New multidisciplinary study could help doctors to predict heart failure

Nearly half of people diagnosed with advanced heart failure (HF) following a major heart attack die within five years. But research supported by GW4 Alliance funding could lead to earlier prediction and intervention – improving life expectancy.

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TV watching linked with potentially fatal blood clots

Take breaks when binge-watching TV to avoid blood clots, say scientists. The warning comes as a study reports that watching TV for four hours a day or more is associated with a 35 per cent higher risk of blood clots compared with less than 2.5 hours. The University of Bristol research is published today in the European Journal of Preventive Cardiology, a journal of the ESC.

The study examined the association between TV viewing and venous thromboembolism (VTE). VTE includes pulmonary embolism (blood clot in the lungs) and deep vein thrombosis (blood clot in a deep vein, usually the legs, which can travel to the lungs and cause pulmonary embolism).

To conduct the study, the University of Bristol researchers conducted a systematic review to collect the available published evidence on the topic and then combined the results using a process called meta-analysis.

Lead author, Dr Setor Kunutsor from the University’s Bristol Medical School explained:

“Combining multiple studies in a meta-analysis provides a larger sample and makes the results more precise and reliable than the findings of an individual study.”

The analysis included three studies with a total of 131,421 participants aged 40 years and older without pre-existing VTE. The amount of time spent watching TV was assessed by questionnaire and participants were categorised as prolonged viewers (watching TV at least four hours per day) and never/seldom viewers (watching TV less than 2.5 hours per day).

The average duration of follow-up in the three studies ranged from 5.1 to 19.8 years. During this period, 964 participants developed VTE. The researchers analysed the relative risk of developing VTE in prolonged versus never/seldom TV watchers. They found that prolonged viewers were 1.35 times more likely to develop VTE compared to never/seldom viewers.

The association was independent of age, sex, body mass index (BMI) and physical activity. Dr Kunutsor said:

“All three studies adjusted for these factors since they are strongly related to the risk of VTE; for instance, older age, higher BMI and physical inactivity are linked with an increased risk of VTE.

“The findings indicate that regardless of physical activity, your BMI, how old you are and your gender, watching many hours of television is a risky activity with regards to developing blood clots.

“Our study findings also suggested that being physically active does not eliminate the increased risk of blood clots associated with prolonged TV watching,” said lead author Dr Kunutsor. “If you are going to binge on TV you need to take breaks. You can stand and stretch every 30 minutes or use a stationary bike. And avoid combining television with unhealthy snacking.”

Dr Kunutsor noted that the findings are based on observational studies and do not prove that extended TV watching causes blood clots.

Regarding the possible reasons for the observed relationship, he said:

“Prolonged TV viewing involves immobilisation which is a risk factor for VTE. This is why people are encouraged to move around after surgery or during a long-haul flight. In addition, when you sit in a cramped position for long periods, blood pools in your extremities rather than circulating and this can cause blood clots. Finally, binge-watchers tend to eat unhealthy snacks which may lead to obesity and high blood pressure which both raise the likelihood of blood clots.”

Dr Kunutsor concluded:

“Our results suggest that we should limit the time we spend in front of the television. Long periods of TV watching should be interspersed with movement to keep the circulation going. Generally speaking, if you sit a lot in your daily life – for example your work involves sitting for hours at a computer – be sure to get up and move around from time to time.”

Read the paper

Television viewing and venous thrombo-embolism: a systematic review and meta-analysis in the European Journal of Preventive Cardiology by Setor Kunutsor, Richard Dey and Jari Laukkanen.

Further information

Authors’ note:

The findings are based on observational studies, so they do not prove cause and effect.

These findings are based on the results of only three studies. More studies are needed to confirm or refute the findings.

Welcome to the BHI Newsletter Autumn 2021

Professor Andy Judge, Head of Section for Cardiovascular Surgery and Vascular Biology, reflects on recent successes.

With the new academic year underway, we welcome our new cohorts of postgraduate taught master’s degree students for the MSc in Perfusion Science and the MSc in Translational Cardiovascular Medicine (TCM). The teaching sessions are now back in person for the campus based TCM students and Perfusion students, and our student numbers are good.

I’m pleased to report that the labs, which closed for three months at the start of the pandemic, have been open since June 2020. Staff are gradually returning to the office at Level 7 of the BRI as the University has launched its blended working trial policy, and we are now seeing more staff in both the labs and offices.

