Hi Reddit! I’m Sian Harding, Professor of Cardiac Pharmacology at Imperial College London. My research focuses on what happens to the cardiac muscle during heart failure.

What is heart failure?

Heart failure in humans is a syndrome characterised by fatigue, breathlessness and water retention. It happens after recovery from an initial cardiac injury and affects more than 500,0000 people in the UK alone, accounting for up to 40% of all deaths worldwide.

Cardiac injury is often due to heart attack but can also be a consequence of genetic defects, infection or chemotherapy. It has a poor prognosis, with mortality similar to some of the worst cancers. Suffering from heart failure means to be at high risk of shorter life expectancy and generally reduced quality of life.

The cardiac muscle cell, or cardiomyocyte, is the building block of the heart. Deterioration of myocyte function during the development of heart failure is a process that is distinct from the original injury to the heart and may be the result of the body's attempt to produce maximum work from a damaged muscle. Characterisation of the functional alterations to the myocyte, and the molecular processes underlying them, has led to ideas for specific treatments for the failing heart.

About my research

My research at the National Heart & Lung Institute is centred on the cardiomyocyte and its role in heart failure. Starting with simply understanding what happens in heart failure and the effects on myocardial function, to developing models and systems around that.

We use several different animal species (mice, rabbits, rats) to either mimic the heart failure syndrome as a whole, for example by tying off part of the heart muscle under anaesthesia, or to imitate just part of it such as the high catecholamine levels.

My research group was also among the first to do work on isolated human cardiomyocytes. Our understanding from this work leads to involvement in gene therapy trials and more recently in using pluripotent stem cells to produce genotype-specific cardiomyocytes.

This allows the possibility of gene editing and creating engineered heart tissue. It can be a really powerful tool for looking at larger scale characteristics like arrhythmia.

About animal research

Research involving animals forms an important element of our work but is not undertaken lightly. My commitment towards the Reduction, Refinement and Replacement principles is evident from my pioneering work with human myocardial tissue. However, to fully mimic and understand what happens to the cardiac muscle during heart failure, some use of animal model is still critical for our research.

We have also recently been using cardiomyocytes made from human induced pluripotent stem cells. These are an exciting new replacement method, as they can be used for making strips of tissue (Engineered Heart Tissue) and mutations can be introduced either by making the cells directly from affected patients or by gene editing. We are also using the Engineered Heart Tissue in our cardiac damage models on the way to a cardiac patch therapy for heart failure.

My commitment to animal welfare is reflected in my role as Chair of the Animal Welfare and Ethical Review Body (AWERB) which reviews Imperial researchers’ animal research to guarantee the combination of best science with the highest standards of animal welfare (http://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/regulation/)

Proof:

https://twitter.com/imperialcollege/status/1194274355603222529

https://www.imperial.ac.uk/people/sian.harding

Reference for this research:

  1. Davies CH, Davia K, Bennett JG, Pepper JR, Poole-Wilson PA, Harding SE. Reduced contraction and altered frequency response of isolated ventricular myocytes from patients with heart failure. Circulation. 1995;92:2540-9.
  2. Schobesberger S, Wright P, Tokar S, Bhargava A, Mansfield C, Glukhov AV, et al. T-tubule remodelling disturbs localized beta2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure. Cardiovasc Res. 2017;113(7):770-82.
  3. Harding SE, Brown LA, del Monte F, O'Gara P, Wynne DG, Poole-Wilson PA. Parallel Changes in the b-Adrenoceptor/Adenylyl Cyclase System between the Failing Human Heart and the Noradrenaline-treated Guinea-pig. In: Nagano M, Takeda N, Dhalla NS, editors. The Cardiomyopathic Heart: Raven Press; 1993.
  4. Hellen N, Pinto RC, Vauchez K, Whiting G, Wheeler JX, Harding SE. Proteomic Analysis Reveals Temporal Changes in Protein Expression in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes In Vitro. Stem Cells Dev. 2019;%20. doi:10.
  5. Smith JGW, Owen T, Bhagwan JR, Mosqueira D, Scott E, Mannhardt I, et al. Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits. Stem Cell Reports. 2018;11(5):1226-43.

