Takotsubo cardiomyopathy: past, present and future with Dana Dawson

A recent study suggests takotsubo cardiomyopathy is consistently being treated incorrectly, and questions have been raised about the future of its management. Here, Professor Dana Dawson speaks to Helena Beer about her experiences of researching this unique condition and what her findings might mean for clinicians and patients.

For Dana Dawson, professor of cardiovascular medicine and consultant cardiologist at the University of Aberdeen and Aberdeen Royal Infirmary, the acute nature of cardiovascular medicine was the draw towards this speciality from the early days of her medical training.

She thrives on the urgency required in the care that she provides, not to mention the ‘huge professional satisfaction’ from resolving life-threatening situations. And an area of her practice where she’s making a particular difference here is around the management of takotsubo cardiomyopathy.

Described in the early 1990s by Japanese cardiologists, takotsubo cardiomyopathy is so named because the shape of the heart in an acute presentation resembles a takotsubo – the Japanese for ‘a pot used for trapping octopus’.

The narrow neck of the takotsubo mirrors the small part of the heart that still functions normally and sustains life, and its bulbous body is reflective of a portion of the left ventricle that balloons out and stops contracting.

Put simply, ‘it’s a very unusual condition and quite unlike anything else’, says Professor Dawson.

Prior to taking up a consultant post in 2010, Professor Dawson had seen no more than two cases of takotsubo cardiomyopathy. When on call, she came across her third, and she admits that she was ‘clueless’ as to why it had occurred. As was the patient.

‘I looked at it and I thought, what on earth is this?’ she says. ‘And I thought, “surely this is something that we need to dig into a bit further? I’m not going to let this go”.’

She stayed true to her word. Some 14 years later, having established the Scottish Takotsubo Registry and with multiple takotsubo research projects under her belt – including some impressive recent results – she’s heading up the European task force group on takotsubo and working towards a consensus on this unique and fascinating condition.

How does takotsubo cardiomyopathy present differently to myocardial infarction, and how commonly do you see it in clinical practice?

Imagine you’re in the community and someone becomes unwell and they clutch their chest, they’ve got pain, they’re breathless and pale. You immediately think of a heart attack and so does the patient.

An ambulance is called, they take an ECG and a blood test and they immediately think the same.

Up until that stage everyone thinks it’s a heart attack and it’s not until a little bit later on in their journey when they come to the cardiac catheterisation laboratory that we see that the heart arteries are actually not obstructed as in a myocardial infarction.

None of the heart arteries are obstructed, and yet the heart muscle is not functioning. So that’s bizarre and that’s when we think, well, the fault is not with the arteries therefore it must be with the muscle.

We put dye in the heart cavity and then see that the balloon is there and that’s when we first think of the takotsubo cardiomyopathy diagnosis.

The number of cases is increasing because of better knowledge among doctors and increased awareness of the public as well. We see this fairly frequently now and in our centre, which is by no means a large centre, we see about three to four cases a month.

Tell us about the psychosomatic element of takotsubo cardiomyopathy

There is another pointer to it being takotsubo: it’s a psychosomatic interaction. The condition is sometimes called stress-induced cardiomyopathy.

It’s possibly the strongest psychosomatic interaction in medicine. The hallmark of the condition is that patients will usually have been through a stressful, emotional, unpleasant or even a very happy episode – a strong emotion of some nature.

But equally these emotions can be triggered by a physical condition. This could be in somebody who’s experiencing an exacerbation or an acute episode of another disease. And here, the jury’s out to decide what was emotional and what was physical because with any acute disease there’s going to be some invested emotional involvement as well.

These triggering emotions are usually quite distinct and important in that person’s life. Patients usually volunteer that information to begin with or if they’re prompted.

So, whatever happens in that individual’s brain, it seems to be able to connect somehow with the heart muscle and the heart muscle takes a stance and balloons.

Are researchers any closer to understanding why emotional triggers cause the heart to react in such a way?

Obviously, the first question that most of these patients are asking you after they recover is, ‘why has this happened to me, and will this happen to me again?’

It’s perhaps unsatisfactory, but we’re not afraid to tell people we don’t really quite know why this has happened to them.

There have been proposals that any great emotion causes a surge of adrenaline and it’s the surge of adrenaline that causes this impact on the heart.

I personally don’t think it’s quite as simple as that. I think there’s a lot more to it and it’s our professional duty to go and find out as much as we possibly can.

On that note, tell us more about your research into takotsubo cardiomyopathy

I find takotsubo cardiomyopathy fascinating because of its multi-organ involvement, the circumstances that generate the onset of the condition and the way it manifests itself.

When we started looking into it, we first established that the levels of energy in the heart muscle were extremely reduced. In fact, they were so reduced that to us it looked almost incompatible with life.

We checked and rechecked our data and when we were certain of what we saw we submitted it for publication.

It was immediately accepted and widely spoken about because it was the first evidence of this energy reduction in takotsubo cardiomyopathy.

We still don’t know why the heart doesn’t generate enough energy so there’s more research to be done there.

The next thing we looked into was what else characterised the heart muscle. We started off with postmortem studies of hearts that were donated by patients who unfortunately died during the acute condition, and that’s when we found there were numerous inflammatory cells in the heart muscle.

