Takotsubo syndrome (TTS) is not a 'new' condition and has likely always existed. There have been a few publications describing a 'stress cardiomyopathy' or 'neurogenic cardiomyopathy' with the signs and symptoms of TTS for around 100 years. In 1990, Japanese researchers called this condition 'takotsubo cardiomyopathy'.1 It was a decade later that cases began to be reported in Western countries. TTS has been known by several different names, but in now generally called 'takotsubo syndrome'.
To understand how TTS affects the heart, it may help to understand how the heart works.
Figure 1: The normal heart and structures
The heart functions as a muscular pump that delivers oxygen and nutrients to the rest of the body and other organs.
The heart has four chambers. The two chambers at the top of the heart are called the right atrium and the left atrium. The two chambers at the bottom of the heart are called the right ventricle and the left ventricle.
The right side of the heart receives blood from the body's circulation after oxygen and nutrients have been delivered to the rest of the body.
The left side of the heart receives oxygen-rich blood from the lungs via the four pulmonary veins and pumps this blood to the rest of the body. The left ventricle has the largest muscle mass of all the heart’s chambers to enable it to pump blood to the rest of the body.
In a normal heart, the left ventricle contracts strongly and uniformly to eject the blood out of the heart to supply the rest of the body.
Ejection fraction (EF) : The left ventricular ejection fraction refers to the percentage of blood ejected from the left ventricle with each heartbeat. It is often referred to as the 'LVEF' or 'EF' and it is an approximate measure of the pumping efficiency of the left ventricle. Experts vary in their opinions about the lower limit of normal for the EF. Some experts say that an EF 50% is normal, but others consider an EF of 50-55% as being borderline. The left ventricle does not empty completely, and so the upper level of normal for EF is considered to be around 70-75%. If you would like to know a bit more about the EF, check out the American Heart Association video 'Ejection fraction measurement and heart failure'.
TTS mainly affects the left ventricle and impairs its ability to pump properly. The wall of the ventricle is weakened and takes on an abnormal shape. This reduces the efficiency of the ventricle to pump the blood to the rest of the body where it is needed. The portion of the ventricular wall affected will give rise to different shapes for the left ventricle.
Commonly recognised forms of TTS are shown in Figure 2.
TTS is associated with varying patterns of ventricular dysfunction. The left ventricle is the chamber most often affected, but dysfunction of the right ventricle may also occur.2
1) The classic pattern (apical ballooning) is the most frequently recognised pattern and is present in up to 80% of patients.
2) The mid-ventricular pattern is characterised by poor contraction (hypokinesis) of the mid left ventricle and hypercontractile apical and basal segments and is present in up to 15% of patients.
3) The inverted (reverse) or basal pattern is characterised by basal and mid-ventricular segment hypokinesis or akinesis (no contraction) with preserved contractility or hypercontractility of apical segments. The basal pattern is present in 2-5% of patients.
4) The recently described focal type of TTS is characterised by hypokinesis or akinesis of an isolated segment (usually an anterolateral segment). It is estimated to be present in up to 1.5% of patients but is not as well recognised as other patterns.3
There are other variants of TTS for which the prevalence is unknown. This may be because they are rare, or alternately, they may be poorly recognised. These variants include:
In the initial phases of TTS, the EF is reduced below 50%. When the EF is very low, it can cause people to feel short of breath as the blood accumulates in the left ventricle. In severe cases where the ventricle cannot pump strongly enough to eject blood out of the ventricle, blood may backlog into the lungs causing a condition known as 'pulmonary oedema'. TTS usually affects the left ventricle, but in some cases may affect the right ventricle. It may even also temporarily affect the function of the top chambers of the heart (the atria).4
TTS has been given several names since it was first recognised – in fact, more than 75 different names have been used in various publications to describe this condition.5 The reason for the name changes is that as we have learned more about the condition, the previous names did not correctly describe the condition. The table below shows the most frequently used names that have been used for TTS.
|Reversible LV dysfunction
|Case reports and series have been published prior to 1990 describing acute reversible left ventricular dysfunction that was not attributed to existing cardiac disease.6,7
|Japanese researchers were the first to name this condition, hence the Japanese name ‘takotsubo’ which refers to a pot used to catch an octopus. The shape of the pot resembled the shape of the heart chamber (the left ventricle) that was affected by TTS (Figure 2). It was initially thought that TTS occurred predominantly in Asian populations (particularly in Japanese women) and there was not much interest in TTS in Western countries until around 15 years after it was recognised in Japan.
|Broken heart syndrome
|Early cases of TTS tended to be noted in older women who had experienced an emotionally stressful event, such as death of a loved one. In the setting of bereavement, the term ‘broken heart syndrome’ is often used. As TTS became more widely recognised, it became clear that TTS occurs in many settings and has triggers that are both physical and emotional, whilst in a third of cases, the trigger is not identifiable.
|For some time it was thought that emotional stress was the only trigger for TTS, and so many cases escaped diagnosis in the early years. It was later recognised that a physical stressor can cause TTS. Even excitement, or a happy event such as a lottery win can cause TTS.8 In some cases, no particular trigger can be identified, but anxiety or depressive disorders or chronic stress may be present.9 As we identify more cases of TTS, it appears that a physical stressor may be the most common trigger.10
|Apical Ballooning Syndrome
|It was thought that TTS could only affect the bottom of the left ventricle (known as the apex). The term frequently used at this time was ‘apical ballooning syndrome’ (ABS) which again described the shape of the left ventricle (Figure 2).
