Tag Archive for: Cardiovascular and Respiratory Disease

Global spotlight on Cambridge heart trial

IVORY trial team

Results of an NIHR Cambridge BRC and NIHR Cambridge CRF supported trial which may help prevent patients from having repeat heart attacks, will be presented at the 30th European Society of Cardiology (ESC) Congress, the largest cardiology conference globally.

The IVORY and IVORY FINALE trial looked at whether a low dose of the cancer drug, known as aldesleukin, could increase the activation of immune cells shown to protect the heart and help patients who have had a heart attack.

Current treatment for heart attacks centres on the re-establishment and maintenance of blood flow in the coronary arteries using blood thinners, with or without stents, as well as cholesterol lowering medication. Despite current optimal therapy, heart attacks can re-occur.  

The team believes the immune system is an important process in the development of atherosclerosis (plaque disease in arteries) which has not been directly harnessed in these patients and attempted to target it using a novel approach.

The researchers found in a previous trial that low doses of aldesleukin, a drug normally used to treat kidney cancer (at much higher doses), stimulates the production of protective immune cells, called Tregs safely in patients with heart attacks.

In the current trial, they tested to see if the drug reduced inflammation in the arteries of patients after an initial heart attack, as inflammation in the arteries has previously been associated with an increase in the risk of recurrent heart attacks and death.

The study was led by researchers at Cambridge University Hospitals (CUH) and the University of Cambridge (UofC) as well as Royal Papworth Hospital, and was supported by the Medical Research Council, the British Heart Foundation, the NIHR Cambridge Biomedical Research Centre and the NIHR Cambridge Clinical Research Facility.

Dr Rouchelle Sriranjan

The results will be unveiled at the ‘late-breaking’ sessions of the 30th European Society of Cardiology (ESC) Congress 2024 in London on 30 August and will be presented by Dr Rouchelle Sriranjan, an interventional cardiology registrar and NIHR clinical lecturer in cardiology, pictured right.

CUH consultant clinical pharmacologist, affiliated associate professor and trial chief investigator, Dr Joseph Cheriyan, said: “We are delighted to be presenting these novel data at the ESC and particularly in the late breaking session, which is a highlight of the conference.

“This study was the product of very intense work by many different teams on the campus in very sick patients and demonstrates the importance of collaborative teamwork. We are very grateful to the patients for their time and dedication to our trial.”

Dr Stephen Hoole was the trial lead for Royal Papworth Hospital, whilst Professor Rudd led the imaging component for the trial.

Professor Ziad Mallat, BHF professor of cardiovascular medicine, UofC, who conceived the trial said: “If positive, this is potentially a new treatment approach that boosts our immune defence mechanisms to tame heart attacks. It could also be an important step forward in the treatment of patients with heart attacks which needs continued exploration.

“Our results should be of interest to the wider cardiovascular community. In addition to our supporters and funders, we would like to thank everyone who has worked so hard on the trial, especially the patients who have taken part.”

Cambridge launches clinical trial to test new drug for a rare lung condition

People with pulmonary sarcoidosis are being invited to take part in an international clinical trial at Cambridge University Hospitals.

The RESOLVE-Lung study, supported by the NIHR Cambridge BRC, is evaluating the safety and effectiveness of a new drug, namilumab, in the treatment of pulmonary sarcoidosis.

Sarcoidosis is a rare inflammatory disease which causes granulomas, tiny clumps of immune cells, to form in any organ or tissue. When it occurs in the lungs it is known as pulmonary sarcoidosis.

Although it most commonly affects the lungs, it can also affect the skin, eyes, joints, nervous system, heart and other parts of the body.

The main symptoms of pulmonary sarcoidosis are shortness of breath and a persistent dry cough, and some people experience pain and discomfort in their chest.

Namilumab is a targeted drug designed to block a molecule which promotes inflammation, thought to be involved in granuloma formation and maintenance. Namilumab has not yet been approved by any health authority for any disease or condition.

Participants in the RESOLVE-Lung study will initially receive monthly injections of namilumab or a placebo (a substance with no therapeutic effect) for approximately six months.

After the initial treatment period, all participants will have the option to receive namilumab for another six months, regardless of whether they initially received namilumab or a placebo.