Other info:

Animal research at Imperial College London: https://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/

Animal research report 2016/17: http://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/annual-report/

UPDATE [12.45PM ET / 5.45PM GMT]: Thanks very much for your great questions everyone. I’m heading off for now but will be checking back in tomorrow, so please do submit any more questions you may have.

And a big thanks to r/IAmA for hosting this AMA!

Comments: 696 • Responses: 31  • Date: 

Prime_Mumbler265 karma

My mother had a heart attack about a month ago. She had bypass surgery. The surgeon told my her heart and arteries were calcified. After they were done they started her heart but it stopped. They went back in to check the work and inserted a device that is apparently a balloon that sits next to the heart and helps blood go into the heart. A few days later it was removed. She was getting better slowly but with many complications. She ate food on her own and walked a few feet. But then she stopped eating. She hasn't walked in a week. Now she's on a feeding tube and suffering from depression. So so much more has happened to her. I'm devastated. The doctor says she has heart failure. Every Doctor and nurse I talked to say different things like she'll get better we just need to wait. I'm scared. She's a single mother and I'm am only child. I don't know what to ask I just want her to get better but I feel like we've stopped going forward. I guess I just want to know if she'll be able to come home? I know you don't know but I'm desperate

ImperialCollege134 karma

Hello Prime_Mumbler. I'm so sorry to hear this. As mentioned on other posts, I am a scientist not a clinician so I’m afraid I'm really not the best person to answer these questions. It's heartwarming to see the Reddit community offering support to you here on this thread, and I'd like to add my well wishes to you and your mother too. Stay strong.

Forgiii193 karma

Question from me as a paramedic: For us (at least in Germany) it's load and go. So basically save the patient from dying right away (checking pulse, blood pressure and treating them if the patient is dying from it) and get him to the hospital as fast as possible without moving him too much or not at all. Now is my chance to ask an expert on something I've always wanted to know. With heart injurys like heart attacks. Are there any special things me as an paramedic could do to further increase the chance of survival which we don't learn while becoming a paramedic Question from me as a normal guy concerned about the health of animals: How do you test this kind of stuff on animals. Is it cruel to the animals? Were there any deaths?

ImperialCollege154 karma

Hi Forgiii, thanks for your question. Paramedics are a vital first line with heart attacks, and what you do has been designed to give people the best chance until they can get to the catheter lab in the hospital. Any new things for you to do will have been thoroughly tested before going into wide use.

For animals, we anesthetize them and tie off part of a blood vessel in the heart to mimic a heart attack. Sometimes they stay under anesthetic to test acute treatments and are humanely killed at the end. Sometimes they are allowed to come round,and they will be treated with painkillers to prevent any discomfort. This is where we test longer term treatments, and we use echo and MRI to see if they are working. If they start to show any signs of heart failure they are humanely killed.

poopellar46 karma

What kind of animals are these tests done on?

ImperialCollege84 karma

Hi there. Thanks for your interest. Mostly mice and rats, for the basic discovery experiments to find out new treatments. When they get close to being ready for people, they must be tested on larger animals such as pigs. We also use rabbits, because they may be enough like human in some heart aspects to be able to replace pig experiments.

Further information about our animal research and welfare at Imperial can be found here: https://www.imperial.ac.uk/research-and-innovation/about-imperial-research/research-integrity/animal-research/

Forgiii-12 karma

So you are saying that in every case the animal dies at the end because you manipulated the heart? I find that very cruel thou it's necessary to advance in medicine.

ImperialCollege27 karma

The law in Europe is very much about preventing suffering to the animal, quite rightly. Our biggest effort is to observe the animal very closely to make sure we pick up the very first signs that it might be in pain or distress. If we can't relieve that by painkillers or anything else, we must end its suffering as quickly and painlessly as possible. We are not even allowed to keep animals into old age, in case they develop distressing ailments.

llyffant24145 karma

Hi Sian. Have you always been intersteded in researching heart failure and cardiomyocytes and why did you decide to specialise in this area?

ImperialCollege237 karma

Hi there. My father-in-law died of heart failure just before I went to University. I could see there was a problem that needed solving. And I had a project at uni which helped me explore this topic, so I was hooked from that point on.

unhappygounlucky93 karma

In your professional opinion is it true that if you tell a heart, an achy breaky heart, something that it might not understand the achy breaky heart might blow up and kill this man?

