Cardiac amyloidosis

By Professor Thibaud Damy – CHU Henri Mondor CRETEIL - FRANCE

What is cardiac amyloidosis?

We talk of cardiac amyloidosis when the heart can no longer function correctly because amyloid fibrils have accumulated inside it. This cardiac infiltration gradually alters the structure and function of the myocardium. Several proteins can be responsible and give their name to the disease (e.g. Type AL cardiac amyloidosis). We cannot a priori speak of a “single” cardiac amyloidosis as there are several diseases which can lead to the production of fibrillar proteins

Which diseases are responsible for cardiac amyloidosis?

Depending on which protein is involved, the other organs that are affected and the means of transmission (hereditary or otherwise), we may distinguish different types of amyloidosis that can be at the origin of cardiac amyloidosis.

Type   Protein concerned Organs concerned Cause
Acquired  Amyloidosis AL amyloidosis Light chain of immuno-globulin (antibodies) heart, kidneys, liver, nerves surplus production of immunoglobulin
  Senile amyloidosis Transthyretin heart, carpal tunnel, ears, lumbar canal ageing
  AA Amyloidosis Serum  Amyloid A rarely the heart, kidney, liver, nerves Inflammatory disease
Hereditary amyloidosis Hereditary Transthyretin Amyloidosis mutated transthyretin heart, nerves carpal tunnel, eye, kidney mutation of the transtheretin gene
  Other mutated proteins fibrinogen, ApoAI  ApoAII, gelsolin variable depending on gene mutation of the disease the protein concerned Lyzozyme

 

The main types of amyloidosis affecting the heart are AL amyloidosis, senile amyloidosis and certain hereditary forms of amyloidosis including transthyretin amyloidosis.

Consequently, cardiac amyloidosis can be isolated or integrated into a disease affecting several other organs and therefore associated with numerous symptoms.

What are the manifestations of cardiac amyloidosis?

The clinical manifestations of the disease are due to two distinct forms of damage to the heart by the amyloid deposit: damage to the heart muscle and a disorder of the rhythm and cardiac conduction.

Deposits in the heart muscle

These deposits are responsible for a thickening of the heart known as “myocardial hypertrophy”. The consequence is that it becomes very rigid, limiting its capacity to fill up. Later it becomes difficult for the heart to contract. This lowers the cardiac output giving rise to various symptoms that go by the name of “heart failure”:

  • Breathlessness during effort, then while resting (talking or lying down)
  • Tiredness in case of effort, then during resting
  • Water retention/ oedema particularly in the legs, weight increase.
  • Palpitations

Deposits in the electric circuit

They disrupt the heart rate, making it either too rapid or too slow and can even lead to cardiac arrest. This disorder can require the fitting of a pacemaker under the skin to control the heartbeats or a defibrillator. The symptoms can include:

  • Feeling faint
  • Syncope
  • Palpitations

How is a cardiac amyloidosis diagnosed ?

Cardiac amyloidosis is looked for in two types of situation:

  • When faced with symptoms like those we have just described. Certain tests are then able to show up heart disorders that indicate cardiac amyloidosis. Thickening of the heart, or myocardial hypertrophy, is highlighted by trans-thoracic echocardiography and an cardiac MRI. A heartbeat disorder is shown up by a standard electrocardiogram (ECG – recording the electric signals of the heart) and an extended one, also called a Holter-Electrocardiogram (Holter ECG). When the disorders have been highlighted, the presence of amyloid deposits must be proved by a biopsy. The heart is then the first or only organ to be affected by amyloidosis.
  • In a patient already affected by a known amyloidosis when he or she develops telling symptoms or during an annual heart check-up. Once again echocardiography, cardiac MRI, ECG and Holter ECG are used.

The definitive diagnosis is based on evidence of a deposit on the biopsy sample. In a case where heart damage appears during the development of an already-known amyloidosis, it is not always necessary to carry out a new biopsy.

Amyloidosis is recognised on biopsies thanks to Congo Red staining. Typing is then carried out to differentiate the various kinds of amyloidosis.

 Deposits of transthyretin amyloidosis (senile amyloidosis or hereditary TTR amyloidosis) can be revealed by a nuclear imagery examination called a DPD/HMDP scintigraphy. Their identification does not always mean that the biopsy will be waived.

Once amyloidosis has been diagnosed, it is necessary to carry out a detailed check-up of the affected organs, which will vary according to their type.

Treatment of cardiac amyloidosis

The treatment offered depends on the type of amyloidosis and the associated symptoms.  Medical care will include two major types of treatment: those which aim to alleviate the symptoms and prevent complications and those which aim to stop the formation of amyloid fibrils. 

