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CHAPTER II

REVIEW OF RELATED LITERATURE

THE SCIENCE BEHIND TAKOTSUBO SYNDROME

a. The role of noradrenaline

Noradrenaline is a hormone and a neurotransmitter produced in the human

body. It is released upon excitement, threat etc. and directly increases the heart

rate. It is released in the fight or flight response.

So what is broken heart syndrome?

Broken heart syndrome was first recorded by Sote et al in 1991. They

discovered that this form of cardiomyopathy involved the left ventricle and

particularly the apex. They found that instead of contracting normally to pump

blood around the body, the ventricle ballooned and expanded. This is due to

akinesia of the distal anterior wall and apical wall and hypercontraction of the

basal wall. Obviously, this would have a severe effect on the blood flow to vital

organs so could be quite problematic. It was named Takotsubo cardiomyopathy

because the appearance of the left ventricle in an angiogram resembles an

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octopus pot, which translates as Takotsubo in Japanese. It is also referred to as

apical ballooning syndrome, due to the ballooning of the apex.

b. Release of catecholamines

In almost all cases of Takotsubo cardiomyopathy, increased levels of

catecholamines (adrenaline, noradrenaline, dopamine) have been found in the

body. There are many things which can induce a release of catecholamines and

emotional excitement or stress are some of them. The catecholamines would be

released to the heart to make it beat harder and faster. This is the most widely

accepted mechanism for Takotsubo but as mentioned earlier, there is no clear

answer.

So why is the apical wall of the left ventricle and the mid-ventricle the

place that is most affected by a surge of these catecholamines? Well, there

are a few anatomical and physiological causes for this.

There is a markedly higher concentration of adrenergic receptors in the

apex of the left ventricle than other parts of the heart and it is these receptors

that noradrenaline and adrenaline will bind to. Also due to increased

responsiveness of the apical myocardium to stimulation of these receptors.

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The apical wall is especially vulnerable structurally as when the rest of

the heart has a three layered myocardial composition, the apex does not and

is therefore a lot thinner.

The area of the apex tends to lose its elasticity a lot more easily after

many extreme expansions and does not correctly go back to its original state.

The apex is a lot more likely to become ischemic as the blood flow is not

large in that area so at any time when blood flow is reduced the apex loses

out quickly.

MAINSPRING OF TAKOTSUBO SYNDROME

The exact cause of takotsubo syndrome is unclear. It's thought that a surge

of stress hormones, such as adrenaline, might temporarily damage the hearts of

some people. How these hormones might hurt the heart or whether something

else is responsible isn't completely clear. A temporary constriction of the large or

small arteries of the heart may play a role.

In this research there are several mechanisms that has been proposed in

connection with the cause of the takotsubo syndrome.

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1. Wraparound LAD: The left anterior descending artery (LAD) supplies the

anterior wall of the left ventricle in the majority of patients. If this artery also

wraps around the apex of the heart, it may be responsible for blood supply to the

apex and the inferior wall of the heart. Some researchers have noted a

correlation between takotsubo and this type of LAD. Other researchers have

shown that this anatomical variant is not common enough to explain takotsubo

cardiomyopathy. This theory would also not explain documented variants where

the midventricular walls or base of the heart does not contract (akinesis).

2. Transient vasospasm: Some of the original researchers of takotsubo

suggested that multiple simultaneous spasms of coronary arteries could cause

enough loss of blood flow to cause transient stunning of the myocardium. Other

researchers have shown that vasospasm is much less common than initially

thought. It has also been noted that when there are vasospasms, even in multiple

arteries, that they do not correlate with the areas of myocardium that are not

contracting.

3. Microvascular dysfunction: The theory gaining the most traction is that

there is dysfunction of the coronary arteries at the level where they are no longer

visible by coronary angiography. This could include microvascular vasospasm.

However, it may well also have some similarities to the diseases such as

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diabetes mellitus. In such disease conditions the microvascular arteries fail to

provide adequate oxygen to the myocardium.

4. Mid-ventricular obstruction, apical stunning It has also been

suggested that a mid-ventricular wall thickening with outflow obstruction is

important in the pathophysiology.

Broken heart syndrome is also often preceded by an intense physical or

emotional event. Some potential triggers of broken heart syndrome are:

Break-ups

News of an unexpected death of a loved one

A frightening medical diagnosis

Domestic abuse

Losing a lot of money

Natural disasters

A surprise party

Job loss

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Divorce

Intense fear

Public speaking

Physical stressors, such as an asthma attack, a car accident or major

surgery

It's also possible that some drugs, rarely, may cause broken heart

syndrome by causing a surge of stress hormones. Drugs that may contribute to

broken heart syndrome include:

Epinephrine (EpiPen, EpiPen Jr), which is used to treat severe allergic reactions

or a severe asthma attack.