ImperialCollege99 karma

Haha! Absolutely, Mr Ray Cyrus knows of what he sings! There is actually a condition called “Broken Heart Syndrome” and it can be caused by grief, excitement and sometimes by watching football! It can cause sudden cardiac death (which I’ve mentioned elsewhere in this AMA), heart rupture or another condition called Takotsubo syndrome, acute heart failure, which is often reversible.

coldonewiththeboys43 karma

How decrimental is the occational use of cocaine for the heart of a healthy adult?

ImperialCollege4 karma

Hi there. I once read a statistic which said that approximately one third of heart attacks in a London A&E on a Saturday night were cocaine-related. It activates the same system as adrenaline to cause arrhythmia.

PTguy77741 karma

I was told in the medical program that I attended, that during heart failure the myocardium of the ipsilateral ventricle hypertrophies and becomes somewhat thicker with no subsequent positive inotropic effect. Could you explain why that is the case, since ordinarily the hypertrophied muscle would create an increased contraction force?

ImperialCollege61 karma

Thanks for your question! Hypertrophy causes an initial increase in force but changes in the cardiac muscle cell then make the force drop again, below the initial value. So even an increase in muscle mass does not increase the force of the heart at that point.

lyreflyn31 karma

Hi there, I'm currently an undergraduate student in the states, but one of my higher-level courses is in cardiovascular biology and this was one of our recent topics! I know a lot of research is being done on cell reprogramming, but I was wondering if any viable research has been done on cardiac fibrosis? As in, is it worthwhile looking into preventative treatments for fibrosis after an MI? Thanks for your time!

ImperialCollege30 karma

Hi Lyreflyn. Yes there is a very active research field for this. But we need some scar formation after MI to prevent cardiac rupture. It’s getting the balance right between this and blocking the widespread fibrosis that causes stiffening and arrhythmia that is tricky. All the best with your studies!

Coolwhip7616 karma

This might be similar to what you studied or know, but my father has drop dead syndrome and he has his heart enlarged. He's got a defibrillator in right now and every couple years he gets the batteries change or something along those lines. Surprisingly he has lived past the limit that doctors set on him by almost half. He currently needs to take many many pills in the morning and struggles to exercise but does a lot of work with his hand and in the shop to keep active. Some of his Doctors say it's a miracle that he is still alive and I believe they're right. But my real question would be what would signs be that his health is declining even though he's already in such a (Bad state) as it is?

ImperialCollege24 karma

Thanks for your question, CoolWhip76. If he finds it harder to exercise, or he is breathless, or he has swelling of the legs. I’m sure his doctors will be looking out for these or any other symptoms though.

SpecterTheGamer14 karma

Can you confirm that the number one cause of deaths by heart failures is because your heart suddenly stops working?

ImperialCollege35 karma

Hi Specter. You are talking about sudden cardiac death I think, when a massive disturbance of the heart rhythm stops blood from being ejected by the heart. Sudden cardiac death happens in apparently normal people, but not often. It also happens as part of a heart attack death. For heart failure death, about half the death is from this and half from a gradual failure of the heart to pump.

Daguvry14 karma

Can you elaborate on meth heart? What exactly destroys the right heart with methamphetamine use? Is it the meth itself (chemically) or how the meth effects heart function (physiological)?

I'm a Respiratory student and almost done. Any advice on anything for my career?

ImperialCollege16 karma

Hi Daguvry. It’s most likely the action of this drug to stimulate neurotransmitters such as catecholamines. Even the natural catecholamine heart stimulants, like adrenaline, act through receptors on the heart cell surface and can cause calcium overload and, if prolonged, cell death.

The National Heart and Lung institute is always looking for good young Respiratory scientists!

sadlyecstatic13 karma

Is there a way to restore cardiac muscle? An artificial replacement? In the future could this be a better solution than a heart transplant?

ImperialCollege31 karma

Good question. The mechanical partial artificial hearts are doing quite well, and are supporting people for years as they wait for a transplant. They have the problem that they must be driven by an external battery, and the wire through the skin can cause infection.

