̽��ֱ�� of Cambridge - cardiac

Heart surgery delays will cost lives, warns research

sc604 — Fri, 17 Jun 2022 09:19:34 +0000

Urgent action is needed to clear the backlog of people with a common heart condition who are waiting for lifesaving treatment, according to research published in the journal BMJ Open. ̽��ֱ��researchers have warned that a lack of action could result in thousands of people dying while waiting for treatment.

̽��ֱ��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 percent will die within two years of symptoms beginning.

Now, an international team of researchers, including from the ̽��ֱ�� of Cambridge, 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. ̽��ֱ��research was funded by the British Heart Foundation and the EPSRC Cambridge Centre for Mathematics of Information in Healthcare.

̽��ֱ��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.

̽��ֱ��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 percent and converting 40 percent of procedures from SAVR to TAVI. This would clear the backlog within 343 days with 784 deaths while people wait for treatment.

“This simple yet relevant model tackles the critical question of how to clear waiting lists and is easy to interpret in practice,” said study co-author Professor Houyuan Jiang from Cambridge Judge Business School.

̽��ֱ��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 life-saving treatment as quickly as possible.

Before the pandemic around 13,500 SAVR and TAVI procedures were performed each year across the UK. Increasing capacity by 20 percent would represent one or two additional TAVI procedures each week per centre.

“We think that with local and national collaboration this increase is achievable,” said study co-author Professor Mamas Mamas from Keele ̽��ֱ��. “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.”

“Our approach does not put the onus on only management or doctors, but creates a joint solution that is easier to implement in practice,” said co-author Professor Feryal Erhun, from Cambridge Judge Business School.

“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,” said Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist. “Cardiac care can’t wait. ̽��ֱ��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.”

Reference:
Christian Philip Stickels et al. 'Aortic stenosis post-COVID-19: a mathematical model on waiting lists and mortality.' BMJ Open (2022). DOI: 10.1136/bmjopen-2021-059309

Adapted from a BHF press release.

Pandemic has delayed lifesaving treatment for thousands of people with severe aortic stenosis.

Our approach does not put the onus on only management or doctors, but creates a joint solution that is easier to implement in practice

Feryal Erhun

Thierry Dosogne via Getty Images

Surgeons performing heart surgery

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Yes

Patching up a broken heart

lw355 — Fri, 16 Jun 2017 15:00:54 +0000

When the body’s repair system kicks in, in an attempt to remove the dead heart cells, a thick layer of scar tissue begins to form. While this damage limitation process is vital to keep the heart pumping and the blood moving, the patient’s problems have really only just begun.

Cardiac scar tissue is different to the rest of the heart. It doesn’t contract or pump because it doesn’t contain any new heart muscle cells. Those that are lost at the time of the heart attack never come back. This loss of function weakens the heart and, depending on the size of the damaged area, affects both the patient’s quality of life and lifespan.

“In many patients, not only is their heart left much weaker than normal but they are unable to increase the amount of blood pumped around the body when needed during exercise,” explains Dr Sanjay Sinha. “I’ve just walked up a flight of stairs… it’s something I take for granted but many patients who’ve survived heart attacks struggle to do even basic things, like getting dressed. While there are treatments that improve the symptoms of heart failure, and some even improve survival to a limited extent, none of them tackles the underlying cause – the loss of up to a billion heart cells.”

̽��ֱ��numbers are stark. “Half a million people have heart failure in the UK. Almost half of them will not be alive in five years because of the damage to their heart. At present, the only way to really improve their heart function is to give them a heart transplant. There are only 200 heart transplants a year in the UK – it’s a drop in the ocean when many thousands need them.”

Sinha wants to mend these hearts so that they work again. “Not just by a few percent improvement but by a hundred percent.”

He leads a team of stem cell biologists in the Cambridge Stem Cell Institute. Over the past five years, with funding from the British Heart Foundation, they have been working with materials scientists Professors Ruth Cameron and Serena Best and biochemist Professor Richard Farndale on an innovative technique for growing heart patches in the laboratory – with the aim of using these to repair weakened cardiac tissue.