Duloxetine (Cymbalta), a medication given to treat nerve problems in people with

diabetes, or as a treatment for depression.

Venlafaxine (Effexor XR), which is a treatment for depression.

Levothyroxine (Synthroid, Levoxyl), a drug given to people whose thyroid glands

don't work properly.

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FEATURES OF TAKOTSUBO CARDIOMYOPATHY SYNDROME

Chest pain and shortness of breath after severe stress (emotional or

physical)

Electrocardiogram abnormalities that mimic those of a heart attack

No evidence of coronary artery obstruction

Movement abnormalities in the left ventricle

Ballooning of the left ventricle

Recovery within a month

PEOPLE WHO LOSE A PARTNER ARE AT RISK FOR TAKOTSUBO

SYNDROME

A growing body of research is showing that the death or loss of a person

close to you cannot only feel like heartbreakit can actually cause physical

changes that can lead to serious heart problems. A new study finds that people

who comes from a break up and whose partner dies are at a significantly higher

risk for atrial fibrillation, or irregular heartbeat, and that effects are lasting.

8 SCIENTIFIC EFFECTS HEARTBREAK HAS ON THE BODY

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1. Your Brain thinks your Physically Hurt

2. You either get really heavy or really thin

3. Youre swimming in stress hormones

4. Youll be depressed

5. Withdrawal is real

6. Youll wonder who you are

7. This wont be the last time heartbreak hits

8. Youll wanted to be alone, but youll need to avoid it.

THE STAGES OF HEARTBREAK:

Someone who is dealing with heartbreak follows patterns similar to those

of the stages of death:

1.Shock and Denial- you may deny the reality of the situation; this provides

emotional protection from feeling overwhelmed by the situation. The shock of

loss allows a state of emptiness to move in, clouding most judgment.

2.Pain and Guilt-after the shock wears off it becomes replaced with suffering and

unbearable pain. Regret for things you did wrong, or things that you werent able

to do with this person adds to further tears. Life feels chaotic during this time, and

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its best to openly discuss feelings and stray from bottling up your emotions

3. Anger and Bargaining- lashing out is a common form of attempting to release

all unspoken emotions. This is the stage where the why why why?! questioning

comes in. The pleas for returned love run rapid, trying to bargain with fate or with

the person who was just lost.

4. Depression, Reflection, and Loneliness- like everyone else in this situation, a

period of sadness clouds and absorb your entire sense of being, leaving feelings

of emptiness. This feeling occurs when you finally realize and accept the

magnitude of your loss. Isolation from people is exceedingly normal, and offers a

time to reflect on the past.

5. Acceptance and an Upward Turn- The feelings of depression lift slightly and

life becomes possible to survive without that person so deeply intertwined with

each activity. The days are a little easier to shuffle through, and you see the

possibility of continuation. The reality of the situation is fully accepted and,

although happiness may not return for some time, the ability to move forward has

occurred.

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THE DANGERS OF BROKEN HEART SYNDROME

If it feels like a heart attack and acts like a heart attack, does that mean

that it is a heart attack? Not necessarily chest pain and tightness, arm pain and

shortness of breath are all hallmark heart attack symptoms, but they are also

signs of another, lesser-known heart conditionTakotsubo (or "broken heart")

syndrome.

HEART ATTACK'S LESS-DANGEROUS DOPPELGANGER

While not as deadly as a full-blown coronary, broken heart syndromealso

referred to as a stress cardiomyopathycan mimic a heart attack in many ways.

Both share similar symptoms, including heart failure, irregular contractions and

cardiac fluid buildup. In fact, the two conditions are so similar that even medical

professionals can have a difficult time distinguishing between them, until certain

cardiac imaging and blood tests are performed.

There is one major difference between the two cardiac conditions. Unlike a

heart attack, people with broken heart syndrome typically don't have visible signs

of heart muscle damage, or plaque build-up in their arteries.

TRIGGERED BY EMOTIONS

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Broken heart syndrome got its name from its primary causeextreme

emotional stress. Friedemann Schaub, M.D., a cardiologist and molecular biology

specialist says that major, life-changing events (such as the death of a loved one,

a divorce, even winning the lottery) can trigger stress hormones to flood a

person's body, causing their heart to go into a dangerous state of overdrive. If

exposed to elevated levels of stress hormones for too long, the heart becomes

enlarged with blood and can no longer pump blood efficiently. "Your hormones

are essentially asking your heart to do the impossible. It's the equivalent of

running all-out on a treadmill for eight hours straight," Schaub says.

HOW YOUR EMOTIONS CAN AFFECT YOUR HEART?

