From coronary heart transplants to implantable units, BHF-funded science has helped to develop improvements that after looks like science fiction. Here’s a preview of what the way forward for drugs may carry subsequent.

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Using digital actuality to enhance coronary heart surgical procedure

Around one in each 200 new child infants has a coronary heart downside that wants surgical procedure or one other process. Professor John Simpson and his group at Evelina London Children’s Hospital and King’s College London are utilizing a BHF grant to work on a digital actuality expertise to enhance these procedures.

He explains: “We take a look at detailed scan photos of a person’s coronary heart in an effort to determine what’s the proper process, on the proper time, with the minimal danger.

“In the final couple of a long time, we’ve gone from 2D to 3D photos. But you’re nonetheless taking a look at them on a flat display screen. Even 3D printed fashions of hearts are usually not excellent – you must break it to see the buildings inside. Also, the 3D fashions present the center at one second in time. But the residing coronary heart is dynamic; it beats, and the valves open and shut.”

With his group’s new expertise, data from coronary heart scans routinely taken in hospitals could be changed into a digital, beating coronary heart. “With the headset on, and joystick in your hand, the digital coronary heart is correct in entrance of you. You can zoom out and in, see it from each angle and look inside,” says Dr Natasha Stephenson, Professor Simpson’s fellow researcher.

In a earlier research, surgeons used the expertise to assessment operations that had already taken place. They discovered that, in comparison with conventional 3D imaging, it gave them a greater understanding of the affected person’s coronary heart and would have helped them higher plan the surgical procedures. Now the group are working in direction of testing this expertise to plan actual procedures, which they hope to do within the subsequent two years.

How will this assist?

“This expertise permits surgeons to grasp what they’ll truly face within the operation,” says Professor Simpson. “You can put a digital machine into the digital coronary heart and see which would be the greatest machine. Or even share the imaging with corporations that may make bespoke units to suit the person’s coronary heart. We hope it will imply higher repairs, fewer problems, shorter hospital stays and higher long-term outcomes.”

These digital actuality photos can be used to indicate sufferers what the problems are with their coronary heart, or used to coach docs.

While Professor Simpson’s focus is on congenital coronary heart ailments, he says, “In the long run, this expertise might additionally assist higher visualise the issues of adults with different kinds of coronary heart illness.”

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Finding new ways to repair damaged heart muscle

After a heart attack, some heart muscle cells can die off, which can lead to heart failure. Dr Nicola Smart is trying to answer questions that might one day help us to help hearts regrow themselves.

“From studies in mice, we know a couple of days after birth, the heart can fully regenerate. A week after birth, it loses that ability,” explains Dr Smart.

To repair itself, the heart needs to grow new blood vessels, as well as new muscle. “In adults, there is some growth of blood vessels, but it happens slowly and inefficiently.”

She and her team at the University of Oxford are studying how different types of cells in different parts of the heart send signals to each other, helping the heart to grow new blood vessels. Through a technique called single-cell RNA-sequencing, she is seeing which of the genes involved in this process are “switched off” (not expressed) in adults.

“Single-cell RNA-sequencing has completely changed our level of understanding. It used to be that we could only look at overall gene expression changes in a heart. That could tell you nothing about how different cells were responding to a heart attack. Now we see which genes are being expressed in each cell, we know even the same types of cells will respond differently in different parts of the heart.”

How will this help?

Dr Smart says we’re just at the start of understanding how this new knowledge might lead to treatments in future. “Regrowing heart muscle and blood vessels is only one part. Other teams are looking at how to limit scarring and how to work with the immune system, which also influences the heart’s ability to regenerate. But if we can bring together all these ideas, we could develop a combination therapy to stimulate the heart to regenerate, and that could prevent more people developing heart failure.”

Scar tissue on the heart: tracking it in real time

Scarring is part of the body’s healing process. But it can cause problems. After a heart attack, too much scarring can stop the heart working well and cause heart failure.

MRI scans are currently used to look at scars that have already formed in people’s hearts. Now BHF-funded research is developing a cutting-edge technique so doctors can track scarring as it happens.

