Column: Cardiologists’

by Amy Marie Slocum

An interview with Dr. Alexander Lyon

Characters in the literary canon who die of broken hearts form a small club. Iseult of Tristan and Iseult (12th century) doesn’t live long past Tristan’s death. Jean Valjean dies in Les Misèrables (1862), after he is separated from his adopted daughter. And after the dog Old Dan dies of injuries in Where the Red Fern Grows (1961), his companion Little Ann gradually wastes away. Although largely considered to be a cop out from a writer’s perspective, deaths by broken heart are surprisingly common in the real world, and have even garnered a title: Takotsubo Syndrome, so named because the Takotsubo-inflicted heart resembles the clay pots pre-industrial Japanese fisherman used to trap octopus. Flaunt spoke to Dr. Alexander Lyon, a Senior Lecturer in Cardiology at Imperial College and a consultant cardiologist at the world renowned Royal Brompton Hospital in London, who is one of the leading doctors in the field of Takotsubo Syndrome.

What is Takotsubo Syndrome?

When it was first described in 1990 – and for the first ten years – people thought of this as some very rare unusual condition. Now the data is showing increasingly more frequent, probably through both increased recognition and diagnosis. Whether there’s actually an increasing prevalence of Takostubo Syndrome is not known. The estimate in the United States would be one hundred thousand cases per annum, a decent number.

We’ve considered them from a doctor’s perspective as falling broadly into two categories: one category of people who develop it from life at home, in their day-to-day living and they come to hospital because they have Takotsubo Syndrome, but of course they don’t know it at the time. What initially looks like a heart attack because the typical presentation is that people will have a severe chest pain, often accompanied by breathlessness and that’s what drives them to call for an ambulance and seek medical attention and attend the emergency department. The other group have a serious medical illness, or may be requiring emergency surgery, and the stress of the illness triggers an episode.

There are several interesting observations: 90% of people who develop Takotsubo Syndrome are female and they tend to be post menopausal – so ladies in their 50s, 60s, 70s, 80s, and 90s. It’s not only women as 10% of cases are male and we see them in younger women as well. But it means one of the factors we consider is Estrogen, and the loss of the Estrogen post-Menopause.

Another striking oberservation is that most patients have a triggering stressful event, which is usually an extremely stressful emotional event, such as the death of their spouse or a close relative. Particularly if it’s been a partner of many years or equally tragic if someone’s child dies and the news that they have lost a loved one can stimulate a huge great surge of Adrenaline in the body with the emotional stress. In the context of bereavement, it’s been known as ‘Broken Heart Syndrome.’ Some people, within hours to a few days of the death of their partner, husband, or wife, can develop this condition because of the emotional rollercoaster of the bereavement. I have patients where it’s been the loss of the family pet – particularly when it’s unexpected – which can trigger it.

Other examples of very strong emotional responses include emotions at weddings – whether it’s the father or the mother of the bride – sometimes it’s the happy emotions of the occasion, sometimes it’s stressful emotions with disagreements and arguments on wedding days that can trigger it, but events at weddings seem to be a common trigger. Stressful arguments – people having arguments within their family, with neighbors, at work, or being overly criticized or reprimanded by bosses and particularly in public areas with colleagues. Very intensely embarrassing and stressful circumstances can trigger it.

There are a growing number of people who have developed Takotsubo Syndrome from very positive emotional experiences. For example: winning the lottery, winning bingo, an unexpected proposal. So the key common theme coming through this is a triggering event that causes a sudden surge in people’s Adrenaline that would be emotional.

We’re now learning that some people have many chronic, long-term stresses in life for a variety of reasons, and the final triggering event may not be such a big one. It may be because they’ve been coping with stresses for months and it’s a final trigger that pushes them over the top. There are other people where their life is absolutely normal and then out of the blue you get a phone call that your loved one has been killed in an accident or dropped dead for whatever reason and that’s enough to trigger Takotsubo Syndrome.

These people come to hospital and initially – to the doctor looking after them – they look like they’re having a heart attack because, first of all, they have this major stress, secondly they’re clutching their chest and they’ve got severe chest pain. The doctor performs an electrical tracing of the heart, what in America is called an EKG and in the UK, ECG, and that shows abnormal patterns that are usually associated with a heart attack. In modern health care, if you present to a hospital emergency care with severe chest pain, an ECG which looks like you’re having a heart attack, and a blood test that might say there is some damage to the heart muscle, you are rushed to have a procedure called an coronary angiogram, which is where we look at the coronary arteries. When people have heart attacks – because there’s a blockage – they get an angiogram where doctors attempt to open the blockage with a balloon and a stent. However, the coronary arteries of Takotsubo Syndrome patients at the time of the angiogram are generally open and blameless.

What is very interesting in Takotsubo patients is the majority of them have a paralysis of the lower half of their heart. So the lower heart and the tip of the heart, which is technically called the apex of the heart, that all is paralyzed and then what happens is because it’s not contracting, it slightly expands. The top part of the heart continues to contract and what this gives an appearance of a silhouette is like a vase with a narrow neck and then a wide bulbous bottom of the chamber. This is what the Japanese cardiologists when they saw the shape they reflected that it looked very similar to the local Japanese fisherman’s octopus pot.