Your emotions can have a profound impact on your physical health and

wellbeing. Research indicates that people who successfully adopt a positive,

yet realistic attitude are 20 percent less likely than those who have a negative,

or even lukewarm approach towards life. This means that adopting proper

stress management techniques is of utmost importanceparticularly for

people who are consistently exposed to stressful situations (i.e. family

caregivers). Schaub, who is also the author of, "The Fear and Anxiety

Solution," says that stress affects your health on three, distinct levels:

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1 Behavioral: Unresolved stress can make you more prone to engaging in

unhealthy behaviors, self-abusive behaviors, such as binging and over-

indulging on food or alcohol, and neglecting to get regular exercise.

2 Physiological: An increase in the levels of stress hormones, such as cortisol

and adrenaline, directly affects you cardiovascular system by elevating blood

pressure and cholesterol levels and decreasing blood flow to the heart.

3 Cellular: Stress hormones also impact your long-term health by latching onto

different cells in your body, weakening them and making them more

susceptible to damage.

He points out that positive emotions, which decrease the amount of stress

hormones swirling around in your blood stream, can have the opposite effect

making you more likely to take care of yourself, and putting less physical stress

on your body.

COMPLICATIONS

In rare cases, broken heart syndrome is fatal. However, most who

experience broken heart syndrome quickly recover and don't have long-lasting

effects.

Other complications of broken heart syndrome include:

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Backup of fluid into your lungs (pulmonary edema)

Low blood pressure (hypotension)

Disruptions in your heartbeat

It's also possible that you may have broken heart syndrome again if you

have another stressful event. However, the odds of this happening are low.

CAN YOU DIE OF A BROKEN HEART?

It may be a well-worn clich, but it is possible to "die of a broken heart,"

according to Nieca Goldberg, M.D., Medical Director of the Joan H. Tisch Center

for Women's Health at NYU Langone Medical Center, if left untreated, broken

heart syndrome can cause dangerous arrhythmias and even cardiogenic shock

(when the heart becomes too weak to circulate enough blood throughout the

body). According to the American Heart Association, cardiogenic shock is the

symptom that typically kills people who suffer major heart attacks. That's why

Goldberg says it's essential for anyone experiencing signs of a cardiac event to

seek immediate medical treatment. The good news is that broken heart

syndrome is a rare condition, affecting only about two percent of people with

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heart problems. It is also reversible, says Schaub. If prompt medical treatment is

sought, someone suffering an episode of stress cardiomyopathy can recover in

as little as a week, typically without sustaining any kind of cardiac scarring

which makes it vastly different from a heart attack. The bad news (at least for

women) is that most people who experience episodes of stress cardiomyopathy

are women age 50 and older. The precise reason why females are more affected

by broken heart syndrome is unknown, but Goldberg hypothesizes that the

answer may lie in how women process stress.

PREPARING FOR THE COMING STORM OF STRESS

The best way to prevent broken heart syndrome is to figure out a way to

stave off the stress surges that cause it. Learn to recognize the signs of

caregiver stress and make a plan for dealing with the day-to-day difficulties of

caring for a loved one. But an elder's care needs can change in an instanthow

can you prepare for the emotional onslaught that accompanies each

unforeseeable shift? The truth is that you can't prepare for every eventuality.

What you can do, says Schaub, is take steps to more effectively manage your

stress:

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Appreciate your efforts and what you do have.

Celebrate the good things. "Most caregivers don't acknowledge how much

they're actually doing," says Schaub. "This makes it seem like they're always

swimming upstream. They can't cure their loved onemany times they can't

even make them comfortable. They never allow themselves to feel a sense of

accomplishment for what they have done for their elder." Remember,

you leave a legacy through caregiving that can be powerful and inspiring, if

you let it.

Care for yourself. Even if it's only for 20 minutes, do something you enjoy

doing every day.

It's also important to prepare for the inevitable passing of a loved one.

Death of a beloved family member is a major cause of broken heart syndrome.

The key, according Schaub, is to avoid denial while the person is still living. This

will enable you to feel comfortable playing a more active role in helping your

loved one pass on. Find peace with them before they go and visualize yourself

having a productive reaction to their death. See yourself handling the stress and

sadness appropriately and honoring them in the way that you feel is best.

PREPARING FOR YOUR APPOINTMENT

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Broken heart syndrome is usually diagnosed in an emergency or hospital

setting, since most people with the condition have symptoms identical to a heart

attack.

Call 911 or emergency medical help or have someone drive you to an

emergency room if you experience new or unexplained chest pain or pressure

that lasts for more than a few moments. Don't waste any time for fear of

embarrassment if it's not a heart attack. Even if there's another cause for your

chest pain, you need to be seen right away.

Have a family member or friend come with you, if possible. Someone who

accompanies you can help soak up all the information provided during your

evaluation.

Share this information on the way to the hospital:

Any symptoms you're experiencing, and how long you've had them.

Your key personal information, including any major stresses, such as the death of

a loved one, or recent life changes, such as the loss of a job.