Professor Marc Dweck and his team at the University of Edinburgh are using PET scanning, a type of very detailed scan that can show how your body’s cells are working. “We’re using a new tracer – a special chemical, which attaches to cells that cause scarring. The tracer sends a signal that we can detect on the scan.

“Right now, we don’t have a clear idea of when scarring occurs following a heart attack. In people who develop heart failure, do they have too much scarring activity or is it that scarring doesn’t ‘turn off’ at the right time?”

His team will try to find the answers by studying people who’ve recently had heart attacks, as well as people who have old scarring from previous heart attacks, and healthy people.

How will this help?

“Understanding how scarring develops may help us predict who will make a good recovery after a heart attack and who will need more treatment to prevent heart failure,” explains Professor Dweck. “We’re talking precision medicine: with better scanning, we can tailor the right treatment to the right patient.”

Blood vessels in a microchip

Pulmonary arterial hypertension (PAH) is a rare but serious condition, which causes high blood pressure in the arteries of the lungs. It can lead to heart failure and can sometimes be fatal. Currently there is no cure. BHF-funded researcher Alex Ainscough, at Imperial College London, is developing a new way to look for treatments.

He’s created a “pulmonary artery on a chip”, in which the innermost layers of the artery walls are recreated inside a silicone rubber microchip just 1mm wide (the same size as the small arteries that are first affected in PAH).

“In traditional research, you look at one type of cell, but in our bodies different cell types interact with each other,” explains Dr Ainscough. “We are trying to make it as representative of the human body as possible.”

By running liquid through the chip, he can mimic the flow of blood in the body, which has a big impact on the cells. He explains: “When you grow cells in a petri dish for research, it’s like they’re in the calm of a lake; but in the body, they are being subjected to forces like a fast-flowing stream.”

He created a model of a diseased artery by using stem cells from people with PAH to create a pulmonary artery on a chip, which led to him discovering a previously unknown way in which PAH develops.

How will this help?

As well as being used as an investigative tool to understand how PAH happens, the pulmonary artery on a chip is being used to try out potential treatments. Dr Ainscough is working with a pharmaceutical company to test some of their existing drugs, as well as new drugs that are in development to treat PAH.

He predicts that in future, organ-on-a-chip models will help make treatments cheaper and quicker to develop. These models more closely match conditions in people compared to traditional petri dish research, so it will be faster to identify promising drugs before moving to clinical trials.

There’s also potential to use these for more personalised medicine. “You could use stem cells from a particular person to create a microchip model to see how they’ll react to a specific drug before giving it to them.”

Read more about personalised medicine

Creating living tissue that grows with children’s hearts

Most babies having surgery for heart defects will need repairs using additional materials such as patches, valves or tubes. These products are either made from animal tissue or synthetic material: they won’t grow with the child and will become scar tissue and gradually deteriorate.

Massimo Caputo, BHF Professor of Congenital Heart Surgery at the University of Bristol, explains: “This means a child might need surgery weeks after they’re born, again after a year or two, then after another five years, and carry on having repeated surgeries all their lives.

“Each surgery can cause more scarring, which can cause problems like heart failure or abnormal heart rhythms. There’s also the mental stress of going through these operations. For years, patients and parents have said to me, ‘Why can’t we have a valve that lasts forever?’”

Thanks to one of our research grants, Professor Caputo is developing a kind of living tissue, made partly from stem cells, that will grow with the child. He’s currently in the process of securing regulatory approval and the first tests in patients should start in two to three years.

How will this help?

This living tissue could reduce the need for multiple surgeries, in adults as well as children. “If you have a valve replacement from animal tissue, this will wear down and you will need to replace it after 10 years. Even if you’re in your 50s or 60s, that could mean multiple surgeries. The tissue I’m working on could be applied to adult surgery too,” says Professor Caputo.

Another benefit is that this tissue could be less likely to be rejected by the body: “A patient’s own stem cells could be used to produce the tissue, so that the immune system recognises it and doesn’t reject it.”

Published 10 June 2022

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By Seth A. Dunbar

Seth Dunbar leads clinical research study operations and quality & compliance. He is experienced working with teams to help drug sponsors better leverage eSource data. With 10+ years of experience Seth brings expertise developing eClinical services that integrate data and technology to help companies optimise study execution.

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