Treatment for alleviating the symptoms

Symptomatic treatments are not specific for amyloidosis. The symptoms of heart failure are treated by diuretics (such as FUROSEMIDE) and a salt-free diet. Heart rhythm disorders, linked to electrical defects can be treated or prevented by a pacemaker. Incidentally, some medication may worsen the symptoms and have to be stopped: for example, beta-blockers (medication which slow down the heart beat) or vasodilators (medication which dilates the blood vessels). Finally, in some cases when the heart becomes very rigid and can no longer contract, the blood stagnates and forms clots which can block arteries far from the heart causing a stroke or pulmonary embolism. To prevent these kinds of complication, the physician may prescribe anti-coagulant treatment to thin the blood.

Anti-amyloid treatments

On the other hand, treatments to stop the formation of amyloid fibrils are adapted to the type of amyloidosis.

Monitoring and development of cardiac amyloidosis

Monitoring is fundamental in the care of a patient with amyloidosis. Its purpose is to follow the progression of the heart condition, to ensure the effectiveness and absence of toxicity of the medication prescribed and to detect as early as possible any damage to other organs. This involves regular detailed clinical examinations, examinations using imagery (ultrasound scan, MRI) and biological tests (dosage of free light chains in the blood, cardiac markers: BNP, NT-proBNP); markers for kidney damage: proteinuria, micro-albuminuria, urinary test strips).

The frequency of the consultations is variable: once or twice a year in the case of a stable pathology, more frequent in case of problems with the control of the disease or therapeutic modifications which need to be revalued. The prognosis of cardiac amyloidosis depends largely on the type of amyloidosis concerned and which other organs are affected. In any case, cardiac amyloidosis is a serious disease. Nevertheless, when it is detected and treated in time, its progression can be stopped for a considerable length of time. In some cases, a gradual improvement in the heart condition is even possible if the treatment began before any irreversible damage was caused by amyloid deposits. 

Questions frequently asked by patients about cardiac amyloidosis

There is a suspicion of cardiac amyloidosis. Why must I undergo tests?

It is important to go as far as a formal diagnosis because amyloid heart damage is due to several very different diseases (amyloidosis) for which therapeutic care will differ.

The diagnosis of cardiac amyloidosis will therefore involve specific medical care depending on the type of amyloidosis to fight against the infiltration of the organs by amyloid fibrils.

The diagnosis of cardiac amyloidosis will also require specialized heart treatment that is different from conventional treatment for heart failure. This will involve reviewing cardiological treatment and preventing complications of this disease, which are unfortunately very common.

In cardiac amyloidosis, the prevention of complications is fundamental!

I am elderly, my partner is elderly…What is the point of going through a complete check-up?

The check-up is prescribed if the diagnosis is likely to change the treatment. It is the case with this disease when the heart is affected. 

If the diagnosis is made on a patient with a history of heart problems, the first stage will be to review the entire ongoing treatment and to stop any potentially harmful or useless medication. Then it will be necessary to propose treatment which will be able to prevent complications. There is no age limit for this.

Cardiac amyloidosis is more frequent among patients over 60 years old, particularly the transthyretin forms. However, the pathology may be hereditary and consequently the tests will have consequences for the whole family (brothers, sisters, children, cousins…).

Even at the age of 90 I can have hereditary transthyretin amyloidosis. A diagnosis of wild or senile amyloidosis can only be made if the gene is analysed and no mutation has been detected.

Why do I have to go to a specialized centre when there’s a hospital next to my home?

Cardiac amyloidosis is a new disease for cardiologists and the different treatments evolve constantly and rapidly. There are many rare heart diseases and physicians cannot know all of them or follow the latest therapies. Besides, the diagnosis of the different types of amyloidosis and their treatment are not easy. It is necessary to set up pluri-disciplinary medical care in specialized expert centres.

In a specialized centre, the cardiologist you consult will know the disease, s/he will be aware of the latest developments and breakthroughs and offer you the best treatment at the time you meet him/her. You will not be obliged to continue with the same cardiologist and s/he can get in touch with your doctor to help you with your treatment and care. If s/he knows you, s/he will have all the necessary information to ensure that the right decisions are made.

I have already had tests (echocardiography, blood tests….). Why do I have to do them again at the reference centre?

Your specialist is bound to have to repeat some of the examinations that you have already done. Most of the tests that you did before you came to the expert centre were to identify amyloidosis among hundreds of other heart diseases. Naturally, the tests could not focus on amyloidosis.