Your personal and family medical history, including other health problems that

you or your close relatives have had, such as diabetes, high cholesterol or

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heart disease. It's also helpful for your doctor to know about any prescription

and over-the-counter medications you're taking.

Any recent trauma to your chest that may have caused an internal injury, such as

a broken rib or pinched nerve.

Once you're at the hospital, it's likely that your medical evaluation will

move ahead rapidly. Based on results from an electrocardiogram (ECG) and

blood tests, your doctor may be able to quickly determine if you are having a

heart attack or give you another explanation for your symptoms. You'll

probably have a number of questions at this point. If you haven't received the

following information, you may want to ask:

What do you think is causing my symptoms?

Could my symptoms be due to the sudden unexpected death of my partner, as

I've never had any symptoms like this before?

What kinds of tests and treatments do I need?

Will I need to stay in the hospital?

What are the risks associated with these treatments?

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Will this happen again?

Do I need to follow any restrictions in my diet or exercise routine after returning

home?

Should I see a specialist after returning home?

Don't hesitate to ask any additional questions that occur to you during

your medical evaluation.

WHAT TO EXPECT FROM THE DOCTOR?

A doctor who sees you for chest pain may ask:

What symptoms are you having?

When did these symptoms begin?

Does your pain radiate to any other parts of your body?

Does your pain momentarily increase with each heartbeat?

What words would you use to describe your pain?

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Does exercise or physical exertion make your symptoms worse?

Are you aware of any history of heart problems in your family?

Are you being treated or have you recently been treated for any other health

conditions?

Have you ever been diagnosed with gastroesophageal reflux disease (GERD)?

TESTS AND DIAGNOSIS

If your doctor suspects you have broken heart syndrome, he or she will use

these exams and tests to make a diagnosis:

Personal history and physical exam. In addition to a standard physical exam,

your doctor will want to know about your medical history, especially whether

you've ever had heart disease symptoms. People who have broken heart

syndrome typically don't have any heart disease symptoms before they're

diagnosed with broken heart syndrome. Also, your doctor will want to know if

you've experienced any major stresses recently, such as the death of a loved

one.

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Electrocardiogram (ECG). In this noninvasive test, a technician will place wires

on your chest that record the electrical impulses that make your heart beat. An

ECG records these electrical signals and can help your doctor detect

irregularities in your heart's rhythm and structure.

Chest X-ray. Your doctor will likely order a chest X-ray of your chest to see if

your heart is enlarged or has the shape that's typical of broken heart

syndrome, or to see if there are any problems in your lungs that could be

causing your symptoms.

Echocardiogram. Your doctor may also order an echocardiogram to see if your

heart is enlarged or has an abnormal shape, a sign of broken heart syndrome.

This noninvasive exam, which includes an ultrasound of your chest, shows

detailed images of your heart's structure and function. Ultrasound waves are

transmitted, and their echoes are recorded with a device called a transducer

that's held outside your body. A computer uses the information from the

transducer to create moving images on a video monitor.

Blood tests. Most people who have broken heart syndrome have an increased

amounts of certain enzymes in their blood. Your doctor may order blood tests

to check for these enzymes to help diagnose broken heart syndrome.

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Coronary angiogram. During a coronary angiogram, a type of dye that's visible

by X-ray machine is injected into the blood vessels of your heart. Then, an X-

ray machine rapidly takes a series of images (angiograms) that give your

doctor a detailed look at the inside of your blood vessels. People with broken

heart syndrome don't usually have any blockages in these blood vessels, while

people who've had a heart attack usually have a blockage that is visible on an

angiogram.

TREATMENTS AND DRUGS

There are no standard treatment guidelines for treating broken heart

syndrome. Treatment is similar to treatment for a heart attack until the diagnosis

is clear. Most people stay in the hospital while they recover .

Once it's clear that broken heart syndrome is the cause of your symptoms,

your doctor will likely prescribe heart medications for you to take while you're in

the hospital, such as angiotensin-converting enzyme (ACE) inhibitors, beta

blockers or diuretics. These medications help reduce the workload on your heart

while you recover and may help prevent further attacks. Many patients make a

full recovery within one to two months. Ask your doctor how long you will need to

continue taking these medications once you recover, as most can be stopped

after a while.

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Procedures that are often used to treat a heart attack, such as balloon

angioplasty and stent placement, or even surgery, are not helpful in treating

broken heart syndrome. These procedures treat blocked arteries, which are not

the cause of broken heart syndrome. However, coronary angiography is often

used to diagnose exactly what's the cause of the chest pain.

PREVENTION

There's a small chance that broken heart syndrome can happen again after

a first episode. There's no proven therapy to prevent additional episodes;

however, many doctors recommend long-term treatment with beta blockers or

similar medications that block the potentially damaging effects of stress

hormones on the heart. Recognizing and managing stress in your life also is very

important.

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