We are working on engineered heart tissue (see this BBC article), which is made from pluripotent stem cells which we turn into cardiac muscle cells. The pluripotent stem cells can be reprogrammed from ordinary skin or blood cells, so we can effectively turn your skin into matching heart tissue. Theoretically, we could implant this in your heart without it being rejected. But there are lots of hurdles to go yet to make it safe and deliver it effectively for patients.

Trinilos9 karma

In medical school we're taught 2 things that didn't make intuitive sense to me:

  1. Digoxin increases contractility and improves symptoms but does nothing to improve mortality. I'm presuming that mortality is associated with hypoperfusion, so why does a drug which improves cardiac output not decrease mortality?

  2. AICDs are considered in heart failure patients so long as their NYHA classification is > IV. Why is this lower limit in place? It seems they'd still benefit from it, so my guess is this is a cost-benefit issue where patients aren't expected to live long enough for the surgery to be worth the risks associated with surgery?

ImperialCollege9 karma

Thanks for your questions, Trinilos. Digoxin, like other drugs which increase contractility, can also increase the chance of getting arrhythmias and so are risky. Some even made mortality worse in clinical trials (so are not used of course).

I can’t answer the second point I’m afraid.

agile_giraffes6 karma

Hello! I am looking into heart failure pathways and wanted to ask:

1) what is the most common severity class at the time of diagnosis?

2) what would you like to see improved in the care pathway?

ImperialCollege13 karma

Hello agile_giraffes. Thanks for your question. I am a scientist not a clinician, so I'm afraid I’m not the best person so these questions sorry.

dronz3r2 karma

What's the difference? I was under the impression that all the medical professionals who went to medical school are doctors and can treat patients.

ImperialCollege14 karma

It's a good question, Dronz3r. In my case, I did a degree in Pharmacology and then a PhD, so I’m a scientist. So I work alongside clinicians but am mainly laboratory based.

blacksheep4314 karma

What are your clinical sources of information if you have questions that your research cannot help decipher? Are there reputed journals or research websites you trust more than others? Thank for your time in breaking down HF!

ImperialCollege5 karma

Definitely the journals help, but I am very lucky to work in the National Heart and Lung Institute, where I have many fantastic clinicians working alongside me. It’s important for biomedical scientists to keep up to date with the reality of patient treatment from active clinicians.

ocean_wavez4 karma

Hi! I’m a nursing student in my last year. What are some signs of heart failure that are commonly missed? What can I do as a nurse to best care for those with heart failure?

ImperialCollege9 karma

Hi Ocean. Breathlessness can be confused with other diseases, like chronic obstructive pulmonary disease (COPD). In fact, because things like heart failure, COPD, kidney failure and dementia all tend to cluster together in older people, it can be difficult to pinpoint the primary disease. This is the current challenge of multimorbidity.

All the best with your last year of studies!

Jayelvee232 karma

Can having chemotherapy 20+ years ago lead to CHF? Or is this coincidental?

ImperialCollege2 karma

Hi Jayelvee. It could be part of it. There is a clear link between the drugs used to treat cancer and possible damage to the heart. As people are living longer after cancer treatment this is being seen more.

Cardiologists are teaming up with cancer specialists to prevent this happening, and to treat cancer patients when it does happen. Us scientists are trying to understand why the damage happens and design better cancer drugs.

elpinguinosensual2 karma

What insight can your research offer front-line healthcare professionals like doctors and nurses? Any advice on patient education?

ImperialCollege2 karma

Thanks for your question. Actually, just last week I spoke at a meeting which explained the new therapies coming through now, like gene and cell therapy, to a wide range of healthcare professionals. These are going to be more and more important, and they have very different properties and potential to normal drugs.

Mungo_Clump2 karma

Deterioration of myocyte function during the development of heart failure is a process that is distinct from the original injury to the heart and may be the result of the body's attempt to produce maximum work from a damaged muscle.

So could this be a case of the body not always knowing what's best? So if you found a way to block this reaction might modern medicine be able to provide a better post-injury treatment that doesn't lead to this type of heart failure?

Also. With all you know about hearts, what lifestyle changes to you enforce, or are you as daft as the rest of us?