Within our section for Cardiovascular Surgery and Vascular Biology at the University, we are delighted to have been able to appoint staff to new posts. Dr Kerry Wadey has been appointed as Lecturer in Cardiovascular Medicine on an open-ended core funded post. Francesco Paneni has been appointed as a Professor in Cardiology and Tom Johnson as an Associate Professor in Cardiology and they are expected to begin working with us at the start of 2022.

A number of staff in our section have had success following the annual University promotions procedure. Jason Johnson has been promoted to Professor of Cardiovascular Pathology, and Umberto Benedetto becomes Professor of Cardiac Surgery. Staff from the Teaching and
Learning for Health Professionals (TLHP) programme have recently joined our department of Translational Health Sciences and come under
the umbrella of our cardiovascular section, where we are delighted to congratulate Andrew Blythe on being promoted to Professor of Medical Education in this year’s annual promotion procedure.

Huge congratulations to all those recently promoted: we wish them continued success in their careers.

Bristol Heart Institute researchers feature in World Heart Day campaign

 

Four Bristol Heart Institute researchers have shared their work in a campaign to mark World Heart Day, 29 September 2021.

The interviews, which appear in the Guardian newspaper’s Cardiovascular Health supplement, cover a broad aspect of the BHI’s work, from tissue engineering to population health.

BHI Director, Professor Gianni Angelini, outlines the BHI’s innovative link between clinicians and scientists, citing the combination of people from different disciplines – basic scientists, clinicians, engineers, epidemiologists and statisticians – as one of the Institute’s key strengths.

Professor of Congenital Cardiac Surgery, Massimo Caputo, talks about how tissue engineering and stem cell therapies could lead to better treatment options for young patients with congenital heart disease.

Dr Giovanni Biglino, Senior Lecturer in Biostatistics, explains how patients and the public are playing an increasing role in cardiovascular research through closer collaborations with clinicians, researchers and artists. This is supporting clinical training and medical research as well as helping patients have a better understanding, and acceptance, of their heart conditions.

Finally, Deborah Lawlor, Professor of Epidemiology, talks about using population health data to identify causes of cardiovascular disease and to predict who is at risk of it. which can lead to prevention, early detection and effective treatment of disease.

See the full BHI World Heart Day campaign

BHI scientist wins national science image contest with heart vessel image

Recreating heart blood vessels
Recreating heart blood vessels. Image credit : Dr Elisa Avolio

A scientist from the Bristol Heart Institute has won the British Heart Foundation’s (BHF) annual ‘Reflections of Research’ image competition. Where science and art collide, the competition challenges BHF-funded scientists to showcase their state-of-the-art heart and circulatory disease research through the generation of captivating images.

Dr Elisa Avolio’s entry ‘recreating heart blood vessels’ was chosen as this year’s judges’ winner. Although at first glance it appears to resemble a luminous jelly fish, the image shows new blood vessel-like structures – pictured in green in the centre – sprouting from a 3D gel.

Dr Avolio of the Bristol Medical School created the structures using a mixture of two types of heart cells – cardiac endothelial cells, which line the inside of every blood vessel, and pericytes, which ‘hug’ the outside of blood vessels to support the vessel and help it function.

During a heart attack, the arteries that supply blood to the heart are blocked, cutting off blood flow. The area of the heart starved of blood and oxygen dies, and it no longer functions to help the heart pump blood around the body. Dr Avolio is researching ways to encourage the formation of new blood vessels to replace those that have died, to restore blood supply to damaged areas of the heart.

Dr Avolio, a post-doctoral research associate, said:

“It is fantastic to have won this year’s Reflections of Research competition. Each year the entries display such variety in the BHF’s work to support heart and circulatory disease research.

“By recreating models of the heart blood vessels, we can see how the cells in blood vessel walls interact with and talk to other cells. This knowledge, along with understanding what molecules promote or block the formation of blood vessels, could be used in the future to develop new treatments for patients after a heart attack.”

Dr Neil Dufton, Lecturer in Inflammatory Sciences at Queen Mary University of London, was this year’s guest judge. He said:

“All of the images shortlisted in this year’s competition offer a stunning glimpse into the cutting-edge work being carried out by BHF scientists.

“The winning image is truly eye-catching. The chaotic mixture of different cells around the outside contrasts perfectly with a ‘through the looking glass’ moment where we see new and exquisitely detailed blood vessels forming in the centre.”

