Heart failure: can you mend a broken heart?

0:11Hello,

0:17welcome to the Naked Scientist podcast, the programme that brings you the biggest breakthroughs and also talks to the major movers and shakers in the worlds of science, technology and medicine. I'm Chris Smith and today we're looking at the topic of heart failure. What is this and can we really mend a broken heart?

0:42Heart failure affects millions worldwide. It's a condition where the heart can't pump blood efficiently and this leads to fatigue, breathlessness and the build-up of fluids around the body. It's traditionally been managed by medication and in rare cases by transplantation. But this week, in partnership with the British Heart Foundation, we're going to explore how science is doing its bit to tackle the problem. In this episode, top cardiologists, frontline healthcare staff and researchers tell us about this common condition and why there might be hope. And we're beginning with Brian Williams, who's Chair of Medicine at UCL and also the Chief Scientific and Medical Officer at British Heart Foundation.

1:21Basically the heart is a big pump and when that pump becomes less efficient, it struggles to pump enough blood around the body. And that starves the vital organs such as the brain, the kidneys, muscles of blood. and as a consequence of that people feel terribly tired, they're not able to do the things they would normally do, it can have adverse effects on the function of kidneys, it can affect the function of the brain etc. So often these patients will complain of overwhelming tiredness and frustration that they're unable to do all the things they would like to be able to do. A principal manifestation is often breathlessness because the inability to pump blood efficiently around the lungs and get enough oxygen is one of the key sort of manifestations that patients first notice with this condition.

2:13And it's not an all or none thing in the sense that anything that leads to a slight reduction in meeting the needs of the body is going to begin to produce these symptoms. So it's like a spectrum rather than a black and white effect. Absolutely. Although it can be very sudden and devastating. For example, if you have a heart attack, that can lead to sudden acute damage, age which dramatically reduces the pumping efficiency of the heart and that can lead to a very sudden onset of symptoms but for the vast majority of patients it's a more gradual process as you described where they begin to notice things are not quite what they were and then over time it continually progresses particularly if they don't get some treatment and intervention.

2:54How many people do you think are in that position? In other words how common is this as a problem? It's interesting I mean, it's been a bit of a Cinderella in cardiovascular medicine. We talk a lot about heart attack and stroke, which, of course, are very important. But heart failure affects around about a million people in the United Kingdom. And that's probably an underestimate because it gets substantially underdiagnosed or often gets diagnosed very late. So, for example, you know, whereas many medical conditions are diagnosed by a GP or in hospital outpatients, four out of five patients who present for the first time with a diagnosis of heart failure actually happens in the emergency department.

3:35So these are happening quite late. People don't realise the symptoms they have are indeed due to heart failure. And often it presents very late. 200 ,000 people per year develop this condition. So it's continually growing. And as the population ages, because this takes time to develop in many people, we're going to see a lot more of this. And I think it's going to become something of an epidemic. You know, I mean, I think it's one of the most miserable conditions to develop if it's not properly treated. A former president of the British Heart Foundation, Peter Weisberg, once said to me that we've become extremely good at saving lives from heart attacks and unfortunately condemned all those survivors to heart failure because we're not very good at preventing the damage that a heart attack does.

4:25so we've now ended up with a legion of people who are finding themselves in this position. Yeah another way of putting that, Peter's right, is we've been a victim of our own success so if you look back 40 or 50 years before all the innovations that have improved the survival of people with heart attack, seven or eight out of ten people who went into hospital with a heart attack didn't leave the hospital, they died from that heart attack. Now many of those patients survive. But if the heart attack has been severe and led to significant damage to the heart, that might not initially cause much in the way of symptoms.

4:59But later in life, that loss of heart muscle function eventually begins to manifest. And that's why we see it presenting sort of midlife and later in most people. There are other causes of heart failure which could present in younger people. They're rarer, but they're also very important. So a patient would present with the sorts of symptoms you've been explaining that would raise concerns among the doctors who saw them how would they investigate it how do you diagnose that someone has heart failure we often do a chest x-ray to look see whether there's any congestion in the lungs which we can see we'll always do an ecg to see whether there's any abnormalities that we can see on the ecg that gives us a clue to what might be causing the heart failure a simple blood test is now available called natriuretic peptide, which we can just send off to the lab.

