that he was going to be small – he was only 4lbs 11oz when he was born – but other than that I was expecting a healthy baby that I would be able to take home to the cot I had ready waiting for him.

“When Callum was born he was unable to breathe for himself. He required immediate resuscitation and was intubated and put on a ventilator. He was then transferred to the Intensive Care Unit at Alder Hey Children’s Hospital in Liverpool. He was extremely unwell, having turned blue due to a lack of oxygen in his blood, and at this point he was given just a 20% chance of survival.

“It was a real ordeal, and not something I would wish on any parent. We know that Callum will need more surgery on his heart in the years to come so, to me, every day is precious. Any research that can give parents like me some understanding of why their child has this condition is a step in the right direction.”

Andrew Stuart, a journalist from 91ֱ�� who was born with Tetralogy of Fallot says:

“At 11 months old I had open heart surgery, a ‘full correction’ of ToF. I was then monitored every two years, with them checking my pulmonary artery and pulmonary valve in particular.

“In 2012, they noticed some leaking in my pulmonary valve, although at that stage it was not severe enough to operate. Then, in 2016, I experienced more symptoms such as palpitations and breathlessness. When they did a scan this time, they could see that the leaking had become much worse and they would need to replace the valve. It was a worrying time as I had no real idea of what open heart surgery would entail and what it would be like afterwards.

“I had the surgery in May this year, and I have felt a lot better since. I am back in work and everything seems to be going OK. The recovery from open heart surgery is a long process and takes months. It's quite an upheaval in your life. I have an MRI scan booked in a couple of months so I will know more then.

“I am 30 now, and I’ve not got children, but I know that if I do have them in the future I would like to know whether there is a higher chance of them having this condition.

“It’s great to know the BHF and the University of Manchester are researching into congenital heart conditions like ToF. The condition means lifelong check-ups and treatment, medication and procedures, and will mean more in the future as I have a tissue donor valve which will need replacing. It has had a big impact because every step along the way is yet another thing, and never the endpoint of treatment.

“I don’t know what caused me to be born with this condition, but I would be very interested to find out!”

Professor Bernard Keavney, BHF Professor of Cardiovascular Medicine at the Institute of Cardiovascular Sciences, University of Manchester, commented:

“Tetralogy of Fallot is a serious congenital heart condition and one that, without surgery, would result in patients dying in virtually all cases. We have always suspected that genes played a part in causing the condition, and with this funding from the BHF we have been able to identify, for the first time, the two genes that have the biggest part to play.

“We hope that this knowledge will help us to support patients to understand more about their genes and how the condition can be passed on through families.”