Dr Charmaine Griffiths, Chief Executive at the British Heart Foundation, was also a competition judge. She added:

“All of this year’s entries beautifully capture aspects of the heart and circulatory system, bringing to life the challenges that BHF scientists work tirelessly to solve.

“The images show how far we’ve come over 60 years of BHF research, and would have been barely imaginable to our founders. I love the winning image not just because of its circular beauty, but also because of the hope it represents for the future of healing damaged hearts.”

Early adulthood education and employment experiences play independent role in later life cardiovascular health

New research has found that education and employment experiences in early adulthood contribute to cardiovascular health inequalities in later life, independent of occupation and family income in mid-adulthood. The findings, published today in the Journal of Epidemiology and Community Health, involve researchers from the University of Cambridge, University of Bristol and UCL Social Research Institute.

There are important differences in health between different sectors of our society, with those who are less educated and in lower status jobs shown to be less healthy and have shorter life expectancy on average than the more privileged. While early adulthood is an important time for both the development of adult socioeconomic position and for development of behaviours related to cardiovascular health, until now the degree to which early adulthood socioeconomic trajectories contribute directly to health differences observed in later life has not been clear.

Researchers from the University of Cambridge, University of Bristol and UCL Social Research Institute analysed health and socioeconomic data collected over several decades from over 12,000 members of the 1970 British Birth Cohort, to determine the contribution of early adulthood to differences in cardiovascular health in mid-adulthood. The scientists used a data-driven method to divide the population into different socioeconomic trajectory groups based on their participation in education, different job types, unemployment or economic inactivity across early adulthood (ages 16-24). They studied the association of these groups with cardiovascular risk factors at age 46, including blood pressure, cholesterol levels, waist circumference. To determine if the association of early adulthood socioeconomic trajectories with cardiovascular health was mediated by socioeconomic status later in life, they examined how correcting for occupation or family income at age 46 affected the link.

Professor Kate Tilling from the MRC Integrative Epidemiology Unit at the University of Bristol, and senior author on the paper, said:

“Measuring socioeconomic position in early adulthood has always been difficult as this is a period of transition when most people’s occupations change over time. The method we’ve developed provides a flexible way to identify early adulthood socioeconomic position, and we hope that it will be used in future to answer other research questions related to this period of life.”

The researchers found that those who spent a longer time in education, going on to employment in professional or managerial roles during early adulthood, had better cardiovascular health more than 20 years later (at age 46) than other groups. Importantly this association wasn’t entirely because of a higher income or higher level job at age 46, suggesting an independent and long-term association of early adulthood influences with health.

The findings indicate that that material factors in mid-adulthood do not contribute to the pathway through which early adulthood socioeconomic trajectory affects mid-life health, and the authors suggest that the development of health behaviours or psychosocial factors such as stress, depression, and job control in early adulthood may play an important role.

Dr Eleanor Winpenny from the MRC Epidemiology Unit at the University of Cambridge, and first author on the paper, said:

“We found that an individual’s education and employment experiences in early adulthood had a far larger impact on measures of cardiovascular health more than twenty years later than their occupation or income at that time did.

“These results suggest that we need to provide more support for young adults to allow healthy development into middle age and prevent disease in later life. Given the added disadvantage to young adults as a result the current coronavirus pandemic, there is an urgent need to understand and mitigate the effect these circumstances may be having on their future health.”

The research was funded by the Medical Research Council and the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and Wellcome, under the auspices of the UK Clinical Research Collaboration.

Paper

Early adulthood socioeconomic trajectories contribute to inequalities in adult cardiovascular health, independently of childhood and adulthood socioeconomic position‘ by Winpenny, E. et al in the Journal of Epidemiology and Community Health

The beating heart of Royal Fort Garden

Bristol Heart Institute interpretation sign

The new interpretation sign for the University of Bristol brings a whole new meaning to the phrase ‘living statue’.

The solid oak monolith is the third instalment in a series of iconic totems dedicated to the University’s research institutes. This sign embodies the work of the Bristol Heart Institute and has been designed to reflect the relationship between human life and nature. Joining many other works of art in the Royal Fort Garden this piece stands proud at three metres high, and if you get close enough you can hear the low thud of a heartbeat coming from deep within the structure day and night.