5:50We can get this routinely done. And if your heart is struggling, the heart muscle itself produces this hormone, natriuretic peptide, and the levels go up in the blood. So that is a pretty good way of determining whether somebody's breathlessness is likely to be related to heart failure. Then we have a closer look at the heart with what's called an echocardiogram. And that's a many, many patients will be aware of this jelly on the chest and a probe that's scanned around the chest to to look directly at the heart with ultrasound. And we can then look at the structure and the function of the heart.

6:26If we want more information, then we resort to MRI, which is magnetic resonance imaging, where you go into one of the scanners, wheeled into the scanner and we look at the heart in a lot more detail. So we have a lot of technology now that enables us to make this diagnosis. But those simple early tests that are available in every hospital, doing the blood test, doing an ECG and a chest x-ray and then doing an echocardiogram, they're relatively straightforward tests that should be available to every patient in every setting. And let's say those tests show a person has a degree of heart failure.

7:03What's the management pathway? How are they then dealt with? Well, that's improved dramatically, Chris, over the last, I would say, 10 to 20 years. That really began to improve when we began to understand what was going on here. When the heart begins to fail, the body produces a reaction with a series of hormonal and neuronal mechanisms that try to offset the development of heart failure. And these are, to some extent, maladaptive. So what that means is, although they're trying to help, in many ways, they make the situation worse. And this involves hormones. One of the systems is called the renin-angiotensin-aldosterone system.

7:44And we can now block that system. The other is an increase in the sympathetic nervous system, the kind of system that gets activated in a flight or fight response. And we can block that with drugs. So we use medications now, a combination of medications that block the renal angiotensin system, that block the aldosterone system, that block that part of the nervous system, to try and interrupt this maladaptive response. And this has been shown to both improve symptoms, but also dramatically improve survival of these patients. Which has got to be good news, hasn't it? That was UCL's Brian Williams there.

8:25So now we know what heart failure is and what sorts of processes can cause it. But as Brian Williams was saying, the condition is often underdiagnosed and picked up quite late because people often don't realise that the symptoms they're getting are down to heart failure. So what shape might those symptoms take? Ruth Goss is now a senior cardiac nurse with British Heart Foundation, but previously she spent a lot of time on the wards looking after patients with this very condition. So what do people most often tend to struggle with? If your heart isn't working as well as it should be, it's going to demand more oxygen.

8:58It's a muscle that wants to work well. So if it can't work as well as it usually can you're going to want to breathe harder to try and get that oxygen in also because it's not pumping effectively it's not pumping blood around your body properly you can then get a fluid build-up so that can happen in your chest and that can make you feel more short of breath or it can happen in sort of your ankles and your legs so people will see leg swelling and those are two of the most common symptoms that we would see with people who are maybe suspecting they might be developing heart failure. Obviously, there's a lot of clinical investigations we need to do, but if someone walked into clinic or hospital, that would be what we would be thinking about.

9:37Who does this tend to happen to? It can happen to anyone, really. It does depend on the mechanism of what's causing the heart failure. Heart failure itself is a term that covers lots of different conditions. So you can have children and young people who have been bored with congenital heart disease who will be living with heart failure because of just the nature of their condition. And then on the other side, you may have people who have had a heart attack and because of the damage done to their heart following the heart attack, their heart is now effectively failing. It's not going to recover.

10:10It's not going to be able to pump as well. And that can happen to people who are sort of middle aged, older. And the heart is also a muscle. We can't prevent it from aging. We can do things to help protect its function. But as we get older, our organs, including our heart, get older. So you can see people who are more elderly developing heart failure just because the heart is tired. So it's not, it's going to happen to these people. It can occur in lots of different ways. And what are the signs that it's getting worse? Is it just an intensification of all the symptoms or do you start to notice other symptoms as well?