In the reference centre, all the physicians are used to seeing cardiac amyloidosis and have gained a great deal of information from tests carried out within the centre. The examinations that we perform are very extensive, dedicated only to amyloidosis and carried out to respond to specific, precise questions, so as to guide us in the best possible way through your treatment.

Every patient who suffers from amyloidosis is different and needs personalised treatment.

I’ve been offered a cardiac biopsy. Isn’t it too risky?

A cardiac biopsy is a second-intention examination. If your physician has prescribed it, it is because, unfortunately, he has no other solution to identify the cause of your disease or to adapt your treatment.

This examination is performed under local anaesthetic. The doctor introduces a small catheter (equipped with a tiny clip) into a vein of the neck or groin. The only thing you will feel is the anaesthetic. The catheter will be pushed up to your heart following the blood vessels. You will not feel anything in particular. The clip will be opened out and a tiny fragment the size of a pinhead will be removed. Complications are rare but, like any examination or operation they can occur. For this reason, it is necessary to discuss the benefit/risk ratio with the doctor.

What is the difference between heart failure and cardiac amyloidosis?

Heart failure is a syndrome that includes many diseases and cardiac amyloidosis is one of them. Heart failure is when the heart is unable to carry out its function of pumping blood to the organs whether during effort or rest. The symptoms of heart failure can therefore concern several diseases. Treatment is based on the European heart failure recommendations. Thanks to these recommendations medical care for heart failure has improved considerably and has been standardised throughout Europe. Unfortunately, amyloidosis is a special case and it is difficult to apply these recommendations to its specific needs.

What are the effects of amyloidosis on my heart?

Amyloid infiltration can go as far as to treble the thickness of the heart. Depending on the type of amyloidosis, any layers of the heart wall can be affected. Amyloid deposits surround the cells of the heart, isolate them and thus prevent them from functioning.

The main function of the heart, which is to carry blood to the organs, will be disrupted. One of the most frequent symptoms of this is breathlessness during effort and then rest. The heart disorder will then lead to a paradoxical reaction of the organism because it is receiving an insufficient supply of blood. It will consequently retain water and salt to increase its perfusion causing major sodium and water retention of up to several kilos and oedema predominant in the legs and abdomen.

Amyloidosis can also affect the electric cells of the heart. This can cause pauses in the heartbeat and ultimately cardiac arrest, acceleration of the heartbeat, non-acceleration of the heart rate during effort and its gradual decrease during rest.

Amyloidosis can also damage the heart valves and cause leaks and a narrowing of the valves (aortic stenosis).

Amyloidosis can affect the pericardium and cause an influx of liquid around the heart.

Why are beta-blockers dangerous in case of cardiac amyloidosis?

AAny medication which slows down the heart rate is dangerous in the presence of cardiac amyloidosis. Beta-blockers are often discussed because they are one of the best treatments for heart failure. Unfortunately, apart from special cases, they cannot be used when there is cardiac amyloidosis.

A heart with amyloidosis is very stiff, so stiff in fact that it has difficulty filling up and the volume  which is going to be ejected into the blood circulation shrinks as the heart inflates. But the cardiac output is dependent on the number of beats per minute and on the volume ejected with each beat. Therefore, if you reduce your heart rate when you have a fixed volume (imposed by the cardiac rigidity involved in amyloidosis), you will reduce the heart rate proportionately. For this reason, it is important to adapt the heart rate to the seriousness of the heart damage. It is all the more important as, with time, the heart rate slows down because of an electric disorder.

Beta-blockers also have the property of reducing the contraction of cardiomyocytes and of intracardiac conduction. But this is also what we wish to preserve in amyloidosis.

Why do I have to be fitted with a pacemaker or a defibrillator?

Amyloidosis can affect the electrical cells of the heart. This can cause pauses in the heartbeat and ultimately cardiac arrest, acceleration of the heartbeat, non- acceleration of the heart rate during effort and its gradual decrease during rest.

There are many different types of electrical equipment which can be implanted. Pacemakers allow the heart to be heard and be stimulated if necessary. In case of a rapid acceleration of the heart rate, defibrillators can administer an electric shock to the heart and calm down the over-active cells.

I suffer from cardiac amyloidosis. What future do I have?

Heart damage is a key element in the prognosis of amyloidosis. Indeed, it is very difficult to live without a heart. For this reason, if the heart is affected, it is essential to preserve it in the best possible state and optimize its functioning. The cardiologists at the expert centres are there to help you.

It should be remembered that each patient is unique when it comes to amyloidosis and treatment and care evolve very rapidly.

Finally, for the most seriously affected patients, it is possible in some cases to envisage a heart implant, in other words replacement of the heart.