“In the past, people have tried injecting cardiomyocytes into damaged hearts in animal models and shown that they can restore some of the muscle that’s been lost,” says Sinha. “But even in the best possible hands, ninety percent of the cells you inject are lost because of the hostile environment.”

Instead, the Cambridge researchers are building tiny beating pieces of heart tissue in Petri dishes. ̽��ֱ��innovation that makes this possible is a scaffold. “ ̽��ֱ��idea is to make a home for heart cells that really suits them to the ground. So they can survive and thrive and function.”

̽��ֱ��scaffold is made of collagen – a highly abundant protein in the animal kingdom. Best and Cameron are experts at creating complex collagen-based structures for a variety of cell types – bone marrow, breast cancer, musculoskeletal – both as implants and as model systems to test new therapeutics.

“ ̽��ֱ��technology we’ve developed for culturing cells is exciting because it is adaptable to a huge range of applications – almost any situation where you’re trying to regenerate new tissue,” explains Best.

Best and Cameron use ‘ice-templating’ to build the scaffold. They freeze a solution of collagen, water and certain biological molecules. When the water crystals form, they push the other molecules to their boundaries. So, when the crystals are vapourised (by dropping the pressure to low levels), what’s left is a complex three-dimensional warren.

“We have immense control over this structure,” adds Cameron. “We can vary the pore structure to make cells align in certain orientations and control the ratios of cell types. We are building communities of millions of cells in an environment that resembles the heart.”

Cardiomyocytes fare better when they are surrounded by other cell types and have something to hold on to. They use proteins on their surface called integrins to touch, stick to and communicate with their environment. Farndale has perfected a ‘toolkit’ that pinpoints exactly which parts of collagen the integrins bind best; he then makes matching peptide fragments to ‘decorate’ the collagen scaffold. This gives cells a foothold in the scaffold and encourages different cell types to move in and populate the structure.

“We don’t just want a cardiac scaffold – we want it to have blood vessels and the same mechanical properties as the heart,” explains Sinha. “If it’s going to contract and function efficiently, it needs a really good blood supply. And the whole three-dimensional structure must be strong enough to survive the hostile environment of a damaged heart.”

Meanwhile, Sinha’s team pioneered the production of the different cell types needed for the patch. Their starting material is human embryonic stem cells, but they have also taken adult human cells and ‘reset’ their developmental clock. “In theory this means we can take a patient’s own cells and make patches that are identical to their own tissue. That said, millions of people are going to need this sort of therapy and so our focus at the moment is on coming up with a system where a small number of patches might be available ‘off the shelf’, with patients receiving the nearest match.

̽��ֱ��team is completing tests on the ideal combination of scaffold structure, peptide decoration and mix of cells to create a beating vascularised tissue. Next, the researchers will work with Dr Thomas Krieg in the Department of Medicine to graft the tissue into a rat heart. Their aim is to show that the patch makes vascular connections, integrates mechanically and electrically with heart muscle, and contracts in synchrony with the rest of the heart. Once they’ve accomplished this, they will scale up the size of the patches for future use in people.

“It’s exciting,” says Sinha. “We are recreating a tissue that has all the components we see in an organ, where the cells start talking together in mysterious and wonderful ways, and they start to work together as they do in the body. Our vision is that this technology will bring hope to the millions of patients worldwide who are suffering from heart failure, and allow them to lead a normal life again.”

It is almost impossible for an injured heart to fully mend itself. Within minutes of being deprived of oxygen – as happens during a heart attack when arteries to the heart are blocked – the heart’s muscle cells start to die. Sanjay Sinha wants to mend these hearts so that they work again.

We are recreating a tissue that has all the components we see in an organ, where the cells start talking together in mysterious and wonderful ways, and they start to work together as they do in the body.