10:44We might notice it in patient symptoms. We might notice that they're feeling more out of breath or I'm struggling to do things like getting up in the morning or medications aren't working as well as they could be and that can be partly because we haven't got them on the right medicines we maybe need to do a bit of playing around with dosages and things there or it may just be the nature of the condition they could just be getting worse so we may notice changes as nurses but when it comes to symptoms we do have to listen to what that person is telling us so if they come into clinic or we're speaking to someone on the helpline at BHF for example we can hear them saying oh I'm feeling a lot more breathless or I'm noticing that my legs are getting a bit more puffy that can be a sign that maybe things aren't going as well as maybe they should be and in some cases we can fix that it's sort of like an acute change and it's a change of medications but for others it is just part of how things are going and their heart is just slowly getting weaker and weaker.

11:41Presumably there's also going to be a strong well-being slash psychological aspect to this because if people end up disabled and impaired in this way they can't do the things that they used to do they can't even do the things they need to do easily that must really wear people down oh absolutely it can be really debilitating so you've got all the physical things to contend with and but then you also have to think about oh well i've now got this incurable condition what does that mean for me like what do I do now some people can't work some people can't travel anymore there's a lot of questions about sort of what happens in the long term what's going to happen to my family how long have I got and even like you said even just to the day-to-day some days they'll wake up in the morning and go actually I can't manage to do anything today and lose that enjoyment of things that when you're healthy you can maybe take for granted like being able to go up and down the stairs, going out for a walk, enjoying the sunshine.

12:40It has such a huge impact on someone's emotional well-being and mental well-being. That's where, as nurses, you can be really supportive in that role. Although the heart is the origin of the problem, that's the pump that's not pumping sufficient quantities of blood to supply the needs of the body, are there therefore knock-on effects on other organs does it accelerate other diseases that we need to look out for and therefore warn people about that or take steps to stop that happening one of the big ones that it can affect is sort of your breathing so your heart and your lungs are obviously connected one helps the other work and vice versa so you can get that oxygen sort of around the body so if you've got that fluid build up in your chest we want to make sure that we're fixing that so that people can feel able to breathe because that in itself will make them feel more tired and make them feel more anxious and also if the lungs aren't working well then we're not going to be getting enough oxygen into the body and then it turns into this knock-on effect.

13:40Another group of organs that we worry about is the kidneys. If you've got lots of extra fluid in the body and that can be sort of from swelling or sitting in your chest we want to make sure that's removed. We want to kind of remove that extra fluid so that we're not putting the heart or the rest of the body under strain. Typically that's done with medicines sometimes called as water tablets which helps like people get rid of that water um but even those medicines can put sort of the kidneys under strain so we want to make sure that while we're looking at the heart we're also wanting to make sure that the kidneys are okay and people are still able to like go to the toilet and their kidney functions all right the heart is so integral to normal bodily functions if it's not working as well as it should be people will start to see changes but breathing and sort of kidneys and sort of seeing that puffiness are the main ones that we look at and worry about when it comes to other organs.

14:35And when a person is diagnosed with heart failure what does that do to their mortality statistics? We know it is an incurable condition. One of the only ways that you can kind of cure it is to have a heart transplant but that is not an option for everyone and it's also it's quite rare. We just don't have enough hearts and things so when it comes to mortality yes we know more people are living with heart failure but that doesn't mean that you've got x number of years left and that's the sort of question that we get asked a lot of like oh how long have I got they can read online or read in books and says oh I've got maybe four or five years that's not true it's very much individuals down to how they are as a person how they are responding to medications and everything else that's going on?

15:21Do they have any other conditions which could be sort of exacerbating things as well? Ruth Goss, who helps to support people living with heart failure. The Naked Scientist podcast is produced in association with Spitfire, cost-effective voice, internet and IP engineering services for UK businesses. Find out how Spitfire can empower your company at spitfire.co.uk.