Up to 100 participants will be enrolled at study sites in the United Kingdom, Europe and the United States.

Dr Akhilesh Jha and Dr Theresia Mikolasch, Co-Principal Investigators of the RESOLVE-Lung study at CUH, said: “Sarcoidosis is a disease that can cause inflammation and scarring of the lungs and is often treated with oral steroids, which are known to have significant side effects.

“The RESOLVE-Lung trial aims to investigate a new treatment for sarcoidosis, which will target inflammation more precisely, and if successful, will provide an alternative option to steroids.

“We are grateful if people with sarcoidosis and clinicians looking after them would consider participating in the study.”

Dr Helen Macdonald, Chief Operating Officer at the NIHR Clinical Research Network East of England, said: “It’s only through research that we can find new treatments for managing long-term conditions such as sarcoidosis. We are hugely grateful to people in the East of England who participate in research, including patients, staff and supporters alike.”

To find out more about the RESOLVE-Lung study, please visit www.sarcoidosistrial.com/en-uk.

Researchers awarded prestigious Academy of Medical Sciences Fellowships

Four NIHR Cambridge BRC researchers have been elected to the Academy of Medical Sciences Fellowship.

Theme Leads Professors James Rowe and Serena Nik-Zainal, together with researchers Professors Charlotte Coles and Emanuele Di Angelantonio, received the awards in recognition of their outstanding biomedical and health research which has translated into benefits for patients and wider society.

James B. Rowe, Prof - Dementia
Neurodegenerative Disease and Dementias Theme Lead Professor James Rowe
Professor Serena Nik Zainal
Genomic Medicine Theme Lead Professor Serena Nik Zainal
Prof Charlotte Coles
Professor Charlotte Coles
Prof Emanuele Di Angelantonio
Prof Emanuele Di Angelantonio

Academy of Medical Sciences President Professor Dame Anne Johnson said: “These new Fellows are pioneering biomedical research and driving life-saving improvements in healthcare. It’s a pleasure to recognise and celebrate their exceptional talent by welcoming them to the Fellowship.”

  • This year Fellows were chosen from 353 candidates, and a shortlist of 126 candidates for peer review. To find out more about the Fellowship visit the Academy of Medical Sciences website.

Gone fishing: highly accurate test for common respiratory viruses uses DNA as ‘bait’

Research supported by NIHR Cambridge BRC has led to a new test that ‘fishes’ for multiple respiratory viruses at once using single strands of DNA as ‘bait’, giving highly accurate results in under an hour.

Cambridge researchers developed the test, which uses DNA ‘nanobait’ to detect the most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time.

In contrast, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. The results are reported in the journal Nature Nanotechnology.

The winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

Similar symptoms, different treatments

“Many respiratory viruses have similar symptoms but require different treatments: we wanted to see if we could search for multiple viruses in parallel,” said Filip Bošković from Cambridge’s Cavendish Laboratory, the paper’s first author. “According to the World Health Organization, respiratory viruses are the cause of death for 20% of children who die under the age of five. If you could come up with a test that could detect multiple viruses quickly and accurately, it could make a huge difference.”

For Bošković, the research is also personal: as a young child, he was in hospital for almost a month with a high fever. Doctors could not figure out the cause of his illness until a PCR machine became available.

“Good diagnostics are the key to good treatments,” said Bošković, who is a PhD student at St John’s College, Cambridge. “People show up at hospital in need of treatment and they might be carrying multiple different viruses, but unless you can discriminate between different viruses, there is a risk patients could receive incorrect treatment.”

PCR tests are powerful, sensitive and accurate, but they require a piece of genome to be copied millions of times, which takes several hours.

The Cambridge researchers wanted to develop a test that uses RNA to detect viruses directly, without the need to copy the genome, but with high enough sensitivity to be useful in a healthcare setting.

“For patients, we know that rapid diagnosis improves their outcome, so being able to detect the infectious agent quickly could save their life,” said co-author Professor Stephen Baker, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease. “For healthcare workers, such a test could be used anywhere, in the UK or in any low- or middle-income setting, which helps ensure patients get the correct treatment quickly and reduce the use of unwarranted antibiotics.”