The first description of this phenomena was in Hiroshima – a city in Japan that lives on the mouth of the estuary that goes out to the sea. They put these pots down onto the shore of the bay and the pot has a dark hole and the octopi think there’s food in them so they swim into them and then can’t escape then they get fished out and taken to the fishing market. That is called a Takotsubo because ‘tako’ is octopus and ‘tsubo’ is pot. So it’s the Japanese fisherman’s octopus pot and it’s got this unusual shape of the heart during the storm of this emotional crisis.

During this storm people can be very sick and in fact there is a mortality rate. Some people die of this condition before they can reach the hospital, with the sudden emotional shock triggering an arrhythmia and they drop down dead. Even in the people with Takotsubo Syndrome who arrive at hospital, approximately 5% of people die of this condition because we don’t have the perfect treatments identified yet. If we use the standard treatment on people with very weak hearts, we think it actually makes the condition worse, not better because the treatments are based on Adrenaline. So if this illness – caused by a massive Adrenaline surge – to then put people on Adrenaline infusions does not make sense and there are signals from health care information that it could potentially make it worse, not better.

We need to learn and understand how to help people with Takotsubo Syndrome, and if people survive the storm – and most do – then over the next few weeks the heart muscle recovers and the area that was paralyzed returns to normal. So when you rescan the heart in three months with an ultrasound scan – called an echocardiogram – or you use a modern scanning system called an MRI, the heart looks as though the area that was paralyzed is recovered. In contrast, if you have a heart attack, and the blood supply is blocked off, it leaves a scar, so that portion of the heart dies in a regular heart attack. Our research suggests that there are special molecular systems which are activated in the heart by the very high Adrenaline levels which protect it.

Adrenaline is a hormone that normally makes our heart beat harder and faster. When you’re exercizing – playing a game of tennis, or going for a run around your local park – you feel your heart beating stronger and faster and that’s because of Adrenaline, amongst other things in your body, going up. But if it goes really high then we know that that can be toxic to the heart and then so what the heart muscle does is it manages to switch from a toxic stimulation pathway in the heart muscle to a protected pathway which allows it to protect itself from this Adrenaline storm. This protective action triggers the heart into this paralysis mode – so it temporarily shuts down. We believe, paradoxically, it’s a protective phenomenon and we’ve done some research that shows that in laboratory studies, that if you block the pathways that contribute to this, the heart muscle dies and it gets worse if you try to interfere.

Takotsubo Syndrome is precipitated by high levels of emotional stress. It is very serious for some people during the acute storm, but providing the patients survive the acute storm, most people do well and get better. Initially, we thought everyone with Takotsubo Syndrome recovered and was fine, but that’s not the case. We now realize there are some people where the Adrenaline storm can cause some injury to the heart. When they have recovered they are still left with problems – they may have heart beating disturbances (arrhythmias), which they feel as palpitations and get unwell, other people get breathless because the heart muscle gets stiffer, other people are left with some chest pains. It can be very difficult and we are learning about this and how to look after these people.

Finally, some people experience more than one episode. So it’s not just that they have a one-off Takotsubo Syndrome attack. They actually have more attacks. I have a clinic at the Royal Brompton Hospital in London where I review people from all over the UK and international patients travelling to London to see me who have these complex types of illness, and we are trying to help them and understand them.

What do you think this says on the effect of emotions on health in general?

Well I think more and more people are understanding that chronic stresses, from work, financial pressure in modern life, and bullying – whether that is in the work place of the family home – all these sorts of stresses are emerging in the world and are driving a deterioration of cardiovascular health. Previously research focused on the link between stress and high blood pressure, vascular disease and heart muscle disease from chronic stress. Takotsubo Syndrome by contrast relates to sudden or acute stress and the cardiac response to acute sudden emotional events that happen. I think there is clearly an overlap and some of patients that I see describe stresses that have been going on for months. And then there is a tipping point. There are some people that have been in hospital with a full-blown storm of Takotsubo Syndrome say ‘well actually I’ve had this before but I ignored it.’ One message is that people who get chest pain should not ignore it because it can be serious, particularly if it is by stress. I expect you have a global readership, so if any of your readers in London think or know that they have experienced an episode and would like to come for a review then we offer this service. I have helped people from all over the world who fly to London and come in and see us at the Royal Brompton Hospital.

The other thing that we are interested in is the strong thing about the female gender component. What we do know is that Estrogen as a hormone acts to calm the Adrenalin system in the body. We have medicines that do this called Beta-Blockers. In addition, while it’s not a Beta-Blocker, Estrogen naturally dampens the body’s responses to Adrenaline. This may be a very good thing because there are two guaranteed stresses in life; the first one for everybody is your own birth ‘coming out of mum’ must be the most stressful event in everybody’s life. The second most stressful event for half the population is being that mum – giving birth. And if every mother that gave birth went into acute heart failure because of Takotsubo Syndrome that would not be a very good way of keeping the species going.

So actually the Estrogen is very good for protecting the mother’s heart from the stresses of labor in childbirth. Of course after menopause you lose that Estrogen and that’s when female hearts get much more sensitive to Adrenaline. There are studies that we have done comparing the male heart and the female heart responses to Adrenaline. When given an Adrenaline bonus the male heart is actually much more likely to stop and have a cardiac arrest than the female heart, unless the female heart comes from a postmenopausal person. Then the heart has lost its Estrogen and begins to behave in this sort of mixed pattern and then we have the Takotsubo Syndrome. It is important to emphasize that this is a hypothesis – it’s not proven. 

Interview by Amy Slocum