15:49Music in the programme is sponsored by Epidemic Sound, perfect music for audio and video productions. This is the Naked Scientist podcast with me Chris Smith and today we are in partnership with the British Heart Foundation to look at the subject of heart failure and how we can repair a heart that's gone wrong. The heart is considered the body's most important organ because it keeps every other organ alive and functioning. It delivers oxygen to our cells, it carries nutrients from food and it removes carbon dioxide and other waste from our bodies. But what does a heart that's failing look like when we compare it with a healthier one?

16:26Well Sian Harding is an emeritus professor of cardiac pharmacology at the National Heart and Lung Institute. The failing heart will be larger to try and compensate for the lack of muscle. It would be contracting very weakly, it might be very stiff as well the walls of the heart might get thicker so you definitely see differences just when they were lying on the slab or when they were stimulated you see differences in their contraction normally though when we exercise a muscle and it gets bigger we'd say that's a good thing it's got stronger so why is it almost the flip side round with the heart a big heart's a bad heart.

17:05This is the heart trying to make up for not having enough muscle by getting bigger and baggier so that every contraction will, although it's weak, will give out a reasonable amount of blood. Or the walls are getting thicker in order to again compensate for each of the individual muscle cells not really contracting very well. And thickening up of the muscle can disturb the rhythm of the heart eventually. And what sorts of insults to the heart would make it do that? Why would we develop a state like that? Sometimes it can be a genetic thing, about 1 in 250 people are going to have some kind of mutation in the heart.

17:50But if something else happens to your heart and you have some kind of stress on it, like high blood pressure, for example, then it can bring out the weakness of that mutation or you could lose muscle and of course a very common way to do that is a heart attack we're really quite good at treating heart attacks now but you have then people who are living now with reduced muscle in their heart they've got stiff scar instead because the heart heart itself interestingly really doesn't regenerate very much whereas your skin will heal over quite quickly your heart has a very small amount of regeneration and really not enough to compensate for a big heart attack.

18:32So you end up with with stiff scar tissue where you used to have muscle that's been lost because you had a heart attack and that's causing the compromise. That's right yes. What do we do about it then so if we've got a situation where the heart's swelling up, becoming too big, too much fluid on board, and it's becoming stiff, it doesn't pump very well. What can we do initially to try to help someone like that? So we have drugs for heart failure, and over my career these have really improved enormously. What they're first of all doing is trying to stop the body from producing these compensatory mechanisms.

19:16So for example, they block adrenaline with beta blockers or have many of the drugs work on the kidneys to increase the flow of urine and reduce water retention so that you get rid of that swelling in the ankles and that breathlessness from the water around the lungs. So they're really stopping the body from making it worse. and some of the other changes you mentioned with things like scar tissue and also fibrous tissue the heart becoming stiff can that be prevented or even reversed with drugs or is that a one-way street once you've got that you have to live with it that's a one-way street at the moment yes Sian Harding at Imperial College London's National Heart and Lung Institute but although as Sian Harding was just mentioning, a damaged heart has traditionally been regarded as difficult to treat and as yet there are no ways of regenerating it.

20:15Mauro Giaka, who's a professor of cardiovascular sciences at King's College London and director of the recently launched Centre of Research Excellence in Advanced Cardiac Therapies, thinks he may be on the cusp of a breakthrough. I asked him how we usually manage heart failure and what he plans to do differently. We have several drugs available for heart failure, but all these drugs desperately try to improve the residual portion of the heart. The heart is still existing, but they don't take any care of the fact that heart failure is, in most of the cases, due to the death of cardiac cells. So for different diseases or simply during life we keep losing cells in the heart, the heart has no capacity of reforming them.

21:06So the revolutionary idea is instead of working on the heart that is there, trying to form a new portion of the heart, so to stimulate cardiac regeneration. Do we have any insights or kind of examples of how this can work or the fact that this is even possible? Yes, it is possible. And this is one of the really exciting parts of our work because other species, for example, salamander or fish, if they have their heart damaged, they can regenerate it completely. And even, for example, newborn mice, newborn pigs, there is also anecdotal evidence that newborn human babies, if their heart is damaged, there is no formation of a scar, no remodeling.