A lot of the patrolling immune cells in blood were actually infiltrating the heart muscle because they were perceiving that there was a problem in there.

Then we asked ourselves the question: are these cells there only in this particular subset of patients who are unfortunate enough to not survive, and is that why they died? Or do these infiltrative cells characterise the disease in everybody?

So, we set out a clinical trial and we looked at patients’ hearts with very sophisticated imaging and we concluded that they were present to a certain extent in everyone’s hearts at the time of presentation.

And then by about six months, the cells were going away and the swelling and the inflammation in the heart was recovering. It took about half a year for recovery to happen, so quite a slow process, despite the fact that the function of the heart recovered much quicker.

We then started to look at the medium to long term recovery of takotsubo cardiomyopathy and looked at patients who had an episode at least a year before. We figured out that about 60% of them were actually not fully recovering.

There were still elements of subtle discoordination and altered movements in the heart muscle. Although it recovered a great deal, it still wasn’t a fully normal functioning muscle.

So, that means that you know the sequelae were there much longer term than we appreciated initially when we were looking at the patients acutely.

How did the Scottish Takotsubo Registry come about, and how has it supported your research?

Back in 2015, we set out the basis of a national registry in Scotland. Each person in Scotland has a unique identifier number and all the conditions that they have in their lives and all their prescriptions are coded against that number.

All that data is centrally held by Public Health Scotland, obviously in an anonymous format, and because we knew of this resource, we set up the registry.

We had to allow some time for it to accrue takotsubo cases and follow up to be able to draw the first conclusions from what happens at national level.

We then looked into the medication and how we treat these patients. There is no designated treatment for takotsubo cardiomyopathy because in medical timelines it’s only just been described.

In the absence of that, what most cardiologists had done was to extrapolate the medication that is normally prescribed to patients with heart attacks because these patients present like a heart attack.

But we found that almost none of these medicines actually are serving these people. Their survival is not influenced at all by any of these standard medications that we extrapolated from the heart attack cohorts.

So, I think the journey only starts here in finding something that helps this condition because the mechanism of it is so different.

Are there any existing drugs that might be suitable for this condition?

So, fortuitously, we’re possibly not starting from scratch. In the longer term, some takotsubo patients developed a form of heart failure with ‘preserved’ ejection fraction.

Perhaps unsurprisingly then, the only medication that had some signal in our analysis of the cohort was the first line therapy commonly used for patients with heart failure.

But because these data come from a registry, there’s a lot of potential bias by prescriber and by indication.

It’s therefore not really an allocation at random, which is what a gold standard clinical trial does. It would have to be tested in a format like that to decide whether it’s suitable, particularly as we’re not discussing the very acute stage, we’re discussing longer-term survival.

It would be exciting to be able to go ahead and look at that in the future.

Did you uncover any surprising results from the trials?

Interestingly enough, takotsubo cardiomyopathy is a condition that occurs by vast majority in women. So, for every nine women affected by the condition, you only have one man.

Cardiovascular diseases are less diagnosed in women so the population base from which to recruit is smaller. But with this condition we found it quite the opposite and it’s been almost like a revolution.

Women were actually very keen in searching for what caused their presentation of takotsubo and were very keen to return to find out whether their heart was better, how it compared with others and even returning in later years to help with longer-term outcome research.

What are the next steps for your research?

I’ve got two avenues of interest in the next decade of research around takotsubo cardiomyopathy.

The first thing I’d like to try and learn more about would be the ‘why?’ question. We’ve got some ideas in mind, and we’ve got some pilot data in house, and I would like to follow those avenues of thought.

The brain and heart interaction – how and why they interact and the means through which they interact – is where I would like to delve in further.

That is fascinating from a scientific perspective to see what happens to the to the human body to be able to go through multiple decades of life and then suddenly to develop a predisposition towards this.

Or perhaps they had that predisposition all the way along. Perhaps it’s something genetic, but perhaps it’s something acquired. We’re looking into both.

And the second avenue is looking into the therapeutic level based on what we know now about takotsubo cardiomyopathy. We know that this is a condition where the heart doesn’t quite recover is well as it should do. This predisposes these people to be more vulnerable and have reduced survival compared to their peers.

And if that is the case, we’ve got the signal of one medication that is already there, so we can try to test it and see whether that can help in the interim and for the longer term.

Are you working towards consensus and official guidelines?

I head a European task force group called the European Society of Cardiology (ESC)’s Takotsubo Disease Study Group, which is under the auspices of the Heart Failure Association of the ESC.

What we discussed only in January was coming up with a European – or possibly an international – consensus. Not a textbook, just a brief expert consensus of what takotsubo cardiomyopathy is, what we need to be mindful of in the acute scenario and in the longer-term scenario, how we treat these patients according to what we know today, and how we follow them up.

We’re leading the multi-centre work in the UK and there are also centres in Sweden, Switzerland, Italy and Germany looking into the condition. We’ve all looked at different areas and from different angles because there’s so much to investigate and we feel there’s enough knowledge now to join forces together and provide an expert consensus.

We’ve asked the ESC if they would endorse the proposal, and we’ll see what their answer is.