Previous designs highlighted the work of the Bristol Population Health and the Bristol Bio Design Institutes.

The new monolith is built from four solid oak panels which have been laser cut and hand painted to represent a human cardiovascular system. Following a couple of years of pandemic enforced hiatus, it’s great to add to the collection and celebrate the work of the Bristol Heart Institute in such a creative way.  

(Photo by Green Hat. Words adapted from text supplied by Green Hat)

Cardiovascular researchers visit Bristol primary school

Giovanni Biglino shows Year 6 students a 3D printed heart model
Giovanni Biglino shows Year 6 students a 3D printed heart model

Drs Lucy Culliford, Andrew Shearn and Giovanni Biglino took part in an outreach activity at Parson Street Primary School in Bedminster, south Bristol. in May 2021.

The visit was organised by Lucy on behalf of the Bristol Trials Unit. The group explained some of their research to the Year 6 students (aged 10 and 11) and, as the visit happened in the same week as Clinical Trials Day, it was also an opportunity for Lucy to ask the students to think about clinical studies, the idea of randomisation and ‘what is a clinical trial?’. The group showed the THERMIC 3 animation video, which was developed as part of the TRECA study exploring children’s and young people’s engagement with clinical trials.

Giovanni gave an overview of the technology involved in 3D printing and Andrew brought a series of heart models, both adult and paediatric, including examples of babies’ hearts with congenital heart disease, which sparked some stimulating conversations with the 53 students who attended.

They explained that 3D printing technology can produce models of human organs using scans taken during routine visits to the hospital. Bristol Royal Hospital for Children use this technique to create heart models from patients with congenital heart disease. Being able to hold a life-size model of the patient’s heart can complement information the surgeon or cardiologist can get from medical imaging – for example, they can practice aspects of the surgery or decide the best route to access a specific part of the heart. The models are also used when explaining the details of the case to a patient or a parent.

The children asked lots of questions about ‘hole in the hearts’, as some had had siblings with this condition. They also asked how smoking can affect the heart, and if the researchers could show them a video of a beating heart.

Lucy said:

“This is the first time we’ve done a talk in a school as part of our outreach activities around Clinical Trials Day, and it was a real pleasure to talk to the children. They were very engaged and although they had only started learning about the heart the day before, they already knew lots about heart anatomy, and had more questions than we had time to answer!”

How to get involved in schools outreach

If you would like to run a schools outreach activity, contact your local school.

Schools often have science weeks, or may be doing a topic related to cardiovascular research. For example, Parson Street Primary School use the Cornerstones curriculum and the year 6s had just started the ‘blood heart’ topic – the following week they had a visitor demonstrating a heart dissection.

Smoking during pregnancy associated with child’s risk of having congenital heart disease

Children born to mothers who smoked during pregnancy were at increased risk of having congenital heart disease, a new study published today [27 May] in the Journal of the American Heart Association has found.

The study was led by the University of Bristol, in an international collaboration with researchers from seven institutions. It brings together data on more than 230,000 families from seven European birth cohorts from the UK, Ireland, the Netherlands, Denmark, Norway and Italy, including the world-renowned Children of the 90s study at the University of Bristol. The research was supported by the British Heart Foundation and the H2020 program of the European Commission.

Each day, around 13 babies in the UK are diagnosed with congenital heart disease. This means the heart or the large blood vessels surrounding the heart have not developed properly in the womb. Identifying causes of congenital heart disease could help prevent some of these cases and ultimately save lives.

Lead author, Kurt Taylor, a PhD student at the University of Bristol said:

“Birth cohorts are unique in that many possess a wealth of data not only in mothers and children, but also in fathers. Crucially, having access to data in the fathers as well as mothers and children allowed us to use a novel study design to investigate possible causes of congenital heart disease.”

The study analysed associations between body mass index, smoking, and alcohol consumption on offspring congenital heart disease. Data on these characteristics were obtained through measurements of weight and height and questionnaires administered during early pregnancy when most of the cohorts began recruitment. Measurements were harmonised across cohorts as part of the LifeCycle project; an initiative that aims to research the role of pregnancy and infancy factors on offspring health and wellbeing across childhood and into adulthood. The researchers were able to test the reliability of their findings by using an approach that compares the results from mothers and fathers to help discern whether the effects they see are “real” or are as a result of other factors.