The researchers based their test on structures built from double strands of DNA with overhanging single strands. These single strands are the ‘bait’: they are programmed to ‘fish’ for specific regions in the RNA of target viruses. The nanobaits are then passed through very tiny holes called nanopores. Nanopore sensing is like a ticker tape reader that transforms molecular structures into digital information in milliseconds. The structure of each nanobait reveals the target virus or its variant.

The researchers showed that the test can easily be reprogrammed to discriminate between viral variants, including variants of the virus that causes COVID-19. The approach enables near 100% specificity due to the precision of the programmable nanobait structures.

“This work elegantly uses new technology to solve multiple current limitations in one go,” said Baker. “One of the things we struggle with most is the rapid and accurate identification of the organisms causing the infection. This technology is a potential game changer; a rapid, low-cost diagnostic platform that is simple and can be used anywhere on any sample.”

A patent on the technology has been filed by Cambridge Enterprise, the University’s commercialisation arm, and co-author Professor Ulrich Keyser has co-founded a company, Cambridge Nucleomics, focused on RNA detection with single-molecule precision.

“Nanobait is based on DNA nanotechnology and will allow for many more exciting applications in the future,” said Keyser, who is based at the Cavendish Laboratory. “For commercial applications and roll-out to the public we will have to convert our nanopore platform into a hand-held device.”

“Bringing together researchers from medicine, physics, engineering and chemistry helped us come up with a truly meaningful solution to a difficult problem,” said Bošković, who received a 2022 PhD award from Cambridge Society for Applied Research for this work.

High blood pressure is directly linked to severe COVID-19

A study led by Addenbrooke’s Hospital and the University of Cambridge has shown that people with high blood pressure are more likely to be admitted to hospital or die from COVID-19, regardless of other factors such as age, sex, ethnicity or BMI.

The research, published this week in the Journal PLOS ONE, is the first study to show the extent to which high blood pressure, known as hypertension, can be directly linked to patients developing severe COVID-19. 

It also showed that the type of medication people were receiving to treat hypertension did not appear to modify this risk.  In addition, those patients who had poorly controlled blood pressure i.e. above treatment targets, were at the highest risk of dying or being hospitalised.

The study findings may help explain why ethnic minority and low-income groups were disproportionately affected by COVID-19, as hypertension is more common in these individuals, and rates of blood pressure control poorer (see notes).

The research has important implications for public health priorities, given that hypertension is already the leading risk factor for death in the UK. 

It also comes as rates of blood pressure control have worsened in the UK, due to the pandemic, with the number or people being screened and identified with the condition dropping as well (see notes).

Holly Pavey is lead author of the study and a British Heart Foundation (BHF) funded PhD student at the University of Cambridge.  She said:

“Before this research, it wasn’t clear to what extent high blood pressure was putting patients at greater risk of hospitalisation or dying from COVID-19.  Other factors such as age, socio-economic status, sex, ethnicity and BMI were all in the frame too as increasing the risk of severe COVID-19.  

“By using data from many thousands of UK volunteers, we found that in individuals who tested positive for COVID-19, those with high blood pressure had a 22% higher risk of being hospitalised of dying from the virus, compared to those without high blood pressure.   This risk was almost doubled for those with poorly controlled blood pressure.”

The research was supported by the NIHR Cambridge Biomedical Research Centre and use data from the UK Biobank, a research database, containing in-depth genetic and health information from half a million UK volunteers. The study included over 16,000 of these individuals who had tested positive for COVID-19 and who had linked GP records, death records and COVID-19 lab results. 

Researchers analysed data up until early 2021, which helped to reduce any bias from new variants of the virus, which were much more transmissible, as well as reducing any bias from the effects of widespread vaccinations.

However, the UK Biobank volunteer population is generally healthier than the general UK population and has relatively few participants from ethnic minority groups, so generalisations to the wider UK population need to be undertaken with caution.

Even though the death and hospitalisation rate due to COVID-19 has been hugely reduced over the last year due to virus mutations, the NHS vaccination program and availability of effective treatments, this research highlights the importance of having well-controlled blood pressure, in case of new, more severe strains of COVID-19 or other viruses in the future.

