The normal heart:
- Is a muscular pump about the size of a fist, located in the center left of the chest.
- It is a major part of the cardiovascular system.
What does the heart do?
- Moves blood carrying oxygen and nutrients around the body through a number of interconnecting pipes of various sizes called arteries and veins
- The normal heart expands and contracts about 100,000 times per day pumping five or six quarts of blood each minute, or about 2,000 gallons per day.
- The heart has two sides, left and right, separated by a muscular wall.
The upper chambers are called atria and the larger lower chambers are known as ventricles.
- Electrical impulses from the hearts natural pacemaker ignite the heart muscle (the myocardium) and cause the heart to beat (contract).
- This electrical signal begins in the sinoatrial (SA) node, located at the top of the right atrium. The SA node is sometimes referred to as the heart’s “natural pacemaker.”
- When an electrical impulse is released from this natural pacemaker, it causes the atria to contract. The signal then passes through the atrioventricular (AV) node.
- The AV node slows the signal and sends it through the muscle fibers of the ventricles, causing them to contract.
- The right side of the heart pumps blood to the lungs where it receives oxygen.
- The blood then re-enters the left side of the heart from the lungs.
- The heart then pumps the oxygen rich blood around the body.
- In healthy people the heart relaxes and contracts between 60 to 100 times a minute.
- When the heart muscles relax the inner chambers fill with blood. When the muscles contract the blood is squeezed out of these chambers into the blood vessels.
What happens when the amyloid protein deposits in the heart?
Cardiac amyloidosis is defined by the presence of extracellular deposition of amyloid with in the heart.
Amyloid deposited in the heart may cause the heart muscle to become stiff over time. If the heart muscle cannot relax enough to fill with blood this leads to accumulation of fluid in the lungs, legs and liver. With time the pumping function decreases, which results in reduced blood flow to the body organs and tissues and may lead to drop in blood pressure.
- The consequences of cardiac amyloidosis are similar in all types of amyloid. They belong to a group called infiltrative cardiomyopathy and result in progressive heart failure.
- Patients with cardiac amyloidosis typically exhibit heart failure with preserved ejection fraction (otherwise known as diastolic heart failure). This is a common form of heart failure in elderly patients and requires diuretic therapy.
- Cardiac amyloidosis may also affect the way electrical signals move through the heart (conduction system). This can lead to faulty heart signals, (heart block) and may require a pace maker. Abnormal heartbeats (arrhythmias) re also common.
Most types of amyloidosis disease are described as systemic meaning that more than one organ will be effected by the amyloid deposition.
Cardiac amyloidosis therefore is rarely seen alone. Damage in other organs can also impact on the working of the heart.
In AL amyloidosis heart failure may go hand in hand with:
- Peripheral and autonomic neuropathy
- Nephrotic syndrome
- Periorbital purpura
In ATTRv heart failure is often seen with peripheral and autonomic neuropathy.
In ATTRwt heart failure is the predominant problem. However, carpal tunnel syndrome, biceps tendon rupture and spinal stenosis may be experienced with atrial fibrillation experienced sometime occurring some time before heart failure.
Symptoms indicating amyloidosis in the heart.
If there is only a small deposition of amyloid in the heart there may be no noticeable symptoms. However, as the deposits build up symptoms will become evident.
These symptoms can often be vague at first and mimic those seen in other diseases which can lead too late diagnosis or a misdiagnosis.
- Breathlessness on effort
- Swelling of the ankles and feet
- Weight loss
- Heart palpitations, Atrial fibrillation.
- Black outs
- A definitive diagnosis of amyloidosis can only be obtained through a biopsy. This involves taking a small piece of tissue from the body, often the fat pad on the tummy, or the lip. It may also mean a more invasive biopsy from the heart.
- This biopsy is then stained in the laboratory with a dye called Congo red.
- If amyloid is present, the biopsy will appear red under normal light and green (apple-green birefringence) under special polarized light.
Identifying the type of amyloidosis is imperative as treatment to slow or stop the precursor protein is different for each type.
A test called Laser Capture mass spectroscopic proteomic analysis may be used with other tests to identify the type of amyloidosis.
Over the decade new diagnostic tools have improved the ability to diagnose cardiac amyloidosis.
These advances include:
- Nuclear bone scintigraphy with DPD.
A DPD is a “bone seeking” tracer which is injected into the bloodstream where it seeks out the bones, especially if there is an abnormality. This tracer has also been shown to seek out the amyloid deposits in the heart.
- DPD scanning is now used for diagnosing ATTR amyloidosis because it is sensitive to amyloid deposits in the heart.
- In ATTR there is good correlation between the amount of the DPD taken up and the size of the amyloid deposits in the heart.
- Asymptomatic cardiac ATTR can be detected in the very early stage.
- Although DPD scanning can be useful in AL cardiac amyloidosis uptake of the tracer only occurs in about 1 in 3 AL amyloidosis patients.
- In AL amyloidosis the amyloid deposits in the heart do NOT correlate with the amount of uptake in the DPD scan.
The tests above have given cardiologists the option in some cases to diagnose and type cardiac amyloidosis without directly proceeding to an invasive heart biopsy.
Cardiac amyloid may also be diagnosed or surmised without a cardiac biopsy if a diagnosis of amyloidosis has already been made through the biopsy of another organ the heart is not functioning well.
A combination of the patient’s symptoms, blood tests and imaging tests are used to assess the function of the heart and the other organs.
Other tests may include:
- Tests for general assessment of the health of the patient. Other health problems that may affect treatment.
- Immunoglobulin FLC assay in patients with unexplained heart failure.