Kurt continued:

“Here, we have shown that mothers who smoke during pregnancy are more likely to have a child with congenital heart disease. Our results also suggest that being overweight or obese at the start of pregnancy or consuming alcohol may not be causes of congenital heart disease, despite previous research suggesting otherwise. These results might help in supporting women of reproductive age not to start smoking. Meanwhile it continues to be appropriate to recommend that women, and men, maintain a healthy weight and limit alcohol consumption prior to and during pregnancy.”

Professor Deborah Lawlor, British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology of the University of Bristol, who oversaw the study, added:

“Smoking rates are declining but remain high in more deprived groups in the UK and other high-income countries and are promoted in low- and middle-income countries. These findings further highlight the need to support smoking cessation globally. Also, if we can work out exactly how maternal smoking increases risk of congenital heart diseases this could identify new ways of preventing these diseases even in the absence of smoking.”

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and cardiologist, said:

“Smoking is one of the biggest risk factors for developing heart and circulatory disease. It is also the greatest cause of health inequality across Europe, but supporting people to quit smoking is one of the most effective things we can do to reduce these inequalities. We need to make it easier for everyone to quit by offering them appropriate smoking cessation support and advice.”

Read the paper

Effect of maternal prepregnancy/early-pregnancy body mass index and pregnancy smoking and alcohol on congenital heart diseases: A parental negative control study‘ by Kurt Taylor et al in The Journal of the American Heart Association [open access]

Restoring respiratory sinus arrhythmia in heart failure

A CiC award will enable Eva Sammut to test the safety and feasibility of a novel device to reinstate RSA in dyssynchronous heart failure.

Confidence in Concept (CiC) awards fund proof of concept studies, which provide robust evidence of the feasibility of a proposed solution to a clinical need.

Dr Eva Sammut, NIHR-funded academic clinical lecturer in Cardiology at the BHI, received a £100K Elizabeth Blackwell Institute MRC CiC award in January to look at the feasibility, safety and effectiveness of a novel device to restore respiratory sinus arrhythmia in patients with heart failure.

Q: Why is your research significant?

Heart failure is a global clinical pandemic with clear unmet clinical need. Despite some advancements in therapy, prognosis remains poor with a 50 per cent five-year mortality representing a significant societal and healthcare burden.

Respiratory sinus arrhythmia (RSA) is a physiological phenomenon of a subtle increase of heart rate during inspiration and the converse during expiration. RSA is a major component of physiological heart rate  variability, a sign of good cardiac health, and is known to be lost in patients with heart failure. Loss of RSA is associated with increased ventricular  arrhythmia and sudden cardiac death. Restoring RSA in heart failure patients could improve their life  expectancy and markedly reduce hospitalisation costs. Existing preclinical models are inadequate to validate the safety of new treatments in this priority area.

Q: What are you developing?

Our group have developed a novel device which is able to reinstate RSA. Our preliminary results are very promising and demonstrate feasibility. Further proof of concept data from an advanced preclinical model is now pivotal to ensure the safety, feasibility and applicability of the new device to  progress it toward bedside to benefit patients.

This project will test the safety and feasibility of this new technology in the setting of dyssynchronous HF. This is a complex form of heart failure that responds poorly to the best available current treatment –  a specialised pacemaker named cardiac  resynchronisation therapy.

This study will be performed at the University’s Translational Biomedical Research Centre facility. We will develop an advanced preclinical model of dyssynchronous heart failure with balloon catheter myocardial infarction and superimposed pacemaker-induced ventricular dyssynchrony. Next, we will use this model to test this novel pacemaker approach to reinstating respiratory sinus arrhythmia in addition to cardiac resynchronisation therapy.

Q: Who are you working with?

A unique multidisciplinary team has been assembled including Professors Julian Paton, Raimondo Ascione and Alain Nogaret, and Drs Tom Johnson, Ed Duncan and Vito Domenico Bruno, who are co-applicants supporting this project.

We are also working in collaboration with Ceryx Medical, a spin out company formed by the universities of Bristol, Bath and Auckland.

Q: What next?

We are delighted to receive this funding to be able to take this exciting new technology to the next  developmental stage. This project is critical to ensure safety, feasibility and applicability of the new device in this setting. If positive results are demonstrated this would pave the way for larger, efficacy translational studies, with a view to reach patients in the NHS  within the next five to six years.

This post first appeared in the March 2021 BHI Newsletter