21:57There is complete reformation of cardiac cells. So in all these conditions, the way regeneration works is through the duplication of the existing cardiac cells. So it is the cardiac cells that have survived damage that start duplicating again, and they stop duplicating until they have reformed completely the tissue. It's like when we have an injury in the skin, and the skin completely re-heals. And we know that other species do, neonates do, and so we want to enforce the human adult heart to do exactly the same. Before we consider how they might be doing it the obvious question is well if a fish can do this why can't an adult human do it?

22:46The question could be why can't do it but this is a capacity that stops a few days after life so newborns can do it but if we wait a couple of weeks this capacity is lost and this is one of the big questions in this field but since this can happen in neonates it means that there are biological programs genetic programs that can permit this to occur and so the big goal is to understand which are these biological programs and try to reproduce these in adults with genetic medicines. Is that what scientists like you are doing trying to unpick what is going on when a salamander or a fish heart is damaged and then regenerates itself asking well what's it doing to make that happen can we copy it yes this is exactly what we are trying to do so i'm trying to copy what these species do another possibility we have is to try to induce the same effect through a genetic medicine so we We have the possibility of stimulating the duplication of cardiac cells by RNAs or by genes.

24:04And we have the possibility of understanding which are the genes that can be effective from this using high throughput robotic screenings. So we have a collection of tens of thousands of RNAs or tens of thousands of genes. and we can screen one by one each of these or in combination, which of these can stimulate the proliferation of cardiac cells. We already know that there are families of RNAs that are particularly good at stimulating the proliferation of cardiac cells. They can induce regeneration when we administer them in animals with myocardial infarction. The fish and the salamanders naturally would be switching on these genes and making these gene signals, but they don't get switched on or something else keeps the system locked off in an adult human.

25:03But you're saying if we can see what those genes are that the fish is using to do this and recapitulate that genetic program in a human heart, we might be able to make a human heart into a fish heart temporarily, essentially. Exactly. This is exactly the objective, to use the same genetic programs. The genes can also be different in the sense that we can use also synthetic genes that activate the same biological program. So we can mimic what occurs in fish and salamander, but our therapeutic molecule could be an engineered version of the RNA or the gene that works in fish and salamander. When a heart is damaged, and you yourself have mentioned that we lose muscle cells and we get a scar, fibrous tissue, and that makes the tissue very stiff.

26:01It makes the heart not beat uniformly and well. So are there not two problems to overcome then with this? we'd have to put back the muscle cells that have been lost and deal with all that scar tissue so have we not got a bigger problem than just making more heart cells so basically what we want to do is to reform a new healthy tissue using genetic medicines so there are different genes that control all these aspects and we want to develop a therapy that first individually and then in combination tackle all these different aspects and reform a portion of cardiac muscle that has been damaged. Obviously you're running this centre and this has been your life's work.

26:46It's a huge dream, it's a goal, it's an ambition but how optimistic are you that this will get us over the line? There are no less than eight regenerative applications that are currently considered at the clinical level. Also with some of the applications we are developing in the centre, we aim to be close to clinical application in the next four or five years and so we are not very far away from that. So it seems that cardiac regeneration can already be obtaining animals so it is not an impossible goal to reach. Well it is very nice to end on an optimistic note isn't it? Mauro Jacka there, the director of the MRC-BHF Centre of Research Excellence in Advanced Cardiac Therapies, on how he's looking at using gene therapy to trigger cardiac regeneration and literally mend a broken heart.

27:42That's where we have to leave it for this week, but do tune in on Friday, of course, for this week's look at the latest breaking science news stories. We'll touch on what Obama said about aliens and also Putin's use of frog poisons. Meanwhile, if you'd like regular updates on what we're up to, do please follow us on LinkedIn and Instagram and we welcome reviews on Apple on Spotify and wherever you get your podcast you can also post questions for us there we do pick them up and we do answer you thank you to everyone who is supporting us here on the show on a regular basis we really appreciate that and if you would like to do your bit and get behind the program and keep the show on the road you can help us at nakedscientist.com forward slash donate we really appreciate it I'm Chris Smith thanks for listening and until next time goodbye Thank you.