ImperialCollege7 karma

Hi Mungo. The problem is that the systems that get activated when the body senses a loss of power in the heart are from ancient evolutionary times. Then, we were more likely to die of injury or accident. So the body is thinking you have to run away from a mammoth or have been bitten by a saber tooth tiger. They are for emergency, and are damaging if they go on too long.

In fact, the drugs we use now for heart failure are almost all to block the body’s response

And yes I am as daft, if not dafter. But even I don't smoke.

equinoxdark2 karma

Sorry for not reading everything you have written in the details box and sorry for asking a normie question but: exactly how much exercise should an average person do to make sure he/she have no heart problems in life?

ImperialCollege3 karma

Not at all, equinox! To answer your question, it's difficult to make one rule for everyone, but definitely more is better – until you get to extreme athletes when there is some doubt. Even a little is better than none.

NealR20002 karma

My brother unexpectedly passed away at 51 and the cause of death was Arrhythmogenic right venticular cardiomyopathy with predominat left ventricular involvement.

Can you please give me a layman's understanding of what happened?

ImperialCollege2 karma

I’m so sorry to hear this. Cardiomyopathy means a disease of the muscle itself, which seems to have started in the right ventricle (which sends blood to the lungs) and then involved the left ventricle (the main one that supplies the body).

Arrhythmic means that there were disturbances of rhythm of beating in the right ventricle. I can’t tell from this whether it was the rhythm disturbance which caused his death in the end.

TurboKid19971 karma

What role does possibly "replenishing" the mitochondria have in repairing the heart after a heart attack? Are you involved in research into this? I have read about a case study where the heart was injected with the patients own mitochondria from muscle and it aided in the recovery of the muscle.

ImperialCollege2 karma

It’s very clear that the mitochondria are defective after a heart attack, so will be producing less energy, and that in turn leads to a poor prognosis. I’m not directly involved in this though, and have not heard of the study you mention.

GoodnightFairLady1 karma

I know that the common atrial tachycardias you see in heart failure are due to overstretching of the myocardium, but what is actually happening at a cellular level that leads to the increased action potentials and/or ectopic pathways causing the tachycardias?

ImperialCollege4 karma

Hi there. There are changes within the cardiac muscle cell itself, which modifies its electrical activity. The action potentials can become longer or the cells can become overloaded with calcium. But also there is a change in the muscle composition, as cells which die are replaced by scar. Then the electrical pathways across the atria get disrupted.

simonbleu1 karma

What happens to the cardiac muscle during heart failure?

ImperialCollege4 karma

Thanks for asking! Heart failure starts with damage to the heart (e.g. from a heart attack, or chemotherapy drugs, or valve disease) or some loss of power in the muscle e.g. from a hidden genetic defect.

The body senses the loss of power and tries to stimulate the heart with adrenaline (and noradrenaline), by changing the shape of the heart, and by loading of water.

This causes further damage over the course of months and years. Eventually, either the heart gets weaker and heart fails completely or there is a sudden massive arrhythmia which causes rapid death. Drugs now are getting better at preventing further damage.

[deleted]1 karma

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ImperialCollege5 karma

Thanks for your question, LOOKFURTHERLEFT. However I'm afraid this is best answered by a clinician.

TruthfullDuck1 karma

So.... what actually happens to the cardiac muscle?

ImperialCollege3 karma

So...

Heart failure starts with damage to the heart (e.g. from a heart attack, or chemotherapy drugs, or valve disease) or some loss of power in the muscle e.g. from a hidden genetic defect.

The body senses the loss of power and tries to stimulate the heart with adrenaline (and noradrenaline), by changing the shape of the heart, and by loading of water.

This causes further damage over the course of months and years. Eventually, either the heart gets weaker and heart fails completely or there is a sudden massive arrhythmia which causes rapid death. Drugs now are getting better at preventing further damage.

EMarkDDS0 karma

As a dentist, the standard of care (a wonderfully ambiguous and ever-changing barometer) is to wait 6 months after a heart attack before treating those patients. Can you offer any guidance on which individuals are most at risk? What the line is between someone you'd be comfortable treating vs someone who should delay any elective treatment for a certain amount of time?

ImperialCollege1 karma

Hi there. I’m not clear why this should be – can you tell me the reasons given for waiting this long?