Ian Wilkinson, a cardiology consultant at Cambridge University Hospitals NHS Foundation Trust (CUH) and Professor of Therapeutics at the University of Cambridge, is the study’s senior author.  He said: “Hypertension remains the leading risk factor for death in the UK and worldwide, despite effective treatments, and disproportionately affects low income groups and individuals from ethnic minority backgrounds.

“Our findings further emphasise the importance of adequate blood pressure control. Unfortunately, post-pandemic, the rates of blood pressure control have worsened, as have the number of people being screened and identified as having high blood pressure. This is now a major public health problem in the UK and needs to be addressed as part of the levelling-up agenda”.

A national trial is currently underway to improve treatments for hypertension, specifically for people from black, Asian and minority ethnic communities.  At the moment most treatments have been tested mainly on white people and it’s not known if these are as effective on other ethnic groups.  

The AIM HY trial is led by Professor Ian Wilkinson and Phil Chowienczyk, Professor of Clinical Cardiovascular Pharmacology, Kings College London and Chief Investigator for the trial. 

Professor Chowienczyk said: “These findings highlight the importance of good blood pressure control, especially in individuals disproportionately affected by high blood pressure and COVID-19, such as those in ethnic minority groups in the UK. The AIM HY_INFORM trial is a major study, funded by the BHF and Medical Research Council, that will determine which drugs are most effective at lowering blood pressure in ethnic minority groups in the UK. This should report at the end of 2023 and will be instrumental in shaping new guidelines for the treatment of hypertension in the UK.”

Heart surgery delays will cost lives, warns research

Urgent action is needed to clear the backlog of people with a common heart condition who are waiting for lifesaving treatment, according to research supported by the British Heart Foundation which was published in BMJ Open. The researchers have warned that a lack of action could result in thousands of people dying while waiting for treatment.

The Covid-19 pandemic has led to thousands of heart procedures being postponed and record waiting lists. Previous work has estimated that 4,989 people in England with severe aortic stenosis missed out on life saving treatment between March and November 2020.

Aortic stenosis develops when the heart’s aortic valve becomes narrowed, restricting blood flow out of the heart. Prompt treatment is vital for people diagnosed with severe aortic stenosis, as around 50 per cent will die within two years of symptoms beginning.

Now, an international team of researchers has modelled the impact that increasing treatment capacity and using a quicker, less invasive treatment option would have on waiting lists. Even in the best-case scenario, they found that the waiting list would take nearly a year to clear and over 700 people would die while waiting for treatment.

The traditional treatment for aortic stenosis involves replacing the narrowed valve, most commonly through open heart surgery (a surgical aortic valve replacement, SAVR). However, a newer keyhole procedure called a transcatheter aortic valve implantation (TAVI) is increasingly being used and is now recommended for patients aged 75 and over.

The researchers investigated the impact that increasing treatment capacity and converting a proportion of operations to the quicker TAVI procedure would have on the backlog. They looked at how long it would take to clear the backlog and the number of people who would die while waiting for treatment.

They found that the best and most achievable option involved a combination of increasing capacity by 20 per cent and converting 40 per cent of procedures from SAVR to TAVI. This would clear the backlog within 343 days with 784 deaths while people wait for treatment.

The team say they want to see greater collaboration at local and national levels to agree the changes needed that can ensure that people with severe aortic stenosis receive lifesaving treatment as quickly as possible.

Professor Mamas Mamas, Professor of Cardiology at Keele University and consultant cardiologist at University Hospitals of North Midlands NHS Trust, was one of the leading researchers in the study. He said: “Before the pandemic around 13,500 SAVR and TAVI procedures were performed each year across the UK. Increasing capacity by 20 per cent would represent one or two additional TAVI procedures each week per centre. We think that with local and national collaboration this increase is achievable. Furthermore, we have created an algorithm that NHS Trusts can use to work out the best approach locally.

“Since November 2020 the UK has been hit with further waves of Covid-19 which have led to extreme pressure on the NHS and additional delays to treatment. We expect that number of people waiting for treatment in recent months will be even higher than the figure we used in our study.