- DPD scan (Radionuclide imaging) TcPYP (myocardial radiotracer) to help establish which type of amyloid a patient has. see above
- Cardiac biomarkers (NT-proBNP and Troponin. (blood tests used in diagnosis, prognosis and monitoring disease).
- Cardiac MRI Scan
- DNA to differentiate between the wild type and the hereditary type of ATTR in patients with no family history.
The goals of treatment for all types of amyloidosis are:
- To try to stop or slow the production of the precursor protein.
- To support and preserve the affected organs through treatment and afterwards.
- To maintain and improve quality of life by offering support education and counseling as needed
Medical care for those with cardiac amyloidosis will usually be given by a multidisciplinary team (not necessarily under one roof and not always seen at the same time) consisting of a cardiologist and a haematologist. Other medical specialists on the team will vary according to other organ involvement. In patient with ATTRwt the cardiologist is usually the primary specialist.
Other members of the team:
- Specialized nurse.
- Psychologist/social worker/counselor
- Exercise physiologist
Treatment for cardiac amyloidosis will depend on the type of amyloidosis a patient has.
There is no “approved” treatment at this time anywhere in the world to stop the production of the abnormal amyloid protein which deposits in the organs and tissues in any type of amyloidosis.
Early diagnosis is the key to optimum treatment and better outcomes in all types of cardiac amyloidosis.
- In AL amyloidosis cardiac involvement progresses more quickly without treatment than in the other types of amyloidosis e.g. ATTRwt. The reason for this is not fully understood but it is felt that the circulating light chains may be toxic to the heart even before they deposit in the heart.
- It is therefore very important that any treatment available to stop or slow the production of the precursor protein is commenced as soon as possible after diagnosis.
Review separate sections on types of amyloidosis from the Patients and Carers menu for more information on treatments.
- Patients with AL amyloidosis will usually be treated with Chemotherapy in combination with novel drugs and steroids.
- Treatments will be determined for the individual patient and depend on the degree of organ involvement.
- Reduction of the light chain in AL amyloidosis following treatment can result in a better clinical outcome in cardiac amyloidosis despite no obvious improvement on the echocardiogram and other tests.
- If a patient receiving treatment for AL amyloidosis reaches remission (CR) or a very good partial remission (VGPR) there is a chance that the amyloid will start to leech out of the heart with the result that heart function may improve. This is usually a very slow process and may take over a year after remission before any change is seen.
Stem Cell Transplant
AL patients with symptomatic cardiac amyloidosis are usually not considered for a stem cell transplant because of the risk.
If this procedure is offered it must be done in an amyloidosis center or unit with experience in transplanting amyloidosis patients.
- Cardiac deposition takes place at a much slower rate in ATTRwt than in AL amyloidosis.
- Patients often learn to live with any changes that cardiac amyloid brings and live almost normal lives for many years.
- Chemotherapy has no place in the treatment of wild type ATTR and supportive care is the main treatment at this time.
- Chemotherapy has no place in the treatment of Hereditary ATTR.
- Supportive treatments are extremely important.
- New drugs to slow the progression of the amyloid protein being trialed overseas.
In Australia Green tea capsules and doxycycline, which have been shown to disrupt the amyloid fibers, may be prescribed to treat ATTR-CA.
Diflunisal, a nonsteroidal anti-inflammatory drug (NSAID), is used in a selected group of ATTR-CA patients with appropriate clinical, renal and hematologic monitoring.
- Supportive treatment is the main treatment at this time.
- For both hereditary and wild type ATTR a number of treatments are being trialed to stop the production of the protein in the liver, to stabilize the protein TTR in the blood or to remove the deposited protein in the organs. At this stage TTR stabilizing drugs have been introduced to therapy but these are not available in Australia as yet.
- In AL with cardiac involvement, a heart transplant is only considered in younger patient with isolated deposits in the heart when a complete remission has been reached after treatment, but the heart remains very damaged after a substantial period of time. After receiving a heart transplant the patient will undergo a stem cell transplant some months later to try to stop or delay the amyloid growing back into the new heart. See Robin’s Story – AL, early remission and a heart transplant.
- ATTRwt. In patients with wild type ATTR heart transplant is rarely considered because of age.
- Hereditary ATTRv. Cardiac transplantation is occasionally considered in patients with TTR-FAC and in some cases heart and liver transplants have been performed.
Supportive treatments are extremely important in managing the symptoms of cardiac amyloidosis and delaying organ failure.
These treatments revolve around fluid balance and heart rhythm.
- Fluid balance is very important and fluid take may be monitored.
- Keeping a diary of fluid intake and daily weight.
- Diuretics are often used with caution to manage fluid issues especially during chemotherapy when steroids are used.
- Monitor blood pressure regularly.
- Limited/gentle exercise.
- Pace makers may be recommended for slow or irregular heart rate.
- Defibrillators are sometime recommended for patients with malignant heart rhythms.
- Support stocking may help with leg oedema.
Some treatments used in other types of heart failure should only be used with caution in cardiac amyloidosis as they can lower already low blood pressure.
- Calcium channel blockers
- Beta blockers
- ACE inhibitors
If the above causes concern DO NOT stop taking the drugs mentioned above without consulting your doctor.
Go to separate section on the types of amyloidosis for more in depth information about the different diseases which may have cardiac involvement.
Advanced amyloidosis in the heart remains a major challenge to treatment and early diagnosis is imperative.
Cardiac Amyloidosis – Treatment Options
Julian Gillmore from the National Amyloidosis Centre in London on Cardiomyopathy in ATTR