|Reverse Takotsubo and midventricular Takotsubo cardiomyopathy
|As time went by, it was recognised that TTS could also affect the top of the left ventricle and this form was called ‘reverse TTS’ or ‘basal TTS’ (see Figure 2). TTS was also identified in the mid-ventricle - this is known as ‘midventricular TTS’. Midventricular TS can occur by itself or together with apical or basal TTS.
|Focal Takotsubo Cardiomyopathy
|New research suggests that TTS can affect a smaller area of the left ventricle, known as ‘localised’ or ‘focal’ TTS’. 11
|Most of the names for this condition included the word ‘cardiomyopathy’. Cardiomyopathy refers to a condition where the ventricle changes shape and does not pump as well as it should. Most cardiomyopathies are long-term conditions. In the initial stages of TTS, the heart resembles a heart affected by cardiomyopathy, but unlike a chronic cardiomyopathy, a heart affected by TTS appears to return to normal shape and function within a few weeks to a few months. Some people have ongoing symptoms such as chest pain, breathlessness and extreme fatigue, even after the shape and function of the heart return to normal. It is thought that this may be due to persistent inflammation.12 Moreover, some people get one or more recurrences of TTS.13 This has led to the term ‘Takotsubo syndrome’, reflecting the range of symptoms and varying degrees of recovery from the condition.
‘Broken heart syndrome’ is easy to remember and has more appeal for the general community compared with the name 'Takotsubo syndrome'. Thus, it is a popular term used in the media for TTS, but it is a misnomer. It leads to an incorrect assumption by those that do not know much about the condition, that TTS is related to lost love or disappointment in a romantic relationship, and this can cause frustration for people with a physical or unidentified cause of TTS. Although lost love, or loss of a loved one, has been known to trigger TTS, this is but one context in which TTS occurs. Some people feel that the term 'broken heart syndrome' diminishes the clinical credibility of TTS and leads some health professionals to be dismissive of the condition, particularly in women.
Several explanations as to why TTS occurs have been proposed, but as yet, there is no full explanation that accounts for all cases of TTS. Our understanding of TTS changes as more cases are identified and more information becomes available. For instance, it was initially thought that TTS only occurred in postmenopausal females, so researchers were looking for an explanation relating to female hormones. Now that we know TTS occurs in men, younger women and children, we have to explore different mechanisms. It was also thought that TTS only affected the lower part (apex) of the left ventricle, and so researchers thought that there may be something different about this section of the heart. Now we know that TTS can affect any part of the ventricle and so researchers have had to move on to other theories. Other explanations have been presented and dismissed as evidence has not supported them. It will take time to fully understand TTS and work toward finding preventative therapies and effective treatments, but there have been some important research findings over the past few years and progress is being made. If you would like to know more about this, visit the page on 'Proposed causative mechanisms' or CLICK HERE.
People who develop TTS are usually found to have high levels of catecholamines in their bloodstream. Catecholamines are substances that are made in the brain, adrenal medulla and nerve tissues. When a person experiences physical or emotional stress, catecholamines are released into the bloodstream and have effects on the body that prepare us for physical activity to help us to deal with the stressor. This is known as the ‘fight or flight’ response. Some typical effects of catecholamines are increased heart rate, blood pressure, and blood glucose levels. The main catecholamines are dopamine, norepinephrine (also known as noradrenalin), and epinephrine (also known as adrenalin). It is generally accepted that catecholamines play a major part in the development of TTS.
For some people who experience chronic stress, the fight-or-flight reaction stays turned on and disrupts body systems and processes such as the immune system, digestive system, reproductive system and growth processes. Chronic stress increases the risk of developing health problems such as heart disease, mental health disorders, headaches and sleep problems.
For most people, there is an identifiable trigger for the development of TTS. For some people this will be an emotional trigger, whilst for others it will be a physical trigger. There is no clearly identifiable trigger for around 30% of people who develop TTS. The trigger is probably there but it has not been identified or known to be a likely cause of TTS.
Emotional triggers may be associated with severe emotional upset such as the death of a loved one or extreme fear due to a life threatening event. TTS can also be triggered by psychologically stressful events that seem far less extreme, such as an argument or loss of a personal possession. TTS can even be triggered by a happy event that triggers strong emotions, such as a family reunion or a lottery win.
Physical triggers for TTS include medical illness, extreme exertion or exercise, physical trauma, heat stress, medical tests and procedures, surgery and anaesthesia and some medications. In some cases it may be that a combination of psychological and physical stress can trigger TTS. TTS triggered by underlying medical illness or trauma has led to the concept of ‘secondary’ TTS. In other words, a person already has a medical illness or trauma, and TTS occurs secondary (or as a result of) the existing illness.
The determinant of TTS occurring is not the actual stressor, but rather the individual person’s response to it. Everyone experiences some degree of emotional and physical stress during their lifetime, but not everyone has an episode of TTS. It is not clear why some people, and not others, develop TTS whilst others who are exposed to the same type of stressor do not.
For further information on triggers that are known to be associated with TTS, visit the 'Associated triggers' page, or CLICK HERE.
It was first thought that TTS only affected post-menopausal women, but cases have since been reported in younger women, men, and even in children and neonates. Although it appears that TTS can occur in males and females across the lifespan, around 90% of reported cases to date occur in post-menopausal women.8 Males more often have a physical trigger for TTS, such as acute medical illness or trauma, and usually have worse outcomes when compared to women.14