“Doing nothing is simply not an option. If we continue as we are currently thousands of people will die from untreated aortic stenosis.”

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist, said: “We welcome the use of innovative cardiovascular procedures that can reduce the need for open heart surgery where appropriate and where their use will provide the greatest benefit to patients.

“But, as this modelling study shows, even increased use of this quicker and less invasive procedure won’t be enough to overcome the impact of Covid-19 related delays and stop people with aortic stenosis dying while waiting for treatment.

“Cardiac care can’t wait. The NHS desperately needs additional resources to help it tackle the backlog of care and ensure that heart patients receive the treatment and care they need.”

This research was part funded by the EPSRC Cambridge Centre for Mathematics of Information in Healthcare and supported by the NIHR Cambridge BRC.

Cambridge researchers awarded Fellow status

Congratulations to our NIHR Cambridge BRC researchers who have been elected as Fellows of the Academy of Medical Sciences.

In 2022, 60 Fellows have been elected for their contributions to biomedical and health science, the highest number elected into the academy in a single year.

The Academy of Medical Sciences aims to advance biomedical and health research and its translation into benefits to society. Fellows are selected from laboratory science, clinical academic medicine, veterinary science, dentistry, medical and nursing care, and other professions allied to medical science including ethics, social science and law.

Prof Miles Parkes

Professor Miles Parkes, director of the NIHR Cambridge BRC and one of our newly elected Fellows said: “I feel very honoured to have been elected as a fellow of the Academy of Medical Sciences and am very grateful both to the colleagues who nominated and supported my application and the many patients and collaborators across who have played a critical role in the success of our IBD research.”

Professor Fiona Gilbert - Imaging theme lead

Professor Fiona Gilbert, Imaging Lead at NIHR Cambridge BRC and newly awarded Fellow said: “Our work here on the Cambridge biomedical campus brings together clinical teams, research and patients, enabling pioneering working in so many fields of medicine and life science.”

Cambridge researchers elected as Fellows

Professor Miles Parkes, Consultant Gastroenterologist and Director, Addenbrooke’s Hospital NIHR Cambridge BRC director

Professor Fiona Gilbert, Head of the Department of Radiology, University of Cambridge and NIHR Cambridge BRC Imaging Theme Lead

Professor Sarah-Jayne Blakemore, Professor of Psychology and Cognitive Neuroscience, University of Cambridge, NIHR Cambridge BRC researcher

Professor David Savage, Professor of Molecular Metabolism, University of Cambridge NIHR Cambridge BRC researcher

Professor Rodrigo Floto, Professor of Respiratory Biology, University of Cambridge

Dr John Marioni, Senior Group Leader, University of Cambridge

Professor Susan Ozanne, Professor of Developmental Endocrinology, University of Cambridge

Professor Anna Philpott, Head of the School of Biological Sciences, University of Cambridge

Cambridge Professors receive NIHR Senior Investigator awards

Congratulations to Professor Emanuele Di Angelantonio, Professor of Clinical Epidemiology and Donor Health and Professor Tamsin Ford, Professor of Child and Adolescent Psychiatry, who have both been newly appointed as Senior Investigators for the NIHR.

Each year the NIHR invites applications into a round of open competition to decide who it awards the prestigious research roles to, based on outstanding contributions to research.

This year, 30 researchers have been newly-appointed to the NIHR Senior Investigator role, two of these have been awarded to NIHR Cambridge BRC researchers.

Professor Emanuele Di Angelantonio said: “I am honoured and proud to receive this recognition from the NIHR. The NIHR has been vital to my research into the fields of cardiovascular disease and blood donation, and I am excited to be able to contribute significantly as senior leader and ambassador.”

Professor Tamsin Ford said: “I am delighted and honoured to receive this award and looking forward to joining the NIHR academy.”

As part of the announcement, Professor Ian Wilkinson, Professor of Cardiology and Cardiovascular Disease, Professor Rebecca Fitzgerald, Professor of Gastroenterology and Hepatology, and Professor Martin White, Professor of Public Health are reappointed as Senior Investigators.

Professor Edward Bullmore, Mental Health and Psychiatry has been awarded Emeritus Senior Investigator.

Find out the full details of the 2022 award winners.

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