Sanjay Sinha

̽��ֱ��District and Jonathan Settle

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Old drug performs new tricks

Anonymous — Mon, 21 Sep 2015 08:24:54 +0000

Spironolactone, one of a range of drugs given according to doctors' preference to patients with resistant hypertension (high blood pressure that doesn't respond to a standard drug treatment), is in fact "outstandingly superior" to the alternatives, researchers have found. They recommend it should now be the first choice for such patients, and say that – for most – this well-known but under-valued drug will bring their condition fully under control.

̽��ֱ��discovery could have a profound impact globally, since hypertension, a major contributor to stroke and heart disease, is so common, affecting as many as one in three adults in some countries. It challenges what the authors describe as "a growing perception" that severe hypertension was beyond the control of existing drug treatments, and gives more clues into what causes the condition.

̽��ֱ��latest research, published today in the Lancet to coincide with their presentation to the British Hypertension Society, emerged from the PATHWAY-2 trial, part of the PATHWAY programme of trials in hypertension funded by the British Heart Foundation and led by Professor Morris Brown, professor of clinical pharmacology at Cambridge ̽��ֱ�� and a Fellow of Gonville & Caius College.

̽��ֱ��findings are drawn from what authors Brown and Professor Bryan Williams of ̽��ֱ�� College London describe as an experimental "shoot-out" between three different drugs used by doctors for years to treat patients if the standard initial cocktail of three hypertension drugs do not work.

Spironolactone 'slugged it out' against a betablocker (bisoprolol) and an alpha-blocker (doxazosin) in the trial, which took six years and involved 314 patients in 14 different centres.

̽��ֱ��patients all suffered from resistant high blood pressure that had not responded to the standard treatment for hypertension: a combination of three drugs (an ACE-inhibitor (or angiotensin-receptor blocker), a calcium channel blocker and a thiazide-type diuretic). They continued with this basic combination throughout, but each of the three trial drugs – and a placebo – was added one at a time, in random order, for 12 weeks each.

In what is known as a "double blind" trial, neither the patients nor the researchers knew which patient was taking which drug when. In a pioneering step, the study also used patients' own blood pressure readings taken at home to minimise so-called "white coat syndrome", in which the stress of being in a clinic causes blood pressure to rise artificially.

Once the resulting data had been analysed, it emerged that almost three quarters of patients in the trial saw a major improvement in blood pressure on spironolactone, with almost 60% hitting a particularly stringent measure of blood pressure control. Of the three drugs trialled, spironolactone was the best at lowering blood pressure in 60% of patients, whereas bisoprolol and doxazosin were the best drug in only 17% and 18% respectively.

"Spironolactone annihilated the opposition," said Brown. "Most patients came right down to normal blood pressure while taking it."

He added: "This is an old drug which has been around for a couple of generations that has resurfaced and is almost a wonder drug for this group of patients. In future it will stimulate us to look for these patients at a much earlier stage so we can treat and maybe even cure them before resistant hypertension occurs."

Doctors appear to have been wary of giving patients spironolactone because it raises the level of potassium in the body. But the study revealed the rise to be only marginal and not dangerous.

̽��ֱ��causes of resistant of hypertension are still poorly understood, but one theory is that the condition could be the result of sodium retention: too much salt in the body.

Spironolactone is a diuretic and helps the body get rid of salt. In the trial, it worked even better than average on patients whom tests showed had high salt levels. Brown said the findings appeared to confirm that, in most patients with resistant hypertension, excessive salt was the problem, probably caused by too much of the adrenal hormone aldosterone.

Instead of seeing the treatment-resistant form of high blood pressure as simply the result of having the condition for a long time or of poor treatment, it should be regarded as a different sub-group of hypertension which would need different investigations and treatments, Brown said.

Patients with the most dangerous type of high blood pressure will be able to receive far more effective treatment after Cambridge-led research reveals the powers of a "wonder drug" that has lain under the noses of doctors for 50 years.

jasleen_kaur

Sphygmomanometer

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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